Template protocol for clinical trials investigating vaccines—Focus on safety elements☆

PubMed Central

Bonhoeffer, Jan; Imoukhuede, Egeruan B.; Aldrovandi, Grace; Bachtiar, Novilia S.; Chan, Eng-Soon; Chang, Soju; Chen, Robert T.; Fernandopulle, Rohini; Goldenthal, Karen L.; Heffelfinger, James D.; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B.; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2015-01-01

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I–IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

[Constraints on publication rights in industry-initiated clinical trials--secondary publication].

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2006-06-19

In 22 of 44 industry-initiated clinical trial protocols from 1994-95, it was noted that the sponsor either owned the data or needed to approve the manuscript; another 18 protocols had other constraints. Furthermore, in 16 trials, the sponsor had access to accumulating data, and in an additional 16 trials the sponsor could stop the trial at any time, for any reason. These facts were not noted in any of the trial reports. We found similar constraints on publication rights in 44 protocols from 2004. This tight sponsor control over industry-initiated trials should be changed.

Patient-Reported Outcome (PRO) Assessment in Clinical Trials: A Systematic Review of Guidance for Trial Protocol Writers

PubMed Central

Calvert, Melanie; Kyte, Derek; Duffy, Helen; Gheorghe, Adrian; Mercieca-Bebber, Rebecca; Ives, Jonathan; Draper, Heather; Brundage, Michael; Blazeby, Jane; King, Madeleine

2014-01-01

Background Evidence suggests there are inconsistencies in patient-reported outcome (PRO) assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers. Methods and Findings We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013) for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts). 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3%) recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency. Conclusions PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in appropriate trial protocols, in order to facilitate rigorous collection/reporting of PRO data, to effectively inform patient care. PMID:25333995

Recruitment failure and futility were the most common reasons for discontinuation of clinical drug trials. Results of a nationwide inception cohort study in the Netherlands.

PubMed

van den Bogert, Cornelis A; Souverein, Patrick C; Brekelmans, Cecile T M; Janssen, Susan W J; Koëter, Gerard H; Leufkens, Hubert G M; Bouter, Lex M

2017-08-01

The objective of the study was to identify the reasons for discontinuation of clinical drug trials and to evaluate whether efficacy-related discontinuations were adequately planned in the trial protocol. All clinical drug trials in the Netherlands, reviewed by institutional review boards in 2007, were followed until December 2015. Data were obtained through the database of the Dutch competent authority (Central Committee on Research Involving Human Subjects [CCMO]) and a questionnaire to the principal investigators. Reasons for trial discontinuation were the primary outcome of the study. Three reasons for discontinuation were analyzed separately: all cause, recruitment failure, and efficacy related (when an interim analysis had demonstrated futility or superiority). Among the efficacy-related discontinuations, we examined whether the data monitoring committee, the stopping rule, and the moment of the interim analysis in the trial progress were specified in the trial protocol. Of the 574 trials, 102 (17.8%) were discontinued. The most common reasons were recruitment failure (33 of 574; 5.7%) and solely efficacy related (30 of 574; 5.2%). Of the efficacy-related discontinuations, 10 of 30 (33.3%) of the trial protocols reported all three aspects in the trial protocol, and 20 of 30 (66.7%) reported at least one aspect in the trial protocol. One out of five clinical drug trials is discontinued before the planned trial end, with recruitment failure and futility as the most common reasons. The target sample size of trials should be feasible, and interim analyses should be adequately described in trial protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Template protocol for clinical trials investigating vaccines--focus on safety elements.

PubMed

Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

2013-11-12

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

Developing a guideline for clinical trial protocol content: Delphi consensus survey

PubMed Central

2012-01-01

Background Recent evidence has highlighted deficiencies in clinical trial protocols, having implications for many groups. Existing guidelines for randomized clinical trial (RCT) protocol content vary substantially and most do not describe systematic methodology for their development. As one of three prespecified steps for the systematic development of a guideline for trial protocol content, the objective of this study was to conduct a three-round Delphi consensus survey to develop and refine minimum content for RCT protocols. Methods Panellists were identified using a multistep iterative approach, met prespecified minimum criteria and represented key stakeholders who develop or use clinical trial protocols. They were asked to rate concepts for importance in a minimum set of items for RCT protocols. The main outcome measures were degree of importance (scale of 1 to 10; higher scores indicating higher importance) and level of consensus for items. Results were presented as medians, interquartile ranges, counts and percentages. Results Ninety-six expert panellists participated in the Delphi consensus survey including trial investigators, methodologists, research ethics board members, funders, industry, regulators and journal editors. Response rates were between 88 and 93% per round. Overall, panellists rated 63 of 88 concepts of high importance (of which 50 had a 25th percentile rating of 8 or greater), 13 of moderate importance (median 6 or 7) and 12 of low importance (median less than or equal to 5) for minimum trial protocol content. General and item-specific comments and subgroup results provided valuable insight for further discussions. Conclusions This Delphi process achieved consensus from a large panel of experts from diverse stakeholder groups on essential content for RCT protocols. It also highlights areas of divergence. These results, complemented by other empirical research and consensus meetings, are helping guide the development of a guideline for protocol content. PMID:23006145

[Development of clinical trial education program for pharmaceutical science students through small group discussion and role-playing using protocol].

PubMed

Imakyure, Osamu; Shuto, Hideki; Nishikawa, Fumi; Hagiwara, Yoshifuka; Inoue, Sachiko; Koyanagi, Taeko; Hirakawa, Masaaki; Kataoka, Yasufumi

2010-08-01

The acquirement of basic knowledge of clinical trials and professional attitude in their practices is a general instructional objective in the Model Core Curriculum for Pharmaceutical Education. Unfortunately, the previous program of clinical trial education was not effective in the acquirement of a professional attitude in their practices. Then, we developed the new clinical trial education program using protocol through small group discussion (SGD) and roll-playing. Our program consists of 7 steps of practical training. In step 1, the students find some problems after presentation of the protocol including case and prescription. In step 2, they analyse the extracted problems and share the information obtained in SGD. In steps 3 and 5, five clinical case scenarios are presented to the students and they discuss which case is suitable for entry to the clinical trial or which case corresponds to the discontinuance criteria in the present designed protocol. In steps 4 and 6, the roll-playing is performed by teachers and students as doctors and clinical research coordinators (CRC) respectively. Further, we conducted a trial practice based on this program for the students. In the student's self-evaluation into five grades, the average score of the skill acquisition level in each step was 3.8-4.7 grade. Our clinical trial education program could be effective in educating the candidates for CRC or clinical pharmacists.

Electronic Clinical Trial Protocol Distribution via the World-Wide Web

PubMed Central

Afrin, Lawrence B.; Kuppuswamy, Valarmathi; Slater, Barbara; Stuart, Robert K.

1997-01-01

Clinical trials today typically are inefficient, paper-based operations. Poor community physician awareness of available trials and difficult referral mechanisms also contribute to poor accrual. The Physicians Research Network (PRN) web was developed for more efficient trial protocol distribution and eligibility inquiries. The Medical University of South Carolina's Hollings Cancer Center trials program and two community oncology practices served as a testbed. In 581 man-hours over 18 months, 147 protocols were loaded into PRN. The trials program eliminated all protocol hardcopies except the masters, reduced photocopier use 59%, and saved 1.0 full-time equivalents (FTE), but 1.0 FTE was needed to manage PRN. There were no known security breaches, downtime, or content-related problems. Therefore, PRN is a paperless, user-preferred, reliable, secure method for distributing protocols and reducing distribution errors and delays because only a single copy of each protocol is maintained. Furthermore, PRN is being extended to serve other aspects of trial operations. PMID:8988471

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees

PubMed Central

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-01-01

A novel Protocol Ethics Tool Kit (‘Ethics Tool Kit’) has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. PMID:26811365

Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials

PubMed Central

Guydish, J.; Manser, S.T.; Jessup, M.; Tajima, B.; Sears, C.; Montini, T.

2010-01-01

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. PMID:20890376

Optimisation of pharmacy content in clinical cancer research protocols: Experience of the United Kingdom Chemotherapy and Pharmacy Advisory Service.

PubMed

Debruyne, Philip R; Johnson, Philip J; Pottel, Lies; Daniels, Susanna; Greer, Rachel; Hodgkinson, Elizabeth; Kelly, Stephen; Lycke, Michelle; Samol, Jens; Mason, Julie; Kimber, Donna; Loucaides, Eileen; Parmar, Mahesh Kb; Harvey, Sally

2015-06-01

Clarity and accuracy of the pharmacy aspects of cancer clinical trial protocols is essential. Inconsistencies and ambiguities in such protocols have the potential to delay research and jeopardise both patient safety and collection of credible data. The Chemotherapy and Pharmacy Advisory Service was established by the UK National Cancer Research Network, currently known as National Institute for Health Research Clinical Research Network, to improve the quality of pharmacy-related content in cancer clinical research protocols. This article reports the scope of Chemotherapy and Pharmacy Advisory Service, its methodology of mandated protocol review and pharmacy-related guidance initiatives and its current impact. Over a 6-year period (2008-2013) since the inception of Chemotherapy and Pharmacy Advisory Service, cancer clinical trial protocols were reviewed by the service, prior to implementation at clinical trial sites. A customised Review Checklist was developed and used by a panel of experts to standardise the review process and report back queries and inconsistencies to chief investigators. Based on common queries, a Standard Protocol Template comprising specific guidance on drug-related content and a Pharmacy Manual Template were developed. In addition, a guidance framework was established to address 'ad hoc' pharmacy-related queries. The most common remarks made at protocol review have been summarised and categorised through retrospective analysis. In order to evaluate the impact of the service, chief investigators were asked to respond to queries made at protocol review and make appropriate changes to their protocols. Responses from chief investigators have been collated and acceptance rates determined. A total of 176 protocols were reviewed. The median number of remarks per protocol was 26, of which 20 were deemed clinically relevant and mainly concerned the drug regimen, support medication, frequency and type of monitoring and drug supply aspects. Further analysis revealed that 62% of chief investigators responded to the review. All responses were positive with an overall acceptance rate of 89% of the proposed protocol changes. Review of pharmacy content of cancer clinical trial protocols is feasible and exposes many undetected clinically relevant issues that could hinder efficient trial conduct. Our service audit revealed that the majority of suggestions were effectively incorporated in the final protocols. The refinement of existing and development of new pharmacy-related guidance documents by Chemotherapy and Pharmacy Advisory Service might aid in better and safer clinical research. © The Author(s) 2015.

The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial.

PubMed

Hershberg, Julie A; Rose, Dorian K; Tilson, Julie K; Brutsch, Bettina; Correa, Anita; Gallichio, Joann; McLeod, Molly; Moore, Craig; Wu, Sam; Duncan, Pamela W; Behrman, Andrea L

2017-01-01

Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice. Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making. In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation. Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).

A privacy preserving protocol for tracking participants in phase I clinical trials.

PubMed

El Emam, Khaled; Farah, Hanna; Samet, Saeed; Essex, Aleksander; Jonker, Elizabeth; Kantarcioglu, Murat; Earle, Craig C

2015-10-01

Some phase 1 clinical trials offer strong financial incentives for healthy individuals to participate in their studies. There is evidence that some individuals enroll in multiple trials concurrently. This creates safety risks and introduces data quality problems into the trials. Our objective was to construct a privacy preserving protocol to track phase 1 participants to detect concurrent enrollment. A protocol using secure probabilistic querying against a database of trial participants that allows for screening during telephone interviews and on-site enrollment was developed. The match variables consisted of demographic information. The accuracy (sensitivity, precision, and negative predictive value) of the matching and its computational performance in seconds were measured under simulated environments. Accuracy was also compared to non-secure matching methods. The protocol performance scales linearly with the database size. At the largest database size of 20,000 participants, a query takes under 20s on a 64 cores machine. Sensitivity, precision, and negative predictive value of the queries were consistently at or above 0.9, and were very similar to non-secure versions of the protocol. The protocol provides a reasonable solution to the concurrent enrollment problems in phase 1 clinical trials, and is able to ensure that personal information about participants is kept secure. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

PubMed

Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

2016-04-01

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Portfolio of prospective clinical trials including brachytherapy: an analysis of the ClinicalTrials.gov database.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Miguelez, Cristina Gutierrez; Strnad, Vratislav; Soldatovic, Ivan; Ghadjar, Pirus; Jeremic, Branislav; Dal Pra, Alan; Aebersold, Daniel M; Lössl, Kristina

2016-03-22

To evaluate the current status of prospective interventional clinical trials that includes brachytherapy (BT) procedures. The records of 175,538 (100 %) clinical trials registered at ClinicalTrials.gov were downloaded on September 2014 and a database was established. Trials using BT as an intervention were identified for further analyses. The selected trials were manually categorized according to indication(s), BT source, applied dose rate, primary sponsor type, location, protocol initiator and funding source. We analyzed trials across 8 available trial protocol elements registered within the database. In total 245 clinical trials were identified, 147 with BT as primary investigated treatment modality and 98 that included BT as an optional treatment component or as part of the standard treatment. Academic centers were the most frequent protocol initiators in trials where BT was the primary investigational treatment modality (p < 0.01). High dose rate (HDR) BT was the most frequently investigated type of BT dose rate (46.3 %) followed by low dose rate (LDR) (42.0 %). Prostate was the most frequently investigated tumor entity in trials with BT as the primary treatment modality (40.1 %) followed by breast cancer (17.0 %). BT was rarely the primary investigated treatment modality for cervical cancer (6.8 %). Most clinical trials using BT are predominantly in early phases, investigator-initiated and with low accrual numbers. Current investigational activities that include BT mainly focus on prostate and breast cancers. Important questions concerning the optimal usage of BT will not be answered in the near future.

A quality analysis of clinical anaesthesia study protocols from the Chinese clinical trials registry according to the SPIRIT statement.

PubMed

Yang, Lei; Chen, Shouming; Yang, Di; Li, Jiajin; Wu, Taixiang; Zuo, Yunxia

2018-05-15

To learn about the overall quality of clinical anaesthesia study protocols from the Chinese Clinical Trials Registry and to discuss the way to improve study protocol quality. We defined completeness of each sub-item in SPIRIT as N/A (not applicable) or with a score of 0, 1, or 2. For each protocol, we calculated the proportion of adequately reported items (score = 2 and N/A) and unreported items (score = 0). Protocol quality was determined according to the proportion of reported items, with values >50% indicating high quality. Protocol quality was determined according to the proportion of reported items. For each sub-item in SPIRIT, we calculated the adequately reported rate (percentage of all protocols with score 2 and NA on one sub-item) as well as the unreported rate (percentage of all protocols with score 0 on one sub-item). Total 126 study protocols were available for assessment. Among these, 88.1% were assessed as being of low quality. By comparison, the percentage of low-quality protocols was 88.9% after the publication of the SPIRIT statement. Among the 51 SPIRIT sub-items, 18 sub-items had an unreported rate above 90% while 16 had a higher adequately reported rate than an unreported rate. The overall quality of clinical anaesthesia study protocols registered in the ChiCTR was poor. A mandatory protocol upload and self-check based on the SPIRIT statement during the trial registration process may improve protocol quality in the future.

Improving Conduct and Feasibility of Clinical Trials to Evaluate Antibacterial Drugs to Treat Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team.

PubMed

Knirsch, Charles; Alemayehu, Demissie; Botgros, Radu; Comic-Savic, Sabrina; Friedland, David; Holland, Thomas L; Merchant, Kunal; Noel, Gary J; Pelfrene, Eric; Reith, Christina; Santiago, Jonas; Tiernan, Rosemary; Tenearts, Pamela; Goldsack, Jennifer C; Fowler, Vance G

2016-08-15

The etiology of hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP) is often multidrug-resistant infections. The evaluation of new antibacterial drugs for efficacy in this population is important, as many antibacterial drugs have demonstrated limitations when studied in this population. HABP/VABP trials are expensive and challenging to conduct due to protocol complexity and low patient enrollment, among other factors. The Clinical Trials Transformation Initiative (CTTI) seeks to advance antibacterial drug development by streamlining HABP/VABP clinical trials to improve efficiency and feasibility while maintaining ethical rigor, patient safety, information value, and scientific validity. In 2013, CTTI engaged a multidisciplinary group of experts to discuss challenges impeding the conduct of HABP/VABP trials. Separate workstreams identified challenges associated with HABP/VABP protocol complexity. The Project Team developed potential solutions to streamline HABP/VABP trials using a Quality by Design approach. CTTI recommendations focus on 4 key areas to improve HABP/VABP trials: informed consent processes/practices, protocol design, choice of an institutional review board (IRB), and trial outcomes. Informed consent processes should include legally authorized representatives. Protocol design decisions should focus on eligibility criteria, prestudy antibacterial therapy considerations, use of new diagnostics, and sample size. CTTI recommends that sponsors use a central IRB and discuss trial endpoints with regulators, including defining a clinical failure and evaluating the impact of concomitant antibacterial drugs. Streamlining HABP/VABP trials by addressing key protocol elements can improve trial startup and patient recruitment/retention, reduce trial complexity and costs, and ensure patient safety while advancing antibacterial drug development. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Involving American Indians and medically underserved rural populations in cancer clinical trials.

PubMed

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Fox Dunn, Emily; Patnaik, Asha

2009-12-01

To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7-11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69-75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4-7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3-16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5-17%). Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group.

Involving American Indians and medically underserved rural populations in cancer clinical trials

PubMed Central

Guadagnolo, B Ashleigh; Petereit, Daniel G; Helbig, Petra; Koop, David; Kussman, Patricia; Dunn, Emily Fox; Patnaik, Asha

2010-01-01

Purpose To assess cancer clinical trial recruitment and reasons for nonaccrual among a rural, medically underserved population served by a community-based cancer care center. Methods We prospectively tracked clinical trial enrollment incidence among all new patients presenting at the Rapid City Regional Cancer Care Institute. Evaluating physicians completed questionnaires for each patient regarding clinical trial enrollment status and primary reasons for nonenrollment. Patients who identified as American Indian were referred to a program where patients were assisted in navigating the medical system by trained, culturally competent staff. Results Between September 2006 and January 2008, 891 new cancer patients were evaluated. Seventy-eight patients (9%; 95% confidence intervals, 7–11%) were enrolled on a clinical treatment trial. For 73% (95% confidence intervals, 69–75%) of patients (646 of 891) lack of relevant protocol availability or protocol inclusion criteria restrictiveness was the reason for nonenrollment. Only 45 (5%; 95% confidence intervals, 4–7%) patients refused enrollment on a trial. Of the 78 enrolled on a trial, 6 (8%; 95% confidence intervals, 3–16%) were American Indian. Three additional American Indian patients were enrolled under a nontreatment cancer control trial, bringing the total percentage enrolled of the 94 American Indians who presented to the clinic to 10% (95% confidence intervals, 5–17%). Limitations Eligibility rates were unable to be calculated and cross validation of the number in the cohort via registries or ICD-9 codes was not performed. Conclusion Clinical trial participation in this medically underserved population was low overall, but approximately 3-fold higher than reported national accrual rates. Lack of availability of protocols for common cancer sites as well as stringent protocol inclusion criteria were the primary obstacles to clinical trial enrollment. Targeted interventions using a Patient Navigation program were used to engage AI patients and may have resulted in higher clinical trial enrollment among this racial/ethnic group. PMID:19933720

Features Associated with Successful Recruitment of Diverse Patients onto Cancer Clinical Trials: Report from the American College of Surgeons Oncology Group

PubMed Central

Diehl, Kathleen M.; Green, Erin M.; Weinberg, Armin; Frederick, Wayne A.; Holmes, Dennis R.; Green, Bettye; Morris, Arden; Kuerer, Henry M.; Beltran, Robert A.; Mendez, Jane; Gines, Venus; Ota, David M.; Nelson, Heidi; Newman, Lisa A.

2018-01-01

Background The clinical trials mechanism of standardized treatment and follow-up for cancer patients with similar stages and patterns of disease is the most powerful approach available for evaluating the efficacy of novel therapies, and clinical trial participation should protect against delivery of care variations associated with racial/ethnic identity and/or socioeconomic status. Unfortunately, disparities in clinical trial accrual persist, with African Americans (AA) and Hispanic/Latino Americans (HA) underrepresented in most studies. Study Design We evaluated the accrual patterns for ten clinical trials conducted by the American College of Surgeons Oncology Group (ACOSOG) 1999–2009, and analyzed results by race/ethnicity as well as study design. Results Eight of ten protocols were successful in recruiting AA and/or HA participants; three of four randomized trials were successful. Features that were present among all of the successfully-recruiting protocols were: (i) studies designed to recruit patients with regional or advanced-stage disease (2/2 protocols); and (ii) studies that involved some investigational systemic therapy (3/3 protocols). Discussion AA and HA cancer patients can be successfully accrued onto randomized clinical trials, but study design affects recruitment patterns. Increased socioeconomic disadvantages observed within minority-ethnicity communities results in barriers to screening and more advanced cancer stage distribution. Improving cancer early detection is critical in the effort to eliminate outcome disparities but existing differences in disease burden results in diminished eligibility for early-stage cancer clinical trials among minority-ethnicity patients. PMID:21681382

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

Fusaro, Vincent A.; Patil, Prasad; Chi, Chih-Lin; Contant, Charles F.; Tonellato, Peter J.

2013-01-01

Background Pharmacogenetics in warfarin clinical trials have failed to show a significant benefit compared to standard clinical therapy. This study demonstrates a computational framework to systematically evaluate pre-clinical trial design of target population, pharmacogenetic algorithms, and dosing protocols to optimize primary outcomes. Methods and Results We programmatically created an end-to-end framework that systematically evaluates warfarin clinical trial designs. The framework includes options to create a patient population, multiple dosing strategies including genetic-based and non-genetic clinical-based, multiple dose adjustment protocols, pharmacokinetic/pharmacodynamics (PK/PD) modeling and international normalization ratio (INR) prediction, as well as various types of outcome measures. We validated the framework by conducting 1,000 simulations of the CoumaGen clinical trial primary endpoints. The simulation predicted a mean time in therapeutic range (TTR) of 70.6% and 72.2% (P = 0.47) in the standard and pharmacogenetic arms, respectively. Then, we evaluated another dosing protocol under the same original conditions and found a significant difference in TTR between the pharmacogenetic and standard arm (78.8% vs. 73.8%; P = 0.0065), respectively. Conclusions We demonstrate that this simulation framework is useful in the pre-clinical assessment phase to study and evaluate design options and provide evidence to optimize the clinical trial for patient efficacy and reduced risk. PMID:23261867

The citation of relevant systematic reviews and randomised trials in published reports of trial protocols.

PubMed

Pandis, Nikolaos; Fleming, Padhraig S; Koletsi, Despina; Hopewell, Sally

2016-12-07

It is important that planned randomised trials are justified and placed in the context of the available evidence. The SPIRIT guidelines for reporting clinical trial protocols recommend that a recent and relevant systematic review should be included. The aim of this study was to assess the use of the existing evidence in order to justify trial conduct. Protocols of randomised trials published over a 1-month period (December 2015) indexed in PubMed were obtained. Data on trial characteristics relating to location, design, funding, conflict of interest and type of evidence included for trial justification was extracted in duplicate and independently by two investigators. The frequency of citation of previous research including relevant systematic reviews and randomised trials was assessed. Overall, 101 protocols for RCTs were identified. Most proposed trials were parallel-group (n = 74; 73.3%). Reference to an earlier systematic review with additional randomised trials was found in 9.9% (n = 10) of protocols and without additional trials in 30.7% (n = 31), while reference was made to randomised trials in isolation in 21.8% (n = 22). Explicit justification for the proposed randomised trial on the basis of being the first to address the research question was made in 17.8% (n = 18) of protocols. A randomised controlled trial was not cited in 10.9% (95% CI: 5.6, 18.7) (n = 11), while in 8.9% (95% CI: 4.2, 16.2) (n = 9) of the protocols a systematic review was cited but did not inform trial design. A relatively high percentage of protocols of randomised trials involves prior citation of randomised trials, systematic reviews or both. However, improvements are required to ensure that it is explicit that clinical trials are justified and shaped by contemporary best evidence.

A quality analysis of clinical anaesthesia study protocols from the Chinese clinical trials registry according to the SPIRIT statement

PubMed Central

Yang, Lei; Chen, Shouming; Yang, Di; Li, Jiajin; Wu, Taixiang; Zuo, Yunxia

2018-01-01

Objective To learn about the overall quality of clinical anaesthesia study protocols from the Chinese Clinical Trials Registry and to discuss the way to improve study protocol quality. Methods We defined completeness of each sub-item in SPIRIT as N/A (not applicable) or with a score of 0, 1, or 2. For each protocol, we calculated the proportion of adequately reported items (score = 2 and N/A) and unreported items (score = 0). Protocol quality was determined according to the proportion of reported items, with values >50% indicating high quality. Protocol quality was determined according to the proportion of reported items. For each sub-item in SPIRIT, we calculated the adequately reported rate (percentage of all protocols with score 2 and NA on one sub-item) as well as the unreported rate (percentage of all protocols with score 0 on one sub-item). Results Total 126 study protocols were available for assessment. Among these, 88.1% were assessed as being of low quality. By comparison, the percentage of low-quality protocols was 88.9% after the publication of the SPIRIT statement. Among the 51 SPIRIT sub-items, 18 sub-items had an unreported rate above 90% while 16 had a higher adequately reported rate than an unreported rate. Conclusions The overall quality of clinical anaesthesia study protocols registered in the ChiCTR was poor. A mandatory protocol upload and self-check based on the SPIRIT statement during the trial registration process may improve protocol quality in the future. PMID:29872509

Rationale, timeline, study design, and protocol overview of the therapeutic hypothermia after pediatric cardiac arrest trials.

PubMed

Moler, Frank W; Silverstein, Faye S; Meert, Kathleen L; Clark, Amy E; Holubkov, Richard; Browning, Brittan; Slomine, Beth S; Christensen, James R; Dean, J Michael

2013-09-01

To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Multicenter randomized controlled trials. Pediatric intensive care and cardiac ICUs in the United States and Canada. Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Therapeutic hypothermia or therapeutic normothermia. From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials.

A data grid for imaging-based clinical trials

NASA Astrophysics Data System (ADS)

Zhou, Zheng; Chao, Sander S.; Lee, Jasper; Liu, Brent; Documet, Jorge; Huang, H. K.

2007-03-01

Clinical trials play a crucial role in testing new drugs or devices in modern medicine. Medical imaging has also become an important tool in clinical trials because images provide a unique and fast diagnosis with visual observation and quantitative assessment. A typical imaging-based clinical trial consists of: 1) A well-defined rigorous clinical trial protocol, 2) a radiology core that has a quality control mechanism, a biostatistics component, and a server for storing and distributing data and analysis results; and 3) many field sites that generate and send image studies to the radiology core. As the number of clinical trials increases, it becomes a challenge for a radiology core servicing multiple trials to have a server robust enough to administrate and quickly distribute information to participating radiologists/clinicians worldwide. The Data Grid can satisfy the aforementioned requirements of imaging based clinical trials. In this paper, we present a Data Grid architecture for imaging-based clinical trials. A Data Grid prototype has been implemented in the Image Processing and Informatics (IPI) Laboratory at the University of Southern California to test and evaluate performance in storing trial images and analysis results for a clinical trial. The implementation methodology and evaluation protocol of the Data Grid are presented.

Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective, Randomized, Controlled Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Logan, Jennifer K.; Tang, Chad; Liao, Zhongxing

Purpose: Challenges can arise when attempting to maximize patient enrollment in clinical trials. There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to clinical trial enrollment, particularly the influence of timing, in context of three prospective, randomized oncology trials where one arm was considered more aggressive than the other. Methods and Materials: From June 2011 to March 2015, patients who were enrolled on 3 prospective institutional protocols (an oligometastatic non-small cell lung cancer [NSCLC] trial and 2 proton vs intensity modulated radiation therapy trials inmore » NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher's exact test, Student's t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results: A total of 309 eligible patients were approached about trial enrollment. The enrollment success rate during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligometastatic protocol: 5 vs 3 appointments [P<.001]; NSCLC protocol: 4 vs 3 appointments [P=.0018]; esophageal protocol: 3 vs 2 appointments [P=.0086]). No other factors or patient characteristics significantly affected enrollment success rate. Conclusion: Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success and may help overcome accrual barriers without compromising trial design.« less

Bridging the gap in complementary and alternative medicine research: manualization as a means of promoting standardization and flexibility of treatment in clinical trials of acupuncture.

PubMed

Schnyer, Rosa N; Allen, John J B

2002-10-01

An important methodological challenge encountered in acupuncture clinical research involves the design of treatment protocols that help ensure standardization and replicability while allowing for the necessary flexibility to tailor treatments to each individual. Manualization of protocols used in clinical trials of acupuncture and other traditionally-based complementary and alternative medicine (CAM) systems facilitates the systematic delivery of replicable and standardized, yet individually-tailored treatments. To facilitate high-quality CAM acupuncture research by outlining a method for the systematic design and implementation of protocols used in CAM clinical trials based on the concept of treatment manualization. A series of treatment manuals was developed to systematically articulate the Chinese medical theoretical and clinical framework for a given Western-defined illness, to increase the quality and consistency of treatment, and to standardize the technical aspects of the protocol. In all, three manuals were developed for National Institutes of Health (NIH)-funded clinical trials of acupuncture for depression, spasticity in cerebral palsy, and repetitive stress injury. In Part I, the rationale underlying these manuals and the challenges encountered in creating them are discussed, and qualitative assessments of their utility are provided. In Part II, a methodology to develop treatment manuals for use in clinical trials is detailed, and examples are given. A treatment manual provides a precise way to train and supervise practitioners, enable evaluation of conformity and competence, facilitate the training process, and increase the ability to identify the active therapeutic ingredients in clinical trials of acupuncture.

Blockchain protocols in clinical trials: Transparency and traceability of consent.

PubMed

Benchoufi, Mehdi; Porcher, Raphael; Ravaud, Philippe

2017-01-01

Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a consistent step toward reproducibility.

Blockchain protocols in clinical trials: Transparency and traceability of consent

PubMed Central

Benchoufi, Mehdi; Porcher, Raphael; Ravaud, Philippe

2018-01-01

Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a consistent step toward reproducibility. PMID:29167732

Rationale, Timeline, Study Design, and Protocol Overview of the Therapeutic Hypothermia After Pediatric Cardiac Arrest Trials

PubMed Central

Moler, Frank W.; Silverstein, Faye S.; Meert, Kathleen L.; Clark, Amy E.; Holubkov, Richard; Browning, Brittan; Slomine, Beth S.; Christensen, James R.; Dean, Michael

2014-01-01

Objective To describe the rationale, timeline, study design, and protocol overview of the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Design Multicenter randomized controlled trials. Setting Pediatric intensive care and cardiac ICUs in the United States and Canada. Patients Children from 48 hours to 18 years old, who have return of circulation after cardiac arrest, who meet trial eligibility criteria, and whose guardians provide written consent. Interventions Therapeutic hypothermia or therapeutic normothermia. Measurements and Main Results From concept inception in 2002 until trial initiation in 2009, 7 years were required to plan and operationalize the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Two National Institute of Child Health and Human Development clinical trial planning grants (R21 and R34) supported feasibility assessment and protocol development. Two clinical research networks, Pediatric Emergency Care Applied Research Network and Collaborative Pediatric Critical Care Research Network, provided infrastructure resources. Two National Heart Lung Blood Institute U01 awards provided funding to conduct separate trials of in-hospital and out-of-hospital cardiac arrest. A pilot vanguard phase that included half the clinical sites began on March 9, 2009, and this was followed by full trial funding through 2015. Conclusions Over a decade will have been required to plan, design, operationalize, and conduct the Therapeutic Hypothermia after Pediatric Cardiac Arrest trials. Details described in this report, such as participation of clinical research networks and clinical trial planning grants utilization, may be of utility for individuals who are planning investigator-initiated, federally supported clinical trials. PMID:23842585

Protecting intellectual property associated with Canadian academic clinical trials - approaches and impact

PubMed Central

2012-01-01

Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation. The ‘open access’ approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism. The ‘restricted access’ approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who ‘needs to know’ about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial. It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results. PMID:23270486

Protecting intellectual property associated with Canadian academic clinical trials--approaches and impact.

PubMed

Ross, Sue; Magee, Laura; Walker, Mark; Wood, Stephen

2012-12-27

Intellectual property is associated with the creative work needed to design clinical trials. Two approaches have developed to protect the intellectual property associated with multicentre trial protocols prior to site initiation. The 'open access' approach involves publishing the protocol, permitting easy access to the complete protocol. The main advantages of the open access approach are that the protocol is freely available to all stakeholders, permitting them to discuss the protocol widely with colleagues, assess the quality and rigour of the protocol, determine the feasibility of conducting the trial at their centre, and after trial completion, to evaluate the reported findings based on a full understanding of the protocol. The main potential disadvantage of this approach is the potential for plagiarism; however if that occurred, it should be easy to identify because of the open access to the original trial protocol, as well as ensure that appropriate sanctions are used to deal with plagiarism. The 'restricted access' approach involves the use of non-disclosure agreements, legal documents that must be signed between the trial lead centre and collaborative sites. Potential sites must guarantee they will not disclose any details of the study before they are permitted to access the protocol. The main advantages of the restricted access approach are for the lead institution and nominated principal investigator, who protect their intellectual property associated with the trial. The main disadvantages are that ownership of the protocol and intellectual property is assigned to the lead institution; defining who 'needs to know' about the study protocol is difficult; and the use of non-disclosure agreements involves review by lawyers and institutional representatives at each site before access is permitted to the protocol, significantly delaying study implementation and adding substantial indirect costs to research institutes. This extra step may discourage sites from joining a trial. It is possible that the restricted access approach may contribute to the failure of well-designed trials without any significant benefit in protecting intellectual property. Funding agencies should formalize rules around open versus restricted access to the study protocol just as they have around open access to results.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

PubMed

Kasenda, Benjamin; von Elm, Erik; You, John J; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Ebrahim, Shanil; Schandelmaier, Stefan; Sun, Xin; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2016-06-01

Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol.

An Analysis of Factors Affecting Successful Clinical Trial Enrollment in the Context of Three Prospective Randomized Control Trials

PubMed Central

Logan, Jennifer K; Tang, Chad; Liao, Zhongxing; Lee, J. Jack; Heymach, John V.; Swisher, Stephen G.; Welsh, James W.; Zhang, Jianjun; Lin, Steven H.; Gomez, Daniel R.

2018-01-01

Purpose Effective clinical trial enrollment can be difficult in a protocol designs that contain one treatment arm that is perceived as being more “aggressive” or “favorable.” There have been limited studies focusing on the barriers to enrollment and the efficacy of alternative study design to improve accrual. We analyzed barriers to enrollment, particularly the influence of timing, in context of three prospective randomized oncology trials where one arm was considered more aggressive. Methods and materials From June 2011 to March 2015, patients who were enrolled on three prospective institutional protocols (an oligometastatic non-small cell lung cancer (NSCLC) trial, and two proton vs. intensity-modulated radiation therapy (IMRT) trials in NSCLC and esophageal cancer) were screened for protocol eligibility. Eligible candidates were approached about trial participation, and patient characteristics (age, sex, T/N categorization) were recorded along with details surrounding trial presentation (appointment number). Fisher’s exact test, Student’s t tests, and multivariate analysis were performed to assess differences between enrolled and refusal patients. Results 309 eligible patients were approached about trial enrollment. The enrollment success rate (ESR) during this time span was 52% (n=160 patients). Enrolled patients were more likely to be presented trial information at an earlier appointment (oligomet protocol: 5 vs. 3 appointments (P<0.001), NSCLC protocol: 4 vs. 3 appointments (P = 0.0018), esophageal protocol: 3 vs. 2 appointments (P = 0.0086No other factors or patient characteristics significantly affected ESR. Conclusion Improvement in enrollment rates for randomized control trials is possible, even in difficult accrual settings. Earlier presentation of trial information to patients is the most influential factor for success, and may help overcome accrual barriers without compromising trial design. PMID:28244413

Lung-MAP Launches: First Precision Medicine Trial From National Clinical Trials Network

Cancer.gov

A unique public-private collaboration today announced the initiation of the Lung Cancer Master Protocol (Lung-MAP) trial, a multi-drug, multi-arm, biomarker-driven clinical trial for patients with advanced squamous cell lung cancer. Squamous cell carcinom

The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures.

PubMed

Wright, Melanie C; Taekman, Jeffrey M; Barber, Linda; Hobbs, Gene; Newman, Mark F; Stafford-Smith, Mark

2005-12-01

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

PubMed

Zhang, Sheng; Liang, Fei; Li, Wenfeng

2017-11-01

The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

SU-F-P-13: NRG Oncology Medical Physics Manpower Survey Quantifying Support Demands for Multi Institutional Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monroe, J; Case Western Reserve University; Boparai, K

Purpose: A survey was taken by NRG Oncology to assess Full Time Equivalent (FTE) contributions to multi institutional clinical trials by medical physicists.No current quantification of physicists’ efforts in FTE units associated with clinical trials is available. The complexity of multi-institutional trials increases with new technologies and techniques. Proper staffing may directly impact the quality of trial data and outcomes. The demands on physics time supporting clinical trials needs to be assessed. Methods: The NRG Oncology Medical Physicist Subcommittee created a sixteen question survey to obtain this FTE data. IROC Houston distributed the survey to their list of 1802 contactmore » physicists. Results: After three weeks, 363 responded (20.1% response). 187 (51.5%) institutions reporting external beam participation were processed. There was a wide range in number of protocols active and supported at each institution. Of the 187 clinics, 134 (71.7%) participate in 0 to 10 trials, 28 (15%) in 11 to 20 trials, 10 (5.3%) in 21 to 30 trials, 9 (4.8%) had 40 to 75 trials. On average, physicist spent 2.7 hours (SD: 6.0) per week supervising or interacting with clinical trial staff. 1.25 hours (SD: 3.37), 1.83 hours (SD: 4.13), and 0.64 hours(SD: 1.13) per week were spent on patient simulation, reviewing treatment plans, and maintaining a DICOM server, respectively. For all protocol credentialing activities, physicist spent an average of 37.05 hours (SD: 96.94) yearly. To support dosimetrists, clinicians, and therapists, physicist spend on average 2.07 hours (SD: 3.52) per week just reading protocols. Physicist attended clinical trial meetings for on average 1.13 hours (SD: 1.85) per month. Conclusion: Responding physicists spend a nontrivial amount of time: 8.8 hours per week (0.22 FTE) supporting, on average, 9 active multi-institutional clinical trials.« less

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases.  CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides comprehensive clinical and administrative support to the National Cancer Institute’s Center for Cancer Research’s (CCR), Office of Regulatory Affairs for protocol development review, regulatory review, and the implementation process as well as oversees medical writing/editing, regulatory/ compliance, and protocol coordination/navigation and administration. KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL The Protocol Coordinator II: Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials Provides deployment of clinical support services for clinical research Streamlines protocol development timeline Provides data and document collection and compilation for regulatory filing with the FDA and other regulatory authorities Provides administrative coordination and general logistical support for regulatory activities Ensures the provision of training for investigators and associate staff to reinforce and enhance a GCP culture Provides quality assurance and quality control oversight Performs regulatory review of clinical protocols, informed consent and other clinical documents Tracks and facilitates a portfolio of protocols through each process step (IRB, RAC, DSMB, Office of Protocol Services) Assists clinical investigators in preparing clinical research protocols, including writing and formatting protocol documents and consent forms Prepares protocol packages for review and ensures that protocol packages include all of the required material and comply with CCR, NCI and NIH policies Collaborates with investigators to resolve any protocol/data issues Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI Institutional Review Board (IRB) and the clinical trial sponsor or the FDA Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events Attends and prepares minutes for the Branch Protocol Review Committees For protocols that are performed with other research centers: contacts coordinators at other centers to obtain review committee approvals at these centers, maintains records of these approvals at the outside centers in the protocol files, and sends protocol amendments and other reports to the participating centers Maintains a schedule of all review committee submission deadline dates and meeting dates Assists clinical investigators in understanding and complying with the entire review process Works closely with the NCI Protocol Review Office in establishing and maintaining a paperless automated document management and tracking system for NCI protocols Converts protocols from Word format to PDF with bookmarks Maintains the PDF version of the most current approved version of each active clinical protocol on a central server    This position has the option to be located in Frederick or Rockville, Maryland.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides comprehensive clinical and administrative support to the National Cancer Institute’s Center for Cancer Research’s (CCR) Protocol Support Office (PSO) for protocol development review, regulatory review, and the implementation process as well as oversees medical writing/editing, regulatory/ compliance, and protocol coordination/navigation and administration. KEY ROLES/RESPONSIBILITIES The Protocol Coordinator III: Provides programmatic and logistical support for the operations of clinical research for Phase I and Phase II clinical trials. Provides deployment of clinical support services for clinical research. Streamlines the protocol development timeline. Provides data and documents collection and compilation for regulatory filing with the U.S. Food and Drug Administration (FDA) and other regulatory authorities.. Provides technical review and report preparation. Provides administrative coordination and general logistical support for regulatory activities. Ensures the provision of training for investigators and associate staff to reinforce and enhance a Good Clinical Practices (GCP) culture. Oversees quality assurance and quality control, performs regulatory review of clinical protocols, informed consent and other clinical documents. Tracks and facilitates a portfolio of protocols through each process step (Institutional Review Board [IRB], Regulatory Affairs Compliance [RAC], Data Safety Monitoring Board [DSMB], Office of Protocol Services). Assists clinical investigators in preparing clinical research protocols, including writing and formatting consent forms. Prepares protocol packages for review and ensures that protocol packages include all of the required material and comply with CCR, NCI and NIH policies. Collaborates with investigators to resolve any protocol/data issues. Coordinates submission of protocols for scientific and ethical review by the Branch scientific review committees, the NCI IRB, and the clinical trial sponsor or the FDA. Monitors the review process and maintains detailed, complete and accurate records for each protocol of the approvals at the various stages of the review process, including new protocol submissions, amendments to protocols, and continuing reviews, as well as other submissions such as adverse events. Attends and prepares minutes for the Branch Protocol Review Committees. Contacts coordinators at other centers for protocols that are performed there to obtain review committee approvals at those centers, maintains records of these approvals and sends protocol amendments and other reports to the participating centers. Maintains a schedule of all review committee submission deadline dates and meeting dates. Assists clinical investigators in understanding and complying with the entire review process. Works closely with the NCI Protocol Review Office in establishing and maintaining a paperless automated document and tracking system for NCI protocols. Converts protocols from Word format to .pdf with bookmarks. Maintains the .pdf version of the most current approved version of each active clinical protocol on a central server. This position is located in Rockville, Maryland.

Ghost Authorship in Industry-Initiated Randomised Trials

PubMed Central

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2007-01-01

Background Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. Methods and Findings We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994–1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%–87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%–98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Conclusions Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available. PMID:17227134

Ghost authorship in industry-initiated randomised trials.

PubMed

Gøtzsche, Peter C; Hróbjartsson, Asbjørn; Johansen, Helle Krogh; Haahr, Mette T; Altman, Douglas G; Chan, An-Wen

2007-01-01

Ghost authorship, the failure to name, as an author, an individual who has made substantial contributions to an article, may result in lack of accountability. The prevalence and nature of ghost authorship in industry-initiated randomised trials is not known. We conducted a cohort study comparing protocols and corresponding publications for industry-initiated trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg in 1994-1995. We defined ghost authorship as present if individuals who wrote the trial protocol, performed the statistical analyses, or wrote the manuscript, were not listed as authors of the publication, or as members of a study group or writing committee, or in an acknowledgment. We identified 44 industry-initiated trials. We did not find any trial protocol or publication that stated explicitly that the clinical study report or the manuscript was to be written or was written by the clinical investigators, and none of the protocols stated that clinical investigators were to be involved with data analysis. We found evidence of ghost authorship for 33 trials (75%; 95% confidence interval 60%-87%). The prevalence of ghost authorship was increased to 91% (40 of 44 articles; 95% confidence interval 78%-98%) when we included cases where a person qualifying for authorship was acknowledged rather than appearing as an author. In 31 trials, the ghost authors we identified were statisticians. It is likely that we have overlooked some ghost authors, as we had very limited information to identify the possible omission of other individuals who would have qualified as authors. Ghost authorship in industry-initiated trials is very common. Its prevalence could be considerably reduced, and transparency improved, if existing guidelines were followed, and if protocols were publicly available.

Accelerating Pediatric Cancer Drug Development: Challenges and Opportunities for Pediatric Master Protocols.

PubMed

Khan, Tahira; Stewart, Mark; Blackman, Samuel; Rousseau, Raphaël; Donoghue, Martha; Cohen, Kenneth; Seibel, Nita; Fleury, Mark; Benettaib, Bouchra; Malik, Raleigh; Vassal, Gilles; Reaman, Gregory

2018-01-01

Although outcomes for children with cancer have significantly improved over the past 40 years, there has been little progress in the treatment of some pediatric cancers, particularly when advanced. Additionally, clinical trial options and availability are often insufficient. Improved genomic and immunologic understanding of pediatric cancers, combined with innovative clinical trial designs, may provide an enhanced opportunity to study childhood cancers. Master protocols, which incorporate the use of precision medicine approaches, coupled with the ability to quickly assess the safety and effectiveness of new therapies, have the potential to accelerate early-phase clinical testing of novel therapeutics and which may result in more rapid approval of new drugs for children with cancer. Designing and conducting master protocols for children requires addressing similar principles and requirements as traditional adult oncology trials, but there are also unique considerations for master protocols conducted in children with cancer. The purpose of this paper is to define the key challenges and opportunities associated with this approach in order to ensure that master protocols can be adapted to benefit children and adolescents and ensure that adequate data are captured to advance, in parallel, the clinical development of investigational agents for children with cancer.

Informed Consent to Study Purpose in Randomized Clinical Trials of Antibiotics, 1991 Through 2011.

PubMed

Doshi, Peter; Hur, Peter; Jones, Mark; Albarmawi, Husam; Jefferson, Tom; Morgan, Daniel J; Spears, Patricia A; Powers, John H

2017-10-01

Potential research participants may assume that randomized trials comparing new interventions with older interventions always hypothesize greater efficacy for the new intervention, as in superiority trials. However, antibiotic trials frequently use "noninferiority" hypotheses allowing a degree of inferior efficacy deemed "clinically acceptable" compared with an older effective drug, in exchange for nonefficacy benefits (eg, decreased adverse effects). Considering these different benefit-harm trade-offs, proper informed consent necessitates supplying different information on the purposes of superiority and noninferiority trials. To determine the degree to which the study purpose is explained to potential participants in randomized clinical trials of antibiotics and the degree to which study protocols justify their selection of noninferiority hypotheses and amount of "clinically acceptable" inferiority. Cross-sectional analysis of study protocols, statistical analysis plans (SAPs), and informed consent forms (ICFs) from clinical study reports submitted to the European Medicines Agency. The ICFs were read by both methodologists and patient investigators. Protocols and SAPs were used as the reference standard to determine prespecified primary hypothesis and record rationale for selection of noninferiority hypotheses and noninferiority margins. This information was cross-referenced against ICFs to determine whether ICFs explained the study purpose. We obtained trial documents from 78 randomized trials with prespecified efficacy hypotheses (6 superiority, 72 noninferiority) for 17 antibiotics conducted between 1991 and 2011 that enrolled 39 407 patients. Fifty were included in the ICF analysis. All ICFs contained sections describing study purpose; however, none consistently conveyed study hypothesis to both methodologists and patient investigators. Methodologists found that 1 of 50 conveyed a study purpose. Patient investigators found that 11 of 50 conveyed a study purpose, 7 accurately and 4 inaccurately compared with the reference standard. Seventy-one of 72 noninferiority trial protocols or SAPs provided no rationale for selection of noninferiority hypothesis. None provided a clinical rationale for the chosen amount of decreased efficacy. Patients were not accurately informed of study purpose, which raises questions regarding the ethics of informed consent in antibiotic trials. Noninferiority and superiority trials entail different benefit-harm trade-offs that must be conveyed for ethical informed consent.

Trends in the number and the quality of trial protocols involving children submitted to a French Institutional Review Board.

PubMed

Gautier, Isabelle; Janiaud, Perrine; Rollet, Nelly; André, Nicolas; Tsimaratos, Michel; Cornu, Catherine; Malik, Salma; Gentile, Stéphanie; Kassaï, Behrouz

2017-08-23

There is a great need for high quality clinical research for children. The European Pediatric Regulation aimed to improve the quality of clinical trials in order to increase the availability of treatments for children. The main purpose of this study was to assess the evolution of both the number and the quality of pediatric trial protocols that were submitted to a French Institutional Review Board (IRB00009118) before and after the initiation of the EU Pediatric Regulation. All protocols submitted to the IRB00009118 between 2003 and 2014 and conducting research on subjects under eighteen years of age were eligible. The quality of randomized clinical trials was assessed according to the guidelines developed by the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Network and ranked using the Jadad score. Out of 622 protocols submitted to the Institutional Review Board (IRB), 21% (133/622) included children. Among these 133 pediatric protocols, the number of submitted pediatric protocols doubled between the two studied periods. From 2003 to 2008, 47 protocols including 21 institutionally sponsored were submitted to the IRB and from 2009 until 2014, 86 protocols including 48 institutionally sponsored were submitted. No significant trend was observed on the quality of RCTs. The overall median score of RCTs on the Jadad scale was high (3.5), 70.0% of protocols had a Jadad score ≥ 3, and 30.0% had a score < 3. Following the EU Pediatric Regulation, the number of pediatric protocols submitted to the IRB00009118 tends to increase, but no change was noticed regarding their quality.

Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials

PubMed Central

Kasenda, Benjamin; von Elm, Erik; You, John J.; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J.; Stegert, Mihaela; Olu, Kelechi K.; Tikkinen, Kari A. O.; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M.; Mertz, Dominik; Akl, Elie A.; Bassler, Dirk; Busse, Jason W.; Nordmann, Alain; Gloy, Viktoria; Ebrahim, Shanil; Schandelmaier, Stefan; Sun, Xin; Vandvik, Per O.; Johnston, Bradley C.; Walter, Martin A.; Burnand, Bernard; Hemkens, Lars G.; Bucher, Heiner C.; Guyatt, Gordon H.; Briel, Matthias

2016-01-01

Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner’s right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors’ independence are common. Journal articles seldom report on publication agreements, and, if they do, statements can be discrepant with the trial protocol. PMID:27352244

From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

PubMed Central

Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

2015-01-01

Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

Evaluating and improving recruitment and retention in an mHealth clinical trial: an example of iterating methods during a trial.

PubMed

Pfammatter, Angela Fidler; Mitsos, Alexa; Wang, Shirlene; Hood, Susan Hammett; Spring, Bonnie

2017-01-01

Recruitment and retention strategy investigations in mHealth clinical trials are rare. Technology presents an opportunity to intensely and remotely evaluate recruitment, use of mobile apps, and retention, leading to new insights for continuous improvement of mHealth trials. The objective of this paper is to present a case study in which a trial evaluated and changed strategies during a clinical trial to improve recruitment, adherence to study protocols, and retention in the mHealth trial. In Fall 2015, the NUYou trial enrolled 150 college freshmen in an mHealth protocol. Three months after study initiation, NUYou struggled to meet recruitment goals and maintain anticipated usage levels of the study smartphone application. Two sets of data were collected to improve recruitment and retention: a survey about recruitment was sent to the target population and surveys regarding usability of the app was sent to the study sample. Survey results informed improvements in recruitment strategies, the study retention protocol, and the smartphone application. Survey results revealed several insights including misunderstanding components of the trial by potential participants, low perceived usefulness of the app, and little recall or impact of the incentive structure. After implementation of user-centered improvements, the second cohort of NUYou recruitment in the fall of 2016 produced an equal sample size in 4 weeks less time. Winter quarter of 2016 compared to 2017 demonstrated an improvement in retention via app use and completion of weekly in-app surveys. Recruitment and retention in clinical trials continues to be a critical challenge and mHealth trials may present both unique challenges and opportunities. To our knowledge, this is the first study to describe a systematic evaluation followed by changes and further evaluation to recruitment, use of the mHealth application, adherence to study protocol, and retention during an mHealth clinical trial. Future work should adopt and explicitly study these processes to optimize both enrollment and retention in these types of trials to preserve validity and reliability of research results.

Post-trial period surveillance for randomised controlled cardiovascular studies: submitted protocols, consent forms and the role of the ethics board.

PubMed

Zia, Mohammad I; Heslegrave, Ronald; Newton, Gary E

2011-12-01

The post-trial period is the time period after the end of study drug administration. It is unclear whether post-trial arrangements for patient surveillance are routinely included in study protocols and consents, and whether research ethics boards (REB) consider the post-trial period. The objective was to determine whether trial protocols and consent forms reviewed by the REB describe procedures for post-trial period surveillance. An observational study of protocols of randomised trials of chronic therapies for cardiac conditions, approved by the REB of two academic institutions affiliated with the University of Toronto in Canada (University Health Network and Mount Sinai Hospital) from 1995 to 2007. Plans for patient surveillance in the post-trial period described in the protocol or in the consent form before and after REB approval were recorded. 42 studies were identified including 18 heart failure and 15 coronary artery disease trials. Only four studies planned a clinical visit after trial termination, and an additional three planned a telephone contact after trial completion. Five trials submitted consent forms to the REB with a discussion of the post-trial period. The majority of protocols and consent forms did not discuss plans for post-trial period surveillance. The post-trial period and the REB approval process could be improved by systematic follow-up being described in the protocol and consent form. The small number of trial protocols evaluated in the study may impair the degree to which the results can be generalised.

Guidelines for randomized clinical trial protocol content: a systematic review

PubMed Central

2012-01-01

Background All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. Methods We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Results Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Conclusions Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed. PMID:23006870

Guidelines for randomized clinical trial protocol content: a systematic review.

PubMed

Tetzlaff, Jennifer M; Chan, An-Wen; Kitchen, Jessica; Sampson, Margaret; Tricco, Andrea C; Moher, David

2012-09-24

All randomized clinical trials (RCTs) require a protocol; however, numerous studies have highlighted protocol deficiencies. Reporting guidelines may improve the content of research reports and, if developed using robust methods, may increase the utility of reports to stakeholders. The objective of this study was to systematically identify and review RCT protocol guidelines, to assess their characteristics and methods of development, and to compare recommendations. We conducted a systematic review of indexed literature (MEDLINE, EMBASE and the Cochrane Methodology Register from inception to September 2010; reference lists; related article features; forward citation searching) and a targeted search of supplementary sources, including a survey of major trial funding agencies in six countries. Records were eligible if they described a content guideline in English or French relevant to RCT protocols. Guidelines were excluded if they specified content for protocols for trials of specific procedures or conditions or were intended to assess trial quality. We extracted guideline characteristics and methods. Content was mapped for a subset of guidelines that described development methods or had institutional endorsement. Forty guidelines published in journals, books and institutional reports were included in the review; seven were specific to RCT protocols. Only eight (20%) described development methods which included informal consensus methods, pilot testing and formal validation; no guideline described all of these methods. No guideline described formal consensus methods or a systematic retrieval of empirical evidence to inform its development. The guidelines included a median of 23 concepts per guideline (interquartile range (IQR) = 14 to 34; range = 7 to 109). Among the subset of guidelines (n = 23) for which content was mapped, approximately 380 concepts were explicitly addressed (median concepts per guideline IQR = 31 (24,80); range = 16 to 150); most concepts were addressed in a minority of guidelines. Existing guidelines for RCT protocol content varied substantially in their recommendations. Few reports described the methods of guideline development, limiting comparisons of guideline validity. Given the importance of protocols to diverse stakeholders, we believe a systematically developed, evidence-informed guideline for clinical trial protocols is needed.

Oncosurgical Management of Liver Limited Stage IV Colorectal Cancer: Preliminary Data and Protocol for a Randomized Controlled Trial.

PubMed

Sutton, Paul; Vimalachandran, Dale; Poston, Graeme; Fenwick, Stephen; Malik, Hassan

2018-05-09

Colorectal cancer is the fourth commonest cancer and second commonest cause of cancer-related death in the United Kingdom. Almost 15% of patients have metastases on presentation. An increasing number of surgical strategies and better neoadjuvant treatment options are responsible for more patients undergoing resection of liver metastases, with prolonged survival in a select group of patients who present with synchronous disease. It is clear that the optimal strategy for the management of these patients remains unclear, and there is certainly a complete absence of Level 1 evidence in the literature. The objective of this study is to undertake preliminary work and devise an outline trial protocol to inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We have undertaken some preliminary work and begun the process of designing a randomized controlled trial and present a draft trial protocol here. This study is at the protocol development stage only, and as such no results are available. There is no funding in place for this study, and no anticipated start date. We have presented preliminary work and an outline trial protocol which we anticipate will inform the future development of clinical studies to investigate the management of patients with liver limited stage IV colorectal cancer. We do not believe that the trial we have designed will answer the most significant clinical questions, nor that it is feasible to be delivered within the United Kingdom's National Health Service at this current time. ©Paul Sutton, Dale Vimalachandran, Graeme Poston, Stephen Fenwick, Hassan Malik. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.05.2018.

Publication and non-publication of clinical trials: longitudinal study of applications submitted to a research ethics committee.

PubMed

von Elm, Erik; Röllin, Alexandra; Blümle, Anette; Huwiler, Karin; Witschi, Mark; Egger, Matthias

2008-04-05

Not all clinical trials are published, which may distort the evidence that is available in the literature. We studied the publication rate of a cohort of clinical trials and identified factors associated with publication and nonpublication of results. We analysed the protocols of randomized clinical trials of drug interventions submitted to the research ethics committee of University Hospital (Inselspital) Bern, Switzerland from 1988 to 1998. We identified full articles published up to 2006 by searching the Cochrane CENTRAL database (issue 02/2006) and by contacting investigators. We analyzed factors associated with the publication of trials using descriptive statistics and logistic regression models. 451 study protocols and 375 corresponding articles were analyzed. 233 protocols resulted in at least one publication, a publication rate of 52%. A total of 366 (81%) trials were commercially funded, 47 (10%) had non-commercial funding. 346 trials (77%) were multi-centre studies and 272 of these (79%) were international collaborations. In the adjusted logistic regression model non-commercial funding (Odds Ratio [OR] 2.42, 95% CI 1.14-5.17), multi-centre status (OR 2.09, 95% CI 1.03-4.24), international collaboration (OR 1.87, 95% CI 0.99-3.55) and a sample size above the median of 236 participants (OR 2.04, 95% CI 1.23-3.39) were associated with full publication. In this cohort of applications to an ethics committee in Switzerland, only about half of clinical drug trials were published. Large multi-centre trials with non-commercial funding were more likely to be published than other trials, but most trials were funded by industry.

Quality assurance of research protocols conducted in the community: the National Institute on Drug Abuse Clinical Trials Network experience.

PubMed

Rosa, Carmen; Campbell, Aimee; Kleppinger, Cynthia; Sampson, Royce; Tyson, Clare; Mamay-Gentilin, Stephanie

2009-04-01

Quality assurance (QA) of clinical trials is essential to protect the welfare of trial participants and the integrity of the data collected. However, there is little detailed information available on specific procedures and outcomes of QA monitoring for clinical trials. This article describes the experience of the National Institute on Drug Abuse's (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) in devising and implementing a three-tiered QA model for rigorous multi-site randomized clinical trials implemented in community-based substance abuse treatment programs. The CTN QA model combined local and national resources and was developed to address the unique needs of clinical trial sites with limited research experience. The authors reviewed internal records maintained by the sponsor, a coordinating site (Lead Nodes), and a local site detailing procedural development, training sessions, protocol violation monitoring, and site visit reporting. Between January 2001 and September 2005, the CTN implemented 21 protocols, of which 18 were randomized clinical trials, one was a quality improvement study and two were surveys. Approximately 160 community-based treatment programs participated in the 19 studies that were monitored, with a total of 6560 participants randomized across the sites. During this time 1937 QA site visits were reported across the three tiers of monitoring and the cost depended on the location of the sites and the salaries of the staff involved. One study reported 109 protocol violations (M = 15.6). Examples are presented to highlight training, protocol violation monitoring, site visit frequency and intensity and cost considerations. : QA data from the entire network were not easily available for review as much of the data were not electronically accessible. The authors reviewed and discussed a representative sample of internal data from the studies and participating sites. The lessons learned from the CTN's experience include the need for balancing thoroughness with efficiency, monitoring early, assessing research staff abilities in order to judge the need for proactive, focused attention, providing targeted training sessions, and developing flexible tools. The CTN model can work for sponsors overseeing studies at sites with limited research experience that require more frequent, in-depth monitoring. We recommend that sponsors not develop a rigid monitoring approach, but work with the study principal investigators to determine the intensity of monitoring needed depending on trial complexity, the risks of the intervention(s), and the experience of the staff with clinical research. After careful evaluation, sponsors should then determine the best approach to site monitoring and what resources will be needed.

Quality assurance of research protocols conducted in the community: The National Institute on Drug Abuse Clinical Trials Network Experience

PubMed Central

Rosa, Carmen; Campbell, Aimee; Kleppinger, Cynthia; Sampson, Royce; Tyson, Clare; Mamay-Gentilin, Stephanie

2009-01-01

Background: Quality assurance (QA) of clinical trials is essential to protect the welfare of trial participants and the integrity of the data collected. However, there is little detailed information available on specific procedures and outcomes of QA monitoring for clinical trials. Purpose: This article describes the experience of the National Institute on Drug Abuse's (NIDA) National Drug Abuse Treatment Clinical Trials Network (CTN) in devising and implementing a three-tiered QA model for rigorous multi-site randomized clinical trials implemented in community-based substance abuse treatment programs. The CTN QA model combined local and national resources and was developed to address the unique needs of clinical trial sites with limited research experience. Methods: The authors reviewed internal records maintained by the sponsor, a coordinating site (Lead Nodes), and a local site detailing procedural development, training sessions, protocol violation monitoring, and site visit reporting. Results: Between January 2001 and September 2005, the CTN implemented 21 protocols, of which 18 were randomized clinical trials, one was a quality improvement study and two were surveys. Approximately 160 community-based treatment programs participated in the 19 studies that were monitored, with a total of 6560 participants randomized across the sites. During this time 1937 QA site visits were reported across the three tiers of monitoring and the cost depended on the location of the sites and the salaries of the staff involved. One study reported 109 protocol violations (M = 15.6). Examples are presented to highlight training, protocol violation monitoring, site visit frequency and intensity and cost considerations. Limitations: QA data from the entire network were not easily available for review as much of the data were not electronically accessible. The authors reviewed and discussed a representative sample of internal data from the studies and participating sites. Conclusions: The lessons learned from the CTN's experience include the need for balancing thoroughness with efficiency, monitoring early, assessing research staff abilities in order to judge the need for proactive, focused attention, providing targeted training sessions, and developing flexible tools. The CTN model can work for sponsors overseeing studies at sites with limited research experience that require more frequent, in-depth monitoring. We recommend that sponsors not develop a rigid monitoring approach, but work with the study principal investigators to determine the intensity of monitoring needed depending on trial complexity, the risks of the intervention(s), and the experience of the staff with clinical research. After careful evaluation, sponsors should then determine the best approach to site monitoring and what resources will be needed. PMID:19342468

Protocol biopsy of the stable renal transplant: a multicenter study of methods and complication rates.

PubMed

Furness, Peter N; Philpott, Carl M; Chorbadjian, Mary T; Nicholson, Michael L; Bosmans, Jean-Louis; Corthouts, Bob L; Bogers, Johannes J P M; Schwarz, Anke; Gwinner, Wilfried; Haller, Hermann; Mengel, Michael; Seron, Daniel; Moreso, Francesc; Cañas, Conception

2003-09-27

Clinical trials in renal transplantation must use surrogate markers of long-term graft survival if conclusions are to be drawn at acceptable speed and cost. Morphologic changes in transplant biopsies provide the earliest available evidence of damage, and "protocol" biopsies from stable grafts can be used to reduce the number of patients needed in clinical trials. This approach has been inhibited by concerns over safety, but the risk of biopsy of a stable kidney, with no active inflammation or acute functional impairment, has never been formally estimated. In accordance with a predefined set of questions, a retrospective audit of a sequential series of protocol biopsies was performed in four major transplant centers. A total of 2,127 biopsy events were assessed for major complications, and 1,486 were assessed for minor ones. There were no deaths. One graft was lost, under circumstances indicating that the loss should have been prevented. Three episodes of hemorrhage required direct intervention. Three further patients required transfusion. There were two episodes of peritonitis, but one was arguably an unrelated event. All serious complications presented within 4 hr of biopsy. The incidence of clinically significant complications after protocol biopsy of a stable renal transplant is low. Direct benefits to the patients concerned (irrespective of the benefit that may accrue in clinical trials) were not formally assessed but seem likely to outweigh the risk of the procedure. We believe that it is ethically justifiable to ask renal transplant recipients to undergo protocol biopsies in clinical trials and routine care.

Data Acquisition for a Patient-directed Intervention Protocol in the Dynamic Intensive Care Unit Setting

PubMed Central

Chlan, Linda; Patterson, Robert P.; Heiderscheit, Annie

2011-01-01

Methods to easily, accurately, and efficiently obtain data in an ICU-based clinical trial can be challenging in this high-tech setting. Patient medical status and the dynamic nature of this clinical setting further complicates data collection. The purpose of this paper is to describe the modifications of commercially available headphones and the application of a data logging device to capture frequency and length of protocol use (music listening or headphones only for noise cancellation) without burdening participants or busy ICU nurses. With the automatic capture of protocol use by research participants, there have been no instances of lost data for this clinical trial. PMID:21382515

Data acquisition for a patient-directed intervention protocol in the dynamic intensive care unit setting.

PubMed

Chlan, Linda; Patterson, Robert P; Heiderscheit, Annie

2011-07-01

Methods to easily, accurately, and efficiently obtain data in an ICU-based clinical trial can be challenging in this high-tech setting. Patient medical status and the dynamic nature of this clinical setting further complicate data collection. The purpose of this paper is to describe the modifications of commercially available headphones and the application of a data logging device to capture frequency and length of protocol use (music listening or headphones only for noise cancellation) without burdening participants or busy ICU nurses. With the automatic capture of protocol use by research participants, there have been no instances of lost data for this clinical trial. Copyright © 2011 Elsevier Inc. All rights reserved.

[Patients' perspective and economic variables as objectives in clinical trials: added value to clinical parameters].

PubMed

Bovaira-García, M J; Soler-Company, E

2012-01-01

Patient-reported outcome (PRO) measures complement traditional biomedical outcome measures. The purpose of this study was to evaluate the use of PRO measures including health-related quality of life (HRQoL) questionnaires as a measurement of efficacy and the frequency of inclusion of economic variables related to direct and indirect costs in the design of clinical trials and phase IV observational studies. Moreover, for the trials quality score were measured, and if there were any relationship between the quality study design score and the PRO inclusion. Retrospective observational study of the clinical trials and phase IV observational studies approved by a Clinical Research Ethics Committee (2008-2010). We gathered data concerning general aspects including medical specialty, pathology, methodological quality based on Jadad scale (0-5), inclusion of PRO and economic variables. For clinical trials including HRQoL measurements, we analysed the type of questionnaire in use. Where there were no HRQoL measurements, we analysed if their inclusion would have been proper or not. A total of 70 protocols (59 CTs and 11 phase IV observational studies) were analysed; 37 (52.8%) included PRO measures, and 3 protocols (4.3%) used them as a primary endpoint. Data analysis by therapeutic area showed that PRO measures were most commonly studied in the fields of endocrinology, neurology, digestive diseases, and cardiology. The average quality score for the trials was 2.8. The trials with more PRO inclusion in their end points had a significantly higher quality score. Only 13 (22%) clinical trials and 2 (18.2%) phase IV observational studies included economic variables. The emergence of economic variables in clinical trials and phase IV observational studies evaluated was low, however, more than half of the revised protocols have included PRO measures, reflecting the importance of these parameters in the assessment of the effectiveness of drug treatments, although its use is still not systematic. Copyright © 2011 SECA. Published by Elsevier Espana. All rights reserved.

Development of a dynamic quality assurance testing protocol for multisite clinical trial DCE-CT accreditation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Driscoll, B.; Keller, H.; Jaffray, D.

2013-08-15

Purpose: Credentialing can have an impact on whether or not a clinical trial produces useful quality data that is comparable between various institutions and scanners. With the recent increase of dynamic contrast enhanced-computed tomography (DCE-CT) usage as a companion biomarker in clinical trials, effective quality assurance, and control methods are required to ensure there is minimal deviation in the results between different scanners and protocols at various institutions. This paper attempts to address this problem by utilizing a dynamic flow imaging phantom to develop and evaluate a DCE-CT quality assurance (QA) protocol.Methods: A previously designed flow phantom, capable of producingmore » predictable and reproducible time concentration curves from contrast injection was fully validated and then utilized to design a DCE-CT QA protocol. The QA protocol involved a set of quantitative metrics including injected and total mass error, as well as goodness of fit comparison to the known truth concentration curves. An additional region of interest (ROI) sensitivity analysis was also developed to provide additional details on intrascanner variability and determine appropriate ROI sizes for quantitative analysis. Both the QA protocol and ROI sensitivity analysis were utilized to test variations in DCE-CT results using different imaging parameters (tube voltage and current) as well as alternate reconstruction methods and imaging techniques. The developed QA protocol and ROI sensitivity analysis was then applied at three institutions that were part of clinical trial involving DCE-CT and results were compared.Results: The inherent specificity of robustness of the phantom was determined through calculation of the total intraday variability and determined to be less than 2.2 ± 1.1% (total calculated output contrast mass error) with a goodness of fit (R{sup 2}) of greater than 0.99 ± 0.0035 (n= 10). The DCE-CT QA protocol was capable of detecting significant deviations from the expected phantom result when scanning at low mAs and low kVp in terms of quantitative metrics (Injected Mass Error 15.4%), goodness of fit (R{sup 2}) of 0.91, and ROI sensitivity (increase in minimum input function ROI radius by 146 ± 86%). These tests also confirmed that the ASIR reconstruction process was beneficial in reducing noise without substantially increasing partial volume effects and that vendor specific modes (e.g., axial shuttle) did not significantly affect the phantom results. The phantom and QA protocol were finally able to quickly (<90 min) and successfully validate the DCE-CT imaging protocol utilized at the three separate institutions of a multicenter clinical trial; thereby enhancing the confidence in the patient data collected.Conclusions: A DCE QA protocol was developed that, in combination with a dynamic multimodality flow phantom, allows the intrascanner variability to be separated from other sources of variability such as the impact of injection protocol and ROI selection. This provides a valuable resource that can be utilized at various clinical trial institutions to test conformance with imaging protocols and accuracy requirements as well as ensure that the scanners are performing as expected for dynamic scans.« less

P-value interpretation and alpha allocation in clinical trials.

PubMed

Moyé, L A

1998-08-01

Although much value has been placed on type I error event probabilities in clinical trials, interpretive difficulties often arise that are directly related to clinical trial complexity. Deviations of the trial execution from its protocol, the presence of multiple treatment arms, and the inclusion of multiple end points complicate the interpretation of an experiment's reported alpha level. The purpose of this manuscript is to formulate the discussion of P values (and power for studies showing no significant differences) on the basis of the event whose relative frequency they represent. Experimental discordance (discrepancies between the protocol's directives and the experiment's execution) is linked to difficulty in alpha and beta interpretation. Mild experimental discordance leads to an acceptable adjustment for alpha or beta, while severe discordance results in their corruption. Finally, guidelines are provided for allocating type I error among a collection of end points in a prospectively designed, randomized controlled clinical trial. When considering secondary end point inclusion in clinical trials, investigators should increase the sample size to preserve the type I error rates at acceptable levels.

How blockchain-timestamped protocols could improve the trustworthiness of medical science

PubMed Central

Irving, Greg; Holden, John

2017-01-01

Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Methods for using blockchain to provide proof of pre-specified endpoints in clinical trial protocols were first reported by Carlisle. We wished to empirically test such an approach using a clinical trial protocol where outcome switching has previously been reported. Here we confirm the use of blockchain as a low cost, independently verifiable method to audit and confirm the reliability of scientific studies. PMID:27239273

How blockchain-timestamped protocols could improve the trustworthiness of medical science.

PubMed

Irving, Greg; Holden, John

2016-01-01

Trust in scientific research is diminished by evidence that data are being manipulated. Outcome switching, data dredging and selective publication are some of the problems that undermine the integrity of published research. Methods for using blockchain to provide proof of pre-specified endpoints in clinical trial protocols were first reported by Carlisle. We wished to empirically test such an approach using a clinical trial protocol where outcome switching has previously been reported. Here we confirm the use of blockchain as a low cost, independently verifiable method to audit and confirm the reliability of scientific studies.

Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya Aids Vaccine Initiative (KAVI), Kenya

PubMed Central

Omosa-Manyonyi, Gloria S.; Jaoko, Walter; Anzala, Omu; Ogutu, Hilda; Wakasiaka, Sabina; Malogo, Roselyn; Nyange, Jacqueline; Njuguna, Pamela; Ndinya-Achola, Jeckoniah; Bhatt, Kirana; Farah, Bashir; Oyaro, Micah; Schmidt, Claudia; Priddy, Frances; Fast, Patricia

2011-01-01

Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 [1]. ClinicalTrials.gov NCT00124007 Protocol IAVI 010 [2] (registration with ClincalTrials.gov is in progress) Protocols IAVI 002 and IAVI 004 are Phase 1 trials only mentioned in introductory paragraphs; details will not be reported. Registration was not required when they were conducted. PMID:21283743

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care

PubMed Central

Kraybill, Ashley; Dember, Laura M.; Joffe, Steven; Karlawish, Jason; Ellenberg, Susan S.; Madden, Vanessa; Halpern, Scott D.

2016-01-01

Background Pragmatic trials comparing standard-of-care interventions may improve the quality of care for future patients, but raise ethical questions about limitations on decisional autonomy. We sought to understand how patients and physicians view and respond to these questions in the contexts of pragmatic trials and of usual clinical care. Methods We conducted scenario-based, semi-structured interviews with 32 patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis in outpatient dialysis units and with 24 nephrologists. Each participant was presented with two hypothetical scenarios in which a protocolized approach to hemodialysis treatment time was adopted for the entire dialysis unit as part of a clinical trial or a new clinical practice. Results A modified grounded theory analysis revealed three major themes: 1) the value of research, 2) the effect of protocolized care on patient and physician autonomy, and 3) information exchange between patients and physicians, including the mechanism of consent. Most patients and physicians were willing to relinquish decisional autonomy and were more willing to relinquish autonomy for research purposes than in clinical care. Patients’ concerns towards clinical trials were tempered by their desires for certainty for a positive outcome and for physician validation. Patients tended to believe that being informed about research was more important than the actual mechanism of consent, and most were content with being able to opt out from participating. Conclusions This qualitative study suggests the general acceptability of a pragmatic clinical trial comparing standard-of-care interventions that limits decisional autonomy for nephrologists and patients receiving hemodialysis. Future studies are needed to determine whether similar findings would emerge among other patients and providers considering other standard-of-care trials. PMID:27833931

Patient and Physician Views about Protocolized Dialysis Treatment in Randomized Trials and Clinical Care.

PubMed

Kraybill, Ashley; Dember, Laura M; Joffe, Steven; Karlawish, Jason; Ellenberg, Susan S; Madden, Vanessa; Halpern, Scott D

2016-01-01

Pragmatic trials comparing standard-of-care interventions may improve the quality of care for future patients, but raise ethical questions about limitations on decisional autonomy. We sought to understand how patients and physicians view and respond to these questions in the contexts of pragmatic trials and of usual clinical care. We conducted scenario-based, semi-structured interviews with 32 patients with end-stage renal disease (ESRD) receiving maintenance hemodialysis in outpatient dialysis units and with 24 nephrologists. Each participant was presented with two hypothetical scenarios in which a protocolized approach to hemodialysis treatment time was adopted for the entire dialysis unit as part of a clinical trial or a new clinical practice. A modified grounded theory analysis revealed three major themes: 1) the value of research, 2) the effect of protocolized care on patient and physician autonomy, and 3) information exchange between patients and physicians, including the mechanism of consent. Most patients and physicians were willing to relinquish decisional autonomy and were more willing to relinquish autonomy for research purposes than in clinical care. Patients' concerns towards clinical trials were tempered by their desires for certainty for a positive outcome and for physician validation. Patients tended to believe that being informed about research was more important than the actual mechanism of consent, and most were content with being able to opt out from participating. This qualitative study suggests the general acceptability of a pragmatic clinical trial comparing standard-of-care interventions that limits decisional autonomy for nephrologists and patients receiving hemodialysis. Future studies are needed to determine whether similar findings would emerge among other patients and providers considering other standard-of-care trials.

Metadata registry and management system based on ISO 11179 for cancer clinical trials information system

PubMed Central

Park, Yu Rang; Kim*, Ju Han

2006-01-01

Standardized management of data elements (DEs) for Case Report Form (CRF) is crucial in Clinical Trials Information System (CTIS). Traditional CTISs utilize organization-specific definitions and storage methods for Des and CRFs. We developed metadata-based DE management system for clinical trials, Clinical and Histopathological Metadata Registry (CHMR), using international standard for metadata registry (ISO 11179) for the management of cancer clinical trials information. CHMR was evaluated in cancer clinical trials with 1625 DEs extracted from the College of American Pathologists Cancer Protocols for 20 major cancers. PMID:17238675

A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

PubMed

DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

2011-06-30

We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

How to design and write a clinical research protocol in Cosmetic Dermatology*

PubMed Central

Bagatin, Ediléia; Miot, Helio A.

2013-01-01

Cosmetic Dermatology is a growing subspecialty. High-quality basic science studies have been published; however, few double-blind, randomized controlled clinical trials, which are the major instrument for evidence-based medicine, have been conducted in this area. Clinical research is essential for the discovery of new knowledge, improvement of scientific basis, resolution of challenges, and good clinical practice. Some basic principles for a successful researcher include interest, availability, persistence, and honesty. It is essential to learn how to write a protocol research and to know the international and national regulatory rules. A complete clinical trial protocol should include question, background, objectives, methodology (design, variable description, sample size, randomization, inclusion and exclusion criteria, intervention, efficacy and safety measures, and statistical analysis), consent form, clinical research form, and references. Institutional ethical review board approval and financial support disclosure are necessary. Publication of positive or negative results should be an authors' commitment. PMID:23539006

Digital pathology in nephrology clinical trials, research, and pathology practice.

PubMed

Barisoni, Laura; Hodgin, Jeffrey B

2017-11-01

In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

Site visits to initiate recruitment in a clinical trial: does it matter who conducts the visit? Protocol for implementation in trials.

PubMed

Nollett, Claire; Kelson, Mark; Hood, Kerenza

2016-11-01

The Study Within a Trial (SWAT) program exists to 'embed research within research, so as to resolve uncertainties about the different ways of designing, conducting, analyzing, and interpreting evaluations of health and social care' (1). Published in this journal in 2013, a template for the first SWAT protocol outlined an investigation into the effects of site visits by the principal investigator on recruitment in multicentre randomized controlled trials (1). We have now designed a SWAT protocol to extend this question and ask 'does it matter who conducts the site visit?' Our aim is to provide a protocol that trials can implement to address this research question. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Head Tilt Posturography to Enhance Balance Control Assessment for Astronauts: A Case Study

NASA Technical Reports Server (NTRS)

Hwang, E. Y.; Paloski, W. H.

2006-01-01

For many years, we have used a standard clinical computerized dynamic posturography (CDP) protocol to assess recovery of integrated sensory-motor function in astronauts returning from space flight. The most reliable indications of postflight crew performance capabilities have been obtained from the sensory organization tests (SOTs) within the CDP protocol, particularly SOTs 5 (eyes closed, surface support sway referenced) and 6 (eyes open, surface support and visual surround sway referenced), which are sensitive to changes in availability and/or utilization of vestibular cues. We have observed, however, that some astronauts exhibiting visible signs of incomplete sensory-motor recovery are able to score within clinical norms on standard SOTs 5 and 6 trials, perhaps as a result of cognitive strategies driven by their naturally competitive natures. To improve the sensitivity of the CDP protocol for assessing recovery of integrated sensory-motor function and fitness to return to duties and/or activities of daily living, we have introduced pitch plane head tilt SOT trials to our protocol. In a preliminary study of 5 short duration (11day missions) astronauts, we showed that they were unable to maintain balance on landing day when performing dynamic head tilt trials, despite scoring within the clinically normal range on the standard SOT trials. The present case report illustrates the advantages of including head tilt trials for assessing sensory-motor recovery in long duration crewmembers.

Quality Assurance for Clinical Trials

PubMed Central

Ibbott, Geoffrey S.; Haworth, Annette; Followill, David S.

2013-01-01

Cooperative groups, of which the Radiation Therapy Oncology Group is one example, conduct national clinical trials that often involve the use of radiation therapy. In preparation for such a trial, the cooperative group prepares a protocol to define the goals of the trial, the rationale for its design, and the details of the treatment procedure to be followed. The Radiological Physics Center (RPC) is one of several quality assurance (QA) offices that is charged with assuring that participating institutions deliver doses that are clinically consistent and comparable. The RPC does this by conducting a variety of independent audits and credentialing processes. The RPC has compiled data showing that credentialing can help institutions comply with the requirements of a cooperative group clinical protocol. Phantom irradiations have been demonstrated to exercise an institution’s procedures for planning and delivering advanced external beam techniques (1–3). Similarly, RPC data indicate that a rapid review of patient treatment records or planning procedures can improve compliance with clinical trials (4). The experiences of the RPC are presented as examples of the contributions that a national clinical trials QA center can make to cooperative group trials. These experiences illustrate the critical need for comprehensive QA to assure that clinical trials are successful and cost-effective. The RPC is supported by grants CA 10953 and CA 81647 from the National Cancer Institute, NIH, DHHS. PMID:24392352

Research Nurse | Center for Cancer Research

Cancer.gov

We are looking for research nurses to join our clinical program to help us manage the care of patients participating in clinical trials. Duties include, but are not limited to, ensuring adherence to ethical practice in the conduct of clinical trials, research protocol compliance and good clinical practice, ensuring patient comprehension of informed consent, management of care

Effects of a Delphi consensus acupuncture treatment protocol on the levels of stress and vascular tone in women undergoing in-vitro fertilization: a randomized clinical trial protocol.

PubMed

Zhang, Yan; Phy, Jennifer; Scott-Johnson, Chris; Garos, Sheila; Orlando, Jennie; Prien, Samuel; Huang, Jaou-Chen

2017-04-04

The variability of published acupuncture protocols for patients undergoing In-Vitro Fertilization (IVF) complicates the interpretation of data and hinders our understanding of acupuncture's impact. In 2012, an acupuncture treatment protocol developed by a Delphi consensus process was published to describe the parameters of best practice acupuncture for Assisted Reproductive Technology and future research. However, there has been no clinical trial utilizing this protocol to assess the effects of acupuncture. This study aims to assess the implementation of Dephi consensus acupuncture protocol and to examine the impact of acupuncture on stress and uterine and ovarian blood flow among women between ages 21-42 years seeking IVF. This study is a one site prospective, two-arm randomized controlled non-blind clinical trial conducted in a medical school-affiliated fertility center . Participants will be randomized 1:1 into either the acupuncture group or the standard of care (no acupuncture) group using computer generated tables. Both groups will have 3 regular clinical visits as their standard IVF care during an approximately 2 to 3 weeks window. Women who are randomized into the acupuncture group would receive three sessions based on the Delphi consensus acupuncture protocol in addition to the standard care. The first treatment will be administered between days 6 to 8 of the stimulated IVF cycle. The second session will be performed on the day of embryo transfer at least 1 h prior to the transfer. The third session will be performed within 48 h post-embryo transfer. Participants will be followed for their pregnancy test and pregnancy outcome when applicable. The outcomes stress and blood flow will be measured by a validated perceived stress scale and vasoactive molecules, respectively. Although recruitment and scheduling could be challenging at times, the Delphi consensus acupuncture protocol was implemented as planned and well-accepted by the patients. Because of the time-specified sessions around patients' IVF cycle, it is highly recommended to have on-site study acupuncturist(s) to accommodate the schedule. ClinicalTrials NCT02591186 registered on October 7, 2015.

Randomized trial for answers to clinical questions: evaluating a pre-appraised versus a MEDLINE search protocol.

PubMed

Patel, Manesh R; Schardt, Connie M; Sanders, Linda L; Keitz, Sheri A

2006-10-01

The paper compares the speed, validity, and applicability of two different protocols for searching the primary medical literature. A randomized trial involving medicine residents was performed. An inpatient general medicine rotation was used. Thirty-two internal medicine residents were block randomized into four groups of eight. Success rate of each search protocol was measured by perceived search time, number of questions answered, and proportion of articles that were applicable and valid. Residents randomized to the MEDLINE-first (protocol A) group searched 120 questions, and residents randomized to the MEDLINE-last (protocol B) searched 133 questions. In protocol A, 104 answers (86.7%) and, in protocol B, 117 answers (88%) were found to clinical questions. In protocol A, residents reported that 26 (25.2%) of the answers were obtained quickly or rated as "fast" (<5 minutes) as opposed to 55 (51.9%) in protocol B, (P = 0.0004). A subset of questions and articles (n = 79) were reviewed by faculty who found that both protocols identified similar numbers of answer articles that addressed the questions and were felt to be valid using critical appraisal criteria. For resident-generated clinical questions, both protocols produced a similarly high percentage of applicable and valid articles. The MEDLINE-last search protocol was perceived to be faster. However, in the MEDLINE-last protocol, a significant portion of questions (23%) still required searching MEDLINE to find an answer.

Practical issues regarding implementing a randomized clinical trial in a homeless population: strategies and lessons learned.

PubMed

Ojo-Fati, Olamide; Joseph, Anne M; Ig-Izevbekhai, Jed; Thomas, Janet L; Everson-Rose, Susan A; Pratt, Rebekah; Raymond, Nancy; Cooney, Ned L; Luo, Xianghua; Okuyemi, Kolawole S

2017-07-05

There is a critical need for objective data to guide effective health promotion and care for homeless populations. However, many investigators exclude homeless populations from clinical trials due to practical concerns about conducting research with this population. This report is based on our experience and lessons learned while conducting two large NIH-funded randomized controlled trials targeting smoking cessation among persons who are homeless. The current report also addresses challenges when conducting clinical trials among homeless populations and offers potential solutions. Homeless individuals face several challenges including the need to negotiate daily access to food, clothing, and shelter. Some of the critical issues investigators encounter include recruitment and retention obstacles; cognitive impairment, mental health and substance abuse disorders; transportation and scheduling challenges; issues pertaining to adequate study compensation; the need for safety protocols for study staff; and issues related to protecting the wellbeing of these potentially vulnerable adults. Anticipating realistic conditions in which to conduct studies with participants who are homeless will help investigators to design efficient protocols and may improve the feasibility of conducting clinical trials involving homeless populations and the quality of the data collected by the researchers. ClinicalTrials.gov, ID: NCT00786149 . Registered on 5 November 2008; ClinicalTrials.gov, ID: NCT01932996 . Registered on 20 November 2014.

How to customize a bona fide psychotherapy for generalized anxiety disorder? A two-arms, patient blinded, ABAB crossed-therapist randomized clinical implementation trial design [IMPLEMENT 2.0].

PubMed

Flückiger, Christoph; Wolfer, Christine; Held, Judith; Hilpert, Peter; Rubel, Julian; Allemand, Mathias; Zinbarg, Richard E; Vîslă, Andreea

2018-04-03

Bona fide psychotherapy approaches are effective treatments for generalized anxiety disorder (GAD) compared to no-treatment conditions. Treatment manuals and protocols allow a relatively high degree of freedom for the way therapists implement these overall treatment packages and there is a systematic lack of knowledge on how therapists should customize these treatments. The present study experimentally examines two implementation strategies of customizing a bona fide psychotherapy approach based on a 16 session time-limited cognitive-behavioral therapy (CBT) protocol and their relation to the post-session and ultimate treatment outcomes. This trial contrasts two different implementation strategies of how to customize the in-session structure of a manual-based CBT-protocol for GAD. The patients will be randomly assigned to two implementation conditions: (1) a systematic focus on subtle changes lasting from 7 to 20 min at the check-in phase of every psychotherapy session and (2) a state-of-the-art (SOTA) check-in phase lasting several minutes mainly focused on the session goals. Potential therapist effects will be examined based on an ABAB crossed-therapist design. Treatment outcomes will be assessed at the following times: post-session outcomes, treatment outcome at post assessment and 6- as well as 12-month follow-up. The proposed randomized clinical implementation trial addresses the clinically relevant question of how to customize a bona fide psychotherapy protocol experimentally contrasting two implementation strategies. Through the development and testing of the proposed implementation design, this trial has the potential to inform therapists about efficacious implementation strategies of how to customize a manual-based treatment protocol in respect to the timing of the in-session structure. This trial was registered at ClinicalTrials.gov ( NCT03079336 ) at March 14, 2017.

Quantifying and visualizing site performance in clinical trials.

PubMed

Yang, Eric; O'Donovan, Christopher; Phillips, JodiLyn; Atkinson, Leone; Ghosh, Krishnendu; Agrafiotis, Dimitris K

2018-03-01

One of the keys to running a successful clinical trial is the selection of high quality clinical sites, i.e., sites that are able to enroll patients quickly, engage them on an ongoing basis to prevent drop-out, and execute the trial in strict accordance to the clinical protocol. Intuitively, the historical track record of a site is one of the strongest predictors of its future performance; however, issues such as data availability and wide differences in protocol complexity can complicate interpretation. Here, we demonstrate how operational data derived from central laboratory services can provide key insights into the performance of clinical sites and help guide operational planning and site selection for new clinical trials. Our methodology uses the metadata associated with laboratory kit shipments to clinical sites (such as trial and anonymized patient identifiers, investigator names and addresses, sample collection and shipment dates, etc.) to reconstruct the complete schedule of patient visits and derive insights about the operational performance of those sites, including screening, enrollment, and drop-out rates and other quality indicators. This information can be displayed in its raw form or normalized to enable direct comparison of site performance across studies of varied design and complexity. Leveraging Covance's market leadership in central laboratory services, we have assembled a database of operational metrics that spans more than 14,000 protocols, 1400 indications, 230,000 unique investigators, and 23 million patient visits and represents a significant fraction of all clinical trials run globally in the last few years. By analyzing this historical data, we are able to assess and compare the performance of clinical investigators across a wide range of therapeutic areas and study designs. This information can be aggregated across trials and geographies to gain further insights into country and regional trends, sometimes with surprising results. The use of operational data from Covance Central Laboratories provides a unique perspective into the performance of clinical sites with respect to many important metrics such as patient enrollment and retention. These metrics can, in turn, be used to guide operational planning and site selection for new clinical trials, thereby accelerating recruitment, improving quality, and reducing cost.

Inconsistencies in quality of life data collection in clinical trials: a potential source of bias? Interviews with research nurses and trialists.

PubMed

Kyte, Derek; Ives, Jonathan; Draper, Heather; Keeley, Thomas; Calvert, Melanie

2013-01-01

Patient-reported outcomes (PROs), such as health-related quality of life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical trials, are valued by patients, and may inform important decisions in the clinical setting. It is of concern, therefore, that preliminary evidence, gained from group discussions at UK-wide Medical Research Council (MRC) quality of life training days, suggests there are inconsistent standards of HRQL data collection in trials and appropriate training and education is often lacking. Our objective was to investigate these reports, to determine if they represented isolated experiences, or were indicative of a potentially wider problem. We undertook a qualitative study, conducting 26 semi-structured interviews with research nurses, data managers, trial coordinators and research facilitators involved in the collection and entry of HRQL data in clinical trials, across one primary care NHS trust, two secondary care NHS trusts and two clinical trials units in the UK. We used conventional content analysis to analyze and interpret our data. Our study participants reported (1) inconsistent standards in HRQL measurement, both between, and within, trials, which appeared to risk the introduction of bias; (2), difficulties in dealing with HRQL data that raised concern for the well-being of the trial participant, which in some instances led to the delivery of non-protocol driven co-interventions, (3), a frequent lack of HRQL protocol content and appropriate training and education of trial staff, and (4) that HRQL data collection could be associated with emotional and/or ethical burden. Our findings suggest there are inconsistencies in the standards of HRQL data collection in some trials resulting from a general lack of HRQL-specific protocol content, training and education. These inconsistencies could lead to biased HRQL trial results. Future research should aim to develop HRQL guidelines and training programmes aimed at supporting researchers to carry out high quality data collection.

Inconsistencies in Quality of Life Data Collection in Clinical Trials: A Potential Source of Bias? Interviews with Research Nurses and Trialists

PubMed Central

Kyte, Derek; Ives, Jonathan; Draper, Heather; Keeley, Thomas; Calvert, Melanie

2013-01-01

Background Patient-reported outcomes (PROs), such as health-related quality of life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical trials, are valued by patients, and may inform important decisions in the clinical setting. It is of concern, therefore, that preliminary evidence, gained from group discussions at UK-wide Medical Research Council (MRC) quality of life training days, suggests there are inconsistent standards of HRQL data collection in trials and appropriate training and education is often lacking. Our objective was to investigate these reports, to determine if they represented isolated experiences, or were indicative of a potentially wider problem. Methods And Findings We undertook a qualitative study, conducting 26 semi-structured interviews with research nurses, data managers, trial coordinators and research facilitators involved in the collection and entry of HRQL data in clinical trials, across one primary care NHS trust, two secondary care NHS trusts and two clinical trials units in the UK. We used conventional content analysis to analyze and interpret our data. Our study participants reported (1) inconsistent standards in HRQL measurement, both between, and within, trials, which appeared to risk the introduction of bias; (2), difficulties in dealing with HRQL data that raised concern for the well-being of the trial participant, which in some instances led to the delivery of non-protocol driven co-interventions, (3), a frequent lack of HRQL protocol content and appropriate training and education of trial staff, and (4) that HRQL data collection could be associated with emotional and/or ethical burden. Conclusions Our findings suggest there are inconsistencies in the standards of HRQL data collection in some trials resulting from a general lack of HRQL-specific protocol content, training and education. These inconsistencies could lead to biased HRQL trial results. Future research should aim to develop HRQL guidelines and training programmes aimed at supporting researchers to carry out high quality data collection. PMID:24124580

Remotely-supervised transcranial direct current stimulation (tDCS) for clinical trials: guidelines for technology and protocols.

PubMed

Charvet, Leigh E; Kasschau, Margaret; Datta, Abhishek; Knotkova, Helena; Stevens, Michael C; Alonzo, Angelo; Loo, Colleen; Krull, Kevin R; Bikson, Marom

2015-01-01

The effect of transcranial direct current stimulation (tDCS) is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: (1) training of staff in tDCS treatment and supervision; (2) assessment of the user's capability to participate in tDCS remotely; (3) ongoing training procedures and materials including assessments of the user and/or caregiver; (4) simple and fail-safe electrode preparation techniques and tDCS headgear; (5) strict dose control for each session; (6) ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol), with corresponding corrective steps as required; (7) monitoring for treatment-emergent adverse effects; (8) guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population's level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care) following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

Blockchain technology for improving clinical research quality.

PubMed

Benchoufi, Mehdi; Ravaud, Philippe

2017-07-19

Reproducibility, data sharing, personal data privacy concerns and patient enrolment in clinical trials are huge medical challenges for contemporary clinical research. A new technology, Blockchain, may be a key to addressing these challenges and should draw the attention of the whole clinical research community.Blockchain brings the Internet to its definitive decentralisation goal. The core principle of Blockchain is that any service relying on trusted third parties can be built in a transparent, decentralised, secure "trustless" manner at the top of the Blockchain (in fact, there is trust, but it is hardcoded in the Blockchain protocol via a complex cryptographic algorithm). Therefore, users have a high degree of control over and autonomy and trust of the data and its integrity. Blockchain allows for reaching a substantial level of historicity and inviolability of data for the whole document flow in a clinical trial. Hence, it ensures traceability, prevents a posteriori reconstruction and allows for securely automating the clinical trial through what are called Smart Contracts. At the same time, the technology ensures fine-grained control of the data, its security and its shareable parameters, for a single patient or group of patients or clinical trial stakeholders.In this commentary article, we explore the core functionalities of Blockchain applied to clinical trials and we illustrate concretely its general principle in the context of consent to a trial protocol. Trying to figure out the potential impact of Blockchain implementations in the setting of clinical trials will shed new light on how modern clinical trial methods could evolve and benefit from Blockchain technologies in order to tackle the aforementioned challenges.

Standardized terminology for clinical trial protocols based on top-level ontological categories.

PubMed

Heller, B; Herre, H; Lippoldt, K; Loeffler, M

2004-01-01

This paper describes a new method for the ontologically based standardization of concepts with regard to the quality assurance of clinical trial protocols. We developed a data dictionary for medical and trial-specific terms in which concepts and relations are defined context-dependently. The data dictionary is provided to different medical research networks by means of the software tool Onto-Builder via the internet. The data dictionary is based on domain-specific ontologies and the top-level ontology of GOL. The concepts and relations described in the data dictionary are represented in natural language, semi-formally or formally according to their use.

Development of Uniform Protocol for Alopecia Areata Clinical Trials.

PubMed

Solomon, James A

2015-11-01

Developing a successful treatment for alopecia areata (AA), clearly has not been at the forefront of the agenda for new drug/device development among the pharmaceutical and medical device industry. The National Alopecia Areata Foundation (NAAF), a patient advocacy group, initiated a plan to facilitate and drive clinical research toward finding safe and efficacious treatments for AA. As such, Alopecia Areata Uniform Protocols for clinical trials to test new treatments for AA were developed. The design of the uniform protocol is to accomplish the development of a plug-and-play template as well as to provide a framework wherein data from studies utilizing the uniform protocol can be compared through consistency of inclusions/exclusions, safety, and outcome assessment measures. A core uniform protocol for use by pharmaceutical companies in testing proof of concept for investigational products to treat AA. The core protocol includes standardized title, informed consent, inclusion/exclusion criteria, disease outcome assessments, and safety assessments. The statistical methodology to assess successful outcomes will also be standardized. The protocol as well as the informed consent form has been approved in concept by Liberty IRB and is ready to present to pharmaceutical companies.

The NIDA Methamphetamine Clinical Trials Group: a strategy to increase clinical trials research capacity.

PubMed

Elkashef, Ahmed; Rawson, Richard A; Smith, Edwina; Pearce, Valerie; Flammino, Frank; Campbell, Jan; Donovick, Roger; Gorodetzky, Charles; Haning, William; Mawhinney, Joseph; McCann, Michael; Weis, Dennis; Williams, Lorie; Ling, Walter; Vocci, Frank

2007-04-01

In order to increase the number of investigative teams and sites conducting research on pharmacological treatments for methamphetamine use disorders, the National Institute on Drug Abuse (NIDA) established an infrastructure of clinical sites in areas where methamphetamine addiction is prevalent. This multi-site infrastructure would serve to run multiple Phases II and III protocols effectively and expeditiously. NIDA collaborated with investigators from the University of California at Los Angeles (UCLA) to set up the Methamphetamine Clinical Trials Group (MCTG). This paper describes the development process, as well as data from a test trial to assess the capability of research-naive sites to recruit research participants and conduct study procedures according to research protocol. Subsequent trials are also described. A total of 151 candidates signed consent; 65 individuals were enrolled and 35 (53.8%) completed the 12 weeks' behavioral trial. Self-reported substance use report (SUR) showed comparable use of methamphetamine across sites with the individual site means ranging from 59% (site 5) to 80% (site 3). Drug use as measured by urinalysis was greatly reduced at week 13 compared to the baseline measure; the average rate of methamphetamine-free urine samples across all participants in sites at week 13 was 53%. The highest percentage of methamphetamine-free samples was 85% at site 5; the lowest was at site 1 (40%). Addiction severity index (ASI) composite scores at baseline and protocol completion for all participants demonstrated improvement in all categories over time, except for the medical composite score. The largest composite score reduction in baseline-protocol completion was in the drug domain (0.23 versus 0.15). The changes in the ASI scores from baseline to week 13 were consistent across all five sites. Outcomes of the behavioral trial indicated that the MCTG recruited well; collected study data accurately and reliably; and created a vehicle that can assess promising pharmacotherapies for methamphetamine addiction treatment medications. The MCTG strategy appears to be a feasible approach to increase NIDA's capacity to conduct clinical trials to evaluate potential pharmacotherapies for methamphetamine addiction.

Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00003730 since 23 August 2012. (http://www.germanctr.de). PMID:24884848

Efficacy and safety of Lian-Ju-Gan-Mao capsules for treating the common cold with wind-heat syndrome: study protocol for a randomized controlled trial.

PubMed

Wang, Shengjun; Jiang, Hongli; Yu, Qin; She, Bin; Mao, Bing

2017-01-05

The common cold is a common and frequent respiratory disease mainly caused by viral infection of the upper respiratory tract. Chinese herbal medicine has been increasingly prescribed to treat the common cold; however, there is a lack of evidence to support the wide utility of this regimen. This protocol describes an ongoing phase II randomized controlled clinical trial, based on the theory of traditional Chinese medicine (TCM), with the objective of evaluating the efficacy and safety of Lian-Ju-Gan-Mao capsules (LJGMC), a Chinese patent medicine, compared with placebo in patients suffering from the common cold with wind-heat syndrome (CCWHS). This is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial. A total of 240 patients will be recruited and randomly assigned to a high-dose group, medium-dose group, low-dose group, and placebo-matched group in a 1:1:1:1 ratio. The treatment course is 3 consecutive days, with a 5-day follow-up. The primary outcome is time to all symptoms' clearance. Secondary outcomes include time to the disappearance of primary symptoms and each secondary symptom, time to fever relief, time to fever clearance, and change in TCM symptom and sign scores. This trial is a well-designed study according to principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide high-quality evidence on the efficacy and safety of LJGMC in treating CCWHS and help to optimize the dose for the next phase III clinical trial. Moreover, the protocol presents a detailed and practical methodology for future clinical trials of drugs developed based on TCM. Chinese Clinical Trial Registry, ChiCTR-IPR-15006504 . Registered on 4 June 2015.

Protocol Information Office (PIO) | Division of Cancer Prevention

Cancer.gov

PIO Instructions and Tools Find instructions, forms, and templates for the management of all types of Division of Cancer Prevention clinical trials.Read more about PIO Instructions and Tools Clinical Trials Reference Materials Model clinical agreements, human subject protection and informed consent models, gender and minority inclusion information, and monitoring policy and

Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study.

PubMed

Sevransky, Jonathan E; Checkley, William; Herrera, Phabiola; Pickering, Brian W; Barr, Juliana; Brown, Samuel M; Chang, Steven Y; Chong, David; Kaufman, David; Fremont, Richard D; Girard, Timothy D; Hoag, Jeffrey; Johnson, Steven B; Kerlin, Mehta P; Liebler, Janice; O'Brien, James; O'Keefe, Terence; Park, Pauline K; Pastores, Stephen M; Patil, Namrata; Pietropaoli, Anthony P; Putman, Maryann; Rice, Todd W; Rotello, Leo; Siner, Jonathan; Sajid, Sahul; Murphy, David J; Martin, Greg S

2015-10-01

Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. A total of 6,179 critically ill patients. Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. None. The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15-21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

A Method of Managing Severe Traumatic Brain Injury in the Absence of Intracranial Pressure Monitoring: The Imaging and Clinical Examination Protocol.

PubMed

Chesnut, Randall M; Temkin, Nancy; Dikmen, Sureyya; Rondina, Carlos; Videtta, Walter; Petroni, Gustavo; Lujan, Silvia; Alanis, Victor; Falcao, Antonio; de la Fuenta, Gustavo; Gonzalez, Luis; Jibaja, Manuel; Lavarden, Arturo; Sandi, Freddy; Mérida, Roberto; Romero, Ricardo; Pridgeon, Jim; Barber, Jason; Machamer, Joan; Chaddock, Kelley

2018-01-01

The imaging and clinical examination (ICE) algorithm used in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial is the only prospectively investigated clinical protocol for traumatic brain injury management without intracranial pressure (ICP) monitoring. As the default literature standard, it warrants careful evaluation. We present the ICE protocol in detail and analyze the demographics, outcome, treatment intensity, frequency of intervention usage, and related adverse events in the ICE-protocol cohort. The 167 ICE protocol patients were young (median 29 years) with a median Glasgow Coma Scale motor score of 4 but with anisocoria or abnormal pupillary reactivity in 40%. This protocol produced outcomes not significantly different from those randomized to the monitor-based protocol (favorable 6-month extended Glasgow Outcome Score in 39%; 41% mortality rate). Agents commonly employed to treat suspected intracranial hypertension included low-/moderate-dose hypertonic saline (72%) and mannitol (57%), mild hyperventilation (adjusted partial pressure of carbon dioxide 30-35 mm Hg in 73%), and pressors to maintain cerebral perfusion (62%). High-dose hyperosmotics or barbiturates were uncommonly used. Adverse event incidence was low and comparable to the BEST TRIP monitored group. Although this protocol should produce similar/acceptable results under circumstances comparable to those in the trial, influences such as longer pre-hospital times and non-specialist transport personnel, plus an intensive care unit model of aggressive physician-intensive care by small groups of neurotrauma-focused intensivists, which differs from most high-resource models, support caution in expecting the same results in dissimilar settings. Finally, this protocol's ICP-titration approach to suspected intracranial hypertension (vs. crisis management for monitored ICP) warrants further study.

Participation in Pediatric Oncology Research Protocols: Racial/ethnic, Language and Age-based Disparities

PubMed Central

Aristizabal, Paula; Singer, Jenelle; Cooper, Renee; Wells, Kristen J.; Nodora, Jesse; Milburn, Mehrzad; Gahagan, Sheila; Schiff, Deborah E.; Martinez, Maria Elena

2015-01-01

Background Survival rates in pediatric oncology have improved dramatically, in part due to high patient participation in clinical trials. Although racial/ethnic inequalities in clinical trial participation have been reported in adults, pediatric data and studies comparing participation rates by socio-demographic characteristics are scarce. The goal of this study was to assess differences in research protocol participation for childhood cancer by age, sex, race/ethnicity, parental language, cancer type and insurance status. Procedure Data on enrollment in any protocol, biospecimen, or therapeutic protocols were collected and analyzed for newly diagnosed pediatric patients with cancer from 2008–2012 at Rady Children’s Hospital. Results Among the 353 patients included in the analysis, 304 (86.1%) were enrolled in any protocol. Enrollment in biospecimen and therapeutic protocols was 84.2% (261/310) and 81.1% (206/254), respectively. Logistic regression analyses revealed significant enrollment underrepresentation in any protocol for Hispanics compared to Non-Hispanic whites (81% vs. 91%; Odds Ratio [OR], 0.43; 95% Confidence Interval [CI], 0.21–0.90; p=0.021) and among children of Spanish-speaking vs. English-speaking parents (78% vs. 89%; OR, 0.45; 95%CI, 0.23–0.87; p=0.016). Compared to patients aged 0–4 years, significant underrepresentation was also found among patients 15–21 years old (92% vs.72%; OR, 0.21; 95% CI, 0.09–0.48; p<0.001). Similar trends were observed when analyzing enrollment in biospecimen and therapeutic protocols separately. Conclusions There was significant underrepresentation in protocol participation for Hispanics, children of Spanish-speaking parents, and patients ages 15–21. Research is urgently needed to understand barriers to research participation among these groups underrepresented in pediatric oncology clinical trials. PMID:25755225

Neuropathological Assessment as an Endpoint in Clinical Trial Design.

PubMed

Gentleman, Steve; Liu, Alan King Lun

2018-01-01

Different neurodegenerative conditions can have complex, overlapping clinical presentations that make accurate diagnosis during life very challenging. For this reason, confirmation of the clinical diagnosis still requires postmortem verification. This is particularly relevant for clinical trials of novel therapeutics where it is important to ascertain what disease and/or pathology modifying effects the therapeutics have had. Furthermore, it is important to confirm that patients in the trial actually had the correct clinical diagnosis as this will have a major bearing on the interpretation of trial results. Here we present a simple protocol for pathological assessment of neurodegenerative changes.

Preliminary clinical trial of immunotherapy for malignant glioma.

PubMed

Ingram, M; Shelden, C H; Jacques, S; Skillen, R G; Bradley, W G; Techy, G B; Freshwater, D B; Abts, R M; Rand, R W

1987-10-01

An immunotherapy protocol based on intracranial implantation of stimulated, autologous lymphocytes into the tumor bed following surgical debulking of malignant glioma is described. Phase I clinical trials in human patients are now in progress. Preliminary data representing the first 39 patients treated are presented briefly.

Targeted full energy and protein delivery in critically ill patients: a study protocol for a pilot randomised control trial (FEED Trial).

PubMed

Fetterplace, Kate; Deane, Adam M; Tierney, Audrey; Beach, Lisa; Knight, Laura D; Rechnitzer, Thomas; Forsyth, Adrienne; Mourtzakis, Marina; Presneill, Jeffrey; MacIsaac, Christopher

2018-01-01

Current guidelines for the provision of protein for critically ill patients are based on incomplete evidence, due to limited data from randomised controlled trials. The present pilot randomised controlled trial is part of a program of work to expand knowledge about the clinical effects of protein delivery to critically ill patients. The primary aim of this pilot study is to determine whether an enteral feeding protocol using a volume target, with additional protein supplementation, delivers a greater amount of protein and energy to mechanically ventilated critically ill patients than a standard nutrition protocol. The secondary aims are to evaluate the potential effects of this feeding strategy on muscle mass and other patient-centred outcomes. This prospective, single-centred, pilot, randomised control trial will include 60 participants who are mechanically ventilated and can be enterally fed. Following informed consent, the participants receiving enteral nutrition in the intensive care unit (ICU) will be allocated using a randomisation algorithm in a 1:1 ratio to the intervention (high-protein daily volume-based feeding protocol, providing 25 kcal/kg and 1.5 g/kg protein) or standard care (hourly rate-based feeding protocol providing 25 kcal/kg and 1 g/kg protein). The co-primary outcomes are the average daily protein and energy delivered to the end of day 15 following randomisation. The secondary outcomes include change in quadriceps muscle layer thickness (QMLT) from baseline (prior to randomisation) to ICU discharge and other nutritional and patient-centred outcomes. This trial aims to examine whether a volume-based feeding protocol with supplemental protein increases protein and energy delivery. The potential effect of such increases on muscle mass loss will be explored. These outcomes will assist in formulating larger randomised control trials to assess mortality and morbidity. Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN: 12615000876594 UTN: U1111-1172-8563.

Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

PubMed

Dekkers, Olaf M; Cevallos, Myriam; Bührer, Jonas; Poncet, Antoine; Ackermann Rau, Sabine; Perneger, Thomas V; Egger, Matthias

2015-05-01

To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries. Copyright © 2015 Elsevier Inc. All rights reserved.

Rationale for the Diabetic Retinopathy Clinical Research Network Treatment Protocol for Center-involved Diabetic Macular Edema

PubMed Central

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M.; Browning, David J.; Chalam, KV; Davis, Matthew; Ferris, Frederick L; Glassman, Adam; Maturi, Raj; Stockdale, Cynthia R.; Topping, Trexler

2011-01-01

Objective Describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Design Discussion of treatment protocol for DME. Participants Subjects with vision loss from DME involving the center of the macula. Methods The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser in eyes with vision loss from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes, compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. In order to share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Main Outcome Measures Clinical guidelines based on a DRCR.net protocol. Results The treatment protocol required real time feedback from a web-based data entry system for intravitreal injections, focal/grid laser, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month, or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Conclusions Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. PMID:22136692

Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema.

PubMed

Aiello, Lloyd Paul; Beck, Roy W; Bressler, Neil M; Browning, David J; Chalam, K V; Davis, Matthew; Ferris, Frederick L; Glassman, Adam R; Maturi, Raj K; Stockdale, Cynthia R; Topping, Trexler M

2011-12-01

To describe the underlying principles used to develop a web-based algorithm that incorporated intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in a Diabetic Retinopathy Clinical Research Network (DRCR.net) randomized clinical trial. Discussion of treatment protocol for DME. Subjects with vision loss resulting from DME involving the center of the macula. The DRCR.net created an algorithm incorporating anti-VEGF injections in a comparative effectiveness randomized clinical trial evaluating intravitreal ranibizumab with prompt or deferred (≥24 weeks) focal/grid laser treatment in eyes with vision loss resulting from center-involved DME. Results confirmed that intravitreal ranibizumab with prompt or deferred laser provides superior visual acuity outcomes compared with prompt laser alone through at least 2 years. Duplication of this algorithm may not be practical for clinical practice. To share their opinion on how ophthalmologists might emulate the study protocol, participating DRCR.net investigators developed guidelines based on the algorithm's underlying rationale. Clinical guidelines based on a DRCR.net protocol. The treatment protocol required real-time feedback from a web-based data entry system for intravitreal injections, focal/grid laser treatment, and follow-up intervals. Guidance from this system indicated whether treatment was required or given at investigator discretion and when follow-up should be scheduled. Clinical treatment guidelines, based on the underlying clinical rationale of the DRCR.net protocol, include repeating treatment monthly as long as there is improvement in edema compared with the previous month or until the retina is no longer thickened. If thickening recurs or worsens after discontinuing treatment, treatment is resumed. Duplication of the approach used in the DRCR.net randomized clinical trial to treat DME involving the center of the macula with intravitreal ranibizumab may not be practical in clinical practice, but likely can be emulated based on an understanding of the underlying rationale for the study protocol. Inherent differences between a web-based treatment algorithm and a clinical approach may lead to differences in outcomes that are impossible to predict. The closer the clinical approach is to the algorithm used in the study, the more likely the outcomes will be similar to those published. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Reporting of methods was better in the Clinical Trials Registry-India than in Indian journal publications.

PubMed

Tharyan, Prathap; George, Aneesh Thomas; Kirubakaran, Richard; Barnabas, Jabez Paul

2013-01-01

We sought to evaluate if editorial policies and the reporting quality of randomized controlled trials (RCTs) had improved since our 2004-05 survey of 151 RCTs in 65 Indian journals, and to compare reporting quality of protocols in the Clinical Trials Registry-India (CTRI). An observational study of endorsement of Consolidated Standards for the Reporting of Trials (CONSORT) and International Committee of Medical Journal Editors (ICMJE) requirements in the instructions to authors in Indian journals, and compliance with selected requirements in all RCTs published during 2007-08 vs. our previous survey and between all RCT protocols in the CTRI on August 31, 2010 and published RCTs from both surveys. Journal policies endorsing the CONSORT statement (22/67, 33%) and ICMJE requirements (35/67, 52%) remained suboptimal, and only 4 of 13 CONSORT items were reported in more than 50% of the 145 RCTs assessed. Reporting of ethical issues had improved significantly, and that of methods addressing internal validity had not improved. Adequate methods were reported significantly more frequently in 768 protocols in the CTRI, than in the 296 published trials. The CTRI template facilitates the reporting of valid methods in registered trial protocols. The suboptimal compliance with CONSORT and ICMJE requirements in RCTs published in Indian journals reduces credibility in the reliability of their results. Copyright © 2013 Elsevier Inc. All rights reserved.

Perceptions of Massage Therapists Participating in a Randomized Controlled Trial

PubMed Central

Perlman, Adam; Dreusicke, Mark; Keever, Teresa; Ali, Ather

2015-01-01

Background Clinical practice and randomized trials often have disparate aims, despite involving similar interventions. Attitudes and expectancies of practitioners influence patient outcomes, and there is growing emphasis on optimizing provider–patient relationships. In this study, we evaluated the experiences of licensed massage therapists involved in a randomized controlled clinical trial using qualitative methodology. Methods Seven massage therapists who were interventionists in a randomized controlled trial participated in structured interviews approximately 30 minutes in length. Interviews focused on their experiences and perceptions regarding aspects of the clinical trial, as well as recommendations for future trials. Transcribed interviews were analyzed for emergent topics and themes using standard qualitative methods. Results Six themes emerged. Therapists discussed 1) promoting the profession of massage therapy through research, 2) mixed views on using standardized protocols, 3) challenges of sham interventions, 4) participant response to the sham intervention, 5) views on scheduling and compensation, and 6) unanticipated benefits of participating in research. Conclusions Therapists largely appreciated the opportunity to promote massage through research. They demonstrated insight and understanding of the rationale for a clinical trial adhering to a standardized protocol. Evaluating the experiences and ideas of complementary and alternative medicine practitioners provides valuable insight that is relevant for the implementation and design of randomized trials. PMID:26388961

Barriers and enablers to implementing clinical treatment protocols for fever, hyperglycaemia, and swallowing dysfunction in the Quality in Acute Stroke Care (QASC) Project--a mixed methods study.

PubMed

Dale, Simeon; Levi, Christopher; Ward, Jeanette; Grimshaw, Jeremy M; Jammali-Blasi, Asmara; D'Este, Catherine; Griffiths, Rhonda; Quinn, Clare; Evans, Malcolm; Cadilhac, Dominique; Cheung, N Wah; Middleton, Sandy

2015-02-01

The Quality in Acute Stroke Care (QASC) trial evaluated systematic implementation of clinical treatment protocols to manage fever, sugar, and swallow (FeSS protocols) in acute stroke care. This cluster-randomised controlled trial was conducted in 19 stroke units in Australia. To describe perceived barriers and enablers preimplementation to the introduction of the FeSS protocols and, postimplementation, to determine which of these barriers eventuated as actual barriers. Preimplementation: Workshops were held at the intervention stroke units (n = 10). The first workshop involved senior clinicians who identified perceived barriers and enablers to implementation of the protocols, the second workshop involved bedside clinicians. Postimplementation, an online survey with stroke champions from intervention sites was conducted. A total of 111 clinicians attended the preimplementation workshops, identifying 22 barriers covering four main themes: (a) need for new policies, (b) limited workforce (capacity), (c) lack of equipment, and (d) education and logistics of training staff. Preimplementation enablers identified were: support by clinical champions, medical staff, nursing management and allied health staff; easy adaptation of current protocols, care-plans, and local policies; and presence of specialist stroke unit staff. Postimplementation, only five of the 22 barriers identified preimplementation were reported as actual barriers to adoption of the FeSS protocols, namely, no previous use of insulin infusions; hyperglycaemic protocols could not be commenced without written orders; medical staff reluctance to use the ASSIST swallowing screening tool; poor level of engagement of medical staff; and doctors' unawareness of the trial. The process of identifying barriers and enablers preimplementation allowed staff to take ownership and to address barriers and plan for change. As only five of the 22 barriers identified preimplementation were reported to be actual barriers at completion of the trial, this suggests that barriers are often overcome whilst some are only ever perceived rather than actual barriers. © 2015 Sigma Theta Tau International.

Efficacy of the unified protocol for the treatment of emotional disorders in the Spanish public mental health system using a group format: study protocol for a multicenter, randomized, non-inferiority controlled trial.

PubMed

Osma, Jorge; Suso-Ribera, Carlos; García-Palacios, Azucena; Crespo-Delgado, Elena; Robert-Flor, Cristina; Sánchez-Guerrero, Ana; Ferreres-Galan, Vanesa; Pérez-Ayerra, Luisa; Malea-Fernández, Amparo; Torres-Alfosea, Mª Ángeles

2018-03-12

Emotional disorders, which include both anxiety and depressive disorders, are the most prevalent psychological disorders according to recent epidemiological studies. Consequently, public costs associated with their treatment have become a matter of concern for public health systems, which face long waiting lists. Because of their high prevalence in the population, finding an effective treatment for emotional disorders has become a key goal of today's clinical psychology. The Unified Protocol for the Transdiagnostic Treatment of Emotional Disorders might serve the aforementioned purpose, as it can be applied to a variety of disorders simultaneously and it can be easily performed in a group format. The study is a multicenter, randomized, non-inferiority controlled clinical trial. Participants will be 220 individuals with emotional disorders, who are randomized to either a treatment as usual (individual cognitive behavioral therapy) or to a Unified Protocol condition in group format. Depression, anxiety, and diagnostic criteria are the primary outcome measures. Secondary measures include the assessment of positive and negative affect, anxiety control, personality traits, overall adjustment, and quality of life. An analysis of treatment satisfaction is also conducted. Assessment points include baseline, post-treatment, and three follow-ups at 3, 6, and 12 months. To control for missing data and possible biases, intention-to-treat and per-protocol analyses will be performed. This is the first randomized, controlled clinical trial to test the effectiveness of a transdiagnostic intervention in a group format for the treatment of emotional disorders in public settings in Spain. Results obtained from this study may have important clinical, social, and economic implications for public mental health settings in Spain. Retrospectively registered at https://clinicaltrials.gov/ . Trial NCT03064477 (March 10, 2017). The trial is active and recruitment is ongoing. Recruitment is expected to finish by January 2020.

Protocol Coordinator | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. KEY ROLES/RESPONSIBILITIES The Protocol Coordinator II: Provides comprehensive clinical and administrative support to the Brain Tumor Trial Collaborative, Neuro-Oncology Branch, NCI, National Institutes of Health Serves as a liaison with Principal Investigators (PIs), the associated study teams and a variety of offices associated with protocol development and approvals Orchestrates meetings with investigators and other key medical staff to identify required support Coordinates the writing and regulatory review processes that occur in tandem, facilitates the bi-directional dialogue and feedback between various teams, and assists investigators and medical writers on the production/revision of clinical research protocols Assists research staff in coordinating/navigating requirements for special circumstances and facilitates access to necessary services Facilitates initiation of intramural research by providing assistance in obtaining required approvals Coordinates with investigators and medical writers to ensure Institutional Review Board (IRB) and Food and Drug Administration (FDA) stipulations are appropriately addressed in a timely manner Provides consultation and assistance for all aspects of the protocol lifecycle including initial Investigational New Drug (IND) submission, IRB submission, continuing review applications, protocol amendments, annual reports, and protocol inactivation with IRB and FDA Tracks a portfolio of protocols through each lifecycle step; processes and tracks appropriate approvals (e.g., IRB, Data and Safety Monitoring Board, Radiation Safety, Office of Protocol Services, etc.) Provides administrative support to Scientific Review Committees (SRC), reviews proposed protocol documents to ensure they are complete, distributes to reviewers, documents meeting minutes, enters data into the IRIS database, facilitates processes to obtain approval to initiate and continue clinical research Creates, maintains and queries an IRB database of approved amendment descriptions Maintains records of the current protocol(s) version, current Informed Consent document(s), FDA Safe to Proceed designation, etc. for each IND Provides expertise in data management including data collection and analysis Develops procedural manuals for clinical trials protocols Participates in quality improvement and assurance involving International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines This position is located at the National Institutes of Health (NIH) in Bethesda, Maryland.

Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

PubMed

McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

2017-01-01

Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

Post-trial follow-up methodology in large randomized controlled trials: a systematic review protocol.

PubMed

Llewellyn-Bennett, Rebecca; Bowman, Louise; Bulbulia, Richard

2016-12-15

Clinical trials typically have a relatively short follow-up period, and may both underestimate potential benefits of treatments investigated, and fail to detect hazards, which can take much longer to emerge. Prolonged follow-up of trial participants after the end of the scheduled trial period can provide important information on both efficacy and safety outcomes. This protocol describes a systematic review to qualitatively compare methods of post-trial follow-up used in large randomized controlled trials. A systematic search of electronic databases and clinical trial registries will use a predefined search strategy. All large (more than 1000 adult participants) randomized controlled trials will be evaluated. Two reviewers will screen and extract data according to this protocol with the aim of 95% concordance of papers checked and discrepancies will be resolved by a third reviewer. Trial methods, participant retention rates and prevalence of missing data will be recorded and compared. The potential for bias will be evaluated using the Cochrane Risk of Bias tool (applied to the methods used during the in-trial period) with the aim of investigating whether the quality of the post-trial follow-up methodology might be predicted by the quality of the methods used for the original trial. Post-trial follow-up can provide valuable information about the long-term benefits and hazards of medical interventions. However, it can be logistically challenging and costly. The aim of this systematic review is to describe how trial participants have been followed-up post-trial in order to inform future post-trial follow-up designs. Not applicable for PROSPERO registration.

Assessing and Managing Risk with Suicidal Individuals

ERIC Educational Resources Information Center

Linehan, Marsh M.; Comtois, Katherine A.; Ward-Ciesielski, Erin F.

2012-01-01

The University of Washington Risk Assessment Protocol (UWRAP) and Risk Assessment and Management Protocol (UWRAMP) have been used in numerous clinical trials treating high-risk suicidal individuals over several years. These protocols structure assessors and treatment providers to provide a thorough suicide risk assessment, review standards of care…

Quality assurance of data collection in the multi-site community randomized trial and prevalence survey of the children's healthy living program.

PubMed

Yamanaka, Ashley; Fialkowski, Marie Kainoa; Wilkens, Lynne; Li, Fenfang; Ettienne, Reynolette; Fleming, Travis; Power, Julianne; Deenik, Jonathan; Coleman, Patricia; Leon Guerrero, Rachael; Novotny, Rachel

2016-09-02

Quality assurance plays an important role in research by assuring data integrity, and thus, valid study results. We aim to describe and share the results of the quality assurance process used to guide the data collection process in a multi-site childhood obesity prevalence study and intervention trial across the US Affiliated Pacific Region. Quality assurance assessments following a standardized protocol were conducted by one assessor in every participating site. Results were summarized to examine and align the implementation of protocol procedures across diverse settings. Data collection protocols focused on food and physical activity were adhered to closely; however, protocols for handling completed forms and ensuring data security showed more variability. Quality assurance protocols are common in the clinical literature but are limited in multi-site community-based studies, especially in underserved populations. The reduction in the number of QA problems found in the second as compared to the first data collection periods for the intervention study attest to the value of this assessment. This paper can serve as a reference for similar studies wishing to implement quality assurance protocols of the data collection process to preserve data integrity and enhance the validity of study findings. NIH clinical trial #NCT01881373.

Protocols and Hospital Mortality in Critically ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study

PubMed Central

Sevransky, Jonathan E.; Checkley, William; Herrera, Phabiola; Pickering, Brian W.; Barr, Juliana; Brown, Samuel M; Chang, Steven Y; Chong, David; Kaufman, David; Fremont, Richard D; Girard, Timothy D; Hoag, Jeffrey; Johnson, Steven B; Kerlin, Mehta P; Liebler, Janice; O'Brien, James; O'Keefe, Terence; Park, Pauline K; Pastores, Stephen M; Patil, Namrata; Pietropaoli, Anthony P; Putman, Maryann; Rice, Todd W.; Rotello, Leo; Siner, Jonathan; Sajid, Sahul; Murphy, David J; Martin, Greg S

2015-01-01

Objective Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized intensive care units have superior patient outcomes compared with less highly protocolized intensive care units. Design Observational study in which participating intensive care units completed a general assessment and enrolled new patients one day each week. Setting and Patients 6179 critically ill patients across 59 intensive care units in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study Interventions: None Measurements and Main Results The primary exposure was the number of intensive care unit protocols; the primary outcome was hospital mortality. 5809 participants were followed prospectively and 5454 patients in 57 intensive care units had complete outcome data. The median number of protocols per intensive care unit was 19 (IQR 15 to 21.5). In single variable analyses, there were no differences in intensive care unit and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in intensive care units with a high vs. low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p=0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between intensive care units with high vs. low numbers of protocols for lung protective ventilation in ARDS (47% vs. 52%; p=0.28) and for spontaneous breathing trials (55% vs. 51%; p=0.27). Conclusions Clinical protocols are highly prevalent in United States intensive care units. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality. PMID:26110488

Shortcomings of protocols of drug trials in relation to sponsorship as identified by Research Ethics Committees: analysis of comments raised during ethical review.

PubMed

van Lent, Marlies; Rongen, Gerard A; Out, Henk J

2014-12-10

Submission of study protocols to research ethics committees (RECs) constitutes one of the earliest stages at which planned trials are documented in detail. Previous studies have investigated the amendments requested from researchers by RECs, but the type of issues raised during REC review have not been compared by sponsor type. The objective of this study was to identify recurring shortcomings in protocols of drug trials based on REC comments and to assess whether these were more common among industry-sponsored or non-industry trials. Retrospective analysis of 226 protocols of drug trials approved in 2010-2011 by three RECs affiliated to academic medical centres in The Netherlands. For each protocol, information on sponsorship, number of participating centres, participating countries, study phase, registration status of the study drug, and type and number of subjects was retrieved. REC comments were extracted from decision letters sent to investigators after review and were classified using a predefined checklist that was based on legislation and guidelines on clinical drug research and previous literature. Most protocols received comments regarding participant information and consent forms (n = 182, 80.5%), methodology and statistical analyses (n = 160, 70.8%), and supporting documentation, including trial agreements and certificates of insurance (n = 154, 68.1%). Of the submitted protocols, 122 (54.0%) were non-industry and 104 (46.0%) were industry-sponsored trials. Non-industry trials more often received comments on subject selection (n = 44, 36.1%) than industry-sponsored trials (n = 18, 17.3%; RR, 1.58; 95% CI, 1.01 to 2.47), and on methodology and statistical analyses (n = 95, 77.9% versus n = 65, 62.5%, respectively; RR, 1.18; 95% CI, 1.01 to 1.37). Non-industry trials less often received comments on supporting documentation (n = 72, 59.0%) than industry-sponsored trials (n = 82, 78.8%; RR, 0.83; 95% CI, 0.72 to 0.95). RECs identified important ethical and methodological shortcomings in protocols of both industry-sponsored and non-industry drug trials. Investigators, especially of non-industry trials, should better prepare their research protocols in order to facilitate the ethical review process.

The Efficacy and Safety of Shen Guo Lao Nian Granule for Common Cold of Qi-Deficiency Syndrome: Study Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase II Clinical Trial

PubMed Central

Fu, Juanjuan; Ding, Hong; Yang, Haimiao; Huang, Yuhong

2017-01-01

Background Common cold is one of the most frequently occurring illnesses in primary healthcare services and represents considerable disease burden. Common cold of Qi-deficiency syndrome (CCQDS) is an important but less addressed traditional Chinese medicine (TCM) pattern. We designed a protocol to explore the efficacy, safety, and optimal dose of Shen Guo Lao Nian Granule (SGLNG) for treating CCQDS. Methods/Design This is a multicenter, randomized, double-blind, placebo-controlled, phase II clinical trial. A total of 240 eligible patients will be recruited from five centers. Patients are randomly assigned to high-dose group, middle-dose group, low-dose group, or control group in a 1 : 1 : 1 : 1 ratio. All drugs are required to be taken 3 times daily for 5 days with a 5-day follow-up period. Primary outcomes are duration of all symptoms, total score reduction on Jackson's scale, and TCM symptoms scale. Secondary outcomes include every single TCM symptom duration and score reduction, TCM main symptoms disappearance rate, curative effects, and comparison between Jackson's scale and TCM symptom scale. Ethics and Trial Registration This study protocol was approved by the Ethics Committee of Clinical Trials and Biomedicine of West China Hospital of Sichuan University (number IRB-2014-12) and registered with the Chinese Clinical Trial Registry (ChiCTR-IPR-15006349). PMID:29430253

Overcoming recruitment challenges in palliative care clinical trials.

PubMed

LeBlanc, Thomas W; Lodato, Jordan E; Currow, David C; Abernethy, Amy P

2013-11-01

Palliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study. The PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications. From an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%). Challenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.

Influence of Clinical Trial Site Enrollment on Patient Characteristics, Protocol Completion, and End Points: Insights From the ASCEND-HF Trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure).

PubMed

Greene, Stephen J; Hernandez, Adrian F; Sun, Jie-Lena; Metra, Marco; Butler, Javed; Ambrosy, Andrew P; Ezekowitz, Justin A; Starling, Randall C; Teerlink, John R; Schulte, Phillip J; Voors, Adriaan A; Armstrong, Paul W; O'Connor, Christopher M; Mentz, Robert J

2016-09-01

Most international acute heart failure trials have failed to show benefit with respect to key end points. The impact of site enrollment and protocol execution on trial performance is unclear. We assessed the impact of varying site enrollment volume among all 7141 acute heart failure patients from the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure). Overall, 398 sites enrolled ≥1 patient, and median enrollment was 12 patients (interquartile range, 5-23). Patients from high enrolling sites (>60 patients/site) tended to have lower ejection fraction, worse New York Heart Association functional class, and lower utilization of guideline-directed medical therapy but fewer comorbidities and lower B-type natriuretic peptide level. Every 10 patient increase (up to 100 patients) in site enrollment correlated with lower likelihood of protocol noncompletion (odds ratio, 0.93; 95% confidence interval [CI], 0.89-0.98). After adjustment, increasing site enrollment predicted higher risk of persistent dyspnea at 6 hours (per 10 patient increase: odds ratio 1.02; 95% CI, 1.01-1.03) but not at 24 hours (odds ratio, 0.99; 95% CI, 0.98-1.00). Higher site enrollment was independently associated with lower risk of 30-day death or rehospitalization (per 10 patient increase: odds ratio, 0.98, 95% CI, 0.96-0.99) but not 180-day mortality (hazard ratio, 0.99; 95% CI, 0.98-1.01). The influence of increasing site enrollment on clinical end points varied across geographic regions with strongest associations in Latin America and Asia-Pacific (all interaction P<0.01). In this large, acute heart failure trial, site enrollment correlated with protocol completion and was independently associated with trial end points. Individual and regional site performance present challenges to be considered in design of future acute heart failure trials. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00475852. © 2016 American Heart Association, Inc.

Ensuring Quality in AFRINEST and SATT

PubMed Central

2013-01-01

Background: Three randomized open-label clinical trials [Simplified Antibiotic Therapy Trial (SATT) Bangladesh, SATT Pakistan and African Neonatal Sepsis Trial (AFRINEST)] were developed to test the equivalence of simplified antibiotic regimens compared with the standard regimen of 7 days of parenteral antibiotics. These trials were originally conceived and designed separately; subsequently, significant efforts were made to develop and implement a common protocol and approach. Previous articles in this supplement briefly describe the specific quality control methods used in the individual trials; this article presents additional information about the systematic approaches used to minimize threats to validity and ensure quality across the trials. Methods: A critical component of quality control for AFRINEST and SATT was striving to eliminate variation in clinical assessments and decisions regarding eligibility, enrollment and treatment outcomes. Ensuring appropriate and consistent clinical judgment was accomplished through standardized approaches applied across the trials, including training, assessment of clinical skills and refresher training. Standardized monitoring procedures were also applied across the trials, including routine (day-to-day) internal monitoring of performance and adherence to protocols, systematic external monitoring by funding agencies and external monitoring by experienced, independent trial monitors. A group of independent experts (Technical Steering Committee/Technical Advisory Group) provided regular monitoring and technical oversight for the trials. Conclusions: Harmonization of AFRINEST and SATT have helped to ensure consistency and quality of implementation, both internally and across the trials as a whole, thereby minimizing potential threats to the validity of the trials’ results. PMID:23945575

Biopsychosocial influence on shoulder pain: rationale and protocol for a pre-clinical trial

PubMed Central

George, Steven Z.; Staud, Roland; Borsa, Paul A.; Wu, Samuel S.; Wallace, Margaret R.; Greenfield, Warren. H.; Mackie, Lauren N.; Fillingim, Roger B.

2017-01-01

Background Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12 month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup. Methods Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation. Conclusion This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain. Trial Registration ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015) PMID:28315479

Design and analysis issues for economic analysis alongside clinical trials.

PubMed

Marshall, Deborah A; Hux, Margaret

2009-07-01

Clinical trials can offer a valuable and efficient opportunity to collect the health resource use and outcomes data for economic evaluation. However, economic and clinical studies differ fundamentally in the question they seek to answer. The design and analysis of trial-based cost-effectiveness studies require special consideration, which are reviewed in this article. Traditional randomized controlled trials, using an experimental design with a controlled protocol, are designed to measure safety and efficacy for product registration. Cost-effectiveness analysis seeks to measure effectiveness in the context of routine clinical practice, and requires collection of health care resources to allow estimation of cost over an equal timeframe for each treatment alternative. In assessing suitability of a trial for economic data collection, the comparator treatment and other protocol factors need to reflect current clinical practice and the trial follow-up must be sufficiently long to capture important costs and effects. The broadest available population and a measure of effectiveness reflecting important benefits for patients are preferred for economic analyses. Special analytical issues include dealing with missing and censored cost data, assessing uncertainty of the incremental cost-effectiveness ratio, and accounting for the underlying heterogeneity in patient subgroups. Careful consideration also needs to be given to data from multinational studies since practice patterns can differ across countries. Although clinical trials can be an efficient opportunity to collect data for economic evaluation, careful consideration of the suitability of the study design, and appropriate analytical methods must be applied to obtain rigorous results.

Knowledge translation interventions for critically ill patients: a systematic review*.

PubMed

Sinuff, Tasnim; Muscedere, John; Adhikari, Neill K J; Stelfox, Henry T; Dodek, Peter; Heyland, Daren K; Rubenfeld, Gordon D; Cook, Deborah J; Pinto, Ruxandra; Manoharan, Venika; Currie, Jan; Cahill, Naomi; Friedrich, Jan O; Amaral, Andre; Piquette, Dominique; Scales, Damon C; Dhanani, Sonny; Garland, Allan

2013-11-01

We systematically reviewed ICU-based knowledge translation studies to assess the impact of knowledge translation interventions on processes and outcomes of care. We searched electronic databases (to July, 2010) without language restrictions and hand-searched reference lists of relevant studies and reviews. Two reviewers independently identified randomized controlled trials and observational studies comparing any ICU-based knowledge translation intervention (e.g., protocols, guidelines, and audit and feedback) to management without a knowledge translation intervention. We focused on clinical topics that were addressed in greater than or equal to five studies. Pairs of reviewers abstracted data on the clinical topic, knowledge translation intervention(s), process of care measures, and patient outcomes. For each individual or combination of knowledge translation intervention(s) addressed in greater than or equal to three studies, we summarized each study using median risk ratio for dichotomous and standardized mean difference for continuous process measures. We used random-effects models. Anticipating a small number of randomized controlled trials, our primary meta-analyses included randomized controlled trials and observational studies. In separate sensitivity analyses, we excluded randomized controlled trials and collapsed protocols, guidelines, and bundles into one category of intervention. We conducted meta-analyses for clinical outcomes (ICU and hospital mortality, ventilator-associated pneumonia, duration of mechanical ventilation, and ICU length of stay) related to interventions that were associated with improvements in processes of care. From 11,742 publications, we included 119 investigations (seven randomized controlled trials, 112 observational studies) on nine clinical topics. Interventions that included protocols with or without education improved continuous process measures (seven observational studies and one randomized controlled trial; standardized mean difference [95% CI]: 0.26 [0.1, 0.42]; p = 0.001 and four observational studies and one randomized controlled trial; 0.83 [0.37, 1.29]; p = 0.0004, respectively). Heterogeneity among studies within topics ranged from low to extreme. The exclusion of randomized controlled trials did not change our results. Single-intervention and lower-quality studies had higher standardized mean differences compared to multiple-intervention and higher-quality studies (p = 0.013 and 0.016, respectively). There were no associated improvements in clinical outcomes. Knowledge translation interventions in the ICU that include protocols with or without education are associated with the greatest improvements in processes of critical care.

The Brustkrebs-Studien.de website for breast cancer patients: User acceptance of a German internet portal offering information on the disease and treatment options, and a clinical trials matching service

PubMed Central

2010-01-01

Background The internet portal http://www.brustkrebs-studien.de (BKS) was launched in 2000 by the German Society of Senology (DGS) and the Baden-Württemberg Institute for Women's Health (IFG) to provide expert-written information on breast cancer online and to encourage and facilitate the participation of breast cancer patients in clinical trials. We describe the development of BKS and its applications, and report on website statistics and user acceptance. Methods Existing registries, including ClinicalTrials.gov, were analysed before we designed BKS, which combines a trial registry, a knowledge portal, and an online second opinion service. An advisory board guided the process. Log files and patient enquiries for trial participation and second opinions were analysed. A two-week user satisfaction survey was conducted online. Results During 10/2005-06/2010, the portal attracted 702,655 visitors, generating 15,507,454 page views. By 06/2010, the website's active scientific community consisted of 189 investigators and physicians, and the registry covered 163 clinical trial protocols. In 2009, 143 patients requested trial enrolment and 119 sought second opinions or individual treatment advice from the expert panel. During the two-week survey in 2008, 5,702 BKS visitors submitted 507 evaluable questionnaires. Portal acceptance was high. Respondents trusted information correctness (80%), welcomed self-matching to clinical trials (79%) and planned to use the portal in the future (76%) and recommend it to others (81%). Conclusions BKS is an established and trusted breast cancer information platform offering up-to-date resources and protocols to the growing physician and patient community to encourage participation in clinical trials. Further studies are needed to assess potential increases in trial enrolment by eligibility matching services. PMID:21126358

Conducting clinical trials in Singapore.

PubMed

Woo, K T

1999-04-01

All clinical trials in Singapore will now have to conform to the Medicines (Clinical Trials) Amended Regulations 1998 and the Singapore Good Clinical Practice (GCP) Guidelines 1998. The Medical Clinical Research Committee (MCRC) has been established to oversee the conduct of clinical drug trials in Singapore and together with the legislations in place, these will ensure that clinical trials conducted in Singapore are properly controlled and the well-being of trial subjects are safe guarded. All clinical drug trials require a Clinical Trial Certificate from the MCRC before the trial can proceed. The hospital ethics committee (EC) vets the application for a trial certificate before it is sent to MCRC. The drug company sponsoring the trial has to indemnify the trial investigators and the hospital for negligence arising from the trial. The MCRC, apart from ensuring the safety of trial subjects, has to provide continuing review of the clinical trial and monitors adverse events in the course of the trial. The EC will conduct continuing review of clinical trials. When a non-drug clinical trial is carried out, the EC will ensure that the proposed protocol addresses ethical concerns and meets regulatory requirements for such trials. There is great potential for pharmaceutical Research & Development (R&D) in Singapore. We must develop our skills and infrastructure in clinical trials to enable Singapore to be a regional hub for R&D of drugs in Asia.

Results of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial.

PubMed

Jameson, Michael G; McNamara, Jo; Bailey, Michael; Metcalfe, Peter E; Holloway, Lois C; Foo, Kerwyn; Do, Viet; Mileshkin, Linda; Creutzberg, Carien L; Khaw, Pearly

2016-08-01

Protocol deviations in Randomised Controlled Trials have been found to result in a significant decrease in survival and local control. In some cases, the magnitude of the detrimental effect can be larger than the anticipated benefits of the interventions involved. The implementation of appropriate quality assurance of radiotherapy measures for clinical trials has been found to result in fewer deviations from protocol. This paper reports on a benchmarking study conducted in preparation for the PORTEC-3 trial in Australasia. A benchmarking CT dataset was sent to each of the Australasian investigators, it was requested they contour and plan the case according to trial protocol using local treatment planning systems. These data was then sent back to Trans-Tasman Oncology Group for collation and analysis. Thirty three investigators from eighteen institutions across Australia and New Zealand took part in the study. The mean clinical target volume (CTV) volume was 383.4 (228.5-497.8) cm(3) and the mean dose to a reference gold standard CTV was 48.8 (46.4-50.3) Gy. Although there were some large differences in the contouring of the CTV and its constituent parts, these did not translate into large variations in dosimetry. Where individual investigators had deviations from the trial contouring protocol, feedback was provided. The results of this study will be used to compare with the international study QA for the PORTEC-3 trial. © 2016 The Royal Australian and New Zealand College of Radiologists.

21 CFR 312.320 - Treatment IND or treatment protocol.

Code of Federal Regulations, 2010 CFR

2010-04-01

... clinical trial under an IND designed to support a marketing application for the expanded access use, or (ii) All clinical trials of the drug have been completed; and (2) Marketing status. The sponsor is actively pursuing marketing approval of the drug for the expanded access use with due diligence; and (3) Evidence...

Designing effective drug and device development programs for hospitalized heart failure: A proposal for pretrial registries

PubMed Central

Greene, Stephen J.; Shah, Ami N.; Butler, Javed; Ambrosy, Andrew P.; Anker, Stefan D.; Chioncel, Ovidiu; Collins, Sean P.; Dinh, Wilfried; Dunnmon, Preston M.; Fonarow, Gregg C.; Lam, Carolyn S. P.; Mentz, Robert J.; Pieske, Burkert; Roessig, Lothar; Rosano, Giuseppe M. C.; Sato, Naoki; Vaduganathan, Muthiah; Gheorghiade, Mihai

2014-01-01

Recent international phase III clinical trials of novel therapies for hospitalized heart failure (HHF) have failed to improve the unacceptably high postdischarge event rate. These large studies have demonstrated notable geographic and site-specific variation in patient profiles and enrollment. Possible contributors to the lack of success in HHF outcome trials include challenges in selecting clinical sites capable of (1) providing adequate numbers of appropriately selected patients and (2) properly executing the study protocol. We propose a “pretrial registry” as a novel tool for improving the efficiency and quality of international HHF trials by focusing on the selection and cultivation of high-quality sites. A pretrial registry may help assess a site’s ability to achieve adequate enrollment of the target patient population, integrate protocol requirements into clinical workflow, and accomplish appropriate follow-up. Although such a process would be associated with additional upfront resource investment, this appropriation may be modest in comparison with the downstream costs associated with maintenance of poorly performing sites, failed clinical trials, and the global health and economic burden of HHF. This review is based on discussions between scientists, clinical trialists, and regulatory representatives regarding methods for improving international HHF trials that took place at the United States Food and Drug Administration on January 12th, 2012. PMID:25066552

[Importance of clinical trial design and standardized implementation in ophthalmology].

PubMed

Xu, Xun

2013-06-01

Clinical trial is an important medical research method, as well as the bridge of translational medicine. The results of scientific evidences are useful to make clinical practice guidelines. At present,much experience of carrying out ophthalmology clinical trials has been obtained and achieved, but there are still some scientific, practical and ethical problems to be solved,because of their impact on the authenticity and reliability of the results. Therefore, attaching great importance to design of the clinical research and implement of the standardization would be the goal and the development direction. Clinical trial design rely on objective, follow international design principles on the ethics,randomization, blinding and placebo setting. During the trial implementation, personnel training,project management and monitoring would help to reduce protocol deviation and ensure data authenticity.

The evaluation of complex clinical trial protocols: resources available to research ethics committees and the use of clinical trial registries--a case study.

PubMed

Homedes, Núria; Ugalde, Antonio

2015-06-01

To assess the potential role of clinical trial (CT) registries and other resources available to research ethics committees (RECs) in the evaluation of complex CT protocols in low-income and middle-income countries. Using a case study approach, the authors examined the decision-making process of a REC in Argentina and its efforts to use available resources to decide on a complex protocol. We also analysed the information in the USA and other CT registries and consulted 24 CT experts in seven countries. Information requested by the Argentinean REC from other national RECs and ethics' experts was not useful to verify the adequacy of the REC's decision whether or not to approve the CT. The responses from the national regulatory agency and the sponsor were not helpful either. The identification of international resources that could assist was beyond the REC's capability. The information in the USA and other CT registries is limited, and at times misleading; and its accuracy is not verified by register keepers. RECs have limited access to experts and institutions that could assist them in their deliberations. Sponsors do not always answer RECs' request for information to properly conduct the ethical and methodological assessment of CT protocols. The usefulness of the CT registries is curtailed by the lack of appropriate codes and by data errors. Information about reasons for rejection, withdrawal or suspension of the trial should be included in the registries. Establishing formal channels of communication among national and foreign RECs and with independent international reference centres could strengthen the ethical review of CT protocols. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

How to write a surgical clinical research protocol: literature review and practical guide.

PubMed

Rosenthal, Rachel; Schäfer, Juliane; Briel, Matthias; Bucher, Heiner C; Oertli, Daniel; Dell-Kuster, Salome

2014-02-01

The study protocol is the core document of every clinical research project. Clinical research in studies involving surgical interventions presents some specific challenges, which need to be accounted for and described in the study protocol. The aim of this review is to provide a practical guide for developing a clinical study protocol for surgical interventions with a focus on methodologic issues. On the basis of an in-depth literature search of methodologic literature and on some cardinal published surgical trials and observational studies, the authors provides a 10-step guide for developing a clinical study protocol in surgery. This practical guide outlines key methodologic issues important when planning an ethically and scientifically sound research project involving surgical interventions, with the ultimate goal of providing high-level evidence relevant for health care decision making in surgery. Copyright © 2014 Elsevier Inc. All rights reserved.

Cognitive behavioral therapy program for cannabis use cessation in first-episode psychosis patients: study protocol for a randomized controlled trial.

PubMed

González-Ortega, Itxaso; Echeburúa, Enrique; García-Alocén, Adriana; Vega, Patricia; González-Pinto, Ana

2016-07-29

The high rate of cannabis use among patients with first-episode psychosis (FEP), as well as the associated negative impact on illness course and treatment outcomes, underlines the need for effective interventions in these populations. However, to date, there have been few clinical treatment trials (of pharmacological or psychological interventions) that have specifically focused on addressing comorbid cannabis use among these patients. The aim of this paper is to describe the design of a study protocol for a randomized controlled trial in which the objective is to assess the efficacy of a specific cognitive behavioral therapy program for cannabis cessation in patients with FEP compared to standard treatment (psychoeducation). This is a single-blind randomized study with 1 year of follow-up. Patients are to be randomly assigned to one of two treatments: (1) specific cognitive behavioral therapy for cannabis cessation composed of 1-hour sessions once a week for 16 weeks, in addition to pharmacological treatment scheduled by the psychiatrist, or (2) a control group (psychoeducation + pharmacological treatment) following the same format as the experimental group. Participants in both groups will be evaluated at baseline (pre-treatment), at 16 weeks (post-treatment), and at 3 and 6 months and 1 year of follow-up. The primary outcome will be that patients in the experimental group will have greater cannabis cessation than patients in the control group at post-treatment. The secondary outcome will be that the experimental group will have better clinical and functional outcomes than the control group. This study provides the description of a clinical trial design based on specific cognitive behavioral therapy for cannabis cessation in FEP patients, aiming to improve clinical and functional outcome, as well as tackling the addictive disorder. NCT02319746 ClinicalTrials.gov Identifier. ClinicalTrials.gov Protocol and Results Registration System (PRS) Receipt Release Date: 15 December 2014.

Opportunistic detection of atrial fibrillation in subjects aged 65 years or older in primare care: a randomised clinical trial of efficacy. DOFA-AP study protocol.

PubMed

Pérula-de-Torres, Luis Á; Martínez-Adell, Miguel Á; González-Blanco, Virginia; Baena-Díez, José M; Martín-Rioboó, Enrique; Parras-Rejano, Juan M; González-Lama, Jesús; Martín-Alvarez, Remedios; Ruiz-Moral, Roger; Fernández-García, José Á; Pérez-Díaz, Modesto; Ruiz-de-Castroviejo, Joaquin; Pérula-de-Torres, Carlos; Valero-Martín, Antonio; Roldán-Villalobos, Ana; Criado-Larumbe, Margarita; Burdoy-Joaquín, Emili; Coma-Solé, Montserrat; Cervera-León, Mercè; Cuixart-Costa, Lluís

2012-10-30

Clinical Practice Guidelines recommend using peripheral blood pulse measuring as a screening test for Atrial Fibrillation. However, there is no adequate evidence supporting the efficacy of such procedure in primary care clinical practice. This paper describes a study protocol designed to verify whether early opportunistic screening for Atrial Fibrillation by measuring blood pulse is more effective than regular practice in subjects aged 65 years attending primary care centers. An cluster-randomized controlled trial conducted in Primary Care Centers of the Spanish National Health Service. A total of 269 physicians and nurses will be allocated to one of the two arms of the trial by stratified randomization with a 3:2 ratio (three practitioners will be assigned to the Control Group for every two practitioners assigned to the Experimental Group). As many as 12 870 patients aged 65 years or older and meeting eligibility criteria will be recruited (8 580 will be allocated to the Experimental Group and 4 290 to the Control Group). Randomization and allocation to trial groups will be carried out by a central computer system. The Experimental Group practitioners will conduct an opportunistic case finding for patients with Atrial Fibrillation, while the Control Group practitioners will follow the regular guidelines. The first step will be finding new Atrial Fibrillation cases. A descriptive inferential analysis will be performed (bivariate and multivariate by multilevel logistic regression analysis). If our hypothesis is confirmed, we expect Primary Care professionals to take a more proactive approach and adopt a new protocol when a patient meeting the established screening criteria is identified. Finally, we expect this measure to be incorporated into Clinical Practice Guidelines. The study is registered as NCT01291953 (ClinicalTrials.gob).

Independent but coordinated trials: insights from the practice-based Opportunities for Weight Reduction Trials Collaborative Research Group.

PubMed

Yeh, Hsin-Chieh; Clark, Jeanne M; Emmons, Karen E; Moore, Reneé H; Bennett, Gary G; Warner, Erica T; Sarwer, David B; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A; Wells, Barbara; Wadden, Thomas A; Colditz, Graham A; Appel, Lawrence J

2010-08-01

The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the 'Practice-based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.' We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. The Collaborative Research Group consists of three individual studies: 'Be Fit, Be Well' (Washington University in St. Louis/Harvard University), 'POWER Hopkins' (Johns Hopkins), and 'POWER-UP' (University of Pennsylvania). There are a total of 15 participating clinics with ~1100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. The challenges of the organizational design include the complex decision-making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols.

NIDA’s Clinical Trials Network: An Opportunity for HIV Research in Community Substance Abuse Treatment Programs

PubMed Central

Tross, Susan; Campbell, Aimee N. C.; Calsyn, Donald A.; Metsch, Lisa R.; Sorensen, James L.; Shoptaw, Steven; Haynes, Louise; Woody, George E.; Malow, Robert M.; Brown, Lawrence S.; Feaster, Daniel J.; Booth, Robert E.; Mandler, Raul N.; Masson, Carmen; Holmes, Beverly W.; Colfax, Grant; Brooks, Audrey J.; Hien, Denise A.; Schackman, Bruce R.; Korthuis, P. Todd; Miele, Gloria M.

2012-01-01

Background/Objectives HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years. Results While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs. Conclusion/Significance While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed. PMID:21854270

NIDA's Clinical Trials Network: an opportunity for HIV research in community substance abuse treatment programs.

PubMed

Tross, Susan; Campbell, Aimee N C; Calsyn, Donald A; Metsch, Lisa R; Sorensen, James L; Shoptaw, Steven; Haynes, Louise; Woody, George E; Malow, Robert M; Brown, Lawrence S; Feaster, Daniel J; Booth, Robert E; Mandler, Raul N; Masson, Carmen; Holmes, Beverly W; Colfax, Grant; Brooks, Audrey J; Hien, Denise A; Schackman, Bruce R; Korthuis, P Todd; Miele, Gloria M

2011-09-01

HIV continues to be a significant problem among substance users and their sexual partners in the United States. The National Drug Abuse Treatment Clinical Trials Network (CTN) offers a national platform for effectiveness trials of HIV interventions in community substance abuse treatment programs. This article presents the HIV activities of the CTN during its first 10 years. While emphasizing CTN HIV protocols, this article reviews the (1) HIV context for this work; (2) the collaborative process among providers, researchers, and National Institute on Drug Abuse CTN staff, on which CTN HIV work was based; (3) results of CTN HIV protocols and HIV secondary analyses in CTN non-HIV protocols; and (4) implications for future HIV intervention effectiveness research in community substance abuse treatment programs. While the feasibility of engaging frontline providers in this research is highlighted, the limitations of small to medium effect sizes and weak adoption and sustainability in everyday practice are also discussed.

Gender research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: a summary of findings.

PubMed

Greenfield, Shelly F; Rosa, Carmen; Putnins, Susan I; Green, Carla A; Brooks, Audrey J; Calsyn, Donald A; Cohen, Lisa R; Erickson, Sarah; Gordon, Susan M; Haynes, Louise; Killeen, Therese; Miele, Gloria; Tross, Susan; Winhusen, Theresa

2011-09-01

The National Institute of Drug Abuse's National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable subgroups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. To review gender-related findings from published CTN clinical trials and related studies from January 2000 to March 2010. CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors; or implemented gender-specific protocols. The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized controlled trials in community settings, of which 4 have been gender-specific. This article summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance-using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods.

Interventions for investigating and identifying the causes of stillbirth.

PubMed

Wojcieszek, Aleena M; Shepherd, Emily; Middleton, Philippa; Gardener, Glenn; Ellwood, David A; McClure, Elizabeth M; Gold, Katherine J; Khong, Teck Yee; Silver, Robert M; Erwich, Jan Jaap Hm; Flenady, Vicki

2018-04-30

Identification of the causes of stillbirth is critical to the primary prevention of stillbirth and to the provision of optimal care in subsequent pregnancies. A wide variety of investigations are available, but there is currently no consensus on the optimal approach. Given their cost and potential to add further emotional burden to parents, there is a need to systematically assess the effect of these interventions on outcomes for parents, including psychosocial outcomes, economic costs, and on rates of diagnosis of the causes of stillbirth. To assess the effect of different tests, protocols or guidelines for investigating and identifying the causes of stillbirth on outcomes for parents, including psychosocial outcomes, economic costs, and rates of diagnosis of the causes of stillbirth. We searched Cochrane Pregnancy and Childbirth's Trials Register (31 August 2017), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (15 May 2017). We planned to include randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. We planned to include studies published as abstract only, provided there was sufficient information to allow us to assess study eligibility. We planned to exclude cross-over trials.Participants included parents (including mothers, fathers, and partners) who had experienced a stillbirth of 20 weeks' gestation or greater.This review focused on interventions for investigating and identifying the causes of stillbirth. Such interventions are likely to be diverse, but could include:* review of maternal and family history, and current pregnancy and birth history;* clinical history of present illness;* maternal investigations (such as ultrasound, amniocentesis, antibody screening, etc.);* examination of the stillborn baby (including full autopsy, partial autopsy or noninvasive components, such as magnetic resonance imaging (MRI), computerised tomography (CT) scanning, and radiography);* umbilical cord examination;* placental examination including histopathology (microscopic examination of placental tissue); and* verbal autopsy (interviews with care providers and support people to ascertain causes, without examination of the baby).We planned to include trials assessing any test, protocol or guideline (or combinations of tests/protocols/guidelines) for investigating the causes of stillbirth, compared with the absence of a test, protocol or guideline, or usual care (further details are presented in the Background, see Description of the intervention).We also planned to include trials comparing any test, protocol or guideline (or combinations of tests/protocols/guidelines) for investigating the causes of stillbirth with another, for example, the use of a limited investigation protocol compared with a comprehensive investigation protocol. Two review authors assessed trial eligibility independently. We excluded five studies that were not RCTs. There were no eligible trials for inclusion in this review. There is currently a lack of RCT evidence regarding the effectiveness of interventions for investigating and identifying the causes of stillbirth. Seeking to determine the causes of stillbirth is an essential component of quality maternity care, but it remains unclear what impact these interventions have on the psychosocial outcomes of parents and families, the rates of diagnosis of the causes of stillbirth, and the care and management of subsequent pregnancies following stillbirth. Due to the absence of trials, this review is unable to inform clinical practice regarding the investigation of stillbirths, and the specific investigations that would determine the causes.Future RCTs addressing this research question would be beneficial, but the settings in which the trials take place, and their design, need to be given careful consideration. Trials need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should also be considered in any future trials.

Vaccine Immunotherapy for Prostate Cancer

DTIC Science & Technology

2012-05-01

adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols have been used in the trial: #1 - Phase II study of Adenovirus/PSA...this award is to conduct a Phase II clinical trial (Study) of an adenovirus/PSA (Ad/PSA) vaccine for the treatment of prostate cancer. Two protocols...suddenly prior to study treatment . And one patient previously reported as a screen failure became eligible and was treated. This subject was not

The Virtual Anemia Trial: An Assessment of Model‐Based In Silico Clinical Trials of Anemia Treatment Algorithms in Patients With Hemodialysis

PubMed Central

Topping, Alice; Kappel, Franz; Thijssen, Stephan; Kotanko, Peter

2018-01-01

In silico approaches have been proposed as a novel strategy to increase the repertoire of clinical trial designs. Realistic simulations of clinical trials can provide valuable information regarding safety and limitations of treatment protocols and have been shown to assist in the cost‐effective planning of clinical studies. In this report, we present a blueprint for the stepwise integration of internal, external, and ecological validity considerations in virtual clinical trials (VCTs). We exemplify this approach in the context of a model‐based in silico clinical trial aimed at anemia treatment in patients undergoing hemodialysis (HD). Hemoglobin levels and subsequent anemia treatment were simulated on a per patient level over the course of a year and compared to real‐life clinical data of 79,426 patients undergoing HD. The novel strategies presented here, aimed to improve external and ecological validity of a VCT, significantly increased the predictive power of the discussed in silico trial. PMID:29368434

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery

PubMed Central

Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-01-01

Introduction Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions—physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. Methods and analysis This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. Ethics and dissemination This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. Trial registration number NCT02921932 (ClinicalTrials.gov) PMID:28778994

Study protocol of a pragmatic, randomised controlled pilot trial: clinical effectiveness on smoking cessation of traditional and complementary medicine interventions, including acupuncture and aromatherapy, in combination with nicotine replacement therapy

PubMed Central

Jang, Soobin; Park, Sunju; Jang, Bo-Hyoung; Park, Yu Lee; Lee, Ju Ah; Cho, Chung-Sik; Go, Ho-Yeon; Shin, Yong Cheol; Ko, Seong-Gyu

2017-01-01

Introduction Nicotine dependence is a disease, and tobacco use is related to 6 million deaths annually worldwide. Recently, in many countries, there has been growing interest in the use of traditional and complementary medicine (T&CM) methods, especially acupuncture, as therapeutic interventions for smoking cessation. The aim of this pilot study is to investigate the effectiveness of T&CM interventions on smoking cessation. Methods and analysis The STOP (Stop Tobacco Programme using traditional Korean medicine) study is designed to be a pragmatic, open-label, randomised pilot trial. This trial will evaluate whether adding T&CM methods (ie, ear and body acupuncture, aromatherapy) to conventional cessation methods (ie, nicotine replacement therapy (NRT), counselling) increases smoking cessation rates. Forty participants over 19 years old who are capable of communicating in Korean will be recruited. They will be current smokers who meet one of the following criteria: (1) smoke more than 10 cigarettes a day, (2) smoke less than 10 cigarettes a day and previously failed to cease smoking, or (3) smoke fewer than 10 cigarettes a day and have a nicotine dependence score (Fagerstrom Test for Nicotine Dependence) of 4 points or more. The trial will consist of 4 weeks of treatment and a 20 week follow-up period. A statistician will perform the statistical analyses for both the intention-to-treat (all randomly assigned participants) and per-protocol (participants who completed the trial without any protocol deviations) data using SAS 9.1.3. Ethics and dissemination This study has been approved by the Institutional Review Board (IRB) of the Dunsan Korean Medicine Hospital of Daejeon University (IRB reference no: DJDSKH-15-BM-11–1, Protocol No. version 4.1.).The protocol will be reapproved by IRB if it requires amendment. The trial will be conducted according to the Declaration of Helsinki, 7th version (2013). This study is designed to minimise the risk to participants, and the investigators will explain the study to the participants in detail. As an ethical clinical trial, the control group will also be given conventional cessation treatments, including NRT and counselling. Participants will be screened and provided with a registration number to protect their personal information. Informed consent will be obtained from the participants prior to enrolling them in the trial. Participants will be allowed to withdraw at anytime without penalty. Trial registration number ClinicalTrials.gov (NCT02768025); pre-results. PMID:28576892

Is a controlled randomised trial the non-plus-ultra design? A contribution to discussion on comparative, controlled, non-randomised trials.

PubMed

Gaus, Wilhelm; Muche, Rainer

2013-05-01

Clinical studies provide formalised experience for evidence-based medicine (EBM). Many people consider a controlled randomised trial (CRT, identical to a randomised controlled trial RCT) to be the non-plus-ultra design. However, CRTs also have limitations. The problem is not randomisation itself but informed consent for randomisation and masking of therapies according to today's legal and ethical standards. We do not want to de-rate CRTs, but we would like to contribute to the discussion on clinical research methodology. Informed consent to a CRT and masking of therapies plainly select patients. The excellent internal validity of CRTs can be counterbalanced by poor external validity, because internal and external validity act as antagonists. In a CRT, patients may feel like guinea pigs, this can decrease compliance, cause protocol violations, reduce self-healing properties, suppress unspecific therapeutic effects and possibly even modify specific efficacy. A control group (comparative study) is most important for the degree of evidence achieved by a trial. Study control by detailed protocol and good clinical practice (controlled study) is second in importance and randomisation and masking is third (thus the sequence CRT instead of RCT). Controlled non-randomised trials are just as ambitious and detailed as CRTs. We recommend clinicians and biometricians to take high quality controlled non-randomised trials into consideration more often. They combine good internal and external validity, better suit daily medical practice, show better patient compliance and fewer protocol violations, deliver estimators unbiased by alienated patients, and perhaps provide a clearer explanation of the achieved success. Copyright © 2013 Elsevier Inc. All rights reserved.

Radiotherapy for Prostate Cancer: is it 'what you do' or 'the way that you do it'? A UK Perspective on Technique and Quality Assurance.

PubMed

Mason, M D; Moore, R; Jones, G; Lewis, G; Donovan, J L; Neal, D E; Hamdy, F C; Lane, J A; Staffurth, J N

2016-09-01

The treatment of prostate cancer has evolved markedly over the last 40 years, including radiotherapy, notably with escalated dose and targeting. However, the optimal treatment for localised disease has not been established in comparative randomised trials. The aim of this article is to describe the history of prostate radiotherapy trials, including their quality assurance processes, and to compare these with the ProtecT trial. The UK ProtecT randomised trial compares external beam conformal radiotherapy, surgery and active monitoring for clinically localised prostate cancer and will report on the primary outcome (disease-specific mortality) in 2016 following recruitment between 1999 and 2009. The embedded quality assurance programme consists of on-site machine dosimetry at the nine trial centres, a retrospective review of outlining and adherence to dose constraints based on the trial protocol in 54 participants (randomly selected, around 10% of the total randomised to radiotherapy, n = 545). These quality assurance processes and results were compared with prostate radiotherapy trials of a comparable era. There has been an increasingly sophisticated quality assurance programme in UK prostate radiotherapy trials over the last 15 years, reflecting dose escalation and treatment complexity. In ProtecT, machine dosimetry results were comparable between trial centres and with the UK RT01 trial. The outlining review showed that most deviations were clinically acceptable, although three (1.4%) may have been of clinical significance and were related to outlining of the prostate. Seminal vesicle outlining varied, possibly due to several prostate trials running concurrently with different protocols. Adherence to dose constraints in ProtecT was considered acceptable, with 80% of randomised participants having two or less deviations and planning target volume coverage was excellent. The ProtecT trial quality assurance results were satisfactory and comparable with trials of its era. Future trials should aim to standardise treatment protocols and quality assurance programmes where possible to reduce complexities for centres involved in multiple trials. Copyright © 2016. Published by Elsevier Ltd.

Opportunistic detection of atrial fibrillation in subjects aged 65 years or older in primare care: a randomised clinical trial of efficacy. DOFA-AP study protocol

PubMed Central

2012-01-01

Background Clinical Practice Guidelines recommend using peripheral blood pulse measuring as a screening test for Atrial Fibrillation. However, there is no adequate evidence supporting the efficacy of such procedure in primary care clinical practice. This paper describes a study protocol designed to verify whether early opportunistic screening for Atrial Fibrillation by measuring blood pulse is more effective than regular practice in subjects aged 65 years attending primary care centers. Methods/design An cluster-randomized controlled trial conducted in Primary Care Centers of the Spanish National Health Service. A total of 269 physicians and nurses will be allocated to one of the two arms of the trial by stratified randomization with a 3:2 ratio (three practitioners will be assigned to the Control Group for every two practitioners assigned to the Experimental Group). As many as 12 870 patients aged 65 years or older and meeting eligibility criteria will be recruited (8 580 will be allocated to the Experimental Group and 4 290 to the Control Group). Randomization and allocation to trial groups will be carried out by a central computer system. The Experimental Group practitioners will conduct an opportunistic case finding for patients with Atrial Fibrillation, while the Control Group practitioners will follow the regular guidelines. The first step will be finding new Atrial Fibrillation cases. A descriptive inferential analysis will be performed (bivariate and multivariate by multilevel logistic regression analysis). Discussion If our hypothesis is confirmed, we expect Primary Care professionals to take a more proactive approach and adopt a new protocol when a patient meeting the established screening criteria is identified. Finally, we expect this measure to be incorporated into Clinical Practice Guidelines. Trial registration The study is registered as NCT01291953 (ClinicalTrials.gob) PMID:23130754

Automatic control of pressure support for ventilator weaning in surgical intensive care patients.

PubMed

Schädler, Dirk; Engel, Christoph; Elke, Gunnar; Pulletz, Sven; Haake, Nils; Frerichs, Inéz; Zick, Günther; Scholz, Jens; Weiler, Norbert

2012-03-15

Despite its ability to reduce overall ventilation time, protocol-guided weaning from mechanical ventilation is not routinely used in daily clinical practice. Clinical implementation of weaning protocols could be facilitated by integration of knowledge-based, closed-loop controlled protocols into respirators. To determine whether automated weaning decreases overall ventilation time compared with weaning based on a standardized written protocol in an unselected surgical patient population. In this prospective controlled trial patients ventilated for longer than 9 hours were randomly allocated to receive either weaning with automatic control of pressure support ventilation (automated-weaning group) or weaning based on a standardized written protocol (control group) using the same ventilation mode. The primary end point of the study was overall ventilation time. Overall ventilation time (median [25th and 75th percentile]) did not significantly differ between the automated-weaning (31 [19-101] h; n = 150) and control groups (39 [20-118] h; n = 150; P = 0.178). Patients who underwent cardiac surgery (n = 132) exhibited significantly shorter overall ventilation times in the automated-weaning (24 [18-57] h) than in the control group (35 [20-93] h; P = 0.035). The automated-weaning group exhibited shorter ventilation times until the first spontaneous breathing trial (1 [0-15] vs. 9 [1-51] h; P = 0.001) and a trend toward fewer tracheostomies (17 vs. 28; P = 0.075). Overall ventilation times did not significantly differ between weaning using automatic control of pressure support ventilation and weaning based on a standardized written protocol. Patients after cardiac surgery may benefit from automated weaning. Implementation of additional control variables besides the level of pressure support may further improve automated-weaning systems. Clinical trial registered with www.clinicaltrials.gov (NCT 00445289).

Biopsychosocial influence on shoulder pain: Rationale and protocol for a pre-clinical trial.

PubMed

George, Steven Z; Staud, Roland; Borsa, Paul A; Wu, Samuel S; Wallace, Margaret R; Greenfield, Warren H; Mackie, Lauren N; Fillingim, Roger B

2017-05-01

Chronic musculoskeletal pain conditions are a prevalent and disabling problem. Preventing chronic musculoskeletal pain requires multifactorial treatment approaches that address its complex etiology. Prior cohort studies identified a high risk subgroup comprised of variation in COMT genotype and pain catastrophizing. This subgroup had increased chance of heightened pain responses (in a pre-clinical model) and higher 12month post-operatives pain intensity ratings (in a clinical model). This pre-clinical trial will test mechanisms and efficacy of personalized pain interventions matched to the genetic and psychological characteristics of the high-risk subgroup. Potential participants will be screened for high risk subgroup membership, appropriateness for exercise-induced muscle injury protocol, and appropriateness for propranolol administration. Eligible participants that consent to the study will then be randomized into one of four treatment groups; 1) personalized pharmaceutical and psychological education; 2) personalized pharmaceutical and general education; 3) placebo pharmaceutical and psychological education; 4) placebo pharmaceutical and psychological education. Over the 5-day study period participants will complete an exercise-induced muscle injury protocol and receive study interventions. Pain and disability assessments will be completed daily, with primary outcomes being duration of shoulder pain (number of days until recovery), peak shoulder pain intensity, and peak shoulder disability. Secondary outcomes include inflammatory markers, psychological mediators, and measures of pain sensitivity regulation. This pre-clinical trial builds on prior cohort studies and its completion will provide foundational data supporting efficacy and mechanisms of personalized interventions for individuals that may be at increased risk for developing chronic shoulder pain. ClinicalTrials.gov registry, NCT02620579 (Registered on November 13, 2015). Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal Opioid Treatment: Human Experimental Research (MOTHER) – Approach, Issues, and Lessons Learned

PubMed Central

Jones, Hendrée E.; Fischer, Gabriele; Heil, Sarah H.; Kaltenbach, Karol; Martin, Peter R.; Coyle, Mara G.; Selby, Peter; Stine, Susan M.; O’Grady, Kevin E.; Arria, Amelia M.

2015-01-01

Aims The Maternal Opioid Treatment: Human Experimental Research (MOTHER) project, an eight-site randomized, double-blind, double-dummy, flexible-dosing, parallel-group clinical trial is described. This study is the most current – and single most comprehensive – research effort to investigate the safety and efficacy of maternal and prenatal exposure to methadone and buprenorphine. Methods The MOTHER study design is outlined, and its basic features are presented. Conclusions At least seven important lessons have been learned from the MOTHER study: (1) an interdisciplinary focus improves the design and methods of a randomized clinical trial; (2) multiple sites in a clinical trial present continuing challenges to the investigative team due to variations in recruitment goals, patient populations, and hospital practices that in turn differentially impact recruitment rates, treatment compliance, and attrition; (3) study design and protocols must be flexible in order to meet the unforeseen demands of both research and clinical management; (4) staff turnover needs to be addressed with a proactive focus on both hiring and training; (5) the implementation of a protocol for the treatment of a particular disorder may identify important ancillary clinical issues worthy of investigation; (6) timely tracking of data in a multi-site trial is both demanding and unforgiving; and, (7) complex multi-site trials pose unanticipated challenges that complicate the choice of statistical methods, thereby placing added demands on investigators to effectively communicate their results. PMID:23106924

Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis.

PubMed

Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C

2016-08-01

Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials. We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants) submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal), which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of seven papers stated that "all adverse events were recorded." For one trial, we identified an additional 1,318 adverse events that were not listed or mentioned in the CSR itself but could be identified through manually counting individual adverse events reported in an appendix. We discovered that the majority of patients had multiple episodes of the same adverse event that were only counted once, though this was not described in the CSRs. We also discovered that participants treated with orlistat experienced twice as many days with adverse events as participants treated with placebo (22.7 d versus 14.9 d, p-value < 0.0001, Student's t test). Furthermore, compared with the placebo group, adverse events in the orlistat group were more severe. None of this was stated in the CSR or in the published paper. Our analysis was restricted to one drug tested in the mid-1990s; our results might therefore not be applicable for newer drugs. In the orlistat trials, we identified important disparities in the reporting of adverse events between protocols, clinical study reports, and published papers. Reports of these trials seemed to have systematically understated adverse events. Based on these findings, systematic reviews of drugs might be improved by including protocols and CSRs in addition to published articles.

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs.

PubMed

Greenberg, Chelsea B; Boria, Pedro A; Borgatti-Jeffreys, Antonella; Raskin, Rose E; Lucroy, Michael D

2007-01-01

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER)

PubMed Central

Williamson, Esther; Lait, Clare; Richmond, Helen; Betteley, Lauren; Lall, Ranjit; Petrou, Stavros; Rees, Sophie; Withers, Emma J; Lamb, Sarah E; Thompson, Alastair M

2018-01-01

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery. Methods This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions. Discussion The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation. Protocol version Version 2.1; dated 11 January 2017 Trial registration number ISRCTN35358984; Pre-results. PMID:29574439

European COMPARative Effectiveness research on blended Depression treatment versus treatment-as-usual (E-COMPARED): study protocol for a randomized controlled, non-inferiority trial in eight European countries.

PubMed

Kleiboer, Annet; Smit, Jan; Bosmans, Judith; Ruwaard, Jeroen; Andersson, Gerhard; Topooco, Naira; Berger, Thomas; Krieger, Tobias; Botella, Cristina; Baños, Rosa; Chevreul, Karine; Araya, Ricardo; Cerga-Pashoja, Arlinda; Cieślak, Roman; Rogala, Anna; Vis, Christiaan; Draisma, Stasja; van Schaik, Anneke; Kemmeren, Lise; Ebert, David; Berking, Matthias; Funk, Burkhardt; Cuijpers, Pim; Riper, Heleen

2016-08-03

Effective, accessible, and affordable depression treatment is of high importance considering the large personal and economic burden of depression. Internet-based treatment is considered a promising clinical and cost-effective alternative to current routine depression treatment strategies such as face-to-face psychotherapy. However, it is not clear whether research findings translate to routine clinical practice such as primary or specialized mental health care. The E-COMPARED project aims to gain knowledge on the clinical and cost-effectiveness of blended depression treatment compared to treatment-as-usual in routine care. E-COMPARED will employ a pragmatic, multinational, randomized controlled, non-inferiority trial in eight European countries. Adults diagnosed with major depressive disorder (MDD) will be recruited in primary care (Germany, Poland, Spain, Sweden, and the United Kingdom) or specialized mental health care (France, The Netherlands, and Switzerland). Regular care for depression is compared to "blended" service delivery combining mobile and Internet technologies with face-to-face treatment in one treatment protocol. Participants will be followed up at 3, 6, and 12 months after baseline to determine clinical improvements in symptoms of depression (primary outcome: Patient Health Questionnaire-9), remission of depression, and cost-effectiveness. Main analyses will be conducted on the pooled data from the eight countries (n = 1200 in total, 150 participants in each country). The E-COMPARED project will provide mental health care stakeholders with evidence-based information and recommendations on the clinical and cost-effectiveness of blended depression treatment. France: ClinicalTrials.gov NCT02542891 . Registered on 4 September 2015; Germany: German Clinical Trials Register DRKS00006866 . Registered on 2 December 2014; The Netherlands: Netherlands Trials Register NTR4962 . Registered on 5 January 2015; Poland: ClinicalTrials.Gov NCT02389660 . Registered on 18 February 2015; Spain: ClinicalTrials.gov NCT02361684 . Registered on 8 January 2015; Sweden: ClinicalTrials.gov NCT02449447 . Registered on 30 March 2015; Switzerland: ClinicalTrials.gov NCT02410616 . Registered on 2 April 2015; United Kingdom: ISRCTN registry, ISRCTN12388725 . Registered on 20 March 2015.

TU-G-BRB-04: Digital Phantoms for Developing Protocols in Particle Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, C.

2015-06-15

Proton therapy, in particular, and ion therapy, just beginning, are becoming an increasing focus of attention in clinical radiation oncology and medical physics. Both modalities have been criticized of lacking convincing evidence from randomized trials proving their efficacy, justifying the higher costs involved in these therapies. This session will provide an overview of the current status of clinical trials in proton therapy, including recent developments in ion therapy. As alluded to in the introductory talk by Dr. Schulte, opinions are diverging widely as to the usefulness and need for clinical trials in particle therapy and the challenge of equipoise. Themore » lectures will highlight some of the challenges that surround clinical trials in particle therapy. One, presented by Dr. Choy from UT Southwestern, is that new technology and even different types of particles such as helium and carbon ions are introduced into this environment, increasing the phase space of clinical variables. The other is the issue of medical physics quality assurance with physical phantoms, presented by Mrs. Taylor from IROC Houston, which is more challenging because 3D and 4D image guidance and active delivery techniques are in relatively early stages of development. The role of digital phantoms in developing clinical treatment planning protocols and as a QA tool will also be highlighted by Dr. Lee from NCI. The symposium will be rounded off by a panel discussion among the Symposium speakers, arguing pro or con the need and readiness for clinical trials in proton and ion therapy. Learning Objectives: To get an update on the current status of clinical trials allowing or mandating proton therapy. Learn about the status of planned clinical trials in the U.S. and worldwide involving ion therapy. Discuss the challenges in the design and QA of clinical trials in particle therapy. Learn about existing and future physical and computational anthropomorphic phantoms for charged particle clinical trial development and support. Research reported in this presentation is supported by the National Cancer Institute of the National; Institutes of Health under Award Number P20CA183640.« less

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster.

PubMed

Liedert, B; Bassus, S; Schneider, C K; Kalinke, U; Löwer, J

2007-01-01

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only. The adverse effects associated with the TGN1412 Phase I trial indicate that the predictive value of pre-clinical animal models requires reevaluation and that, in certain cases, some issues of clinical trial protocols such as dose fixing may need refinement or redesign. Concrete safety measures, which have been proposed as a consequence of the TGN1412 event include introduction of criteria for high-risk antibodies, sequential inclusion of trial participants and implementation of pre-Phase I studies where dose calculation is based on the pre-clinical No Effect Level instead of the No Observed Adverse Effect Level. The recently established European clinical trials database (EUDRACT Database) is a further safety tool to expedite the sharing of relevant information between scientific authorities.

Compliance revisited: pharmaceutical drug trials in the era of the contract research organization.

PubMed

Jonvallen, Petra

2009-12-01

Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co-ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that trial participants comply with the protocol. Using an analytical distinction between 'classical' management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug.

Time to publication for publicly funded clinical trials in Australia: an observational study.

PubMed

Strand, Linn Beate; Clarke, Philip; Graves, Nicholas; Barnett, Adrian G

2017-03-22

To examine the length of time between receiving funding and publishing the protocol and main paper for randomised controlled trials. An observational study using survival analysis. Publicly funded health and medical research in Australia. Randomised controlled trials funded by the National Health and Medical Research Council of Australia between 2008 and 2010. Time from funding to the protocol paper and main results paper. Multiple variable survival models examining whether study characteristics predicted publication times. We found 77 studies with a total funding of $A59 million. The median time to publication of the protocol paper was 6.4 years after funding (95% CI 4.1 to 8.1). The proportion with a published protocol paper 8 years after funding was 0.61 (95% CI 0.48 to 0.74). The median time to publication of the main results paper was 7.1 years after funding (95% CI 6.3 to 7.6). The proportion with a published main results paper 8 years after funding was 0.72 (95% CI 0.56 to 0.87). The HRs for how study characteristics might influence timing were generally close to one with narrow CIs, the notable exception was that a longer study length lengthened the time to the main paper (HR=0.62 per extra study year, 95% CI 0.43 to 0.89). Despite the widespread registration of clinical trials, there remain serious concerns of trial results not being published or being published with a long delay. We have found that these same concerns apply to protocol papers, which should be publishable soon after funding. Funding agencies could set a target of publishing the protocol paper within 18 months of funding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairchild, Alysa, E-mail: alysa.fairchild@albertahealthservices.ca; Straube, William; Laurie, Fran

2013-10-01

Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Diseasemore » sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.« less

Does Quality of Radiotherapy Predict Outcomes of Multicentre Cooperative Group Trials? A Literature Review

PubMed Central

Fairchild, Alysa; Straube, William; Laurie, Fran; Followill, David

2013-01-01

Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question. PMID:23683829

Clinical Trials Targeting Aging and Age-Related Multimorbidity

PubMed Central

Crimmins, Eileen M; Grossardt, Brandon R; Crandall, Jill P; Gelfond, Jonathan A L; Harris, Tamara B; Kritchevsky, Stephen B; Manson, JoAnn E; Robinson, Jennifer G; Rocca, Walter A; Temprosa, Marinella; Thomas, Fridtjof; Wallace, Robert; Barzilai, Nir

2017-01-01

Abstract Background There is growing interest in identifying interventions that may increase health span by targeting biological processes underlying aging. The design of efficient and rigorous clinical trials to assess these interventions requires careful consideration of eligibility criteria, outcomes, sample size, and monitoring plans. Methods Experienced geriatrics researchers and clinical trialists collaborated to provide advice on clinical trial design. Results Outcomes based on the accumulation and incidence of age-related chronic diseases are attractive for clinical trials targeting aging. Accumulation and incidence rates of multimorbidity outcomes were developed by selecting at-risk subsets of individuals from three large cohort studies of older individuals. These provide representative benchmark data for decisions on eligibility, duration, and assessment protocols. Monitoring rules should be sensitive to targeting aging-related, rather than disease-specific, outcomes. Conclusions Clinical trials targeting aging are feasible, but require careful design consideration and monitoring rules. PMID:28364543

A Semantic Web-based System for Mining Genetic Mutations in Cancer Clinical Trials.

PubMed

Priya, Sambhawa; Jiang, Guoqian; Dasari, Surendra; Zimmermann, Michael T; Wang, Chen; Heflin, Jeff; Chute, Christopher G

2015-01-01

Textual eligibility criteria in clinical trial protocols contain important information about potential clinically relevant pharmacogenomic events. Manual curation for harvesting this evidence is intractable as it is error prone and time consuming. In this paper, we develop and evaluate a Semantic Web-based system that captures and manages mutation evidences and related contextual information from cancer clinical trials. The system has 2 main components: an NLP-based annotator and a Semantic Web ontology-based annotation manager. We evaluated the performance of the annotator in terms of precision and recall. We demonstrated the usefulness of the system by conducting case studies in retrieving relevant clinical trials using a collection of mutations identified from TCGA Leukemia patients and Atlas of Genetics and Cytogenetics in Oncology and Haematology. In conclusion, our system using Semantic Web technologies provides an effective framework for extraction, annotation, standardization and management of genetic mutations in cancer clinical trials.

Imaging Radiation Doses and Associated Risks and Benefits in Subjects Participating in Breast Cancer Clinical Trials

PubMed Central

Spera, Gonzalo; Meyer, Carlos; Cabral, Pablo; Mackey, John R.

2015-01-01

Background. Medical imaging is commonly required in breast cancer (BC) clinical trials to assess the efficacy and/or safety of study interventions. Despite the lack of definitive epidemiological data linking imaging radiation with cancer development in adults, concerns exist about the risks of imaging radiation-induced malignancies (IRIMs) in subjects exposed to repetitive imaging. We estimated the imaging radiation dose and IRIM risk in subjects participating in BC trials. Materials and Methods. The imaging protocol requirements in 10 phase III trials in the adjuvant and advanced settings were assessed to estimate the effective radiation dose received by a typical and fully compliant subject in each trial. For each study, the excess lifetime attributable cancer risk (LAR) was calculated using the National Cancer Institute’s Radiation Risk Assessment Tool, version 3.7.1. Dose and risk calculations were performed for both imaging intensive and nonintensive approaches to reflect the variability in imaging performed within the studies. Results. The total effective imaging radiation dose was 0.4–262.2 mSv in adjuvant trials and 26–241.3 mSv in metastatic studies. The dose variability resulted from differing protocol requirements and imaging intensity approaches, with computed tomography, multigated acquisition scans, and bone scans as the major contributors. The mean LAR was 1.87–2,410/100,000 in adjuvant trials (IRIM: 0.0002%–2.41% of randomized subjects) and 6.9–67.3/100,000 in metastatic studies (IRIM: 0.007%–0.067% of subjects). Conclusion. IRIMs are infrequent events. In adjuvant trials, aligning the protocol requirements with the clinical guidelines’ surveillance recommendations and substituting radiating procedures with equivalent nonradiating ones would reduce IRIM risk. No significant risk has been observed in metastatic trials, and potential concerns on IRIMs are not justified. Implications for Practice: Medical imaging is key in breast cancer (BC) clinical trials. Most of these procedures expose patients to ionizing radiation, and the risk of second cancer development after imaging has prompted recent concerns and controversy. Using accepted calculation models, the number of malignancies were estimated that were potentially attributable to the imaging procedures performed during a patient’s participation in BC clinical trials. The results show that for patients participating in metastatic trials, the risk of imaging radiation-induced malignancies is negligible. In adjuvant trials, some second cancers due to imaging could be expected, and measures can be taken to reduce their risk. PMID:26025934

UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride: Rationale, Indications, and Consent

PubMed Central

Horst, Jeremy A; Ellenikiotis, Hellene; Milgrom, Peter M

2016-01-01

The Food and Drug Administration recently cleared silver diamine fluoride for reducing tooth sensitivity. Clinical trials document arrest and prevention of dental caries by silver diamine fluoride; this off-label use is now permissible and appropriate under U.S. law. A CDT code was approved for caries arresting medicaments for 2016 to facilitate documentation and billing. We present a systematic review, clinical indications, clinical protocol, and consent procedure to guide application for caries arrest treatment. PMID:26897901

A teaching intervention in a contouring dummy run improved target volume delineation in locally advanced non-small cell lung cancer: Reducing the interobserver variability in multicentre clinical studies.

PubMed

Schimek-Jasch, Tanja; Troost, Esther G C; Rücker, Gerta; Prokic, Vesna; Avlar, Melanie; Duncker-Rohr, Viola; Mix, Michael; Doll, Christian; Grosu, Anca-Ligia; Nestle, Ursula

2015-06-01

Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(κ) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.

Study protocol of a mixed-methods evaluation of a cluster randomized trial to improve the safety of NSAID and antiplatelet prescribing: data-driven quality improvement in primary care.

PubMed

Grant, Aileen; Dreischulte, Tobias; Treweek, Shaun; Guthrie, Bruce

2012-08-28

Trials of complex interventions are criticized for being 'black box', so the UK Medical Research Council recommends carrying out a process evaluation to explain the trial findings. We believe it is good practice to pre-specify and publish process evaluation protocols to set standards and minimize bias. Unlike protocols for trials, little guidance or standards exist for the reporting of process evaluations. This paper presents the mixed-method process evaluation protocol of a cluster randomized trial, drawing on a framework designed by the authors. This mixed-method evaluation is based on four research questions and maps data collection to a logic model of how the data-driven quality improvement in primary care (DQIP) intervention is expected to work. Data collection will be predominately by qualitative case studies in eight to ten of the trial practices, focus groups with patients affected by the intervention and quantitative analysis of routine practice data, trial outcome and questionnaire data and data from the DQIP intervention. We believe that pre-specifying the intentions of a process evaluation can help to minimize bias arising from potentially misleading post-hoc analysis. We recognize it is also important to retain flexibility to examine the unexpected and the unintended. From that perspective, a mixed-methods evaluation allows the combination of exploratory and flexible qualitative work, and more pre-specified quantitative analysis, with each method contributing to the design, implementation and interpretation of the other.As well as strengthening the study the authors hope to stimulate discussion among their academic colleagues about publishing protocols for evaluations of randomized trials of complex interventions. DATA-DRIVEN QUALITY IMPROVEMENT IN PRIMARY CARE TRIAL REGISTRATION: ClinicalTrials.gov: NCT01425502.

The Virtual Anemia Trial: An Assessment of Model-Based In Silico Clinical Trials of Anemia Treatment Algorithms in Patients With Hemodialysis.

PubMed

Fuertinger, Doris H; Topping, Alice; Kappel, Franz; Thijssen, Stephan; Kotanko, Peter

2018-04-01

In silico approaches have been proposed as a novel strategy to increase the repertoire of clinical trial designs. Realistic simulations of clinical trials can provide valuable information regarding safety and limitations of treatment protocols and have been shown to assist in the cost-effective planning of clinical studies. In this report, we present a blueprint for the stepwise integration of internal, external, and ecological validity considerations in virtual clinical trials (VCTs). We exemplify this approach in the context of a model-based in silico clinical trial aimed at anemia treatment in patients undergoing hemodialysis (HD). Hemoglobin levels and subsequent anemia treatment were simulated on a per patient level over the course of a year and compared to real-life clinical data of 79,426 patients undergoing HD. The novel strategies presented here, aimed to improve external and ecological validity of a VCT, significantly increased the predictive power of the discussed in silico trial. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Examining clinical supervision as a mechanism for changes in practice: a research protocol.

PubMed

Dilworth, Sophie; Higgins, Isabel; Parker, Vicki; Kelly, Brian; Turner, Jane

2014-02-01

This paper describes the research protocol for a study exploring if and how clinical supervision facilitates change in practice relating to psychosocial aspects of care for Health Professionals, who have been trained to deliver a psychosocial intervention to adults with cancer. There is a recognized need to implement care that is in line with clinical practice guidelines for the psychosocial care of adults with cancer. Clinical supervision is recommended as a means to support Health Professionals in providing the recommended psychosocial care. A qualitative design embedded within an experimental, stepped wedge randomized control trial. The study will use discourse analysis to analyse audio-recorded data collected in clinical supervision sessions that are being delivered as one element of a large randomized control trial. The sessions will be attended primarily by nurses, but including physiotherapists, radiation therapists, occupational therapists. The Health Professionals are participants in a randomized control trial designed to reduce anxiety and depression of distressed adults with cancer. The sessions will be facilitated by psychiatrists experienced in psycho-oncology and the provision of clinical supervision. The proposed research is designed specifically to facilitate exploration of the mechanisms by which clinical supervision enables Health Professionals to deliver a brief, tailored psychosocial intervention in the context of their everyday practice. This is the first study to use discourse analysis embedded within an experimental randomized control trial to explore the mechanisms of change generated within clinical supervision by analysing the discourse within the clinical supervision sessions. © 2013 John Wiley & Sons Ltd.

Protocol for a single-centre, randomised controlled study of a preoperative rehabilitation bundle in the frail and elderly undergoing abdominal surgery.

PubMed

Abdullah, Hairil Rizal; Lien, Victoria Peixin; Ong, Hwee Kuan; Er, Pei Ling; Hao, Ying; Khan, Shariq Ali; Liu, Christopher Weiyang

2017-08-04

Frail patients have decreased physiological reserves and consequently, they are unable to recover as quickly from surgery. Frailty, as an entity, is a risk factor of increased morbidity and mortality. It is also associated with a longer time to discharge. This trial is undertaken to determine if a novel prehabilitation protocol (10-day bundle of interventions-physiotherapy, nutritional supplementation and cognitive training) can reduce the postoperative length of stay of frail patients who are undergoing elective abdominal surgery, compared with standard care. This is a prospective, single-centre, randomised controlled trial with two parallel arms. 62 patients who are frail and undergoing elective abdominal surgery will be recruited and randomised to receive either a novel prehabilitation protocol or standard care. Participants will receive telephone reminders preoperatively to encourage protocol compliance. Data will be collected for up to 30 days postoperatively. The primary outcome of the trial will be the postoperative length of stay and the secondary outcomes are the postoperative complications and functional recovery during the hospital admission. This study has been approved by the Singapore General Hospital Institutional Review Board (CIRB Ref: 2016/2584). The study is also listed on ClinicalTrials.gov (Trial number: NCT02921932). All participants will sign an informed consent form before randomisation and translators will be made available to non-English speaking patients. The results of this study will be published in peer-reviewed journals as well as national and international conferences. The data collected will also be made available in a public data repository. NCT02921932 (ClinicalTrials.gov). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Gender Research in the National Institute on Drug Abuse National Treatment Clinical Trials Network: A Summary of Findings

PubMed Central

Greenfield, Shelly F.; Rosa, Carmen; Putnins, Susan I.; Green, Carla A.; Brooks, Audrey J.; Calsyn, Donald A.; Cohen, Lisa R.; Erickson, Sarah; Gordon, Susan M.; Haynes, Louise; Killeen, Therese; Miele, Gloria; Tross, Susan; Winhusen, Theresa

2011-01-01

Background The NIDA National Drug Abuse Treatment Clinical Trials Network (CTN) was established to foster translation of research into practice in substance abuse treatment settings. The CTN provides a unique opportunity to examine in multi-site, translational clinical trials, the outcomes of treatment interventions targeting vulnerable sub-groups of women; the comparative effectiveness of gender-specific protocols to reduce risk behaviors; and gender differences in clinical outcomes. Objectives To review gender-related findings from published CTN clinical trials and related studies from January, 2000 through March, 2010. Methods CTN studies were selected for review if they focused on treatment outcomes or services for special populations of women with substance use disorders (SUDs) including those with trauma histories, pregnancy, co-occurring eating and other psychiatric disorders and HIV risk behaviors; or implemented gender-specific protocols. Results The CTN has randomized 11,500 participants (41% women) across 200 clinics in 24 randomized clinical trials in community settings, of which 4 have been gender-specific. This paper summarizes gender-related findings from CTN clinical trials and related studies, focusing on trauma histories, pregnancy, co-occurring eating and other psychiatric disorders, and HIV risk behaviors. Conclusions These published studies have expanded the evidence base regarding interventions for vulnerable groups of women with SUDs as well as gender-specific interventions to reduce HIV risk behaviors in substance using men and women. The results also underscore the complexity of accounting for gender in the design of clinical trials and analysis of results. Scientific Relevance To fully understand the relevance of gender-specific moderators and mediators of outcome, it is essential that future translational studies adopt more sophisticated approaches to understanding and measuring gender-relevant factors and plan sample sizes that are adequate to support more nuanced analytic methods. PMID:21854272

FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study.

PubMed

Marin Dos Santos, Douglas H; Atallah, Álvaro N

2015-01-01

The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the platform ClinicalTrials (available at https://www.clinicaltrials.gov). We accessed ClinicalTrials.gov and evaluated the compliance of researchers and sponsors with the FDAAA. Our sample comprised 243 protocols of clinical trials of biological monoclonal antibodies (mAb) adalimumab, bevacizumab, infliximab, rituximab, and trastuzumab. We demonstrate that the new legislation has positively affected transparency patterns in clinical research, through a significant increase in publication and online reporting rates after the enactment of the law. Poorly designed trials, however, remain a challenge to be overcome, due to a high prevalence of methodological flaws. These flaws affect the quality of clinical information available, breaching ethical duties of sponsors and researchers, as well as the human right to health.

FDAAA legislation is working, but methodological flaws undermine the reliability of clinical trials: a cross-sectional study

PubMed Central

Atallah, Álvaro N.

2015-01-01

The relationship between clinical research and the pharmaceutical industry has placed clinical trials in jeopardy. According to the medical literature, more than 70% of clinical trials are industry-funded. Many of these trials remain unpublished or have methodological flaws that distort their results. In 2007, it was signed into law the Food and Drug Administration Amendments Act (FDAAA), aiming to provide publicly access to a broad range of biomedical information to be made available on the platform ClinicalTrials (available at https://www.clinicaltrials.gov). We accessed ClinicalTrials.gov and evaluated the compliance of researchers and sponsors with the FDAAA. Our sample comprised 243 protocols of clinical trials of biological monoclonal antibodies (mAb) adalimumab, bevacizumab, infliximab, rituximab, and trastuzumab. We demonstrate that the new legislation has positively affected transparency patterns in clinical research, through a significant increase in publication and online reporting rates after the enactment of the law. Poorly designed trials, however, remain a challenge to be overcome, due to a high prevalence of methodological flaws. These flaws affect the quality of clinical information available, breaching ethical duties of sponsors and researchers, as well as the human right to health. PMID:26131374

Pediatric Diabetic Ketoacidosis, Fluid Therapy and Cerebral Injury: The Design of a Factorial Randomized Controlled Trial

PubMed Central

Glaser, Nicole S.; Ghetti, Simona; Casper, T. Charles; Dean, J. Michael; Kuppermann, Nathan

2013-01-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the United States and worldwide. The optimal protocol for intravenous fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of intravenous fluid infusion and the development of cerebral edema, the most common and most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and cerebral edema have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (Fluid Therapies Under Investigation in DKA) Study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial-design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically-overt CE, and long-term neurocognitive outcomes following DKA. PMID:23490311

Building a Protocol Expressway: The Case of Mayo Clinic Cancer Center

PubMed Central

McJoynt, Terre A.; Hirzallah, Muhanad A.; Satele, Daniel V.; Pitzen, Jason H.; Alberts, Steven R.; Rajkumar, S. Vincent

2009-01-01

Purpose Inconsistencies and errors resulting from nonstandard processes, together with redundancies, rework, and excess workload, lead to extended time frames for clinical trial protocol development. This results in dissatisfaction among sponsors, investigators, and staff and restricts the availability of novel treatment options for patients. Methods A team of experts from Mayo Clinic formed, including Protocol Development Unit staff and management from the three Mayo Clinic campuses (Florida, Minnesota, and Arizona), a systems and procedures analyst, a quality office analyst, and two physician members to address the identified deficiencies. The current-state process was intensively reviewed, and improvement steps were taken to accelerate the development and approval of cancer-related clinical trials. The primary goal was to decrease the time from receipt of a new protocol through submission to an approving authority, such as the National Cancer Institute or institutional review board. Results Using the Define, Measure, Analyze, Improve, Control (DMAIC) framework infused with Lean waste-reduction methodologies, areas were identified for improvement, including enhancing first-time quality and processing new studies on a first-in/first-out basis. The project was successful in improving the mean turnaround time for internally authored protocols (P < .001) from 25.00 weeks (n = 41; range, 3.43 to 94.14 weeks) to 10.15 weeks (n = 14; range, 4.00 to 22.14 weeks). The mean turnaround time for externally authored protocols was improved (P < .001) from 20.61 weeks (n = 85; range, 3.29 to 108.57 weeks) to 7.79 weeks (n = 50; range, 2.00 to 20.86 weeks). Conclusion DMAIC framework combined with Lean methodologies is an effective tool to structure the definition, planning, analysis, and implementation of significant process changes. PMID:19564529

Building a protocol expressway: the case of Mayo Clinic Cancer Center.

PubMed

McJoynt, Terre A; Hirzallah, Muhanad A; Satele, Daniel V; Pitzen, Jason H; Alberts, Steven R; Rajkumar, S Vincent

2009-08-10

Inconsistencies and errors resulting from nonstandard processes, together with redundancies, rework, and excess workload, lead to extended time frames for clinical trial protocol development. This results in dissatisfaction among sponsors, investigators, and staff and restricts the availability of novel treatment options for patients. A team of experts from Mayo Clinic formed, including Protocol Development Unit staff and management from the three Mayo Clinic campuses (Florida, Minnesota, and Arizona), a systems and procedures analyst, a quality office analyst, and two physician members to address the identified deficiencies. The current-state process was intensively reviewed, and improvement steps were taken to accelerate the development and approval of cancer-related clinical trials. The primary goal was to decrease the time from receipt of a new protocol through submission to an approving authority, such as the National Cancer Institute or institutional review board. Using the Define, Measure, Analyze, Improve, Control (DMAIC) framework infused with Lean waste-reduction methodologies, areas were identified for improvement, including enhancing first-time quality and processing new studies on a first-in/first-out basis. The project was successful in improving the mean turnaround time for internally authored protocols (P < .001) from 25.00 weeks (n = 41; range, 3.43 to 94.14 weeks) to 10.15 weeks (n = 14; range, 4.00 to 22.14 weeks). The mean turnaround time for externally authored protocols was improved (P < .001) from 20.61 weeks (n = 85; range, 3.29 to 108.57 weeks) to 7.79 weeks (n = 50; range, 2.00 to 20.86 weeks). DMAIC framework combined with Lean methodologies is an effective tool to structure the definition, planning, analysis, and implementation of significant process changes.

Mapping Evidence-Based Treatments for Children and Adolescents: Application of the Distillation and Matching Model to 615 Treatments from 322 Randomized Trials

ERIC Educational Resources Information Center

Chorpita, Bruce F.; Daleiden, Eric L.

2009-01-01

This study applied the distillation and matching model to 322 randomized clinical trials for child mental health treatments. The model involved initial data reduction of 615 treatment protocol descriptions by means of a set of codes describing discrete clinical strategies, referred to as practice elements. Practice elements were then summarized in…

Challenges and potential solutions to meeting accrual goals in a Phase II chemoprevention trial for prostate cancer.

PubMed

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

2012-03-01

The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety-four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. Copyright © 2011 Elsevier Inc. All rights reserved.

Challenges and Potential Solutions to Meeting Accrual Goals in a Phase II Chemoprevention Trial for Prostate Cancer

PubMed Central

Kumar, Nagi; Crocker, Theresa; Smith, Tiffany; Pow-Sang, Julio; Spiess, Philippe E.; Egan, Kathleen; Quinn, Gwen; Schell, Michael; Sebti, Said; Kazi, Aslam; Chuang, Tian; Salup, Raoul; Helal, Mohamed; Zagaja, Gregory; Trabulsi, Edouard; McLarty, Jerry; Fazili, Tajammul; Williams, Christopher R.; Schreiber, Fred; Slaton, Joel; Anderson, J Kyle

2011-01-01

Objective The goal of this report is to describe the on going strategies, successes, challenges and solutions for recruitment in this multi-center, phase II chemoprevention trial targeting men at high risk for prostate cancer. Methods We developed and implemented a multi-center clinical trial in institutions with supportive infrastructure, lead by a recruitment team of experienced and committed physicians and clinical trial staff, implementing multi-media and community outreach strategies to meet recruitment goals. Screening logs were reviewed to identify trends as well as patient, protocol and infrastructure -related barriers impacting accrual and revisions to protocol implemented. Results Between January 2008 and February 2011 a total of 3547 individuals were prescreened with 94% (n=3092) determined to be ineligible based on diagnosis of cancer or benign biopsy results. Of these, 216 were considered eligible for further screening with 52% (n=113) declining to participate due to patient related factors and 14% (n=29) eliminated due to protocol-related criteria for exclusion. Ninety four (94) subjects consented to participate with 34% of these subjects (n=74) meeting all eligibility criteria to be randomized to receive study agent or placebo. Across all sites, 99% of the recruitment of subjects in this clinical trial is via physician recruitment and referral with less than 1% responding to other recruitment strategies. Conclusion A contemporary approach to subject recruitment and frequent evaluation is needed to assure responsiveness to emerging challenges to accrual and the evolving scientific literature. A focus on investing on improving systems for physician recruitment may be key to meeting recruitment target in chemoprevention trials. PMID:22101219

Theory-driven group-based complex intervention to support self-management of osteoarthritis and low back pain in primary care physiotherapy: protocol for a cluster randomised controlled feasibility trial (SOLAS)

PubMed Central

Hurley, Deirdre A; Hall, Amanda M; Currie-Murphy, Laura; Pincus, Tamar; Kamper, Steve; Maher, Chris; McDonough, Suzanne M; Lonsdale, Chris; Walsh, Nicola E; Guerin, Suzanne; Segurado, Ricardo; Matthews, James

2016-01-01

Introduction International clinical guidelines consistently endorse the promotion of self-management (SM), including physical activity for patients with chronic low back pain (CLBP) and osteoarthritis (OA). Patients frequently receive individual treatment and advice to self-manage from physiotherapists in primary care, but the successful implementation of a clinical and cost-effective group SM programme is a key priority for health service managers in Ireland to maximise long-term outcomes and efficient use of limited and costly resources. Methods/analysis This protocol describes an assessor-blinded cluster randomised controlled feasibility trial of a group-based education and exercise intervention underpinned by self-determination theory designed to support an increase in SM behaviour in patients with CLBP and OA in primary care physiotherapy. The primary care clinic will be the unit of randomisation (cluster), with each clinic randomised to 1 of 2 groups providing the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention or usual individual physiotherapy. Patients are followed up at 6 weeks, 2 and 6 months. The primary outcomes are the (1) acceptability and demand of the intervention to patients and physiotherapists, (2) feasibility and optimal study design/procedures and sample size for a definitive trial. Secondary outcomes include exploratory analyses of: point estimates, 95% CIs, change scores and effect sizes in physical function, pain and disability outcomes; process of change in target SM behaviours and selected mediators; and the cost of the intervention to inform a definitive trial. Ethics/dissemination This feasibility trial protocol was approved by the UCD Human Research Ethics—Sciences Committee (LS-13-54 Currie-Hurley) and research access has been granted by the Health Services Executive Primary Care Research Committee in January 2014. The study findings will be disseminated to the research, clinical and health service communities through publication in peer-reviewed journals, presentation at national and international academic and clinical conferences. Trial registration number ISRCTN 49875385; Pre-results. PMID:26801470

Development and implementation of clinical trial protocol templates at the National Institute of Allergy and Infectious Diseases.

PubMed

Bridge, Heather; Smolskis, Mary; Bianchine, Peter; Dixon, Dennis O; Kelly, Grace; Herpin, Betsey; Tavel, Jorge

2009-08-01

A clinical research protocol document must reflect both sound scientific rationale as well as local, national and, when applicable, international regulatory and human subject protections requirements. These requirements originate from a variety of sources, undergo frequent revision and are subject to interpretation. Tools to assist clinical investigators in the production of clinical protocols could facilitate navigating these requirements and ultimately increase the efficiency of clinical research. The National Institute of Allergy and Infectious Diseases (NIAID) developed templates for investigators to serve as the foundation for protocol development. These protocol templates are designed as tools to support investigators in developing clinical protocols. NIAID established a series of working groups to determine how to improve its capacity to conduct clinical research more efficiently and effectively. The Protocol Template Working Group was convened to determine what protocol templates currently existed within NIAID and whether standard NIAID protocol templates should be produced. After review and assessment of existing protocol documents and requirements, the group reached consensus about required and optional content, determined the format and identified methods for distribution as well as education of investigators in the use of these templates. The templates were approved by the NIAID Executive Committee in 2006 and posted as part of the NIAID Clinical Research Toolkit [1] website for broad access. These documents require scheduled revisions to stay current with regulatory and policy changes. The structure of any clinical protocol template, whether comprehensive or specific to a particular study phase, setting or design, affects how it is used by investigators. Each structure presents its own set of advantages and disadvantages. While useful, protocol templates are not stand-alone tools for creating an optimal protocol document, but must be complemented by institutional resources and support. Education and guidance of investigators in the appropriate use of templates is necessary to ensure a complete yet concise protocol document. Due to changing regulatory requirements, clinical protocol templates cannot become static, but require frequent revisions.

OARSI Clinical Trials Recommendations: Hand imaging in clinical trials in osteoarthritis.

PubMed

Hunter, D J; Arden, N; Cicuttini, F; Crema, M D; Dardzinski, B; Duryea, J; Guermazi, A; Haugen, I K; Kloppenburg, M; Maheu, E; Miller, C G; Martel-Pelletier, J; Ochoa-Albíztegui, R E; Pelletier, J-P; Peterfy, C; Roemer, F; Gold, G E

2015-05-01

Tremendous advances have occurred in our understanding of the pathogenesis of hand osteoarthritis (OA) and these are beginning to be applied to trials targeted at modification of the disease course. The purpose of this expert opinion, consensus driven exercise is to provide detail on how one might use and apply hand imaging assessments in disease modifying clinical trials. It includes information on acquisition methods/techniques (including guidance on positioning for radiography, sequence/protocol recommendations/hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, sequences artifacts); quality assurance/control procedures; measurement methods; measurement performance (reliability, responsiveness, validity); recommendations for trials; and research recommendations. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor–transduced T cells

PubMed Central

Dudley, Mark E.; Feldman, Steven A.; Wilson, Wyndham H.; Spaner, David E.; Maric, Irina; Stetler-Stevenson, Maryalice; Phan, Giao Q.; Hughes, Marybeth S.; Sherry, Richard M.; Yang, James C.; Kammula, Udai S.; Devillier, Laura; Carpenter, Robert; Nathan, Debbie-Ann N.; Morgan, Richard A.; Laurencot, Carolyn; Rosenberg, Steven A.

2012-01-01

We conducted a clinical trial to assess adoptive transfer of T cells genetically modified to express an anti-CD19 chimeric Ag receptor (CAR). Our clinical protocol consisted of chemotherapy followed by an infusion of anti–CD19-CAR–transduced T cells and a course of IL-2. Six of the 8 patients treated on our protocol obtained remissions of their advanced, progressive B-cell malignancies. Four of the 8 patients treated on the protocol had long-term depletion of normal polyclonal CD19+ B-lineage cells. Cells containing the anti-CD19 CAR gene were detected in the blood of all patients. Four of the 8 treated patients had prominent elevations in serum levels of the inflammatory cytokines IFNγ and TNF. The severity of acute toxicities experienced by the patients correlated with serum IFNγ and TNF levels. The infused anti–CD19-CAR–transduced T cells were a possible source of these inflammatory cytokines because we demonstrated peripheral blood T cells that produced TNF and IFNγ ex vivo in a CD19-specific manner after anti–CD19-CAR–transduced T-cell infusions. Anti–CD19-CAR–transduced T cells have great promise to improve the treatment of B-cell malignancies because of a potent ability to eradicate CD19+ cells in vivo; however, reversible cytokine-associated toxicities occurred after CAR–transduced T-cell infusions. This trial was registered with ClinicalTrials.gov as NCT00924326. PMID:22160384

Evidence-based protocol for structural rehabilitation of the spine and posture: review of clinical biomechanics of posture (CBP®) publications

PubMed Central

Oakley, Paul A.; Harrison, Donald D.; Harrison, Deed E.; Haas, Jason W.

2005-01-01

BACKGROUND Although practice protocols exist for SMT and functional rehabilitation, no practice protocols exist for structural rehabilitation. Traditional chiropractic practice guidelines have been limited to acute and chronic pain treatment, with limited inclusion of functional and exclusion of structural rehabilitation procedures. OBJECTIVE (1) To derive an evidence-based practice protocol for structural rehabilitation from publications on Clinical Biomechanics of Posture (CBP®) methods, and (2) to compare the evidence for Diversified, SMT, and CBP®. METHODS Clinical control trials utilizing CBP® methods and spinal manipulative therapy (SMT) were obtained from searches in Mantis, CINAHL, and Index Medicus. Using data from SMT review articles, evidence for Diversified Technique (as taught in chiropractic colleges), SMT, and CBP® were rated and compared. RESULTS From the evidence from Clinical Control Trials on SMT and CBP®, there is very little evidence support for Diversified (our rating = 18), as taught in chiropractic colleges, for the treatment of pain subjects, while CBP® (our rating = 46) and SMT for neck pain (rating = 58) and low back pain (our rating = 202) have evidence-based support. CONCLUSIONS While CBP® Technique has approximately as much evidence-based support as SMT for neck pain, CBP® has more evidence to support its methods than the Diversified technique taught in chiropractic colleges, but not as much as SMT for low back pain. The evolution of chiropractic specialization has occurred, and doctors providing structural-based chiropractic care require protocol guidelines for patient quality assurance and standardization. A structural rehabilitation protocol was developed based on evidence from CBP® publications. PMID:17549209

A Systematic Review on Immediate Loading of Implants Used to Support Overdentures Opposed by Conventional Prostheses: Factors That Might Influence Clinical Outcomes.

PubMed

Zygogiannis, Kostas; Wismeijer, Daniel; Aartman, Irene Ha; Osman, Reham B

2016-01-01

Different treatment protocols in terms of number, diameter, and suprastructure design have been proposed for immediately loaded implants that are used to support mandibular overdentures opposed by maxillary conventional dentures. The aim of this study was to investigate the influence of these protocols on survival rates as well as clinical and prosthodontic outcomes. Several electronic databases were searched for all relevant articles published from 1966 to June 2014. Only randomized controlled trials and prospective studies with a minimum follow-up of 12 months were selected. The primary outcomes of interest were the success and survival rates of the implants. Prosthodontic complications were also evaluated. Fourteen studies fulfilled the inclusion criteria. Of the studies identified, nine were randomized controlled trials and five were prospective studies. The mean follow-up period was 3 years or less for the vast majority of the studies. The reported survival and success rates were comparable to that of conventional loading for most of the included studies. No specific immediate loading protocol seemed to perform better in terms of clinical and prosthodontic outcomes. Immediate loading protocols of mandibular overdentures seem to be a viable alternative to conventional loading. It was not possible to recommend a specific treatment protocol related to the number, diameter of the implants, and attachment system used. Long-term, well-designed studies comparing different immediate loading modalities could help to establish a protocol that delivers the most clinically predictable, efficient, and cost-effective outcome for edentulous patients in need of implant overdentures.

Total ankle replacement versus arthrodesis (TARVA): protocol for a multicentre randomised controlled trial

PubMed Central

Goldberg, Andrew J; Zaidi, Razi; Thomson, Claire; Doré, Caroline J; Cro, Suzie; Round, Jeff; Molloy, Andrew; Davies, Mark; Karski, Michael; Kim, Louise; Cooke, Paul

2016-01-01

Introduction Total ankle replacement (TAR) or ankle arthrodesis (fusion) is the main surgical treatments for end-stage ankle osteoarthritis (OA). The popularity of ankle replacement is increasing while ankle fusion rates remain static. Both treatments have efficacy but to date all studies comparing the 2 have been observational without randomisation, and there are no published guidelines as to the most appropriate management. The TAR versus arthrodesis (TARVA) trial aims to compare the clinical and cost-effectiveness of TAR against ankle arthrodesis in the treatment of end-stage ankle OA in patients aged 50–85 years. Methods and analysis TARVA is a multicentre randomised controlled trial that will randomise 328 patients aged 50–85 years with end-stage ankle arthritis. The 2 arms of the study will be TAR or ankle arthrodesis with 164 patients in each group. Up to 16 UK centres will participate. Patients will have clinical assessments and complete questionnaires before their operation and at 6, 12, 26 and 52 weeks after surgery. The primary clinical outcome of the study is a validated patient-reported outcome measure, the Manchester Oxford foot questionnaire, captured preoperatively and 12 months after surgery. Secondary outcomes include quality-of-life scores, complications, revision, reoperation and a health economic analysis. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (London, Bloomsbury 14/LO/0807). This manuscript is based on V.5.0 of the protocol. The trial findings will be disseminated through peer-reviewed publications and conference presentations. Trial registration number NCT02128555. PMID:27601503

Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401.

PubMed

Hurria, Arti; Cirrincione, Constance T; Muss, Hyman B; Kornblith, Alice B; Barry, William; Artz, Andrew S; Schmieder, Linda; Ansari, Rafat; Tew, William P; Weckstein, Douglas; Kirshner, Jeffrey; Togawa, Kayo; Hansen, Kurt; Katheria, Vani; Stone, Richard; Galinsky, Ilene; Postiglione, John; Cohen, Harvey Jay

2011-04-01

Factors captured in a geriatric assessment can predict morbidity and mortality in older adults, but are not routinely measured in cancer clinical trials. This study evaluated the implementation of a geriatric assessment tool in the cooperative group setting. Patients age ≥ 65 with cancer, who enrolled on cooperative group cancer trials, were eligible to enroll on Cancer and Leukemia Group B (CALGB) 360401. They completed a geriatric assessment tool before initiation of protocol therapy, consisting of valid and reliable geriatric assessment measures which are primarily self-administered and require minimal resources and time by healthcare providers. The assessment measures functional status, comorbidity, cognitive function, psychological state, social support, and nutritional status. The protocol specified criteria for incorporation of the tool in future cooperative group trials was based on the time to completion and percent of patients who could complete their portion without assistance. Patient satisfaction with the tool was captured. Of the 93 patients who enrolled in this study, five (5%) met criteria for cognitive impairment and three did not complete the cognitive screen, leaving 85 assessable patients (median age, 72 years). The median time to complete the geriatric assessment tool was 22 minutes, 87% of patients (n = 74) completed their portion without assistance, 92% (n = 78) were satisfied with the questionnaire length, 95% (n = 81) reported no difficult questions, and 96% (n = 82) reported no upsetting questions. One hundred percent of health care professionals completed their portion. This brief, primarily self-administered geriatric assessment tool met the protocol specified criteria for inclusion in future cooperative group clinical trials.

Clinical epidemiology survey of the traditional Chinese medicine etiology and syndrome differentiation of coronary artery disease: study protocol of a multicenter trial.

PubMed

Bi, Ying-fei; Mao, Jing-yuan; Wang, Xian-liang; Hou, Ya-zhu; Lu, Yi-zhu; Soh, Shan Bin; Zhang, Bo-li

2012-06-01

Coronary artery disease (CAD), a common disease with high incidence and mortality rate, has seriously threatened the health and life of the public. Traditional Chinese medicine (TCM) has an important role in the prevention and treatment of this disease. Through clinical epidemiological survey, a deeper understanding of TCM etiology and syndrome characteristics in CAD would further improve clinical efficacy in the treatment of this disease. The preliminary clinical questionnaire for TCM etiology and syndrome differentiation in CAD was designed after literature reviews and analysis. Through a series of clinical pre-surveys, expert consultation and demonstration, the formal TCM clinical epidemiology questionnaire on the etiology and syndrome differentiation in CAD was finalized, after which, the study protocol, inclusive and exclusive criteria and related quality control measures were prepared. The multiregional clinical epidemiological survey with more than 5000 participants with CAD will be carried out in 41 TCM hospitals of China for investigating the TCM etiology and syndrome differentiation of CAD. Multiregion large sample size clinical epidemiology survey on TCM etiology and syndrome differentiation in CAD will provide further evidence in preventing CAD and improving the standardization process of syndrome research. This study protocol was registered at the Chinese Clinical Trial Registry on November 27, 2011 in both Chinese and English editions and the registration number is ChiCTR-ECS-11001728.

Support and assessment for fall emergency referrals (SAFER 2) research protocol: cluster randomised trial of the clinical and cost effectiveness of new protocols for emergency ambulance paramedics to assess and refer to appropriate community-based care

PubMed Central

Snooks, Helen; Anthony, Rebecca; Chatters, Robin; Cheung, Wai-Yee; Dale, Jeremy; Donohoe, Rachael; Gaze, Sarah; Halter, Mary; Koniotou, Marina; Logan, Phillippa; Lyons, Ronan; Mason, Suzanne; Nicholl, Jon; Phillips, Ceri; Phillips, Judith; Russell, Ian; Siriwardena, A Niroshan; Wani, Mushtaq; Watkins, Alan; Whitfield, Richard; Wilson, Lynsey

2012-01-01

Introduction Emergency calls to ambulance services are frequent for older people who have fallen, but ambulance crews often leave patients at the scene without ongoing care. Evidence shows that when left at home with no further support older people often experience subsequent falls which result in injury and emergency-department attendances. SAFER 2 is an evaluation of a new clinical protocol which allows paramedics to assess and refer older people who have fallen, and do not need hospital care, to community-based falls services. In this protocol paper, we report methods and progress during trial implementation. SAFER 2 is recruiting patients through three ambulance services. A successful trial will provide robust evidence about the value of this new model of care, and enable ambulance services to use resources efficiently. Design Pragmatic cluster randomised trial. Methods and analysis We randomly allocated 25 participating ambulance stations (clusters) in three services to intervention or control group. Intervention paramedics received training and clinical protocols for assessing and referring older people who have fallen to community-based falls services when appropriate, while control paramedics deliver care as usual. Patients are eligible for the trial if they are aged 65 or over; resident in a participating falls service catchment area; and attended by a trial paramedic following an emergency call coded as a fall without priority symptoms. The principal outcome is the rate of further emergency contacts (or death), for any cause and for falls. Secondary outcomes include further falls, health-related quality of life, ‘fear of falling’, patient satisfaction reported by participants through postal questionnaires at 1 and 6 months, and quality and pathways of care at the index incident. We shall compare National Health Service (NHS) and patient/carer costs between intervention and control groups and estimate quality-adjusted life years (QALYs) gained from the intervention and thus incremental cost per QALY. We shall estimate wider system effects on key-performance indicators. We shall interview 60 intervention patients, and conduct focus groups with contributing NHS staff to explore their experiences of the assessment and referral service. We shall analyse quantitative trial data by ‘treatment allocated’; and qualitative data using content analysis. Ethics and dissemination The Research Ethics Committee for Wales gave ethical approval and each participating centre gave NHS Research and Development approval. We shall disseminate study findings through peer-reviewed publications and conference presentations. Trial Registration: ISRCTN 60481756 PMID:23148348

Ethnography, fidelity, and the evidence that anthropology adds: supplementing the fidelity process in a clinical trial of supported employment.

PubMed

Smith-Morris, Carolyn; Lopez, Gilberto; Ottomanelli, Lisa; Goetz, Lance; Dixon-Lawson, Kimberly

2014-06-01

This discussion considers the role and findings of ethnographic research within a clinical trial of supported employment for veterans with spinal cord injury. Contributing to qualitative evaluation research and to debates over anthropological evidence vis-à-vis clinical trials, we demonstrate how enactors of a randomized controlled trial can simultaneously attend to both the trial's evidentiary and procedural requirements and to the lived experiences and needs of patients and clinicians. Three major findings are described: (1) contextual information essential to fidelity efforts within the trial; (2) the role of human interrelationships and idiosyncratic networks in the trial's success; and (3) a mapping of the power and authority structures relevant to the staff's ability to perform the protocol. We emphasize strengths of anthropological ethnography in clinical trials that include the provision of complementary, qualitative data, the capture of otherwise unmeasured parts of the trial, and the realization of important information for the translation of the clinical findings into new settings. © 2014 by the American Anthropological Association.

The behavioral dynamics of clinical trials.

PubMed

Leventhal, H; Nerenz, D R; Leventhal, E A; Love, R R; Bendena, L M

1991-01-01

Two ways of approaching the design of long-term clinical trials are presented and contrasted. The first, termed the "static" view, emphasizes close adherence to formal rules of study design. The second, termed the "dynamic" view, emphasizes the behavioral aspects of patient participation in trials of long duration. The dynamic view is discussed in detail, with discussion of how recruitment of participants, random assignment to conditions, compliance with protocol, and measurement of outcomes are affected by behavioral dynamics. Data from a recently completed tamoxifen toxicity trial are used to illustrate the points and to focus the discussion of behavioral dynamics on the design of a chemoprevention trial for breast cancer using tamoxifen.

A randomised trial of non-mydriatic ultra-wide field retinal imaging versus usual care to screen for diabetic eye disease: rationale and protocol for the Clearsight trial

PubMed Central

Mahon, Lewis W; Klar, Neil S; Schulz, David C; Gonder, John R; Hramiak, Irene M; Mahon, Jeffrey L

2017-01-01

Introduction Suboptimal screening for diabetic eye disease is a major cause of preventable vision loss. Screening barriers include mydriasis and the extra time patients need to attend dedicated eye screening appointments. In the Clearsight trial, we are testing whether screening by non-mydriatic ultra-wide field (NM UWF) imaging on the day patients attend their diabetes outpatient clinic visit improves detection of clinically important eye disease compared with usual screening. Methods and analysis Patients with diabetes due for a screening eye exam by the 2013 Canadian Diabetes Association (CDA) practice guidelines are being randomised to on-site screening by NM UWF imaging on the day of their clinic visit or to usual screening where, per CDA guidelines, they are encouraged to arrange an exam by an optometrist. The primary outcome is actionable eye disease (AED) based on a need for referral to ophthalmology and/or increased ocular surveillance. The primary analysis will use an intention-to-screen approach that compares the proportions of detected AED between on-site and usual screening groups under a superiority hypothesis in favour of on-site screening. With 740 randomised participants, the study will have 80% power to detect ≥5% absolute increase in the AED rate among on-site screening versus usual screening participants. This difference translates into a number-needed-to-screen by on-site screening of 20 to detect 1 additional person with AED. Ethics and dissemination The protocol was approved by the institutional review board of Western University. The findings of the trial will be disseminated directly to participants and through peer-reviewed publications and conference presentations. Trial registration number ClinicalTrials.Gov NCT02579837 (registered 16 October 2015). Protocol issue date 18 November 2015. PMID:28775182

SU-G-206-01: A Fully Automated CT Tool to Facilitate Phantom Image QA for Quantitative Imaging in Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wahi-Anwar, M; Lo, P; Kim, H

Purpose: The use of Quantitative Imaging (QI) methods in Clinical Trials requires both verification of adherence to a specified protocol and an assessment of scanner performance under that protocol, which are currently accomplished manually. This work introduces automated phantom identification and image QA measure extraction towards a fully-automated CT phantom QA system to perform these functions and facilitate the use of Quantitative Imaging methods in clinical trials. Methods: This study used a retrospective cohort of CT phantom scans from existing clinical trial protocols - totaling 84 phantoms, across 3 phantom types using various scanners and protocols. The QA system identifiesmore » the input phantom scan through an ensemble of threshold-based classifiers. Each classifier - corresponding to a phantom type - contains a template slice, which is compared to the input scan on a slice-by-slice basis, resulting in slice-wise similarity metric values for each slice compared. Pre-trained thresholds (established from a training set of phantom images matching the template type) are used to filter the similarity distribution, and the slice with the most optimal local mean similarity, with local neighboring slices meeting the threshold requirement, is chosen as the classifier’s matched slice (if it existed). The classifier with the matched slice possessing the most optimal local mean similarity is then chosen as the ensemble’s best matching slice. If the best matching slice exists, image QA algorithm and ROIs corresponding to the matching classifier extracted the image QA measures. Results: Automated phantom identification performed with 84.5% accuracy and 88.8% sensitivity on 84 phantoms. Automated image quality measurements (following standard protocol) on identified water phantoms (n=35) matched user QA decisions with 100% accuracy. Conclusion: We provide a fullyautomated CT phantom QA system consistent with manual QA performance. Further work will include parallel component to automatically verify image acquisition parameters and automated adherence to specifications. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics; NIH Grant support from: U01 CA181156.« less

The Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study: the updated final trial protocol and rationale of post-initiation trial modifications.

PubMed

Viecelli, Andrea K; Pascoe, Elaine; Polkinghorne, Kevan R; Hawley, Carmel; Paul-Brent, Peta-Anne; Badve, Sunil V; Cass, Alan; Heritier, Stephane; Kerr, Peter G; Mori, Trevor A; Robertson, Amanda; Seong, Hooi L; Irish, Ashley B

2015-06-27

The FAVOURED study is an international multicentre, double-blind, placebo-controlled trial which commenced recruitment in 2008 and examines whether omega-3 polyunsaturated fatty acids (omega-3 PUFAs) either alone or in combination with aspirin will effectively reduce primary access failure of de novo arteriovenous fistulae (AVF) in patients with stage 4 and 5 chronic kidney disease. Publication of new evidence derived from additional studies of clopidogrel and a high screen failure rate due to prevalent aspirin usage prompted an updated trial design. The original trial protocol published in 2009 has undergone two major amendments, which were implemented in 2011. Firstly, the primary outcome 'early thrombosis' at 3 months following AVF creation was broadened to a more clinically relevant outcome of 'AVF access failure'; a composite of thrombosis, AVF abandonment and cannulation failure at 12 months. Secondly, participants unable to cease using aspirin were allowed to be enrolled and randomised to omega-3 PUFAs or placebo. The revised primary aim of the FAVOURED study is to test the hypothesis that omega-3 PUFAs will reduce rates of AVF access failure within 12 months following AVF surgery. The secondary aims are to examine the effect of omega-3 PUFAs and aspirin on the individual components of the primary end-point, to examine the safety of study interventions and assess central venous catheter requirement as a result of access failure. This multicentre international clinical trial was amended to address the clinically relevant question of whether the usability of de novo AVF at 12 months can be improved by the early use of omega-3 PUFAs and to a lesser extent aspirin. This study protocol amendment was made in response to a large trial demonstrating that clopidogrel is effective in safely preventing primary AVF thrombosis, but ineffective at increasing functional patency. Secondly, including patients taking aspirin will enroll a more representative cohort of haemodialysis patients, who are significantly older with a higher prevalence of cardiovascular disease and diabetes which may increase event rates and the power of the study. Australia & New Zealand Clinical Trial Register (ACTRN12607000569404).

Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial.

PubMed

Mir, Fatima; Nisar, Imran; Tikmani, Shiyam S; Baloch, Benazir; Shakoor, Sadia; Jehan, Fyezah; Ahmed, Imran; Cousens, Simon; Zaidi, Anita K M

2017-02-01

Parenteral antibiotic therapy for young infants (aged 0-59 days) with suspected sepsis is sometimes not available or feasible in countries with high neonatal mortality. Outpatient treatment could save lives in such settings. We aimed to assess the equivalence of two simplified antibiotic regimens, comprising fewer injections and oral rather than parenteral administration, compared with a reference treatment for young infants with clinical severe infection. We undertook the Simplified Antibiotic Therapy Trial (SATT), a three-arm, randomised, open-label, equivalence trial in five communities in Karachi, Pakistan. We enrolled young infants (aged 0-59 days) who either presented at a primary health-care clinic or were identified by a community health worker with signs of clinical severe infection. We included infants who were not critically ill and whose family refused admission. We randomly assigned infants to either intramuscular procaine benzylpenicillin and gentamicin once a day for 7 days (reference); oral amoxicillin twice daily and intramuscular gentamicin once a day for 7 days; or intramuscular procaine benzylpenicillin and gentamicin once a day for 2 days followed by oral amoxicillin twice daily for 5 days. The primary outcome was treatment failure within 7 days of enrolment and the primary analysis was per protocol. We judged experimental treatments as efficacious as the reference if the upper bound of the 95% CI for the difference in treatment failure was less than 5·0. This trial is registered at ClinicalTrials.gov, number NCT01027429. Between Jan 1, 2010, and Dec 26, 2013, 2780 infants were deemed eligible for the trial, of whom 2453 (88%) were enrolled. Because of inadequate clinical follow-up or treatment adherence, 2251 infants were included in the per-protocol analysis. 820 infants (747 per protocol) were assigned the reference treatment of procaine benzylpenicillin and gentamicin, 816 (751 per protocol) were allocated amoxicillin and gentamicin, and 817 (753 per protocol) were assigned procaine benzylpenicillin, gentamicin, and amoxicillin. Treatment failure within 7 days of enrolment was reported in 90 (12%) infants who received procaine benzylpenicillin and gentamicin (reference), 76 (10%) of those given amoxicillin and gentamicin (risk difference with reference -1·9, 95% CI -5·1 to 1·3), and 99 (13%) of those treated with procaine benzylpenicillin, gentamicin, and amoxicillin (risk difference with reference 1·1, -2·3 to 4·5). Two simplified antibiotic regimens requiring fewer injections are equivalent to a reference treatment for young infants with signs of clinical severe infection but without signs of critical illness. The use of these simplified regimens has the potential to increase access to treatment for sick young infants who cannot be referred to hospital. The Saving Newborn Lives initiative of Save the Children, through support from the Bill & Melinda Gates, and by WHO and USAID. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.

The natural history of conducting and reporting clinical trials: interviews with trialists.

PubMed

Smyth, Rebecca M D; Jacoby, Ann; Altman, Douglas G; Gamble, Carrol; Williamson, Paula R

2015-01-26

To investigate the nature of the research process as a whole, factors that might influence the way in which research is carried out, and how researchers ultimately report their findings. Semi-structured qualitative telephone interviews with authors of trials, identified from two sources: trials published since 2002 included in Cochrane systematic reviews selected for the ORBIT project; and trial reports randomly sampled from 14,758 indexed on PubMed over the 12-month period from August 2007 to July 2008. A total of 268 trials were identified for inclusion, 183 published since 2002 and included in the Cochrane systematic reviews selected for the ORBIT project and 85 randomly selected published trials indexed on PubMed. The response rate from researchers in the former group was 21% (38/183) and in the latter group was 25% (21/85). Overall, 59 trialists were interviewed from the two different sources. A number of major but related themes emerged regarding the conduct and reporting of trials: establishment of the research question; identification of outcome variables; use of and adherence to the study protocol; conduct of the research; reporting and publishing of findings. Our results reveal that, although a substantial proportion of trialists identify outcome variables based on their clinical experience and knowing experts in the field, there can be insufficient reference to previous research in the planning of a new trial. We have revealed problems with trial recruitment: not reaching the target sample size, over-estimation of recruitment potential and recruiting clinicians not being in equipoise. We found a wide variation in the completeness of protocols, in terms of detailing study rationale, outlining the proposed methods, trial organisation and ethical considerations. Our results confirm that the conduct and reporting of some trials can be inadequate. Interviews with researchers identified aspects of clinical research that can be especially challenging: establishing appropriate and relevant outcome variables to measure, use of and adherence to the study protocol, recruiting of study participants and reporting and publishing the study findings. Our trialists considered the prestige and impact factors of academic journals to be the most important criteria for selecting those to which they would submit manuscripts.

Comparing community and specialty provider-based recruitment in a randomized clinical trial: clinical trial in fecal incontinence.

PubMed

Whitebird, Robin R; Bliss, Donna Zimmaro; Savik, Kay; Lowry, Ann; Jung, Hans-Joachim G

2010-12-01

Recruitment of participants to clinical trials remains a significant challenge, especially for research addressing topics of a sensitive nature such as fecal incontinence (FI). In the Fiber Study, a randomized controlled trial on symptom management for FI, we successfully enrolled 189 community-living adults through collaborations with specialty-based and community-based settings, each employing methods tailored to the organizational characteristics of their site. Results show that using the two settings increased racial and ethnic diversity of the sample and inclusion of informal caregivers. There were no differential effects on enrollment, final eligibility, or completion of protocol by site. Strategic collaborations with complementary sites can achieve sample recruitment goals for clinical trials on topics that are sensitive or known to be underreported. Copyright © 2010 Wiley Periodicals, Inc.

Pilot study of a point-of-use decision support tool for cancer clinical trials eligibility.

PubMed

Breitfeld, P P; Weisburd, M; Overhage, J M; Sledge, G; Tierney, W M

1999-01-01

Many adults with cancer are not enrolled in clinical trials because caregivers do not have the time to match the patient's clinical findings with varying eligibility criteria associated with multiple trials for which the patient might be eligible. The authors developed a point-of-use portable decision support tool (DS-TRIEL) to automate this matching process. The support tool consists of a hand-held computer with a programmable relational database. A two-level hierarchic decision framework was used for the identification of eligible subjects for two open breast cancer clinical trials. The hand-held computer also provides protocol consent forms and schemas to further help the busy oncologist. This decision support tool and the decision framework on which it is based could be used for multiple trials and different cancer sites.

Pilot Study of a Point-of-use Decision Support Tool for Cancer Clinical Trials Eligibility

PubMed Central

Breitfeld, Philip P.; Weisburd, Marina; Overhage, J. Marc; Sledge, George; Tierney, William M.

1999-01-01

Many adults with cancer are not enrolled in clinical trials because caregivers do not have the time to match the patient's clinical findings with varying eligibility criteria associated with multiple trials for which the patient might be eligible. The authors developed a point-of-use portable decision support tool (DS-TRIEL) to automate this matching process. The support tool consists of a hand-held computer with a programmable relational database. A two-level hierarchic decision framework was used for the identification of eligible subjects for two open breast cancer clinical trials. The hand-held computer also provides protocol consent forms and schemas to further help the busy oncologist. This decision support tool and the decision framework on which it is based could be used for multiple trials and different cancer sites. PMID:10579605

The pharmaceutical industry's responsibility for protecting human subjects of clinical trials in developing nations.

PubMed

Kelleher, Finnuala

2004-01-01

Pharmaceutical companies increasingly perform clinical trials in developing nations. Governments of host nations see the trials as a way to provide otherwise unaffordable medical care, while trial sponsors are drawn to those countries by lower costs, the prevalence of diseases rare in developed nations, and large numbers of impoverished patients. Local governments, however, fail to police trials, and the FDA does not monitor trials in foreign countries, resulting in the routine violation of international standards for the protection of human subjects. This Note proposes independent accreditation of those institutions involved in clinical trials--the institutional review boards which oversee trial protocol; the organizations, such as pharmaceutical companies, which sponsor the trials; and the research organizations that conduct the trials. Accreditation, similar to that used in the footwear and apparel industries, would increase the transparency of pharmaceutical trials and would enable the United States government and consumers to hold trial sponsors accountable for their actions.

Cost-evaluation model for clinical trials in a hospital pharmacy service.

PubMed

Idoate, A; Ortega, A; Carrera, F J; Aldaz, A; Giráldez, J

1995-09-22

A cost-evaluation model was applied to clinical trial protocols to estimate their cost for the hospital pharmacy service. The steps taken in the drug management of clinical research were identified. Fixed costs (common to all clinical trials) and variable costs (peculiar to each clinical trial) were determined for each step. The number of patients, the number of operations, the planned services (receptions, storage, drug dispensing), the timing and difficulty of the study (randomization) were included in the variable costs. The economic assessment of these items was based on the costs of the materials and means used, the cost of staff time and finally the cost of drug storage during the clinical trial. This model was applied to 24 clinical trials carried out in the University Clinic of Navarra. 83% of all pharmacy costs of a clinical trial were variable. Drug dispensing, stock management and return drugs account for 94% of the time expended. The approximate cost of the pharmacy providing investigational services was $1,766 per trial or $174 per patient. Drug storage costs were not an important source of expenditure among the variable costs (7.4%). The best way to determine the cost of a trial is to calculate the number of operations.

Challenges in the design and implementation of the Multicenter Uveitis Steroid Treatment (MUST) Trial--lessons for comparative effectiveness trials.

PubMed

Holbrook, Janet T; Kempen, John H; Prusakowski, Nancy A; Altaweel, Michael M; Jabs, Douglas A

2011-12-01

Randomized clinical trials (RCTs) are an important component of comparative effectiveness (CE) research because they are the optimal design for head-to-head comparisons of different treatment options. To describe decisions made in the design of the Multicenter Uveitis Steroid Treatment (MUST) Trial to ensure that the results would be widely generalizable. Review of design and implementation decisions and their rationale for the trial. The MUST Trial is a multicenter randomized controlled CE trial evaluating a novel local therapy (intraocular fluocinolone acetonide implant) versus the systemic therapy standard of care for noninfectious uveitis. Decisions made in protocol design in order to broaden enrollment included allowing patients with very poor vision and media opacity to enroll and including clinical sites outside the United States. The treatment protocol was designed to follow standard care. The primary outcome, visual acuity, is important to patients and can be evaluated in all eyes with uveitis. Other outcomes include patient-reported visual function, quality of life, and disease and treatment related complications. The trial population is too small for subgroup analyses that are of interest and the trial is being conducted at tertiary medical centers. CE trials require greater emphasis on generalizability than many RCTs but otherwise face similar challenges for design choices as any RCT. The increase in heterogeneity in patients and treatment required to ensure generalizability can be balanced with a rigorous approach to implementation, outcome assessment, and statistical design. This approach requires significant resources that may limit implementation in many RCTs, especially in clinical practice settings.

Safety Profile of Good Manufacturing Practice Manufactured Interferon γ-Primed Mesenchymal Stem/Stromal Cells for Clinical Trials.

PubMed

Guess, Adam J; Daneault, Beth; Wang, Rongzhang; Bradbury, Hillary; La Perle, Krista M D; Fitch, James; Hedrick, Sheri L; Hamelberg, Elizabeth; Astbury, Caroline; White, Peter; Overolt, Kathleen; Rangarajan, Hemalatha; Abu-Arja, Rolla; Devine, Steven M; Otsuru, Satoru; Dominici, Massimo; O'Donnell, Lynn; Horwitz, Edwin M

2017-10-01

Mesenchymal stem/stromal cells (MSCs) are widely studied by both academia and industry for a broad array of clinical indications. The collective body of data provides compelling evidence of the clinical safety of MSC therapy. However, generally accepted proof of therapeutic efficacy has not yet been reported. In an effort to generate a more effective therapeutic cell product, investigators are focused on modifying MSC processing protocols to enhance the intrinsic biologic activity. Here, we report a Good Manufacturing Practice-compliant two-step MSC manufacturing protocol to generate MSCs or interferon γ (IFNγ) primed MSCs which allows freshly expanded cells to be infused in patients on a predetermined schedule. This protocol eliminates the need to infuse cryopreserved, just thawed cells which may reduce the immune modulatory activity. Moreover, using (IFNγ) as a prototypic cytokine, we demonstrate the feasibility of priming the cells with any biologic agent. We then characterized MSCs and IFNγ primed MSCs prepared with our protocol, by karyotype, in vitro potential for malignant transformation, biodistribution, effect on engraftment of transplanted hematopoietic cells, and in vivo toxicity in immune deficient mice including a complete post-mortem examination. We found no evidence of toxicity attributable to the MSC or IFNγ primed MSCs. Our data suggest that the clinical risk of infusing MSCs or IFNγ primed MSCs produced by our two-step protocol is not greater than MSCs currently in practice. While actual proof of safety requires phase I clinical trials, our data support the use of either cell product in new clinical studies. Stem Cells Translational Medicine 2017;6:1868-1879. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Implementing an intravenous insulin protocol in your practice: practical advice to overcome clinical, administrative, and financial barriers.

PubMed

Kelly, Janet L; Hirsch, Irl B; Furnary, Anthony P

2006-01-01

Diabetes mellitus is the fourth most common comorbid condition among hospitalized patients, and 30% of patients undergoing open-heart surgery have diabetes. The link between hyperglycemia and poor outcome has been well described, and large clinical trials have shown that aggressive control of blood glucose with an insulin infusion can improve these outcomes. The barriers to implementing an insulin infusion protocol are numerous, despite the fact that doing so is paramount to clinical success. Barriers include safety concerns, such as fear of hypoglycemia, insufficient nursing staff to patient ratios, lack of administrative and physician support, various system and procedural issues, and resistance to change. Key steps to overcome the barriers include building support with multidisciplinary champions, involving key staff, educating staff, and administrators of the clinical and economic benefits of improving glycemic control, setting realistic goals, selecting a validated insulin infusion protocol, and internally marketing the success of the protocol.

Guided Internet-based versus face-to-face clinical care in the management of tinnitus: study protocol for a multi-centre randomised controlled trial.

PubMed

Beukes, Eldré W; Baguley, David M; Allen, Peter M; Manchaiah, Vinaya; Andersson, Gerhard

2017-04-21

Innovative strategies are required to improve access to evidence-based tinnitus interventions. A guided Internet-based cognitive behavioural therapy (iCBT) intervention for tinnitus was therefore developed for a U.K. Initial clinical trials indicated efficacy of iCBT at reducing tinnitus severity and associated comorbidities such as insomnia and depression. The aim of this phase III randomised controlled trial is to compare this new iCBT intervention with an established intervention, namely face-to-face clinical care for tinnitus. This will be a multi-centre study undertaken across three hospitals in the East of England. The design is a randomised, two-arm, parallel-group, non-inferiority trial with a 2-month follow-up. The experimental group will receive the guided iCBT intervention, whereas the active control group will receive the usual face-to-face clinical care. An independent researcher will randomly assign participants, using a computer-generated randomisation schedule, after stratification for tinnitus severity. There will be 46 participants in each group. The primary assessment measure will be the Tinnitus Functional Index. Data analysis will establish whether non-inferiority is achieved using a pre-defined non-inferiority margin. This protocol outlines phase III of a clinical trial comparing a new iCBT with established face-to-face care for tinnitus. If guided iCBT for tinnitus proves to be as effective as the usual tinnitus care, it may be a viable additional management route for individuals with tinnitus. This could increase access to evidence-based effective tinnitus care and reduce the pressures on existing health care systems. ClinicalTrials.gov identifier: NCT02665975 . Registered on 22 January 2016.

A Randomized Clinical Trial of Cognitive-Behavioral Treatment for PTSD in Women

DTIC Science & Technology

2003-10-01

Post Traumatic Stress Disorder ( PTSD ) in 384 female veterans and active duty personnel at 11 sites. This is a VA Cooperative Study. Walter...14. SUBJECT TERMS 15. NUMBER OF PAGES Post - Traumatic Stress Disorder 6 16. PRICE CODE 17. SECURITY CLASSIFICATION 18. SECURITY CLASSIFICATION 19...Clinical Trial of Cognitive-Behavioral Treatment for Post Traumatic Stress Disorder in Women for this study, from the protocol Additionally, a new

Implementation of an anonymisation tool for clinical trials using a clinical trial processor integrated with an existing trial patient data information system.

PubMed

Aryanto, Kadek Y E; Broekema, André; Oudkerk, Matthijs; van Ooijen, Peter M A

2012-01-01

To present an adapted Clinical Trial Processor (CTP) test set-up for receiving, anonymising and saving Digital Imaging and Communications in Medicine (DICOM) data using external input from the original database of an existing clinical study information system to guide the anonymisation process. Two methods are presented for an adapted CTP test set-up. In the first method, images are pushed from the Picture Archiving and Communication System (PACS) using the DICOM protocol through a local network. In the second method, images are transferred through the internet using the HTTPS protocol. In total 25,000 images from 50 patients were moved from the PACS, anonymised and stored within roughly 2 h using the first method. In the second method, an average of 10 images per minute were transferred and processed over a residential connection. In both methods, no duplicated images were stored when previous images were retransferred. The anonymised images are stored in appropriate directories. The CTP can transfer and process DICOM images correctly in a very easy set-up providing a fast, secure and stable environment. The adapted CTP allows easy integration into an environment in which patient data are already included in an existing information system.

Jail-to-community treatment continuum for adults with co-occurring substance use and mental disorders: study protocol for a pilot randomized controlled trial.

PubMed

Van Dorn, Richard A; Desmarais, Sarah L; Rade, Candalyn B; Burris, Elizabeth N; Cuddeback, Gary S; Johnson, Kiersten L; Tueller, Stephen J; Comfort, Megan L; Mueser, Kim T

2017-08-04

Adults with co-occurring mental and substance use disorders (CODs) are overrepresented in jails. In-custody barriers to treatment, including a lack of evidence-based treatment options and the often short periods of incarceration, and limited communication between jails and community-based treatment agencies that can hinder immediate enrollment into community care once released have contributed to a cycle of limited treatment engagement, unaddressed criminogenic risks, and (re)arrest among this vulnerable and high-risk population. This paper describes a study that will develop research and communication protocols and adapt two evidence-based treatments, dual-diagnosis motivational interviewing (DDMI) and integrated group therapy (IGT), for delivery to adults with CODs across a jail-to-community treatment continuum. Adaptations to DDMI and IGT were guided by the Risk-Need-Responsivity model and the National Institute of Corrections' implementation competencies; the development of the implementation framework and communication protocols were guided by the Evidence-Based Interagency Implementation Model for community corrections and the Inter-organizational Relationship model, respectively. Implementation and evaluation of the protocols and adapted interventions will occur via an open trial and a pilot randomized trial. The clinical intervention consists of two in-jail DDMI sessions and 12 in-community IGT sessions. Twelve adults with CODs and four clinicians will participate in the open trial to evaluate the acceptability and feasibility of, and fidelity to, the interventions and research and communication protocols. The pilot controlled trial will be conducted with 60 inmates who will be randomized to either DDMI-IGT or treatment as usual. A baseline assessment will be conducted in jail, and four community-based assessments will be conducted during a 6-month follow-up period. Implementation, clinical, public health, and treatment preference outcomes will be evaluated. Findings have the potential to improve both jail- and community-based treatment services for adults with CODs as well as inform methods for conducting rigorous pilot implementation and evaluation research in correctional settings and as inmates re-enter the community. Findings will contribute to a growing area of work focused on interrupting the cycle of limited treatment engagement, unaddressed criminogenic risks, and (re)arrest among adults with CODs. ClinicalTrials.gov, NCT02214667 . Registered on 10 August 2014.

Effects of Vestibular Rehabilitation on Balance Control in Older People with Chronic Dizziness: A Randomized Clinical Trial.

PubMed

Ricci, Natalia Aquaroni; Aratani, Mayra Cristina; Caovilla, Heloísa Helena; Ganança, Fernando Freitas

2016-04-01

The aim of this study was to compare the effects of vestibular rehabilitation protocols on balance control in elderly with dizziness. This is a randomized clinical trial with 3-mo follow-up period. The sample was composed of 82 older individuals with chronic dizziness from vestibular disorders. The control group was treated according to the Conventional Cawthorne & Cooksey protocol (n = 40), and the experimental group was submitted to a Multimodal Cawthorne & Cooksey protocol (n = 42). Measures included Dynamic Gait Index, fall history, hand grip strength, Time Up-and-Go Test, sit-to-stand test, multidirectional reach, and static balance tests. With the exception of history of falls, Forward Functional Reach, Unipedal Right and Left Leg Eyes Closed, and Sensorial Romberg Eyes Open, all outcomes improved after treatments. Such results persisted at follow-up period, with the exception of the Tandem Eyes Open and the Timed Up-and-Go manual. The between-group differences for Sensorial Romberg Eyes Closed (4.27 secs) and Unipedal Left Leg Eyes Open (4.08 secs) were significant after treatment, favoring the Multimodal protocol. Both protocols resulted in improvement on elderly's balance control, which was maintained during a short-term period. The multimodal protocol presented better performance on specific static balance tests.

In vivo procedures for assessment of hair greasiness.

PubMed

Knott, C A; Daykin, K; Ryan, J

1983-06-01

Synopsis Greasy hair is a common problem in Europe. The first step in developing anti-grease hair products must be to establish a sensitive protocol for measuring any changes in perceived hair greasiness. Sensitive clinical trials and in vivo evaluation methods of determining hair greasiness have been developed that show significant differences in the perceived hair greasiness following the use of different shampoos. Products tested in two clinical trials for efficacy as anti-grease shampoos were an anti-grease shampoo containing 2% 3,4-thiolanediol as the active ingredient, and a baby shampoo based on mild surfactants. The same placebo shampoo based on ether sulphates used in typical European shampoo formulations was used in both tests. A shampoo containing 2% zinc pyrithione was included in the trials as a control, since there were indications that this would increase the amount of hair greasiness. Neither of the test products were shown to be effective anti-grease shampoos. The shampoo containing 2% zinc pyrithione was shown to produce significantly more greasiness than both the placebo and the test shampoos. Since significant differences could be shown between the different shampoos, the protocol and in vivo evaluation techniques used in these clinical trials are considered to be validated.

Evaluating real-time internet therapy and online self-help for problematic alcohol consumers: a three-arm RCT protocol.

PubMed

Blankers, Matthijs; Koeter, Maarten; Schippers, Gerard M

2009-01-14

Only a minority of all alcohol- and drug abusers is receiving professional care. In an attempt to narrow this treatment gap, treatment facilities experiment with online healthcare. Therefore, it is important to test the (cost-)effectiveness of online health interventions in a randomized clinical trial. This paper presents the protocol of a three-arm randomized clinical trial to test the (cost-) effectiveness of online treatment for problem drinkers. Self-help online, therapy online and a waiting list are tested against each other. Primary outcome is change in alcohol consumption. Secondary outcome measures include quality of life and working ability. Incremental cost-effectiveness ratios for self-help online alcohol and therapy online alcohol will be calculated. The predictive validity of participant characteristics on treatment adherence and outcome will be explored. To our best knowledge, this randomized clinical trial will be the first to test the effectiveness of therapy online against both self-help online and a waiting-list. It will provide evidence on (cost-) effectiveness of online treatment for problem drinkers and investigate outcome predictors. This trial is registered in the Dutch Trialregister (Cochrane Collaboration) and traceable as NTR-TC1155.

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831)

PubMed Central

Kean, James D.; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

2015-01-01

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6–14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners’ Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Trial registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831. PMID:26633481

Comparison of propofol and dexmedetomidine infused overnight to treat hyperactive and mixed ICU delirium: a protocol for the Basel ProDex clinical trial

PubMed Central

Ledergerber, Katrin; von Felten, Stefanie; Sutter, Raoul; Rüegg, Stephan; Gantner, Lukas; Zimmermann, Sibylle; Blum, Andrea; Steiner, Luzius A; Marsch, Stephan; Siegemund, Martin

2017-01-01

Background/objectives Delirium is a neurobehavioural disturbance that frequently develops particularly in the intensive care unit (ICU) population. It was first described more than half a century ago, where it was already discovered as a state that might come along with serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. However, in most cases, there is still lack of proof for causal relationship. Its presence frequently remains unrecognised due to suggested predominance of the hypoactive form. Furthermore, in the general ICU population, it has been shown that the duration of delirium is associated with worse long-term cognitive function. Due to the multifactorial origin of delirium, we have several but no incontestable treatment options. Nonetheless, delirium bears a high burden for patient, family members and the medical care team. The Basel ProDex Study targets improvement of hyperactive and mixed delirium therapy in critically ill patients. We will focus on reducing the duration and severity of delirium by implementing dexmedetomidine into the treatment plan. Dexmedetomidine compared with other sedatives shows fewer side effects representing a better risk profile for delirium treatment in general. This could further contribute to higher patient safety. The aim of the BaProDex Trial is to assess the superiority of dexmedetomidine to propofol for treatment of hyperactive and mixed delirium in the ICU. We hypothesise that dexmedetomidine, compared with propofol administered at night, shortens both the duration and severity of delirium. Methods/design The Basel ProDex Study is an investigator-initiated, one-institutional, two-centre randomised controlled clinical trial for the treatment of delirium with dexmedetomidine versus propofol in 316 critically ill patients suffering from hyperactive and mixed delirium. The primary outcome measure is delirium duration in hours. Secondary outcomes include delirium-free days at day 28, death at day 28, delirium severity, amount of ventilator days, amount of rescue sedation with haloperidol, length of ICU and hospital stay, and pharmaceutical economic analysis of the treatments. Sample size was estimated to be able to show the superiority of dexmedetomidine compared with propofol regarding the duration of delirium in hours. The trial will be externally monitored according to good clinical practice (GCP) requirements. There are no interim analyses planned for this trial. Ethics and dissemination This study will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonization- Good Clinical Practice (ICH-GCP) or Europäische Norm International Organization for Standardization (ISO EN 14155; as far as applicable) as well as all national legal and regulatory requirements. Only the study team will have access to trial specific data. Anonymisation will be achieved by a unique patient identification code. Trial data will be archived for a minimum of 10 years after study termination. We plan to publish the data in a major peer-reviewed clinical journal. Trials registration ClinicalTrials.gov Identifier: NCT02807467 Protocol version Clinical Study Protocol Version 2, 16.08.2016 PMID:28710219

Characteristics of randomised trials on diseases in the digestive system registered in ClinicalTrials.gov: a retrospective analysis.

PubMed

Wildt, Signe; Krag, Aleksander; Gluud, Liselotte

2011-01-01

Objectives To evaluate the adequacy of reporting of protocols for randomised trials on diseases of the digestive system registered in http://ClinicalTrials.gov and the consistency between primary outcomes, secondary outcomes and sample size specified in http://ClinicalTrials.gov and published trials. Methods Randomised phase III trials on adult patients with gastrointestinal diseases registered before January 2009 in http://ClinicalTrials.gov were eligible for inclusion. From http://ClinicalTrials.gov all data elements in the database required by the International Committee of Medical Journal Editors (ICMJE) member journals were extracted. The subsequent publications for registered trials were identified. For published trials, data concerning publication date, primary and secondary endpoint, sample size, and whether the journal adhered to ICMJE principles were extracted. Differences between primary and secondary outcomes, sample size and sample size calculations data in http://ClinicalTrials.gov and in the published paper were registered. Results 105 trials were evaluated. 66 trials (63%) were published. 30% of trials were registered incorrectly after their completion date. Several data elements of the required ICMJE data list were not filled in, with missing data in 22% and 11%, respectively, of cases concerning the primary outcome measure and sample size. In 26% of the published papers, data on sample size calculations were missing and discrepancies between sample size reporting in http://ClinicalTrials.gov and published trials existed. Conclusion The quality of registration of randomised controlled trials still needs improvement.

Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

PubMed

Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

2018-01-30

It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

PubMed

Shih, Sophy T F; Davis-Lameloise, Nathalie; Janus, Edward D; Wildey, Carol; Versace, Vincent L; Hagger, Virginia; Asproloupos, Dino; O'Reilly, Sharleen L; Phillips, Paddy A; Ackland, Michael; Skinner, Timothy; Oats, Jeremy; Carter, Rob; Best, James D; Dunbar, James A

2014-06-30

The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

Positive imagery cognitive bias modification (CBM) and internet-based cognitive behavioural therapy (iCBT) versus control CBM and iCBT for depression: study protocol for a parallel-group randomised controlled trial.

PubMed

Williams, Alishia D; Blackwell, Simon E; Holmes, Emily A; Andrews, Gavin

2013-10-29

The current randomised controlled trial will evaluate the efficacy of an internet-delivered positive imagery cognitive bias modification (CBM) intervention for depression when compared with an active control condition and help establish the additive benefit of positive imagery CBM when delivered in combination with internet cognitive behavioural therapy for depression. Patients meeting diagnostic criteria for a current major depressive episode will be recruited through the research arm of a not-for-profit clinical and research unit in Australia. The minimum sample size for each group (α set at 0.05, power at 0.80) was identified as 29, but at least 10% more will be recruited to hedge against expected attrition. We will measure the impact of CBM on primary measures of depressive symptoms (Beck Depression Inventory-second edition (BDI-II), Patient Health Questionnaire (PHQ9)) and interpretive bias (ambiguous scenarios test-depression), and on a secondary measure of psychological distress (Kessler-10 (K10)) following the 1-week CBM intervention. Secondary outcome measures of psychological distress (K10), as well as disability (WHO disability assessment schedule-II), repetitive negative thinking (repetitive thinking questionnaire), and anxiety (state trait anxiety inventory-trait version) will be evaluated following completion of the 11-week combined intervention, in addition to the BDI-II and PHQ9. Intent-to-treat marginal and mixed effect models using restricted maximum likelihood estimation will be used to evaluate the primary hypotheses. Clinically significant change will be defined as high-end state functioning (a BDI-II score <14) combined with a total score reduction greater than the reliable change index score. Maintenance of gains will be assessed at 3-month follow-up. The current trial protocol has been approved by the Human Research Ethics Committee of St Vincent's Hospital and the University of New South Wales, Sydney. Australian New Zealand Clinical Trials Registry: ACTRN12613000139774 and Clinicaltrials.gov: NCT01787513. This trial protocol is written in compliance with the Standard Protocol Items: recommendations for Interventional Trials (SPIRIT) guidelines.

Patient perspectives: Kundalini yoga meditation techniques for psycho-oncology and as potential therapies for cancer.

PubMed

Shannahoff-Khalsa, David S

2005-03-01

The ancient system of Kundalini Yoga (KY) includes a vast array of meditation techniques. Some were discovered to be specific for treating psychiatric disorders and others are supposedly beneficial for treating cancers. To date, 2 clinical trials have been conducted for treating obsessive-compulsive disorder (OCD). The first was an open uncontrolled trial and the second a single-blinded randomized controlled trial (RCT) comparing a KY protocol against the Relaxation Response and Mindfulness Meditation (RRMM) techniques combined. Both trials showed efficacy on all psychological scales using the KY protocol; however, the RCT showed no efficacy on any scale with the RRMM control group. The KY protocol employed an OCD-specific meditation technique combined with other techniques that are individually specific for anxiety, low energy, fear, anger, meeting mental challenges, and turning negative thoughts into positive thoughts. In addition to OCD symptoms, other symptoms, including anxiety and depression, were also significantly reduced. Elements of the KY protocol other than the OCD-specific technique also may have applications for psycho-oncology patients and are described here. Two depression-specific KY techniques are described that also help combat mental fatigue and low energy. A 7-part protocol is described that would be used in KY practice to affect the full spectrum of emotions and distress that complicate a cancer diagnosis. In addition, there are KY techniques that practitioners have used in treating cancer. These techniques have not yet been subjected to formal clinical trials but are described here as potential adjunctive therapies. A case history demonstrating rapid onset of acute relief of intense fear in a terminal breast cancer patient using a KY technique specific for fear is presented. A second case history is reported for a surviving male diagnosed in 1988 with terminal prostate cancer who has used KY therapy long term as part of a self-directed integrative care approach.

Variation in standards of research compensation and child assent practices: a comparison of 69 institutional review board-approved informed permission and assent forms for 3 multicenter pediatric clinical trials.

PubMed

Kimberly, Michael B; Hoehn, K Sarah; Feudtner, Chris; Nelson, Robert M; Schreiner, Mark

2006-05-01

To systematically compare standards for compensation and child participant assent in informed permission, assent, and consent forms (IP-A-CFs) approved by 55 local institutional review boards (IRBs) reviewing 3 standardized multicenter research protocols. Sixty-nine principal investigators participating in any of 3 national, multicenter clinical trials submitted standardized research protocols for their trials to their local IRBs for approval. Copies of the subsequently IRB-approved IP-A-CFs were then forwarded to an academic clinical research organization. This collection of IRB-approved forms allowed for a quasiexperimental retrospective evaluation of the variation in informed permission, assent, and consent standards operationalized by the local IRBs. Standards for compensation and child participant assent varied substantially across 69 IRB-approved IP-A-CFs. Among the 48 IP-A-CFs offering compensation, monetary compensation was offered by 33 as reimbursement for travel, parking, or food expenses, whereas monetary or material compensation was offered by 22 for subject inconvenience and by 13 for subject time. Compensation ranged widely within and across studies (study 1, $180-1425; study 2, $0-500; and study 3, $0-100). Regarding child participant assent, among the 57 IP-A-CFs that included a form of assent documentation, 33 included a line for assent on the informed permission or consent form, whereas 35 included a separate form written in simplified language. Of the IP-A-CFs that stipulated the documentation of assent, 31 specified > or =1 age ranges for obtaining assent. Informed permission or consent forms were addressed either to parents or child participants. In response to identical clinical trial protocols, local IRBs generate IP-A-CFs that vary considerably regarding compensation and child participant assent.

Strengthening of the Hip and Core Versus Knee Muscles for the Treatment of Patellofemoral Pain: A Multicenter Randomized Controlled Trial

PubMed Central

Ferber, Reed; Bolgla, Lori; Earl-Boehm, Jennifer E.; Emery, Carolyn; Hamstra-Wright, Karrie

2015-01-01

Context: Patellofemoral pain (PFP) is the most common injury in running and jumping athletes. Randomized controlled trials suggest that incorporating hip and core strengthening (HIP) with knee-focused rehabilitation (KNEE) improves PFP outcomes. However, no randomized controlled trials have, to our knowledge, directly compared HIP and KNEE programs. Objective: To compare PFP pain, function, hip- and knee-muscle strength, and core endurance between KNEE and HIP protocols after 6 weeks of rehabilitation. We hypothesized greater improvements in (1) pain and function, (2) hip strength and core endurance for patients with PFP involved in the HIP protocol, and (3) knee strength for patients involved in the KNEE protocol. Design: Randomized controlled clinical trial. Setting: Four clinical research laboratories in Calgary, Alberta; Chicago, Illinois; Milwaukee, Wisconsin; and Augusta, Georgia. Patients or Other Participants: Of 721 patients with PFP screened, 199 (27.6%) met the inclusion criteria (66 men [31.2%], 133 women [66.8%], age = 29.0 ± 7.1 years, height = 170.4 ± 9.4 cm, weight = 67.6 ± 13.5 kg). Intervention(s): Patients with PFP were randomly assigned to a 6-week KNEE or HIP protocol. Main Outcome Measure(s): Primary variables were self-reported visual analog scale and Anterior Knee Pain Scale measures, which were conducted weekly. Secondary variables were muscle strength and core endurance measured at baseline and at 6 weeks. Results: Compared with baseline, both the visual analog scale and the Anterior Knee Pain Scale improved for patients with PFP in both the HIP and KNEE protocols (P < .001), but the visual analog scale scores for those in the HIP protocol were reduced 1 week earlier than in the KNEE group. Both groups increased in strength (P < .001), but those in the HIP protocol gained more in hip-abductor (P = .01) and -extensor (P = .01) strength and posterior core endurance (P = .05) compared with the KNEE group. Conclusions: Both the HIP and KNEE rehabilitation protocols produced improvements in PFP, function, and strength over 6 weeks. Although outcomes were similar, the HIP protocol resulted in earlier resolution of pain and greater overall gains in strength compared with the KNEE protocol. PMID:25365133

The Effect of Coded Healing Abutments on Treatment Duration and Clinical Outcome: A Randomized Controlled Clinical Trial Comparing Encode and Conventional Impression Protocols.

PubMed

Abduo, Jaafar; Chen, Chen; Le Breton, Eugene; Radu, Alexandra; Szeto, Josephine; Judge, Roy; Darby, Ivan

To compare the Encode impression protocol (Biomet 3i) with the conventional impression protocol in terms of treatment duration, clinical accuracy, and outcome up to the first postplacement review of single-implant crowns. A total of 45 implants were included in this study. The implants were randomly allocated to the Encode group (23 implants) or the conventional group (22 implants). At the time of surgery, all implants received two-piece Encode healing abutments. The implants were restored 3 months after insertion. In the conventional protocol, open-tray implant-level impressions were taken and the implants were restored with prefabricated abutments and porcelain-fused-to-metal (PFM) crowns. For the implants in the Encode group, closed-tray impressions of the healing abutments were taken. The generated casts were sent to the Biomet 3i scanning/milling center for custom abutment manufacturing on which PFM crowns were fabricated. Treatment duration (laboratory and clinical), clinical accuracy of occlusal and proximal contacts, and outcome (esthetics, patient satisfaction, and crown contour) were evaluated with the aid of a series of questionnaires. The Encode protocol required significantly less laboratory time (18 minutes) than the conventional protocol for adjustment of the abutments. The impression pour time, time for the laboratory to return the crown, time for crown insertion at the final appointment, and total clinical time for crown insertion did not differ significantly between the two protocols. Likewise, clinical accuracy, esthetics, and patient satisfaction were similar for the two protocols. The two protocols were clinically comparable. The Encode protocol is advantageous in reducing the laboratory time before crown fabrication.

Comparison of two progressive treadmill tests in patients with peripheral arterial disease.

PubMed

Riebe, D; Patterson, R B; Braun, C M

2001-11-01

In a vascular rehabilitation program, 28% of our frail elderly patients are unable to be tested with traditional progressive exercise protocols at program entry due to the high (2.0 miles/h or 3.2 km/h) initial treadmill speeds. The purpose of this investigation was to compare a new progressive treadmill protocol which has a reduced initial speed (1.0 mile/h or 1.6 km/h) to an established protocol performed at 2.0 miles/h (3.2 km/h) to determine the comparability and reproducibility of the new protocol. Eleven patients with arterial claudication performed three symptom-limited exercise tests in random order. Two tests used the new protocol while the remaining trial used the established protocol. Claudication pain was measured using a 5-point scale. Oxygen consumption, heart rate, minute ventilation, respiratory exchange ratio and blood pressure at peak exercise were similar among the three trials. There were strong intraclass correlations for peak oxygen consumption (r = 0.97), onset of claudication (r = 0.96) and maximum walking time (r = 0.98) between the two trials using the new protocol. There was also a significant correlation between the new protocol and the established protocol for peak oxygen consumption (r = 0.90) and maximum walking time (r = 0.89). The new progressive treadmill protocol represents a valid, reliable protocol for patients with arterial claudication. This protocol may be useful for testing patients with a low functional capacity so that clinically appropriate exercise prescriptions can be established and the efficacy of treatments can be determined.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: protocol for a feasibility randomized pilot trial.

PubMed

Johnstone, Jennie; Meade, Maureen; Marshall, John; Heyland, Daren K; Surette, Michael G; Bowdish, Dawn Me; Lauzier, Francois; Thebane, Lehana; Cook, Deborah J

2015-01-01

Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate. Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 10 10 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded. The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and hospital length of stay, and mortality. The morbidity, mortality, and cost of VAP underscore the need for cost-effective prophylactic interventions. The PROSPECT Pilot Trial is the initial step toward rigorously evaluating whether probiotics decrease nosocomial infections, have no effect, or actually cause infections in critically ill patients. ClinicalTrials.gov. NCT01782755.

The feasibility of a randomized controlled trial of esophagectomy for esophageal cancer - the ROMIO (Randomized Oesophagectomy: Minimally Invasive or Open) study: protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background There is a need for evidence of the clinical effectiveness of minimally invasive surgery for the treatment of esophageal cancer, but randomized controlled trials in surgery are often difficult to conduct. The ROMIO (Randomized Open or Minimally Invasive Oesophagectomy) study will establish the feasibility of a main trial which will examine the clinical and cost-effectiveness of minimally invasive and open surgical procedures for the treatment of esophageal cancer. Methods/Design A pilot randomized controlled trial (RCT), in two centers (University Hospitals Bristol NHS Foundation Trust and Plymouth Hospitals NHS Trust) will examine numbers of incident and eligible patients who consent to participate in the ROMIO study. Interventions will include esophagectomy by: (1) open gastric mobilization and right thoracotomy, (2) laparoscopic gastric mobilization and right thoracotomy, and (3) totally minimally invasive surgery (in the Bristol center only). The primary outcomes of the feasibility study will be measures of recruitment, successful development of methods to monitor quality of surgery and fidelity to a surgical protocol, and development of a core outcome set to evaluate esophageal cancer surgery. The study will test patient-reported outcomes measures to assess recovery, methods to blind participants, assessments of surgical morbidity, and methods to capture cost and resource use. ROMIO will integrate methods to monitor and improve recruitment using audio recordings of consultations between recruiting surgeons, nurses, and patients to provide feedback for recruiting staff. Discussion The ROMIO study aims to establish efficient methods to undertake a main trial of minimally invasive surgery versus open surgery for esophageal cancer. Trial registration The pilot trial has Current Controlled Trials registration number ISRCTN59036820(25/02/2013) at http://www.controlled-trials.com; the ROMIO trial record at that site gives a link to the original version of the study protocol. PMID:24888266

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial

PubMed Central

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-01-01

Introduction Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. Methods and analysis RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. Ethics and dissemination The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. Trial registration number ISRCTN03978701. PMID:26297361

Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET)

PubMed Central

2013-01-01

Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as against returning incidental genetic findings in clinical trials. For instance, reporting incidental findings in clinical trials may improve the investigator-participant relationship and the satisfaction of participation, but it may also blur the line between clinical care and research. The issues of whether and how to return incidental genetic findings, including the costs of doing so, should be considered when developing clinical trial protocols. Once decided, plans related to sharing individual results from the aim(s) of the trial, as well as incidental findings, should be discussed explicitly in the consent form. Institutional Review Boards (IRBs) and other study-specific governing bodies should be part of the decision as to if, when, and how to return incidental findings, including when plans in this regard are being reconsidered. PMID:23363732

Clinical Trials: More than an Assessment of Treatment Effect – LXV Edward Jackson Memorial Lecture

PubMed Central

Ferris, Frederick L.

2008-01-01

Purpose To review the development of clinical trials and demonstrate their value beyond the assessment of the treatment effect. Design Retrospective literature review Methods Retrospective literature review Results There has been a rapid increase in the number of clinical trials in ophthalmology as assessed by the number of ophthalmic publications and the number of ongoing National Eye Institute (NEI) sponsored clinical trials over the last four decades. The public health significance of the results of these NEI clinical trials goes beyond the demonstration of treatment effects and side effects. From these trials we learn about the clinical course and risk factors of disease allowing us to better determine who and when to treat. Furthermore, the collaboration of investigators, as they develop and carry out protocols, facilitates incorporation of new ideas into the practice of medicine. Conclusions The practice of medicine is increasingly dependent on the results of carefully designed clinical trials. The determination as to whether a new treatment is safe and effective is important, but the additional information we can obtain regarding natural history, risk factors, and patient satisfaction adds immeasurably to our ability to care for our patients. PMID:19100353

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial

PubMed Central

López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

2017-01-01

Introduction Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. Methods and analysis The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Ethics and dissemination Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Discussion Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. Trial registration number The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. PMID:28601833

Theory-driven group-based complex intervention to support self-management of osteoarthritis and low back pain in primary care physiotherapy: protocol for a cluster randomised controlled feasibility trial (SOLAS).

PubMed

Hurley, Deirdre A; Hall, Amanda M; Currie-Murphy, Laura; Pincus, Tamar; Kamper, Steve; Maher, Chris; McDonough, Suzanne M; Lonsdale, Chris; Walsh, Nicola E; Guerin, Suzanne; Segurado, Ricardo; Matthews, James

2016-01-21

International clinical guidelines consistently endorse the promotion of self-management (SM), including physical activity for patients with chronic low back pain (CLBP) and osteoarthritis (OA). Patients frequently receive individual treatment and advice to self-manage from physiotherapists in primary care, but the successful implementation of a clinical and cost-effective group SM programme is a key priority for health service managers in Ireland to maximise long-term outcomes and efficient use of limited and costly resources. This protocol describes an assessor-blinded cluster randomised controlled feasibility trial of a group-based education and exercise intervention underpinned by self-determination theory designed to support an increase in SM behaviour in patients with CLBP and OA in primary care physiotherapy. The primary care clinic will be the unit of randomisation (cluster), with each clinic randomised to 1 of 2 groups providing the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention or usual individual physiotherapy. Patients are followed up at 6 weeks, 2 and 6 months. The primary outcomes are the (1) acceptability and demand of the intervention to patients and physiotherapists, (2) feasibility and optimal study design/procedures and sample size for a definitive trial. Secondary outcomes include exploratory analyses of: point estimates, 95% CIs, change scores and effect sizes in physical function, pain and disability outcomes; process of change in target SM behaviours and selected mediators; and the cost of the intervention to inform a definitive trial. This feasibility trial protocol was approved by the UCD Human Research Ethics-Sciences Committee (LS-13-54 Currie-Hurley) and research access has been granted by the Health Services Executive Primary Care Research Committee in January 2014. The study findings will be disseminated to the research, clinical and health service communities through publication in peer-reviewed journals, presentation at national and international academic and clinical conferences. ISRCTN 49875385; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: the design of a factorial randomized controlled trial.

PubMed

Glaser, Nicole S; Ghetti, Simona; Casper, T Charles; Dean, J Michael; Kuppermann, Nathan

2013-09-01

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the USA and worldwide. The optimal protocol for intravenous (IV) fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of IV fluid infusion and the development of cerebral edema (CE), the most common and the most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and CE have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently, there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (FLuid therapies Under Investigation in DKA) study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically overt CE and long-term neurocognitive outcomes following DKA. © 2013 John Wiley & Sons A/S.

Pressure ulcer risk assessment and prevention: a systematic comparative effectiveness review.

PubMed

Chou, Roger; Dana, Tracy; Bougatsos, Christina; Blazina, Ian; Starmer, Amy J; Reitel, Katie; Buckley, David I

2013-07-02

Pressure ulcers are associated with substantial health burdens but may be preventable. To review the clinical utility of pressure ulcer risk assessment instruments and the comparative effectiveness of preventive interventions in persons at higher risk. MEDLINE (1946 through November 2012), CINAHL, the Cochrane Library, grant databases, clinical trial registries, and reference lists. Randomized trials and observational studies on effects of using risk assessment on clinical outcomes and randomized trials of preventive interventions on clinical outcomes. Multiple investigators abstracted and checked study details and quality using predefined criteria. One good-quality trial found no evidence that use of a pressure ulcer risk assessment instrument, with or without a protocolized intervention strategy based on assessed risk, reduces risk for incident pressure ulcers compared with less standardized risk assessment based on nurses' clinical judgment. In higher-risk populations, 1 good-quality and 4 fair-quality randomized trials found that more advanced static support surfaces were associated with lower risk for pressure ulcers compared with standard mattresses (relative risk range, 0.20 to 0.60). Evidence on the effectiveness of low-air-loss and alternating-air mattresses was limited, with some trials showing no clear differences from advanced static support surfaces. Evidence on the effectiveness of nutritional supplementation, repositioning, and skin care interventions versus usual care was limited and had methodological shortcomings, precluding strong conclusions. Only English-language articles were included, publication bias could not be formally assessed, and most studies had methodological shortcomings. More advanced static support surfaces are more effective than standard mattresses for preventing ulcers in higher-risk populations. The effectiveness of formal risk assessment instruments and associated intervention protocols compared with less standardized assessment methods and the effectiveness of other preventive interventions compared with usual care have not been clearly established.

Umbilical cord mesenchyme stem cell local intramuscular injection for treatment of uterine niche: Protocol for a prospective, randomized, double-blinded, placebo-controlled clinical trial.

PubMed

Fan, Dazhi; Wu, Shuzhen; Ye, Shaoxin; Wang, Wen; Guo, Xiaoling; Liu, Zhengping

2017-11-01

Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche. This phase II clinical trial is a single-center, prospective, randomized, double-blind, placebo-controlled with 2 arms. One hundred twenty primiparous participants will be randomly (1:1 ratio) assigned to receive direct intramuscular injection of MSCs (a dose of 1*10 cells in 1 mL of 0.9% saline) (MSCs group) or an identical-appearing 1 mL of 0.9% saline (placebo-controlled group) near the uterine incision. The primary outcome of this trial is to evaluate the proportion of participants at 6 months who is found uterine niche in the uterus by transvaginal utrasonography. Adverse events will be documented in a case report form. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. This trial is the first investigation of the potential for therapeutic use of MSCs for the management of uterine niche after cesarean delivery. This protocol will help to determine the efficacy and safety of MSCs treatment in uterine niche and bridge the gap with regards to the current preclinical and clinical evidence. NCT02968459 (Clinical Trials.gov: http://clinicaltrials.gov/).

Quality assurance of the SCOPE 1 trial in oesophageal radiotherapy.

PubMed

Wills, Lucy; Maggs, Rhydian; Lewis, Geraint; Jones, Gareth; Nixon, Lisette; Staffurth, John; Crosby, Tom

2017-11-15

SCOPE 1 was the first UK based multi-centre trial involving radiotherapy of the oesophagus. A comprehensive radiotherapy trials quality assurance programme was launched with two main aims: 1. To assist centres, where needed, to adapt their radiotherapy techniques in order to achieve protocol compliance and thereby enable their participation in the trial. 2. To support the trial's clinical outcomes by ensuring the consistent planning and delivery of radiotherapy across all participating centres. A detailed information package was provided and centres were required to complete a benchmark case in which the delineated target volumes and organs at risk, dose distribution and completion of a plan assessment form were assessed prior to recruiting patients into the trial. Upon recruiting, the quality assurance (QA) programme continued to monitor the outlining and planning of radiotherapy treatments. Completion of a questionnaire was requested in order to gather information about each centre's equipment and techniques relating to their trial participation and to assess the impact of the trial nationally on standard practice for radiotherapy of the oesophagus. During the trial, advice was available for individual planning issues, and was circulated amongst the SCOPE 1 community in response to common areas of concern using bulletins. 36 centres were supported through QA processes to enable their participation in SCOPE1. We discuss the issues which have arisen throughout this process and present details of the benchmark case solutions, centre questionnaires and on-trial protocol compliance. The range of submitted benchmark case GTV volumes was 29.8-67.8cm 3 ; and PTV volumes 221.9-513.3 cm 3 . For the dose distributions associated with these volumes, the percentage volume of the lungs receiving 20Gy (V20Gy) ranged from 20.4 to 33.5%. Similarly, heart V40Gy ranged from 16.1 to 33.0%. Incidence of incorrect outlining of OAR volumes increased from 50% of centres at benchmark case, to 64% on trial. Sixty-five percent of centres, who returned the trial questionnaire, stated that their standard practice had changed as a result of their participation in the SCOPE1 trial. The SCOPE 1 QA programme outcomes lend support to the trial's clinical conclusions. The range of patient planning outcomes for the benchmark case indicated, at the outset of the trial, the significant degree of variation present in UK oesophageal radiotherapy planning outcomes, despite the presence of a protocol. This supports the case for increasingly detailed definition of practice by means of consensus protocols, training and peer review. The incidence of minor inconsistencies of technique highlights the potential for improved QA systems and the need for sufficient resource for this to be addressed within future trials. As indicated in questionnaire responses, the QA exercise as a whole has contributed to greater consistency of oesophageal radiotherapy in the UK via the adoption into standard practice of elements of the protocol. The SCOPE1 trial is an International Standard Randomized Controlled Trial, ISRCTN47718479 .

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial

PubMed Central

Wade, Julia; Holding, Peter N; Bonnington, Susan; Rooshenas, Leila; Lane, J Athene; Salter, C Elizabeth; Tilling, Kate; Speakman, Mark J; Brewster, Simon F; Evans, Simon; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L

2015-01-01

Objectives To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial. Design Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability. Setting Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK. Participants Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM. Results Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care. Conclusions The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice. Trial registration numbers NCT02044172; ISRCTN20141297. PMID:26384727

Strategies to Support Recruitment of Patients with Life-limiting illness for Research: The Palliative Care Research Cooperative Group

PubMed Central

Hanson, Laura C.; Bull, Janet; Wessell, Kathryn; Massie, Lisa; Bennett, Rachael E.; Kutner, Jean S.; Aziz, Noreen M.; Abernethy, Amy

2014-01-01

Context The Palliative Care Research Cooperative group (PCRC) is the first clinical trials cooperative for palliative care in the United States. Objectives To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial. Methods The parent study was a multi-site randomized controlled trial enrolling adults with life expectancy anticipated to be 1–6 months, randomized to discontinue statins (intervention) vs. to continue on statins (control). To study recruitment best practices, we conducted semi-structured interviews with 18 site Principal Investigators (PI) and Clinical Research Coordinators (CRC), and reviewed recruitment rates. Interviews covered 3 topics – 1) successful strategies for recruitment, 2) barriers to recruitment, and 3) optimal roles of the PI and CRC. Results All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment. The parent study completed recruitment of n=381 patients. Site enrollment ranged from 1–109 participants, with an average of 25 enrolled per site. Five major barriers included difficulty locating eligible patients, severity of illness, family and provider protectiveness, seeking patients in multiple settings, and lack of resources for recruitment activities. Five effective recruitment strategies included systematic screening of patient lists, thoughtful messaging to make research relevant, flexible protocols to accommodate patients’ needs, support from clinical champions, and the additional resources of a trials cooperative group. Conclusion The recruitment experience from the multi-site PCRC yields new insights into methods for effective recruitment to palliative care clinical trials. These results will inform training materials for the PCRC and may assist other investigators in the field. PMID:24863152

Tobacco dependence counseling in a randomized multisite clinical trial

PubMed Central

Croghan, Ivana T.; Trautman, Judith A.; Winhusen, Theresa; Ebbert, Jon O.; Kropp, Frankie; Schroeder, Darrell R.; Hurt, Richard D.

2012-01-01

Pharmacotherapy trials for treating tobacco dependence would benefit from behavioral interventions providing treatment consistent with clinical practice guidelines but not directing participants to treatments not evaluated in the trial. The Smoke Free and Living It© behavioral intervention manual includes participant and interventionist guides and is designed to provide both practical counseling and intra-treatment support. We utilized this intervention manual in a multicenter, randomized clinical trial of smokers with attention deficit hyperactivity disorder. In this study, we evaluated how the interventional manual performed in a “train-the-trainer” model requiring uniform counseling across 6 sites and 15 interventionists. We analyzed the skill-adherence of the interventionists and the intervention-adherence of the participants. The 255 randomized participants completed 9.3 ± 2.8 sessions (mean ± SD), with 157 participants (61.6%) completing all 11 of the sessions and 221 (86.7%) completing at least 6 of the 11 sessions. Of the 163 sessions for which the study interventionists were evaluated, 156 (95.7%) were rated as adherent to protocol and “meeting expectations” on at least 6 of 7 established criteria, illustrating that fidelity can be maintained with minimal supervision. The self-help and interventionists guides of the Smoke Free and Living It manual can thus be used to provide behavioral intervention with a high rate of adherence by both the interventionists and the participants. This manual meets the requirements of the United States Public Health Service Clinical Practice Guideline, can be adapted to specific research protocols, and provides a useful option for behavioral intervention during clinical trials for smoking cessation. PMID:22406192

Tobacco dependence counseling in a randomized multisite clinical trial.

PubMed

Croghan, Ivana T; Trautman, Judith A; Winhusen, Theresa; Ebbert, Jon O; Kropp, Frankie B; Schroeder, Darrell R; Hurt, Richard D

2012-07-01

Pharmacotherapy trials for treating tobacco dependence would benefit from behavioral interventions providing treatment consistent with clinical practice guidelines but not directing participants to treatments not evaluated in the trial. The Smoke Free and Living It© behavioral intervention manual includes participant and interventionist guides and is designed to provide both practical counseling and intra-treatment support. We utilized this intervention manual in a multicenter, randomized clinical trial of smokers with attention deficit hyperactivity disorder. In this study, we evaluated how the interventional manual performed in a "train-the-trainer" model requiring uniform counseling across 6 sites and 15 interventionists. We analyzed the skill-adherence of the interventionists and the intervention-adherence of the participants. The 255 randomized participants completed 9.3±2.8 sessions (mean±SD), with 157 participants (61.6%) completing all 11 of the sessions and 221 (86.7%) completing at least 6 of the 11 sessions. Of the 163 sessions for which the study interventionists were evaluated, 156 (95.7%) were rated as adherent to protocol and "meeting expectations" on at least 6 of 7 established criteria, illustrating that fidelity can be maintained with minimal supervision. The self-help and interventionists guides of the Smoke Free and Living It manual can thus be used to provide behavioral intervention with a high rate of adherence by both the interventionists and the participants. This manual meets the requirements of the United States Public Health Service Clinical Practice Guideline, can be adapted to specific research protocols, and provides a useful option for behavioral intervention during clinical trials for smoking cessation. Copyright © 2012 Elsevier Inc. All rights reserved.

Osteopathic manipulative treatment and pain in preterms: study protocol for a randomised controlled trial.

PubMed

Cerritelli, Francesco; Cicchitti, Luca; Martelli, Marta; Barlafante, Gina; Renzetti, Cinzia; Pizzolorusso, Gianfranco; Lupacchini, Mariacristina; D'Orazio, Marianna; Marinelli, Benedetta; Cozzolino, Vincenzo; Fusilli, Paola; D'Incecco, Carmine

2015-03-08

Recent evidence proved the necessity to improve health care and pain management in newborns. Osteopathic manipulative treatment (OMT) has been largely used to treat painful syndromes as well as term and preterm newborns. Recent studies have demonstrated positive results of osteopathy in reducing length of stay and costs. However, no trials were carried out on pain in newborns. The aim of the present clinical trial is to explore the effectiveness of osteopathic treatment in reducing pain in a sample of preterms. A three-armed single blinded placebo-control randomised controlled trial protocol has been designed to primarily evaluate the extent to which OMT is effective in reducing pain in preterms. One hundred and twenty newborns will be enrolled from one tertiary neonatal intensive care unit in central Italy and randomised in three groups: study, sham and control. The study group will be further prospectively randomised in two subgroups: experienced osteopaths and students. All preterms will receive standard medical care. Osteopathic treatment will be applied to the study group only whilst 'soft touch' will be administer to the sham group only. Newborns will undergo manual sessions once a week for the entire period of hospitalisation. Blinding will be assured for neonatal staff and outcome assessor. Primary outcome will be the mean difference in baseline score changes of PIPP questionnaire between discharge and entry among the three groups. Secondary outcomes will be: mean difference in length of stay and costs between groups. Statistical analyses will use per-protocol analysis method. Missing data will be handled using last observation carried forward imputation technique. The present single blinded randomised controlled trial has been designed to explore potential advantages of OMT in the management of newborns' pain. Currently, based on a patient-centred need-based approach, this research will be looking at the benefit of osteopathic care rather than the efficacy of a specific technique or a pre-determined protocol. The protocol has been registered on ClinicalTrials.gov ( NCT02146677 ) on 20 May 2014.

Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

PubMed

Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

2014-10-29

Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

A single-blinded, randomized, parallel group superiority trial investigating the effects of footwear and custom foot orthoses versus footwear alone in individuals with patellofemoral joint osteoarthritis: a phase II pilot trial protocol.

PubMed

Wyndow, Narelle; Crossley, Kay M; Vicenzino, Bill; Tucker, Kylie; Collins, Natalie J

2017-01-01

Patellofemoral joint osteoarthritis is a common condition, yet information regarding conservative management is lacking. Foot orthoses are an effective intervention for improving pain and function in younger individuals with patellofemoral pain and may be effective in those with patellofemoral osteoarthritis. This pilot study will seek to establish the feasibility of a phase III randomised controlled trial to investigate whether foot orthoses worn in prescribed motion controlled footwear are superior to prescribed motion control footwear alone in the management of patellofemoral osteoarthritis. This phase II pilot clinical trial is designed as a randomized, single-blind, parallel group, two arm, superiority trial. The trial will recruit 44 participants from Queensland and Tasmania, Australia. Volunteers aged 40 years and over must have clinical symptoms and radiographic evidence of patellofemoral osteoarthritis to be eligible for inclusion. Those eligible will be randomized to receive either foot orthoses and prescribed motion control shoes, or prescribed motion control shoes alone, to be worn for a period of 4 months. The feasibility of a phase III clinical trial will be evaluated by assessing factors such as recruitment rate, number of eligible participants, participant compliance with the study protocol, adverse events, and drop-out rate. A secondary aim of the study will be to determine completion rates and calculate effect sizes for patient reported outcome measures such as knee-related symptoms, function, quality of life, kinesiophobia, self-efficacy, general and mental health, and physical activity at 2 and 4 months. Primary outcomes will be reported descriptively while effect sizes and 95% confidence intervals will be calculated for the secondary outcome measures. Data will be analysed using an intention-to-treat principle. The results of this pilot trial will help determine the feasibility of a phase III clinical trial investigating whether foot orthoses plus motion control footwear are superior to motion control footwear alone in individuals with patellofemoral osteoarthritis. A Phase III clinical trial will help guide footwear and foot orthoses recommendations in the clinical management of this disorder. Retrospectively registered with the Australian New Zealand Clinical Trials Registry: ACTRN12615000002583. Date registered: 07/01/15.

The transvaginal hybrid NOTES versus conventionally assisted laparoscopic sigmoid resection for diverticular disease (TRANSVERSAL) trial: study protocol for a randomized controlled trial.

PubMed

Senft, Jonas D; Warschkow, Rene; Diener, Markus K; Tarantino, Ignazio; Steinemann, Daniel C; Lamm, Sebastian; Simon, Thomas; Zerz, Andreas; Müller-Stich, Beat P; Linke, Georg R

2014-11-20

Natural orifice transluminal endoscopic surgery (NOTES) is the consequence of further development of minimally invasive surgery to reduce abdominal incisions and surgical trauma. The potential benefits are expected to be less postoperative pain, faster convalescence, and reduced risk for incisional hernias and wound infections compared to conventional methods. Recent clinical studies have demonstrated the feasibility and safety of transvaginal NOTES, and transvaginal access is currently the most frequent clinically applied route for NOTES procedures. However, despite increasing clinical application, no firm clinical evidence is available for objective assessment of the potential benefits and risks of transvaginal NOTES compared to the current surgical standard. The TRANSVERSAL trial is designed as a randomized controlled trial to compare transvaginal hybrid NOTES and laparoscopic-assisted sigmoid resection. Female patients referred to elective sigmoid resection due to complicated or reoccurring diverticulitis of the sigmoid colon are considered eligible. The primary endpoint will be pain intensity during mobilization 24 hours postoperatively as measured by the blinded patient and blinded assessor on a visual analogue scale (VAS). Secondary outcomes include daily pain intensity and analgesic use, patient mobility, intraoperative complications, morbidity, length of stay, quality of life, and sexual function. Follow-up visits are scheduled 3, 12, and 36 months after surgery. A total sample size of 58 patients was determined for the analysis of the primary endpoint. The confirmatory analysis will be performed based on the intention-to-treat (ITT) principle. The TRANSVERSAL trial is the first study to compare transvaginal hybrid NOTES and conventionally assisted laparoscopic surgery for colonic resection in a randomized controlled setting. The results of the TRANSVERSAL trial will allow objective assessment of the potential benefits and risks of NOTES compared to the current surgical standard for sigmoid resection. The trial protocol was registered in the German Clinical Trials Register ( DRKS00005995) on March 27, 2014.

Millon Clinical Multiaxial Inventory-III Subtypes of Opioid Dependence: Validity and Matching to Behavioral Therapies

ERIC Educational Resources Information Center

Ball, Samuel A.; Nich, Charla; Rounsaville, Bruce J.; Eagan, Dorothy; Carroll, Kathleen M.

2004-01-01

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were…

Participatory design of a collaborative clinical trial protocol writing system.

PubMed

Weng, Chunhua; McDonald, David W; Sparks, Dana; McCoy, Jason; Gennari, John H

2007-06-01

To explore concrete approaches to socio-technical design of collaborative healthcare information systems and to design a groupware technology for collaborative clinical trial protocol writing. We conducted "quick and dirty ethnography" through semi-structured interviews, observational studies, and work artifacts analysis to understand the group work for protocol development. We used participatory design through evolutionary prototyping to explore the feature space of a collaborative writing system. Our design strategies include role-based user advocacy, formative evaluation, and change management. Quick and dirty ethnography helped us efficiently understand relevant work practice, and participatory design helped us engage users into design and bring out their tacit work knowledge. Our approach that intertwined both techniques helped achieve a "work-informed and user-oriented" design. This research leads to a collaborative writing system that supports in situ communication, group awareness, and effective work progress tracking. The usability evaluation results have been satisfactory. The system design is being transferred to an organizational tool for daily use.

Cross-System Evaluation of Clinical Trial Search Engines

PubMed Central

Jiang, Silis Y.; Weng, Chunhua

2014-01-01

Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities. PMID:25954590

Cross-system evaluation of clinical trial search engines.

PubMed

Jiang, Silis Y; Weng, Chunhua

2014-01-01

Clinical trials are fundamental to the advancement of medicine but constantly face recruitment difficulties. Various clinical trial search engines have been designed to help health consumers identify trials for which they may be eligible. Unfortunately, knowledge of the usefulness and usability of their designs remains scarce. In this study, we used mixed methods, including time-motion analysis, think-aloud protocol, and survey, to evaluate five popular clinical trial search engines with 11 users. Differences in user preferences and time spent on each system were observed and correlated with user characteristics. In general, searching for applicable trials using these systems is a cognitively demanding task. Our results show that user perceptions of these systems are multifactorial. The survey indicated eTACTS being the generally preferred system, but this finding did not persist among all mixed methods. This study confirms the value of mixed-methods for a comprehensive system evaluation. Future system designers must be aware that different users groups expect different functionalities.

Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

PubMed Central

Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

2011-01-01

Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an alternative organizational model to conduct independent, yet coordinated trials. Such a model is increasingly being used in NHLBI supported trials , especially given the interest in comparative effectiveness research. Nevertheless, the ultimate utility of this model will not be fully understood until the trials are completed. PMID:20573639

Paediatric clinical research from the perspective of hospital pharmacists from France and Canada.

PubMed

Guérin, Aurélie; Tanguay, Cynthia; Lebel, Denis; Prot-Labarthe, Sonia; Bourdon, Olivier; Bussières, Jean-François

2014-12-01

To compare pharmacy support for paediatric research services in France and Canada and to describe the perception of pharmacists and rank the paediatric clinical research issues. This was a cross-sectional descriptive study. All paediatric hospitals from Canada and the main hospitals from France were contacted. A survey was conducted from May-September 2012. Descriptive statistics were performed. Results from 11 paediatric hospitals in Canada (11/12, 92%) and 11 (11/18, 61%) in France were obtained. There was a similar number of ongoing paediatric clinical trials per hospital in France versus Canada (38 (10-81) versus 20 (4-178)). A lower number of pharmacists per hospital was observed in France (17 (11.5-35) versus 45 (18.9-76.8)), but a similar number of pharmacists were assigned to clinical trials (1.5 (1-3) versus 1.9 (0.2-17.4)). Institutional protocols represented the majority of paediatric clinical trials in France (61% (14-100) versus 25% (0-100)). Similar pharmacy support services were offered, but the majority of French respondents also offered help for institutional protocol development (91 versus 50% P = 0.063). The main issues associated with paediatric clinical research were absence of financial interest from the pharmaceutical industry, prohibitive cost versus profit ratio, small patient cohorts and the non-availability of the appropriate drug formulations. Difficulties related to pharmaceutical compounding were identified as the main hindrance to paediatric clinical research; particular attention should be paid to these details when setting up a paediatric trial. © 2014 Royal Pharmaceutical Society.

Cost-Effectiveness Analysis of Biogeneric Recombinant Activated Factor VII (AryoSeven™) and Activated Prothrombin Complex Concentrates (FEIBA™) to Treat Hemophilia A Patients with Inhibitors in Iran.

PubMed

Golestani, Mina; Eshghi, Peyman; Rasekh, Hamid Reza; Cheraghali, Abdoll Majid; Salamzadeh, Jamshid; Naderi, Majid; Managhchi, Mohammad Reza; Hoorfar, Hamid; Toogeh, Gholam Reza; Imani, Ali; Khodayari, Mohammad Taghi; Habibpanah, Behnaz; Hantooshzadeh, Razieh

2016-01-01

Nowadays, bypassing agents such as recombinant activated factor VII (rFVIIa) and activated prothrombin complex concentrates (aPCC) are used to treat bleeding episodes in the Hemophilia patients with inhibitors. AryoSeven® is an Iranian biogeneric rFVIIa with homogeneity of efficacy and the nature to NovoSeven in a comparative trial. The current clinical trial aimed to evaluate the cost-effectiveness of FEIBA and AryoSeven® by Decision Analytic Model according to the Iranian healthcare system. An open label, multi-center, cross-over clinical trial was designed. Patients were categorized into 3 groups based on their prior tendency to one or none of the products. To determine the premium therapeutic strategy, the Incremental cost-effectiveness ratio (ICER) was calculated. Protocol F led to more treatment success in group F than the other groups (P= 0.03). Also, there was a significant statistical difference between the mean of effectiveness scores in the groups using protocol F (P = 0.01). The effectiveness of protocol F and A were 89% and 72%, respectively. ICER cost US$ to manage an episode of bleeding to get one more unit of effectiveness using FEIBA VS. AryoSeven. Although the results showed that AryoSeven was more cost-effective compared to FEIBA, the two strategies were undominated. In other words, both medicines can be applied in the first line of the treatment if the cost of FEIBA was reduced. The present clinical trial was registered at IRCT website, under ID No.2013020612380N1.

Development of a core outcome set for medication review in older patients with multimorbidity and polypharmacy: a study protocol.

PubMed

Beuscart, Jean-Baptiste; Dalleur, Olivia; Boland, Benoit; Thevelin, Stefanie; Knol, Wilma; Cullinan, Shane; Schneider, Claudio; O'Mahony, Denis; Rodondi, Nicolas; Spinewine, Anne

2017-01-01

Medication review has been advocated to address the challenge of polypharmacy in older patients, yet there is no consensus on how best to evaluate its efficacy. Heterogeneity of outcomes reported in clinical trials can hinder the comparison of clinical trial findings in systematic reviews. Moreover, the outcomes that matter most to older patients might be under-reported or disregarded altogether. A core outcome set can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials in any particular field of research. As part of the European Commission-funded project, called OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly, this paper describes the methods used to develop a core outcome set for clinical trials of medication review in older patients with multimorbidity. The study was designed in several steps. First, a systematic review established which outcomes were measured in published and ongoing clinical trials of medication review in older patients. Second, we undertook semistructured interviews with older patients and carers aimed at identifying additional relevant outcomes. Then, a multilanguage European Delphi survey adapted to older patients was designed. The international Delphi survey was conducted with older patients, health care professionals, researchers, and clinical experts in geriatric pharmacotherapy to validate outcomes to be included in the core outcome set. Consensus meetings were conducted to validate the results. We present the method for developing a core outcome set for medication review in older patients with multimorbidity. This study protocol could be used as a basis to develop core outcome sets in other fields of geriatric research.

Testing devices or experimental systems? Cancer clinical trials take the genomic turn.

PubMed

Nelson, Nicole C; Keating, Peter; Cambrosio, Alberto; Aguilar-Mahecha, Adriana; Basik, Mark

2014-06-01

Clinical trials are often described as machine-like systems for generating specific information concerning drug safety and efficacy, and are understood as a component of the industrial drug development processes. This paper argues that contemporary clinical trials in oncology are not reducible to mere drug testing. Drawing on ethnographic fieldwork and interviews with researchers in the field of oncology from 2010 to 2013, we introduce a conceptual contrast between trials as testing machines and trials as clinical experimental systems to draw attention to the ways trials are increasingly being used to ask open-ended scientific questions. When viewed as testing machines, clinical trials are seen as a means to produce answers to straightforward questions and deviations from the protocol are seen as bugs in the system; but practitioners can also treat trials as clinical experimental systems to investigate as yet undefined problems and where heterogeneity becomes a means to produce novel biological or clinical insights. The rise of "biomarker-driven" clinical trials in oncology, which link measurable biological characteristics such as genetic mutations to clinical features such as a patient's response to a particular drug, exemplifies a trend towards more experimental styles of clinical work. These transformations are congruent with changes in the institutional structure of clinical research in oncology, including a movement towards more flexible, networked research arrangements, and towards using individual patients as model systems for asking biological questions. Copyright © 2014 Elsevier Ltd. All rights reserved.

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer

PubMed Central

2014-01-01

Background The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be ‘cherry-picked’, such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. Methods/Design This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. Discussion A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. Trials and registration This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013). PMID:24885068

A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol (ANZCTRN12612000827831).

PubMed

Kean, James D; Kaufman, Jordy; Lomas, Justine; Goh, Antionette; White, David; Simpson, David; Scholey, Andrew; Singh, Hemant; Sarris, Jerome; Zangara, Andrea; Stough, Con

2015-12-02

Clinical diagnoses of Attention Deficit Hyperactivity Disorder (ADHD) and the use of prescription medications for its treatment have increased in recent years. Current treatments may involve the administration of amphetamine-type substances, a treatment path many parents are apprehensive to take. Therefore, alternative pharmacological treatments are required. Few nutritional or pharmacological alternatives that reduce ADHD associated symptoms (hyperactivity and inattention) have been subjected to rigorous clinical trials. Bacopa monnieri is a perennial creeping herb. CDRI 08 is a special extract of Bacopa monnieri which has been subjected to hundreds of scientific studies and has been shown in human randomized controlled trials (RCTs) to improve memory, attention, and mood. It is hypothesised that chronic administration of CDRI 08 will improve attention, concentration and behaviour in children with high levels of hyperactivity and/or inattention. This paper reports the protocol for the first 16-week, randomized, placebo-controlled, double-blind, parallel groups trial examining the efficacy and safety of CDRI 08 in male children aged 6-14 years with high levels of inattention and hyperactivity. The primary outcome variable will be the level of hyperactivity and inattention measured by the Conners' Parent Rating Scale (CPRS). Secondary outcome variables include cognition, mood, sleep, and EEG. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000827831.

A National Strategy to Develop Pragmatic Clinical Trials Infrastructure

PubMed Central

Guise, Jeanne‐Marie; Dolor, Rowena J.; Meissner, Paul; Tunis, Sean; Krishnan, Jerry A.; Pace, Wilson D.; Saltz, Joel; Hersh, William R.; Michener, Lloyd; Carey, Timothy S.

2014-01-01

Abstract An important challenge in comparative effectiveness research is the lack of infrastructure to support pragmatic clinical trials, which compare interventions in usual practice settings and subjects. These trials present challenges that differ from those of classical efficacy trials, which are conducted under ideal circumstances, in patients selected for their suitability, and with highly controlled protocols. In 2012, we launched a 1‐year learning network to identify high‐priority pragmatic clinical trials and to deploy research infrastructure through the NIH Clinical and Translational Science Awards Consortium that could be used to launch and sustain them. The network and infrastructure were initiated as a learning ground and shared resource for investigators and communities interested in developing pragmatic clinical trials. We followed a three‐stage process of developing the network, prioritizing proposed trials, and implementing learning exercises that culminated in a 1‐day network meeting at the end of the year. The year‐long project resulted in five recommendations related to developing the network, enhancing community engagement, addressing regulatory challenges, advancing information technology, and developing research methods. The recommendations can be implemented within 24 months and are designed to lead toward a sustained national infrastructure for pragmatic trials. PMID:24472114

Development and Implementation of Clinical Trial Protocol Templates at the National Institute of Allergy and Infectious Diseases

PubMed Central

Bridge, Heather; Smolskis, Mary; Bianchine, Peter; Dixon, Dennis O.; Kelly, Grace; Herpin, Betsey; Tavel, Jorge

2009-01-01

Background: A clinical research protocol document must reflect both sound scientific rationale as well as local, national and, when applicable, international regulatory and human subject protections requirements. These requirements originate from a variety of sources, undergo frequent revision and are subject to interpretation. Tools to assist clinical investigators in the production of clinical protocols could facilitate navigating these requirements and ultimately increase the efficiency of clinical research. Purpose: The National Institute of Allergy and Infectious Diseases (NIAID) developed templates for investigators to serve as the foundation for protocol development. These protocol templates are designed as tools to support investigators in developing clinical protocols. Methods: NIAID established a series of working groups to determine how to improve its capacity to conduct clinical research more efficiently and effectively. The Protocol Template Working Group was convened to determine what protocol templates currently existed within NIAID and whether standard NIAID protocol templates should be produced. After review and assessment of existing protocol documents and requirements, the group reached consensus about required and optional content, determined the format and identified methods for distribution as well as education of investigators in the use of these templates. Results: The templates were approved by the NIAID Executive Committee in 2006 and posted as part of the NIAID Clinical Research Toolkit[1]website for broad access. These documents require scheduled revisions to stay current with regulatory and policy changes. Limitations: The structure of any clinical protocol template, whether comprehensive or specific to a particular study phase, setting or design, affects how it is used by investigators. Each structure presents its own set of advantages and disadvantages. While useful, protocol templates are not stand-alone tools for creating an optimal protocol document but must be complemented by institutional resources and support. Education and guidance of investigators in the appropriate use of templates is necessary to ensure a complete yet concise protocol document. Due to changing regulatory requirements, clinical protocol templates cannot become static but require frequent revisions. Conclusions: Standard protocol templates that meet applicable regulations can be important tools to assist investigators in the effective conduct of clinical research, but they require dedicated resources and ongoing input from key stakeholders. PMID:19625326

Central institutional review board review for an academic trial network.

PubMed

Kaufmann, Petra; O'Rourke, P Pearl

2015-03-01

Translating discoveries into therapeutics is often delayed by lengthy start-up periods for multicenter clinical trials. One cause of delay can be multiple institutional review board (IRB) reviews of the same protocol. When developing the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT; hereafter, NN), the National Institute of Neurological Disorders and Stroke (NINDS) established a central IRB (CIRB) based at Massachusetts General Hospital, the academic medical center that received the NN clinical coordinating center grant. The 25 NN sites, located at U.S. academic institutions, agreed to required CIRB use for NN trials. To delineate roles and establish legal relationships between the NN sites and the CIRB, the CIRB executed reliance agreements with the sites and their affiliates that hold federalwide assurance for the protection of human subjects (FWA); this took, on average, 84 days. The first NN protocol reviewed by the CIRB achieved full approval to allow participant enrollment within 56 days and went from grant award to the first patient visit in less than four months. The authors describe anticipated challenges related to institutional oversight responsibilities versus regulatory CIRB review as well as unanticipated challenges related to working with complex organizations that include multiple FWA-holding affiliates. The authors anticipate that CIRB use will decrease NN trial start-up time and thus promote efficient trial implementation. They plan to collect data on timelines and costs associated with CIRB use. The NINDS plans to promote CIRB use in future initiatives.

The role of the Data and Safety Monitoring Board in a clinical trial: The CRISIS Study

PubMed Central

Holubkov, Richard; Casper, T. Charles; Dean, J. Michael; Anand, K. J. S.; Zimmerman, Jerry; Meert, Kathleen L.; Newth, Christopher J. L.; Berger, John; Harrison, Rick; Willson, Douglas F.; Nicholson, Carol

2012-01-01

Objective Randomized clinical trials are commonly overseen by a data and safety monitoring board (DSMB) comprised of experts in medicine, ethics, and biostatistics. DSMB responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. DSMB decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate DSMB oversight into the design, monitoring, and reporting of randomized trials. Design Case study, narrative review. Methods The DSMB’s role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. Findings The NIH-appointed CRISIS DSMB was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested DSMB interim review before opening CRISIS to children below one year of age. The first interim analysis found higher 28-day mortality in one treatment arm. The DSMB maintained trial closure to younger children, and requested a second interim data review six months later. At this second meeting, mortality was no longer of concern, while a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the DSMB elected to examine conditional power, and unmask treatment arm identities. Upon finding somewhat greater efficacy in the placebo arm, the DSMB recommended stopping CRISIS due to futility. Conclusions The design and operating procedures of a multicenter randomized trial must consider a pivotal DSMB role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The DSMB must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups. PMID:23392377

Optimizing Radiation Therapy Quality Assurance in Clinical Trials: A TROG 08.03 RAVES Substudy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trada, Yuvnik, E-mail: yuvnik@gmail.com; Kneebone, Andrew; Paneghel, Andrea

2015-12-01

Purpose: To explore site- and clinician-level factors associated with protocol violations requiring real-time-review (RTR) resubmission in a multicenter clinical trial to help tailor future quality assurance (QA) protocols. Methods and Materials: RAVES (Radiation Therapy–Adjuvant vs Early Salvage) (Trans-Tasman Radiation Oncology Group 08.03) is a randomized trial comparing adjuvant with early salvage radiation therapy in men with positive surgical margins or pT3 disease after prostatectomy. Quality assurance in RAVES required each clinician and site to submit a credentialing dummy run (DR) and for each patient's radiation therapy plan to undergo external RTR before treatment. Prospectively defined major violations from trial protocol requiredmore » remedy and resubmission. Site and clinician factors associated with RTR resubmission were examined using hierarchical modeling. Results: Data were collected from 171 consecutive patients, treated by 46 clinicians at 32 hospitals. There were 47 RTR resubmissions (27%) due to 65 major violations. The relative rate of resubmission decreased by 29% per year as the study progressed (odds ratio OR. 0.71, P=.02). The majority of resubmissions were due to contouring violations (39 of 65) and dosimetric violations (22 of 65). For each additional patient accrued, significant decreases in RTR resubmission were seen at both clinician level (OR 0.75, P=.02) and site level (OR 0.72, P=.01). The rate of resubmission due to dosimetric violations was only 1.6% after the first 5 patients. Use of IMRT was associated with lower rates of resubmission compared with 3-dimensional conformal radiation therapy (OR 0.38, P=.05). Conclusion: Several low- and high-risk factors that may assist with tailoring future clinical trial QA were identified. Because the real-time resubmission rate was largely independent of the credentialing exercise, some form of RTR QA is recommended. The greatest benefit from QA was derived early in trial activation and clinician experience.« less

CONCEPTUAL AND METHODOLOGICAL ISSUES IN DESIGNING A RANDOMIZED CONTROLLED TREATMENT TRIAL FOR GERIATRIC BIPOLAR DISORDER: GERI-BD

PubMed Central

Young, Robert C.; Schulberg, Herbert C.; Gildengers, Ariel G.; Sajatovic, Martha; Mulsant, Benoit H.; Gyulai, Laszlo; Beyer, John; Marangell, Lauren; Kunik, Mark; Have, Thomas Ten; Bruce, Martha L.; Gur, Ruben; Marino, Patricia; Evans, Jovier D.; Reynolds, Charles F.; Alexopoulos, George S.

2010-01-01

Aim This report considers the conceptual and methodological concerns confronting clinical investigators seeking to generate knowledge regarding the tolerability and benefits of pharmacotherapy in geriatric bipolar (BP) patients. Method There is continuing need for evidence-based guidelines derived from randomized controlled trials that will enhance drug treatment of geriatric BP patients. We, therefore, present the complex conceptual and methodological choices encountered in designing a multi-site clinical trial and the decisions reached by the investigators with the intention that study findings are pertinent to, and can facilitate, routine treatment decisions. Results Guided by a literature review and input from peers, the tolerability and anti-manic effect of lithium and valproate were judged to be the key mood stabilizers to investigate with regard to treating BP I manic, mixed and hypomanic states. The patient selection criteria are intended to generate a sample that experiences common treatment needs but which also represents the variety of older patients seen in university-based clinical settings. The clinical protocol guides titratation of lithium and valproate to target serum concentrations, with lower levels allowed when necessitated by limited tolerability. The protocol emphasizes initial monotherapy. However, augmentation with risperidone is permitted after three weeks when indicated by operational criteria. Conclusions A randomized controlled trial that both investigates commonly prescribed mood stabilizers and maximizes patient participation can meaningfully address high priority clinical concerns directly relevant to the routine pharmacologic treatment of geriatric BP patients. PMID:20148867

The remote prayer delusion: clinical trials that attempt to detect supernatural intervention are as futile as they are unethical.

PubMed

Paul, G

2008-09-01

Extreme rates of premature death prior to the advent of modern medicine, very low rates of premature death in First World nations with low rates of prayer, and the least flawed of a large series of clinical trials indicate that remote prayer is not efficacious in treating illness. Mass contamination of sample cohorts renders such clinical studies inherently ineffectual. The required supernatural and paranormal mechanisms render them implausible. The possibility that the latter are not benign, and the potentially adverse psychological impact of certain protocols, renders these medical trials unethical. Resources should no longer be wasted on medical efforts to detect the supernatural and paranormal.

PAT: an intelligent authoring tool for facilitating clinical trial design.

PubMed

Tagaris, Anastasios; Andronikou, Vassiliki; Karanastasis, Efstathios; Chondrogiannis, Efthymios; Tsirmpas, Charalambos; Varvarigou, Theodora; Koutsouris, Dimitris

2014-01-01

Great investments are made by both private and public funds and a wealth of research findings is published, the research and development pipeline phases quite low productivity and tremendous delays. In this paper, we present a novel authoring tool which has been designed and developed for facilitating study design. Its underlying models are based on a thorough analysis of existing clinical trial protocols (CTPs) and eligibility criteria (EC) published in clinicaltrials.gov by domain experts. Moreover, its integration with intelligent decision support services and mechanisms linking the study design process with healthcare patient data as well as its direct access to literature designate it as a powerful tool offering great support to researchers during clinical trial design.

Establishing an effective TMS protocol for craving in substance addiction: Is it possible?

PubMed

Enokibara, Mailu; Trevizol, Alisson; Shiozawa, Pedro; Cordeiro, Quirino

2016-01-01

Repetitive transcranial magnetic stimulation (TMS) is a non-invasive tool with known therapeutic efficacy in various neuropsychiatric disorders, such as depression, schizophrenia, mania, and anxiety disorders. We hereby, briefly present a brief review and meta-analysis on the use of TMS for craving in substance addiction. We present our brief review and meta-analysis following the recommendations of the Cochrane group. A total of eight randomized controlled trials fulfilled eligibility criteria and were selected. A total of 199 patients were studied. We found active stimulation to be superior than sham protocols only for trials focused on right DLPFC (with Hedge's g = 1.48; ES (95%CI: 0.126-2.834), p = 0.032. Main meta-analysis limitations include small number of studies, high heterogeneity among studies, and high publication bias. However challenging, our exploratory analysis underscored the amelioration of craving in substance addiction for trials using high frequency TMS protocols over the right DLPFC. We hereby, propose the use of this particular TMS protocol as a promising tool in clinical research. © American Academy of Addiction Psychiatry.

Study protocol of a randomized controlled trial comparing integrative body-mind-spirit intervention and cognitive behavioral therapy in fostering quality of life of patients with lung cancer and their family caregivers.

PubMed

Lau, Bobo Hi-Po; Chow, Amy Y M; Wong, Daniel F K; Chan, Jessie S M; Chan, Celia H Y; Ho, Rainbow T H; So, Tsz-Him; Lam, Tai-Chung; Lee, Victor Ho-Fun; Lee, Anne W M; Chow, Sau Fong; Chan, Cecilia L W

2018-01-01

Compared to cancers at other sites, lung cancer often results in greater psychosocial distress to both the patients and their caregivers, due to the poor prognosis and survival rate, as well as the heavy symptom burden. In recent years, making protocols of proposed or on-going studies publicly available via clinical trial registries and/or peer-reviewed journals has benefited health sciences with timely communication of the latest research trends and improved transparency in reporting. However, such practice is yet to be a common sight in evidence-informed social work. Hence, this paper discusses the value of publishing protocols in social work research and presents the protocol of a randomized controlled trial that compares the effectiveness of integrative body-mind-spirit intervention with cognitive behavioral therapy for enhancing quality of life of patients with lung cancer and their family caregivers. The data collection process was still on-going at the time of manuscript submission.

Hand-suture versus stapling for closure of loop ileostomy: HASTA-Trial: a study rationale and design for a randomized controlled trial

PubMed Central

2011-01-01

Background Colorectal cancer is the second most common tumor in developed countries, with a lifetime prevalence of 5%. About one third of these tumors are located in the rectum. Surgery in terms of low anterior resection with mesorectal excision is the central element in the treatment of rectal cancer being the only option for definite cure. Creating a protective diverting stoma prevents complications like anastomotic failure and meanwhile is the standard procedure. Bowel obstruction is one of the main and the clinically and economically most relevant complication following closure of loop ileostomy. The best surgical technique for closure of loop ileostomy has not been defined yet. Methods/Design A study protocol was developed on the basis of the only randomized controlled mono-center trial to solve clinical equipoise concerning the optimal surgical technique for closure of loop ileostomy after low anterior resection due to rectal cancer. The HASTA trial is a multi-center pragmatic randomized controlled surgical trial with two parallel groups to compare hand-suture versus stapling for closure of loop ileostomy. It will include 334 randomized patients undergoing closure of loop ileostomy after low anterior resection with protective ileostomy due to rectal cancer in approximately 20 centers consisting of German hospitals of all level of health care. The primary endpoint is the rate of bowel obstruction within 30 days after ileostomy closure. In addition, a set of surgical and general variables including quality of life will be analyzed with a follow-up of 12 months. An investigators meeting with a practical session will help to minimize performance bias and enforce protocol adherence. Centers are monitored centrally as well as on-site before and during recruitment phase to assure inclusion, treatment and follow up according to the protocol. Discussion Aim of the HASTA trial is to evaluate the efficacy of hand-suture versus stapling for closure of loop ileostomy in patients with rectal cancer. Trial registration German Clinical Trial Register Number: DRKS00000040 PMID:21303515

Development of a novel imaging informatics-based system with an intelligent workflow engine (IWEIS) to support imaging-based clinical trials

PubMed Central

Wang, Ximing; Liu, Brent J; Martinez, Clarisa; Zhang, Xuejun; Winstein, Carolee J

2015-01-01

Imaging based clinical trials can benefit from a solution to efficiently collect, analyze, and distribute multimedia data at various stages within the workflow. Currently, the data management needs of these trials are typically addressed with custom-built systems. However, software development of the custom- built systems for versatile workflows can be resource-consuming. To address these challenges, we present a system with a workflow engine for imaging based clinical trials. The system enables a project coordinator to build a data collection and management system specifically related to study protocol workflow without programming. Web Access to DICOM Objects (WADO) module with novel features is integrated to further facilitate imaging related study. The system was initially evaluated by an imaging based rehabilitation clinical trial. The evaluation shows that the cost of the development of system can be much reduced compared to the custom-built system. By providing a solution to customize a system and automate the workflow, the system will save on development time and reduce errors especially for imaging clinical trials. PMID:25870169

Review and publication of protocol submissions to Trials - what have we learned in 10 years?

PubMed

Li, Tianjing; Boutron, Isabelle; Al-Shahi Salman, Rustam; Cobo, Erik; Flemyng, Ella; Grimshaw, Jeremy M; Altman, Douglas G

2016-12-16

Trials has 10 years of experience in providing open access publication of protocols for randomised controlled trials. In this editorial, the senior editors and editors-in-chief of Trials discuss editorial issues regarding managing trial protocol submissions, including the content and format of the protocol, timing of submission, approaches to tracking protocol amendments, and the purpose of peer reviewing a protocol submission. With the clarification and guidance provided, we hope we can make the process of publishing trial protocols more efficient and useful to trial investigators and readers.

Intermittent Fasting: Is the Wait Worth the Weight?

PubMed

Stockman, Mary-Catherine; Thomas, Dylan; Burke, Jacquelyn; Apovian, Caroline M

2018-06-01

We review the underlying mechanisms and potential benefits of intermittent fasting (IF) from animal models and recent clinical trials. Numerous variations of IF exist, and study protocols vary greatly in their interpretations of this weight loss trend. Most human IF studies result in minimal weight loss and marginal improvements in metabolic biomarkers, though outcomes vary. Some animal models have found that IF reduces oxidative stress, improves cognition, and delays aging. Additionally, IF has anti-inflammatory effects, promotes autophagy, and benefits the gut microbiome. The benefit-to-harm ratio varies by model, IF protocol, age at initiation, and duration. We provide an integrated perspective on potential benefits of IF as well as key areas for future investigation. In clinical trials, caloric restriction and IF result in similar degrees of weight loss and improvement in insulin sensitivity. Although these data suggest that IF may be a promising weight loss method, IF trials have been of moderate sample size and limited duration. More rigorous research is needed.

A core outcome set for all types of cardiac surgery effectiveness trials: a study protocol for an international eDelphi survey to achieve consensus on what to measure and the subsequent selection of measurement instruments.

PubMed

Moza, A; Benstoem, C; Autschbach, R; Stoppe, C; Goetzenich, A

2015-12-02

Cardiovascular disease (CVD) is a major contributor to the burden of disease and the number one cause of death worldwide. From 1990 until today, more people died from coronary heart disease than from any other cause. CVD is regularly treated with minimally or non-minimally invasive off- or on-pump cardiothoracic surgery and several interventions related to the outcome of the surgical procedures have been evaluated in clinical trials, but heterogeneity in outcome reporting hinders comparison of interventions across trials and limits the ability of research synthesis. This problem is encountered with the introduction of core outcome sets (COSs), which should be measured and reported, as a minimum, in all clinical trials for a specific clinical field. This study protocol describes the methods used to develop a COS for all types of cardiac surgery effectiveness trials. We aim to reach consensus on what to measure in an international three-round eDelphi exercise involving adult patients in need or after cardiothoracic surgery, cardiothoracic surgeons, cardiologists, anaesthesiologists, nursing staff and researchers with expertise in this particular field of medical research. Subsequently, outcome measurement instruments (how to measure) will be determined. Recommendations on COS development given by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative and the Outcome Measures in Rheumatology (OMERACT) Initiative were followed. The proposed COS aims to provide methodological guidance for future cardiothoracic surgical trials to ensure the comparability of effects of interventions across studies and enable research synthesis. This does not imply that primary outcomes should always and exclusively be those of the COS. However, to ensure the comparability of results across trials, the outcomes included in this COS should be considered for inclusion besides measuring trial-specific clinical endpoints.

Aging of monolithic zirconia dental prostheses: Protocol for a 5-year prospective clinical study using ex vivo analyses.

PubMed

Koenig, Vinciane; Wulfman, Claudine P; Derbanne, Mathieu A; Dupont, Nathalie M; Le Goff, Stéphane O; Tang, Mie-Leng; Seidel, Laurence; Dewael, Thibaut Y; Vanheusden, Alain J; Mainjot, Amélie K

2016-12-15

Recent introduction of computer-aided design/computer-aided manufacturing (CAD/CAM) monolithic zirconia dental prostheses raises the issue of material low thermal degradation (LTD), a well-known problem with zirconia hip prostheses. This phenomenon could be accentuated by masticatory mechanical stress. Until now zirconia LTD process has only been studied in vitro . This work introduces an original protocol to evaluate LTD process of monolithic zirconia prostheses in the oral environment and to study their general clinical behavior, notably in terms of wear. 101 posterior monolithic zirconia tooth elements (molars and premolars) are included in a 5-year prospective clinical trial. On each element, several areas between 1 and 2 mm 2 (6 on molars, 4 on premolars) are determined on restoration surface: areas submitted or non-submitted to mastication mechanical stress, glazed or non-glazed. Before prosthesis placement, ex vivo analyses regarding LTD and wear are performed using Raman spectroscopy, SEM imagery and 3D laser profilometry. After placement, restorations are clinically evaluated following criteria of the World Dental Federation (FDI), complemented by the analysis of fracture clinical risk factors. Two independent examiners perform the evaluations. Clinical evaluation and ex vivo analyses are carried out after 6 months and then each year for up to 5 years. For clinicians and patients, the results of this trial will justify the use of monolithic zirconia restorations in dental practice. For researchers, the originality of a clinical study including ex vivo analyses of material aging will provide important data regarding zirconia properties.Trial registration: ClinicalTrials.gov Identifier: NCT02150226.

Highly Efficient Training, Refinement, and Validation of a Knowledge-based Planning Quality-Control System for Radiation Therapy Clinical Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Nan; Carmona, Ruben; Sirak, Igor

Purpose: To demonstrate an efficient method for training and validation of a knowledge-based planning (KBP) system as a radiation therapy clinical trial plan quality-control system. Methods and Materials: We analyzed 86 patients with stage IB through IVA cervical cancer treated with intensity modulated radiation therapy at 2 institutions according to the standards of the INTERTECC (International Evaluation of Radiotherapy Technology Effectiveness in Cervical Cancer, National Clinical Trials Network identifier: 01554397) protocol. The protocol used a planning target volume and 2 primary organs at risk: pelvic bone marrow (PBM) and bowel. Secondary organs at risk were rectum and bladder. Initial unfiltered dose-volumemore » histogram (DVH) estimation models were trained using all 86 plans. Refined training sets were created by removing sub-optimal plans from the unfiltered sample, and DVH estimation models… and DVH estimation models were constructed by identifying 30 of 86 plans emphasizing PBM sparing (comparing protocol-specified dosimetric cutpoints V{sub 10} (percentage volume of PBM receiving at least 10 Gy dose) and V{sub 20} (percentage volume of PBM receiving at least 20 Gy dose) with unfiltered predictions) and another 30 of 86 plans emphasizing bowel sparing (comparing V{sub 40} (absolute volume of bowel receiving at least 40 Gy dose) and V{sub 45} (absolute volume of bowel receiving at least 45 Gy dose), 9 in common with the PBM set). To obtain deliverable KBP plans, refined models must inform patient-specific optimization objectives and/or priorities (an auto-planning “routine”). Four candidate routines emphasizing different tradeoffs were composed, and a script was developed to automatically re-plan multiple patients with each routine. After selection of the routine that best met protocol objectives in the 51-patient training sample (KBP{sub FINAL}), protocol-specific DVH metrics and normal tissue complication probability were compared for original versus KBP{sub FINAL} plans across the 35-patient validation set. Paired t tests were used to test differences between planning sets. Results: KBP{sub FINAL} plans outperformed manual planning across the validation set in all protocol-specific DVH cutpoints. The mean normal tissue complication probability for gastrointestinal toxicity was lower for KBP{sub FINAL} versus validation-set plans (48.7% vs 53.8%, P<.001). Similarly, the estimated mean white blood cell count nadir was higher (2.77 vs 2.49 k/mL, P<.001) with KBP{sub FINAL} plans, indicating lowered probability of hematologic toxicity. Conclusions: This work demonstrates that a KBP system can be efficiently trained and refined for use in radiation therapy clinical trials with minimal effort. This patient-specific plan quality control resulted in improvements on protocol-specific dosimetric endpoints.« less

Transverse occiput position: Using manual Rotation to aid Normal birth and improve delivery OUTcomes (TURN-OUT): A study protocol for a randomised controlled trial.

PubMed

de Vries, Bradley; Phipps, Hala; Kuah, Sabrina; Pardey, John; Ludlow, Joanne; Bisits, Andrew; Park, Felicity; Kowalski, David; Hyett, Jon A

2015-08-18

Fetal occiput transverse position in the form of deep transverse arrest has long been associated with caesarean section and instrumental vaginal delivery. Occiput transverse position incidentally found in the second stage of labour is also associated with operative delivery in high risk cohorts. There is evidence from cohort studies that prophylactic manual rotation reduces the caesarean section rate. This is a protocol for a double blind, multicentre, randomised, controlled clinical trial to define whether this intervention decreases the operative delivery (caesarean section, forceps or vacuum delivery) rate. Eligible participants will be ≥37 weeks pregnant, with a singleton pregnancy, and a cephalic presentation in the occiput transverse position on transabdominal ultrasound early in the second stage of labour. Based on a background risk of operative delivery of 49%, for a reduction to 35%, an alpha value of 0.05 and a beta value of 0.2, 416 participants will need to be enrolled. Participants will be randomised to either prophylactic manual rotation or a sham procedure. The primary outcome will be operative delivery. Secondary outcomes will be caesarean section, significant maternal mortality and morbidity, and significant perinatal mortality and morbidity. Analysis will be on an intention-to-treat basis. Primary and secondary outcomes will be compared using a chi-squared test. A logistic regression for the primary outcome will be undertaken to account for potential confounders. This study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, Sydney, Australia, (protocol number: X110410). This trial addresses an important clinical question concerning a commonly used procedure which has the potential to reduce operative delivery and its associated complications. Some issues discussed in the protocol include methods of assessing risk of bias due to inadequate masking of a procedural interventions, variations in intervention efficacy due to operator experience and the recruitment difficulties associated with intrapartum studies. This trial was registered with the Australian New Zealand Clinical Trials Registry (identifier: ACTRN12613000005752 ) on 4 January 2013.

Clinical Trials of Blood Pressure Lowering and Antihypertensive Medication: Is Cognitive Measurement State-of-the-Art?

PubMed

Elias, Merrill F; Torres, Rachael V; Davey, Adam

2018-05-07

Randomized controlled trials of blood pressure (BP) lowering and antihypertensive medication use on cognitive outcomes have often been disappointing, reporting mixed findings and small effect sizes. We evaluate the extent to which cognitive assessment protocols used in these trials approach state-of-the-art. Overall, we find that a primary focus on cognition and the systematic selection of cognitive outcomes across trials take a backseat to other trial goals. Twelve trials investigating change in cognitive functioning were examined and none met criteria for state-of-the-art assessment, including use of at least 4 tests indexing 2 cognitive domains. Four trials investigating incident dementia were also examined. Each trial used state-of-the-art diagnostic criteria to assess dementia, although follow-up periods were relatively short, with only 2 trials lasting for at least 3 years. Weaknesses in each trial may act to obscure or weaken the positive effects of BP lowering on cognitive functioning. Improving trial designs in terms of cognitive outcomes selected and length of follow-up periods employed could lead to more promising findings. We offer logical steps to achieve state-of-the-art assessment protocols, with examples, in hopes of improving future trials.

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study.

PubMed

Dalziel, Stuart R; Furyk, Jeremy; Bonisch, Megan; Oakley, Ed; Borland, Meredith; Neutze, Jocelyn; Donath, Susan; Sharpe, Cynthia; Harvey, Simon; Davidson, Andrew; Craig, Simon; Phillips, Natalie; George, Shane; Rao, Arjun; Cheng, Nicholas; Zhang, Michael; Sinn, Kam; Kochar, Amit; Brabyn, Christine; Babl, Franz E

2017-06-22

Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines. Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

Variation in Anticonvulsant Selection and Electroencephalographic Monitoring Following Severe Traumatic Brain Injury in Children-Understanding Resource Availability in Sites Participating in a Comparative Effectiveness Study.

PubMed

Kurz, Jonathan E; Poloyac, Samuel M; Abend, Nicholas S; Fabio, Anthony; Bell, Michael J; Wainwright, Mark S

2016-07-01

Early posttraumatic seizures may contribute to worsened outcomes after traumatic brain injury. Evidence to guide the evaluation and management of early posttraumatic seizures in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring, seizure prophylaxis, and the management of early posttraumatic seizures to provide essential information for trial design and the development of posttraumatic seizure management pathways. Surveys were sent to site principal investigators at all 43 sites participating in the Approaches and Decisions in Acute Pediatric TBI trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to 1) implement continuous electroencephalographic monitoring, 2) posttraumatic seizure prophylaxis, 3) treat acute posttraumatic seizures, 4) treat status epilepticus and refractory status epilepticus, and 5) monitor antiseizure drug levels. Institutions comprised a mixture of free-standing children's hospitals and university medical centers across the United States and Europe. Site principal investigators of the Approaches and Decisions in Acute Pediatric TBI trial. None. Continuous electroencephalographic monitoring was available in the PICU in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic antiseizure medications is anticipated in children (93%); yet, a minority reports that a specified protocol for treatment of posttraumatic seizures is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for refractory status epilepticus (81%). The presence of treatment protocols for seizure prophylaxis, early posttraumatic seizures, posttraumatic status epilepticus, and refractory status epilepticus was associated with decreased reported medications (all p < 0.05). This study reports the current management practices for early posttraumatic seizures in select academic centers after pediatric severe traumatic brain injury. The substantial variation in continuous electroencephalographic monitoring implementation, choice of seizure prophylaxis medications, and management of early posttraumatic seizures across institutions was reported, signifying the areas of clinical uncertainty that will help provide focused design of clinical trials. Although sites with treatment protocols reported a decreased number of medications for the scenarios described, completion of the Approaches and Decisions in Acute Pediatric TBI trial will be able to determine if these protocols lead to decreased variability in medication administration in children at the clinical sites.

Key observations from the NHLBI Asthma Clinical Research Network.

PubMed

Szefler, Stanley J; Chinchilli, Vernon M; Israel, Elliot; Denlinger, Loren Clark; Lemanske, Robert F; Calhoun, William; Peters, Stephen P

2012-05-01

The National Heart, Lung and Blood Institute (NHLBI) Asthma Clinical Research Network (ACRN) recently completed its work after 20 years of collaboration as a multicentre clinical trial network. When formed, its stated mission was to perform multiple controlled clinical trials for treating patients with asthma by dispassionately examining new and existing therapies, and to rapidly communicate its findings to the medical community. The ACRN conducted 15 major clinical trials. In addition, clinical data, manual of operations, protocols and template informed consents from all ACRN trials are available via NHLBI BioLINCC (https://biolincc.nhlbi.nih.gov/studies/). This network contributed major insights into the use of inhaled corticosteroids, short-acting and long-acting ß-adrenergic agonists, leukotriene receptor antagonists, and novel agents (tiotropium, colchicine and macrolide antibiotics). They also pioneered studies of the variability in drug response, predictors of treatment response and pharmacogenetics. This review highlights the major research observations from the ACRN that have impacted the current management of asthma.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol of a controlled clinical trial developed by consensus of an international study group. Part three: individual patient, complication algorithm and quality manage.

PubMed

Stinner, B; Bauhofer, A; Lorenz, W; Rothmund, M; Plaul, U; Torossian, A; Celik, I; Sitter, H; Koller, M; Black, A; Duda, D; Encke, A; Greger, B; van Goor, H; Hanisch, E; Hesterberg, R; Klose, K J; Lacaine, F; Lorijn, R H; Margolis, C; Neugebauer, E; Nyström, P O; Reemst, P H; Schein, M; Solovera, J

2001-05-01

Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). A randomised, placebo controlled, double-blinded, single-centre study is performed at an University Hospital (n = 40 patients for each group). This part presents the course of the individual patient and a complication algorithm for the management of anastomotic leakage and quality management. In part three of the protocol, the three major sections include: The course of the individual patient using a comprehensive graphic display, including the perioperative period, hospital stay and post discharge outcome. A center based clinical practice guideline for the management of the most important postoperative complication--anastomotic leakage--including evidence based support for each step of the algorithm. Data management, ethics and organisational structure. Future studies with immune modifiers will also fail if not better structured (reduction of variance) to achieve uniform patient management in a complex clinical scenario. This new type of a single-centre trial aims to reduce the gap between animal experiments and clinical trials or--if it fails--at least demonstrates new ways for explaining the failures.

Department of Defense prostate cancer clinical trials consortium: a new instrument for prostate cancer clinical research.

PubMed

Morris, Michael J; Basch, Ethan M; Wilding, George; Hussain, Maha; Carducci, Michael A; Higano, Celestia; Kantoff, Philip; Oh, William K; Small, Eric J; George, Daniel; Mathew, Paul; Beer, Tomasz M; Slovin, Susan F; Ryan, Charles; Logothetis, Christopher; Scher, Howard I

2009-01-01

In 2005, the US Department of Defense, through the US Army Medical Research and Materiel Command, Office of the Congressionally Directed Medical Research Programs, created a funding mechanism to form a clinical trials consortium to conduct phase I and II studies in prostate cancer. This is the first report of the Prostate Cancer Clinical Trials Consortium (PCCTC). The Department of Defense award supports a consortium of 10 prostate cancer research centers. Memorial Sloan-Kettering Cancer Center was awarded the Coordinating Center grant for the consortium and charged with creating an infrastructure to conduct early-phase multicenter clinical trials. Each participating center was required to introduce >or=1 clinical trial per year and maintain accrual of a minimum of 35 patients per year. The PCCTC was launched in 2006 and now encompasses 10 leading prostate cancer research centers. Fifty-one trials have been opened, and 1386 patients have been accrued at member sites. Members share an online clinical trial management system for protocol tracking, electronic data capture, and data storage. A legal framework has been instituted, and standard operating procedures, an administrative structure, editorial support, centralized budgeting, and mechanisms for scientific review are established. The PCCTC fulfills a congressional directive to create a clinical trials instrument dedicated to early-phase prostate cancer studies. The member institutions have built an administrative, informatics, legal, financial, statistical, and scientific infrastructure to support this endeavor. Clinical trials are open and accruing in excess of federally mandated goals.

Investigations of botanicals on food intake, satiety, weight loss, and oxidative stress: a study protocol of a double-blind, placebo-controlled, crossover study

PubMed Central

Anton, Stephen D.; Shuster, Jonathan; Leeuwenburgh, Christiaan

2013-01-01

Background Botanicals represent an important and underexplored source of potential new therapies that may facilitate caloric restriction and thereby produce long-term weight loss. In particular, one promising botanical that may reduce food intake and body weight by affecting neuroendocrine pathways related to satiety is Garcinia cambogia (Garcinia cambogia Desr.)-derived (−)-hydroxycitric acid (HCA). Methods and Design The objective of this article is to describe the protocol of a clinical trial designed to directly test the effect that Garcinia cambogia-derived HCA has on food intake, satiety, weight loss, and oxidative stress levels, and to serve as a model for similar trials. A total of 48 healthy, overweight and obese individuals (body mass index; BMI range = 25.0 – 39.9) between the ages of 50 to 70 will participate in this double-blind, placebo-controlled, crossover study designed to examine the effects of two doses of Garcinia cambogia-derived HCA on food intake, satiety, weight loss, and oxidative stress levels. This trial will take place at the University of Florida (UF)’s Aging and Rehabilitation Research Center (ARRC) and UF Clinical Research Center (CRC). Food intake represents the primary outcome measure and is calculated based on the total calories consumed at breakfast, lunch, and dinner meals during each test meal day at the CRC. This study can be completed with far fewer subjects than a parallel design. Discussion Of the numerous botanical compounds, the compound Garcinia cambogia-derived HCA was selected for testing in the present study because of its potential to safely reduce food intake, body weight, and oxidative stress levels. We will review potential mechanisms of action and safety parameters throughout this clinical trial, which is registered at ClinicalTrials.gov under NCT01238887. Trial registration ClinicalTrials.gov (Identifier: NCT01238887). PMID:22088584

Standardized peripheral blood mononuclear cell culture assay for determination of drug susceptibilities of clinical human immunodeficiency virus type 1 isolates. The RV-43 Study Group, the AIDS Clinical Trials Group Virology Committee Resistance Working Group.

PubMed Central

Japour, A J; Mayers, D L; Johnson, V A; Kuritzkes, D R; Beckett, L A; Arduino, J M; Lane, J; Black, R J; Reichelderfer, P S; D'Aquila, R T

1993-01-01

A standardized antiviral drug susceptibility assay for clinical human immunodeficiency virus type 1 (HIV-1) isolates has been developed for use in clinical trials. The protocol is a two-step procedure that first involves cocultivation of patient infected peripheral blood mononuclear cells (PBMC) with seronegative phytohemagglutinin-stimulated donor PBMC to obtain an HIV-1 stock. The virus stock is titrated for viral infectivity (50% tissue culture infective dose) by use of serial fourfold virus dilutions in donor PBMC. A standardized inoculum of 1,000 50% tissue culture infective doses per 10(6) cells is used in the second step of the procedure to acutely infect seronegative donor PBMC in a 7-day microtiter plate assay with triplicate wells containing zidovudine (ZDV) concentrations ranging from 0 to 5.0 microM. The ZDV 50% inhibitory concentrations (IC50) for reference ZDV-susceptible and ZDV-resistant HIV-1 isolates ranged from 0.002 to 0.113 microM and from 0.15 to > 5.0 microM, respectively. Use of this consensus protocol reduced interlaboratory variability for ZDV IC50 determinations with reference HIV-1 isolates. Among eight laboratories, the coefficient of variation ranged from 0.85 to 1.25 with different PBMC protocols and was reduced to 0.39 to 0.98 with the standardized assay. Among the clinical HIV-1 isolates assayed by the standardized drug susceptibility assay, the median ZDV IC50 increased gradually with more ZDV therapy. This protocol provides an efficient and reproducible means to assess the in vitro susceptibility to antiretroviral agents of virtually all clinical HIV-1 isolates. PMID:8517697

Treatment of Co-Occurring Substance Abuse and Suicidality among Adolescents: A Randomized Trial

ERIC Educational Resources Information Center

Esposito-Smythers, Christianne; Spirito, Anthony; Kahler, Christopher W.; Hunt, Jeffrey; Monti, Peter

2011-01-01

Objective: This study tested a cognitive-behavioral treatment protocol for adolescents with a co-occurring alcohol or other drug use disorder (AOD) and suicidality in a randomized clinical trial. Method: Forty adolescents (M[subscript age] = 15 years; 68% female, 89% White) and their families recruited from an inpatient psychiatric hospital were…

Cognitive Behavioral Therapy for 4- to 7-Year-Old Children with Anxiety Disorders: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Hirshfeld-Becker, Dina R.; Masek, Bruce; Henin, Aude; Blakely, Lauren Raezer; Pollock-Wurman, Rachel A.; McQuade, Julia; DePetrillo, Lillian; Briesch, Jacquelyn; Ollendick, Thomas H.; Rosenbaum, Jerrold F.; Biederman, Joseph

2010-01-01

Objective: To examine the efficacy of a developmentally appropriate parent-child cognitive behavioral therapy (CBT) protocol for anxiety disorders in children ages 4-7 years. Method: Design: Randomized wait-list controlled trial. Conduct: Sixty-four children (53% female, mean age 5.4 years, 80% European American) with anxiety disorders were…

The CONSENSUS study: protocol for a mixed methods study to establish which outcomes should be included in a core outcome set for oropharyngeal cancer.

PubMed

Waters, Aoife Mi; Tudur Smith, Catrin; Young, Bridget; Jones, Terry M

2014-05-13

The incidence of oropharyngeal cancer is increasing in the developed world. This has led to a large rise in research activity and clinical trials in this area, yet there is no consensus on which outcomes should be measured. As a result, the outcomes measured often differ between trials of comparable interventions, making the combination or comparison of results between trials impossible. Outcomes may also be 'cherry-picked', such that favourable results are reported, and less favourable results withheld. The development of a minimum outcome reporting standard, known as a core outcome set, goes some way to addressing these problems. Core outcome sets are ideally developed using a patient-centred approach so that the outcomes measured are relevant to patients and clinical practice. Core outcome sets drive up the quality and relevance of research by ensuring that the right outcomes are consistently measured and reported in trials in specific areas of health or healthcare. This is a mixed methods study involving three phases to develop a core outcome set for oropharyngeal cancer clinical trials. Firstly, a systematic review will establish which outcomes are measured in published oropharyngeal cancer randomised controlled trials (RCTs). Secondly, qualitative interviews with patients and carers in the UK and the USA will aim to establish which outcomes are important to these stakeholders. Data from these first two stages will be used to develop a comprehensive list of outcomes to be considered for inclusion in the core outcome set. In the third stage, patients and clinicians will participate in an iterative consensus exercise known as a Delphi study to refine the contents of the core outcome set. This protocol lays out the methodology to be implemented in the CONSENSUS study. A core outcome set defines a minimum outcome reporting standard for clinical trials in a particular area of health or healthcare. Its consistent implementation in oropharyngeal cancer clinical trials will improve the quality and relevance of research. This study is registered at the National Institute for Health Research (NIHR) Clinical Research Network (CRN) portfolio, ID 13823 (17 January 2013).

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial.

PubMed

Wade, Julia; Holding, Peter N; Bonnington, Susan; Rooshenas, Leila; Lane, J Athene; Salter, C Elizabeth; Tilling, Kate; Speakman, Mark J; Brewster, Simon F; Evans, Simon; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L

2015-09-18

To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial. Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability. Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK. Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM. Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care. The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice. NCT02044172; ISRCTN20141297. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The "ComPAS Trial" combined treatment model for acute malnutrition: study protocol for the economic evaluation.

PubMed

Lelijveld, Natasha; Bailey, Jeanette; Mayberry, Amy; Trenouth, Lani; N'Diaye, Dieynaba S; Haghparast-Bidgoli, Hassan; Puett, Chloe

2018-04-24

Acute malnutrition is currently divided into severe (SAM) and moderate (MAM) based on level of wasting. SAM and MAM currently have separate treatment protocols and products, managed by separate international agencies. For SAM, the dose of treatment is allocated by the child's weight. A combined and simplified protocol for SAM and MAM, with a standardised dose of ready-to-use therapeutic food (RUTF), is being trialled for non-inferior recovery rates and may be more cost-effective than the current standard protocols for treating SAM and MAM. This is the protocol for the economic evaluation of the ComPAS trial, a cluster-randomised controlled, non-inferiority trial that compares a novel combined protocol for treating uncomplicated acute malnutrition compared to the current standard protocol in South Sudan and Kenya. We will calculate the total economic costs of both protocols from a societal perspective, using accounting data, interviews and survey questionnaires. The incremental cost of implementing the combined protocol will be estimated, and all costs and outcomes will be presented as a cost-consequence analysis. Incremental cost-effectiveness ratio will be calculated for primary and secondary outcome, if statistically significant. We hypothesise that implementing the combined protocol will be cost-effective due to streamlined logistics at clinic level, reduced length of treatment, especially for MAM, and reduced dosages of RUTF. The findings of this economic evaluation will be important for policymakers, especially given the hypothesised non-inferiority of the main health outcomes. The publication of this protocol aims to improve rigour of conduct and transparency of data collection and analysis. It is also intended to promote inclusion of economic evaluation in other nutrition intervention studies, especially for MAM, and improve comparability with other studies. ISRCTN 30393230 , date: 16/03/2017.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all.

PubMed

Papageorgiou, Spyridon N; Antonoglou, Georgios N; Sándor, George K; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date.

Randomized clinical trials in orthodontics are rarely registered a priori and often published late or not at all

PubMed Central

Antonoglou, Georgios N.; Sándor, George K.; Eliades, Theodore

2017-01-01

A priori registration of randomized clinical trials is crucial to the transparency and credibility of their findings. Aim of this study was to assess the frequency with which registered and completed randomized trials in orthodontics are published. We searched ClinicalTrials.gov and ISRCTN for registered randomized clinical trials in orthodontics that had been completed up to January 2017 and judged the publication status and date of registered trials using a systematic protocol. Statistical analysis included descriptive statistics, chi-square or Fisher exact tests, and Kaplan-Meier survival estimates. From the 266 orthodontic trials registered up to January 2017, 80 trials had been completed and included in the present study. Among these 80 included trials, the majority (76%) were registered retrospectively, while only 33 (41%) were published at the time. The median time from completion to publication was 20.1 months (interquartile range: 9.1 to 31.6 months), while survival analysis indicated that less than 10% of the trials were published after 5 years from their completion. Finally, 22 (28%) of completed trials remain unpublished even after 5 years from their completion. Publication rates of registered randomized trials in orthodontics remained low, even 5 years after their completion date. PMID:28777820

A Consensus-Based Interpretation of the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure Trial.

PubMed

Chesnut, Randall M; Bleck, Thomas P; Citerio, Giuseppe; Classen, Jan; Cooper, D James; Coplin, William M; Diringer, Michael N; Grände, Per-Olof; Hemphill, J Claude; Hutchinson, Peter J; Le Roux, Peter; Mayer, Stephan A; Menon, David K; Myburgh, John A; Okonkwo, David O; Robertson, Claudia S; Sahuquillo, Juan; Stocchetti, Nino; Sung, Gene; Temkin, Nancy; Vespa, Paul M; Videtta, Walter; Yonas, Howard

2015-11-15

Widely-varying published and presented analyses of the Benchmark Evidence From South American Trials: Treatment of Intracranial Pressure (BEST TRIP) randomized controlled trial of intracranial pressure (ICP) monitoring have suggested denying trial generalizability, questioning the need for ICP monitoring in severe traumatic brain injury (sTBI), re-assessing current clinical approaches to monitored ICP, and initiating a general ICP-monitoring moratorium. In response to this dissonance, 23 clinically-active, international opinion leaders in acute-care sTBI management met to draft a consensus statement to interpret this study. A Delphi method-based approach employed iterative pre-meeting polling to codify the group's general opinions, followed by an in-person meeting wherein individual statements were refined. Statements required an agreement threshold of more than 70% by blinded voting for approval. Seven precisely-worded statements resulted, with agreement levels of 83% to 100%. These statements, which should be read in toto to properly reflect the group's consensus positions, conclude that the BEST TRIP trial: 1) studied protocols, not ICP-monitoring per se; 2) applies only to those protocols and specific study groups and should not be generalized to other treatment approaches or patient groups; 3) strongly calls for further research on ICP interpretation and use; 4) should be applied cautiously to regions with much different treatment milieu; 5) did not investigate the utility of treating monitored ICP in the specific patient group with established intracranial hypertension; 6) should not change the practice of those currently monitoring ICP; and 7) provided a protocol, used in non-monitored study patients, that should be considered when treating without ICP monitoring. Consideration of these statements can clarify study interpretation.

Effectiveness of a specific manual approach to the suboccipital region in patients with chronic mechanical neck pain and rotation deficit in the upper cervical spine: study protocol for a randomized controlled trial.

PubMed

González Rueda, Vanessa; López de Celis, Carlos; Barra López, Martín Eusebio; Carrasco Uribarren, Andoni; Castillo Tomás, Sara; Hidalgo García, Cesar

2017-09-05

Mechanical neck pain is a highly prevalent problem in primary healthcare settings. Many of these patients have restricted mobility of the cervical spine. Several manual techniques have been recommended for restoring cervical mobility, but their effectiveness in these patients is unknown. The aim of the present study is to compare the effectiveness of two types of specific techniques of the upper neck region: the pressure maintained suboccipital inhibition technique (PMSIT) and the translatory dorsal glide mobilization (TDGM) C0-C1 technique, as adjuncts to a protocolized physiotherapy treatment of the neck region in subjects with chronic mechanical neck pain and rotation deficit in the upper cervical spine. A randomized, prospective, double-blind (patient and evaluator) clinical trial. The participants (n = 78) will be randomly distributed into three groups. The Control Group will receive a protocolized treatment for 3 weeks, the Mobilization Group will receive the same protocolized treatment and 6 sessions (2 per week) of the TDGM C0-C1 technique, and the Pressure Group will receive the same protocolized treatment and 6 sessions (2 per week) of the PMSIT technique. The intensity of pain (VAS), neck disability (NDI), the cervical range of motion (CROM), headache intensity (HIT-6) and the rating of clinical change (GROC scale) will be measured. The measurements will be performed at baseline, post-treatment and 3 months after the end of treatment, by the same physiotherapist blinded to the group assigned to the subject. We believe that an approach including manual treatment to upper cervical dysfunction will be more effective in these patients. Furthermore, the PMSIT technique acts mostly on the musculature, while the TDGM technique acts on the joint. We expect to clarify which component is more effective in improving the upper cervical mobility. ClinicalTrials.gov NCT02832232 . Registered on July 13th, 2016.

Review of guidelines and literature for handling missing data in longitudinal clinical trials with a case study.

PubMed

Liu, M; Wei, L; Zhang, J

2006-01-01

Missing data in clinical trials are inevitable. We highlight the ICH guidelines and CPMP points to consider on missing data. Specifically, we outline how we should consider missing data issues when designing, planning and conducting studies to minimize missing data impact. We also go beyond the coverage of the above two documents, provide a more detailed review of the basic concepts of missing data and frequently used terminologies, and examples of the typical missing data mechanism, and discuss technical details and literature for several frequently used statistical methods and associated software. Finally, we provide a case study where the principles outlined in this paper are applied to one clinical program at protocol design, data analysis plan and other stages of a clinical trial.

Strategies to support recruitment of patients with life-limiting illness for research: the Palliative Care Research Cooperative Group.

PubMed

Hanson, Laura C; Bull, Janet; Wessell, Kathryn; Massie, Lisa; Bennett, Rachael E; Kutner, Jean S; Aziz, Noreen M; Abernethy, Amy

2014-12-01

The Palliative Care Research Cooperative Group (PCRC) is the first clinical trials cooperative for palliative care in the U.S. To describe barriers and strategies for recruitment during the inaugural PCRC clinical trial. The parent study was a multisite randomized controlled trial enrolling adults with life expectancy anticipated to be one to six months, randomized to discontinue statins (intervention) vs. to continue on statins (control). To study recruitment best practices, we conducted semistructured interviews with 18 site principal investigators (PIs) and clinical research coordinators (CRCs) and reviewed recruitment rates. Interviews covered three topics: 1) successful strategies for recruitment, 2) barriers to recruitment, and 3) optimal roles of the PI and CRC. All eligible site PIs and CRCs completed interviews and provided data on statin protocol recruitment. The parent study completed recruitment of 381 patients. Site enrollment ranged from 1 to 109 participants, with an average of 25 enrolled per site. Five major barriers included difficulty locating eligible patients, severity of illness, family and provider protectiveness, seeking patients in multiple settings, and lack of resources for recruitment activities. Five effective recruitment strategies included systematic screening of patient lists, thoughtful messaging to make research relevant, flexible protocols to accommodate patients' needs, support from clinical champions, and the additional resources of a trials cooperative group. The recruitment experience from the multisite PCRC yields new insights into methods for effective recruitment to palliative care clinical trials. These results will inform training materials for the PCRC and may assist other investigators in the field. Copyright © 2014 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

A risk-management approach for effective integration of biomarkers in clinical trials: perspectives of an NCI, NCRI, and EORTC working group.

PubMed

Hall, Jacqueline Anne; Salgado, Roberto; Lively, Tracy; Sweep, Fred; Schuh, Anna

2014-04-01

Clinical cancer research today often includes testing the value of biomarkers to direct treatment and for drug development. However, the practical challenges of integration of molecular information into clinical trial protocols are increasingly appreciated. Inherent difficulties include evidence gaps in available biomarker data, a paucity of robust assay methods, and the design of appropriate studies within the constraints of feasible trial operations, and finite resources. Scalable and proportionate approaches are needed to systematically cope with these challenges. Therefore, we assembled international experts from three clinical trials organisations to identify the common challenges and common solutions. We present a practical risk-assessment framework allowing targeting of scarce resources to crucial issues coupled with a library of useful resources and a simple actionable checklist of recommendations. We hope that these practical methods will be useful for running biomarker-driven trials and ultimately help to develop biomarkers that are ready for integration in routine practice. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigator initiated IBD trials in the US: Facts, obstacles and answers

PubMed Central

Herfarth, Hans H; Jackson, Susan; Schliebe, Barbara G.; Martin, Christopher; Ivanova, Anastasia; Anton, Kristen; Sandler, Robert S; Long, Millie D; Isaacs, Kim L; Osterman, Mark T; Sands, Bruce E; Higgins, Peter D; Lewis, James D

2016-01-01

Investigator initiated randomized clinical trials (IITs) are the backbone of academic clinical research. IITs complement the large clinical studies sponsored by industry and address questions, which are usually not the main focus of a commercially directed research but have the purpose to confirm, improve or refute clinically important questions with regard to diagnostic and therapeutic approaches in patient care. The aim of this review is to illustrate the necessary steps to start and complete an IIT in the field of inflammatory bowel diseases (IBD) in the US. The initial milestones for an investigator include structuring a protocol, planning and building of the trial infrastructure, accurately estimating the costs of the trial and gauging the time span for recruitment. Once the trial has begun it is important to keep patient recruitment on target, monitor of the data quality, and document treatment emergent adverse events. This article provides a framework for the different phases of an IIT and outlines potential hurdles, which could hinder a successful execution. PMID:27598744

Challenges in preparing and implementing a clinical trial at field level in an Ebola emergency: A case study in Guinea, West Africa.

PubMed

Carazo Perez, Sara; Folkesson, Elin; Anglaret, Xavier; Beavogui, Abdoul-Habib; Berbain, Emmanuel; Camara, Alseny-Modet; Depoortere, Evelyn; Lefevre, Annabelle; Maes, Piet; Malme, Kristian Nødtvedt; Malvy, Jean-Marie Denis; Ombelet, Sien; Poelaert, Geertrui; Sissoko, Daouda; Tounkara, Alexis; Trbovic, Pierre; Piguet, Pascal; Antierens, Annick

2017-06-01

During the large Ebola outbreak that affected West Africa in 2014 and 2015, studies were launched to evaluate potential treatments for the disease. A clinical trial to evaluate the effectiveness of the antiviral drug favipiravir was conducted in Guinea. This paper describes the main challenges of the implementation of the trial in the Ebola treatment center of Guéckédou. Following the principles of the Good Clinical Research Practices, we explored the aspects of the community's communication and engagement, ethical conduct, trial protocol compliance, informed consent of participants, ongoing benefit/risk assessment, record keeping, confidentiality of patients and study data, and roles and responsibilities of the actors involved. We concluded that several challenges have to be addressed to successfully implement a clinical trial during an international medical emergency but that the potential for collaboration between research teams and humanitarian organizations needs to be highlighted.

Barriers to participation in clinical trials: a physician survey.

PubMed

Mahmud, A; Zalay, O; Springer, A; Arts, K; Eisenhauer, E

2018-04-01

Clinical trials are vital for evidence-based cancer care. Oncologist engagement in clinical trials has an effect on patient recruitment, which in turn can affect trial success. Identifying barriers to clinical trial participation might enable interventions that could help to increase physician participation. To assess factors affecting physician engagement in oncology trials, a national survey was conducted using the online SurveyMonkey tool (SurveyMonkey, San Mateo, CA, U.S.A.; http://www.surveymonkey.com). Physicians associated with the Canadian Cancer Clinical Trials Network and the Canadian Cancer Trials Group were asked about their specialty, years of experience, barriers to participation, and motivating interventions, which included an open-ended question inviting survey takers to suggest interventions. The survey collected 207 anonymous responses. Respondents were predominantly medical oncologists (46.4%), followed by radiation oncologists (24.6%). Almost 70% of the respondents had more than 10 years of experience. Significant time constraints included extra paperwork (77%), patient education (54%), and extended follow-up or clinic visits (53%). Timing of events within trials was also a barrier to participation (55%). Most respondents favoured clinical work credits (72%), academic credits (67%), a clinical trial alert system (75%), a regular meeting to review trial protocols (65%), and a screening log to aid in patient accrual (67%) as motivational strategies. Suggested interventions included increased support staff, streamlined regulatory burden, and provision of greater funding for trials and easier access to ancillary services. The present study confirms that Canadian oncologists are willing to participate in clinical research, but face multiple barriers to trial participation. Those barriers could be mitigated by the implementation of several interventions identified in the study.

A randomized controlled trial of the effect of prednisone omission from a multidrug chemotherapy protocol on treatment outcome in dogs with peripheral nodal lymphomas.

PubMed

Childress, Michael O; Ramos-Vara, José A; Ruple, Audrey

2016-11-01

OBJECTIVE To determine the effect of prednisone omission from a multidrug chemotherapy protocol on outcome in dogs with peripheral nodal lymphomas. DESIGN Single-center, nonblinded, parallel-group, randomized, controlled trial. ANIMALS 40 client-owned dogs with a histopathologically confirmed diagnosis of peripheral nodal lymphoma and an expected survival time of > 4 weeks with treatment. PROCEDURES Treatment consisted of a combination of L-asparaginase, cyclophosphamide, doxorubicin, vincristine, and prednisone (L-CHOP) or an identical protocol except for the omission of prednisone (L-CHO). The primary outcome of interest was progression-free survival time. Veterinary caregivers and assessors of outcome were not blinded to treatment assignment. Treatment assignment was concealed from the owners of study dogs prior to enrollment, but was revealed after written informed consent was provided. RESULTS The trial was terminated early because of slow enrollment. The 40 dogs successfully enrolled in the study were randomly assigned to the L-CHOP (n = 18) or L-CHO (22) group; results for all 40 dogs were analyzed with respect to the primary outcome. Median progression-free survival time was 142.5 days for dogs receiving L-CHO and 292 days for dogs receiving L-CHOP (hazard ratio, 1.79; 95% confidence interval, 0.85 to 3.75). Serious adverse events were more common among dogs receiving L-CHO. However, this difference was not significant. CONCLUSIONS AND CLINICAL RELEVANCE The exclusion of prednisone from the L-CHOP protocol did not appear to result in improved progression-free survival time for dogs with peripheral nodal lymphomas. However, the present trial was likely underpowered to detect a clinically meaningful difference in progression-free survival time between groups.

Electroacupuncture versus sham electroacupuncture for urinary retention in poststroke patients: study protocol for a multicenter, randomized controlled trial.

PubMed

Shin, Seungwon; Lee, Jiwon; Yoo, Junghee; Lim, Sung Min; Lee, Euiju

2016-04-12

This study protocol evaluates the effectiveness of adjuvant electroacupuncture (EA) for urinary retention in poststroke patients undergoing conventional treatments, in comparison with that of a sham control. A multicenter, blinded, randomized controlled trial will be conducted in three hospitals in the Republic of Korea. We are recruiting 54 stroke survivors (aged >19 years), who were diagnosed with urinary retention based on the results of two consecutive post-void residual (PVR) tests, and dividing them randomly into two arms: the EA and Park-sham control groups. They will receive ten sessions of EA or sham treatment for 2 weeks. The participants will be blinded with non-penetrating needles and fake sounds of EA stimulators. The daily PVR ratio will be primarily measured at baseline and at the end of the study to statistically test the effectiveness of EA for poststroke urinary retention. Then, the Korean version of the Qualiveen Questionnaire, the Korean version of the International Prostate Symptom Score, and the blinding index will be assessed. After each EA session or sham EA, adverse events will be reported to evaluate the safety of EA. Results will be analyzed by using the independent t-test or Mann-Whitney U test, based on both intention-to-treat and per-protocol principles. The findings will provide clinical evidence for the effectiveness of EA treatment to improve urinary retention in stroke survivors. This study protocol was registered in ClinicalTrials.gov (NCT02472288) on 10 June 2015.

Feasibility of a Centralized Clinical Trials Coverage Analysis: A Joint Initiative of the American Society of Clinical Oncology and the National Cancer Institute.

PubMed

Szczepanek, Connie M; Hurley, Patricia; Good, Marjorie J; Denicoff, Andrea; Willenberg, Kelly; Dawson, Casey; Kurbegov, Dax

2017-06-01

Clinical trial billing compliance is a challenge that is faced by overburdened clinical trials sites. The requirements place institutions and research sites at increased potential for financial risk. To reduce their risk, sites develop a coverage analysis (CA) before opening each trial. For multisite trials, this translates into system-wide redundancies, inconsistencies, trial delays, and potential costs to sites and patients. These factors exacerbate low accrual rates to cancer clinical trials. ASCO and the National Cancer Institute (NCI) collaborated to address this problem. An ASCO Research Community Forum working group proposed the concept of providing centrally developed CAs to research sites at protocol startup. The group collaborated with NCI and billing compliance experts to hold a symposium for key stakeholders to share knowledge, build skills, provide tools to conduct centralized CAs, and strategize about the next steps. Forty-eight attendees, who represented a range of stakeholders, participated in the symposium. As a result of this initiative, NCI directed the Cancer Trials Support Unit to convene a working group with NCI's National Clinical Trials Network (NCTN) and Community Oncology Research Program (NCORP) to develop tools and processes for generating CAs for their trials. A CA template with core elements was developed and is being adapted in a pilot project across NCTN Group and NCORP Research Bases. Centralized CAs for multisite trials-using standardized tools and templates-are feasible. They have the potential to reduce risk for patients and sites, forecast budget needs, and help decrease trial startup times that impede patient access and accrual to clinical trials.

A blinded randomised placebo-controlled trial investigating the efficacy of morphine analgesia for procedural pain in infants: Trial protocol.

PubMed

Slater, Rebeccah; Hartley, Caroline; Moultrie, Fiona; Adams, Eleri; Juszczak, Ed; Rogers, Richard; Norman, Jane E; Patel, Chetan; Stanbury, Kayleigh; Hoskin, Amy; Green, Gabrielle

2016-11-15

Infant pain has both immediate and long-term negative consequences, yet in clinical practice it is often undertreated. To date, few pain-relieving drugs have been tested in infants. Morphine is a potent analgesic that provides effective pain relief in adults, but there is inconclusive evidence for its effectiveness in infants. The purpose of this study is to establish whether oral morphine provides effective analgesia for procedural pain in infants. A blinded, placebo-controlled, parallel-group randomized, phase II, clinical trial will be undertaken to determine whether morphine sulphate administered orally prior to clinically-required retinopathy of prematurity (ROP) screening and heel lancing provides effective analgesia. 
156 infants between 34 and 42 weeks' gestational age who require a clinical heel lance and ROP screening on the same test occasion will be included in the trial. Infants will be randomised to receive either a single dose of morphine sulphate (100 μg/kg) or placebo. Each infant will be monitored for 48 hours and safety data will be collected during the 24 hours following drug administration. The primary outcome will be the Premature Infant Pain Profile-revised (PIPP-R) score 30 seconds after ROP screening. The co-primary outcome will be the magnitude of nociceptive-specific brain activity evoked by a clinically-required heel lance. Infant clinical stability will be assessed by comparing the number of episodes of bradycardia, tachycardia, desaturation and apnoea, and changes in respiratory support requirements in the 24-hour periods before and after the clinical intervention. In addition, drug safety will be assessed by considering the occurrence of apnoeic and hypotensive episodes requiring intervention in the 24-hour period following drug administration. This study has been published as an Accepted Protocol Summary by The Lancet .

Community vs. Clinic-Based Modular Treatment of Children with Early-Onset ODD or CD: A Clinical Trial with 3-Year Follow-Up

ERIC Educational Resources Information Center

Kolko, David J.; Dorn, Lorah D.; Bukstein, Oscar G.; Pardini, Dustin; Holden, Elizabeth A.; Hart, Jonathan

2009-01-01

This study examines the treatment outcomes of 139, 6-11 year-old, clinically referred boys and girls diagnosed with Oppositional Defiant Disorder (ODD) or Conduct Disorder (CD) who were randomly assigned to a modular-based treatment protocol that was applied by research study clinicians either in the community (COMM) or a clinic office (CLINIC).…

From assessment to improvement of elderly care in general practice using decision support to increase adherence to ACOVE quality indicators: study protocol for randomized control trial

PubMed Central

2014-01-01

Background Previous efforts such as Assessing Care of Vulnerable Elders (ACOVE) provide quality indicators for assessing the care of elderly patients, but thus far little has been done to leverage this knowledge to improve care for these patients. We describe a clinical decision support system to improve general practitioner (GP) adherence to ACOVE quality indicators and a protocol for investigating impact on GPs’ adherence to the rules. Design We propose two randomized controlled trials among a group of Dutch GP teams on adherence to ACOVE quality indicators. In both trials a clinical decision support system provides un-intrusive feedback appearing as a color-coded, dynamically updated, list of items needing attention. The first trial pertains to real-time automatically verifiable rules. The second trial concerns non-automatically verifiable rules (adherence cannot be established by the clinical decision support system itself, but the GPs report whether they will adhere to the rules). In both trials we will randomize teams of GPs caring for the same patients into two groups, A and B. For the automatically verifiable rules, group A GPs receive support only for a specific inter-related subset of rules, and group B GPs receive support only for the remainder of the rules. For non-automatically verifiable rules, group A GPs receive feedback framed as actions with positive consequences, and group B GPs receive feedback framed as inaction with negative consequences. GPs indicate whether they adhere to non-automatically verifiable rules. In both trials, the main outcome measure is mean adherence, automatically derived or self-reported, to the rules. Discussion We relied on active end-user involvement in selecting the rules to support, and on a model for providing feedback displayed as color-coded real-time messages concerning the patient visiting the GP at that time, without interrupting the GP’s workflow with pop-ups. While these aspects are believed to increase clinical decision support system acceptance and its impact on adherence to the selected clinical rules, systems with these properties have not yet been evaluated. Trial registration Controlled Trials NTR3566 PMID:24642339

Effectiveness of Aquatic Therapy vs Land-based Therapy for Balance and Pain in Women with Fibromyalgia: a study protocol for a randomised controlled trial.

PubMed

Rivas Neira, Sabela; Pasqual Marques, Amélia; Pegito Pérez, Irene; Fernández Cervantes, Ramón; Vivas Costa, Jamile

2017-01-19

Fibromyalgia is a disease with an increasing incidence. It impairs the quality of life of patients and decreases their functional capacity. Aquatic therapy has already been used for managing the symptoms of this syndrome. However, aquatic therapy has only recently been introduced as a treatment modality for improving proprioception in fibromyalgia. The main objective of this study is to determine the effectiveness of two physiotherapy protocols, one in and one out of water, for improving balance and decreasing pain in women with fibromyalgia. The study protocol will be a single-blind randomised controlled trial. Forty women diagnosed with fibromyalgia will be randomly assigned into 2 groups: Aquatic Therapy (n = 20) or Land-based Therapy (n = 20). Both interventions include 60-min therapy sessions, structured into 4 sections: Warm-up, Proprioceptive Exercises, Stretching and Relaxation. These sessions will be carried out 3 times a week for 3 months. Primary outcomes are balance (static and dynamic) and pain (intensity and threshold). Secondary outcomes include functional balance, quality of life, quality of sleep, fatigue, self-confidence in balance and physical ability. Outcome measures will be evaluated at baseline, at the end of the 3-month intervention period, and 6-weeks post-treatment. Statistical analysis will be carried out using the SPSS 21.0 program for Windows and a significance level of p ≤ 0.05 will be used for all tests. This study protocol details two physiotherapy interventions in women with fibromyalgia to improve balance and decrease pain: aquatic therapy and land-based therapy. In current literature there is a lack of methodological rigour and a limited number of studies that describe physiotherapy protocols to manage fibromyalgia symptoms. High-quality scientific works are required to highlight physiotherapy as one of the most recommended treatment options for this syndrome. Date of publication in ClinicalTrials.gov: 18/02/2016. ClinicalTrials.gov Identifier: NCT02695875 .

Buprenorphine During Pregnancy Reduces Neonate Distress

MedlinePlus

... supported clinical trial, the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study, has found buprenorphine to be ... to the two medications. They surmise that the experimental treatment protocols may have moved patients from morphine ...

Design of the multicenter standardized supervised exercise training intervention for the claudication: exercise vs endoluminal revascularization (CLEVER) study.

PubMed

Bronas, Ulf G; Hirsch, Alan T; Murphy, Timothy; Badenhop, Dalynn; Collins, Tracie C; Ehrman, Jonathan K; Ershow, Abby G; Lewis, Beth; Treat-Jacobson, Diane J; Walsh, M Eileen; Oldenburg, Niki; Regensteiner, Judith G

2009-11-01

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

A cluster randomised controlled trial evaluating the effectiveness and cost-effectiveness of the daily mile on childhood obesity and wellbeing; the Birmingham daily mile protocol.

PubMed

Breheny, Katie; Adab, Peymane; Passmore, Sandra; Martin, James; Lancashire, Emma; Hemming, Karla; Frew, Emma

2018-01-11

Childhood obesity prevention is a public health priority. Children spend a large proportion of their waking time in school; therefore this is an appropriate setting to implement obesity prevention initiatives. Anecdotal reports suggest that implementing The Daily Mile in schools has had positive effects on childhood obesity, academic attainment and wellbeing. This trial aims to measure the effectiveness of The Daily Mile for improving health and wellbeing. This protocol describes a cluster randomised controlled trial (RCT) in 40 primary schools located in Birmingham, UK. Eligible participants are children in years 3 (aged 7-8) and 5 (aged 9-10). The study compares The Daily Mile (intervention) to usual practice (control) in relation to health and wellbeing. The Daily Mile intervention involves an additional 15 min of running or walking integrated into the school day, throughout a 12 month study period. The primary clinical outcome is body mass index (BMI) z-scores at 12 months following introduction of the intervention. The cost per Quality Adjusted Life Year (QALY) is the primary outcome of the economic evaluation. Secondary outcomes include wellbeing, physical fitness and teacher reported academic attainment. This study is the first RCT investigating the clinical and cost-effectiveness of The Daily Mile. A range of outcomes will be measured to evaluate the broader wellbeing and academic benefits in addition to clinical outcomes typically measured in childhood obesity prevention trials. The intervention is simple and low-cost, therefore if the benefits are demonstrated it has enormous potential to influence future policy. ISRCTN: 12698269 . Date protocol registered 27th October 2016.

Challenges in recruitment and retention of clinical trial subjects.

PubMed

Kadam, Rashmi Ashish; Borde, Sanghratna Umakant; Madas, Sapna Amol; Salvi, Sundeep Santosh; Limaye, Sneha Saurabh

2016-01-01

Successful recruitment of patients is known to be one of the most challenging aspects in conduct of randomized controlled trials. Inadequate patient retention during conduct of trial affects conclusive results. To assess the level of challenges faced by Indian investigators in recruitment and retention of trial subjects. We developed a survey questionnaire on challenges encountered by investigators in subject recruitment and retention which was hosted on a web portal. Seventy-three investigators from India participated in the survey. The frequently encountered challenges in subject recruitment were complexity of study protocol (38%), lack of awareness about clinical trials in patients (37%), and sociocultural issues related to trial participation (37%). About 63% of participants strongly agreed that creating a positive awareness about clinical trials among people through press and media, having a dedicated clinical research coordinator for trial (50.7%), and designing a recruitment strategy prior to study initiation (46.6%) would enhance recruitment. Almost 50.7% of participants agreed that interacting with medical community in vicinity of the study site and educating patients about clinical trials during routine outpatient department visits (46.6%) would enhance recruitment. Experiencing a serious adverse event, subject's fear for study procedures (47%) and side effects (44%) were thought to have a moderate effect on subject retention. Our survey has put forth factors related to negative publicity by media, lack of patient education about clinical trials; complex study designs are barriers to clinical trial recruitment in India. It is essential to devise innovative and effective strategies focusing on education of public and mass media about clinical research in India.

ESCAschool study: trial protocol of an adaptive treatment approach for school-age children with ADHD including two randomised trials.

PubMed

Döpfner, Manfred; Hautmann, Christopher; Dose, Christina; Banaschewski, Tobias; Becker, Katja; Brandeis, Daniel; Holtmann, Martin; Jans, Thomas; Jenkner, Carolin; Millenet, Sabina; Renner, Tobias; Romanos, Marcel; von Wirth, Elena

2017-07-24

The ESCAschool study addresses the treatment of school-age children with attention-deficit/hyperactivity disorder (ADHD) in a large multicentre trial. It aims to investigate three interrelated topics: (i) Clinical guidelines often recommend a stepped care approach, including different treatment strategies for children with mild to moderate and severe ADHD symptoms, respectively. However, this approach has not yet been empirically validated. (ii) Behavioural interventions and neurofeedback have been shown to be effective, but the superiority of combined treatment approaches such as medication plus behaviour therapy or medication plus neurofeedback compared to medication alone remains questionable. (iii) Growing evidence indicates that telephone-assisted self-help interventions are effective in the treatment of ADHD. However, larger randomised controlled trials (RCTs) are lacking. This report presents the ESCAschool trial protocol. In an adaptive treatment design, two RCTs and additional observational treatment arms are considered. The target sample size of ESCAschool is 521 children with ADHD. Based on their baseline ADHD symptom severity, the children will be assigned to one of two groups (mild to moderate symptom group and severe symptom group). The adaptive design includes two treatment phases (Step 1 and Step 2). According to clinical guidelines, different treatment protocols will be followed for the two severity groups. In the moderate group, the efficacy of telephone-assisted self-help for parents and teachers will be tested against waitlist control in Step 1 (RCT I). The severe group will receive pharmacotherapy combined with psychoeducation in Step 1. For both groups, treatment response will be determined after Step 1 treatment (no, partial or full response). In severe group children demonstrating partial response to medication, in Step 2, the efficacy of (1) counselling, (2) behaviour therapy and (3) neurofeedback will be tested (RCT II). All other treatment arms in Step 2 (severe group: no or full response; moderate group: no, partial or full response) are observational. The ESCAschool trial will provide evidence-based answers to several important questions for clinical practice following a stepped care approach. The adaptive study design will also provide new insights into the effects of additional treatments in children with partial response. German Clinical Trials Register (DRKS) DRKS00008973 . Registered 18 December 2015.

Wound-healing outcomes using standardized assessment and care in clinical practice.

PubMed

Bolton, Laura; McNees, Patrick; van Rijswijk, Lia; de Leon, Jean; Lyder, Courtney; Kobza, Laura; Edman, Kelly; Scheurich, Anne; Shannon, Ron; Toth, Michelle

2004-01-01

Wound-healing outcomes applying standardized protocols have typically been measured within controlled clinical trials, not natural settings. Standardized protocols of wound care have been validated for clinical use, creating an opportunity to measure the resulting outcomes. Wound-healing outcomes were explored during clinical use of standardized validated protocols of care based on patient and wound assessments. This was a prospective multicenter study of wound-healing outcomes management in real-world clinical practice. Healing outcomes from March 26 to October 31, 2001, were recorded on patients in 3 long-term care facilities, 1 long-term acute care hospital, and 12 home care agencies for wounds selected by staff to receive care based on computer-generated validated wound care algorithms. After diagnosis, wound dimensions and status were assessed using a tool adapted from the Pressure Sore Status Toolfor use on all wounds. Wound, ostomy, and continence nursing professionals accessed consistent protocols of care, via telemedicine in home care or paper forms in long-term care. A physician entered assessments into a desktop computer in the wound clinic. Based on evidence that healing proceeds faster with fewer infections in environments without gauze, the protocols generally avoided gauze dressings. Most of the 767 wounds selected to receive the standardized-protocols of care were stage III-IV pressure ulcers (n = 373; mean healing time 62 days) or full-thickness venous ulcers (n = 124; mean healing time 57 days). Partial-thickness wounds healed faster than same-etiology full-thickness wounds. These results provide benchmarks for natural-setting healing outcomes and help to define and address wound care challenges. Outcomes primarily using nongauze protocols of care matched or surpassed best previously published results on similar wounds using gauze-based protocols of care, including protocols applying gauze impregnated with growth factors or other agents.

NRG Oncology medical physicists' manpower survey quantifying support demands for multi-institutional clinical trials.

PubMed

Monroe, James I; Boparai, Karan; Xiao, Ying; Followill, David; Galvin, James M; Klein, Eric E; Low, Daniel A; Moran, Jean M; Zhong, Haoyu; Sohn, Jason W

2018-02-04

A survey was created by NRG to assess a medical physicists' percent full time equivalent (FTE) contribution to multi-institutional clinical trials. A 2012 American Society for Radiation Oncology report, "Safety Is No Accident," quantified medical physics staffing contributions in FTE factors for clinical departments. No quantification of FTE effort associated with clinical trials was included. To address this lack of information, the NRG Medical Physics Subcommittee decided to obtain manpower data from the medical physics community to quantify the amount of time medical physicists spent supporting clinical trials. A survey, consisting of 16 questions, was designed to obtain information regarding physicists' time spent supporting clinical trials. The survey was distributed to medical physicists at 1996 radiation therapy institutions included on the membership rosters of the 5 National Clinical Trials Network clinical trial groups. Of the 451 institutions who responded, 50% (226) reported currently participating in radiation therapy trials. On average, the designated physicist at each institution spent 2.4 hours (standard deviation [SD], 5.5) per week supervising or interacting with clinical trial staff. On average, 1.2 hours (SD, 3.1), 1.8 hours (SD, 3.9), and 0.6 hours (SD, 1.1) per week were spent on trial patient simulations, treatment plan reviews, and maintaining a Digital Imaging and Communications in Medicine server, respectively. For all trial credentialing activities, physicists spent an average of 32 hours (SD, 57.2) yearly. Reading protocols and supporting dosimetrists, clinicians, and therapists took an average of 2.1 hours (SD, 3.4) per week. Physicists also attended clinical trial meetings, on average, 1.2 hours (SD, 1.9) per month. On average, physicist spent a nontrivial total of 9 hours per week (0.21 FTE) supporting an average of 10 active clinical trials. This time commitment indicates the complexity of radiation therapy clinical trials and should be taken into account when staffing radiation therapy institutions. Copyright © 2018 Elsevier Inc. All rights reserved.

Pediatric oncology clinical trial participation where the geography is vast: Development of a clinical research system for tertiary and satellite centers in Ontario, Canada.

PubMed

Alexander, Sarah; Greenberg, Mark; Malkin, David; Portwine, Carol; Johnston, Donna; Silva, Mariana; Zelcer, Shayna; Sonshine, Samantha; Manzo, Janet; Bennett, Carla; Brodeur-Robb, Kathy; Deveault, Catherine; Ramachandran, Nivetha; Gibson, Paul

2018-04-01

Opportunities for participation in clinical trials are a core component of the care of children with cancer. In Ontario, many pediatric patients live long distances from their cancer center. This paper describes the work that was done in order to allow patients participating in Children's Oncology Group trials to receive care, including research protocol related care, jointly between the tertiary pediatric cancer center and the closer-to-home satellite center. The system is a pragmatic risk-based model, supporting excellence in care while ensuring good conduct of the research in compliance with applicable regulations and guidelines, including ethics oversight. © 2017 Wiley Periodicals, Inc.

Exploring Decision-Making of HIV-Infected Hispanics and African Americans Participating in Clinical Trials

PubMed Central

Rivera-Goba, Migdalia V.; Dominguez, Dinora C.; Stoll, Pamela; Grady, Christine; Ramos, Catalina; Mican, JoAnn M.

2011-01-01

Underrepresentation of HIV-infected Hispanics and African Americans in clinical trials seriously limits our understanding of the benefits and risks of treatment in these populations. This qualitative study examined factors that racial/ethnic minority patients consider when making decisions regarding research participation. Thirty-five HIV-infected Hispanic and African American patients enrolled in clinical research protocols at the National Institutes of Health were recruited to participate in focus groups and in-depth interviews. The sample of mostly men (n = 22), had a mean age of 45, nearly equal representation of race/ethnicity, and diagnosed 2 to 22 years ago. Baseline questionnaires included demographics and measures of social support and acculturation. Interviewers had similar racial/ethnic, cultural, and linguistic backgrounds as the participants. Four major themes around participants’ decisions to enroll in clinical trials emerged: Enhancers, Barriers, Beliefs, and Psychosocial Context. Results may help researchers develop strategies to facilitate inclusion of HIV-infected Hispanics and African Americans into clinical trials. PMID:21256054

The use of DRG for identifying clinical trials centers with high recruitment potential: a feasability study.

PubMed

Aegerter, Philippe; Bendersky, Noelle; Tran, Thi-Chien; Ropers, Jacques; Taright, Namik; Chatellier, Gilles

2014-01-01

Recruitment of large samples of patients is crucial for evidence level and efficacy of clinical trials (CT). Clinical Trial Recruitment Support Systems (CTRSS) used to estimate patient recruitment are generally specific to Hospital Information Systems and few were evaluated on a large number of trials. Our aim was to assess, on a large number of CT, the usefulness of commonly available data as Diagnosis Related Groups (DRG) databases in order to estimate potential recruitment. We used the DRG database of a large French multicenter medical institution (1.2 million inpatient stays and 400 new trials each year). Eligibility criteria of protocols were broken down into in atomic entities (diagnosis, procedures, treatments...) then translated into codes and operators recorded in a standardized form. A program parsed the forms and generated requests on the DRG database. A large majority of selection criteria could be coded and final estimations of number of eligible patients were close to observed ones (median difference = 25). Such a system could be part of the feasability evaluation and center selection process before the start of the clinical trial.

Stochastic targeted (STAR) glycemic control: design, safety, and performance.

PubMed

Evans, Alicia; Le Compte, Aaron; Tan, Chia-Siong; Ward, Logan; Steel, James; Pretty, Christopher G; Penning, Sophie; Suhaimi, Fatanah; Shaw, Geoffrey M; Desaive, Thomas; Chase, J Geoffrey

2012-01-01

Tight glycemic control (TGC) has shown benefits but has been difficult to achieve consistently. STAR (Stochastic TARgeted) is a flexible, model-based TGC approach that directly accounts for intra- and interpatient variability with a stochastically derived maximum 5% risk of blood glucose (BG) below 72 mg/dl. This research assesses the safety, efficacy, and clinical burden of a STAR TGC controller modulating both insulin and nutrition inputs in virtual and clinical pilot trials. Clinically validated virtual trials using data from 370 patients in the SPRINT (Specialized Relative Insulin and Nutrition Titration) study were used to design the STAR protocol and test its safety, performance, and required clinical effort prior to clinical pilot trials. Insulin and nutrition interventions were given every 1-3 h as chosen by the nurse to allow them to manage workload. Interventions were designed to maximize the overlap of the model-predicted (5-95(th) percentile) range of BG outcomes with the 72-117 mg/dl band and thus provide a maximum 5% risk of BG <72 mg/dl. Interventions were calculated using clinically validated computer models of human metabolism and its variability in critical illness. Carbohydrate intake (all sources) was selected to maximize intake up to 100% of the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/SCCM) goal (25 kg/kcal/h). Insulin doses were limited (8 U/h maximum), with limited increases based on current rate (0.5-2.0 U/h). Initial clinical pilot trials involved 3 patients covering ~450 h. Approval was granted by the Upper South A Regional Ethics Committee. Virtual trials indicate that STAR provides similar glycemic control performance to SPRINT with 2-3 h (maximum) measurement intervals. Time in the 72-126 mg/dl and 72-145 mg/dl bands was equivalent for all controllers, indicating that glycemic outcome differences between protocols were only shifted in this range. Safety from hypoglycemia was improved. Importantly, STAR using 2-3 h (maximum) intervention intervals reduced clinical burden up to 30%, which is clinically very significant. Initial clinical trials showed glycemic performance, safety, and management of inter- and intrapatient variability that matched or exceeded the virtual trial results. In virtual trials, STAR TGC provided tight control that maximized the likelihood of BG in a clinically specified glycemic band and reduced hypoglycemia with a maximum 5% (or lower) expected risk of light hypoglycemia (BG <72 mg/dl) via model-based management of intra- and interpatient variability. Clinical workload was self-managed and reduced up to 30% compared with SPRINT. Initial pilot clinical trials matched or exceeded these virtual results. © 2012 Diabetes Technology Society.

Statistical controversies in clinical research: basket trials, umbrella trials, and other master protocols: a review and examples

PubMed Central

Renfro, L. A.; Sargent, D. J.

2017-01-01

Abstract In recent years, cancers once viewed as relatively homogeneous in terms of organ location and treatment strategy are now better understood to be increasingly heterogeneous across biomarker and genetically defined patient subgroups. This has produced a shift toward development of biomarker-targeted agents during a time when funding for cancer research has been limited; as a result, the need for improved operational efficiency in studying many agent-and-target combinations in parallel has emerged. Platform trials, basket trials, and umbrella trials are new approaches to clinical research driven by this need for enhanced efficiency in the modern era of increasingly specific cancer subpopulations and decreased resources to study treatments for individual cancer subtypes in a traditional way. In this review, we provide an overview of these new types of clinical trial designs, including discussions of motivation for their use, recommended terminology, examples, and challenges encountered in their application. PMID:28177494

A randomized trial of protocol-based care for early septic shock.

PubMed

Yealy, Donald M; Kellum, John A; Huang, David T; Barnato, Amber E; Weissfeld, Lisa A; Pike, Francis; Terndrup, Thomas; Wang, Henry E; Hou, Peter C; LoVecchio, Frank; Filbin, Michael R; Shapiro, Nathan I; Angus, Derek C

2014-05-01

In a single-center study published more than a decade ago involving patients presenting to the emergency department with severe sepsis and septic shock, mortality was markedly lower among those who were treated according to a 6-hour protocol of early goal-directed therapy (EGDT), in which intravenous fluids, vasopressors, inotropes, and blood transfusions were adjusted to reach central hemodynamic targets, than among those receiving usual care. We conducted a trial to determine whether these findings were generalizable and whether all aspects of the protocol were necessary. In 31 emergency departments in the United States, we randomly assigned patients with septic shock to one of three groups for 6 hours of resuscitation: protocol-based EGDT; protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions; or usual care. The primary end point was 60-day in-hospital mortality. We tested sequentially whether protocol-based care (EGDT and standard-therapy groups combined) was superior to usual care and whether protocol-based EGDT was superior to protocol-based standard therapy. Secondary outcomes included longer-term mortality and the need for organ support. We enrolled 1341 patients, of whom 439 were randomly assigned to protocol-based EGDT, 446 to protocol-based standard therapy, and 456 to usual care. Resuscitation strategies differed significantly with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions. By 60 days, there were 92 deaths in the protocol-based EGDT group (21.0%), 81 in the protocol-based standard-therapy group (18.2%), and 86 in the usual-care group (18.9%) (relative risk with protocol-based therapy vs. usual care, 1.04; 95% confidence interval [CI], 0.82 to 1.31; P=0.83; relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI, 0.88 to 1.51; P=0.31). There were no significant differences in 90-day mortality, 1-year mortality, or the need for organ support. In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in the emergency department did not improve outcomes. (Funded by the National Institute of General Medical Sciences; ProCESS ClinicalTrials.gov number, NCT00510835.).

OARSI Clinical Trials Recommendations for Hip Imaging in Osteoarthritis

PubMed Central

Gold, Garry E.; Cicuttini, Flavia; Crema, Michel D.; Eckstein, Felix; Guermazi, Ali; Kijowski, Richard; Link, Thomas M.; Maheu, Emmanuel; Martel-Pelletier, Johanne; Miller, Colin G.; Pelletier, Jean-Pierre; Peterfy, Charles G.; Potter, Hollis G.; Roemer, Frank W.; Hunter, David. J

2015-01-01

Imaging of hip in osteoarthritis (OA) has seen considerable progress in the past decade, with the introduction of new techniques that may be more sensitive to structural disease changes. The purpose of this expert opinion, consensus driven recommendation is to provide detail on how to apply hip imaging in disease modifying clinical trials. It includes information on acquisition methods/ techniques (including guidance on positioning for radiography, sequence/protocol recommendations/ hardware for MRI); commonly encountered problems (including positioning, hardware and coil failures, artifacts associated with various MRI sequences); quality assurance/ control procedures; measurement methods; measurement performance (reliability, responsiveness, and validity); recommendations for trials; and research recommendations. PMID:25952344

Efficacy of Chinese auriculotherapy for stress in nursing staff: a randomized clinical trial

PubMed Central

Kurebayashi, Leonice Fumiko Sato; da Silva, Maria Júlia Paes

2014-01-01

Objective this randomized single blind clinical study aimed to evaluate the efficacy of auriculotherapy with and without a protocol for reducing stress levels among nursing staff. Method a total of 175 nursing professionals with medium and high scores according to Vasconcelos' Stress Symptoms List were divided into 3 groups: Control (58), Group with protocol (58), Group with no protocol (59). They were assessed at the baseline, after 12 sessions, and at the follow-up (30 days). Results in the analysis of variance, statistically significant differences between the Control and Intervention groups were found in the two evaluations (p<0.05) with greater size of effect indices (Cohen) for the No protocol group. The Yang Liver 1 and 2, Kidney, Brain Stem and Shen Men were the points most used. Conclusion individualized auriculotherapy, with no protocol, could expand the scope of the technique for stress reduction compared with auriculotherapy with a protocol. NCT: 01420835 PMID:25029046

A phase II trial for the efficacy of physiotherapy intervention for early-onset hip osteoarthritis: study protocol for a randomised controlled trial.

PubMed

Kemp, Joanne L; Moore, Kate; Fransen, Marlene; Russell, Trevor G; Crossley, Kay M

2015-01-27

Early-onset hip osteoarthritis is commonly seen in people undergoing hip arthroscopy and is associated with increased pain, reduced ability to participate in physical activity, reduced quality of life and reduced range of motion and muscle strength. Despite this, the efficacy of non-surgical interventions such as exercise therapies remains unknown. The primary aim is to establish the feasibility of a phase III randomised controlled trial investigating a targeted physiotherapy intervention for people with early-onset hip osteoarthritis. The secondary aims are to determine the size of treatment effects of a physiotherapy intervention, targeted to improve hip joint range and hip-related symptoms in early-onset hip osteoarthritis following hip arthroscopy, compared to a health-education control. This protocol describes a randomised, assessor- and participant-blind, controlled clinical trial. We will include 20 participants who are (i) aged between 18 and 50 years; (ii) have undergone hip arthroscopy during the past six to 12 months; (iii) have early-onset hip osteoarthritis (defined as chondrolabral pathology) at the time of hip arthroscopy; and (iv) experience hip-related pain during activities. Primary outcome will be the feasibility of a phase III clinical trial. Secondary outcomes will be (i) perceived global change score; (ii) hip-related symptoms (measured using the Hip disability and Osteoarthritis Outcome Score (HOOS) pain subscale, activity subscale, and sport and recreation subscale); (iii) hip quality of life (measured using the HOOS quality of life subscale and International Hip Outcome tool; (iv) hip muscle strength and (v) hip range of motion. The physiotherapy intervention is semi-standardised, including joint and soft tissue mobilisation and stretching, hip and trunk muscle retraining and functional and activity-specific retraining and education. The control intervention encompasses individualised health education, with the same frequency and duration as the intervention. The trial primary end-point is the conclusion of the 12-week intervention, and follow-up measures will be collected at the 12-week post-baseline assessment. The findings of this study will provide guidance regarding the feasibility of a full-scale phase III randomised controlled trial, prior to its undertaking. The trial protocol was registered with the Australian Clinical Trials Registry (number: 12614000426684 ) on 17 April 2014.

Trial publication after registration in ClinicalTrials.Gov: a cross-sectional analysis.

PubMed

Ross, Joseph S; Mulvey, Gregory K; Hines, Elizabeth M; Nissen, Steven E; Krumholz, Harlan M

2009-09-01

ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication. We examined reporting of registration information among a cross-section of trials that had been registered at ClinicalTrials.gov after December 31, 1999 and updated as having been completed by June 8, 2007, excluding phase I trials. We then determined publication status among a random 10% subsample by searching MEDLINE using a systematic protocol, after excluding trials completed after December 31, 2005 to allow at least 2 y for publication following completion. Among the full sample of completed trials (n = 7,515), nearly 100% reported all data elements mandated by ClinicalTrials.gov, such as intervention and sponsorship. Optional data element reporting varied, with 53% reporting trial end date, 66% reporting primary outcome, and 87% reporting trial start date. Among the 10% subsample, less than half (311 of 677, 46%) of trials were published, among which 96 (31%) provided a citation within ClinicalTrials.gov of a publication describing trial results. Trials primarily sponsored by industry (40%, 144 of 357) were less likely to be published when compared with nonindustry/nongovernment sponsored trials (56%, 110 of 198; p<0.001), but there was no significant difference when compared with government sponsored trials (47%, 57 of 122; p = 0.22). Among trials that reported an end date, 75 of 123 (61%) completed prior to 2004, 50 of 96 (52%) completed during 2004, and 62 of 149 (42%) completed during 2005 were published (p = 0.006). Reporting of optional data elements varied and publication rates among completed trials registered within ClinicalTrials.gov were low. Without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited. Please see later in the article for the Editors' Summary.

Immigrant family skills-building to prevent tobacco use in Latino youth: study protocol for a community-based participatory randomized controlled trial

PubMed Central

2012-01-01

Background Despite declines over recent years, youth tobacco and other substance use rates remain high. Latino youth are at equal or increased risk for lifetime tobacco, alcohol, marijuana, and other illicit drug use compared with their white peers. Family plays an important and influential role in the lives of youth, and longitudinal research suggests that improving parenting skills may reduce youth substance use. However, few interventions are oriented towards immigrant Latino families, and none have been developed and evaluated using a community-based participatory research (CBPR) process that may increase the effectiveness and sustainability of such projects. Therefore, using CBPR principles, we developed a randomized clinical trial to assess the efficacy of a family-skills training intervention to prevent tobacco and other substance use intentions in Latino youth. Methods/Design In collaboration with seven Latino community-serving agencies, we will recruit and randomize 336 immigrant families, into intervention or delayed treatment conditions. The primary outcome is youth intention to smoke 6 months post intervention. The intervention consists of eight parent and four youth sessions targeting parenting skills and parent–youth relational factors associated with lower smoking and other substance use in youth. Discussion We present the study protocol for a family intervention using a CBPR randomized clinical trial to prevent smoking among Latino youth. The results of this trial will contribute to the limited information on effective and sustainable primary prevention programs for tobacco and other substance use directed at the growing US Latino communities. Trial registration ClinicalTrials.gov: NCT01442753 PMID:23253201

Improving delirium care in the intensive care unit: The design of a pragmatic study

PubMed Central

2011-01-01

Background Delirium prevalence in the intensive care unit (ICU) is high. Numerous psychotropic agents are used to manage delirium in the ICU with limited data regarding their efficacy or harms. Methods/Design This is a randomized controlled trial of 428 patients aged 18 and older suffering from delirium and admitted to the ICU of Wishard Memorial Hospital in Indianapolis. Subjects assigned to the intervention group will receive a multicomponent pharmacological management protocol for delirium (PMD) and those assigned to the control group will receive no change in their usual ICU care. The primary outcomes of the trial are (1) delirium severity as measured by the Delirium Rating Scale revised-98 (DRS-R-98) and (2) delirium duration as determined by the Confusion Assessment Method for the ICU (CAM-ICU). The PMD protocol targets the three neurotransmitter systems thought to be compromised in delirious patients: dopamine, acetylcholine, and gamma-aminobutyric acid. The PMD protocol will target the reduction of anticholinergic medications and benzodiazepines, and introduce a low-dose of haloperidol at 0.5-1 mg for 7 days. The protocol will be delivered by a combination of computer (artificial intelligence) and pharmacist (human intelligence) decision support system to increase adherence to the PMD protocol. Discussion The proposed study will evaluate the content and the delivery process of a multicomponent pharmacological management program for delirium in the ICU. Trial Registration ClinicalTrials.gov: NCT00842608 PMID:21645330

Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

PubMed

Kamath, Mohan S; Maheshwari, Abha; Bhattacharya, Siladitya; Lor, Kar Yee; Gibreel, Ahmed

2017-11-02

Gonadotropins are the most commonly used medications for controlled ovarian stimulation in in vitro fertilisation (IVF). However, they are expensive and invasive, and are associated with the risk of ovarian hyperstimulation syndrome (OHSS). Recent calls for more patient-friendly regimens have led to growing interest in the use of clomiphene citrate (CC) and aromatase inhibitors with or without gonadotropins to reduce the burden of hormonal injections. It is currently unknown whether regimens using CC or aromatase inhibitors such as letrozole (Ltz) are as effective as gonadotropins alone. To determine the effectiveness and safety of regimens including oral induction medication (such as clomiphene citrate or letrozole) versus gonadotropin-only regimens for controlled ovarian stimulation in IVF or intracytoplasmic sperm injection (ICSI) treatment. We searched the following databases: Cochrane Gynaecology and Fertility Group Specialised Register (searched January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL CRSO), MEDLINE (1946 to January 2017), Embase (1980 to January 2017), and reference lists of relevant articles. We also searched trials registries ClinicalTrials.gov (clinicaltrials.gov/) and the World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch/Default.aspx). We handsearched relevant conference proceedings. We included randomized controlled trials (RCTs). The primary outcomes were live-birth rate (LBR) and OHSS. Three review authors independently assessed trial eligibility and risk of bias. We calculated risk ratios (RR) and Peto odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MD) for continuous outcomes. We analyzed the general population of women undergoing IVF treatment and (as a separate analysis) women identified as poor responders. We assessed the overall quality of the evidence using the GRADE approach. We included 27 studies in the updated review. Most of the new trials in the updated review included poor responders and evaluated Ltz protocols. We could perform meta-analysis with data from 22 studies including a total of 3599 participants. The quality of the evidence for different comparisons ranged from low to moderate. The main limitations in the quality of the evidence were risk of bias associated with poor reporting of study methods, and imprecision.In the general population of women undergoing IVF, it is unclear whether CC or Ltz used with or without gonadotropins compared to use of gonadotropins along with gonadotropin-releasing hormone (GnRH) agonists or antagonists resulted in a difference in live birth (RR 0.92, 95% CI 0.66 to 1.27, 4 RCTs, n = 493, I 2 = 0%, low-quality evidence) or clinical pregnancy rate (RR 1.00, 95% CI 0.86 to 1.16, 12 RCTs, n = 1998, I 2 = 3%, moderate-quality evidence). This means that for a typical clinic with 23% LBR using a GnRH agonist regimen, switching to CC or Ltz protocols would be expected to result in LBRs between 15% and 30%. Clomiphene citrate or Ltz protocols were associated with a reduction in the incidence of OHSS (Peto OR 0.21, 95% CI 0.11 to 0.41, 5 RCTs, n = 1067, I 2 = 0%, low-quality evidence). This means that for a typical clinic with 6% prevalence of OHSS associated with a GnRH regimen, switching to CC or Ltz protocols would be expected to reduce the incidence to between 0.5% and 2.5%. We found evidence of an increase in cycle cancellation rate with the CC protocol compared to gonadotropins in GnRH protocols (RR 1.87, 95% CI 1.43 to 2.45, 9 RCTs, n = 1784, I 2 = 61%, low-quality evidence). There was moderate quality evidence of a decrease in the mean number of ampoules used,) and mean number of oocytes collected with CC with or without gonadotropins compared to the gonadotropins in GnRH agonist protocols, though data were too heterogeneous to pool.Similarly, in the poor-responder population, it is unclear whether there was any difference in rates of live birth (RR 1.16, 95% CI 0.49 to 2.79, 2 RCTs, n = 357, I 2 = 38%, low-quality evidence) or clinical pregnancy (RR 0.85, 95% CI 0.64 to 1.12, 8 RCTs, n = 1462, I 2 = 0%, low-quality evidence) following CC or Ltz with or without gonadotropin versus gonadotropin and GnRH protocol. This means that for a typical clinic with a 5% LBR in the poor responders using a GnRH protocol, switching to CC or Ltz protocols would be expected to yield LBRs between 2% to 14%. There was low quality evidence that the CC or Ltz protocols were associated with an increase in the cycle cancellation rate (RR 1.46, 95% CI 1.18 to 1.81, 10 RCTs, n = 1601, I 2 = 64%) and moderate quality evidence of a decrease in the mean number of gonadotropin ampoules used and the mean number of oocytes collected, though data were too heterogeneous to pool. The adverse effects of these protocols were poorly reported. In addition, data on foetal abnormalities following use of CC or Ltz protocols are lacking. We found no conclusive evidence indicating that clomiphene citrate or letrozole with or without gonadotropins differed from gonadotropins in GnRH agonist or antagonist protocols with respect to their effects on live-birth or pregnancy rates, either in the general population of women undergoing IVF treatment or in women who were poor responders. Use of clomiphene or letrozole led to a reduction in the amount of gonadotropins required and the incidence of OHSS. However, use of clomiphene citrate or letrozole may be associated with a significant increase in the incidence of cycle cancellations, as well as reductions in the mean number of oocytes retrieved in both the general IVF population and the poor responders. Larger, high-quality randomized trials are needed to reach a firm conclusion before they are adopted into routine clinical practice.

Clinical trials recruitment planning: A proposed framework from the Clinical Trials Transformation Initiative.

PubMed

Huang, Grant D; Bull, Jonca; Johnston McKee, Kelly; Mahon, Elizabeth; Harper, Beth; Roberts, Jamie N

2018-03-01

Patient recruitment is widely recognized as a key determinant of success for clinical trials. Yet a substantial number of trials fail to reach recruitment goals-a situation that has important scientific, financial, ethical, and policy implications. Further, there are important effects on stakeholders who directly contribute to the trial including investigators, sponsors, and study participants. Despite efforts over multiple decades to identify and address barriers, recruitment challenges persist. To advance a more comprehensive approach to trial recruitment, the Clinical Trials Transformation Initiative (CTTI) convened a project team to examine the challenges and to issue actionable, evidence-based recommendations for improving recruitment planning that extend beyond common study-specific strategies. We describe our multi-stakeholder effort to develop a framework that delineates three areas essential to strategic recruitment planning efforts: (1) trial design and protocol development, (2) trial feasibility and site selection, and (3) communication. Our recommendations propose an upstream approach to recruitment planning that has the potential to produce greater impact and reduce downstream barriers. Additionally, we offer tools to help facilitate adoption of the recommendations. We hope that our framework and recommendations will serve as a guide for initial efforts in clinical trial recruitment planning irrespective of disease or intervention focus, provide a common basis for discussions in this area and generate targets for further analysis and continual improvement. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Issues and controversies of hepatocellular carcinoma-targeted therapy clinical trials in Asia: experts' opinion.

PubMed

Chen, Pei-Jer; Furuse, Junji; Han, Kwang-Hyub; Hsu, Chiun; Lim, Ho-Yeong; Moon, Hanlim; Qin, Shukui; Ye, Sheng-Long; Yeoh, Ee-Min; Yeo, Winnie

2010-11-01

Asia has a disproportionate share of the world's burden of hepatocellular carcinoma (HCC). However, the highly regarded clinical practice guidelines and recommendations for the design and conduct of clinical trials for HCC largely reflect Western practice. In order to design mutually beneficial international clinical trials of promising targeted therapies, it is imperative to understand how the aetiology, staging and treatment of HCC differ between Asian and Western countries. Our group, comprising experts in oncology and hepatology from countries that constitute the Eastern Asian region, convened to compare and contrast our current practices, evaluate potential compliance with the clinical trial recommendations, and offer suggestions for modifications that would enhance international collaboration. Here, we describe the results of our discussions, including recommendations for appropriate patient stratification based on potentially important differences in HCC aetiology, identification of practices that may confound interpretation of clinical trial outcomes (traditional Chinese medicine; antivirals that target hepatitis B virus; heterogeneous embolization procedures), suggestions for utilizing a common staging system in study protocols, recognition that sorafenib usage is limited by financial constraints and potentially increased toxicity in Asian patients, and expansion of patient populations that should be eligible for initial clinical trials with new agents. © 2010 John Wiley & Sons A/S.

Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review

PubMed Central

Hall, Deborah A; Szczepek, Agnieszka J; Kennedy, Veronica; Haider, Haúla

2015-01-01

Introduction In Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, ‘domains’) are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, ‘what’) is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process. Methods and analysis Deciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials. Ethics and dissemination No ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer-reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. Trial registration number The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. PMID:26560061

MRI signal intensity of anterior cruciate ligament graft after transtibial versus anteromedial portal technique (TRANSIG): design of a randomized controlled clinical trial.

PubMed

Ruiter, Simeon J S; Brouwer, Reinoud W; Meys, Tim W G M; Slump, Cornelis H; van Raay, Jos J A M

2016-08-10

There are two primary surgical techniques to reconstruct the anterior cruciate ligament (ACL), transtibial (TT) technique and anteromedial portal (AMP) technique. Currently, there is no consensus which surgical technique elicits the best clinical and functional outcomes. MRI-derived measures of the signal intensity (SI) of the ACL graft have been described as an independent predictor of graft properties. The purpose of this study is to compare the MRI derived SI measurements of the ACL graft one year after ACL reconstruction, in order to compare the outcomes of both the AMP and TT ACL reconstruction technique. Thirty-six patients will be included in a randomized controlled trial. Patients who are admitted for primary unilateral ACL reconstruction will be included in the study. Exclusion criteria are a history of previous surgery on the ipsilateral knee, re-rupture of the ipsilateral ACL graft, associated ligamentous injuries or meniscal tear of the ipsilateral knee, unhealthy contralateral knee, contra-indications for MRI and a preference for one of the two surgical techniques and/or orthopaedic surgeon. Primary outcome is MRI Signal intensity ratio (SIR) of the ACL graft. Secondary outcome measures are the International Knee Documentation Committee (IKDC) Knee Examination Form,the Knee injury and Osteoarthritis Outcome Scores (KOOS) and the Anterior Cruciate Ligament OsteoArthritis Score (ACLOAS). Differences between MRI SIR assessment with the current MRI protocol (proton density weighted imaging protocol) and the additional T2*-weighted gradient-echo protocol will be assessed. There is no consensus regarding the TT or AMP ACL reconstruction technique. SI measurements with MRI have been used in other clinical studies for evaluation of the ACL graft and maturation after ACL reconstruction compared to clinical and functional outcomes. This randomized controlled trial has been designed to compare the TT technique with the AMP technique with the use of MRI SI of the graft after ACL reconstruction. Netherlands Trial Registry NTR5410 (registered on August 24, 2015).

Revealed versus concealed criteria for placental insufficiency in an unselected obstetric population in late pregnancy (RATIO37): randomised controlled trial study protocol

PubMed Central

Figueras, Francesc; Gratacos, Eduard; Rial, Marta; Gull, Ilan; Krofta, Ladislav; Lubusky, Marek; Rogelio, Cruz-Martinez; Mónica, Cruz-Lemini; Miguel, Martinez-Rodriguez; Socias, Pamela; Aleuanlli, Cristina; Cordero, Mauro C Parra

2017-01-01

Introduction Fetal growth restriction (FGR) affects 5%–10% of all pregnancies, contributing to 30%–50% of stillbirths. Unfortunately, growth restriction often is not detected antenatally. The last weeks of pregnancy are critical for preventing stillbirth among babies with FGR because there is a pronounced increase in stillbirths among growth-restricted fetuses after 37 weeks of pregnancy. Here we present a protocol (V.1, 23 May 2016) for the RATIO37 trial, which evaluates an integrated strategy for accurately selecting at-risk fetuses for delivery at term. The protocol is based on the combination of fetal biometry and cerebroplacental ratio (CPR). The primary objective is to reduce stillbirth rates. The secondary aims are to detect low birth weights and adverse perinatal outcomes. Methods and analysis The study is designed as multicentre (Spain, Chile, Mexico,Czech Republic and Israel), open-label, randomised trial with parallel groups. Singleton pregnancies will be invited to participate after routine second-trimester ultrasound scan (19+0–22+6 weeks of gestation), and participants will be randomly allocated to receive revealed or concealed CPR evaluation. Then, a routine ultrasound and Doppler scan will be performed at 36+0–37+6 weeks. Sociodemographic and clinical data will be collected at enrolment. Ultrasound and Doppler variables will be recorded at 36+0–37+6 weeks of pregnancy. Perinatal outcomes will be recorded after delivery. Univariate (with estimated effect size and its 95% CI) and multivariate (mixed-effects logistic regression) comparisons between groups will be performed. Ethics and dissemination The study will be conducted in accordance with the principles of Good Clinical Practice. This study was accepted by the Clinical Research Ethics Committee of Hospital Clinic Barcelona on 23May 2016. Subsequent approval by individual ethical committees and competent authorities was granted. The study results will be published in peer-reviewed journals and disseminated at international conferences. Trial registration number NCT02907242; pre-results. PMID:28619771

Rehabilitation for the management of knee osteoarthritis using comprehensive traditional Chinese medicine in community health centers: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background It is becoming increasingly necessary for community health centers to make rehabilitation services available to patients with osteoarthritis of the knee. However, for a number of reasons, including a lack of expertise, the small size of community health centers and the availability of only simple medical equipment, conventional rehabilitation therapy has not been widely used in China. Consequently, most patients with knee osteoarthritis seek treatment in high-grade hospitals. However, many patients cannot manage the techniques that they were taught in the hospital. Methods such as acupuncture, tuina, Chinese medical herb fumigation-washing and t’ai chi are easy to do and have been reported to have curative effects in those with knee osteoarthritis. To date, there have been no randomized controlled trials validating comprehensive traditional Chinese medicine for the rehabilitation of knee osteoarthritis in a community health center. Furthermore, there is no standard rehabilitation protocol using traditional Chinese medicine for knee osteoarthritis. The aim of the current study is to develop a comprehensive rehabilitation protocol using traditional Chinese medicine for the management of knee osteoarthritis in a community health center. Method/design This will be a randomized controlled clinical trial with blinded assessment. There will be a 4-week intervention utilizing rehabilitation protocols from traditional Chinese medicine and conventional therapy. Follow-up will be conducted for a period of 12 weeks. A total of 722 participants with knee osteoarthritis will be recruited. Participants will be randomly divided into two groups: experimental and control. Primary outcomes will include range of motion, girth measurement, the visual analogue scale, and results from the manual muscle, six-minute walking and stair-climbing tests. Secondary outcomes will include average daily consumption of pain medication, ability to perform daily tasks and health-related quality-of-life assessments. Other outcomes will include rate of adverse events and economic effects. Relative cost-effectiveness will be determined from health service usage and outcome data. Discussion The primary aim of this trial is to develop a standard protocol for traditional Chinese medicine, which can be adopted by community health centers in China and worldwide, for the rehabilitation of patients with knee osteoarthritis. Trial registration Clinical Trials Registration: ChiCTR-TRC-12002538 PMID:24188276

Lessons Learned From The Investigational Device Exemption (IDE) Review of Children's Oncology Group Trial AAML1031

PubMed Central

Meshinchi, Soheil; Hunger, Stephen P.; Aplenc, Richard; Adamson, Peter C.; Jessup, J. Milburn

2012-01-01

The FDA is now exerting its regulatory authority over molecular diagnostics and their assays used for medical-decision making in clinical trials by performing pre-Investigational Device Exemption (IDE) reviews in all phases of clinical trials. This review assesses the analytical performance of the assay for the diagnostic and considers how that performance affects the diagnostic and the patient and their risks and benefits from treatment. This manuscript reviews the process of the first review that was performed on a new Children's Oncology Group (COG) Phase III trial in Acute Myelogenous Leukemia. The lessons learned and recommendations for how to prepare for and incorporate this new level of regulatory review into the protocol development process are presented. PMID:22422407

Research Nurse | Center for Cancer Research

Cancer.gov

We are looking for a Research Nurse (Accrual Site Coordinator) to join our neuro-oncology clinical team to help us provide administrative and coordination support for the Brain Tumor Trials Collaborative (BTTC). Duties include, but are not limited to, monitoring and overseeing activities pertaining to clinical protocols and administrative operations supporting the BTTC, with

Evaluation of the anti-fatigue effects of a traditional herbal drug, Gongjin-dan, under insufficient sleep conditions: study protocol for a randomised controlled trial.

PubMed

Son, Mi Ju; Im, Hwi-Jin; Kim, Young-Eun; Ku, Boncho; Lee, Jun-Hwan; Son, Chang-Gue

2016-08-22

Many herbal medicines are traditionally used as anti-fatigue agents in east Asian countries; however, there is a dearth of clinical evidence supporting the anti-fatigue effects of such medicines and their mechanisms. This study is a feasibility trial to assess the clinical efficacy of Gongjin-dan (GJD) and verify its mechanisms by exploring fatigue outcomes, including endocrine and immunological biomarkers in humans. To investigate the anti-fatigue effects of GJD and the mechanism underlying these effects, a randomised, double-blind, placebo-controlled crossover clinical trial was designed. Participants (24 healthy male volunteers) will be hospitalised for 4 days (3 nights), during which acute fatigue and stress conditions will be induced by sleep deprivation, and GJD or a placebo will be administered (twice daily). The primary outcome will be changes in serum cortisol levels, measured in the morning, as an objective biomarker of sleep deprivation-induced fatigue and stress. The secondary outcomes will include: the Fatigue Severity Scale; the Brief Fatigue Inventory, and the Leeds Sleep Evaluation Questionnaire scores; levels of salivary cortisol, epinephrine, norepinephrine, oxidative stress-related biomarkers, homocysteine, and immunological factors; and heart rate variability. After a washout period of more than 4 weeks, a second treatment phase will commence in which participants who were previously administered the placebo will receive the drug and vice versa, following the same treatment regime as in the first phase. This study protocol provides a unique opportunity to enhance our understanding of fatigue and the effects of GJD on fatigue in terms of endocrine and immunological mechanisms by validating the study design and determining feasibility. Findings from this trial will help researchers to design a pilot or definitive clinical trial of traditional herbal medicine for chronic fatigue. Korean National Clinical Trial Registry CRIS; KCT0001681 , registered on 29 October 2015.

Enhancing Insights into Pulmonary Vascular Disease through a Precision Medicine Approach. A Joint NHLBI-Cardiovascular Medical Research and Education Fund Workshop Report.

PubMed

Newman, John H; Rich, Stuart; Abman, Steven H; Alexander, John H; Barnard, John; Beck, Gerald J; Benza, Raymond L; Bull, Todd M; Chan, Stephen Y; Chun, Hyung J; Doogan, Declan; Dupuis, Jocelyn; Erzurum, Serpil C; Frantz, Robert P; Geraci, Mark; Gillies, Hunter; Gladwin, Mark; Gray, Michael P; Hemnes, Anna R; Herbst, Roy S; Hernandez, Adrian F; Hill, Nicholas S; Horn, Evelyn M; Hunter, Kendall; Jing, Zhi-Cheng; Johns, Roger; Kaul, Sanjay; Kawut, Steven M; Lahm, Tim; Leopold, Jane A; Lewis, Greg D; Mathai, Stephen C; McLaughlin, Vallerie V; Michelakis, Evangelos D; Nathan, Steven D; Nichols, William; Page, Grier; Rabinovitch, Marlene; Rich, Jonathan; Rischard, Franz; Rounds, Sharon; Shah, Sanjiv J; Tapson, Victor F; Lowy, Naomi; Stockbridge, Norman; Weinmann, Gail; Xiao, Lei

2017-06-15

The Division of Lung Diseases of the NHLBI and the Cardiovascular Medical Education and Research Fund held a workshop to discuss how to leverage the anticipated scientific output from the recently launched "Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics" (PVDOMICS) program to develop newer approaches to pulmonary vascular disease. PVDOMICS is a collaborative, protocol-driven network to analyze all patient populations with pulmonary hypertension to define novel pulmonary vascular disease (PVD) phenotypes. Stakeholders, including basic, translational, and clinical investigators; clinicians; patient advocacy organizations; regulatory agencies; and pharmaceutical industry experts, joined to discuss the application of precision medicine to PVD clinical trials. Recommendations were generated for discussion of research priorities in line with NHLBI Strategic Vision Goals that include: (1) A national effort, involving all the stakeholders, should seek to coordinate biosamples and biodata from all funded programs to a web-based repository so that information can be shared and correlated with other research projects. Example programs sponsored by NHLBI include PVDOMICS, Pulmonary Hypertension Breakthrough Initiative, the National Biological Sample and Data Repository for PAH, and the National Precision Medicine Initiative. (2) A task force to develop a master clinical trials protocol for PVD to apply precision medicine principles to future clinical trials. Specific features include: (a) adoption of smaller clinical trials that incorporate biomarker-guided enrichment strategies, using adaptive and innovative statistical designs; and (b) development of newer endpoints that reflect well-defined and clinically meaningful changes. (3) Development of updated and systematic variables in imaging, hemodynamic, cellular, genomic, and metabolic tests that will help precisely identify individual and shared features of PVD and serve as the basis of novel phenotypes for therapeutic interventions.

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

PubMed Central

Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

2016-01-01

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

Lessons learned: Infrastructure development and financial management for large, publically funded, international trials

PubMed Central

Larson, Gregg S; Carey, Cate; Grarup, Jesper; Hudson, Fleur; Sachi, Karen; Vjecha, Michael J; Gordin, Fred

2015-01-01

Background/Aims Randomized clinical trials are widely recognized as essential to address world-wide clinical and public health research questions. However, for many conditions, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost. We identify approaches and practices for large, publicly-funded, international trials that reduce cost without compromising data integrity, and recommend an approach to cost reporting that permits comparison of clinical trials. Methods We describe the organizational and financial characteristics of INSIGHT, an infectious disease research network that conducts multiple, large, long-term, international trials, and examine challenges associated with simple and streamlined governance and an infrastructure and financial management model that is based on performance, transparency, and accountability. Results It is possible to reduce costs of participant follow-up and not compromise clinical trial quality or integrity. The INSIGHT network has successfully completed four large HIV trials using cost-efficient practices that have not adversely affected investigator enthusiasm, accrual rates, loss-to-follow-up, adherence to the protocol, and completion of data collection. This experience is relevant to the conduct of large, publically funded trials in other disease areas, particularly trials dependent on international collaborations. Conclusion New approaches, or creative adaption of traditional clinical trial infrastructure and financial management tools, can render large, international clinical trials more cost-efficient by emphasizing structural simplicity; minimal up-front costs; payments for performance; and uniform algorithms and fees-for-service, irrespective of location. However, challenges remain. They include institutional resistance to financial change, growing trial complexity, and the difficulty of sustaining network infrastructure absent stable research work. There is also a need for more central monitoring, improved and harmonized regulations, and a widely-applied metric for measuring and comparing cost efficiency in clinical trials. ClinicalTrials.gov is recommended as a location where standardized trial cost information could be made publicly accessible. PMID:26908541

Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study.

PubMed

Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross; Haque, Rashidul; Zaman, K; Petri, William A; Kirkpatrick, Beth D

2018-03-05

The low efficacy of rotavirus vaccines in clinical trials performed in low-resource settings may be partially explained by acquired immunity from natural exposure, especially in settings with high disease incidence. In a clinical trial of monovalent rotavirus vaccine in Bangladesh, we compared the original per-protocol efficacy estimate to efficacy derived from a recurrent events survival model in which children were considered naturally exposed and potentially immune after their first rotavirus diarrhea (RVD) episode. We then simulated trial cohorts to estimate the expected impact of prior exposure on efficacy estimates for varying rotavirus incidence rates and vaccine efficacies. Accounting for natural immunity increased the per-protocol vaccine efficacy estimate against severe RVD from 63.1% (95% confidence interval [CI], 33.0%-79.7%) to 70.2% (95% CI, 44.5%-84.0%) in the postvaccination period, and original year 2 efficacy was underestimated by 14%. The simulations demonstrated that this expected impact increases linearly with RVD incidence, will be greatest for vaccine efficacies near 50%, and can reach 20% in settings with high incidence and low efficacy. High rotavirus incidence leads to predictably lower vaccine efficacy estimates due to the acquisition of natural immunity in unvaccinated children, and this phenomenon should be considered when comparing efficacy estimates across settings. NCT01375647.

ICONE: An International Consortium of Neuro Endovascular Centres.

PubMed

Raymond, J; White, P; Kallmes, D F; Spears, J; Marotta, T; Roy, D; Guilbert, F; Weill, A; Nguyen, T; Molyneux, A J; Cloft, H; Cekirge, S; Saatci, I; Bracard, S; Meder, J F; Moret, J; Cognard, C; Qureshi, A I; Turk, A S; Berenstein, A

2008-06-30

The proliferation of new endovascular devices and therapeutic strategies calls for a prudentand rational evaluation of their clinical benefit. This evaluation must be done in an effective manner and in collaboration with industry. Such research initiative requires organisation a land methodological support to survive and thrive in a competitive environment. We propose the formation of an international consortium, an academic alliance committed to the pursuit of effective neurovascular therapies. Such a consortium would be dedicated to the designand execution of basic science, device developmentand clinical trials. The Consortium is owned and operated by its members. Members are international leaders in neurointerventional research and clinical practice. The Consortium brings competency, knowledge, and expertise to industry as well as to its membership across aspectrum of research initiatives such as: expedited review of clinical trials, protocol development, surveys and systematic reviews; laboratory expertise and support for research design and grant applications to public agencies. Once objectives and protocols are approved, the Consortium provides a stable network of centers capable of timely realization of clinical trials or pre clinical investigations in an optimal environment. The Consortium is a non-profit organization. The potential revenue generated from clientsponsored financial agreements will be redirected to the academic and research objectives of the organization. The Consortium wishes to work inconcert with industry, to support emerging trends in neurovascular therapeutic development. The Consortium is a realistic endeavour optimally structured to promote excellence through scientific appraisal of our treatments, and to accelerate technical progress while maximizing patients' safety and welfare.

Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due to Enterobacteriaceae (SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial.

PubMed

López-Cortés, Luis Eduardo; Rosso-Fernández, Clara; Núñez-Núñez, María; Lavín-Alconero, Lucía; Bravo-Ferrer, José; Barriga, Ángel; Delgado, Mercedes; Lupión, Carmen; Retamar, Pilar; Rodríguez-Baño, Jesús

2017-06-09

Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable. The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic 'real-practice' trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due to Enterobacteriaceae . The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals. Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals. Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation. The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov: NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Improving mood with psychoanalytic and cognitive therapies (IMPACT): a pragmatic effectiveness superiority trial to investigate whether specialised psychological treatment reduces the risk for relapse in adolescents with moderate to severe unipolar depression: study protocol for a randomised controlled trial.

PubMed

Goodyer, Ian M; Tsancheva, Sonya; Byford, Sarah; Dubicka, Bernadka; Hill, Jonathan; Kelvin, Raphael; Reynolds, Shirley; Roberts, Christopher; Senior, Robert; Suckling, John; Wilkinson, Paul; Target, Mary; Fonagy, Peter

2011-07-13

Up to 70% of adolescents with moderate to severe unipolar major depression respond to psychological treatment plus Fluoxetine (20-50 mg) with symptom reduction and improved social function reported by 24 weeks after beginning treatment. Around 20% of non responders appear treatment resistant and 30% of responders relapse within 2 years. The specific efficacy of different psychological therapies and the moderators and mediators that influence risk for relapse are unclear. The cost-effectiveness and safety of psychological treatments remain poorly evaluated. Improving Mood with Psychoanalytic and Cognitive Therapies, the IMPACT Study, will determine whether Cognitive Behavioural Therapy or Short Term Psychoanalytic Therapy is superior in reducing relapse compared with Specialist Clinical Care. The study is a multicentre pragmatic effectiveness superiority randomised clinical trial: Cognitive Behavioural Therapy consists of 20 sessions over 30 weeks, Short Term Psychoanalytic Psychotherapy 30 sessions over 30 weeks and Specialist Clinical Care 12 sessions over 20 weeks. We will recruit 540 patients with 180 randomised to each arm. Patients will be reassessed at 6, 12, 36, 52 and 86 weeks. Methodological aspects of the study are systematic recruitment, explicit inclusion criteria, reliability checks of assessments with control for rater shift, research assessors independent of treatment team and blind to randomization, analysis by intention to treat, data management using remote data entry, measures of quality assurance, advanced statistical analysis, manualised treatment protocols, checks of adherence and competence of therapists and assessment of cost-effectiveness. We will also determine whether time to recovery and/or relapse are moderated by variations in brain structure and function and selected genetic and hormone biomarkers taken at entry. The objective of this clinical trial is to determine whether there are specific effects of specialist psychotherapy that reduce relapse in unipolar major depression in adolescents and thereby costs of treatment to society. We also anticipate being able to utilise psychotherapy experience, neuroimaging, genetic and hormone measures to reveal what techniques and their protocols may work best for which patients. Current Controlled Trials ISRCTN83033550.

RITPBC: B-cell depleting therapy (rituximab) as a treatment for fatigue in primary biliary cirrhosis: study protocol for a randomised controlled trial.

PubMed

Jopson, Laura; Newton, Julia L; Palmer, Jeremy; Floudas, Achilleas; Isaacs, John; Qian, Jessica; Wilkinson, Jennifer; Trenell, Mike; Blamire, Andrew; Howel, Denise; Jones, David E

2015-08-20

Primary biliary cirrhosis (PBC) is an autoimmune liver disease with approximately 50% of patients experiencing fatigue. This can be a particularly debilitating symptom, affecting quality of life and resulting in social isolation. Fatigue is highlighted by patients as a priority for research and patient support groups were involved in designing this trial. This is the first randomised controlled trial to investigate a treatment for fatigue in PBC. The trial protocol is innovative as it utilises novel magnetic resonance spectroscopy (MRS) techniques as an outcome measure. The protocol will be valuable to research groups planning clinical trials targeting fatigue in PBC and also transferrable to other conditions associated with fatigue. RITPBC is a Medical Research Council (MRC) and National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation Programme (EME)-funded project. It is a phase II, single-centre, randomised controlled, double-blinded trial comparing rituximab with placebo in fatigued PBC patients. 78 patients with PBC and moderate to severe fatigue will be randomised to receive two infusions of rituximab or placebo. The study aims to assess whether rituximab improves fatigue in patients with PBC, the safety, and tolerability of rituximab in PBC and the sustainability of any beneficial actions. The primary outcome will be an improvement in fatigue domain score of the PBC-40, a disease-specific quality of life measure, evaluated at 12-week assessment. Secondary outcome measures include novel MRS techniques assessing muscle bioenergetic function, physical activity, anaerobic threshold and symptom, and quality of life measures. The trial started recruiting in October 2012 and recruitment is ongoing. The trial has ethical approval from the NRES Committee North East, has Clinical Trial Authorisation from MHRA and local R&D approval. Trial results will be communicated to participants, presented at national and international meetings and published in peer-reviewed journals. ISRCTN03978701. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A study protocol to investigate the management of depression and challenging behaviors associated with dementia in aged care settings.

PubMed

McCabe, Marita P; Mellor, David; Davison, Tanya E; Karantzas, Gery; von Treuer, Kathryn; O'Connor, Daniel W

2013-09-19

The high occurrence and under-treatment of clinical depression and behavioral and psychological symptoms of dementia (BPSD) within aged care settings is concerning, yet training programs aimed at improving the detection and management of these problems have generally been ineffective. This article presents a study protocol to evaluate a training intervention for facility managers/registered nurses working in aged care facilities that focuses on organisational processes and culture as well as knowledge, skills and self-efficacy. A Randomised Control Trial (RCT) will be implemented across 18 aged care facilities (divided into three conditions). Participants will be senior registered nurses and personal care attendants employed in the aged care facility. The first condition will receive the training program (Staff as Change Agents - Enhancing and Sustaining Mental Health in Aged Care), the second condition will receive the training program and clinical support, and the third condition will receive no intervention. Pre-, post-, 6-month and 12-month follow-up measures of staff and residents will be used to demonstrate how upskilling clinical leaders using our transformational training approach, as well as the use of a structured screening, referral and monitoring protocol, can address the mental health needs of older people in residential care. The expected outcome of this study is the validation of an evidence-based training program to improve the management of depression and BPSD among older people in residential care settings by establishing routine practices related to mental health. This relatively brief but highly focussed training package will be readily rolled out to a larger number of residential care facilities at a relatively low cost. Australia and New Zealand Clinical Trials Register (ANZCTR): The Universal Trial Number (UTN) is U1111-1141-0109.

Nurse clinic versus home delivery of evidence-based community leg ulcer care: A randomized health services trial

PubMed Central

Harrison, Margaret B; Graham, Ian D; Lorimer, Karen; VandenKerkhof, Elizabeth; Buchanan, Maureen; Wells, Phil S; Brandys, Tim; Pierscianowski, Tadeusz

2008-01-01

Background International studies report that nurse clinics improve healing rates for the leg ulcer population. However, these studies did not necessarily deliver similar standards of care based on evidence in the treatment venues (home and clinic). A rigorous evaluation of home versus clinic care is required to determine healing rates with equivalent care and establish the acceptability of clinic-delivered care. Methods Health Services RCT was conducted where mobile individuals were allocated to either home or nurse clinic for leg ulcer management. In both arms, care was delivered by specially trained nurses, following an evidence protocol. Primary outcome: 3-month healing rates. Secondary outcomes: durability of healing (recurrence), time free of ulcers, HRQL, satisfaction, resource use. Data were collected at base-line, every 3 months until healing occurred, with 1 year follow-up. Analysis was by intention to treat. Results 126 participants, 65 randomized to receive care in their homes, 61 to nurse-run clinics. No differences found between groups at baseline on socio-demographic, HRQL or clinical characteristics. mean age 69 years, 68% females, 84% English-speaking, half with previous episode of ulceration, 60% ulcers at inclusion < 5 cm2 for < 6 months. No differences in 3-month healing rates: clinic 58.3% compared to home care at 56.7% (p = 0.5) or in secondary outcomes. Conclusion Our findings indicate that organization of care not the setting where care is delivered influences healing rates. Key factors are a system that supports delivery of evidence-based recommendations with care being provided by a trained nursing team resulting in equivalent healing rates, HRQL whether care is delivered in the home or in a community nurse-led clinic. Trial registration ClinicalTrials.gov Protocol Registration System: NCT00656383 PMID:19036149

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT)

PubMed Central

Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-01

Introduction Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. Methods and analysis A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver ‘active’ interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to ‘active’ intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. Ethics and dissemination The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. Trial registration number ISRCTN 71002650; Pre-results. PMID:26781504

Enhancing clinical evidence by proactively building quality into clinical trials.

PubMed

Meeker-O'Connell, Ann; Glessner, Coleen; Behm, Mark; Mulinde, Jean; Roach, Nancy; Sweeney, Fergus; Tenaerts, Pamela; Landray, Martin J

2016-08-01

Stakeholders across the clinical trial enterprise have expressed concern that the current clinical trial enterprise is unsustainable. The cost and complexity of trials have continued to increase, threatening our ability to generate reliable evidence essential for making appropriate decisions concerning the benefits and harms associated with clinical interventions. Overcoming this inefficiency rests on improving protocol design, trial planning, and quality oversight. The Clinical Trials Transformation Initiative convened a project to evaluate methods to prospectively build quality into the scientific and operational design of clinical trials ("quality-by-design"), such that trials are feasible to conduct and important errors are prevented rather than remediated. A working group evaluated aspects of trial design and oversight and developed the Clinical Trials Transformation Initiative quality-by-design principles document, outlining a series of factors generally relevant to the reliability of trial conclusions and to patient safety. These principles were then applied and further refined during a series of hands-on workshops to evaluate their utility in facilitating proactive, cross-functional dialogue, and decision-making about trial design and planning. Following these workshops, independent qualitative interviews were conducted with 19 workshop attendees to explore the potential challenges for implementing a quality-by-design approach to clinical trials. The Clinical Trials Transformation Initiative project team subsequently developed recommendations and an online resource guide to support implementation of this approach. The Clinical Trials Transformation Initiative quality-by-design principles provide a framework for assuring that clinical trials adequately safeguard participants and provide reliable information on which to make decisions on the effects of treatments. The quality-by-design workshops highlighted the value of active discussions incorporating the different perspectives within and external to an organization (e.g. clinical investigators, research site staff, and trial participants) in improving trial design. Workshop participants also recognized the value of focusing oversight on those aspects of the trial where errors would have a major impact on participant safety and reliability of results. Applying the Clinical Trials Transformation Initiative quality-by-design recommendations and principles should enable organizations to prioritize the most critical determinants of a trial's quality, identify non-essential activities that can be eliminated to streamline trial conduct and oversight, and formulate appropriate plans to define, avoid, mitigate, monitor, and address important errors. © The Author(s) 2016.

Connecting Smartphone and Wearable Fitness Tracker Data with a Nationally Used Electronic Health Record System for Diabetes Education to Facilitate Behavioral Goal Monitoring in Diabetes Care: Protocol for a Pragmatic Multi-Site Randomized Trial.

PubMed

Wang, Jing; Coleman, Deidra Carroll; Kanter, Justin; Ummer, Brad; Siminerio, Linda

2018-04-02

Mobile and wearable technology have been shown to be effective in improving diabetes self-management; however, integrating data from these technologies into clinical diabetes care to facilitate behavioral goal monitoring has not been explored. The objective of this paper is to report on a study protocol for a pragmatic multi-site trial along with the intervention components, including the detailed connected health interface. This interface was developed to integrate patient self-monitoring data collected from a wearable fitness tracker and its companion smartphone app to an electronic health record system for diabetes self-management education and support (DSMES) to facilitate behavioral goal monitoring. A 3-month multi-site pragmatic clinical trial was conducted with eligible patients with diabetes mellitus from DSMES programs. The Chronicle Diabetes system is currently freely available to diabetes educators through American Diabetes Association-recognized DSMES programs to set patient nutrition and physical activity goals. To integrate the goal-setting and self-monitoring intervention into the DSMES process, a connected interface in the Chronicle Diabetes system was developed. With the connected interface, patient self-monitoring information collected from smartphones and wearable fitness trackers can facilitate educators' monitoring of patients' adherence to their goals. Feasibility outcomes of the 3-month trial included hemoglobin A 1c levels, weight, and the usability of the connected system. An interface designed to connect data from a wearable fitness tracker with a companion smartphone app for nutrition and physical activity self-monitoring into a diabetes education electronic health record system was successfully developed to enable diabetes educators to facilitate goal setting and monitoring. A total of 60 eligible patients with type 2 diabetes mellitus were randomized into either group 1) standard diabetes education or 2) standard education enhanced with the connected system. Data collection for the 3-month pragmatic trial is completed. Data analysis is in progress. If results of the pragmatic multi-site clinical trial show preliminary efficacy and usability of the connected system, a large-scale implementation trial will be conducted. ClinicalTrials.gov NCT02664233; https://clinicaltrials.gov/ct2/show/NCT02664233 (Archived by WebCite at http://www.webcitation.org/6yDEwXHo5). ©Jing Wang, Deidra Carroll Coleman, Justin Kanter, Brad Ummer, Linda Siminerio. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 02.04.2018.

COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES): statistical and economic analysis plan for a randomised controlled trial.

PubMed

Robinson, Emily J; Goldstein, Laura H; McCrone, Paul; Perdue, Iain; Chalder, Trudie; Mellers, John D C; Richardson, Mark P; Murray, Joanna; Reuber, Markus; Medford, Nick; Stone, Jon; Carson, Alan; Landau, Sabine

2017-06-06

Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee. The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS. The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials. ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014).

Reporting of clinical trials: a review of research funders' guidelines

PubMed Central

Dwan, Kerry; Gamble, Carrol; Williamson, Paula R; Altman, Douglas G

2008-01-01

Background Randomised controlled trials (RCTs) represent the gold standard methodological design to evaluate the effectiveness of an intervention in humans but they are subject to bias, including study publication bias and outcome reporting bias. National and international organisations and charities give recommendations for good research practice in relation to RCTs but to date no review of these guidelines has been undertaken with respect to reporting bias. Methods National and international organisations and UK based charities listed on the Association for Medical Research Charities website were contacted in 2007; they were considered eligible for this review if they funded RCTs. Guidelines were obtained and assessed in relation to what was written about trial registration, protocol adherence and trial publication. It was also noted whether any monitoring against these guidelines was undertaken. This information was necessary to discover how much guidance researchers are given on the publication of results, in order to prevent study publication bias and outcome reporting bias. Results Seventeen organisations and 56 charities were eligible of 140 surveyed for this review, although there was no response from 12. Trial registration, protocol adherence, trial publication and monitoring against the guidelines were often explicitly discussed or implicitly referred too. However, only eleven of these organisations or charities mentioned the publication of negative as well as positive outcomes and just three of the organisations specifically stated that the statistical analysis plan should be strictly adhered to and all changes should be reported. Conclusion Our review indicates that there is a need to provide more detailed guidance for those conducting and reporting clinical trials to help prevent the selective reporting of results. Statements found in the guidelines generally refer to publication bias rather than outcome reporting bias. Current guidelines need to be updated and include the statement that all primary and secondary outcomes prespecified in the protocol should be fully reported and should not be selected for inclusion in the final report based on their results. PMID:19032743

CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy

DTIC Science & Technology

2012-09-01

Cardiac Outcome Measures in Children with Muscular Dystrophy o Cardiac MRI Protocol: PITT0110 - Cardiac Magnetic Resonance: A Parallel Protocol...permitted during the study. Study drug. The study drug was PTX (Trental; Sanofi- Aventis U.S. LLC, Bridgewater, NJ) tablets , an FDA-approved pharmaceutical...that is available for oral administration as 400-mg oblong tablets . Both the study drug PTX and placebo were overencapsulated by Capsugel (Pfizer Inc

WE-A-BRC-02: Lessons Learned: Clinical Trials and Operations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, S.

Quality and safety in healthcare are inextricably linked. There are compelling data that link poor quality radiation therapy to inferior patient survival. Radiation Oncology clinical trial protocol deviations often involve incorrect target volume delineation or dosing, akin to radiotherapy incidents which also often involve partial geometric miss or improper radiation dosing. When patients with radiation protocol variations are compared to those without significant protocol variations, clinical outcome is negatively impacted. Traditionally, quality assurance in radiation oncology has been driven largely by new technological advances, and safety improvement has been driven by reactive responses to past system failures and prescriptive mandatesmore » recommended by professional organizations and promulgated by regulators. Prescriptive approaches to quality and safety alone often do not address the huge variety of process and technique used in radiation oncology. Risk-based assessments of radiotherapy processes provide a mechanism to enhance quality and safety, both for new and for established techniques. It is imperative that we explore such a paradigm shift at this time, when expectations from patients as well as providers are rising while available resources are falling. There is much we can learn from our past experiences to be applied towards the new risk-based assessments. Learning Objectives: Understand the impact of clinical and technical quality on outcomes Understand the importance of quality care in radiation oncology Learn to assess the impact of quality on clinical outcomes D. Followill, NIH Grant CA180803.« less

Assessing Clinical Trial-Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool.

PubMed

Good, Marjorie J; Hurley, Patricia; Woo, Kaitlin M; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

2016-05-01

Clinical research program managers are regularly faced with the quandary of determining how much of a workload research staff members can manage while they balance clinical practice and still achieve clinical trial accrual goals, maintain data quality and protocol compliance, and stay within budget. A tool was developed to measure clinical trial-associated workload, to apply objective metrics toward documentation of work, and to provide clearer insight to better meet clinical research program challenges and aid in balancing staff workloads. A project was conducted to assess the feasibility and utility of using this tool in diverse research settings. Community-based research programs were recruited to collect and enter clinical trial-associated monthly workload data into a web-based tool for 6 consecutive months. Descriptive statistics were computed for self-reported program characteristics and workload data, including staff acuity scores and number of patient encounters. Fifty-one research programs that represented 30 states participated. Median staff acuity scores were highest for staff with patients enrolled in studies and receiving treatment, relative to staff with patients in follow-up status. Treatment trials typically resulted in higher median staff acuity, relative to cancer control, observational/registry, and prevention trials. Industry trials exhibited higher median staff acuity scores than trials sponsored by the National Institutes of Health/National Cancer Institute, academic institutions, or others. The results from this project demonstrate that trial-specific acuity measurement is a better measure of workload than simply counting the number of patients. The tool was shown to be feasible and useable in diverse community-based research settings. Copyright © 2016 by American Society of Clinical Oncology.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

PubMed

Zhang, Ying; Sun, Jin; Zhang, Yun-Jiao; Chai, Qian-Yun; Zhang, Kang; Ma, Hong-Li; Wu, Xiao-Ke; Liu, Jian-Ping

2016-10-21

Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Genome-wide Association Study of Virologic Response with Efavirenz- or Abacavir-containing Regimens in AIDS Clinical Trials Group Protocols

PubMed Central

Lehmann, David S.; Ribaudo, Heather J.; Daar, Eric S.; Gulick, Roy M.; Haubrich, Richard H.; Robbins, Gregory K.; de Bakker, Paul I.W.; Haas, David W.; McLaren, Paul J.

2015-01-01

Background Efavirenz and abacavir are components of recommended first-line regimens for human immunodeficiency virus (HIV)-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among subjects randomized to efavirenz- or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. Methods Virologic response and genome-wide genotype data were available from treatment-naive subjects randomized to efavirenz-containing (n=1,596) or abacavir-containing (n=786) regimens in ACTG protocols 384, A5142, A5095, and A5202. Results Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (p<5×10−8) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz, and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not reveal associations, nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. Conclusions No single polymorphism is strongly associated with virologic failure with efavirenz- or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by non-genetic factors, may reveal associations not apparent herein. PMID:25461247

Genome-wide association study of virologic response with efavirenz-containing or abacavir-containing regimens in AIDS clinical trials group protocols.

PubMed

Lehmann, David S; Ribaudo, Heather J; Daar, Eric S; Gulick, Roy M; Haubrich, Richard H; Robbins, Gregory K; de Bakker, Paul I W; Haas, David W; McLaren, Paul J

2015-02-01

Efavirenz and abacavir are components of recommended first-line regimens for HIV-1 infection. We used genome-wide genotyping and clinical data to explore genetic associations with virologic failure among patients randomized to efavirenz-containing or abacavir-containing regimens in AIDS Clinical Trials Group (ACTG) protocols. Virologic response and genome-wide genotype data were available from treatment-naive patients randomized to efavirenz-containing (n=1596) or abacavir-containing (n = 786) regimens in ACTG protocols 384, A5142, A5095, and A5202. Meta-analysis of association results across race/ethnic groups showed no genome-wide significant associations (P < 5 × 10) with virologic response for either efavirenz or abacavir. Our sample size provided 80% power to detect a genotype relative risk of 1.8 for efavirenz and 2.4 for abacavir. Analyses focused on CYP2B genotypes that define the lowest plasma efavirenz exposure stratum did not show associations nor did analysis limited to gene sets predicted to be relevant to efavirenz and abacavir disposition. No single polymorphism is associated strongly with virologic failure with efavirenz-containing or abacavir-containing regimens. Analyses to better consider context, and that minimize confounding by nongenetic factors, may show associations not apparent here.

Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory.

PubMed

Hróbjartsson, Asbjørn; Pildal, Julie; Chan, An-Wen; Haahr, Mette T; Altman, Douglas G; Gøtzsche, Peter C

2009-09-01

To compare the reporting on blinding in protocols and articles describing randomized controlled trials. We studied 73 protocols of trials approved by the scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding publications. Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., "open" vs. "double blind"). The proportion of "double-blind" trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients, health care providers, and data collectors had been blinded. In 4 of the 52 trials (7%), the protocols clarified that all three key trial persons had been blinded. The reporting on blinding in both trial protocols and publications is often inadequate. We suggest developing international guidelines for the reporting of trial protocols and public access to protocols.

Evolutionary cognitive therapy versus standard cognitive therapy for depression: a protocol for a blinded, randomized, superiority clinical trial.

PubMed

Giosan, Cezar; Cobeanu, Oana; Mogoase, Cristina; Muresan, Vlad; Malta, Loretta S; Wyka, Katarzyna; Szentagotai, Aurora

2014-03-19

Depression is estimated to become the leading cause of disease burden globally by 2030. Despite existing efficacious treatments (both medical and psychotherapeutic), a large proportion of patients do not respond to therapy. Recent insights from evolutionary psychology suggest that, in addition to targeting the proximal causes of depression (for example, targeting dysfunctional beliefs by cognitive behavioral therapy), the distal or evolutionary causes (for example, inclusive fitness) should also be addressed. A randomized superiority trial is conducted to develop and test an evolutionary-driven cognitive therapy protocol for depression, and to compare its efficacy against standard cognitive therapy for depression. Romanian-speaking adults (18 years or older) with elevated Beck Depression Inventory (BDI) scores (>13), current diagnosis of major depressive disorder or major depressive episode (MDD or MDE), and MDD with comorbid dysthymia, as evaluated by the Structured Clinical Interview for DSM-IV (SCID), are included in the study. Participants are randomized to one of two conditions: 1) evolutionary-driven cognitive therapy (ED-CT) or 2) cognitive therapy (CT). Both groups undergo 12 psychotherapy sessions, and data are collected at baseline, mid-treatment, post-treatment, and the 3-month follow-up. Primary outcomes are depressive symptomatology and a categorical diagnosis of depression post-treatment. This randomized trial compares the newly proposed ED-CT with a classic CT protocol for depression. To our knowledge, this is the first attempt to integrate insights from evolutionary theories of depression into the treatment of this condition in a controlled manner. This study can thus add substantially to the body of knowledge on validated treatments for depression. Current Controlled Trials ISRCTN64664414The trial was registered in June 2013. The first participant was enrolled on October 3, 2012.

Proposed primary endpoints for use in clinical trials that compare treatment options for bloodstream infection in adults: a consensus definition.

PubMed

Harris, P N A; McNamara, J F; Lye, D C; Davis, J S; Bernard, L; Cheng, A C; Doi, Y; Fowler, V G; Kaye, K S; Leibovici, L; Lipman, J; Llewelyn, M J; Munoz-Price, S; Paul, M; Peleg, A Y; Rodríguez-Baño, J; Rogers, B A; Seifert, H; Thamlikitkul, V; Thwaites, G; Tong, S Y C; Turnidge, J; Utili, R; Webb, S A R; Paterson, D L

2017-08-01

To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.

Feasibility of a clinical trial of vision therapy for treatment of amblyopia.

PubMed

Lyon, Don W; Hopkins, Kristine; Chu, Raymond H; Tamkins, Susanna M; Cotter, Susan A; Melia, B Michele; Holmes, Jonathan M; Repka, Michael X; Wheeler, David T; Sala, Nicholas A; Dumas, Janette; Silbert, David I

2013-05-01

We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, aged 7 to less than 13 years, with amblyopia (20/40-20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis might be required to allow enrollment of a broader group of subjects.

Feasibility of a Clinical Trial of Vision Therapy for Treatment of Amblyopia

PubMed Central

Lyon, Don W.; Hopkins, Kristine; Chu, Raymond H.; Tamkins, Susanna M.; Cotter, Susan A.; Melia, B. Michele; Holmes, Jonathan M.; Repka, Michael X.; Wheeler, David T.; Sala, Nicholas A.; Dumas, Janette; Silbert, David I.

2013-01-01

Purpose We conducted a pilot randomized clinical trial of office-based active vision therapy for the treatment of childhood amblyopia to determine the feasibility of conducting a full-scale randomized clinical trial. Methods A training and certification program and manual of procedures were developed to certify therapists to administer a standardized vision therapy program in ophthalmology and optometry offices consisting of weekly visits for 16 weeks. Nineteen children, 7 to less than 13 years of age, with amblyopia (20/40–20/100) were randomly assigned to receive either 2 hours of daily patching with active vision therapy or 2 hours of daily patching with placebo vision therapy. Results Therapists in diverse practice settings were successfully trained and certified to perform standardized vision therapy in strict adherence with protocol. Subjects completed 85% of required weekly in-office vision therapy visits. Eligibility criteria based on age, visual acuity, and stereoacuity, designed to identify children able to complete a standardized vision therapy program and judged likely to benefit from this treatment, led to a high proportion of screened subjects being judged ineligible, resulting in insufficient recruitment. There were difficulties in retrieving adherence data for the computerized home therapy procedures. Conclusions This study demonstrated that a 16-week treatment trial of vision therapy was feasible with respect to maintaining protocol adherence; however, recruitment under the proposed eligibility criteria, necessitated by the standardized approach to vision therapy, was not successful. A randomized clinical trial of in-office vision therapy for the treatment of amblyopia would require broadening of the eligibility criteria and improved methods to gather objective data regarding the home therapy. A more flexible approach that customizes vision therapy based on subject age, visual acuity, and stereopsis, might be required to allow enrollment of a broader group of subjects. PMID:23563444

Developing Substance Use Programming for Person-Oriented Recovery and Treatment (SUPPORT): protocol for a pilot randomized controlled trial.

PubMed

Watson, Dennis P; Ray, Bradley; Robison, Lisa; Xu, Huiping; Edwards, Rhiannon; Salyers, Michelle P; Hill, James; Shue, Sarah

2017-01-01

There is a lack of evidence-based substance use disorder treatment and services targeting returning inmates. Substance Use Programming for Person-Oriented Recovery and Treatment (SUPPORT) is a community-driven, recovery-oriented approach to substance abuse care which has the potential to address this service gap. SUPPORT is modeled after Indiana's Access to Recovery program, which was closed due to lack of federal support despite positive improvements in clients' recovery outcomes. SUPPORT builds on noted limitations of Indiana's Access to Recovery program. The ultimate goal of this project is to establish SUPPORT as an effective and scalable recovery-oriented system of care. A necessary step we must take before launching a large clinical trial is pilot testing the SUPPORT intervention. The pilot will take place at Public Advocates in Community Re-Entry (PACE), nonprofit serving individuals with felony convictions who are located in Marion County, Indiana (Indianapolis). The pilot will follow a basic parallel randomized design to compare clients receiving SUPPORT with clients receiving standard services. A total of 80 clients within 3 months of prison release will be recruited to participate and randomly assigned to one of the two intervention arms. Quantitative measures will be collected at multiple time points to understand SUPPORT's impact on recovery capital and outcomes. We will also collect qualitative data from SUPPORT clients to better understand their program and post-discharge experiences. Successful completion of this pilot will prepare us to conduct a multi-site clinical trial. The ultimate goal of this future work is to develop an evidence-based and scalable approach to treating substance use disorder among persons returning to society after incarceration. ClinicalTrials.gov (Clinical Trials ID: NCT03132753 and Protocol Number: 1511731907). Registered 28 April 2017.

[Prevention and handling of missing data in clinical trials].

PubMed

Jiang, Zhi-wei; Li, Chan-juan; Wang, Ling; Xia, Jie-lai

2015-11-01

Missing data is a common but unavoidable issue in clinical trials. It not only lowers the trial power, but brings the bias to the trial results. Therefore, on one hand, the missing data handling methods are employed in data analysis. On the other hand, it is vital to prevent the missing data in the trials. Prevention of missing data should take the first place. From the perspective of data, firstly, some measures should be taken at the stages of protocol design, data collection and data check to enhance the patients' compliance and reduce the unnecessary missing data. Secondly, the causes of confirmed missing data in the trials should be notified and recorded in detail, which are very important to determine the mechanism of missing data and choose the suitable missing data handling methods, e.g., last observation carried forward (LOCF); multiple imputation (MI); mixed-effect model repeated measure (MMRM), etc.

Transdiagnostic and Transcultural: Pilot Study of Unified Protocol for Depressive and Anxiety Disorders in Japan.

PubMed

Ito, Masaya; Horikoshi, Masaru; Kato, Noriko; Oe, Yuki; Fujisato, Hiroko; Nakajima, Shun; Kanie, Ayako; Miyamae, Mitsuhiro; Takebayashi, Yoshitake; Horita, Ryo; Usuki, Masato; Nakagawa, Atsuo; Ono, Yutaka

2016-05-01

Unified protocol (UP) is a transdiagnostic cognitive behavior therapy for emotional disorders. It remains unknown whether UP is applicable for use in non-Western countries and for depressive disorders. We therefore examined its feasibility for a Japanese clinical population using this clinical trial design, which is multicentered, open-labeled, and single-armed (Clinical registry: UMIN000008322). The primary outcome was severity of anxiety symptoms, as assessed using Structured Interview Guide for the Hamilton Anxiety Rating Scale. Secondary outcomes were depressive symptoms, clinical global impression, functioning, quality of life, affectivity, emotion regulation, and adverse events. Of the 28 prospective participants, 17 were eligible and enrolled (depressive disorders=9, anxiety disorders=8). Severity of anxiety symptoms, which decreased significantly after the intervention, remained low for 3months (Hedges' g=1.29, 95% CI=0.56-2.06). Similar tendencies were observed for secondary outcome measures. No severe adverse event occurred. Two participants dropped out of the intervention. High treatment adherence and interrater reliability were confirmed. Results suggest the feasibility of UP in the Japanese context sufficient to warrant a larger clinical trial. Copyright © 2016. Published by Elsevier Ltd.

The role of the Data and Safety Monitoring Board in a clinical trial: the CRISIS study.

PubMed

Holubkov, Richard; Casper, T Charles; Dean, J Michael; Anand, K J S; Zimmerman, Jerry; Meert, Kathleen L; Newth, Christopher J L; Berger, John; Harrison, Rick; Willson, Douglas F; Nicholson, Carol

2013-05-01

Randomized clinical trials are commonly overseen by a Data and Safety Monitoring Board comprised of experts in medicine, ethics, and biostatistics. Data and Safety Monitoring Board responsibilities include protocol approval, interim review of study enrollment, protocol compliance, safety, and efficacy data. Data and Safety Monitoring Board decisions can affect study design and conduct, as well as reported findings. Researchers must incorporate Data and Safety Monitoring Board oversight into the design, monitoring, and reporting of randomized trials. Case study, narrative review. The Data and Safety Monitoring Board's role during the comparative pediatric Critical Illness Stress-Induced Immune Suppression (CRISIS) Prevention Trial is described. The National Institutes of Health-appointed CRISIS Data and Safety Monitoring Board was charged with monitoring sample size adequacy and feasibility, safety with respect to adverse events and 28-day mortality, and efficacy with respect to the primary nosocomial infection/sepsis outcome. The Federal Drug Administration also requested Data and Safety Monitoring Board interim review before opening CRISIS to children below 1 yr of age. The first interim analysis found higher 28-day mortality in one treatment arm. The Data and Safety Monitoring Board maintained trial closure to younger children and requested a second interim data review 6 months later. At this second meeting, mortality was no longer of concern, whereas a weak efficacy trend of lower infection/sepsis rates in one study arm emerged. As over 40% of total patients had been enrolled, the Data and Safety Monitoring Board elected to examine conditional power and unmask treatment arm identities. On finding somewhat greater efficacy in the placebo arm, the Data and Safety Monitoring Board recommended stopping CRISIS due to futility. The design and operating procedures of a multicenter randomized trial must consider a pivotal Data and Safety Monitoring Board role. Maximum study design flexibility must be allowed, and investigators must be prepared for protocol modifications due to interim findings. The Data and Safety Monitoring Board must have sufficient clinical and statistical expertise to assess potential importance of interim treatment differences in the setting of multiple looks at accumulating data with numerous outcomes and subgroups.

Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study.

PubMed

Ramagopalan, Sreeram; Skingsley, Andrew P; Handunnetthi, Lahiru; Klingel, Michelle; Magnus, Daniel; Pakpoor, Julia; Goldacre, Ben

2014-01-01

An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed.  Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

The efficacy and safety of Baoji Tablets for treating common cold with summer-heat and dampness syndrome: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Despite the high incidence and the economic impact of the common cold, there are still no effective therapeutic options available. Although traditional Chinese medicine (TCM) is widely used in China to treat the common cold, there is still a lack of high-quality clinical trials. This article sets forth the protocol for a high-quality trial of a new TCM drug, Baoji Tablets, which is designed to treat the common cold with summer-heat and dampness syndrome (CCSDS). The trial is evaluating both the efficacy and safety of Baoji Tablets. Methods/design This study is designed as a multicenter, phase II, parallel-group, double-blind, double-dummy, randomized and placebo-controlled trial. A total of 288 patients will be recruited from four centers. The new tablets group are administered Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. The old pills group are administered dummy Baoji Tablets 0.9 g and Baoji Pills 3.7 g. The placebo control group are administered dummy Baoji Tablets 0.9 g and dummy Baoji Pills 3.7 g. All drugs are taken three times daily for 3 days. The primary outcome is the duration of all symptoms. Secondary outcomes include the duration of primary and secondary symptoms, changes in primary and secondary symptom scores and cumulative symptom score at day 4, as well as an evaluation of treatment efficacy. Discussion This is the first multicenter, double-blind, double-dummy, randomized and placebo-controlled trial designated to treat CCSDS in an adult population from China. It will establish the basis for a scientific and objective assessment of the efficacy and safety of Baoji Tablets for treating CCSDS, and provide evidence for a phase III clinical trial. Trial registration This study is registered with the Chinese Clinical Trial Registry. The registration number is ChiCTR-TRC-13003197. PMID:24359521

Prostate biopsies assisted by comanipulated probe-holder: first in man.

PubMed

Vitrani, Marie-Aude; Baumann, Michael; Reversat, David; Morel, Guillaume; Moreau-Gaudry, Alexandre; Mozer, Pierre

2016-06-01

A comanipulator for assisting endorectal prostate biopsies is evaluated through a first-in-man clinical trial. This lightweight system, based on conventional robotic components, possesses six degrees of freedom. It uses three electric motors and three brakes. It features a free mode, where its low friction and inertia allow for natural manipulation of the probe and a locked mode, exhibiting both a very low stiffness and a high steady-state precision. Clinical trials focusing on the free mode and the locked mode of the robot are presented. The objective was to evaluate the practical usability and performance of the robot during clinical procedures. A research protocol for a prospective randomized clinical trial has been designed. Its specific goal was to compare the accuracy of biopsies performed with and without the assistance of the comanipulator. The accuracy is compared between biopsies performed with and without the assistance of the comanipulator, across the 10 first patients included in the trial. Results show a statistically significant increase in the precision.

Sequential psychological and pharmacological therapies for comorbid and primary insomnia: study protocol for a randomized controlled trial.

PubMed

Morin, Charles M; Edinger, Jack D; Krystal, Andrew D; Buysse, Daniel J; Beaulieu-Bonneau, Simon; Ivers, Hans

2016-03-03

Chronic insomnia is a prevalent disorder associated with significant psychosocial, health, and economic impacts. Cognitive behavioral therapies (CBTs) and benzodiazepine receptor agonist (BzRA) medications are the most widely supported therapeutic approaches for insomnia management. However, few investigations have directly compared their relative and combined benefits, and even fewer have tested the benefits of sequential treatment for those who do not respond to initial insomnia therapy. Moreover, insomnia treatment studies have been limited by small, highly screened study samples, fixed-dose, and fixed-agent pharmacotherapy strategies that do not represent usual clinical practices. This study will address these limitations. This is a two-site randomized controlled trial, which will enroll 224 adults who meet the criteria for a chronic insomnia disorder with or without comorbid psychiatric disorders. Prospective participants will complete clinical assessments and polysomnography and then will be randomly assigned to first-stage therapy involving either behavioral therapy (BT) or zolpidem. Treatment outcomes will be assessed after 6 weeks, and treatment remitters will be followed for the next 12 months on maintenance therapy. Those not achieving remission will be offered randomization to a second, 6-week treatment, again involving either pharmacotherapy (zolpidem or trazodone) or psychological therapy (BT or cognitive therapy (CT)). All participants will be re-evaluated 12 weeks after the protocol initiation and at 3-, 6-, 9-, and 12-month follow-ups. Insomnia remission, defined categorically as a score < 8 on the Insomnia Severity Index, a patient-reported outcome, will serve as the primary endpoint for treatment comparisons. Secondary outcomes will include sleep parameters derived from daily sleep diaries and from polysomnography, subjective measures of fatigue, mood, quality of life, and functional impairments; and measures of adverse events; dropout rates; and treatment acceptability. Centrally trained therapists will administer therapies according to manualized, albeit flexible, treatment algorithms. This clinical trial will provide new information about optimal treatment sequencing and will have direct implication for the development of clinical guidelines for managing chronic insomnia with and without comorbid psychiatric conditions. ClinicalTrials.gov Identifier: NCT01651442 , Protocol version 4, 20 April 2011, registered 26 June 2012.

Protocol for an online randomised controlled trial to evaluate the clinical and cost-effectiveness of a peer-supported self-management intervention for relatives of people with psychosis or bipolar disorder: Relatives Education And Coping Toolkit (REACT).

PubMed

Lobban, Fiona; Robinson, Heather; Appelbe, Duncan; Barraclough, Johanna; Bedson, Emma; Collinge, Lizzi; Dodd, Susanna; Flowers, Sue; Honary, Mahsa; Johnson, Sonia; Mateus, Ceu; Mezes, Barbara; Minns, Valerie; Murray, Elizabeth; Walker, Andrew; Williamson, Paula; Wintermeyer, Catherine; Jones, Steven

2017-07-18

Despite clinical guidelines recommendations, many relatives of people with psychosis or bipolar disorder do not currently receive the support they need. Online information and support may offer a solution. This single-blind, parallel, online randomised controlled trial will determine clinical and cost-effectiveness of the Relatives Education And Coping Toolkit (REACT) (including an online resource directory (RD)), compared with RD only, for relatives of people with psychosis or bipolar disorder. Both groups continue to receive treatment as usual. Independent, web-based variable, block, individual randomisation will be used across 666 relatives. Primary outcome is distress at 24 weeks (measured by General Health Questionnaire; GHQ-28) compared between groups using analysis of covariance, adjusting for baseline score. Secondary clinical outcomes are carer well-being and support. Cost-effectiveness analysis will determine cost of a significant unit change (three-point reduction) in the GHQ-28. Costs include offering and supporting the intervention in the REACT arm, relevant healthcare care costs including health professional contacts, medications prescribed and time off (or ability to) work for the relative. Cost utility analysis will be calculated as the marginal cost of changes in quality-adjusted life years, based on EuroQol. We will explore relatives' beliefs, perceived coping and amount of REACT toolkit use as possible outcome mediators. We have embedded two methodological substudies in the protocol to determine the relative effectiveness of a low-value (£10) versus higher value (£20) incentive, and an unconditional versus conditional incentive, on improving follow-up rates. The trial has ethical approval from Lancaster National Research Ethics Service (NRES)Committee (15/NW/0732) and is overseen by an independent Data Monitoring and Ethics Committee and Trial Steering Committee. Protocol version 1.5 was approved on 9 January 2017. All updates to protocols are uploaded to the National Institute for Health Research (NIHR) Journals Library. A full statistical analysis plan is available at https://figshare.com/account/home#/projects/19975. Publications will be in peer-reviewed journals (open access wherever possible). Requests for access to the data at the end of the study will be reviewed and granted where appropriate by the Trial Management Group. ISRCTN72019945, pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Red light photodynamic therapy for actinic keratosis using 37 J/cm2 : Fractionated irradiation with 12.3 mW/cm2 after 30 minutes incubation time compared to standard continuous irradiation with 75 mW/cm2 after 3 hours incubation time using a mathematical modeling.

PubMed

Vignion-Dewalle, Anne-Sophie; Baert, Gregory; Devos, Laura; Thecua, Elise; Vicentini, Claire; Mortier, Laurent; Mordon, Serge

2017-09-01

Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for dermatological conditions. Although, the standard PDT protocol for the treatment of actinic keratoses in Europe has shown to be effective, treatment-associated pain is often observed in patients. Different modifications to this protocol attempted to decrease pain have been investigated. The decrease in fluence rate seems to be a promising solution. Moreover, it has been suggested that light fractionation significantly increases the efficacy of PDT. Based on a flexible light-emitting textile, the FLEXITHERALIGHT device specifically provides a fractionated illumination at a fluence rate more than six times lower than that of the standard protocol. In a recently completed clinical trial of PDT for the treatment of actinic keratosis, the non-inferiority of a protocol involving illumination with the FLEXITHERALIGHT device after a short incubation time and referred to as the FLEXITHERALIGHT protocol has been assessed compared to the standard protocol. In this paper, we propose a comparison of the two above mentioned 635 nm red light protocols with 37 J/cm 2 in the PDT treatment of actinic keratosis: the standard protocol and the FLEXITHERALIGHT one through a mathematical modeling. This mathematical modeling, which slightly differs from the one we have already published, enables the local damage induced by the therapy to be estimated. The comparison performed in terms of the local damage induced by the therapy demonstrates that the FLEXITHERALIGHT protocol with lower fluence rate, light fractionation and shorter incubation time is somewhat less efficient than the standard protocol. Nevertheless, from the clinical trial results, the FLEXITHERALIGHT protocol results in non-inferior response rates compared to the standard protocol. This finding raises the question of whether the PDT local damage achieved by the FLEXITHERALIGHT protocol (respectively, the standard protocol) is sufficient (respectively, excessive) to destroy actinic keratosis cells. Lasers Surg. Med. 49:686-697, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A Randomized Phase II Dose-Response Exercise Trial among Colon Cancer Survivors: Purpose, Study Design, Methods, and Recruitment Results

PubMed Central

Brown, Justin C.; Troxel, Andrea B.; Ky, Bonnie; Damjanov, Nevena; Zemel, Babette S.; Rickels, Michael R.; Rhim, Andrew D.; Rustgi, Anil K.; Courneya, Kerry S.; Schmitz, Kathryn H.

2016-01-01

Background Observational studies indicate that higher volumes of physical activity are associated with improved disease outcomes among colon cancer survivors. The aim of this report is to describe the purpose, study design, methods, and recruitment results of the COURAGE trial, a National Cancer Institute (NCI) sponsored, phase II, randomized, dose-response exercise trial among colon cancer survivors. Methods/Results The primary objective of the COURAGE trial is to quantify the feasibility, safety, and physiologic effects of low-dose (150 min·wk−1) and high-dose (300 min·wk−1) moderate-intensity aerobic exercise compared to usual-care control group over six months. The exercise groups are provided with in-home treadmills and heart rate monitors. Between January and July 2015, 1,433 letters were mailed using a population-based state cancer registry; 126 colon cancer survivors inquired about participation, and 39 were randomized onto the study protocol. Age was associated with inquiry about study participation (P<0.001) and randomization onto the study protocol (P<0.001). No other demographic, clinical, or geographic characteristics were associated with study inquiry or randomization. The final trial participant was randomized in August 2015. Six month endpoint data collection was completed in February 2016. Discussion The recruitment of colon cancer survivors into an exercise trial is feasible. The findings from this trial will inform key design aspects for future phase 2 and phase 3 randomized controlled trials to examine the efficacy of exercise to improve clinical outcomes among colon cancer survivors. PMID:26970181

Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study.

PubMed

Piek, Christine J; van Spil, Willem Evert; Junius, Greet; Dekker, Aldo

2011-04-13

Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149) and dogs treated according to the prednisolone protocol (P protocol; n = 73). At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77%) in the P protocol group and 69% (95% CI 59-80%) in the AP protocol group, respectively. Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

Enhancing Therapeutic Gains: Examination of Fidelity to the Model for the Intensive Mental Health Program

ERIC Educational Resources Information Center

Randall, Camille J.; Biggs, Bridget K.

2008-01-01

Given that the development of treatment fidelity assessment protocol is an integral but too frequently ignored aspect of clinical trials for psychological treatments, the Intensive Mental Health Program (IMHP) sought to build fidelity activities into training, program evaluation, and clinical recordkeeping from the outset of a 3 year study period.…

Clinical trial regulation in Argentina: overview and analysis of regulatory framework, use of existing tools, and researchers' perspectives to identify potential barriers.

PubMed

White, Lauren; Ortiz, Zulma; Cuervo, Luis G; Reveiz, Ludovic

2011-11-01

To review and analyze the regulatory framework of clinical trial registration, use of existing tools (publicly accessible national/international registration databases), and users' perspectives to identify possible barriers to registration compliance by sponsors and researchers in Argentina. Internationally registered trials recruiting patients in Argentina were found through clincialtrials.gov and the International Clinical Trial Registration Platform (ICTRP) and compared with publically available clinical trials registered through the National Administration of Drugs, Foods, and Medical Devices (ANMAT). A questionnaire addressing hypothesized attitudinal, knowledge-related, idiomatic, technical, economic, and regulatory barriers that could discourage or impede registration of clinical trials was developed, and semi-structured, in-depth interviews were conducted with a purposively selected sample of researchers (investigators, sponsors, and monitors) in Argentina. A response rate of 74.3% (n = 29) was achieved, and 27 interviews were ultimately used for analysis. Results suggested that the high proportion of foreign-sponsored or multinational trials (64.8% of all protocols approved by ANMAT from 1994-2006) may contribute to a communication gap between locally based investigators and foreign-based administrative officials. A lack of knowledge about available international registration tools and limited awareness of the importance of registration were also identified as limiting factors for local investigators and sponsors. To increase compliance and promote clinical trial registration in Argentina, national health authorities, sponsors, and local investigators could take the following steps: implement a grassroots educational campaign to improve clinical trial regulation, support local investigator-sponsor-initiated clinical trials, and/or encourage local and regional scientific journal compliance with standards from the International Committee of Medical Journal Editors (ICMJE) and/or the World Association of Medical Editors (WAME).

Personalized Information or Basic Information in Helping Patients Make Decisions About Participating in a Clinical Trial

ClinicalTrials.gov

2013-08-20

Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

Variation in anticonvulsant selection and EEG monitoring following severe traumatic brain injury in children – Understanding resource availability in sites participating in a comparative effectiveness study

PubMed Central

Kurz, Jonathan E.; Poloyac, Samuel M.; Abend, Nicholas S.; Fabio, Anthony; Bell, Michael J.; Wainwright, Mark S.

2016-01-01

Objective Early post-traumatic seizures (PTS) may contribute to worsened outcomes after traumatic brain injury (TBI). Evidence to guide the evaluation and management of early PTS in children is limited. We undertook a survey of current practices of continuous electroencephalographic monitoring (cEEG), seizure prophylaxis and the management of early PTS to provide essential information for trial design and the development of PTS management pathways. Design Surveys were sent to site principal investigators at all 43 sites participating in the ADAPT (Approaches and Decisions in Acute Pediatric TBI) trial at the time of the survey. Surveys consisted of 12 questions addressing strategies to (i) implement cEEG monitoring, (ii) PTS prophylaxis, (iii) treat acute PTS, (iv) treat status epilepticus (SE) and refractory status epilepticus (RSE) and (v) monitor anti-seizure drug levels. Setting Institutions comprised a mixture of free-standing children’s hospitals and university medical centers across the United States and Europe. Measurements and Main Results cEEG monitoring was available in the pediatric intensive care unit in the overwhelming majority of clinical sites (98%); however, the plans to operationalize such monitoring for children varied considerably. A similar majority of sites report that administration of prophylactic anti-seizure medications is anticipated in children (93%), yet a minority reports that a specified protocol for treatment of PTS is in place (43%). Reported medication choices varied substantially between sites, but the majority of sites reported pentobarbital for RSE (81%). Presence of an treatment protocols for seizure prophylaxis, early PTS, post-traumatic SE and RSE was associated with decreased reported medications (all p < 0.05). Conclusions This study reports the current management practices for early PTS in select academic centers after pediatric severe TBI. The substantial variation in cEEG implementation, choice of seizure prophylaxis medications, and management of early PTS across institutions was reported, signifying areas of clinical uncertainty that will help provide for focused design of clinical trials. While sites with treatment protocols reported decreased number of medications for the scenarios described, completion of the ADAPT Trial will be able to determine if these protocols lead to decreased variability in medication administration in children at the clinical sites. PMID:27243415

A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

PubMed

Bruce, Julie; Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

2016-01-18

Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the recommended SPIRIT Checklist. Amendments will be reported to relevant regulatory parties. ISRCTN 71002650; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

A neuromuscular exercise programme versus standard care for patients with traumatic anterior shoulder instability: study protocol for a randomised controlled trial (the SINEX study).

PubMed

Eshoj, Henrik; Rasmussen, Sten; Frich, Lars Henrik; Hvass, Inge; Christensen, Robin; Jensen, Steen Lund; Søndergaard, Jens; Søgaard, Karen; Juul-Kristensen, Birgit

2017-02-28

Anterior shoulder dislocation is a common injury and may have considerable impact on shoulder-related quality of life (QoL). If not warranted for initial stabilising surgery, patients are mostly left with little to no post-traumatic rehabilitation. This may be due to lack of evidence-based exercise programmes. In similar, high-impact injuries (e.g. anterior cruciate ligament tears in the knee) neuromuscular exercise has shown large success in improving physical function and QoL. Thus, the objective of this trial is to compare a nonoperative neuromuscular exercise shoulder programme with standard care in patients with traumatic anterior shoulder dislocations (TASD). Randomised, assessor-blinded, controlled, multicentre trial. Eighty patients with a TASD will be recruited from three orthopaedic departments in Denmark. Patients with primary or recurrent anterior shoulder dislocations due to at least one traumatic event will be randomised to 12 weeks of either a standardised, individualised or physiotherapist-supervised neuromuscular shoulder exercise programme or standard care (self-managed shoulder exercise programme). Patients will be stratified according to injury status (primary or recurrent). Primary outcome will be change from baseline to 12 weeks in the patient-reported QoL outcome questionnaire, the Western Ontario Shoulder Instability Index (WOSI). This trial will be the first study to compare the efficacy and safety of two different nonoperative exercise treatment strategies for patients with TASD. Moreover, this is also the first study to investigate nonoperative treatment effects in patients with recurrent shoulder dislocations. Lastly, this study will add knowledge to the shared decision-making process of treatment strategies for clinical practice. ClinicalTrials.gov, identifier: NCT02371928 . Registered on 9 February 2015 at the National Institutes of Health Clinical Trials Protocol Registration System.

A modified Mediterranean dietary intervention for adults with major depression: Dietary protocol and feasibility data from the SMILES trial.

PubMed

Opie, Rachelle S; O'Neil, Adrienne; Jacka, Felice N; Pizzinga, Josephine; Itsiopoulos, Catherine

2017-04-19

The SMILES trial was the first randomized controlled trial (RCT) explicitly designed to evaluate a dietary intervention, conducted by qualified dietitians, for reducing depressive symptomatology in adults with clinical depression. Here we detail the development of the prescribed diet (modified Mediterranean diet (ModiMedDiet)) for individuals with major depressive disorders (MDDs) that was designed specifically for the SMILES trial. We also present data demonstrating the extent to which this intervention achieved improvements in diet quality. The ModiMedDiet was designed using a combination of existing dietary guidelines and scientific evidence from the emerging field of nutritional psychiatric epidemiology. Sixty-seven community dwelling individuals (Melbourne, Australia) aged 18 years or over, with current poor quality diets, and MDDs were enrolled into the SMILES trial. A retention rate of 93.9 and 73.5% was observed for the dietary intervention and social support control group, respectively. The dietary intervention (ModiMedDiet) consisted of seven individual nutrition counselling sessions delivered by a qualified dietitian. The control condition comprised a social support protocol matched to the same visit schedule and length. This manuscript details the first prescriptive individualized dietary intervention delivered by dietitians for adults with major depression. Significant improvements in dietary quality were observed among individuals randomized to the ModiMedDiet group. These dietary improvements were also found to be associated with changes in depressive symptoms. The ModiMedDiet, a novel and individually tailored intervention designed specifically for adults with major depression, can be effectively implemented in clinical practice to manage this highly prevalent and debilitating condition. Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12612000251820. Registered 29 February 2012.

Treating Patients Who Strain the Research Psychotherapy Paradigm

PubMed Central

Markowitz, John C.; Kaplowitz, Matthew; Suh, Eun-Jung; Meehan, Kevin; Neria, Yuval; Jonker, Hanske; Rafaeli, Alexandra; Lovell, Karina

2013-01-01

Background Clinical trials of psychotherapy require diagnostic homogeneity, which implies a convergence of clinical presentations. Yet research study patients present diversely, and patients who do not fit a treatment paradigm may greatly complicate delivery of the study psychotherapy. The research literature has not addressed this issue. Methods The authors use case illustrations of three psychotherapies – Prolonged Exposure, Relaxation Therapy, and Interpersonal Psychotherapy – from an ongoing psychotherapy outcome trial of posttraumatic stress disorder to describe psychotherapeutic responses to complex, “atypical” patients who strain standard treatment paradigms. Results Therapists required flexibility, and occasionally deviations from strict protocol, in treating heterodox patients. Conclusions Such heterogeneity of presentation may have implications for psychotherapy outcome in research trials. Despite lack of discussion in the literature, many trials may face such issues. PMID:22759936

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

PubMed Central

Stauder, Reinhard; van Munster, Barbara C.

2014-01-01

Introduction. Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. Methods. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Conclusion. Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. PMID:25170014

Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry.

PubMed

Hamaker, Marije E; Stauder, Reinhard; van Munster, Barbara C

2014-10-01

Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. ©AlphaMed Press.

Preventing Caries in Preschoolers: Successful Initiation of an Innovative Community-Based Clinical Trial in Navajo Nation Head Start

PubMed Central

Quissell, David O.; Bryant, Lucinda L.; Braun, Patricia A.; Cudeii, Diana; Johs, Nikolas; Smith, Vongphone L.; George, Carmen; Henderson, William G.; Albino, Judith

2014-01-01

Navajo Nation children have the greatest prevalence of early childhood caries in the United States. This protocol describes an innovative combination of community-based participatory research and clinical trial methods to rigorously test a lay native Community Oral Health Specialists-delivered oral health intervention, with the goal of reducing the progression of disease and improving family knowledge and behaviors. Methods/Design This cluster-randomized trial designed by researchers at the Center for Native Oral Health Research at the University of Colorado in conjunction with members of the Navajo Nation community compares outcomes between the manualized 2-year oral health fluoride varnish-oral health promotion intervention and usual care in the community (child-caregiver dyads from 26 Head Start classrooms in each study arm; total of 1016 dyads). Outcome assessment includes annual dental screening and an annual caregiver survey of knowledge, attitudes and behaviors; collection of cost data will support cost-benefit analyses. Discussion The study protocol meets all standards required of randomized clinical trials. Aligned with principles of community-based participatory research, extended interaction between members of the Navajo community and researchers preceded study initiation, and collaboration between project staff and a wide variety of community members informed the study design and implementation. We believe the benefits of adding CBPR methods to those of randomized clinical studies outweigh the barriers and constraints, especially in studies of health disparities and in challenging settings. When done well, this innovative mix of methods will increase the likelihood of valid results that communities can use. PMID:24469238

Efficacy and safety of electroacupuncture in acute decompensated heart failure: a study protocol for a randomized, patient- and assessor-blinded, sham controlled trial.

PubMed

Leem, Jungtae; Lee, Seung Min Kathy; Park, Jun Hyeong; Lee, Suji; Chung, Hyemoon; Lee, Jung Myung; Kim, Weon; Lee, Sanghoon; Woo, Jong Shin

2017-07-11

The purpose of this trial is to evaluate the effectiveness and safety of electroacupuncture in the treatment of acute decompensated heart failure compared with sham electroacupuncture. This protocol is for a randomized, sham controlled, patient- and assessor-blinded, parallel group, single center clinical trial that can overcome the limitations of previous trials examining acupuncture and heart failure. Forty-four acute decompensated heart failure patients admitted to the cardiology ward will be randomly assigned into the electroacupuncture treatment group (n = 22) or the sham electroacupuncture control group (n = 22). Participants will receive electroacupuncture treatment for 5 days of their hospital stay. The primary outcome of this study is the difference in total diuretic dose between the two groups during hospitalization. On the day of discharge, follow-up heart rate variability, routine blood tests, cardiac biomarkers, high-sensitivity C-reactive protein (hs-CRP) level, and N-terminal pro b-type natriuretic peptide (NT-pro BNP) level will be assessed. Four weeks after discharge, hs-CRP, NT-pro BNP, heart failure symptoms, quality of life, and a pattern identification questionnaire will be used for follow-up analysis. Six months after discharge, major cardiac adverse events and cardiac function measured by echocardiography will be assessed. Adverse events will be recorded during every visit. The result of this clinical trial will offer evidence of the effectiveness and safety of electroacupuncture for acute decompensated heart failure. Clinical Research Information Service: KCT0002249 .

Assessing barriers to a rational chemoprevention trial design in young patients with familial adenomatous polyposis.

PubMed

Wood, Joanna P; Howells, Lynne M; Brown, Karen; Thomas, Anne L

2017-07-01

Familial adenomatous polyposis coli (FAP) is an autosomal dominant condition caused by a germline mutation in the adenomatous polyposis coli gene. Colonic adenomas form and almost all patients will develop colorectal cancer if they are not managed at an early stage. The safest preventive strategy is surgical resection of the colon, most commonly performed in late teenage years. There is a paucity of trials investigating the use of primary chemoprevention to delay polyp formation in paediatric FAP. There are extensive preclinical and early clinical data demonstrating that curcumin may be a safe and effective chemotherapeutic agent in reducing the polyp burden in this disease. We ultimately proposed to design and conduct a clinical study to assess whether curcumin treatment delays the need for surgery and/or prevents cancer in young patients with FAP. Research into clinical trial protocols has demonstrated that assessing patients' perceptions at the initial stage leads to better outcomes. We therefore conducted a questionnaire study of patients and parents of children affected by FAP to gain information to aid the protocol design. Results demonstrated that there are some FAP patients for whom this study is relevant and desirable. Those with a personal history of curcumin use reported that it was well tolerated. However, the response rate was poor (25%), indicating that there are potential difficulties ensuring adequate recruitment to the proposed trial. This report draws on lessons learnt from prior trials and the findings from the questionnaire to outline the challenges faced in designing such a study.

Feasibility and Efficacy of the Nintendo Wii Gaming System to Improve Balance Performance Post-Stroke: Protocol of a Phase II Randomized Controlled Trial in an Inpatient Rehabilitation Setting.

PubMed

Bower, Kelly J; Clark, Ross A; McGinley, Jennifer L; Martin, Clarissa L; Miller, Kimberly J

2013-04-01

Balance deficits following stroke are common and debilitating. Commercially available gaming systems, such as the Nintendo(®) (Kyoto, Japan) Wii™, have been widely adopted clinically; however, there is limited evidence supporting their feasibility and efficacy for improving balance performance following stroke. The aim of this trial is to investigate the clinical feasibility and efficacy of using the Nintendo Wii gaming system as an adjunct to standard care to improve balance performance following stroke in an inpatient rehabilitation setting. Thirty participants undergoing inpatient stroke rehabilitation will be recruited into this Phase II, single-blind, randomized controlled trial. Participants will be allocated into a Balance or Upper Limb Group, and both groups will perform activities using the Nintendo Wii in addition to their standard care. Participants will attend three 45-minute sessions per week, for a minimum of 2 and a maximum of 4 weeks. The main focus of the study is to investigate the feasibility of the intervention protocol. This will be evaluated through recruitment, retention, adherence, acceptability, and safety. The Step Test and Functional Reach Test will be the primary efficacy outcomes. Secondary outcomes will include force platform, mobility, and upper limb measures. Assessments will occur at baseline, 2 weeks, and 4 weeks after study entry. To the authors' knowledge, this will be the largest randomized clinical trial to investigate the feasibility and efficacy of the Nintendo Wii gaming system for improving balance performance in a stroke population. The results will inform the design of a Phase III multicenter trial.

Cognitive and adaptive measurement endpoints for clinical trials in mucopolysaccharidoses types I, II, and III: A review of the literature.

PubMed

Janzen, Darren; Delaney, Kathleen A; Shapiro, Elsa G

2017-06-01

Sensitive, reliable measurement instruments are critical for the evaluation of disease progression and new treatments that affect the brain in the mucopolysaccharidoses (MPS). MPS I, II, and III have early onset clinical phenotypes that affect the brain during development and result in devastating cognitive decline and ultimately death without treatment. Comparisons of outcomes are hindered by diverse protocols and approaches to assessment including applicability to international trials necessary in rare diseases. We review both cognitive and adaptive measures with the goal of providing evidence to a Delphi panel to come to a consensus about recommendations for clinical trials for various age groups. The results of the consensus panel are reported in an accompanying article. The following data were gathered (from internet resources and from test manuals) for each measure and summarized in the discussion: reliability, validity, date and adequacy of normative data, applicability of the measure's metrics, cross cultural validity including translations and adaptations, feasibility in the MPS population, familiarity to sites, sensitivity to change, and interpretability. If, resulting from this consensus, standard protocols are used for both natural history and treatment studies, patients, their families, and health care providers will benefit from the ability to compare study outcomes. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Neck-specific training with a cognitive behavioural approach compared with prescribed physical activity in patients with cervical radiculopathy: a protocol of a prospective randomised clinical trial.

PubMed

Dedering, Åsa; Halvorsen, Marie; Cleland, Joshua; Svensson, Mikael; Peolsson, Anneli

2014-08-12

Patients with cervical radiculopathy often have neck- and arm pain, neurological changes, activity limitations and difficulties in returning to work. Most patients are not candidates for surgery but are often treated with different conservative approaches and may be sick-listed for long periods. The purpose of the current study is to compare the effectiveness of neck-specific training versus prescribed physical activity. The current protocol is a two armed intervention randomised clinical trial comparing the outcomes of patients receiving neck specific training or prescribed physical activity. A total of 144 patients with cervical radiculopathy will be randomly allocated to either of the two interventions. The interventions will be delivered by experienced physiotherapists and last 14 weeks. The primary outcome variable is neck- and arm pain intensity measured with a Visual Analogue Scale accompanied with secondary outcome measures of impairments and subjective health measurements collected before intervention and at 3, 6, 12 and 24 months after base-line assessment. We anticipate that the results of this study will provide evidence to support recommendations as to the effectiveness of conservative interventions for patients with cervical radiculopathy. ClinicalTrials.gov identifier: NCT01831271.

The implementation and adherence to evidence-based protocols for psychotherapy for depression: the perspective of therapists in Dutch specialized mental healthcare.

PubMed

Bruijniks, Sanne J E; Franx, Gerdien; Huibers, Marcus J H

2018-06-14

Although psychotherapy is an effective treatment for depression, a large number of patients still do not receive care according to the protocols that are used in clinical trials. Instead, patients often receive a modified version of the original intervention. It is not clear how and when treatment protocols are used or modified in the Dutch specialized mental health care and whether these changes lead to suboptimal adherence to treatment protocols. In the context of an ongoing multicenter trial that investigates whether twice-weekly sessions of protocolized interpersonal psychotherapy (IPT) and cognitive behavioral therapy (CBT) for depression lead to better treatment outcomes compared to once-weekly sessions, two focus groups using semi-structured interviews were organized. Aims were to increase insight in the adherence to and modifications of CBT and IPT protocols in the Dutch specialized mental health care for depression. Participants were fifteen therapists from seven mental health locations part of five mental health organizations. Verbatim transcripts were coded and analyzed using qualitative software. Three themes emerged: modification as the common practice, professional and patient factors influencing the adherence to protocols and organizational boundaries and flexibility. Treatment modification appeared to happen on a frequent basis, even in the context of a trial. Definitions of treatment modifications were multiple and varied from using intuition to flexible use of the same protocol. Therapist training and supervision, the years of work experience and individual characteristics of the therapist and the patient were mentioned to influence the adherence to protocols. Modifications of the therapists depended very much on the culture within the mental health locations, who differed in terms of the flexibility offered to therapists to choose and modify treatment protocols. Not all treatment modifications were in line with existing evidence or guidelines. Regular supervision, team meetings and a shared vision were identified as crucial factors to increase adherence to treatment protocols, whereas additional organizational factors, among which a change of mindset, may facilitate adequate implementation.

Tolerance in Nonhuman Primates by Delayed Mixed Chimerism

DTIC Science & Technology

2017-12-01

person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control ...induction of mixed chimerism in a non -human primate (NHP) model. This approach, in contrast to protocols which have already reached clinical trials...principle of delayed induction of mixed chimerism in a non -human primate (NHP) model. This approach, in contrast to protocols which have already reached

The OPERA trial: a protocol for the process evaluation of a randomised trial of an exercise intervention for older people in residential and nursing accommodation

PubMed Central

2011-01-01

Background The OPERA trial is large cluster randomised trial testing a physical activity intervention to address depression amongst people living in nursing and residential homes for older people. A process evaluation was commissioned alongside the trial and we report the protocol for this process evaluation. Challenges included the cognitive and physical ability of the participants, the need to respect the privacy of all home residents, including study non-participants, and the physical structure of the homes. Evaluation activity had to be organised around the structured timetable of homes, leaving limited opportunities for data collection. The aims of this process evaluation are to provide findings that will assist in the interpretation of the clinical trial results, and to inform potential implementation of the physical activity intervention on a wider scale. Methods/design Quantitative data on recruitment of homes and individuals is being collected. For homes in the intervention arm, data on dose and fidelity of the intervention delivered; including individual rates of participation in exercise classes are collected. In the control homes, uptake and delivery of depression awareness training is monitored. These data will be combined with qualitative data from an in-depth study of a purposive sample of eight homes (six intervention and two control). Discussion Although process evaluations are increasingly funded alongside trials, it is still rare to see the findings published, and even rarer to see the protocol for such an evaluation published. Process evaluations have the potential to assist in interpreting and understanding trial results as well as informing future roll-outs of interventions. If such evaluations are funded they should also be reported and reviewed in a similar way to the trial outcome evaluation. Trial Registration ISRCTN No: ISRCTN43769277 PMID:21288341

Chewing gum for the treatment of postoperative nausea and vomiting: a pilot randomized controlled trial.

PubMed

Darvall, J N; Handscombe, M; Leslie, K

2017-01-01

A novel treatment, chewing gum, may be non-inferior to ondansetron in inhibiting postoperative nausea and vomiting (PONV) in female patients after laparoscopic or breast surgery. In this pilot study, we tested the feasibility of a large randomized controlled trial. We randomized 94 female patients undergoing laparoscopic or breast surgery to ondansetron 4 mg i.v. or chewing gum if PONV was experienced in the postanaesthesia care unit (PACU). The primary outcome was full resolution of PONV, with non-inferiority defined as a difference between groups of <15% in a per protocol analysis. Secondary outcomes were PACU stay duration, anti-emetic rescue use, and acceptability of anti-emetic treatment. The feasibility of implementing the protocol in a larger trial was assessed. Postoperative nausea and vomiting in the PACU occurred in 13 (28%) ondansetron patients and 15 (31%) chewing gum patients (P=0.75). Three chewing gum patients could not chew gum when they developed PONV. On a per protocol basis, full resolution of PONV occurred in five of 13 (39%) ondansetron vs nine of 12 (75%) chewing gum patients [risk difference 37% (6.3-67%), P=0.07]. There was no difference in secondary outcomes between groups. Recruitment was satisfactory, the protocol was acceptable to anaesthetists and nurses, and data collection was complete. In this pilot trial, chewing gum was not inferior to ondansetron for treatment of PONV after general anaesthesia for laparoscopic or breast surgery in female patients. Our findings demonstrate the feasibility of a larger, multicentred randomized controlled trial to investigate this novel therapy. Australian New Zealand Clinical Trials Registry: ACTRN12615001327572. © The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.

PubMed

Brittain, Clare; Childs, Margaret; Duley, Lelia; Harding, Jan; Hepburn, Trish; Meakin, Garry; Montgomery, Alan A; Tan, Wei; Ross, Jonathan D C

2016-11-24

Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea. This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness. The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate whether gentamicin is not clinically worse than ceftriaxone for the treatment of gonorrhoea. This will inform clinical practice and policy for the treatment of gonorrhoea when current therapy with cephalosporins is no longer effective, or is contraindicated. International Standard Randomised Controlled Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol version 2.0 17 June 2015.

Exploring barriers and facilitators to participation of male-to-female transgender persons in preventive HIV vaccine clinical trials.

PubMed

Andrasik, Michele Peake; Yoon, Ro; Mooney, Jessica; Broder, Gail; Bolton, Marcus; Votto, Teress; Davis-Vogel, Annet

2014-06-01

Observed seroincidence and prevalence rates in male-to-female (MTF) transgender individuals highlight the need for effective targeted HIV prevention strategies for this community. In order to develop an effective vaccine that can be used by transgender women, researchers must understand and address existing structural issues that present barriers to this group's participation in HIV vaccine clinical trials. Overcoming barriers to participation is important for ensuring HIV vaccine acceptability and efficacy for the MTF transgender community. To explore barriers and facilitators to MTF transgender participation in preventive HIV vaccine clinical trials, the HIV Vaccine Trials Network conducted focus groups among transgender women in four urban areas (Atlanta, Boston, Philadelphia, and San Francisco). Barriers and facilitators to engagement of transgender women in preventive HIV vaccine clinical trials led to the following recommendations: (a) transgender cultural competency training, (b) creating trans-friendly environments, (c) true partnerships with local trans-friendly organizations and health care providers, (d) protocols that focus on transgender specific issues, and (e) data collection and tracking of transgender individuals. These results have implications for the conduct of HIV vaccine trials, as well as engagement of transgender women in research programs in general.

Strengthening the reliability and credibility of observational epidemiology studies by creating an Observational Studies Register.

PubMed

Swaen, Gerard M H; Carmichael, Neil; Doe, John

2011-05-01

To evaluate the need for the creation of a system in which observational epidemiology studies are registered; an Observational Studies Register (OSR). The current scientific process for observational epidemiology studies is described. Next, a parallel is made with the clinical trials area, where the creation of clinical trial registers has greatly restored and improved their credibility and reliability. Next, the advantages and disadvantages of an OSR are compared. The advantages of an OSR outweigh its disadvantages. The creation of an OSR, similar to the existing Clinical Trials Registers, will improve the assessment of publication bias and will provide an opportunity to compare the original study protocol with the results reported in the publication. Reliability, credibility, and transparency of observational epidemiology studies are strengthened by the creation of an OSR. We propose a structured, collaborative, and coordinated approach for observational epidemiology studies that can provide solutions for existing weaknesses and will strengthen credibility and reliability, similar to the approach currently used in clinical trials, where Clinical Trials Registers have played a key role in strengthening their scientific value. Copyright © 2011 Elsevier Inc. All rights reserved.

Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials.

PubMed

Larson, Gregg S; Carey, Cate; Grarup, Jesper; Hudson, Fleur; Sachi, Karen; Vjecha, Michael J; Gordin, Fred

2016-04-01

Randomized clinical trials are widely recognized as essential to address worldwide clinical and public health research questions. However, their size and duration can overwhelm available public and private resources. To remain competitive in international research settings, advocates and practitioners of clinical trials must implement practices that reduce their cost. We identify approaches and practices for large, publicly funded, international trials that reduce cost without compromising data integrity and recommend an approach to cost reporting that permits comparison of clinical trials. We describe the organizational and financial characteristics of The International Network for Strategic Initiatives in Global HIV Trials, an infectious disease research network that conducts multiple, large, long-term, international trials, and examine challenges associated with simple and streamlined governance and an infrastructure and financial management model that is based on performance, transparency, and accountability. It is possible to reduce costs of participants' follow-up and not compromise clinical trial quality or integrity. The International Network for Strategic Initiatives in Global HIV Trials network has successfully completed three large HIV trials using cost-efficient practices that have not adversely affected investigator enthusiasm, accrual rates, loss-to-follow-up, adherence to the protocol, and completion of data collection. This experience is relevant to the conduct of large, publicly funded trials in other disease areas, particularly trials dependent on international collaborations. New approaches, or creative adaption of traditional clinical trial infrastructure and financial management tools, can render large, international clinical trials more cost-efficient by emphasizing structural simplicity, minimal up-front costs, payments for performance, and uniform algorithms and fees-for-service, irrespective of location. However, challenges remain. They include institutional resistance to financial change, growing trial complexity, and the difficulty of sustaining network infrastructure absent stable research work. There is also a need for more central monitoring, improved and harmonized regulations, and a widely applied metric for measuring and comparing cost efficiency in clinical trials. ClinicalTrials.gov is recommended as a location where standardized trial cost information could be made publicly accessible. © The Author(s) 2016.

Combining novel technologies with improved logistics to reduce hemodialysis vascular access dysfunction.

PubMed

Roy-Chaudhury, P; Lee, T; Duncan, H; El-Khatib, M

2009-01-01

Hemodialysis (HD) vascular access dysfunction is currently a huge clinical problem for which there are no effective therapies. There are, however, a number of promising technologies that are currently at the experimental or clinical trial stage. We believe that the application of these novel technologies in combination with better clinical protocols for vascular access care could significantly reduce the current problems associated with HD vascular access.

The role and potential contribution of clinical research nurses to clinical trials.

PubMed

Spilsbury, Karen; Petherick, Emily; Cullum, Nicky; Nelson, Andrea; Nixon, Jane; Mason, Su

2008-02-01

This study explores the scope and potential contribution of the Clinical Research Nurse (CRN) role to clinical trials of a nursing-specific topic. Over the past two decades, there have been increases in the numbers of nurses working as CRNs because of the increasing global demand for clinical trials. CRNs can influence the quality of clinical trials but the scope and contribution of the role to clinical trials is not known. Qualitative focus group study. A focus group interview was carried out with CRNs (n = 9) employed on a large, multi-centre (six NHS Trusts) randomized controlled trial of pressure area care. The focus group interview was recorded, alongside field notes of participant interactions and behaviours, and transcribed verbatim. Data were analysed for thematic content and process. CRNs described their transition to a clinical research role. They reported a lack of confidence, role conflict as researcher and nurse, the challenges of gaining cooperation of clinical nursing staff to comply with trial protocols and difficulties maintaining their own motivation. CRNs provided their perceptions and observations of pressure area care and prevention. They identified areas of inadequate treatment, management and care, influenced by organizational and clinical aspects of care delivery. The study reveals challenges associated with training and management of CRNs. CRNs are usually associated with trial recruitment and data collection. This study highlights the additional contributions of CRNs for the study of topics specific to nursing as the result of their unique placement in the research centres as informal 'participant observers.' Such observations enhance understanding of the contexts being studied. These findings are relevant to the design and conduct of research studies of nursing care and practice and present ways for investigators to optimize the skills and knowledge of nurses working as CRNs.

What Do We Really Know About the Safety of Tai Chi?: A Systematic Review of Adverse Event Reports in Randomized Trials

PubMed Central

Wayne, Peter M.; Berkowitz, Danielle L.; Litrownik, Daniel E.; Buring, Julie E.; Yeh, Gloria Y.

2014-01-01

Objective Systematically review frequency and quality of adverse event (AE) reports in randomized clinical trials (RCTs) of Tai Chi (TC). Data Sources Electronic searches of PubMed/MEDLINE and additional databases from inception through March 2013 of English-language RCTs. Search terms were tai chi, taiji, tai chi chuan. Data were independently extracted by two investigators. Study Selection We included all available randomized controlled trials (RCTs) that were published in English and used Tai Chi as an intervention. Inclusion and exclusion of studies were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data Extraction Eligible RCTs were categorized with respect to AE reporting: 1) No mention of protocols for monitoring AEs or reports of AEs; 2) Reports of AEs either with or without explicit protocols for monitoring AEs. Data Synthesis 153 eligible RCTs were identified, most targeting older adults. Only 50 eligible trials (33%) included reporting of AEs, and of these, only 18 trials (12% overall) also reported an explicit AE monitoring protocol. Protocols varied with respect to rigor of systematic monitoring in both Tai Chi and comparison groups. Reported AEs were typically minor and expected, and primarily musculoskeletal related (e.g., knee and back pain); no intervention-related serious AEs were reported. Conclusions Tai Chi is unlikely to result in serious adverse events, but may be associated with minor musculoskeletal aches and pains. However, poor and inconsistent reporting of AEs greatly limits the conclusions that can be drawn regarding the safety of Tai Chi. PMID:24878398

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments

PubMed Central

2011-01-01

Background No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes - the "sentinel lesion approach". Methods/design MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Results Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. Conclusions In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS - the sentinel lesion approach - serving as proof of principle for its future wider applicability. Trial registration ClinicalTrials.gov (NCT00395200). PMID:21366911

Acupuncture for patients with functional dyspepsia: study protocol of a randomised controlled trial

PubMed Central

Zheng, Hui; Xu, Jing; Li, Juan; Li, Xiang; Zhao, Ling; Chang, Xiaorong; Liu, Mi; Gong, Biao; Li, Xuezhi; Liang, Fanrong

2013-01-01

Introduction Whether acupuncture is efficacious for patients with functional dyspepsia is still controversial. So we designed a randomised controlled trial to settle the problem. Methods and analysis We designed a multicentre, two-arm, sham-controlled clinical trial. 200 participants with functional dyspepsia will be randomly assigned to the true acupuncture (TA) group and sham acupuncture (SA) group in a 1:1 ratio. Participants in the TA group will receive acupuncture at points selected according to syndrome differentiation. Participants in the sham acupuncture group will receive penetrations at sham points. Participants in both groups will receive 20 sessions of electroacupuncture in 4 weeks, five times continuously with a 2 day rest in a week. The primary outcome is the proportion of patients reporting the absence of dyspeptic symptoms at 16 weeks after inclusion. The secondary outcome includes a Short-Form Leeds Dyspepsia Questionnaire, the Chinese version of the 36-Item Short Form Survey, the Chinese version of the Nepean dyspepsia index, etc. Ethics and dissemination The study protocol has been approved by the institutional review boards and ethics committees of the first affiliated hospital of Chengdu University of TCM, the first affiliated hospital of Hunan University of TCM and Chongqing Medical University, respectively (from April to August 2012). The results of this trial will be disseminated in a peer-reviewed journal and presented at international congresses. Trials registration ClinicalTrials.gov NCT01671670. PMID:23901030

Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects: The PROMOTE Study Protocol.

PubMed

Hensel, Kendi L; Carnes, Michael S; Stoll, Scott T

2016-11-01

The structural and physiologic changes in a woman's body during pregnancy can predispose pregnant women to low back pain and its associated disability, as well as to complications of pregnancy, labor, and delivery. Anecdotal and empirical evidence has indicated that osteopathic manipulative treatment (OMT) may be efficacious in improving pain and functionality in women who are pregnant. Based on that premise, the Pregnancy Research on Osteopathic Manipulation Optimizing Treatment Effects (PROMOTE) study was designed as a prospective, randomized, placebo-controlled, and blinded clinical trial to evaluate the efficacy of an OMT protocol for pain during third-trimester pregnancy. The OMT protocol developed for the PROMOTE study was based on physiologic theory and the concept of the interrelationship of structure and function. The 12 well-defined, standardized OMT techniques used in the protocol are commonly taught at osteopathic medical schools in the United States. These techniques can be easily replicated as a 20-minute protocol applied in conjunction with usual prenatal care, thus making it feasible to implement into clinical practice. This article presents an overview of the study design and treatment protocols used in the PROMOTE study.

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial – challenges, enablers and lessons learned

PubMed Central

Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard

2018-01-01

ABSTRACT A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research. PMID:29382251

Setting up a clinical trial for a novel disease: a case study of the Doxycycline for the Treatment of Nodding Syndrome Trial - challenges, enablers and lessons learned.

PubMed

Anguzu, Ronald; Akun, Pamela R; Ogwang, Rodney; Shour, Abdul Rahman; Sekibira, Rogers; Ningwa, Albert; Nakamya, Phellister; Abbo, Catherine; Mwaka, Amos D; Opar, Bernard; Idro, Richard

2018-01-01

A large amount of preparation goes into setting up trials. Different challenges and lessons are experienced. Our trial, testing a treatment for nodding syndrome, an acquired neurological disorder of unknown cause affecting thousands of children in Eastern Africa, provides a unique case study. As part of a study to determine the aetiology, understand pathogenesis and develop specific treatment, we set up a clinical trial in a remote district hospital in Uganda. This paper describes our experiences and documents supportive structures (enablers), challenges faced and lessons learned during set-up of the trial. Protocol development started in September 2015 with phased recruitment of a critical study team. The team spent 12 months preparing trial documents, procurement and training on procedures. Potential recruitment sites were pre-visited, and district and local leaders met as key stakeholders. Key enablers were supportive local leadership and investment by the district and Ministry of Health. The main challenges were community fears about nodding syndrome, adverse experiences of the community during previous research and political involvement. Other challenges included the number and delays in protocol approvals and lengthy procurement processes. This hard-to-reach area has frequent power and Internet fluctuations, which may affect cold chains for study samples, communication and data management. These concerns decreased with a pilot community engagement programme. Experiences and lessons learnt can reduce the duration of processes involved in trial-site set-up. A programme of community engagement and local leader involvement may be key to the success of a trial and in reducing community opposition towards participation in research.

Complementary religious and spiritual interventions in physical health and quality of life: A systematic review of randomized controlled clinical trials

PubMed Central

Lucchetti, Giancarlo; Menezes, Paulo Rossi; Vallada, Homero

2017-01-01

Objective To examine whether religious and spiritual interventions (RSIs) can promote physical health and quality of life in individuals. Methods The following databases were used to conduct a systematic review: PubMed, Scopus, Web of Science, EMBASE, PsycINFO, Cochrane, and Scielo. Randomized controlled trials that evaluated RSIs regarding physical health outcomes and/or quality of life in English, Spanish or Portuguese were included. RSI protocols performed at a distance (i.e. intercessory prayer) or for psychiatric disorders were excluded. This study consisted of two phases: (a) reading titles and abstracts, and (b) assessing the full articles and their methodological quality using the Cochrane Back Review Group scale. Results In total, 7,070 articles were identified in the search, but 6884 were excluded in phase 1 because they were off topic or repeated in databases. Among the 186 articles included in phase 2, 140 were excluded because they did not fit the inclusion criteria and 16 did not have adequate randomization process. Thus, a final selection of 30 articles remained. The participants of the selected studies were classified in three groups: chronic patients (e.g., cancer, obesity, pain), healthy individuals and healthcare professionals. The outcomes assessed included quality of life, physical activity, pain, cardiac outcomes, promotion of health behaviors, clinical practice of healthcare professionals and satisfaction with protocols. The divergence concerning scales and protocols proposed did not allow a meta-analysis. RSIs as a psychotherapy approach were performed in 40% of the studies, and the control group was more likely to use an educational intervention (56.7%). The results revealed small effect sizes favoring RSIs in quality of life and pain outcomes and very small effects sizes in physical activity, promotion of health behaviors and clinical practice of health professionals compared with other complementary strategies. Other outcomes, such as cardiac measures and satisfaction with the protocols, revealed no evidence for RSIs. Regarding the quality of the selected articles according to the Cochrane Back Review Group Scale, the average score was 6.83 (SD = 9.08) on a scale of 11, demonstrating robustness in the studies. Conclusion Clinical trials on RSIs demonstrated that they had small benefits compared with other complementary health therapies by reducing pain and weight, improving quality of life and promoting health behaviors. The lack of clinical trials that included biological outcomes and the diversity of approaches indicate a need for more studies to understand the possible mechanisms of action of RSIs and their roles in health care. PMID:29049421

Development of Strategies to Increase Enrollment in Clinical Trials for Children With Cancer

ClinicalTrials.gov

2014-02-12

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Extragonadal Germ Cell Tumor; Leukemia; Liver Cancer; Lymphoma; Neuroblastoma; Ovarian Cancer; Psychosocial Effects of Cancer and Its Treatment; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Percutaneous coronary intervention versus coronary artery bypass grafting: where are we after NOBLE and EXCEL?

PubMed

Fortier, Jacqueline H; Shaw, Richard E; Glineur, David; Grau, Juan B

2017-11-01

The publication of the NOBLE and EXCEL trials, with seemingly conflicting results, brought into question whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) is better for low-risk patients with left main coronary artery stenosis (LMCAS). This review appraises the methods and results of NOBLE and EXCEL, contextualizes them within the literature, and determines how they may affect clinical practice. We appraised the trials and describe differences in methodology and results. NOBLE recruited primarily isolated LMCAS, and found that CABG was superior to PCI. EXCEL's population included patients LMCAS in the context of multivessel CAD, and found PCI and CABG were comparable. Both trials enrolled young patients with few comorbidities, and there was more protocol-mandated consistency in the procedural techniques and medical therapy of patients receiving PCI. The generalizability of these trials is limited by the use of young, healthy patients at highly skilled centres that rarely reflect typical clinical practice. If these studies are to maintain relevance, trialists must address the lack of protocolization of surgical interventions and inconsistent medical therapies. Unfortunately, the limitations of NOBLE and EXCEL mean that we are no closer to answering the question of what is the optimal treatment for patients with LMCAS.

Behavioral Interventions to Prevent or Delay Dementia: Protocol for a Randomized Comparative Effectiveness Study

PubMed Central

Chandler, Melanie; Locke, Dona EC; Fields, Julie; Phatak, Vaishali; Crook, Julia; Hanna, Sherrie; Lunde, Angela; Morris, Miranda; Graff-Radford, Michelle; Hughes, Christine A; Lepore, Susan; Cuc, Andrea; Caselli, Maria; Hurst, Duane; Wethe, Jennifer; Francone, Andrea; Eilertsen, Jeanne; Lucas, Pauline; Hoffman Snyder, Charlene; Kuang, LeeAnn; Becker, Marigrace; Dean, Pamela; Diehl, Nancy; Lofquist, Marvin; Vanderhook, Shirley; Myles, Diana; Cochran, Denise

2017-01-01

Background Currently, people at risk for dementia and their caregivers are confronted with confusing choices about what behavioral interventions are most effective. Objective The objective of this study is to determine which empirically supported behavioral interventions most impact the outcomes highly valued by patients with mild cognitive impairment and their partners. Methods This protocol describes a comparative effectiveness trial targeting 300 participants with mild cognitive impairment and their study partners. The trial is being conducted at the Mayo Clinic campuses in Arizona, Florida, Minnesota, and the University of Washington in Seattle. The study examines the contribution of five behavioral interventions (yoga, memory compensation training, computerized cognitive training, support groups, and wellness education) on primary outcomes of participant and partner quality of life and self-efficacy. In this unique 10-day multicomponent intervention, groups of couples were randomized to have one of the five interventions withheld while receiving the other four. Although the longitudinal follow-up is still under way, enrollment results are available and reported. Results In total, 272 couples have been enrolled in the trial and follow-up visits continue. Outcomes will be assessed at the end-of-intervention and 6-, 12-, and 18-month follow-ups. We anticipate reporting on our primary and secondary outcomes across time points in the next 2 years. Conclusions This paper describes the protocol for a randomized comparative effectiveness study of behavioral interventions to prevent or delay dementia. We describe of the rationale, design, power analysis, and analysis plan. Also because enrollment is complete and we are in follow-up phases of the study, we have included enrollment data from the trial. Trial Registration  ClinicalTrials.gov NCT02265757; http://clinicaltrials.gov/ctsshow/ NCT02265757 (Archived by WebCite at http://www.webcitation.org/6ueRfwSYv) PMID:29180344

Immediate vs. delayed insertion of intrauterine contraception after second trimester abortion: study protocol for a randomized controlled trial

PubMed Central

2011-01-01

Background We describe the rationale and protocol for a randomized controlled trial (RCT) to assess whether intrauterine contraception placed immediately after a second trimester abortion will result in fewer pregnancies than current recommended practice of intended placement at 4 weeks post-abortion. Decision analysis suggests the novel strategy could substantially reduce subsequent unintended pregnancies and abortions. This paper highlights considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Methods/Design Consenting women choosing to use intrauterine contraception after abortion for a pregnancy of 12 to 24 weeks will be randomized to insertion timing groups either immediately (experimental intervention) or four weeks (recommended care) post abortion. Primary outcome measure is pregnancy rate at one year. Secondary outcomes include: cumulative pregnancy rates over five year follow-up period, comprehensive health economic analyses comparing immediate and delayed insertion groups, and device retention rates, complication rates (infection, expulsion) and, contraceptive method satisfaction. Web-based Contraception Satisfaction Questionnaires, clinical records and British Columbia linked health databases will be used to assess primary and secondary outcomes. Enrolment at all clinics in the province performing second trimester abortions began in May 2010 and is expected to complete in late 2011. Data on one year outcomes will be available for analysis in 2014. Discussion The RCT design combined with access to clinical records at all provincial abortion clinics, and to information in provincial single-payer linked administrative health databases, birth registry and hospital records, offers a unique opportunity to evaluate such an approach by determining pregnancy rate at one through five years among enrolled women. We highlight considerations of design, implementation and evaluation of a trial expected to provide rigorous evidence for appropriate insertion timing and health economics of intrauterine contraception after second trimester abortion. Trial registration Current Controlled Trials ISRCTN19506752 PMID:21672213

Rapamycin treatment for amyotrophic lateral sclerosis: Protocol for a phase II randomized, double-blind, placebo-controlled, multicenter, clinical trial (RAP-ALS trial).

PubMed

Mandrioli, Jessica; D'Amico, Roberto; Zucchi, Elisabetta; Gessani, Annalisa; Fini, Nicola; Fasano, Antonio; Caponnetto, Claudia; Chiò, Adriano; Dalla Bella, Eleonora; Lunetta, Christian; Mazzini, Letizia; Marinou, Kalliopi; Sorarù, Gianni; de Biasi, Sara; Lo Tartaro, Domenico; Pinti, Marcello; Cossarizza, Andrea

2018-06-01

Misfolded aggregated proteins and neuroinflammation significantly contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, hence representing therapeutic targets to modify disease expression. Rapamycin inhibits mechanistic target of Rapamycin (mTOR) pathway and enhances autophagy with demonstrated beneficial effects in neurodegeneration in cell line and animal models, improving phenotype in SQSTM1 zebrafish, in Drosophila model of ALS-TDP, and in the TDP43 mouse model, in which it reduced neuronal loss and TDP43 inclusions. Rapamycin also expands regulatory T lymphocytes (Treg) and increased Treg levels are associated with slow progression in ALS patients.Therefore, we planned a randomized clinical trial testing Rapamycin treatment in ALS patients. RAP-ALS is a phase II randomized, double-blind, placebo-controlled, multicenter (8 ALS centers in Italy), clinical trial. The primary aim is to assess whether Rapamycin administration increases Tregs number in treated patients compared with control arm. Secondary aims include the assessment of safety and tolerability of Rapamycin in patients with ALS; the minimum dosage to have Rapamycin in cerebrospinal fluid; changes in immunological (activation and homing of T, B, NK cell subpopulations) and inflammatory markers, and on mTOR downstream pathway (S6RP phosphorylation); clinical activity (ALS Functional Rating Scale-Revised, survival, forced vital capacity); and quality of life (ALSAQ40 scale). Rapamycin potentially targets mechanisms at play in ALS (i.e., autophagy and neuroinflammation), with promising preclinical studies. It is an already approved drug, with known pharmacokinetics, already available and therefore with significant possibility of rapid translation to daily clinics. Findings will provide reliable data for further potential trials. The study protocol was approved by the Ethics Committee of Azienda Ospedaliero Universitaria of Modena and by the Ethics Committees of participating centers (Eudract n. 2016-002399-28) based on the Helsinki declaration.

Acupuncture to Reduce HIV-Associated Inflammation

PubMed Central

Swanson, Barbara; Keithley, Joyce K.; Johnson, Angela; Fogg, Louis; Adeyemi, Oluwatoyin; Sha, Beverly E.; Snell, Kimberly A.

2015-01-01

Background. HIV infection is associated with systemic inflammation that can increase risk for cardiovascular events. Acupuncture has been shown to have immunomodulatory effects and to improve symptoms in persons with inflammatory conditions. Objective. To test the anti-inflammatory effects of an acupuncture protocol that targets the cholinergic anti-inflammatory pathway (CAIP), a neural mechanism whose activation has been shown to reduce the release of proinflammatory cytokines, in persons with HIV-associated inflammation. Design, Setting, Participants, and Interventions. Double-blind, placebo-controlled clinical trial conducted in an outpatient clinic located in a medically underserved urban neighborhood. Twenty-five clinically-stable HIV-infected persons on antiretroviral therapy were randomized to receive once weekly CAIP-based acupuncture or sham acupuncture. Main Outcome Measures. Outcomes included plasma concentrations of high sensitivity C-reactive protein and D-dimer and fasting lipids. Results. Twenty-five participants completed the protocol (treatment group n = 12, control group n = 13). No adverse events related to the acupuncture protocol were observed. Compared to baseline values, the two groups did not significantly differ in any outcome measures at the end of the acupuncture protocol. Conclusions. CAIP-based acupuncture did not favorably modulate inflammatory or lipid parameters. Additional studies are warranted of CAIP-based protocols of different frequencies/durations. PMID:25922615

Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial.

PubMed

Kaasch, Achim J; Fätkenheuer, Gerd; Prinz-Langenohl, Reinhild; Paulus, Ursula; Hellmich, Martin; Weiß, Verena; Jung, Norma; Rieg, Siegbert; Kern, Winfried V; Seifert, Harald

2015-10-09

Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. Methods/Design A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. Discussion The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index – normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed. PMID:24716713

Efficacy of pre-exercise low-level laser therapy on isokinetic muscle performance in individuals with type 2 diabetes mellitus: study protocol for a randomized controlled trial.

PubMed

Gomes, Cid André Fidelis de Paula; Leal-Junior, Ernesto Cesar Pinto; Biasotto-Gonzalez, Daniela Aparecida; El-Hage, Yasmin; Politti, Fabiano; Gonzalez, Tabajara de Oliveira; Dibai-Filho, Almir Vieira; de Oliveira, Adriano Rodrigues; Frigero, Marcelo; Antonialli, Fernanda Colella; Vanin, Adriane Aver; de Tarso Camillo de Carvalho, Paulo

2014-04-09

Type 2 diabetes, also known non-insulin-dependent diabetes, is the most prevalent type of the disease and involves defects in the secretion and action of insulin. The aim of the proposed study is to evaluate the efficacy of pre-exercise low-level laser therapy (LLLT) on muscle performance of the quadriceps femoris in individuals with type 2 diabetes. A double-blind, randomized, controlled clinical trial will be carried out in two treatment phases. In the first phase, quadriceps muscle performance will be evaluated using an isokinetic dynamometer and the levels of creatine kinase and lactate dehydrogenase (biochemical markers of muscle damage) will be determined. The participants will then be allocated to four LLLT groups through a randomization process using opaque envelopes: Group A (4 Joules), Group B (6 Joules), Group C (8 Joules) and Group D (0 Joules; placebo). Following the administration of LLLT, the participants will be submitted to an isokinetic eccentric muscle fatigue protocol involving the quadriceps muscle bilaterally. Muscle performance and biochemical markers of muscle damage will be evaluated again immediately after as well as 24 and 48 hours after the experimental protocol. One week after the last evaluation the second phase will begin, during which Groups A, B and C will receive the LLLT protocol that achieved the best muscle performance in phase 1 for a period of 4 weeks. At the end of this period, muscle performance will be evaluated again. The protocol for this study is registered with the World Health Organization under Universal Trial Number U1111-1146-7109. The purpose of this randomized clinical trial is to evaluate the efficacy of pre-exercise LLLT on the performance of the quadriceps muscle (peak torque, total muscle work, maximum power and fatigue index - normalized by body mass) in individuals with DM-2. The study will support the practice of evidence-based to the use of LLLT in improving muscle performance in Individuals with DM-2. Data will be published after the study is completed.

A Herbal Medicine, Gongjindan, in Subjects with Chronic Dizziness (GOODNESS Study): Study Protocol for a Prospective, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Clinical Trial for Effectiveness, Safety, and Cost-Effectiveness

PubMed Central

Kim, Jinyoung; Cho, Jae-Heung

2017-01-01

This study protocol aims to explore the effectiveness, safety, and cost-effectiveness of a herbal medication, Gongjindan (GJD), in patients with chronic dizziness. This will be a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-group, clinical trial. Seventy-eight patients diagnosed with Meniere's disease, psychogenic dizziness, or dizziness of unknown cause will be randomized and allocated to either a GJD or a placebo group in a 1 : 1 ratio. Participants will be orally given 3.75 g GJD or placebo in pill form once a day for 56 days. The primary outcome measure will be the Dizziness Handicap Inventory score. Secondary outcome measures will be as follows: severity (mean vertigo scale and visual analogue scale) and frequency of dizziness, balance function (Berg Balance Scale), fatigue (Fatigue Severity Scale) and deficiency pattern/syndrome (qi blood yin yang-deficiency questionnaire) levels, and depression (Korean version of Beck's Depression Inventory) and anxiety (State-Trait Anxiety Inventory) levels. To assess safety, adverse events, including laboratory test results, will be monitored. Further, the incremental cost-effectiveness ratio will be calculated based on quality-adjusted life years (from the EuroQoL five dimensions' questionnaire) and medical expenses. Data will be statistically analyzed at a significance level of 0.05 (two-sided). This trial is registered with ClinicalTrials.gov NCT03219515, in July 2017. PMID:29387128

The use of autologous platelet-rich plasma in the orthopedic setting.

PubMed

Cohn, Claudia S; Lockhart, Evelyn; McCullough, J Jeffrey

2015-07-01

Autologous platelet-rich plasma (aPRP) is widely used with orthopedic patients to help treat injuries to tendons, cartilage, ligaments, and muscle. A comprehensive review of the literature was conducted to evaluate aPRP's efficacy and compare available methods. In addition, the production and administration of aPRP were explored. A literature search was performed. Randomized controlled clinical trials (RCTs) in orthopedic procedures on adult patients were included and assessed for methodologic quality. The main outcomes were pain relief, increase in function, structural integrity, and "healing" based on various validated scales. Twelve RCTs and one controlled cohort were included (four lateral epicondylitis, two chronic Achilles tendinopathy, two anterior cruciate ligament injury, and five rotator cuff injuries). Four trials reported some benefit from aPRP versus controls while eight trials found no benefit from aPRP applications versus control. One study had too many patients withdraw from the control arm for acceptable data interpretation. All protocols used a different aPRP formulation or method of delivery or application. Despite its popularity, there are no standardized criteria that define aPRP. Different techniques yield wide variability in terms of platelet count and concentration. These variations make it difficult to compare clinical trials that use aPRP or draw conclusions concerning its clinical efficacy in orthopedic procedures. Blood bankers have experience in the production of standardized blood components. This expertise may be used to develop and implement protocols for the production and administration of aPRP, as well as quality control measures. © 2015 AABB.

The NAPRESSIM trial: the use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine in elective hepatobiliary surgery: a study protocol and statistical analysis plan for a randomised controlled trial.

PubMed

Cosgrave, David; Galligan, Marie; Soukhin, Era; McMullan, Victoria; McGuinness, Siobhan; Puttappa, Anand; Conlon, Niamh; Boylan, John; Hussain, Rabia; Doran, Peter; Nichol, Alistair

2017-12-29

Intrathecally administered morphine is effective as part of a postoperative analgesia regimen following major hepatopancreaticobiliary surgery. However, the potential for postoperative respiratory depression at the doses required for effective analgesia currently limits its clinical use. The use of a low-dose, prophylactic naloxone infusion following intrathecally administered morphine may significantly reduce postoperative respiratory depression. The NAPRESSIM trial aims to answer this question. 'The use of low-dose, prophylactic naloxone infusion to prevent respiratory depression with intrathecally administered morphine' trial is an investigator-led, single-centre, randomised, double-blind, placebo-controlled, double-arm comparator study. The trial will recruit 96 patients aged > 18 years, undergoing major open hepatopancreaticobiliary resections, who are receiving intrathecally administered morphine as part of a standard anaesthetic regimen. It aims to investigate whether the prophylactic administration of naloxone via intravenous infusion compared to placebo will reduce the proportion of episodes of respiratory depression in this cohort of patients. Trial patients will receive an infusion of naloxone or placebo, commenced within 1 h of postoperative extubation continued until the first postoperative morning. The primary outcome is the rate of respiratory depression in the intervention group as compared to the placebo group. Secondary outcomes include pain scores, rates of nausea and vomiting, pruritus, sedation scores and adverse outcomes. We will also employ a novel, non-invasive, respiratory minute volume monitor (ExSpiron 1Xi, Respiratory Motion, Inc., 411 Waverley Oaks Road, Building 1, Suite 150, Waltham, MA, USA) to assess the monitor's accuracy for detecting respiratory depression. The trial aims to provide a clear management plan to prevent respiratory depression after the intrathecal administration of morphine, and thereby improve patient safety. ClinicalTrials.gov, ID: NCT02885948 . Registered retrospectively on 4 July 2016. Protocol Version 2.0, 3 April 2017. Protocol identification (code or reference number): UCDCRC/15/006 EudraCT registration number: 2015-003504-22. Registered on 5 August 2015.

Effectiveness of De Qi during acupuncture for the treatment of tinnitus: study protocol for a randomized controlled trial.

PubMed

Xie, Hui; Li, Xinrong; Lai, Jiaqin; Zhou, Yanan; Wang, Caiying; Liang, Jiao

2014-10-15

Acupuncture has been used in China to treat tinnitus for a long time. There is debate as to whether or not De Qi is a key factor in achieving the efficacy of acupuncture. However, there is no sufficient evidence obtained from randomized controlled trials to confirm the role of De Qi in the treatment of acupuncture for tinnitus. This study aims to identify the effect of De Qi for patients who receive acupuncture to alleviate tinnitus by a prospective, double-blind, randomized, sham-controlled trial. This study compares two acupuncture groups (with or without manipulation) in 292 patients with a history of subjective tinnitus. The trial will be conducted in the Teaching Hospital of Chengdu University of Traditional Chinese Medicine. In the study, the patients will be randomly assigned into two groups according to a computer-generated randomization list and assessed prior to treatment. Then, they will receive 5 daily sessions of 30 minutes each time for 4 consecutive weeks and undergo a 12-week follow-up phase. The administration of acupuncture follows the guidelines for clinical research on acupuncture (WHO Regional Publication, Western Pacific Series Number 15, 1995), and is performed double-blind by physicians well-trained in acupuncture. The measures of outcome include the subjective symptoms scores and quantitative sensations of De Qi evaluated by Visual Analog Scales (VAS) and the Chinese version of the 'modified' Massachusetts General Hospital Acupuncture Sensation Scale (C-MMASS). Furthermore, adverse events are recorded and analyzed. If any subjects are withdrawn from the trial, intention-to-treat analysis (ITT) and per-protocol (PP) analysis will be performed. The key features of this trial include the randomization procedures, large sample and the standardized protocol to evaluate De Qi qualitatively and quantitatively in the treatment of acupuncture for tinnitus. The trial will be the first study with a high evidence level in China to assess the efficacy of De Qi in the treatment of tinnitus in a randomized, double-blind, sham-controlled manner. Chinese Clinical Trial Registry: ChiCTR-TRC-14004720 (6 May 2014).

Finnish Degenerative Meniscal Lesion Study (FIDELITY): a protocol for a randomised, placebo surgery controlled trial on the efficacy of arthroscopic partial meniscectomy for patients with degenerative meniscus injury with a novel ‘RCT within-a-cohort’ study design

PubMed Central

Sihvonen, Raine; Paavola, Mika; Malmivaara, Antti; Järvinen, Teppo L N

2013-01-01

Introduction Arthroscopic partial meniscectomy (APM) to treat degenerative meniscus injury is the most common orthopaedic procedure. However, valid evidence of the efficacy of APM is lacking. Controlling for the placebo effect of any medical intervention is important, but seems particularly pertinent for the assessment of APM, as the symptoms commonly attributed to a degenerative meniscal injury (medial joint line symptoms and perceived disability) are subjective and display considerable fluctuation, and accordingly difficult to gauge objectively. Methods and analysis A multicentre, parallel randomised, placebo surgery controlled trial is being carried out to assess the efficacy of APM for patients from 35 to 65 years of age with a degenerative meniscus injury. Patients with degenerative medial meniscus tear and medial joint line symptoms, without clinical or radiographic osteoarthritis of the index knee, were enrolled and then randomly assigned (1 : 1) to either APM or diagnostic arthroscopy (placebo surgery). Patients are followed up for 12 months. According to the prior power calculation, 140 patients were randomised. The two randomised patient groups will be compared at 12 months with intention-to-treat analysis. To safeguard against bias, patients, healthcare providers, data collectors, data analysts, outcome adjudicators and the researchers interpreting the findings will be blind to the patients’ interventions (APM/placebo). Primary outcomes are Lysholm knee score (a generic knee instrument), knee pain (using a numerical rating scale), and WOMET score (a disease-specific, health-related quality of life index). The secondary outcome is 15D (a generic quality of life instrument). Further, in one of the five centres recruiting patients for the randomised controlled trial (RCT), all patients scheduled for knee arthroscopy due to a degenerative meniscus injury are prospectively followed up using the same protocol as in the RCT to provide an external validation cohort. In this article, we present and discuss our study design, focusing particularly on the internal and external validity of our trial and the ethics of carrying out a placebo surgery controlled trial. Ethics and dissemination The protocol has been approved by the institutional review board of the Pirkanmaa Hospital District and the trial has been duly registered at ClinicalTrials.gov. The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. Trial registration ClinicalTrials.gov, number NCT00549172. PMID:23474796

Institutional mistrust in the organization of pharmaceutical clinical trials

PubMed Central

2010-01-01

In this paper I explore the politics of trust in the clinical testing of pharmaceuticals in the US. Specifically, I analyze trust in terms of its institutional manifestations in the pharmaceutical clinical trials industry. In the process of testing new drugs, pharmaceutical companies must (1) protect their proprietary information from the clinicians who conduct their studies, and (2) find a way to ensure human subjects' compliance to study protocols. Concern with these two critical issues leads drug companies to approach clinicians and research subjects with an attitude of mistrust and the desire to exert control over their activities. This orientation results in an institutionalization of mistrust that structures the relationships and activities required for the clinical development of new pharmaceutical products. PMID:18633728

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

Treatment of Adolescent Marijuana Abuse: A Randomized Clinical Trial. Presentation 1: Structure of the Cannabis Youth Treatment Study.

ERIC Educational Resources Information Center

Titus, Janet C.; Dennis, Michael L.; Diamond, Guy; Godley, Susan H.; Babor, Thomas; Donaldson, Jean; Herrell, James; Tims, Frank; Webb, Charles

The Cannabis Youth Treatment (CYT) study is a multi-site randomized field experiment examining five outpatient treatment protocols for adolescents who abuse or are dependent on marijuana. The purpose of the CYT project is twofold: (a) to test the relative clinical effectiveness and cost-effectiveness of five promising interventions targeted at…

University of Washington Prostate Cancer Clinical Trials Consortium Application

DTIC Science & Technology

2011-04-01

13-25 Appendix 1: Protocol Evaluation Form Appendix 2: Community Symposia Flyer Appendix 3: Publications...Network Affiliate partners in the community . These and selected local practices receive quarterly correspondence that reviews our open clinical...studies: 09-002 (COU 301), 09-003 (AFFIRM), 09-004 (S0421), 09-005 (COU 302), 09-006 (doc dasatinib). Task 3. Maintain Communications with Consortium

Stem cells in bone diseases: current clinical practice.

PubMed

Beyth, Shaul; Schroeder, Josh; Liebergall, Meir

2011-01-01

Bone is an obvious candidate tissue for stem cell therapy. This review provides an update of existing stem cell-based clinical treatments for bone pathologies. A systematic computerized literature search was conducted. The following databases were accessed on 10 February 2011: NIH clinical trials database, PubMed, Ovid and Cochrane Reviews. Stem cell therapy offers new options for bone conditions, both acquired and inherited. There is still no agreement on the exact definition of 'mesenchymal stem cells'. Consequently, it is difficult to appreciate the effect of culture expansion and the feasibility of allogeneic transplantation. Based on the sound foundations of pre-clinical research, stem cell-based treatments and protocols have recently emerged. Well-designed prospective clinical trials are needed in order to establish and develop stem cell therapy for bone diseases.

Short structured general mental health in service training programme in Kenya improves patient health and social outcomes but not detection of mental health problems - a pragmatic cluster randomised controlled trial

PubMed Central

2013-01-01

Trial design A pragmatic cluster randomised controlled trial. Methods Participants: Clusters were primary health care clinics on the Ministry of Health list. Clients were eligible if they were aged 18 and over. Interventions: Two members of staff from each intervention clinic received the training programme. Clients in both intervention and control clinics subsequently received normal routine care from their health workers. Objective: To examine the impact of a mental health inservice training on routine detection of mental disorder in the clinics and on client outcomes. Outcomes: The primary outcome was the rate of accurate routine clinic detection of mental disorder and the secondary outcome was client recovery over a twelve week follow up period. Randomisation: clinics were randomised to intervention and control groups using a table of random numbers. Blinding: researchers and clients were blind to group assignment. Results Numbers randomised: 49 and 50 clinics were assigned to intervention and control groups respectively. 12 GHQ positive clients per clinic were identified for follow up. Numbers analysed: 468 and 478 clients were followed up for three months in intervention and control groups respectively. Outcome: At twelve weeks after training of the intervention group, the rate of accurate routine clinic detection of mental disorder was greater than 0 in 5% versus 0% of the intervention and control groups respectively, in both the intention to treat analysis (p = 0.50) and the per protocol analysis (p =0.50). Standardised effect sizes for client improvement were 0.34 (95% CI = (0.01,0.68)) for the General Health Questionnaire, 0.39 ((95% CI = (0.22, 0.61)) for the EQ and 0.49 (95% CI = (0.11,0.87)) for WHODAS (using ITT analysis); and 0.43 (95% CI = (0.09,0.76)) for the GHQ, 0.44 (95% CI = (0.22,0.65)) for the EQ and 0.58 (95% CI = (0.18,0.97)) for WHODAS (using per protocol analysis). Harms: None identified. Conclusion The training programme did not result in significantly improved recorded diagnostic rates of mental disorders in the routine clinic consultation register, but did have significant effects on patient outcomes in routine clinical practice. Trial registration International Standard Randomised Controlled Trial Number Register ISRCTN53515024. PMID:24188964

The limits of evidence in drug approval and availability: a case study of cilostazol and naftidrofuryl for the treatment of intermittent claudication.

PubMed

Hong, Haeyeon; Mackey, William C

2014-08-01

Despite numerous efforts to develop effective medications for the treatment of intermittent claudication (IC) over the past 4 decades, a gold standard medical management option has yet to be defined. Although not life-threatening, IC interferes with mobility and activities of daily living, significantly impairing quality of life and potentially causing depression. Cilostazol, the leading pharmacologic agent for IC in the United States, was approved by the US Food and Drug Administration (FDA) in 1999 based on controversial data. Meanwhile, naftidrofuryl, the first-line pharmacologic agent for IC in the United Kingdom and Europe, has never been approved by the FDA and therefore is not available in the United States. The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect impossible. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted, because the manufacturers of these agents have much to lose and little to gain from such a study. This article provides an overview of the pharmacology of cilostazol and naftidrofuryl, and the clinical studies leading to their approval and clinical acceptance. It further explores the possible sources of bias in analyzing these clinical trials, some of which have been brought to light by the National Institute for Health and Clinical Excellence (NICE) of the United Kingdom in its technology appraisal guidance. It also speculates the ways in which economic incentives may affect drug-marketing decisions. A literature review of pharmacology and clinical trials for cilostazol and naftidrofuryl was performed in PubMed. The majority of included clinical trials were initially identified through the most recent Cochrane review articles as well as the FDA's approval packet for cilostazol. The technology appraisal guidance of the National Institute for Health and Care Excellence of the United Kingdom and the manufacturer's response to this guidance document were located via an online search engine. The clinical data for cilostazol and naftidrofuryl are plagued by flaws related to lack of protocol standardization, objective endpoints, and strict eligibility criteria in study subjects, making identification of a true treatment effect difficult. Furthermore, no prospective randomized trial comparing the efficacy of cilostazol and naftidrofuryl has been conducted. The history of the evaluation, approval, and marketing of these drugs illustrates the limitations of data in the regulatory approval and marketing of agents whose benefit is subjective and difficult to quantify. Implementation of a standardized protocol with strict eligibility criteria, objective quantifiable measurement of drug effect, and validated endpoints will eventually allow development of an ideal pharmacotherapy for IC. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial

PubMed Central

Stergiopoulos, Stella; Calvert, Sara B; Brown, Carrie A; Awatin, Josephine; Tenaerts, Pamela; Holland, Thomas L; DiMasi, Joseph A; Getz, Kenneth A

2018-01-01

Abstract Background Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs. PMID:29020279

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial.

PubMed

Giesbrecht, Edward M; Miller, William C; Eng, Janice J; Mitchell, Ian M; Woodgate, Roberta L; Goldsmith, Charles H

2013-10-24

Many older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial. A 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life. The EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model for wheelchair skills training has great potential for clinical uptake and opportunity for future enhancements. Theory-driven design can foster learning and adherence for older adults. Establishing the feasibility of the study protocol and estimating effect size for the primary clinical outcome measure will be used to develop a multi-site randomized controlled trial to test the guiding hypotheses. Clinical Trials NCT01740635.

MRI of penile fracture: what should be a tailored protocol in emergency?

PubMed

Esposito, Andrea Alessandro; Giannitto, Caterina; Muzzupappa, Claudia; Maccagnoni, Sara; Gadda, Franco; Albo, Giancarlo; Biondetti, Pietro Raimondo

2016-09-01

To conduct a review of literature to summarize the existing MRI protocols for penile trauma, suggesting a tailored protocol to reduce costs and time of examination. A systematic search was performed in Medline, Embase, Cochrane Library, and Cinahl databases from 1995 to 2015 to identify studies evaluating penis trauma with MRI examination. Studies were included if there was the description of MRI protocol with at least sequences and orthogonal planes used. We chose a systematic approach for data extraction and descriptive synthesis. 12 articles were included in our study. Among the list of 12 articles: 2 were case reports, 3 were clinical series, and 7 were reviews. Clinical trials were not found. There is no unanimous consensus among the authors. Summarizing the data, the most used protocol is characterized by T2 sequences in three orthogonal planes plus T1 sequences in one plane (either axial or sagittal) without contrast medium injection. There is a lack of a standard protocol. A tailored protocol to answer the diagnostic question, reducing costs and time of examination, is characterized by T2 sequences in three orthogonal planes plus at least a T1 sequence (either axial or sagittal plane).

Safety study and characterization of E1A-liposome complex gene-delivery protocol in an ovarian cancer model.

PubMed

Xing, X; Zhang, S; Chang, J Y; Tucker, S D; Chen, H; Huang, L; Hung, M C

1998-11-01

A phase I clinical trial of E1A-liposome complex is currently ongoing in patients with HER-2/neu-overexpressing breast or ovarian cancers. To optimize the E1A-liposome complex for a further stage of clinical trial, several aspects of the current protocol have been examined in an animal model. In the orthotopic ovarian cancer model, different doses of lipid in the the E1A-liposome complex, which is currently used in clinical trials, were tested for the in vivo gene-transfer efficacy and tumor-suppression function. A lowered lipid dose--1/13 of the previous amount--produced gene expression level and E1A tumor-suppression efficacy similar to that of the original protocol. Mini-E1A, an E1A construct without its immortalization domain and yet capable of repressing HER-2/neu, was proved to be as potent as E1A in suppressing tumor development in vivo. These changes in the E1A-liposome complex will significantly reduce any potential adverse effects caused by lipid vector and E1A DNA. To examine further whether residual E1A DNA may still exist in normal organs after the E1A-liposome treatment, PCR was used to detect E1A DNA in mice that survived for 1 1/2 years after the last treatment. E1A DNA was detected only in the lungs and kidneys, but not in livers, hearts, spleens, brains, uterus or the ovaries. Furthermore, resistance of the E1A DNA extracted from tissues to the digestion of Dpnl restriction enzyme, which can cleave the methylated E1A plasmid DNA generated by methylation-competent bacteria, suggested integration of E1A DNA into the chromosome of the lungs and kidneys. Experimental results presented here provide important information for safety concerns and for the design of future phase II and phase III trials.

Strategies for ensuring quality data from Indian investigational sites

PubMed Central

Hajos, Antal K.; Kamble, Sujal K.

2011-01-01

The topic of ensuring quality and compliance is and must be a top priority in the conduct of clinical trials, as warranted by regulatory guidelines as well as the inherent responsibility of the professionals conducting such research. Fast-growing emerging clinical geographies such as India demand special attention due to rapid growth and associated factors that may put study quality at risk. In this paper, we used the basic principle of PDCA (Plan, Do, Check, and Adjust) to structure the processes of a clinical trial from protocol to final analysis in order to highlight the interactive nature of involved people and processes required to ensure quality of data and site functioning. PMID:21731855

Multicenter Clinical Trial of Keratin Biomaterials for Peripheral Nerve Regeneration

DTIC Science & Technology

2013-10-01

As soon as the IND is available, our team will be able to obtain final approval for the study protocol from the Copernicus Group, an independent... Copernicus Group, an independent IRB located in Research Triangle Park, North Carolina. Due to the conflict of interest policies at the Wake Forest...School of Medicine, Dr. Li was asked to send the protocol to an independent review board.  October 13, 2010: The Copernicus Group granted conditional

Perspective: Recommendations for benchmarking pre-clinical studies of nanomedicines

PubMed Central

Dawidczyk, Charlene M.; Russell, Luisa M.; Searson, Peter C.

2015-01-01

Nanoparticle-based delivery systems provide new opportunities to overcome the limitations associated with traditional small molecule drug therapy for cancer, and to achieve both therapeutic and diagnostic functions in the same platform. Pre-clinical trials are generally designed to assess therapeutic potential and not to optimize the design of the delivery platform. Consequently, progress in developing design rules for cancer nanomedicines has been slow, hindering progress in the field. Despite the large number of pre-clinical trials, several factors restrict comparison and benchmarking of different platforms, including variability in experimental design, reporting of results, and the lack of quantitative data. To solve this problem, we review the variables involved in the design of pre-clinical trials and propose a protocol for benchmarking that we recommend be included in in vivo pre-clinical studies of drug delivery platforms for cancer therapy. This strategy will contribute to building the scientific knowledge base that enables development of design rules and accelerates the translation of new technologies. PMID:26249177

Absorbed dose-to-water protocol applied to synchrotron-generated x-rays at very high dose rates

NASA Astrophysics Data System (ADS)

Fournier, P.; Crosbie, J. C.; Cornelius, I.; Berkvens, P.; Donzelli, M.; Clavel, A. H.; Rosenfeld, A. B.; Petasecca, M.; Lerch, M. L. F.; Bräuer-Krisch, E.

2016-07-01

Microbeam radiation therapy (MRT) is a new radiation treatment modality in the pre-clinical stage of development at the ID17 Biomedical Beamline of the European synchrotron radiation facility (ESRF) in Grenoble, France. MRT exploits the dose volume effect that is made possible through the spatial fractionation of the high dose rate synchrotron-generated x-ray beam into an array of microbeams. As an important step towards the development of a dosimetry protocol for MRT, we have applied the International Atomic Energy Agency’s TRS 398 absorbed dose-to-water protocol to the synchrotron x-ray beam in the case of the broad beam irradiation geometry (i.e. prior to spatial fractionation into microbeams). The very high dose rates observed here mean the ion recombination correction factor, k s , is the most challenging to quantify of all the necessary corrections to apply for ionization chamber based absolute dosimetry. In the course of this study, we have developed a new method, the so called ‘current ramping’ method, to determine k s for the specific irradiation and filtering conditions typically utilized throughout the development of MRT. Using the new approach we deduced an ion recombination correction factor of 1.047 for the maximum ESRF storage ring current (200 mA) under typical beam spectral filtering conditions in MRT. MRT trials are currently underway with veterinary patients at the ESRF that require additional filtering, and we have estimated a correction factor of 1.025 for these filtration conditions for the same ESRF storage ring current. The protocol described herein provides reference dosimetry data for the associated Treatment Planning System utilized in the current veterinary trials and anticipated future human clinical trials.

Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification.

PubMed

Stephens, John R; Liles, E Allen; Dancel, Ria; Gilchrist, Michael; Kirsch, Jonathan; DeWalt, Darren A

2014-04-01

Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates. To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol's implementation. Review of best evidence by ad hoc task force and subsequent creation of standardized protocol. Prospective observational evaluation of initial protocol implementation. Patients presenting for alcohol detoxification. Development and implementation of a protocol for evaluation and treatment of patients requesting alcohol detoxification. Number of admissions per month with primary alcohol related diagnosis (DRG), 30-day readmission rate, and length of stay, all measured before and after protocol implementation. We identified one randomized clinical trial and three cohort studies to inform the choice of inpatient versus outpatient detoxification, along with one prior protocol in this population, and combined that data with clinical experience to create an institutional protocol. After implementation, the average number of alcohol related admissions was 15.9 per month, compared with 18.9 per month before implementation (p = 0.037). There was no difference in readmission rate or length of stay. Creation and utilization of a protocol led to standardization of care for patients requesting detoxification from alcohol. Initial evaluation of protocol implementation showed a decrease in number of admissions.

Using electronic health records for clinical research: the case of the EHR4CR project.

PubMed

De Moor, Georges; Sundgren, Mats; Kalra, Dipak; Schmidt, Andreas; Dugas, Martin; Claerhout, Brecht; Karakoyun, Töresin; Ohmann, Christian; Lastic, Pierre-Yves; Ammour, Nadir; Kush, Rebecca; Dupont, Danielle; Cuggia, Marc; Daniel, Christel; Thienpont, Geert; Coorevits, Pascal

2015-02-01

To describe the IMI EHR4CR project which is designing and developing, and aims to demonstrate, a scalable, widely acceptable and efficient approach to interoperability between EHR systems and clinical research systems. The IMI EHR4CR project is combining and extending several previously isolated state-of-the-art technical components through a new approach to develop a platform for reusing EHR data to support medical research. This will be achieved through multiple but unified initiatives across different major disease areas (e.g. cardiovascular, cancer) and clinical research use cases (protocol feasibility, patient identification and recruitment, clinical trial execution and serious adverse event reporting), with various local and national stakeholders across several countries and therefore under various legal frameworks. An initial instance of the platform has been built, providing communication, security and terminology services to the eleven participating hospitals and ten pharmaceutical companies located in seven European countries. Proof-of-concept demonstrators have been built and evaluated for the protocol feasibility and patient recruitment scenarios. The specifications of the clinical trial execution and the adverse event reporting scenarios have been documented and reviewed. Through a combination of a consortium that brings collectively many years of experience from previous relevant EU projects and of the global conduct of clinical trials, of an approach to ethics that engages many important stakeholders across Europe to ensure acceptability, of a robust iterative design methodology for the platform services that is anchored on requirements of an underlying Service Oriented Architecture that has been designed to be scalable and adaptable, EHR4CR could be well placed to deliver a sound, useful and well accepted pan-European solution for the reuse of hospital EHR data to support clinical research studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Credentialing of radiotherapy centres in Australasia for TROG 09.02 (Chisel), a Phase III clinical trial on stereotactic ablative body radiotherapy of early stage lung cancer.

PubMed

Kron, Tomas; Chesson, Brent; Hardcastle, Nicholas; Crain, Melissa; Clements, Natalie; Burns, Mark; Ball, David

2018-05-01

A randomised clinical trial comparing stereotactic ablative body radiotherapy (SABR) with conventional radiotherapy for early stage lung cancer has been conducted in Australia and New Zealand under the auspices of the TransTasman Radiation Oncology Group (NCT01014130). We report on the technical credentialing program as prerequisite for centres joining the trial. Participating centres were asked to develop treatment plans for two test cases to assess their ability to create plans according to protocol. Dose delivery in the presence of inhomogeneity and motion was assessed during a site visit using a phantom with moving inserts. Site visits for the trial were conducted in 16 Australian and 3 New Zealand radiotherapy facilities. The tests with low density inhomogeneities confirmed shortcomings of the AAA algorithm for dose calculation. Dose was assessed for a typical treatment delivery including at least one non-coplanar beam in a stationary and moving phantom. This end-to-end test confirmed that all participating centres were able to deliver stereotactic ablative body radiotherapy with the required accuracy while the planning study demonstrated that they were able to produce acceptable plans for both test cases. The credentialing process documented that participating centres were able to deliver dose as required in the trial protocol. It also gave an opportunity to provide education about the trial and discuss technical issues such as four-dimensional CT, small field dosimetry and patient immobilisation with staff in participating centres. Advances in knowledge: Credentialing is an important quality assurance tool for radiotherapy trials using advanced technology. In addition to confirming technical competence, it provides an opportunity for education and discussion about the trial.

A protocol for the Hamilton Rating Scale for Depression: Item scoring rules, Rater training, and outcome accuracy with data on its application in a clinical trial.

PubMed

Rohan, Kelly J; Rough, Jennifer N; Evans, Maggie; Ho, Sheau-Yan; Meyerhoff, Jonah; Roberts, Lorinda M; Vacek, Pamela M

2016-08-01

We present a fully articulated protocol for the Hamilton Rating Scale for Depression (HAM-D), including item scoring rules, rater training procedures, and a data management algorithm to increase accuracy of scores prior to outcome analyses. The latter involves identifying potentially inaccurate scores as interviews with discrepancies between two independent raters on the basis of either scores >=5-point difference) or meeting threshold for depression recurrence status, a long-term treatment outcome with public health significance. Discrepancies are resolved by assigning two new raters, identifying items with disagreement per an algorithm, and reaching consensus on the most accurate scores for those items. These methods were applied in a clinical trial where the primary outcome was the Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder version (SIGH-SAD), which includes the 21-item HAM-D and 8 items assessing atypical symptoms. 177 seasonally depressed adult patients were enrolled and interviewed at 10 time points across treatment and the 2-year followup interval for a total of 1589 completed interviews with 1535 (96.6%) archived. Inter-rater reliability ranged from ICCs of .923-.967. Only 86 (5.6%) interviews met criteria for a between-rater discrepancy. HAM-D items "Depressed Mood", "Work and Activities", "Middle Insomnia", and "Hypochondriasis" and Atypical items "Fatigability" and "Hypersomnia" contributed most to discrepancies. Generalizability beyond well-trained, experienced raters in a clinical trial is unknown. Researchers might want to consider adopting this protocol in part or full. Clinicians might want to tailor it to their needs. Copyright © 2016 Elsevier B.V. All rights reserved.

EON: a component-based approach to automation of protocol-directed therapy.

PubMed Central

Musen, M A; Tu, S W; Das, A K; Shahar, Y

1996-01-01

Provision of automated support for planning protocol-directed therapy requires a computer program to take as input clinical data stored in an electronic patient-record system and to generate as output recommendations for therapeutic interventions and laboratory testing that are defined by applicable protocols. This paper presents a synthesis of research carried out at Stanford University to model the therapy-planning task and to demonstrate a component-based architecture for building protocol-based decision-support systems. We have constructed general-purpose software components that (1) interpret abstract protocol specifications to construct appropriate patient-specific treatment plans; (2) infer from time-stamped patient data higher-level, interval-based, abstract concepts; (3) perform time-oriented queries on a time-oriented patient database; and (4) allow acquisition and maintenance of protocol knowledge in a manner that facilitates efficient processing both by humans and by computers. We have implemented these components in a computer system known as EON. Each of the components has been developed, evaluated, and reported independently. We have evaluated the integration of the components as a composite architecture by implementing T-HELPER, a computer-based patient-record system that uses EON to offer advice regarding the management of patients who are following clinical trial protocols for AIDS or HIV infection. A test of the reuse of the software components in a different clinical domain demonstrated rapid development of a prototype application to support protocol-based care of patients who have breast cancer. PMID:8930854

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial.

PubMed

Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske; Géczi, Lajos; Hotte, Sebastien J; Mainwaring, Paul N; Saad, Fred; Souza, Ciro; Tay, Miah H; Garrido, José M Tello; Galli, Luca; Londhe, Anil; De Porre, Peter; Goon, Betty; Lee, Emma; McGowan, Tracy; Naini, Vahid; Todd, Mary B; Molina, Arturo; George, Daniel J

2014-10-01

In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. We did a multicentre, open-label, early-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time to clinical progression) were gathered to guide treatment decisions. We included in our analysis all patients who received at least one dose of abiraterone acetate. This study is registered with ClinicalTrials.gov, number NCT01217697. Between Nov 17, 2010, and Sept 30, 2013, 2314 patients were enrolled into the early-access protocol trial. Median follow-up was 5·7 months (IQR 3·5-10·6). 952 (41%) patients had a grade 3 or 4 treatment-related adverse event, and grade 3 or 4 serious adverse events were recorded in 585 (25%) people. The most common grade 3 and 4 adverse events were hepatotoxicity (188 [8%]), hypertension (99 [4%]), cardiac disorders (52 [2%]), osteoporosis (31 [1%]), hypokalaemia (28 [1%]), and fluid retention or oedema (23 [1%]). 172 (7%) patients discontinued the study because of adverse events (64 [3%] were drug-related), as assessed by the investigator, and 171 (7%) people died. The funder assessed causes of death, which were due to disease progression (85 [4%]), an unrelated adverse experience (72 [3%]), and unknown reasons (14 [1%]). Of the 86 deaths not attributable to disease progression, 18 (<1%) were caused by a drug-related adverse event, as assessed by the investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes. Janssen Research & Development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Study protocol for "Study of Practices Enabling Implementation and Adaptation in the Safety Net (SPREAD-NET)": a pragmatic trial comparing implementation strategies.

PubMed

Gold, Rachel; Hollombe, Celine; Bunce, Arwen; Nelson, Christine; Davis, James V; Cowburn, Stuart; Perrin, Nancy; DeVoe, Jennifer; Mossman, Ned; Boles, Bruce; Horberg, Michael; Dearing, James W; Jaworski, Victoria; Cohen, Deborah; Smith, David

2015-10-16

Little research has directly compared the effectiveness of implementation strategies in any setting, and we know of no prior trials directly comparing how effectively different combinations of strategies support implementation in community health centers. This paper outlines the protocol of the Study of Practices Enabling Implementation and Adaptation in the Safety Net (SPREAD-NET), a trial designed to compare the effectiveness of several common strategies for supporting implementation of an intervention and explore contextual factors that impact the strategies' effectiveness in the community health center setting. This cluster-randomized trial compares how three increasingly hands-on implementation strategies support adoption of an evidence-based diabetes quality improvement intervention in 29 community health centers, managed by 12 healthcare organizations. The strategies are as follows: (arm 1) a toolkit, presented in paper and electronic form, which includes a training webinar; (arm 2) toolkit plus in-person training with a focus on practice change and change management strategies; and (arm 3) toolkit, in-person training, plus practice facilitation with on-site visits. We use a mixed methods approach to data collection and analysis: (i) baseline surveys on study clinic characteristics, to explore how these characteristics impact the clinics' ability to implement the tools and the effectiveness of each implementation strategy; (ii) quantitative data on change in rates of guideline-concordant prescribing; and (iii) qualitative data on the "how" and "why" underlying the quantitative results. The outcomes of interest are clinic-level results, categorized using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, within an interrupted time-series design with segmented regression models. This pragmatic trial will compare how well each implementation strategy works in "real-world" practices. Having a better understanding of how different strategies support implementation efforts could positively impact the field of implementation science, by comparing practical, generalizable methods for implementing clinical innovations in community health centers. Bridging this gap in the literature is a critical step towards the national long-term goal of effectively disseminating and implementing effective interventions into community health centers. ClinicalTrials.gov, NCT02325531.

[Declaration of the Chilean Academy of Medicine of Law 20.850 "On clinical trials of pharmaceutical products and medical devices" and of the bylaw that will regulate its application].

PubMed

López, Gloría; Valdés, Gloría; Roessler, Emilio; Valdivieso, Vicente

2017-04-01

In Chile, high cost treatments required by selected medical conditions are financed by the State, according to Law 20.850. A bylaw under discussion by the Senate regulates clinical trials, posing complex issues that will endanger local interest in front-line research: 1) The exclusive and mandatory control bestowed to the Institute of Public Health during all stages of the trials and also the surveillance of institutions performing clinical trials, overriding their Clinical Research Review Boards; 2) The 10 year period during which any adverse event is assumed to have been caused by the medication or devise evaluated by the trial, unless the contrary is proven in a judicial process; 3) Individuals submitted to the trials are entitled to free post trial access to the treatment received during the study, financed by the trial supporting entities and as long as the drug or devise is considered to be useful. While agreeing with the need to have a National Registry of Clinical Trials, we predict that the mentioned critical issues in the bylaw will lead to difficulties and unnecessary judicial processes, thus limiting clinicians' interest in performing research. We propose to modify the bylaw, excluding responsibilities on events associated with the natural evolution of the medical condition, with patients' ageing or with comorbidities and clinical events considered unpredictable when the protocol was accepted. We recommend that the free post trial access should be a joint decision involving the patient and the attending physician, taking in consideration that the volunteer has been exposed to risks and burdens, or when discontinuation of treatment entails a vital risk until the treatment under study has been approved and becomes available in the national market.

Internet-based intervention programme for obese adolescents and their families (Next.Step): research protocol of a controlled trial.

PubMed

Sousa, Pedro; Fonseca, Helena; Gaspar, Pedro; Gaspar, Filomena

2014-04-01

This paper describes the design and rationale of a controlled trial that aims to determine the effectiveness of an intervention programme in which the internet is used. Adolescent obesity is a major health problem, there being urgency to find effective interventions that induce behavioural change. The inclusion of the internet in the intervention may improve adolescents' adherence to the weight management programme and lead to adoption of healthier lifestyles. A clinical trial with a control group (non-randomized). Participants are adolescents with appointments at a paediatric obesity clinic (Portugal). Sample size was calculated according to the power analysis. The experimental group will follow the standard treatment protocol and receive free access to the e-therapeutic platform. The control group will follow the standard treatment protocol and join a waiting list. Intervention length will be 36 weeks (24 weeks of direct intervention with a follow-up for 12 weeks). This study was approved by the Ethical Committee for Health (Lisbon, Portugal) in January 2012 and funded by the Foundation for Science and Technology (Portugal) in December 2012. The results of this research will promote reflection on new approaches directed to treat adolescent obesity and on the promotion of healthy behaviours. We expect to gather empirical evidence of the intervention programme effectiveness. The expectations lie on the population health gains, empowerment in decision-making and adoption of healthier lifestyles. © 2013 John Wiley & Sons Ltd.

Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients (POPPI): protocol for a cluster-randomised clinical trial of a complex intervention

PubMed Central

Richards-Belle, Alvin; Mouncey, Paul R; Wade, Dorothy; Brewin, Chris R; Emerson, Lydia M; Grieve, Richard; Harrison, David A; Harvey, Sheila; Howell, David; Mythen, Monty; Sadique, Zia; Smyth, Deborah; Weinman, John; Welch, John; Rowan, Kathryn M

2018-01-01

Introduction Acute psychological stress, as well as unusual experiences including hallucinations and delusions, are common in critical care unit patients and have been linked to post-critical care psychological morbidity such as post-traumatic stress disorder (PTSD), depression and anxiety. Little high-quality research has been conducted to evaluate psychological interventions that could alleviate longer-term psychological morbidity in the critical care unit setting. Our research team developed and piloted a nurse-led psychological intervention, aimed at reducing patient-reported PTSD symptom severity and other adverse psychological outcomes at 6 months, for evaluation in the POPPI trial. Methods and analysis This is a multicentre, parallel group, cluster-randomised clinical trial with a staggered roll-out of the intervention. The trial is being carried out at 24 (12 intervention, 12 control) NHS adult, general, critical care units in the UK and is evaluating the clinical effectiveness and cost-effectiveness of a nurse-led preventative psychological intervention in reducing patient-reported PTSD symptom severity and other psychological morbidity at 6 months. All sites deliver usual care for 5 months (baseline period). Intervention group sites are then trained to carry out the POPPI intervention, and transition to delivering the intervention for the rest of the recruitment period. Control group sites deliver usual care for the duration of the recruitment period. The trial also includes a process evaluation conducted independently of the trial team. Ethics and dissemination This protocol was reviewed and approved by the National Research Ethics Service South Central - Oxford B Research Ethics Committee (reference: 15/SC/0287). The first patient was recruited in September 2015 and results will be disseminated in 2018. The results will be presented at national and international conferences and published in peer reviewed medical journals. Trial registration number ISRCTN53448131; Pre-results. PMID:29439083

Feasibility of the Enhancing Participation In the Community by improving Wheelchair Skills (EPIC Wheels) program: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background Many older adults rely on a manual wheelchair for mobility but typically receive little, if any, training on how to use their wheelchair effectively and independently. Standardized skill training is an effective intervention, but limited access to clinician trainers is a substantive barrier. Enhancing Participation in the Community by Improving Wheelchair Skills (EPIC Wheels) is a 1-month monitored home training program for improving mobility skills in older novice manual wheelchair users, integrating principles from andragogy and social cognitive theory. The purpose of this study is to determine whether feasibility indicators and primary clinical outcome measures of the EPIC Wheels program are sufficiently robust to justify conducting a subsequent multi-site randomized controlled trial. Methods A 2 × 2 factorial randomized controlled trial at two sites will compare improvement in wheelchair mobility skills between an EPIC Wheels treatment group and a computer-game control group, with additional wheelchair use introduced as a second factor. A total of 40 community-dwelling manual wheelchair users at least 55 years old and living in two Canadian metropolitan cities (n = 20 × 2) will be recruited. Feasibility indicators related to study process, resources, management, and treatment issues will be collected during data collection and at the end of the study period, and evaluated against proposed criteria. Clinical outcome measures will be collected at baseline (pre-randomization) and post-intervention. The primary clinical outcome measure is wheelchair skill capacity, as determined by the Wheelchair Skills Test, version 4.1. Secondary clinical outcome measures include wheelchair skill safety, satisfaction with performance, wheelchair confidence, life-space mobility, divided-attention, and health-related quality of life. Discussion The EPIC Wheels training program offers several innovative features. The convenient, portable, economical, and adaptable tablet-based, home program model for wheelchair skills training has great potential for clinical uptake and opportunity for future enhancements. Theory-driven design can foster learning and adherence for older adults. Establishing the feasibility of the study protocol and estimating effect size for the primary clinical outcome measure will be used to develop a multi-site randomized controlled trial to test the guiding hypotheses. Trial registration Clinical Trials NCT01740635. PMID:24156396

Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2.

PubMed

Jack, Clifford R; Barnes, Josephine; Bernstein, Matt A; Borowski, Bret J; Brewer, James; Clegg, Shona; Dale, Anders M; Carmichael, Owen; Ching, Christopher; DeCarli, Charles; Desikan, Rahul S; Fennema-Notestine, Christine; Fjell, Anders M; Fletcher, Evan; Fox, Nick C; Gunter, Jeff; Gutman, Boris A; Holland, Dominic; Hua, Xue; Insel, Philip; Kantarci, Kejal; Killiany, Ron J; Krueger, Gunnar; Leung, Kelvin K; Mackin, Scott; Maillard, Pauline; Malone, Ian B; Mattsson, Niklas; McEvoy, Linda; Modat, Marc; Mueller, Susanne; Nosheny, Rachel; Ourselin, Sebastien; Schuff, Norbert; Senjem, Matthew L; Simonson, Alix; Thompson, Paul M; Rettmann, Dan; Vemuri, Prashanthi; Walhovd, Kristine; Zhao, Yansong; Zuk, Samantha; Weiner, Michael

2015-07-01

Alzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders. We review the contributions of the MRI core from present and past cycles of ADNI (ADNI-1, -Grand Opportunity and -2). We also review plans for the future-ADNI-3. Contributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials. Over the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Granulocyte-colony stimulating factor in the prevention of postoperative infectious complications and sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). Protocol for a controlled clinical trial developed by consensus of an international study group. Part two: design of the study.

PubMed

Bauhofer, A; Lorenz, W; Stinner, B; Rothmund, M; Koller, M; Sitter, H; Celik, I; Farndon, J R; Fingerhut, A; Hay, J M; Lefering, R; Lorijn, R; Nyström, P O; Schäfer, H; Schein, M; Solomkin, J; Troidl, H; Volk, H D; Wittmann, D H; Wyatt, J

2001-04-01

Presentation of a new type of a study protocol for evaluation of the effectiveness of an immune modifier (rhG-CSF, filgrastim): prevention of postoperative infectious complications and of sub-optimal recovery from operation in patients with colorectal cancer and increased preoperative risk (ASA 3 and 4). This part describes the design of the randomised, placebo controlled, double-blinded, single-centre study performed at an university hospital (n = 40 patients for each group). The trial design includes the following elements for a prototype protocol: * The study population is restricted to patients with colorectal cancer, including a left sided resection and an increased perioperative risk (ASA 3 and 4). * Patients are allocated by random to the control or treatment group. * The double blinding strategy of the trial is assessed by psychometric indices. * An endpoint construct with quality of life (EORTC QLQ-C30) and a recovery index (modified Mc Peek index) are used as primary endpoints. Qualitative analysis of clinical relevance of the endpoints is performed by both patients and doctors. * Statistical analysis uses an area under the curve (AUC) model for improvement of quality of life on leaving hospital and two and six months after operation. A confirmatory statistical model with quality of life as the first primary endpoint in the hierarchic test procedure is used. Expectations of patients and surgeons and the negative affect are analysed by social psychological scales. This study design differs from other trials on preoperative prophylaxis and postoperative recovery, and has been developed to try a new concept and avoid previous failures.

Tranexamic Acid versus Placebo to Prevent Blood Transfusion during Radical Cystectomy for Bladder Cancer (TACT): Study Protocol for a Randomized Controlled Trial.

PubMed

Breau, Rodney H; Lavallée, Luke T; Cnossen, Sonya; Witiuk, Kelsey; Cagiannos, Ilias; Momoli, Franco; Bryson, Gregory; Kanji, Salmaan; Morash, Christopher; Turgeon, Alexis; Zarychanski, Ryan; Mallick, Ranjeeta; Knoll, Greg; Fergusson, Dean A

2018-05-02

Radical cystectomy for bladder cancer is associated with a high risk of needing red blood cell transfusion. Tranexamic acid reduces blood loss during cardiac and orthopedic surgery, but no study has yet evaluated tranexamic acid use during cystectomy. A randomized, double-blind (surgeon-, anesthesiologist-, patient-, data-monitor-blinded), placebo-controlled trial of tranexamic acid during cystectomy was initiated in June 2013. Prior to incision, the intervention arm participants receive a 10 mg/kg loading dose of intravenously administered tranexamic acid, followed by a 5 mg/kg/h maintenance infusion. In the control arm, the patient receives an identical volume of normal saline that is indistinguishable from the intervention. The primary outcome is any blood transfusion from the start of surgery up to 30 days post operative. There are no strict criteria to mandate the transfusion of blood products. The decision to transfuse is entirely at the discretion of the treating physicians who are blinded to patient allocation. Physicians are allowed to utilize all resources to make transfusion decisions, including serum hemoglobin concentration and vital signs. To date, 147 patients of a planned 354 have been randomized to the study. This protocol reviews pertinent data relating to blood transfusion during radical cystectomy, highlighting the need to identify methods for reducing blood loss and preventing transfusion in patients receiving radical cystectomy. It explains the clinical rationale for using tranexamic acid to reduce blood loss during cystectomy, and outlines the study methods of our ongoing randomized controlled trial. Canadian Institute for Health Research (CIHR) Protocol: MOP-342559; ClinicalTrials.gov, ID: NCT01869413. Registered on 5 June 2013.

Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis: a systematic review.

PubMed

Bonnett, Laura Jayne; Ken-Dror, Gie; Davies, Geraint Rhys

2018-02-21

Despite more than 60 years of clinical trials, tuberculosis (TB) still causes a high global burden of mortality and morbidity. Treatment currently requires multiple drugs in combination, taken over a prolonged period. New drugs are needed to shorten treatment duration, prevent resistance and reduce adverse events. However, to improve on current methodology in drug development, a more complete understanding of the existing clinical evidence base is required. A systematic review was undertaken to summarise outcomes reported in phase III trials of patients with newly diagnosed pulmonary TB. A systematic search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. Of 248 included studies, 229 considered "on-treatment" outcomes whilst 148 reported "off-treatment" outcomes. There was wide variation and ambiguity in the definition of reported outcomes, including their relationship to treatment and in the time points evaluated. Additional challenges were observed regarding the analysis approach taken (per protocol versus intention to treat) and the varying durations of "intensive" and "continuation" phases of treatment. Bacteriological outcomes were most frequently reported but radiological and clinical data were often included as an implicit or explicit component of the overall definition of outcome. Terminology used to define long-term outcomes in phase III trials is inconsistent, reflecting evolving differences in protocols and practices. For successful future cumulative meta-analysis, the findings of this review suggest that greater availability of individual patient data and the development of a core outcome set would be desirable. In the meantime, we propose a simple and logical approach which should facilitate combination of key evidence and inform improvements in the methodology of TB drug development and clinical trials.

Evaluation of effect of low-level laser therapy on adolescents with temporomandibular disorder: study protocol for a randomized controlled trial

PubMed Central

2013-01-01

Background A number of problems involving the temporomandibular joint (TMJ) and associated structures can lead to temporomandibular disorder (TMD). The aim of the proposed study is to assess the effect of low-level laser therapy on occlusal contacts, mandibular movements, electromyography activity in the muscles of mastication and pain in adolescents with TMD. Methods/Design A randomized, controlled, double-blind, clinical trial will be carried out involving 85 male and female adolescents between 15 and 18 years of age. The research diagnostic criteria for TMD will be used to assess all individuals who agree to participate. All participants will be submitted to a clinical examination and electromyographic analysis of the masseter muscles and anterior bundle of the temporal muscles bilaterally, to determine TMD. Based on the clinical findings, the participants will be classified as having or not having TMD. Those with TMD will be divided into four groups, three of which will receive low-level laser therapy and one of which will receive a placebo treatment. The treatments will involve the TMJ region alone, the masseter and temporal muscles alone, or both these regions together. The data will be submitted to descriptive statistical analysis. The chi-square test and Fisher’s exact test will be used to determine associations among the categorical variables. The Student’s t test and analysis of variance will be used for the comparison of mean electromyographic signals. Pearson’s correlation coefficients will be calculated for the analysis of correlations among the continuous variables. Trial registration The protocol for this study has been submitted to Clinical Trials – registration number (NCT01846000). PMID:23876095

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials.

PubMed

Krishnan, Rahul; Ko, David; Foster, Clarence E; Liu, Wendy; Smink, A M; de Haan, Bart; De Vos, Paul; Lakey, Jonathan R T

2017-01-01

Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of significant parameters of bioencapsulation device design and manufacture (i.e., purification protocols, surface-modification grafting techniques, alginate composition modifications) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specific pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defining characteristics of the response itself.

LesionTracker: Extensible Open-Source Zero-Footprint Web Viewer for Cancer Imaging Research and Clinical Trials.

PubMed

Urban, Trinity; Ziegler, Erik; Lewis, Rob; Hafey, Chris; Sadow, Cheryl; Van den Abbeele, Annick D; Harris, Gordon J

2017-11-01

Oncology clinical trials have become increasingly dependent upon image-based surrogate endpoints for determining patient eligibility and treatment efficacy. As therapeutics have evolved and multiplied in number, the tumor metrics criteria used to characterize therapeutic response have become progressively more varied and complex. The growing intricacies of image-based response evaluation, together with rising expectations for rapid and consistent results reporting, make it difficult for site radiologists to adequately address local and multicenter imaging demands. These challenges demonstrate the need for advanced cancer imaging informatics tools that can help ensure protocol-compliant image evaluation while simultaneously promoting reviewer efficiency. LesionTracker is a quantitative imaging package optimized for oncology clinical trial workflows. The goal of the project is to create an open source zero-footprint viewer for image analysis that is designed to be extensible as well as capable of being integrated into third-party systems for advanced imaging tools and clinical trials informatics platforms. Cancer Res; 77(21); e119-22. ©2017 AACR . ©2017 American Association for Cancer Research.

The AQUA-FONTIS study: protocol of a multidisciplinary, cross-sectional and prospective longitudinal study for developing standardized diagnostics and classification of non-thyroidal illness syndrome

PubMed Central

Dietrich, Johannes W; Stachon, Axel; Antic, Biljana; Klein, Harald H; Hering, Steffen

2008-01-01

Background Non-thyroidal illness syndrome (NTIS) is a characteristic functional constellation of thyrotropic feedback control that frequently occurs in critically ill patients. Although this condition is associated with significantly increased morbidity and mortality, there is still controversy on whether NTIS is caused by artefacts, is a form of beneficial adaptation, or is a disorder requiring treatment. Trials investigating substitution therapy of NTIS revealed contradictory results. The comparison of heterogeneous patient cohorts may be the cause for those inconsistencies. Objectives Primary objective of this study is the identification and differentiation of different functional states of thyrotropic feedback control in order to define relevant evaluation criteria for the prognosis of affected patients. Furthermore, we intend to assess the significance of an innovative physiological index approach (SPINA) in differential diagnosis between NTIS and latent (so-called "sub-clinical") thyrotoxicosis. Secondary objective is observation of variables that quantify distinct components of NTIS in the context of independent predictors of evolution, survival or pathophysiological condition and influencing or disturbing factors like medication. Design The approach to a quantitative follow-up of non-thyroidal illness syndrome (AQUA FONTIS study) is designed as both a cross-sectional and prospective longitudinal observation trial in critically ill patients. Patients are observed in at least two evaluation points with consecutive assessments of thyroid status, physiological and clinical data in additional weekly observations up to discharge. A second part of the study investigates the neuropsychological impact of NTIS and medium-term outcomes. The study design incorporates a two-module structure that covers a reduced protocol in form of an observation trial before patients give informed consent. Additional investigations are performed if and after patients agree in participation. Trial Registration ClinicalTrials.gov NCT00591032 PMID:18851740

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

PubMed

Murakami, Naoya; Kato, Shingo; Nakano, Takashi; Uno, Takashi; Yamanaka, Takeharu; Sakurai, Hideyuki; Yoshimura, Ryoichi; Hiratsuka, Junichi; Kuroda, Yuki; Yoshio, Kotaro; Itami, Jun

2016-08-17

This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. UMIN000019081 ; Registration date: 2015/9/30.

The neurophysiological effects of dry needling in patients with upper trapezius myofascial trigger points: study protocol of a controlled clinical trial

PubMed Central

Abbaszadeh-Amirdehi, Maryam; Ansari, Noureddin Nakhostin; Naghdi, Soofia; Olyaei, Gholamreza; Nourbakhsh, Mohammad Reza

2013-01-01

Introduction Dry needling (DN) is an effective method for the treatment of myofascial trigger points (MTrPs). There is no report on the neurophysiological effects of DN in patients with MTrPs. The aim of the present study will be to assess the immediate neurophysiological efficacy of deep DN in patients with upper trapezius MTrPs. Methods and analysis A prospective, controlled clinical trial was designed to include patients with upper trapezius MTrPs and volunteered healthy participants to receive one session of DN. The primary outcome measures are neuromuscular junction response and sympathetic skin response. The secondary outcomes are pain intensity and pressure pain threshold. Data will be collected at baseline and immediately after intervention. Ethics and dissemination This study protocol has been approved by the Research Council, School of Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences. The results of the study will be disseminated in a peer-reviewed journal and presented at international congresses. PMID:23793673

An overview of interstitial brachytherapy and hyperthermia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandt, B.B.; Harney, J.

Interstitial thermoradiotherapy, an experimental cancer treatment that combines interstitial radiation implants (brachytherapy) and interstitial hyperthermia, is in the early stages of investigation. In accordance with the procedure used in a current national trial protocol, a 60-minute hyperthermia treatment is administered after catheters are placed into the tumor area while the patient is under general anesthesia. This is immediately followed by loading of radioactive Iridium-192 seeds into the catheters for a defined period of time. Once the prescribed radiation dose is delivered, the radioactive sources are removed and a second, 60-minute hyperthermia treatment is administered. Clinical trials with hyperthermia in combinationmore » with radiation have increased in recent years. Nurses caring for these patients need to become more knowledgeable about this investigational therapy. This paper provides an overview of the biologic rationale for this therapy, as well as a description of the delivery method and clinical application. Specific related nursing interventions are defined in a nursing protocol.23 references.« less

How individual participant data meta-analyses have influenced trial design, conduct, and analysis.

PubMed

Tierney, Jayne F; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L; Burdett, Sarah

2015-11-01

To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis

PubMed Central

Tierney, Jayne F.; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L.; Burdett, Sarah; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B.W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J.P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

2015-01-01

Objectives To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Study Design and Setting Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. Results We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. Conclusions IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. PMID:26186982

"I understood…but some parts were confusing and hard to grasp": Patients' perception of informed consent forms and clinical trials in Eldoret, Kenya.

PubMed

Naanyu, Violet; Some, Fatma F; Siika, Abraham M

2014-01-01

A signed informed consent (IC) form proves voluntary participation in a study. Yet the development of accessible and understandable IC forms comes with its own set of challenges, particularly when conducting international research. This study explores understanding by participants in an Eldoret-based clinical trial of IC and its implications as well as whether they will volunteer for future trials. In mid-2010, in-depth interviews with trial participants were recorded in audio format. Content analysis provides a description of trial participants' experiences and thoughts. All participants were informed about the trial and its voluntariness and they consented. However, some were too ill to scrutinize trial details. Thus, they relied on their health care provider's advice, or on their guardians. In general, participants understood their role and were happy to volunteer or invite others to participate in future trials. They also emphasised the importance of an open on-going dialogue in order for participants to be able to ask questions. Clinical trial participants in Eldoret seem to understand their role, but rely on providers and guardians when consenting. They are very willing to participate in future trials. Evaluation of research participants' opinions may improve trial protocols, increase comprehension and guard against manipulation of study participants. In addition, this research focus should guide development of consent forms and process that facilitates a truly IC.

Physician Assistant/Sr. Nurse Practitioner | Center for Cancer Research

Cancer.gov

PROGRAM DESCRIPTION Within the Leidos Biomedical Research Inc.’s Clinical Research Directorate, the Clinical Monitoring Research Program (CMRP) provides high-quality comprehensive and strategic operational support to the high-profile domestic and international clinical research initiatives of the National Cancer Institute (NCI), National Institute of Allergy and Infectious Diseases (NIAID), Clinical Center (CC), National Institute of Heart, Lung and Blood Institute (NHLBI), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Center for Advancing Translational Sciences (NCATS), National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Mental Health (NIMH). Since its inception in 2001, CMRP’s ability to provide rapid responses, high-quality solutions, and to recruit and retain experts with a variety of backgrounds to meet the growing research portfolios of NCI, NIAID, CC, NHLBI, NIAMS, NCATS, NINDS, and NIMH has led to the considerable expansion of the program and its repertoire of support services. CMRP’s support services are strategically aligned with the program’s mission to provide comprehensive, dedicated support to assist National Institutes of Health researchers in providing the highest quality of clinical research in compliance with applicable regulations and guidelines, maintaining data integrity, and protecting human subjects. For the scientific advancement of clinical research, CMRP services include comprehensive clinical trials, regulatory, pharmacovigilance, protocol navigation and development, and programmatic and project management support for facilitating the conduct of 400+ Phase I, II, and III domestic and international trials on a yearly basis. These trials investigate the prevention, diagnosis, treatment of, and therapies for cancer, influenza, HIV, and other infectious diseases and viruses such as hepatitis C, tuberculosis, malaria, and Ebola virus; heart, lung, and blood diseases and conditions; parasitic infections; rheumatic and inflammatory diseases; and rare and neglected diseases. CMRP’s collaborative approach to clinical research and the expertise and dedication of staff to the continuation and success of the program’s mission has contributed to improving the overall standards of public health on a global scale. The Clinical Monitoring Research Program (CMRP) provides quality Physician Assistant and/or Nurse Practitioner clinical research services in support of the Urologic Oncology Branch (UOB), National Cancer Institute’s (NCI’s), Center for Cancer Research (CCR). KEY ROLES/RESPONSIBILITIES - THIS POSITION IS CONTINGENT UPON FUNDING APPROVAL The Physician Extender: Provides clinical care in collaboration with physicians and health care professionals. Performs a comprehensive physical assessment and documents findings in the appropriate format following institutional and protocol standards. Assesses the patient's general health status through observation and the use of appropriate screening procedures. Acquires patient data through health history taking that includes family history and significant social information. Explains the care management/discharge plan to all members of the covering team (inpatient NPs, attendings) at sign-out. Provides teaching and guidance related to the patient's current state of health and understanding of his/her disease to promote optimal performance. Coordinates study enrollment, collaborates with nursing staff to provide protocol treatment, and provides follow-up care for patients participating in clinical trials. Assists the Principal Investigator (PI) in assuring informed consent forms have been signed, obtaining written consent for treatment, pharmacokinetics, and assessing patients on the study for complications. Calculates the dose of and prescribes chemotherapy, investigational agents, medications, intravenous fluids and blood products according to established protocol, institutional, and practice guidelines. Provides guidance in the management of specific problems for the patient resulting from chemotherapy, immunotherapy or other treatments. Manages appropriate referrals to other specialists as indicated. Screens new patient calls and provides phone triage for active patients. Orders radiological studies, following protocols and patient care guidelines. Orders and interprets lab studies. Attends new patient consultations with the patient and family for the purpose of explaining the diagnosis, protocol, and treatment program, and establishing a rapport. Completes initial and follow-up assessment(s), progress notes and written correspondence to multidisciplinary personnel. Serves as a clinical liaison to area hospices and/or home care agencies as needed or as appropriate. Acts as a clinical liaison between inpatient and outpatient nurses in order to provide continuity of care to the hospitalized patient. Maintains documented evidence of weekly case review with the collaborating physician. Attends and participates in multidisciplinary meetings. Practices within boundaries established by the Nurse Practice Act, State of Maryland and Medical Board of the Clinical Center. Liaises with Leidos Biomed and various NCI staff to initiate and complete tasks relating to medicine and clinical protocols, and all activities related to nursing. Performs clinical data recording and medical chart entries. Dictates admission and discharge summaries. This position is located in Bethesda, Maryland.

Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial.

PubMed

Martin, Naomi H; Ibrahim, Fowzia; Tom, Brian; Galloway, James; Wailoo, Allan; Tosh, Jonathan; Lempp, Heidi; Prothero, Louise; Georgopoulou, Sofia; Sturt, Jackie; Scott, David L

2017-12-08

Uncontrolled active rheumatoid arthritis can lead to increasing disability and reduced quality of life over time. 'Treating to target' has been shown to be effective in active established disease and also in early disease. However, there is a lack of nationally agreed treatment protocols for patients with established rheumatoid arthritis who have intermediate disease activity. This trial is designed to investigate whether intensive management of disease leads to a greater number of remissions at 12 months. Levels of disability and quality of life, and acceptability and cost-effectiveness of the intervention will also be examined. The trial is a 12-month, pragmatic, randomised, open-label, two-arm, parallel-group, multicentre trial undertaken at specialist rheumatology centres across England. Three hundred and ninety-eight patients with established rheumatoid arthritis will be recruited. They will currently have intermediate disease activity (disease activity score for 28 joints assessed using an erythrocyte sedimentation rate of 3.2 to 5.1 with at least three active joints) and will be taking at least one disease-modifying anti-rheumatic drug. Participants will be randomly selected to receive intensive management or standard care. Intensive management will involve monthly clinical reviews with a specialist health practitioner, where drug treatment will be optimised and an individualised treatment support programme delivered based on several principles of motivational interviewing to address identified problem areas, such as pain, fatigue and adherence. Standard care will follow standard local pathways and will be in line with current English guidelines from the National Institute for Health and Clinical Excellence. Patients will be assessed initially and at 6 and 12 months through self-completed questionnaires and clinical evaluation. The trial will establish whether the known benefits of intensive treatment strategies in active rheumatoid arthritis are also seen in patients with established rheumatoid arthritis who have moderately active disease. It will evaluate both the clinical and cost-effectiveness of intensive treatment. Current Controlled Trials, ID: ISRCTN70160382 . Registered on 16 January 2014.

Randomised controlled trial of exercise to prevent shoulder problems in women undergoing breast cancer treatment: study protocol for the prevention of shoulder problems trial (UK PROSPER).

PubMed

Bruce, Julie; Williamson, Esther; Lait, Clare; Richmond, Helen; Betteley, Lauren; Lall, Ranjit; Petrou, Stavros; Rees, Sophie; Withers, Emma J; Lamb, Sarah E; Thompson, Alastair M

2018-03-23

Musculoskeletal shoulder problems are common after breast cancer treatment. Early postoperative exercises targeting the upper limb may improve shoulder function. This protocol describes a National Institute for Health Research-funded randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of an early supervised structured exercise programme compared with usual care, for women at high risk of developing shoulder problems after breast cancer surgery. This pragmatic two-armed, multicentre RCT is underway within secondary care in the UK. PRevention Of Shoulder ProblEms tRial (PROSPER) aims to recruit 350 women from approximately 15 UK centres with follow-up at 6 weeks, 6 and 12 months after randomisation. Recruitment processes and intervention development were optimised through qualitative research during a 6-month internal pilot phase. Participants are randomised to the PROSPER intervention or best practice usual care only. The PROSPER intervention is delivered by physiotherapists and incorporates three main components: shoulder-specific exercises targeting range of movement and strength; general physical activity and behavioural strategies to encourage adherence and support exercise behaviour. The primary outcome is upper arm function assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire at 12 months postrandomisation. Secondary outcomes include DASH subscales, acute and chronic pain, complications, health-related quality of life and healthcare resource use. We will interview a subsample of 20 participants to explore their experiences of the trial interventions. The PROSPER study is the first multicentre UK clinical trial to investigate the clinical and cost-effectiveness of supported exercise in the prevention of shoulder problems in high-risk women undergoing breast cancer surgery. The findings will inform future clinical practice and provide valuable insight into the role of physiotherapy-supported exercise in breast cancer rehabilitation. Version 2.1; dated 11 January 2017 TRIAL REGISTRATION NUMBER: ISRCTN35358984; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Robinson Protocol: a treadmill anaerobic performance test.

PubMed

Robinson, Ellyn M; Graham, Louise B; Headley, Samuel A

2004-08-01

The current investigation was designed to further examine the reliability of the Robinson protocol, which is a run-to-exhaustion treadmill test. Robinson (10) originally examined this protocol with 5 subjects. The significance of the initial exploratory study was the impetus for expanding the study to examine the reliability of the protocol with a larger sample. Fifteen male subjects participated in 3 trial runs on the treadmill. The first trial was a modified McConnell (7) test to determine the aerobic capacity of each subject. The second and third trials were identical Robinson protocols (10). The first trial run mean, in seconds (262.04 +/- 74.50), was not significantly different from the second trial run mean (257.30 +/- 72.65), p = 0.526 (2 tailed). As expected, trial 1 and trial 2 were highly correlated (intraclass) (r = 0.927, p < 0.001). These results provide additional support for the hypothesis that the Robinson protocol with a greater subject pool is a reliable protocol that can be used in research studies interested in examining various physiological interventions or anaerobic training.

Establishing the effectiveness, cost-effectiveness and student experience of a Simulation-based education Training program On the Prevention of Falls (STOP-Falls) among hospitalised inpatients: a protocol for a randomised controlled trial

PubMed Central

Williams, Cylie; Kiegaldie, Debra; Kaplonyi, Jessica; Haines, Terry

2016-01-01

Introduction Simulation-based education (SBE) is now commonly used across health professional disciplines to teach a range of skills. The evidence base supporting the effectiveness of this approach for improving patient health outcomes is relatively narrow, focused mainly on the development of procedural skills. However, there are other simulation approaches used to support non-procedure specific skills that are in need of further investigation. This cluster, cross-over randomised controlled trial with a concurrent economic evaluation (cost per fall prevented) trial will evaluate the effectiveness, cost-effectiveness and student experience of health professional students undertaking simulation training for the prevention of falls among hospitalised inpatients. This research will target the students within the established undergraduate student placements of Monash University medicine, nursing and allied health across Peninsula Health acute and subacute inpatient wards. Methods and analysis The intervention will train the students in how to provide the Safe Recovery program, the only single intervention approach demonstrated to reduce falls in hospitals. This will involve redevelopment of the Safe Recovery program into a one-to-many participant SBE program, so that groups of students learn the communication skills and falls prevention knowledge necessary for delivery of the program. The primary outcome of this research will be patient falls across participating inpatient wards, with secondary outcomes including student satisfaction with the SBE and knowledge gain, ward-level practice change and cost of acute/rehabilitation care for each patient measured using clinical costing data. Ethics and dissemination The Human Research Ethics Committees of Peninsula Health (LRR/15/PH/11) and Monash University (CF15/3523-2015001384) have approved this research. The participant information and consent forms provide information on privacy, storage of results and dissemination. Registration of this trial has been completed with the Australian and New Zealand Clinical Trials Registry: ACTRN12615000817549. This study protocol has been prepared according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. Trial registration number ACTRN12615000817549; Pre-results. PMID:27256087

Inherited Retinal Degenerative Disease Clinical Trial Network. Addendum

DTIC Science & Technology

2010-10-01

by retinitis pigmentosa (RP) and other forms of rare inherited retinal degenerative diseases is estimated at approximately 200,000 individuals. RP... Retinitis Pigmentosa ). NNRI is awaiting final protocol review and HRPO approval for NNRI and the three enrolling clinical sites- the CTEC site at...acid) in individuals with autosomal dominant retinitis pigmentosa , with the ability to expand the enrollment to individuals with autosomal recessive

The Effect of Cognitive-Behavioral Therapy versus Treatment as Usual for Anxiety in Children with Autism Spectrum Disorders: A Randomized, Controlled Trial

ERIC Educational Resources Information Center

Storch, Eric A.; Arnold, Elysse B.; Lewin, Adam B.; Nadeau, Josh M.; Jones, Anna M.; De Nadai, Alessandro S.; Mutch, P. Jane; Selles, Robert R.; Ung, Danielle; Murphy, Tanya K.

2013-01-01

Objective: To examine the efficacy of a modular cognitive-behavioral therapy (CBT) protocol relative to treatment as usual (TAU) among children with high-functioning autism spectrum disorders (ASD) and clinically significant anxiety. Method: A total of 45 children (7-11 years of age) with high-functioning ASD and clinically significant anxiety…

A protocol for a systematic review for perioperative pregabalin use.

PubMed

Eipe, Naveen; Penning, John; Ansari, Mohammed; Yazdi, Fatemeh; Ahmadzai, Nadera

2012-09-13

Perioperative pain management has recently been revolutionized with the recognition of novel mechanisms and introduction of newer drugs. Many randomized trials have studied the use of the gabapentinoid anti-epileptic, pregabalin, in acute pain. Published systematic reviews suggest that using pregabalin for perioperative pain management may decrease analgesic requirements and pain scores, at the expense of troublesome side effects. A major limitation of the extant reviews is the lack of rigorous investigation of clinical characteristics that would maximize the benefit harms ratio in favor of surgical patients. We posit that effects of pregabalin for perioperative pain management vary by the type of surgical pain model and propose this systematic review protocol to update previous systematic reviews and investigate the heterogeneity in findings across subgroups of surgical pain models. Using a peer-reviewed search strategy, we will search key databases for clinical trials on perioperative pregabalin use in adults. The electronic searches will be supplemented by scanning the reference lists of included studies. No limits of language, country or year will be imposed. Outcomes will include pain; use of co-analgesia, particularly opioids; enhanced recovery; and drug-related harms. We will focus on the identification of surgical models and patient characteristics that have shown benefit and adverse effects from pregabalin.Two clinical experts will independently screen the studies for inclusion using eligibility criteria established a priori. Data extracted by the reviewers will then be verified. Publication bias will be assessed, as will risk of bias using the Cochrane Risk of Bias tool. Meta-analysis and meta-regression are planned if the studies are deemed statistically, methodologically and clinically homogenous. Evidence will be graded for its strength for a select number of outcomes. We will explore the findings of perioperative clinical trials studying the use of pregabalin for acute pain. We will comment on the implications of the findings and provide further direction for the appropriate use of pregabalin in acute pain. This protocol will attempt to bridge the growing gap between clinical experience and emerging evidence, and has the potential to aid future guideline development in the perioperative use of pregabalin. PROSPERO registration number CRD42012002078.

Detection and management of familial hypercholesterolaemia in primary care in Australia: protocol for a pragmatic cluster intervention study with pre-post intervention comparisons.

PubMed

Arnold-Reed, Diane E; Brett, Tom; Troeung, Lakkhina; Vickery, Alistair; Garton-Smith, Jacquie; Bell, Damon; Pang, Jing; Grace, Tegan; Bulsara, Caroline; Li, Ian; Bulsara, Max; Watts, Gerald F

2017-10-22

Familial hypercholesterolaemia (FH), an autosomal dominant disorder of lipid metabolism, results in accelerated onset of atherosclerosis if left untreated. Lifelong treatment with diet, lifestyle modifications and statins enable a normal lifespan for most patients. Early diagnosis is critical. This protocol trials a primary care-based model of care (MoC) to improve detection and management of FH. Pragmatic cluster intervention study with pre-post intervention comparisons in Australian general practices. At study baseline, current FH detection practice is assessed. Medical records over 2 years are electronically scanned using a data extraction tool (TARB-Ex) to identify patients at increased risk. High-risk patients are clinically reviewed to provide definitive, phenotypic diagnosis using Dutch Lipid Clinic Network Criteria. Once an index family member with FH is identified, the primary care team undertake cascade testing of first-degree relatives to identify other patients with FH. Management guidance based on disease complexity is provided to the primary care team. Study follow-up to 12 months with TARB-Ex rerun to identify total number of new FH cases diagnosed over study period (via TARB-Ex, cascade testing and new cases presenting). At study conclusion, patient and clinical staff perceptions of enablers/barriers and suggested improvements to the approach will be examined. Resources at each stage will be traced to determine the economic implications of implementing the MoC and costed from health system perspective. Primary outcomes: increase in number of index cases clinically identified; reduction in low-density lipoprotein cholesterol of treated cases. increase in the number of family cases detected/contacted; cost implications of the MoC. Study approval by The University of Notre Dame Australia Human Research Ethics Committee Protocol ID: 0 16 067F. Registration: Australian New Zealand Clinical Trials Registry ID: 12616000630415. Information will be disseminated via research seminars, conference presentations, journal articles, media releases and community forums. Australian New Zealand Clinical Trials Registry ID 12616000630415; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

SU-F-J-49: IGRT Credentialing in NCTN Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lowenstein, J; Molineu, A; Followill, D

Purpose: To make Image Guided Radiation Therapy (IGRT) credentialing a more unified, consistent and efficient process across the entire National Clinical Trial Network (NCTN). Methods: IGRT plays a role in several advanced NCTN trials. Previously an institution had to be IGRT credentialed for each protocol. When institutions were allowed to use previous credentials for new protocols it was limited to the same disease site as the original credentialing. The credentialing was analyzed by the physics PI of the protocol. We consulted with several of these physicists to determine what is important to consider when reviewing submissions and to learn waysmore » to apply credentialing more broadly. Results: For trials open in 2016, IGRT credentialing can be simplified to cover either boney anatomy or soft tissue. This revised credentialing will cover all disease sites based on the type of anatomy, unless otherwise stated within the protocol. Institutions will submit will complete an online questionnaire about their IGRT procedures. Boney anatomy requirements will include submission of data from 2 sequential fraction of both a patient aligned with boney anatomy and pelvic patient. Soft tissue will require similar submissions for a patient aligned using soft tissue and a pelvic patient. Institutions will only be required to submit the pelvic patient once. Data should be in DICOM format and includes planning CT set, RT structure set, RT plan file, RT dose file, localization images and spatial registration file (if available). Reviews will be done by IROC-Houston staff who will continue to provide feedback to the sites. Conclusion: This revised IGRT credentialing process will bring consistency, a savings in time and effort for both the IROC Houston QA office and to those institutions wanting to be credentialed to participate in NCTN Trials. Sponsored by NIH/NCI CA10953.« less

American Society of Clinical Oncology policy statement: oversight of clinical research.

PubMed

2003-06-15

Well-publicized lapses in the review or implementation of clinical research studies have raised public questions about the integrity of the clinical research process. Public trust in the integrity of research is critical not only for funding and participation in clinical trials but also for confidence in the treatments that result from the trials. The questions raised by these unfortunate cases pose an important opportunity to reassess the clinical trials oversight system to ensure the integrity of clinical research and the safety of those who enroll in clinical trials. Since its inception, the American Society of Clinical Oncology (ASCO) has worked for the advancement of cancer treatments through clinical research and to help patients gain prompt access to scientifically excellent and ethically unimpeachable clinical trials. As an extension of its mission, ASCO is affirming with this policy statement the critical importance of a robust review and oversight system to ensure that clinical trials participants give fully informed consent and that their safety is a top priority. Ensuring the integrity of research cannot be stressed enough because of its seminal connection to the advancement of clinical cancer treatment. The overall goal of this policy is to enhance public trust in the cancer clinical trials process. To achieve this, the following elements are essential: 1. Ensure safety precautions for clinical trial participants and their fully informed consent. 2. Ensure the validity and integrity of scientific research. 3. Enhance the educational training of clinical scientists and research staff to ensure the highest standards of research conduct. 4. Promote accountability and responsibility among all those involved in clinical research (not just those serving on institutional review boards [IRBs], but also institutional officials, researchers, sponsors, and participants) and ensure support for an effective oversight process. 5. Enhance the professional and public understanding of clinical research oversight. 6. Enhance the efficiency and cost-effectiveness of the clinical research oversight system. This policy statement makes recommendations in several areas that serve as principles to support an improved system of oversight for clinical research. ASCO will work with all parties involved in the clinical research system to develop the steps necessary to implement these recommendations. Centralized Trial Review: A large percentage of oncology clinical trials are coordinated through the National Cancer Institute's (NCI) system of cooperative groups, which already incorporates centralized scientific review. As such, there is a tremendous opportunity to employ a centralized mechanism to provide ethical review by highly trained IRB members, allowing local IRBs to take advantage of the financial and time efficiencies that central review provides. Centralized review boards (CRBs) would also contribute consistency and efficiency to the process. Once successfully completed, the review would represent an approval to open the protocol at all of the institutions that have subscribed to the centralized review system. Local IRBs would be able to devote time usually spent on initial review to ongoing monitoring of the trial taking place at their institution. Considering the enormous size and complexity of the clinical research enterprise, ASCO envisions multiple CRBs, which could be distributed as regional review boards. Central review will use a single protocol and consent form, and monitor and evaluate adverse events (AEs) on a global basis, eliminating many of the time-consuming steps for the local IRB. Global monitoring and assessment of AEs has real potential to enhance trial participants' safety by giving local institutions more information on the overall trial and enabling them to devote more time to ongoing review of the trial onsite. Use of a CRB also has real potential to reduce the costs of clinical trial oversight by allowing local IRBs to eliminate the costs of initial review. These efficiencies will likely lead to institutions redirecting funds toward monitoring ongoing trials. Although a CRB has potential to improve the efficiency of the process, a CRB could also have tremendous ability to delay valuable trials. Checks and balances must be included in the newly devised system to ensure timely review and appeals of CRB actions. ASCO proposes the advent of a new pilot program for centralizing review of clinical trials. It requires clear engagement of all stakeholders in planning the experiment, clear articulation of the goals, and assurance of federal regulatory protection for institutions choosing to participate. If successful, this CRB pilot project could be expanded to include multi-institutional industry-sponsored research. Education and Training:Education and training are critical to the ultimate success of an improved oversight system. All members of the research team should receive comprehensive education on conducting scientifically and ethically valid clinical research. The curriculum should also include information on the prevailing local and federal regulations that pertain to the clinical trials process. IRB members should also receive ongoing education and training in the review of clinical research protocols. IRB training should pay particular attention to nonscientific members to give them the tools necessary to speak on behalf of research participants. ASCO should develop a curriculum that focuses on the proper conduct of human research and emphasize ethically sound clinical research in the context of its Annual Meeting. Informed Consent: Investigators and review boards have specific roles to play in ensuring the education of trial participants through the informed consent process, both when they are considering trial enrollment and as they participate in the trial. Review boards and investigators should focus primarily on the informed consent process, rather than the informed consent documents. Federal Oversight: The federal government has an important role to play in the oversight of clinical research. This role should be expanded to cover all research, not just that which is funded by the federal government or conducted with the oversight of the Food and Drug Administration (FDA). The Department of Health and Human Services (HHS) Office for Human Research Protections (OHRP) and the FDA should provide clear regulatory support and guidance for local institutions that choose to employ a CRB. In the case of the pilot CRB discussed in this policy statement, it should serve as the preferred option for the cancer cooperative group clinical trials. Ideally, the federal government should unify and streamline its regulations for the oversight of clinical research. Resources Supporting Clinical Research Infrastructure:An effective oversight process demands the highest quality scientific and ethical review and onsite monitoring of the safety of trial participants. This can only be accomplished by the involvement of an experienced IRB that receives funding, resources, and institutional support enabling it to fulfill its mandate. Critical to the integrity of research is the absence of bias in the process. ASCO strongly recommends the adoption of standards for the identification, management, and, where appropriate, elimination of conflicts of interests, whether they are actual, potential, or apparent.

Statistical analysis plan for the family-led rehabilitation after stroke in India (ATTEND) trial: A multicenter randomized controlled trial of a new model of stroke rehabilitation compared to usual care.

PubMed

Billot, Laurent; Lindley, Richard I; Harvey, Lisa A; Maulik, Pallab K; Hackett, Maree L; Murthy, Gudlavalleti Vs; Anderson, Craig S; Shamanna, Bindiganavale R; Jan, Stephen; Walker, Marion; Forster, Anne; Langhorne, Peter; Verma, Shweta J; Felix, Cynthia; Alim, Mohammed; Gandhi, Dorcas Bc; Pandian, Jeyaraj Durai

2017-02-01

Background In low- and middle-income countries, few patients receive organized rehabilitation after stroke, yet the burden of chronic diseases such as stroke is increasing in these countries. Affordable models of effective rehabilitation could have a major impact. The ATTEND trial is evaluating a family-led caregiver delivered rehabilitation program after stroke. Objective To publish the detailed statistical analysis plan for the ATTEND trial prior to trial unblinding. Methods Based upon the published registration and protocol, the blinded steering committee and management team, led by the trial statistician, have developed a statistical analysis plan. The plan has been informed by the chosen outcome measures, the data collection forms and knowledge of key baseline data. Results The resulting statistical analysis plan is consistent with best practice and will allow open and transparent reporting. Conclusions Publication of the trial statistical analysis plan reduces potential bias in trial reporting, and clearly outlines pre-specified analyses. Clinical Trial Registrations India CTRI/2013/04/003557; Australian New Zealand Clinical Trials Registry ACTRN1261000078752; Universal Trial Number U1111-1138-6707.

Association Between In-Office And At-Home Tooth Bleaching: A Single Blind Randomized Clinical Trial.

PubMed

Rodrigues, João Lima; Rocha, Patrícia Souza; Pardim, Silvia Letícia de Souza; Machado, Ana Cláudia Vieira; Faria-E-Silva, André Luis; Seraidarian, Paulo Isaías

2018-01-01

This controlled randomized clinical trial evaluated the effect of associating at-home and in-office bleaching procedures on tooth sensitivity (TS) and bleaching effectiveness. Forty patients subjected to on session of in-office bleaching with 38% peroxide hydrogen. Subsequently, the patients were randomly allocated to receive a second session of in-office bleaching or to use a tray containing 10% carbamide peroxide delivered during 7 consecutive days. The worst TS score reported during or after each bleaching procedure was recorded using a verbal rating scale and TS risk (score different from 0) was calculated. Color changes were measured 7 days after each in-office session (for patients receiving in-office procedures only) or after the end of at-home bleaching (for the combined protocol), and 6 months after the last procedure for both bleaching protocols. Color was assessed by a spectrophotometer and by color match with the Vita Classical and Bleach guide scales. Statistical analyses were carried out to assess possible differences between the protocols regarding the outcomes and to analyze the effect of time of assessment on color changes. The bleaching protocol did not affect the risk for and the maximum level of TS reported, irrespective of the time of assessment. In the color evaluation, the bleaching protocol also did not affect the ultimate tooth color. In conclusion, after one in-office bleaching session, there was no difference in bleaching effectiveness and TS between performing a second in-office session and associating it with 1-week at-home bleaching.

The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments.

PubMed

Connick, Peter; Kolappan, Madhan; Patani, Rickie; Scott, Michael A; Crawley, Charles; He, Xiao-Ling; Richardson, Karen; Barber, Kelly; Webber, Daniel J; Wheeler-Kingshott, Claudia A M; Tozer, Daniel J; Samson, Rebecca S; Thomas, David L; Du, Ming-Qing; Luan, Shi L; Michell, Andrew W; Altmann, Daniel R; Thompson, Alan J; Miller, David H; Compston, Alastair; Chandran, Siddharthan

2011-03-02

No treatments are currently available that slow, stop, or reverse disease progression in established multiple sclerosis (MS). The Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of treatment with a candidate cell-based therapy, and will inform the wider challenge of designing early phase clinical trials to evaluate putative neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial protocol, we describe a novel methodology based on detailed assessment of the anterior visual pathway as a model of wider disease processes--the "sentinel lesion approach". MSCIMS is a phase IIA study of autologous mesenchymal stem cells (MSCs) in secondary progressive MS. A pre-test : post-test design is used with healthy controls providing normative data for inter-session variability. Complementary eligibility criteria and outcomes are used to select participants with disease affecting the anterior visual pathway. Ten participants with MS and eight healthy controls were recruited between October 2008 and March 2009. Mesenchymal stem cells were successfully isolated, expanded and characterised in vitro for all participants in the treatment arm. In addition to determining the safety and feasibility of the intervention and informing design of future studies to address efficacy, MSCIMS adopts a novel strategy for testing neuroprotective agents in MS--the sentinel lesion approach--serving as proof of principle for its future wider applicability. ClinicalTrials.gov (NCT00395200).

Treatment of ARDS With Prone Positioning.

PubMed

Scholten, Eric L; Beitler, Jeremy R; Prisk, G Kim; Malhotra, Atul

2017-01-01

Prone positioning was first proposed in the 1970s as a method to improve gas exchange in ARDS. Subsequent observations of dramatic improvement in oxygenation with simple patient rotation motivated the next several decades of research. This work elucidated the physiological mechanisms underlying changes in gas exchange and respiratory mechanics with prone ventilation. However, translating physiological improvements into a clinical benefit has proved challenging; several contemporary trials showed no major clinical benefits with prone positioning. By optimizing patient selection and treatment protocols, the recent Proning Severe ARDS Patients (PROSEVA) trial demonstrated a significant mortality benefit with prone ventilation. This trial, and subsequent meta-analyses, support the role of prone positioning as an effective therapy to reduce mortality in severe ARDS, particularly when applied early with other lung-protective strategies. This review discusses the physiological principles, clinical evidence, and practical application of prone ventilation in ARDS. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Quality of life and sleep quality are similarly improved after aquatic or dry-land aerobic training in patients with type 2 diabetes: A randomized clinical trial.

PubMed

S Delevatti, Rodrigo; Schuch, Felipe Barreto; Kanitz, Ana Carolina; Alberton, Cristine L; Marson, Elisa Corrêa; Lisboa, Salime Chedid; Pinho, Carolina Dertzbocher Feil; Bregagnol, Luciana Peruchena; Becker, Maríndia Teixeira; Kruel, Luiz Fernando M

2018-05-01

To compare the effects of two aerobic training models in water and on dry-land on quality of life, depressive symptoms and sleep quality in patients with type 2 diabetes. Randomized clinical trial. Thirty-five patients with type 2 diabetes were randomly assigned to aquatic aerobic training group (n=17) or dry-land aerobic training group (n=18). Exercise training length was of 12 weeks, performed in three weekly sessions (45min/session), with intensity progressing from 85% to 100% of heart rate of anaerobic threshold during interventions. All outcomes were evaluated at baseline and 12 weeks later. In per protocol analysis, physical and psychological domains of quality of life improved in both groups (p<0.05) without between-group differences. Overall quality of life and sleep quality improved in both groups (p<0.05), without between-group differences in per protocol and intention to treat analysis. No changes on depressive symptoms were observed in both groups at follow-up. Aerobic training in an aquatic environment provides similar effects to aerobic training in a dry-land environment on quality of life, depressive symptoms and sleep quality in patients with type 2 diabetes. Clinical trial reg. no. NCT01956357, clinicaltrials.gov. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Methods for a multicenter randomized trial for mixed urinary incontinence: rationale and patient-centeredness of the ESTEEM trial.

PubMed

Sung, Vivian W; Borello-France, Diane; Dunivan, Gena; Gantz, Marie; Lukacz, Emily S; Moalli, Pamela; Newman, Diane K; Richter, Holly E; Ridgeway, Beri; Smith, Ariana L; Weidner, Alison C; Meikle, Susan

2016-10-01

Mixed urinary incontinence (MUI) can be a challenging condition to manage. We describe the protocol design and rationale for the Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence (ESTEEM) trial, designed to compare a combined conservative and surgical treatment approach versus surgery alone for improving patient-centered MUI outcomes at 12 months. ESTEEM is a multisite, prospective, randomized trial of female participants with MUI randomized to a standardized perioperative behavioral/pelvic floor exercise intervention plus midurethral sling versus midurethral sling alone. We describe our methods and four challenges encountered during the design phase: defining the study population, selecting relevant patient-centered outcomes, determining sample size estimates using a patient-reported outcome measure, and designing an analysis plan that accommodates MUI failure rates. A central theme in the design was patient centeredness, which guided many key decisions. Our primary outcome is patient-reported MUI symptoms measured using the Urogenital Distress Inventory (UDI) score at 12 months. Secondary outcomes include quality of life, sexual function, cost-effectiveness, time to failure, and need for additional treatment. The final study design was implemented in November 2013 across eight clinical sites in the Pelvic Floor Disorders Network. As of 27 February 2016, 433 total/472 targeted participants had been randomized. We describe the ESTEEM protocol and our methods for reaching consensus for methodological challenges in designing a trial for MUI by maintaining the patient perspective at the core of key decisions. This trial will provide information that can directly impact patient care and clinical decision making.

Missing data handling in non-inferiority and equivalence trials: A systematic review.

PubMed

Rabe, Brooke A; Day, Simon; Fiero, Mallorie H; Bell, Melanie L

2018-05-25

Non-inferiority (NI) and equivalence clinical trials test whether a new treatment is therapeutically no worse than, or equivalent to, an existing standard of care. Missing data in clinical trials have been shown to reduce statistical power and potentially bias estimates of effect size; however, in NI and equivalence trials, they present additional issues. For instance, they may decrease sensitivity to differences between treatment groups and bias toward the alternative hypothesis of NI (or equivalence). Our primary aim was to review the extent of and methods for handling missing data (model-based methods, single imputation, multiple imputation, complete case), the analysis sets used (Intention-To-Treat, Per-Protocol, or both), and whether sensitivity analyses were used to explore departures from assumptions about the missing data. We conducted a systematic review of NI and equivalence trials published between May 2015 and April 2016 by searching the PubMed database. Articles were reviewed primarily by 2 reviewers, with 6 articles reviewed by both reviewers to establish consensus. Of 109 selected articles, 93% reported some missing data in the primary outcome. Among those, 50% reported complete case analysis, and 28% reported single imputation approaches for handling missing data. Only 32% reported conducting analyses of both intention-to-treat and per-protocol populations. Only 11% conducted any sensitivity analyses to test assumptions with respect to missing data. Missing data are common in NI and equivalence trials, and they are often handled by methods which may bias estimates and lead to incorrect conclusions. Copyright © 2018 John Wiley & Sons, Ltd.

Evaluation of the Gold Coast Integrated Care for patients with chronic disease or high risk of hospitalisation through a non-randomised controlled clinical trial: a pilot study protocol.

PubMed

Scuffham, Paul A; Mihala, Gabor; Ward, Lauren; McMurray, Anne; Connor, Martin

2017-07-02

Chronic diseases are the leading cause of illness, disability and death in Australia. The prevalence and associated health expenditure are projected to soar. There is no 'whole system' approach to healthcare in Australia. To overcome this fragmentation, the Gold Coast Hospital and Health Service (GCHHS) is developing a new model known as Gold Coast Integrated Care (GCIC). To evaluate GCIC a 4-year pilot trial commenced in March 2015. This protocol paper describes the evaluation of GCIC. A pragmatic non-randomised controlled clinical trial is conducted to test the hypothesis that GCIC will result in improved health and well-being at no additional cost to the healthcare system. Using a mixed methods approach, impact, outcome and process evaluations will be undertaken to assess the effectiveness and acceptability, including the balance of costs between primary and public secondary care sectors, staff and training requirements, clinical service delivery, and trial implementation.Fifteen general practices have agreed to deliver GCIC. One thousand five hundred of their adult patients with treated chronic diseases, high risk of hospitalisation or healthcare utilisation were recruited to the intervention arm. Approximately 3000 patients not associated with the participating general practices were identified as controls using propensity matching which will provide service utilisation and disease data for usual care.Baseline data and follow-up observations are collected annually until the end of 2018. Quantitative analyses will measure patient healthcare costs, utilisation of health services, and health outcomes, and general practice clinical service delivery according to clinical guidelines (number of foot exams, HbA1c tests). Qualitative analyses will focus on patient and staff experiences, satisfaction, engagement and implementation of the programme as planned. Approval was received from the GCHHS and Griffith University. The study is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12616000821493). Findings will be communicated via yearly reports to funding bodies and scientific publications. ACTRN12616000821493; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Evaluation and implementation of highly challenging balance training in clinical practice for people with Parkinson's disease: protocol for the HiBalance effectiveness-implementation trial.

PubMed

Leavy, Breiffni; Kwak, Lydia; Hagströmer, Maria; Franzén, Erika

2017-02-07

If people with progressive neurological diseases are to avail of evidence-based rehabilitation, programs found effective in randomized controlled trials (RCT's) must firstly be adapted and tested in clinical effectiveness studies as a means of strengthening their evidence base. This paper describes the protocol for an effectiveness-implementation trial that will assess the clinical effectiveness of a highly challenging balance training program (the HiBalance program) for people with mild-moderate Parkinson's disease (PD) while simultaneously collecting data concerning the way in which the program is implemented. The HiBalance program is systemically designed to target balance impairments in PD and has been shown effective at improving balance control and gait in a previous RCT. Study aims are to i) determine the effectiveness of the adapted HiBalance program on performance and self-rated outcomes such as balance control, gait and physical activity level ii) conduct a process evaluation of program implementation at the various clinics iii) determine barriers and facilitators to program implementation in these settings. This effectiveness-implementation type 1 hybrid study will use a non-randomized controlled design with consecutive inclusion of people with PD at multiple clinical sites. A mixed method approach will be used to collect clinical effectiveness data and process evaluation data which is both quantitative and qualitative in nature. The consolidated framework for implementation research (CFIR) will be used to guide the planning and collection of data concerning implementation barriers and facilitators. The HiBalance program will be provided by physical therapists as a part of standard rehabilitation care at the clinical sites, while the evaluation of the implementation process will be performed by the research group and funded by research grants. An effectiveness-implementation study design benefits patients by speeding up the process of translating findings from research settings to routine health care. Findings from this study will also be highly relevant for those working with neurological rehabilitation when faced with decisions concerning the translation of training programs from efficacy studies to everyday clinical practice. ClinicalTrials.gov march 2016, NCT02727478 .

A randomized noninferiority trial of condensed protocols for genetic risk disclosure of Alzheimer's disease.

PubMed

Green, Robert C; Christensen, Kurt D; Cupples, L Adrienne; Relkin, Norman R; Whitehouse, Peter J; Royal, Charmaine D M; Obisesan, Thomas O; Cook-Deegan, Robert; Linnenbringer, Erin; Butson, Melissa Barber; Fasaye, Grace-Ann; Levinson, Elana; Roberts, J Scott

2015-10-01

Conventional multisession genetic counseling is currently recommended when disclosing apolipoprotein E (APOE) genotype for the risk of Alzheimer's disease (AD) in cognitively normal individuals. The objective of this study was to evaluate the safety of brief disclosure protocols for disclosing APOE genotype for the risk of AD. A randomized, multicenter noninferiority trial was conducted at four sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared with condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Preplanned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Three hundred and forty-three adults (mean age 58.3, range 33-86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n = 115), CP-GC protocol (n = 116), or CP-MD protocol (n = 112). Mean postdisclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC with SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all P < .001 on noninferiority tests), establishing noninferiority for condensed protocols. Results were similar between European Americans and African Americans. These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

International Study to Predict Optimized Treatment for Depression (iSPOT-D), a randomized clinical trial: rationale and protocol.

PubMed

Williams, Leanne M; Rush, A John; Koslow, Stephen H; Wisniewski, Stephen R; Cooper, Nicholas J; Nemeroff, Charles B; Schatzberg, Alan F; Gordon, Evian

2011-01-05

Clinically useful treatment moderators of Major Depressive Disorder (MDD) have not yet been identified, though some baseline predictors of treatment outcome have been proposed. The aim of iSPOT-D is to identify pretreatment measures that predict or moderate MDD treatment response or remission to escitalopram, sertraline or venlafaxine; and develop a model that incorporates multiple predictors and moderators. The International Study to Predict Optimized Treatment - in Depression (iSPOT-D) is a multi-centre, international, randomized, prospective, open-label trial. It is enrolling 2016 MDD outpatients (ages 18-65) from primary or specialty care practices (672 per treatment arm; 672 age-, sex- and education-matched healthy controls). Study-eligible patients are antidepressant medication (ADM) naïve or willing to undergo a one-week wash-out of any non-protocol ADM, and cannot have had an inadequate response to protocol ADM. Baseline assessments include symptoms; distress; daily function; cognitive performance; electroencephalogram and event-related potentials; heart rate and genetic measures. A subset of these baseline assessments are repeated after eight weeks of treatment. Outcomes include the 17-item Hamilton Rating Scale for Depression (primary) and self-reported depressive symptoms, social functioning, quality of life, emotional regulation, and side-effect burden (secondary). Participants may then enter a naturalistic telephone follow-up at weeks 12, 16, 24 and 52. The first half of the sample will be used to identify potential predictors and moderators, and the second half to replicate and confirm. First enrolment was in December 2008, and is ongoing. iSPOT-D evaluates clinical and biological predictors of treatment response in the largest known sample of MDD collected worldwide. International Study to Predict Optimised Treatment - in Depression (iSPOT-D) ClinicalTrials.gov Identifier: NCT00693849. URL: http://clinicaltrials.gov/ct2/show/NCT00693849?term=International+Study+to+Predict+Optimized+Treatment+for+Depression&rank=1

Current-reported outcome domains in studies of adults with a focus on the treatment of tinnitus: protocol for a systematic review.

PubMed

Hall, Deborah A; Szczepek, Agnieszka J; Kennedy, Veronica; Haider, Haúla

2015-11-11

In Europe alone, over 70 million people experience tinnitus. Despite its considerable socioeconomic relevance, progress in developing successful treatments has been limited. Clinical effectiveness is judged according to change in primary outcome measures, but because tinnitus is a subjective condition, the definition of outcomes is challenging and it remains unclear which distinct aspects of tinnitus (ie, 'domains') are most relevant for assessment. The development of a minimum outcome reporting standard would go a long way towards addressing these problems. In 2006, a consensus meeting recommended using 1 of 4 questionnaires for tinnitus severity as an outcome in clinical trials, in part because of availability in different language translations. Our initiative takes an approach motivated by clinimetrics, first by determining what to measure before seeking to determine how to measure it. Agreeing on the domains that contribute to tinnitus severity (ie, 'what') is the first step towards achieving a minimum outcome reporting standard for tinnitus that has been reached via a methodologically rigorous and transparent process. Deciding what should be the core set of outcomes requires a great deal of discussion and so lends itself well to international effort. This protocol lays out the first-step methodology in defining a Core Domain Set for clinical trials of tinnitus by establishing existing knowledge and practice with respect to which outcome domains have been measured and which instruments used in recent registered and published clinical trials. No ethical issues are foreseen. Findings will be reported at national and international ear, nose and throat (ENT) and audiology conferences and in a peer-reviewed journal, using PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis) guidelines. The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Connecting Smartphone and Wearable Fitness Tracker Data with a Nationally Used Electronic Health Record System for Diabetes Education to Facilitate Behavioral Goal Monitoring in Diabetes Care: Protocol for a Pragmatic Multi-Site Randomized Trial

PubMed Central

Coleman, Deidra Carroll; Kanter, Justin; Ummer, Brad; Siminerio, Linda

2018-01-01

Background Mobile and wearable technology have been shown to be effective in improving diabetes self-management; however, integrating data from these technologies into clinical diabetes care to facilitate behavioral goal monitoring has not been explored. Objective The objective of this paper is to report on a study protocol for a pragmatic multi-site trial along with the intervention components, including the detailed connected health interface. This interface was developed to integrate patient self-monitoring data collected from a wearable fitness tracker and its companion smartphone app to an electronic health record system for diabetes self-management education and support (DSMES) to facilitate behavioral goal monitoring. Methods A 3-month multi-site pragmatic clinical trial was conducted with eligible patients with diabetes mellitus from DSMES programs. The Chronicle Diabetes system is currently freely available to diabetes educators through American Diabetes Association–recognized DSMES programs to set patient nutrition and physical activity goals. To integrate the goal-setting and self-monitoring intervention into the DSMES process, a connected interface in the Chronicle Diabetes system was developed. With the connected interface, patient self-monitoring information collected from smartphones and wearable fitness trackers can facilitate educators’ monitoring of patients’ adherence to their goals. Feasibility outcomes of the 3-month trial included hemoglobin A1c levels, weight, and the usability of the connected system. Results An interface designed to connect data from a wearable fitness tracker with a companion smartphone app for nutrition and physical activity self-monitoring into a diabetes education electronic health record system was successfully developed to enable diabetes educators to facilitate goal setting and monitoring. A total of 60 eligible patients with type 2 diabetes mellitus were randomized into either group 1) standard diabetes education or 2) standard education enhanced with the connected system. Data collection for the 3-month pragmatic trial is completed. Data analysis is in progress. Conclusions If results of the pragmatic multi-site clinical trial show preliminary efficacy and usability of the connected system, a large-scale implementation trial will be conducted. Trial Registration ClinicalTrials.gov NCT02664233; https://clinicaltrials.gov/ct2/show/NCT02664233 (Archived by WebCite at http://www.webcitation.org/6yDEwXHo5) PMID:29610111

mHealth Technology and Nurse Health Coaching to Improve Health in Diabetes: Protocol for a Randomized Controlled Trial.

PubMed

Miyamoto, Sheridan; Dharmar, Madan; Fazio, Sarina; Tang-Feldman, Yajarayma; Young, Heather M

2018-02-15

Chronic diseases, including diabetes mellitus, are the leading cause of mortality and disability in the United States. Current solutions focus primarily on diagnosis and pharmacological treatment, yet there is increasing evidence that patient-centered models of care are more successful in improving and addressing chronic disease outcomes. The objective of this clinical trial is to evaluate the impact of a mobile health (mHealth) enabled nurse health coaching intervention on self-efficacy among adults with type-2 diabetes mellitus. A randomized controlled trial was conducted at an academic health system in Northern California. A total of 300 participants with type-2 diabetes were scheduled to be enrolled through three primary care clinics. Participants were randomized to either usual care or intervention. All participants received training on use of the health system patient portal. Participants in the intervention arm received six scheduled health-coaching telephone calls with a registered nurse and were provided with an activity tracker and mobile application that integrated data into the electronic health record (EHR) to track their daily activity and health behavior decisions. All participants completed a baseline survey and follow-up surveys at 3 and 9 months. Primary and secondary outcomes include diabetes self-efficacy, hemoglobin A 1c (HbA 1c ), and quality of life measures. Data collection for this trial, funded by the Patient-Centered Outcomes Research Institute, will be completed by December 2017. Results from the trial will be available mid-2018. This protocol details a patient-centered intervention using nurse health coaching, mHealth technologies, and integration of patient-generated data into the EHR. The aim of the intervention is to enhance self-efficacy and health outcomes by providing participants with a mechanism to track daily activity by offering coaching support to set reasonable and attainable health goals, and by creating a complete feedback loop by bringing patient-generated data into the EHR. ClinicalTrials.gov NCT02672176; https://clinicaltrials.gov/ct2/show/NCT02672176 (Archived by WebCite at http://www.webcitation.org/6xEQXe1M5). ©Sheridan Miyamoto, Madan Dharmar, Sarina Fazio, Yajarayma Tang-Feldman, Heather M Young. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.02.2018.

Legal and ethical obligations to conduct a clinical drug trial in Australia as an investigator initiated and sponsored study for an overseas pharmaceutical company.

PubMed

Beran, Roy G

2004-01-01

Most multi-centre trials are both financed and sponsored by the pharmaceutical company involved. What follows will map the path adopted for an investigator initiated and sponsored study for a new indication of an established medication. The chief investigators of a company-sponsored, investigator-initiated, multi-centre, placebo-controlled study of an established medication, Pharmaceutical Benefit Scheme (PBS) listed for treatment of one condition but trialled in the management of another condition (trial of off-label use), were approached to submit a protocol to repeat the type of study with a different compound. The new study would test a different agent, also PBS listed, for the same condition as in the initial study and with the same off-licence application. The company would finance the study, provide the medication and matched placebo but only review the investigator-initiated protocol which would be sponsored by the principal investigator. This required the investigator to implement the trial, as would normally be done by the pharmaceutical company, yet also act as its principal investigator. The principal investigator, with colleagues and a Clinical Research Organisation (CRO), developed a protocol, adapted for the new agent, and submitted it for approval. Upon acceptance a contract was negotiated with the pharmaceutical company which had to overcome jurisdictional conflicts between common law and civil law legal systems. A CRO was contracted to undertake administrative functions which dictated special contractual agreements to overcome possible conflicts of interest for a sponsor/investigator to protect patient interests. There was need to find indemnification insurance with jurisdictional problems, co-investigators, ethics committee approvals and finance management as just some of the difficulties encountered. The paper will outline how these obstacles were overcome and how ethical and legal issues were respected through compromise. The ethical and legal obligations were addressed in a fashion which allowed the conduct of a trial adopting a proven methodology but novel infrastructure such that it was a totally independent study with regards conduct and reporting of final data, irrespective of the results being either positive or negative. This may represent a more acceptable way to ensure that future clinical trials are devoid of undue influence from the pharmaceutical industry which may still fund the study.

Using Minitel Network and New Software Engineering Techniques for Randomized Clinical Trials Management

PubMed Central

Lepage, E.; Tavernier, H.; Bouhaddou, O.; Jais, JP.; Gisselbrecht, C.; Aurengo, A.; Boiron, M.

1989-01-01

The usual Randomized Clinical Trials (RCT) management using an anachronic procedure involving a flowsheet exchange between the remote centers and the coordinating center presents a number of inadequacies. Eligibility criteria are not always verified by the coordinating center before inclusion in the trial and randomization. Laboratory tests and therapeutic adjustments are frequently decided from memory by the clinician which often leads to data oversight and variability of therapeutic decisions. This results in protocol deviations and alteration of the efficiency of the RCT. HICREN is a medical consultation system designed to take into account the different difficulties encountered during RCT driving. The system integrates a clinical database with artificial intelligence technics to manage clinical trial data on non-expensive and widely available Minitel® terminals. Randomization is then possible, after eligibility criteria are satisfied, anytime and anywhere in France through the national telematic network. HICREN also includes an intuitive graphic interface to increase physician's compliance: a user friendly dialogue manager supports on line data entry with multi-windowing facilities and pull down menus. Interactive data validation is achieved through an interface to dedicated C programs. Patient follow up is achieved by an expert system that proposes appropriate dose of treatment according to the rules defined in the trial. At present, HICREN is implemented on the CISARC system for conducting three randomized clinical trials and one epidemiologic study.

Streamlining Safety Data Collection in Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Trials: Recommendations of the Clinical Trials Transformation Initiative Antibacterial Drug Development Project Team.

PubMed

Donnelly, Helen; Alemayehu, Demissie; Botgros, Radu; Comic-Savic, Sabrina; Eisenstein, Barry; Lorenz, Benjamin; Merchant, Kunal; Pelfrene, Eric; Reith, Christina; Santiago, Jonas; Tiernan, Rosemary; Wunderink, Richard; Tenaerts, Pamela; Knirsch, Charles

2016-08-15

Resistant bacteria are one of the leading causes of hospital-acquired/ventilator-associated bacterial pneumonia (HABP/VABP). HABP/VABP trials are complex and difficult to conduct due to the large number of medical procedures, adverse events, and concomitant medications involved. Differences in the legislative frameworks between different regions of the world may also lead to excessive data collection. The Clinical Trials Transformation Initiative (CTTI) seeks to advance antibacterial drug development (ABDD) by streamlining clinical trials to improve efficiency and feasibility while maintaining ethical rigor, patient safety, information value, and scientific validity. In 2013, CTTI engaged a multidisciplinary group of experts to discuss challenges impeding the conduct of HABP/VABP trials. Separate workstreams identified challenges associated with current data collection processes. Experts defined "data collection" as the act of capturing and reporting certain data on the case report form as opposed to recording of data as part of routine clinical care. The ABDD Project Team developed strategies for streamlining safety data collection in HABP/VABP trials using a Quality by Design approach. Current safety data collection processes in HABP/VABP trials often include extraneous information. More targeted strategies for safety data collection in HABP/VABP trials will rely on optimal protocol design and prespecification of which safety data are essential to satisfy regulatory reporting requirements. A consensus and a cultural change in clinical trial design and conduct, which involve recognition of the need for more efficient data collection, are urgently needed to advance ABDD and to improve HABP/VABP trials in particular. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

An Argument for Fewer Clinical Trials.

PubMed

Borgerson, Kirstin

2016-11-01

The volume of clinical research is increasing exponentially-far beyond our ability to process and absorb the results. Given this situation, it may be beneficial to consider reducing the flow at its source. In what follows, I will motivate and critically evaluate the following proposal: researchers should conduct fewer clinical trials. More specifically, I c onsider whether researchers should be permitted to conduct only clinical research of very high quality and, in turn, whether research ethics committees (RECs) should prohibit all other, lower-quality research, even when it might appear to meet some minimal ethical standard. Following a close analysis of the social-value requirement of ethical clinical research, I argue that this proposal is defensible. The problem identified in this paper has two parts, quantity and quality, and some clarification is needed about the latter because "quality" is a highly contested term in the medical literature. When some scholars advocate for high-quality trials, they mean large-scale, simple, explanatory randomized controlled trials. Others, including myself, have defended a different characterization of high-quality research that tends more toward pragmatic trial design and the use of methods other than RCTs. Pragmatic trials aim to provide evidence that directly supports clinical decision-making in "usual" care settings. Unlike explanatory trials, which aim to abstract away from particular settings and patients, in the hopes of creating ideal conditions for the success of an intervention, pragmatic trials deliberately pursue knowledge of high applicability, through the use of representative subjects, clinically important questions, flexible treatment protocols, patient-oriented outcome measures, and so on. I see applicability as a marker of high-quality research. The context in which research is meant to be applied should be the context in which new interventions are evaluated. © 2016 The Hastings Center.

TIGA-CUB - manualised psychoanalytic child psychotherapy versus treatment as usual for children aged 5-11 years with treatment-resistant conduct disorders and their primary carers: study protocol for a randomised controlled feasibility trial.

PubMed

Edginton, Elizabeth; Walwyn, Rebecca; Burton, Kayleigh; Cicero, Robert; Graham, Liz; Reed, Sadie; Tubeuf, Sandy; Twiddy, Maureen; Wright-Hughes, Alex; Ellis, Lynda; Evans, Dot; Hughes, Tom; Midgley, Nick; Wallis, Paul; Cottrell, David

2017-09-15

The National Institute for Health and Care Excellence (NICE) recommends evidence-based parenting programmes as a first-line intervention for conduct disorders (CD) in children aged 5-11 years. As these are not effective in 25-33% of cases, NICE has requested research into second-line interventions. Child and Adolescent Psychotherapists (CAPTs) address highly complex problems where first-line treatments have failed and there have been small-scale studies of Psychoanalytic Child Psychotherapy (PCP) for CD. A feasibility trial is needed to determine whether a confirmatory trial of manualised PCP (mPCP) versus Treatment as Usual (TaU) for CD is practicable or needs refinement. The aim of this paper is to publish the abridged protocol of this feasibility trial. TIGA-CUB (Trial on improving Inter-Generational Attachment for Children Undergoing Behaviour problems) is a two-arm, pragmatic, parallel-group, multicentre, individually randomised (1:1) controlled feasibility trial (target n = 60) with blinded outcome assessment (at 4 and 8 months), which aims to develop an optimum practicable protocol for a confirmatory, pragmatic, randomised controlled trial (RCT) (primary outcome: child's behaviour; secondary outcomes: parental reflective functioning and mental health, child and parent quality of life), comparing mPCP and TaU as second-line treatments for children aged 5-11 years with treatment-resistant CD and inter-generational attachment difficulties, and for their primary carers. Child-primary carer dyads will be recruited following a referral to, or re-referral within, National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) after an unsuccessful first-line parenting intervention. PCP will be delivered by qualified CAPTs working in routine NHS clinical practice, using a trial-specific PCP manual (a brief version of established PCP clinical practice). Outcomes are: (1) feasibility of recruitment methods, (2) uptake and follow-up rates, (3) therapeutic delivery, treatment retention and attendance, intervention adherence rates, (4) follow-up data collection, and (5) statistical, health economics, process evaluation, and qualitative outcomes. TIGA-CUB will provide important information on the feasibility and potential challenges of undertaking a confirmatory RCT to evaluate the effectiveness and cost-effectiveness of mPCP. Current Controlled Trials, ID: ISRCTN86725795 . Registered on 31 May 2016.

A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial

PubMed Central

Deeks, Jonathan J; Griffith, Michael; Lip, Gregory YH; Mehta, Samir; Slinn, Gemma; Stanbury, Mary; Steeds, Richard P; Townend, Jonathan N

2017-01-01

Background and objective Atrial fibrillation (AF) is common and causes impaired quality of life, an increased risk of stroke and death as well as frequent hospital admissions. The majority of patients with AF require control of heart rate. In this article, we summarise the limited evidence from clinical trials that guides prescription, and present the rationale and protocol for a new randomised trial. As rate control has not yet been shown to reduce mortality, there is a clear need to compare the impact of therapy on quality of life, cardiac function and exercise capacity. Such a trial should concentrate on the long-term effects of treatment in the largest proportion of patients with AF, those with symptomatic permanent AF, with the aim of improving patient well-being. Design and intervention The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) trial will enrol 160 participants with a prospective, randomised, open-label, blinded end point design comparing initial rate control with digoxin or bisoprolol. This will be the first head-to-head randomised trial of digoxin and beta-blockers in AF. Participants Recruited patients will be aged ≥60 years with permanent AF and symptoms of breathlessness (equivalent to New York Heart Association class II or above), with few exclusion criteria to maximise generalisability to routine clinical practice. Outcome measures The primary outcome is patient-reported quality of life, with secondary outcomes including echocardiographic ventricular function, exercise capacity and biomarkers of cellular and clinical response. Follow-up will occur at 6 and 12 months, with feasibility components to inform the design of a future trial powered to detect a difference in hospital admission. The RATE-AF trial will underpin an integrated approach to management including biomarkers, functions and symptoms that will guide future research into optimal, personalised rate control in patients with AF. Ethics and dissemination East Midlands-Derby Research Ethics Committee (16/EM/0178); peer-reviewed publications. Trial registration Clinicaltrials.gov: NCT02391337; ISRCTN: 95259705. Pre-results. PMID:28729311

Protocol for the PREHAB study—Pre-operative Rehabilitation for reduction of Hospitalization After coronary Bypass and valvular surgery: a randomised controlled trial

PubMed Central

Stammers, Andrew N; Kehler, D Scott; Afilalo, Jonathan; Avery, Lorraine J; Bagshaw, Sean M; Grocott, Hilary P; Légaré, Jean-Francois; Logsetty, Sarvesh; Metge, Colleen; Nguyen, Thang; Rockwood, Kenneth; Sareen, Jitender; Sawatzky, Jo-Ann; Tangri, Navdeep; Giacomantonio, Nicholas; Hassan, Ansar; Duhamel, Todd A; Arora, Rakesh C

2015-01-01

Introduction Frailty is a geriatric syndrome characterised by reductions in muscle mass, strength, endurance and activity level. The frailty syndrome, prevalent in 25–50% of patients undergoing cardiac surgery, is associated with increased rates of mortality and major morbidity as well as function decline postoperatively. This trial will compare a preoperative, interdisciplinary exercise and health promotion intervention to current standard of care (StanC) for elective coronary artery bypass and valvular surgery patients for the purpose of determining if the intervention improves 3-month and 12-month clinical outcomes among a population of frail patients waiting for elective cardiac surgery. Methods and analysis This is a multicentre, randomised, open end point, controlled trial using assessor blinding and intent-to-treat analysis. Two-hundred and forty-four elective cardiac surgical patients will be recruited and randomised to receive either StanC or StanC plus an 8-week exercise and education intervention at a certified medical fitness facility. Patients will attend two weekly sessions and aerobic exercise will be prescribed at 40–60% of heart rate reserve. Data collection will occur at baseline, 1–2 weeks preoperatively, and at 3 and 12 months postoperatively. The primary outcome of the trial will be the proportion of patients requiring a hospital length of stay greater than 7 days. Potential impact of study The healthcare team is faced with an increasingly complex older adult patient population. As such, this trial aims to provide novel evidence supporting a health intervention to ensure that frail, older adult patients thrive after undergoing cardiac surgery. Ethics and dissemination Trial results will be published in peer-reviewed journals, and presented at national and international scientific meetings. The University of Manitoba Health Research Ethics Board has approved the study protocol V.1.3, dated 11 August 2014 (H2014:208). Trial registration number The trial has been registered on ClinicalTrials.gov, a registry and results database of privately and publicly funded clinical studies (NCT02219815). PMID:25753362

The Men's Safer Sex (MenSS) trial: protocol for a pilot randomised controlled trial of an interactive digital intervention to increase condom use in men

PubMed Central

Bailey, Julia V; Webster, Rosie; Hunter, Rachael; Freemantle, Nick; Rait, Greta; Michie, Susan; Estcourt, Claudia; Anderson, Jane; Gerressu, Makeda; Stephenson, Judith; Ang, Chee Siang; Hart, Graham; Dhanjal, Sacha; Murray, Elizabeth

2015-01-01

Introduction Sexually transmitted infections (STI) are a major public health problem. Condoms provide effective protection but there are many barriers to use. Face-to-face health promotion interventions are resource-intensive and show mixed results. Interactive digital interventions may provide a suitable alternative, allowing private access to personally tailored behaviour change support. We have developed an interactive digital intervention (the Men's Safer Sex (MenSS) website) which aims to increase condom use in men. We describe the protocol for a pilot trial to assess the feasibility of a full-scale randomised controlled trial of the MenSS website in addition to usual sexual health clinical care. Methods and analysis Participants: Men aged 16 or over who report female sexual partners and recent unprotected sex or suspected acute STI. Participants (N=166) will be enrolled using a tablet computer in clinic waiting rooms. All trial procedures will be online, that is, eligibility checks; study consent; trial registration; automated random allocation; and data submission. At baseline and at 3, 6 and 12 months, an online questionnaire will assess condom use, self-reported STI diagnoses, and mediators of condom use (eg, knowledge, intention). Reminders will be by email and mobile phone. The primary outcome is condom use, measured at 3 months. STI rates will be recorded from sexual health clinic medical records at 12 months. The feasibility of a cost-effectiveness analysis will be assessed, to calculate incremental cost per STI prevented (Chlamydia or Gonorrhoea), from the NHS perspective. Ethics and dissemination Ethical approval: City and East NHS Research Ethics Committee (reference number 13 LO 1801). Findings will be made available through publication in peer-reviewed journals, and to participants and members of the public via Twitter and from the University College London eHealth Unit website. Raw data will be made available on request. Trial registration number Current Controlled Trials. ISRCTN18649610. Registered 15 October 2013 http://www.controlled-trials.com/ISRCTN18649610. PMID:25687900

The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe blunt head injury compared with management by paramedics.

PubMed

Garner, Alan A; Fearnside, Michael; Gebski, Val

2013-09-14

The utility of advanced prehospital interventions for severe blunt traumatic brain injury (BTI) remains controversial. Of all trauma patient subgroups it has been anticipated that this patient group would most benefit from advanced prehospital interventions as hypoxia and hypotension have been demonstrated to be associated with poor outcomes and these factors may be amenable to prehospital intervention. Supporting evidence is largely lacking however. In particular the efficacy of early anaesthesia/muscle relaxant assisted intubation has proved difficult to substantiate. This article describes the design and protocol of the Head Injury Retrieval Trial (HIRT) which is a randomised controlled single centre trial of physician prehospital care (delivering advanced interventions such as rapid sequence intubation and blood transfusion) in addition to paramedic care for severe blunt TBI compared with paramedic care alone. Primary endpoint is Glasgow Outcome Scale score at six months post injury. Issues with trial integrity resulting from drop ins from standard care to the treatment arm as the result of policy changes by the local ambulance system are discussed. This randomised controlled trial will contribute to the evaluation of the efficacy of advance prehospital interventions in severe blunt TBI. ClinicalTrials.gov: NCT00112398.