Financial management of a large multisite randomized clinical trial.

PubMed

Sheffet, Alice J; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E; Longbottom, Mary E; Howard, Virginia J; Marler, John R; Brott, Thomas G

2014-08-01

The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years' funding ($21 112 866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2500 randomized participants at 40 sites. Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Projections of the original grant's fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant's fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2500 targeted sample size, 138 (5·5%) were randomized during the first five years and 1387 (55·5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13 845) of the projected per-patient costs ($152 992) of the fixed model. Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. © 2014 The Authors. International Journal of Stroke © 2014 World Stroke Organization.

Financial Management of a Large Multi-site Randomized Clinical Trial

PubMed Central

Sheffet, Alice J.; Flaxman, Linda; Tom, MeeLee; Hughes, Susan E.; Longbottom, Mary E.; Howard, Virginia J.; Marler, John R.; Brott, Thomas G.

2014-01-01

Background The Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) received five years’ funding ($21,112,866) from the National Institutes of Health to compare carotid stenting to surgery for stroke prevention in 2,500 randomized participants at 40 sites. Aims Herein we evaluate the change in the CREST budget from a fixed to variable-cost model and recommend strategies for the financial management of large-scale clinical trials. Methods Projections of the original grant’s fixed-cost model were compared to the actual costs of the revised variable-cost model. The original grant’s fixed-cost budget included salaries, fringe benefits, and other direct and indirect costs. For the variable-cost model, the costs were actual payments to the clinical sites and core centers based upon actual trial enrollment. We compared annual direct and indirect costs and per-patient cost for both the fixed and variable models. Differences between clinical site and core center expenditures were also calculated. Results Using a variable-cost budget for clinical sites, funding was extended by no-cost extension from five to eight years. Randomizing sites tripled from 34 to 109. Of the 2,500 targeted sample size, 138 (5.5%) were randomized during the first five years and 1,387 (55.5%) during the no-cost extension. The actual per-patient costs of the variable model were 9% ($13,845) of the projected per-patient costs ($152,992) of the fixed model. Conclusions Performance-based budgets conserve funding, promote compliance, and allow for additional sites at modest additional cost. Costs of large-scale clinical trials can thus be reduced through effective management without compromising scientific integrity. PMID:24661748

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.

Current practices in patient-reported outcome (PRO) data collection in clinical trials: a cross-sectional survey of UK trial staff and management.

PubMed

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

2016-10-03

Patient-reported outcome measures (PROMs) collected in clinical trials should be administered in a standardised way across sites and routinely screened for avoidable missing data in order to maximise data quality/minimise risk of bias. Recent qualitative findings, however, have raised concerns about the consistency of PROM administration in UK trials. The purpose of this study was to determine the generalisability of these findings across the wider community of trial personnel. Online cross-sectional survey. Participants were recruited from 55 UK Clinical Research Collaboration Registered Clinical Trials Units and 19 Comprehensive Local Research Networks. Research nurses, data managers/coordinators, trial managers and chief/principal investigators involved in clinical trials collecting PROMs. We undertook descriptive analyses of the quantitative data and directed thematic analysis of free-text comments. Factors associated with the management of missing PRO data were explored using logistic regression. Survey data from 767 respondents supported the generalisability of qualitative study findings, suggesting inconsistencies in PROM administration with regard to: the level of assistance given to trial participants; the timing of PROM completion in relation to the clinical consultation; and the management of missing data. Having ≥10 years experience in a research role was significantly associated with the appropriate management of missing PROM data (OR 2.26 (95% CI 1.06 to 4.82), p=0.035). There was a consensus that more PROM guidance was needed in future trials and agreement between professional groups about the necessary components. There are inconsistencies in the way PROMs are administered by trial staff. Such inconsistencies may reduce the quality of data and have the potential to introduce bias. There is a need for improved guidance in future trials that support trial personnel in conducting optimal PROM data collection to inform patient care. Published by the

Heterogeneity prevails: the state of clinical trial data management in Europe - results of a survey of ECRIN centres

PubMed Central

2010-01-01

Background The use of Clinical Data Management Systems (CDMS) has become essential in clinical trials to handle the increasing amount of data that must be collected and analyzed. With a CDMS trial data are captured at investigator sites with "electronic Case Report Forms". Although more and more of these electronic data management systems are used in academic research centres an overview of CDMS products and of available data management and quality management resources for academic clinical trials in Europe is missing. Methods The ECRIN (European Clinical Research Infrastructure Network) data management working group conducted a two-part standardized survey on data management, software tools, and quality management for clinical trials. The questionnaires were answered by nearly 80 centres/units (with an overall response rate of 47% and 43%) from 12 European countries and EORTC. Results Our survey shows that about 90% of centres have a CDMS in routine use. Of these CDMS nearly 50% are commercial systems; Open Source solutions don't play a major role. In general, solutions used for clinical data management are very heterogeneous: 20 different commercial CDMS products (7 Open Source solutions) in addition to 17/18 proprietary systems are in use. The most widely employed CDMS products are MACRO™ and Capture System™, followed by solutions that are used in at least 3 centres: eResearch Network™, CleanWeb™, GCP Base™ and SAS™. Although quality management systems for data management are in place in most centres/units, there exist some deficits in the area of system validation. Conclusions Because the considerable heterogeneity of data management software solutions may be a hindrance to cooperation based on trial data exchange, standards like CDISC (Clinical Data Interchange Standard Consortium) should be implemented more widely. In a heterogeneous environment the use of data standards can simplify data exchange, increase the quality of data and prepare centres

Clinical Trials | Division of Cancer Prevention

Cancer.gov

Information about actively enrolling, ongoing, and completed clinical trials of cancer prevention, early detection, and supportive care, including phase I, II, and III agent and action trials and clinical trials management. |

[Establishing the acupuncture-moxibustion clinical trial registry and improving the transparence of clinical trials of acupuncture and moxibustion].

PubMed

Liu, Yali; He, Liyun; Liu, Jia; Yang, Xingyue; Yan, Dongning; Wang, Xin; Luo, Lin; Li, Hongjiao; Yan, Shiyan; Wen, Tiancai; Bai, Wenjing; Wu, Taixiang; Liu, Baoyan

2017-07-12

As a kind of intervention measures of traditional Chinese medicine, acupuncture-moxibustion is highly adopted on global clinical practice. Even though the global clinical trial registration system was established more than 10 years ago, the proportion of acupuncture-moxibustion clinical trial registration is still very low; and it is very problematic on the methodological quality and report quality in the published acupuncture-moxibustion clinical trials. In order to manage particularly the acupuncture-moxibustion clinical trials, China Academy of Chinese Medical Sciences, collaborated with China Association of Acupuncture and Moxibustion and World Federation of Acupuncture Societies, established the Acupuncture-Moxibustion Clinical Trail Registry (AMCTR). AMCTR is a secondary registry platform affiliated to the Chinese Clinical Trial Registry (ChiCTR) and WHO International Clinical Trials Registry Platform (ICTRP), specifically for the acceptance and management of clinical trials in the field of acupuncture and moxibustion. It is a nonprofit academic organization, located in China Academy of Chinese Medical Sciences.

Malaria Diagnostics in Clinical Trials

PubMed Central

Murphy, Sean C.; Shott, Joseph P.; Parikh, Sunil; Etter, Paige; Prescott, William R.; Stewart, V. Ann

2013-01-01

Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests. PMID:24062484

Real-Time Enrollment Dashboard For Multisite Clinical Trials.

PubMed

Mattingly, William A; Kelley, Robert R; Wiemken, Timothy L; Chariker, Julia H; Peyrani, Paula; Guinn, Brian E; Binford, Laura E; Buckner, Kimberley; Ramirez, Julio

2015-10-30

Achieving patient recruitment goals are critical for the successful completion of a clinical trial. We designed and developed a web-based dashboard for assisting in the management of clinical trial screening and enrollment. We use the dashboard to assist in the management of two observational studies of community-acquired pneumonia. Clinical research associates and managers using the dashboard were surveyed to determine its effectiveness as compared with traditional direct communication. The dashboard has been in use since it was first introduced in May of 2014. Of the 23 staff responding to the survey, 77% felt that it was easier or much easier to use the dashboard for communication than to use direct communication. We have designed and implemented a visualization dashboard for managing multi-site clinical trial enrollment in two community acquired pneumonia studies. Information dashboards are a useful tool for clinical trial management. They can be used as a standalone trial information tool or included into a larger management system.

Reengineering a database for clinical trials management: lessons for system architects.

PubMed

Brandt, C A; Nadkarni, P; Marenco, L; Karras, B T; Lu, C; Schacter, L; Fisk, J M; Miller, P L

2000-10-01

This paper describes the process of enhancing Trial/DB, a database system for clinical studies management. The system's enhancements have been driven by the need to maximize the effectiveness of developer personnel in supporting numerous and diverse users, of study designers in setting up new studies, and of administrators in managing ongoing studies. Trial/DB was originally designed to work over a local area network within a single institution, and basic architectural changes were necessary to make it work over the Internet efficiently as well as securely. Further, as its use spread to diverse communities of users, changes were made to let the processes of study design and project management adapt to the working styles of the principal investigators and administrators for each study. The lessons learned in the process should prove instructive for system architects as well as managers of electronic patient record systems.

Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system.

PubMed

Zhao, Wenle; Pauls, Keith

2016-04-01

Centralized outcome adjudication has been used widely in multicenter clinical trials in order to prevent potential biases and to reduce variations in important safety and efficacy outcome assessments. Adjudication procedures could vary significantly among different studies. In practice, the coordination of outcome adjudication procedures in many multicenter clinical trials remains as a manual process with low efficiency and high risk of delay. Motivated by the demands from two large clinical trial networks, a generic outcome adjudication module has been developed by the network's data management center within a homegrown clinical trial management system. In this article, the system design strategy and database structure are presented. A generic database model was created to transfer different adjudication procedures into a unified set of sequential adjudication steps. Each adjudication step was defined by one activate condition, one lock condition, one to five categorical data items to capture adjudication results, and one free text field for general comments. Based on this model, a generic outcome adjudication user interface and a generic data processing program were developed within a homegrown clinical trial management system to provide automated coordination of outcome adjudication. By the end of 2014, this generic outcome adjudication module had been implemented in 10 multicenter trials. A total of 29 adjudication procedures were defined with the number of adjudication steps varying from 1 to 7. The implementation of a new adjudication procedure in this generic module took an experienced programmer 1 or 2 days. A total of 7336 outcome events had been adjudicated and 16,235 adjudication step activities had been recorded. In a multicenter trial, 1144 safety outcome event submissions went through a three-step adjudication procedure and reported a median of 3.95 days from safety event case report form submission to adjudication completion. In another trial

Architecture design of a generic centralized adjudication module integrated in a web-based clinical trial management system

PubMed Central

Zhao, Wenle; Pauls, Keith

2015-01-01

Background Centralized outcome adjudication has been used widely in multi-center clinical trials in order to prevent potential biases and to reduce variations in important safety and efficacy outcome assessments. Adjudication procedures could vary significantly among different studies. In practice, the coordination of outcome adjudication procedures in many multicenter clinical trials remains as a manual process with low efficiency and high risk of delay. Motivated by the demands from two large clinical trial networks, a generic outcome adjudication module has been developed by the network’s data management center within a homegrown clinical trial management system. In this paper, the system design strategy and database structure are presented. Methods A generic database model was created to transfer different adjudication procedures into a unified set of sequential adjudication steps. Each adjudication step was defined by one activate condition, one lock condition, one to five categorical data items to capture adjudication results, and one free text field for general comments. Based on this model, a generic outcome adjudication user interface and a generic data processing program were developed within a homegrown clinical trial management system to provide automated coordination of outcome adjudication. Results By the end of 2014, this generic outcome adjudication module had been implemented in 10 multicenter trials. A total of 29 adjudication procedures were defined with the number of adjudication steps varying from 1 to 7. The implementation of a new adjudication procedure in this generic module took an experienced programmer one or two days. A total of 7,336 outcome events had been adjudicated and 16,235 adjudication step activities had been recorded. In a multicenter trial, 1144 safety outcome event submissions went through a three-step adjudication procedure and reported a median of 3.95 days from safety event case report form submission to adjudication

Innovations in clinical trials informatics.

PubMed

Summers, Ron; Vyas, Hiten; Dudhal, Nilesh; Doherty, Neil F; Coombs, Crispin R; Hepworth, Mark

2008-01-01

This paper will investigate innovations in information management for use in clinical trials. The application typifies a complex, adaptive, distributed and information-rich environment for which continuous innovation is necessary. Organisational innovation is highlighted as well as the technical innovations in workflow processes and their representation as an integrated set of web services. Benefits realization uncovers further innovations in the business strand of the work undertaken. Following the description of the development of this information management system, the semantic web is postulated as a possible solution to tame the complexity related to information management issues found within clinical trials support systems.

Data management of clinical trials during an outbreak of Ebola virus disease.

PubMed

Hossmann, Stefanie; Haynes, Alan G; Spoerri, Adrian; Diatta, Ibrahima Dina; Aboubacar, Barry; Egger, Matthias; Rintelen, Felix; Trelle, Sven

2017-10-23

Clinical trial data management (DM) conducted during outbreaks like that of Ebola virus disease (EVD) in West Africa, 2014-2016, has to adapt to specific, unique circumstances. CTU Bern was asked to set up a safe data capture/management system that could be launched within a few weeks and cover two different vaccine trials. This article describes some of the challenges we faced and our solutions during the two different trials. Setting up a DM system was split into four phases/tasks: (1) quick set-up of the (electronic) data capture system (EDC) and mobile infrastructure in Bern, (2) moving the EDC and infrastructure to Conakry, Guinea and implementation of a local data management centre (DMC), (3) running the DMC, and (4) data cleaning. The DMC had to meet the following criteria: (1) quick implementation, (2) efficient maintenance and handling of data, and (3) procedures to guarantee data quality. The EDC (REDCap) was setup as a local area network. In order to ensure high data quality, double data entry, and then review of inconsistencies and offline plausibility checks were implemented. From the start of CTU Bern's involvement to the productive EDC took 11 weeks. It was necessary to adapt processes for dealing with data continuously throughout the trial conduct phase. The data management team processed 171,794 case report form pages from a total of 14,203 participants in the period between March and December 2015. Data management is a key task supporting trial conduct. For trials in emergency situations, many of our approaches are suitable, but we also provide a list of aspects that might be done differently. Copyright © 2017. Published by Elsevier Ltd.

Marketing and clinical trials: a case study

PubMed Central

Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

2007-01-01

Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

Marketing and clinical trials: a case study.

PubMed

Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

2007-11-20

Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. The case study demonstrates that trials need various categories of people to buy in - hence, to be successful, trialists must embrace marketing strategies to some extent. The performance of future clinical trials could be enhanced if trialists routinely considered these factors.

A Randomized Clinical Trial of the Collaborative Assessment and Management of Suicidality vs. Enhanced Care as Usual for Sucidal Soldiers

DTIC Science & Technology

2017-06-01

Research Projects : Patient Perspectives on Successful Management of Suicide Risk in Military and Civilian Samples Masters Student: Kaitlyn R. Schuler...Award Number: W81XWH-11-1-0164 TITLE: "A Randomized Clinical Trial of the Collaborative Assessment & Management of Suicidality vs. Enhanced Care...REPORT TYPE Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE "A Randomized Clinical Trial of the Collaborative Assessment & Management

Implementing a low-cost web-based clinical trial management system for community studies: a case study.

PubMed

Geyer, John; Myers, Kathleen; Vander Stoep, Ann; McCarty, Carolyn; Palmer, Nancy; DeSalvo, Amy

2011-10-01

Clinical trials with multiple intervention locations and a single research coordinating center can be logistically difficult to implement. Increasingly, web-based systems are used to provide clinical trial support with many commercial, open source, and proprietary systems in use. New web-based tools are available which can be customized without programming expertise to deliver web-based clinical trial management and data collection functions. To demonstrate the feasibility of utilizing low-cost configurable applications to create a customized web-based data collection and study management system for a five intervention site randomized clinical trial establishing the efficacy of providing evidence-based treatment via teleconferencing to children with attention-deficit hyperactivity disorder. The sites are small communities that would not usually be included in traditional randomized trials. A major goal was to develop database that participants could access from computers in their home communities for direct data entry. Discussed is the selection process leading to the identification and utilization of a cost-effective and user-friendly set of tools capable of customization for data collection and study management tasks. An online assessment collection application, template-based web portal creation application, and web-accessible Access 2007 database were selected and customized to provide the following features: schedule appointments, administer and monitor online secure assessments, issue subject incentives, and securely transmit electronic documents between sites. Each tool was configured by users with limited programming expertise. As of June 2011, the system has successfully been used with 125 participants in 5 communities, who have completed 536 sets of assessment questionnaires, 8 community therapists, and 11 research staff at the research coordinating center. Total automation of processes is not possible with the current set of tools as each is loosely

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.

Paperless clinical trials: Myth or reality?

PubMed Central

Gupta, Sandeep K.

2015-01-01

There is an urgent need to expedite the time-to-market for new drugs and to make the approval process simpler. But clinical trials are a complex process and the increased complexity leads to decreased efficiency. Hence, pharmaceutical organizations want to move toward a more technology-driven clinical trial process for recording, analyzing, reporting, archiving, etc., In recent times, the progress has certainly been made in developing paperless systems that improve data capture and management. The adaptation of paperless processes may require major changes to existing procedures. But this is in the best interests of these organizations to remain competitive because a paperless clinical trial would lead to a consistent and streamlined framework. Moreover, all major regulatory authorities also advocate adoption of paperless trial. But challenges still remain toward implementation of paperless clinical trial process. PMID:26288464

A comparative analysis of quality management standards for contract research organisations in clinical trials.

PubMed

Murray, Elizabeth; McAdam, Rodney

2007-01-01

This article compares and contrasts the main quality standards in the highly regulated pharmaceutical industry with specific focus on Good Clinical Practice (GCP), the standard for designing, conducting, recording and reporting clinical trials involving human participants. Comparison is made to ISO quality standards, which can be applied to all industries and types of organisation. The study is then narrowed to that of contract research organisations (CROs) involved in the conduct of clinical trials. The paper concludes that the ISO 9000 series of quality standards can act as a company-wide framework for quality management within such organisations by helping to direct quality efforts on a long-term basis without any loss of compliance. This study is valuable because comparative analysis in this domain is uncommon.

A Randomized Clinical Trial of Alternative Stress Management Interventions in Persons with HIV Infection

ERIC Educational Resources Information Center

McCain, Nancy L.; Gray, D. Patricia; Elswick, R. K., Jr.; Robins, Jolynne W.; Tuck, Inez; Walter, Jeanne M.; Rausch, Sarah M.; Ketchum, Jessica McKinney

2008-01-01

Research in psychoneuroimmunology suggests that immunosuppression associated with perceived stress may contribute to disease progression in persons with HIV infection. While stress management interventions may enhance immune function, few alternative approaches have yet been tested. This randomized clinical trial was conducted to test effects of…

Third party laboratory data management: Perspective with respect to clinical data management.

PubMed

Johnson, Jasmin; Kanagali, Vishwanath; Prabu, D

2014-01-01

Third party lab vendor provides support for laboratory, biological samples analytics data, collected during the clinical trial. Third party laboratory data is considered to be very significant for the clinical trial data management process. Although outsourcing these services is considered to be advantageous for clinical trials, there are some risks involved. Hence, pharmaceutical companies proactively select, track and evaluate third party vendors on a regular basis before, during and after the completion of the contract. The data manager has a significant role to play in effective management of third party vendor data.

Third party laboratory data management: Perspective with respect to clinical data management

PubMed Central

Johnson, Jasmin; Kanagali, Vishwanath; Prabu, D.

2014-01-01

Third party lab vendor provides support for laboratory, biological samples analytics data, collected during the clinical trial. Third party laboratory data is considered to be very significant for the clinical trial data management process. Although outsourcing these services is considered to be advantageous for clinical trials, there are some risks involved. Hence, pharmaceutical companies proactively select, track and evaluate third party vendors on a regular basis before, during and after the completion of the contract. The data manager has a significant role to play in effective management of third party vendor data. PMID:24551587

Processes to manage analyses and publications in a phase III multicenter randomized clinical trial

PubMed Central

2014-01-01

Background The timely publication of findings in peer-reviewed journals is a primary goal of clinical research. In clinical trials, the processes leading to publication can be complex from choice and prioritization of analytic topics through to journal submission and revisions. As little literature exists on the publication process for multicenter trials, we describe the development, implementation, and effectiveness of such a process in a multicenter trial. Methods The Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial included a data coordinating center (DCC) and clinical centers that recruited and followed more than 1,000 patients. Publication guidelines were approved by the steering committee, and the publications committee monitored the publication process from selection of topics to publication. Results A total of 73 manuscripts were published in 23 peer-reviewed journals. When manuscripts were closely tracked, the median time for analyses and drafting of manuscripts was 8 months. The median time for data analyses was 5 months and the median time for manuscript drafting was 3 months. The median time for publications committee review, submission, and journal acceptance was 7 months, and the median time from analytic start to journal acceptance was 18 months. Conclusions Effective publication guidelines must be comprehensive, implemented early in a trial, and require active management by study investigators. Successful collaboration, such as in the HALT-C trial, can serve as a model for others involved in multidisciplinary and multicenter research programs. Trial registration The HALT-C Trial was registered with clinicaltrials.gov (NCT00006164). PMID:24886378

[Basic considerations during outsourcing of clinical data management services].

PubMed

Shen, Tong; Liu, Yan

2015-11-01

With worldwide improvements in the regulations of international and domestic clinical trial conductions, the quality of clinical trials and trial data management are receiving a great deal of attention. To ensure the quality of clinical trials, maintain business flexibilities and effectively utilize internal and external resources, the outsourcing model is used in the management of clinical data in operation of pharmaceutical companies. The essential criteria of a successful outsourcing mode in clinical trial are selection of qualified contract research organizations (CRO); establishment of appropriate outsourcing model, and generation of effective quality control systems to ensure the authenticity, integrity and accuracy of the clinical trial data.

Using the web for recruitment, screen, tracking, data management, and quality control in a dietary assessment clinical validation trial.

PubMed

Arab, Lenore; Hahn, Harry; Henry, Judith; Chacko, Sara; Winter, Ashley; Cambou, Mary C

2010-03-01

Screening and tracking subjects and data management in clinical trials require significant investments in manpower that can be reduced through the use of web-based systems. To support a validation trial of various dietary assessment tools that required multiple clinic visits and eight repeats of online assessments, we developed an interactive web-based system to automate all levels of management of a biomarker-based clinical trial. The "Energetics System" was developed to support 1) the work of the study coordinator in recruiting, screening and tracking subject flow, 2) the need of the principal investigator to review study progress, and 3) continuous data analysis. The system was designed to automate web-based self-screening into the trial. It supported scheduling tasks and triggered tailored messaging for late and non-responders. For the investigators, it provided real-time status overviews on all subjects, created electronic case reports, supported data queries and prepared analytic data files. Encryption and multi-level password protection were used to insure data privacy. The system was programmed iteratively and required six months of a web programmer's time along with active team engagement. In this study the enhancement in speed and efficiency of recruitment and quality of data collection as a result of this system outweighed the initial investment. Web-based systems have the potential to streamline the process of recruitment and day-to-day management of clinical trials in addition to improving efficiency and quality. Because of their added value they should be considered for trials of moderate size or complexity. Copyright 2009 Elsevier Inc. All rights reserved.

Unfulfilled translation opportunities in industry sponsored clinical trials.

PubMed

Smed, Marie; Getz, Kenneth A

2013-05-01

Knowledge generated by site representatives through their participation in clinical trials is valuable for testing new products in use and obtaining final market approval. The leverage of this important knowledge is however challenged as the former direct relationships between in-house staff in the industry and site representatives are changing. The process of clinical trials has increased in complexity over the years, resulting in additional management layers. Besides an increase in internal management layers, sponsors often also outsource various tasks related to clinical trials to a CRO (Contract Research Organization) and thereby adding another link in the relationships between site and sponsor. These changes are intended to optimize the time-consuming and costly trial phases; however, there is a need to study whether valuable knowledge and experience is compromised in the process. Limited research exists on the full range of clinical practice insights obtained by investigators during and after clinical trials and how well these insights are transferred to study sponsors. This study explores the important knowledge-transfer processes between sites and sponsors and to what extent sites' knowledge gained in clinical trials is utilized by the industry. Responses from 451 global investigative site representatives are included in the study. The analysis of the extensive dataset reveals that the current processes of collaboration between sites and the industry restrict the leverage of valuable knowledge gained by physicians in the process of clinical trials. These restrictions to knowledge-transfer between site and sponsor are further challenged if CRO partners are integrated in the trial process. Copyright © 2013 Elsevier Inc. All rights reserved.

Is laser acupuncture an effective complementary therapy for obesity management? A systematic review of clinical trials.

PubMed

Namazi, Nazli; Khodamoradi, Kajal; Larijani, Bagher; Ayati, Mohammad Hossein

2017-12-01

Complementary therapies may increase the success rate of weight loss via a calorie-restricted diet. Acupuncture is a popular complementary therapy for obesity management. To our knowledge, no studies have summarised the effects of laser acupuncture (LA) on obesity. To evaluate the efficacy of LA, in particular with respect to its impact on anthropometric features and appetite in obese adults, by conducting a systematic review of previous clinical trials. We searched PubMed/Medline, Scopus, Web of Science, the Cochrane Library, Embase and Google Scholar electronic databases for papers published through October 2016. All clinical trials in English containing either anthropometric indices or appetite parameters were included. Two reviewers independently examined studies based on a predefined form for data extraction and the Jadad scale for quality assessment in order to minimise bias throughout the evaluation. After screening the papers, seven clinical trials met the criteria and were included in the systematic review. Positive effects of LA therapy were seen in body weight (n=3), body mass index (n=5), waist circumference (n=4), hip circumference (n=3), waist to hip ratio (n=4) and % fat mass (n=3). Appetite parameters were reported in one study, which showed that LA can reduce appetite and increase the sensation of feeling full. Although some studies have indicated beneficial effects for LA on obesity, the lack of evidence with high methodological quality made it impossible to reach a definitive conclusion about the efficacy of LA for obesity management. Further high-quality, randomised, sham-controlled clinical trials with a larger sample size are needed to shed light on the efficacy of LA for obesity management and weight maintenance. © 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.

Chronic hand eczema--self-management and prognosis: a study protocol for a randomised clinical trial.

PubMed

Mollerup, Annette; Veien, Niels Kren; Johansen, Jeanne Duus

2012-06-12

Hand eczema has a one-year prevalence of approximately 10 % in the general Danish population. Often the disease becomes chronic with numerous implications for the individual's daily life, occupation and quality of life. However, no guidelines of self-management recommendations beyond the acute stage are given. Self-management of the disease is pivotal and involves self-monitoring of the condition, medication adherence, and preventive behaviour. Interventions best to support the individual in this ongoing process need to be developed. This paper describes the design of a randomised clinical trial to test a newly developed intervention of individual counselling versus conventional information. 300 patients consecutively referred to dermatologic treatment at two different settings are individually randomised to either the intervention programme, named 'The Healthy Skin Clinic' or to the control group. Block-wise randomisation according to setting and gender is carried out.The intervention offers a tool for self-monitoring; basic and specific individual counselling; the possibility of asynchronous communication with the intervention team; and an electronic patient dialogue forum. Primary outcome variable is objective assessment of the hand eczema severity performed at baseline prior to randomisation, and repeated at six months follow-up. Secondary outcome variables are dermatology related life quality and perceived global burden of disease. The trial aims at evaluating a newly developed guidance programme which is expected to support self-management of patients referred to dermatology treatment due to chronic hand eczema. The design of the protocol is pragmatic with blinding of neither participants nor the investigator. Thus, in the interpretation of the results, the investigator takes into account effects that may be attributed to actors of the interventions rather than the intervention per se as well of potential observer bias. Inclusion criterions are wide in order

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

A Randomized Clinical Trial of a Money Management Intervention for Veterans With Psychiatric Disabilities.

PubMed

Elbogen, Eric B; Hamer, Robert M; Swanson, Jeffrey W; Swartz, Marvin S

2016-10-01

The study evaluated an intervention to help veterans with psychiatric disabilities, who face a unique set of challenges concerning money management. A randomized clinical trial was conducted of a brief (one to three hours) psychoeducational, recovery-oriented money management intervention called $teps for Achieving Financial Empowerment ($AFE). Analyses revealed no main effects on outcomes of random assignment to $AFE (N=67) or a control condition consisting of usual care (N=77). Veterans who reported using $AFE skills showed significantly lower impulsive buying, more responsible spending, higher rates of engaging in vocational activities, and greater number of work hours compared with veterans in the control condition. Findings have clinical implications for case management services involving informal money management assistance. Offering veterans with psychiatric disabilities a one-time money management intervention is unlikely to lead to substantial changes. Results imply that efforts to improve psychosocial outcomes among veterans must not only teach but also increase use of money management skills.

[An Investigation of the Role Responsibilities of Clinical Research Nurses in Conducting Clinical Trials].

PubMed

Kao, Chi-Yin; Huang, Guey-Shiun; Dai, Yu-Tzu; Pai, Ya-Ying; Hu, Wen-Yu

2015-06-01

Clinical research nurses (CRNs) play an important role in improving the quality of clinical trials. In Taiwan, the increasing number of clinical trials has increased the number of practicing CRNs. Understanding the role responsibilities of CRNs is necessary to promote professionalism in this nursing category. This study investigates the role responsibilities of CRNs in conducting clinical trials / research. A questionnaire survey was conducted in a medical center in Taipei City, Taiwan. Eighty CRNs that were registered to facilitate and conduct clinical trials at this research site completed the survey. "Subject protection" was the CRN role responsibility most recognized by participants, followed by "research coordination and management", "subject clinical care", and "advanced professional nursing". Higher recognition scores were associated with higher importance scores and lower difficulty scores. Participants with trial training had significantly higher difficulty scores for "subject clinical care" and "research coordination and management" than their peers without this training (p < .05). Participants who had participated in a long-term trial-training course earned higher importance scores for "CRN four-subthemes role responsibilities" (p <.05) and lower difficulty scores for "subject protection", "research coordination and management" (p <.005) than their short-term course peers. "Recognition of overall responsibilities" and "receiving trial training" were the significant predictors of difficulty in performing CRN role responsibilities, explaining 21.9% of the total variance. To further promote CRN as a professional career in Taiwan, the findings of this study recommend identifying the core competences of CRNs and adding CRN-related study materials into the advanced nursing curriculum. Long-term and systematic educational training may help CRNs understand the importance of their role responsibilities, better recognize their professional role, and reflect these

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

PubMed

Califf, Robert M; Zarin, Deborah A; Kramer, Judith M; Sherman, Rachel E; Aberle, Laura H; Tasneem, Asba

2012-05-02

Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0

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.

Using the Web for Recruitment, Screening, Tracking, Data Management, and Quality Control in a Dietary Assessment Clinical Validation Trial

PubMed Central

Hahn, Harry; Henry, Judith; Chacko, Sara; Winter, Ashley; Cambou, Mary C

2010-01-01

Screening and tracking subjects and data management in clinical trials require significant investments in manpower that can be reduced through the use of web-based systems. To support a validation trial of various dietary assessment tools that required multiple clinic visits and eight repeats of online assessments, we developed an interactive web-based system to automate all levels of management of a biomarker-based clinical trial. The “Energetics System” was developed to support 1) the work of the study coordinator in recruiting, screening and tracking subject flow, 2) the need of the principal investigator to review study progress, and 3) continuous data analysis. The system was designed to automate web-based self-screening into the trial. It supported scheduling tasks and triggered tailored messaging for late and non-responders. For the investigators, it provided real time status overviews on all subjects, created electronic case reports, supported data queries and prepared analytic data files. Encryption and multi-level password protection were used to insure data privacy. The system was programmed iteratively and required six months of a web programmer's time along with active team engagement. In this study the enhancement in speed and efficiency of recruitment and quality of data collection as a result of this system outweighed the initial investment. Web-based systems have the potential to streamline the process of recruitment and day-to-day management of clinical trials in addition to improving efficiency and quality. Because of their added value they should be considered for trials of moderate size or complexity. Grant support: NIH funded R01CA105048. PMID:19925884

Clinical trial design for orthodontists.

PubMed

Pandis, Nikolaos; Cobourne, Martyn T

2013-06-01

High-quality research should form the basis of all clinical practice. Randomized controlled trials currently provide the gold standard for investigating the effectiveness of treatment interventions and these are increasingly being used in orthodontics. Here we discuss the reasons why this form of investigation provides the most useful evidence for assessing treatment outcome. The methods available to achieve true randomization, a fundamental component in the design of these trials, are also discussed. In addition, we focus on how to minimize bias in clinical research, not only during the design and management of a trial, but also when disseminating results. We focus on the importance of using control groups correctly and describe methods that are available to adequately power a trial. Finally, we emphasise the importance of accurate and transparent reporting, which facilitates correct communication and assessment of the evidence.

Recent clinical trials in valvular heart disease.

PubMed

Kiss, Daniel; Anwaruddin, Saif

2017-07-01

With widespread adoption of transcatheter aortic valve replacement, there has been a change in the approach to management of valvular heart disease. New interest has taken hold in transcatheter therapies for valvular heart disease, as well as research into pathophysiology and progression of disease. Additionally, several key trials have further refined our understanding of surgical management of valvular heart disease. This review will elucidate recent clinical trial data leading to changes in practice. There have been several landmark trials expanding the indications for transcatheter aortic valve replacement. Additionally, although still early, trials are beginning to demonstrate the feasibility and safety of transcatheter mitral valves. Options for transcatheter management of right-sided valvular disease continue to evolve, and these are areas of active investigation. The emergence of novel therapies for valvular heart disease has expanded the management options available, allowing physicians to better individualize treatment of patients with valvular heart disease. This review will focus on the recent (within 2 years) trials in this field of interest.

Ethics in clinical drug trial research in private practice.

PubMed

Beran, R G; Beran, M E

2006-09-01

Private clinics and clinicians have been involved in clinical drug trials for approximately two decades. This paper reviews the ethical consideration inherent in this process. Involvement of a single community based, private, Australian neurological clinic in the conduct of trials was audited. Changes in ethical considerations were analysed. The clinic previously audited its clinical trial involvement, starting with pharmaceutical company orchestrated trials. These were vetted by hospital based ethics committees (ECs) which then refused to review private research. A private EC accommodating NH & MRC standards was formed to assess private research. Indemnity concerns forced return to institutional ECs with government guaranteed indemnification. Trials evolved to investigator initiated, company sponsored studies thence a company asking the clinic to devise, sponsor and manage a trial. The latter relegated trial co-ordination to the clinic which would control publication thereby creating new ethical standards. Private practice trial involvement evolved from reluctant inclusion to a pivotal role in privately sponsored studies. Access to ECs is government endorsed and publication is independent for investigator-sponsored trials. There has been modification of standard operating procedures and enhanced ethical standards.

Clinical Trials: A Congressional Focus of Need.

PubMed

Coltman

1997-01-01

Senator Specter, Honorable Members of the Committee, it is my high privilege to speak on behalf of a subject near and dear to my heart. I have been involved in the care of patients with cancer and in cancer clinical trials for the past 34 years. I chair the Southwest Oncology Group, the largest National Cancer Institute-supported cancer clinical research organization. In 1996, this Group enrolled 6,359 patients to therapeutic cancer clinical trials from all 50 states (Fig. 1), and completed the randomization of 18,867 normal, healthy men into the intergroup Prostate Cancer Prevention Trial. Cancer clinical trials are always designed to improve the outcomes of cancer patients. However, only 2%-3% of all eligible cancer patients in this country are treated on these cutting-edge trials. It is clear that this number must increase dramatically in order for us to be able to translate the monumental advances emanating from the basic cancer research laboratories into effective diagnosis, prevention and treatment strategies for patients with and at high risk for cancer. This low accrual is related to multiple factors: First, managed care has had a negative impact related to its refusal to reimburse for the clinical care aspects of patients on cancer clinical trials. During my presentation to the President's Cancer Panel in San Antonio in September, I shared three thoughts as to what the Panel should be asking as they pursue the question of "Managed Care's Role in the War on Cancer": &bul; "Should managed care bear a portion of the costs of clinical research as a form of R & D?" &bul; "What State or Federal legislation is needed to assure that managed care patients have access to cancer clinical research?" &bul; "Will there be any future for cancer clinical research when the managed care tidal wave finally reaches Chicago and New York?" The NCI-Department of Defense and the NCI-Department of Veterans Affairs Interagency Agreements are superb models of what needs to be done

Advances in the management of multiple sclerosis spasticity: recent clinical trials.

PubMed

Fernández, Oscar

2014-01-01

Most patients with multiple sclerosis (MS) experience spasticity as the clinical course evolves. Associated symptoms include (often painful) spasms, urinary dysfunction and sleep disturbances. THC:CBD oromucosal spray (Sativex®) is approved for symptom improvement in adult patients with moderate to severe MS-related spasticity who have not responded adequately to other antispasticity medication and who demonstrate clinically significant improvement in spasticity-related symptoms during an initial trial of therapy. In pivotal clinical trials of THC:CBD oromucosal spray, a meaningful proportion of patients with treatment-resistant MS spasticity achieved clinically relevant improvement with active treatment versus placebo. The utility of a 4-week trial of therapy to identify patients who respond to treatment was demonstrated in an enriched-design study. THC:CBD oromucosal spray was well tolerated in these studies, with no evidence of effects typically associated with recreational cannabis use. In a subsequent post approval clinical trial, THC:CBD oromucosal spray had no statistically significant effect on cognition and mood compared with placebo. Moreover, after 50 weeks' treatment, approximately two-thirds of patients, physicians and caregivers reported improvement from baseline in spasticity based on global impressions of change. Key Messages: In phase III clinical trials, approximately one-third of MS patients with treatment-resistant spasticity had a clinically relevant and statistically significant response to THC:CBD oromucosal spray. In addition to a reduction in spasticity, responders experienced meaningful relief from associated symptoms. THC:CBD oromucosal spray was generally well tolerated and efficacy was maintained over the longer term. A post-approval clinical trial indicated no effect of THC:CBD oromucosal spray on cognition or mood after 50 weeks of use. © 2014 S. Karger AG, Basel.

Clinical trial management of participant recruitment, enrollment, engagement, and retention in the SMART study using a Marketing and Information Technology (MARKIT) model

PubMed Central

Gupta, Anjali; Calfas, Karen J.; Marshall, Simon J.; Robinson, Thomas N.; Rock, Cheryl L.; Huang, Jeannie S.; Epstein-Corbin, Melanie; Servetas, Christina; Donohue, Michael C.; Norman, Gregory J.; Raab, Fredric; Merchant, Gina; Fowler, James H.; Griswold, William G.; Fogg, B.J.; Patrick, Kevin

2015-01-01

Advances in information technology and near ubiquity of the Internet have spawned novel modes of communication and unprecedented insights into human behavior via the digital footprint. Health behavior randomized controlled trials (RCTs), especially technology-based, can leverage these advances to improve the overall clinical trials management process and benefit from improvements at every stage, from recruitment and enrollment to engagement and retention. In this paper, we report the results for recruitment and retention of participants in the SMART study and introduce a new model for clinical trials management that is a result of interdisciplinary team science. The MARKIT model brings together best practices from information technology, marketing, and clinical research into a single framework to maximize efforts for recruitment, enrollment, engagement, and retention of participants into a RCT. These practices may have contributed to the study’s on-time recruitment that was within budget, 86% retention at 24 months, and a minimum of 57% engagement with the intervention over the 2-year RCT. Use of technology in combination with marketing practices may enable investigators to reach a larger and more diverse community of participants to take part in technology-based clinical trials, help maximize limited resources, and lead to more cost-effective and efficient clinical trial management of study participants as modes of communication evolve among the target population of participants. PMID:25866383

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.

Impact of a clinical trial initiative on clinical trial enrollment in a multidisciplinary prostate cancer clinic.

PubMed

Madsen, Lydia T; Kuban, Deborah A; Choi, Seungtaek; Davis, John W; Kim, Jeri; Lee, Andrew K; Domain, Delora; Levy, Larry; Pisters, Louis L; Pettaway, Curtis A; Ward, John F; Logothetis, Christopher; Hoffman, Karen E

2014-07-01

Clinical oncology trials are hampered by low accrual rates, with fewer than 5% of adult patients with cancer treated on study. Clinical trial enrollment was evaluated at The University of Texas MD Anderson Cancer Center's Multidisciplinary Prostate Cancer Clinic (MPCC) to assess whether a clinical trial initiative, introduced in 2006, impacted enrollment. The trial initiative included posting trial-specific information in clinic, educating patients about appropriate clinical trial options during the treatment recommendation discussion, and providing patients with trial-specific educational information. The investigators evaluated the frequency of clinical trial enrollment for men with newly diagnosed prostate cancer seen in the MPCC from 2004 to 2008. Logistic regression evaluated the impact of patient characteristics and the clinical trial initiative on trial enrollment. The median age of the 1370 men was 64 years; 32% had low-risk, 49% had intermediate-risk, and 19% had high-risk disease. Overall, 74% enrolled in at least one trial and 29% enrolled in more than one trial. Trial enrollment increased from 39% before the initiative (127/326) to 84% (880/1044) after the trial initiative. Patient enrollment increased in laboratory studies (from 25% to 80%), quality-of-life studies (from 10% to 26%), and studies evaluating investigational treatments and systemic agents (from 6% to 15%) after the trial initiative. In multivariate analysis, younger men (P<.001) and men seen after implementation of the clinical trial initiative (P<.001) were more likely to enroll in trials. Clinical trial enrollment in the MPCC was substantially higher than that seen nationally in adult patients with cancer, and enrollment rates increased after the introduction of a clinical trial initiative. Copyright © 2014 by the National Comprehensive Cancer Network.

Improving patient recruitment to multicentre clinical trials: the case for employing a data manager in a district general hospital-based oncology centre.

PubMed

Street, A; Strong, J; Karp, S

2001-01-01

One of the most frequently cited reasons for poor recruitment to multicentre randomized clinical trials is the additional workload placed on clinical staff. We report the effect on patient recruitment of employing a data manager to support clinical staff in an English district general hospital (DGH). In addition, we explore the effect data managers have on the quality of data collected, proxied by the number of queries arising with the trial organizers. We estimate that the cost of employing a data manager on a full-time basis is 502 per patient recruited but may amount to 326 if the appointment is part-time. Data quality is high when full responsibility lies with a data manager but falls when responsibility is shared. Whether the costs of employing a data manager to recruit patients from a DGH are worth incurring depends on the value placed on the speed at which multicentre trials can be completed, how important it is to broaden the research base beyond the traditional setting of teaching hospitals, and the amount of evaluative data required.

Understanding Clinical Trials

Cancer.gov

Watch these videos to learn about some basic aspects of cancer clinical trials such as the different phases of clinical trials, methods used to protect patient safety, and how the costs of clinical trials are covered.

Recognizing and managing a deteriorating patient: a randomized controlled trial investigating the effectiveness of clinical simulation in improving clinical performance in undergraduate nursing students.

PubMed

Stayt, Louise Caroline; Merriman, Clair; Ricketts, Barry; Morton, Sean; Simpson, Trevor

2015-11-01

To report the results of a randomized controlled trial which explored the effectiveness of clinical simulation in improving the clinical performance of recognizing and managing an adult deteriorating patient in hospital. There is evidence that final year undergraduate nurses may lack knowledge, clinical skills and situation awareness required to manage a deteriorating patient competently. The effectiveness of clinical simulation as a strategy to teach the skills required to recognize and manage the early signs of deterioration needs to be evaluated. This study was a two centre phase II single, randomized, controlled trial with single blinded assessments. Data were collected in July 2013. Ninety-eight first year nursing students were randomized either into a control group, where they received a traditional lecture, or an intervention group where they received simulation. Participants completed a pre- and postintervention objective structured clinical examination. General Perceived Self Efficacy and Self-Reported Competency scores were measured before and after the intervention. Student satisfaction with teaching was also surveyed. The intervention group performed significantly better in the post-objective structured clinical examination. There was no significant difference in the postintervention General Perceived Self Efficacy and Self-Reported Competency scores between the control and intervention group. The intervention group was significantly more satisfied with their teaching method. Simulation-based education may be an effective educational strategy to teach nurses the skills to effectively recognize and manage a deteriorating patient. © 2015 John Wiley & Sons Ltd.

Factors associated with reporting results for pulmonary clinical trials in ClinicalTrials.gov.

PubMed

Riley, Isaretta L; Boulware, L Ebony; Sun, Jie-Lena; Chiswell, Karen; Que, Loretta G; Kraft, Monica; Todd, Jamie L; Palmer, Scott M; Anderson, Monique L

2018-02-01

Background/aims The Food and Drug Administration Amendments Act mandates that applicable clinical trials report basic summary results to the ClinicalTrials.gov database within 1 year of trial completion or termination. We aimed to determine the proportion of pulmonary trials reporting basic summary results to ClinicalTrials.gov and assess factors associated with reporting. Methods We identified pulmonary clinical trials subject to the Food and Drug Administration Amendments Act (called highly likely applicable clinical trials) that were completed or terminated between 2008 and 2012 and reported results by September 2013. We estimated the cumulative percentage of applicable clinical trials reporting results by pulmonary disease category. Multivariable Cox regression modeling identified characteristics independently associated with results reporting. Results Of 1450 pulmonary highly likely applicable clinical trials, 380 (26%) examined respiratory neoplasms, 238 (16%) asthma, 175 (12%) chronic obstructive pulmonary disease, and 657 (45%) other respiratory diseases. Most (75%) were pharmaceutical highly likely applicable clinical trials and 71% were industry-funded. Approximately 15% of highly likely applicable clinical trials reported results within 1 year of trial completion, while 55% reported results over the 5-year study period. Earlier phase highly likely applicable clinical trials were less likely to report results compared to phase 4 highly likely applicable clinical trials (phases 1/2 and 2 (adjusted hazard ratio 0.41 (95% confidence interval: 0.31-0.54)), phases 2/3 and 3 (adjusted hazard ratio 0.55 (95% confidence interval: 0.42-0.72)) and phase not applicable (adjusted hazard ratio 0.43 (95% confidence interval: 0.29-0.63)). Pulmonary highly likely applicable clinical trials without Food and Drug Administration oversight were less likely to report results compared with those with oversight (adjusted hazard ratio 0.65 (95% confidence interval: 0

Clinical trial management of participant recruitment, enrollment, engagement, and retention in the SMART study using a Marketing and Information Technology (MARKIT) model.

PubMed

Gupta, Anjali; Calfas, Karen J; Marshall, Simon J; Robinson, Thomas N; Rock, Cheryl L; Huang, Jeannie S; Epstein-Corbin, Melanie; Servetas, Christina; Donohue, Michael C; Norman, Gregory J; Raab, Fredric; Merchant, Gina; Fowler, James H; Griswold, William G; Fogg, B J; Patrick, Kevin

2015-05-01

Advances in information technology and near ubiquity of the Internet have spawned novel modes of communication and unprecedented insights into human behavior via the digital footprint. Health behavior randomized controlled trials (RCTs), especially technology-based, can leverage these advances to improve the overall clinical trials management process and benefit from improvements at every stage, from recruitment and enrollment to engagement and retention. In this paper, we report the results for recruitment and retention of participants in the SMART study and introduce a new model for clinical trials management that is a result of interdisciplinary team science. The MARKIT model brings together best practices from information technology, marketing, and clinical research into a single framework to maximize efforts for recruitment, enrollment, engagement, and retention of participants into a RCT. These practices may have contributed to the study's on-time recruitment that was within budget, 86% retention at 24 months, and a minimum of 57% engagement with the intervention over the 2-year RCT. Use of technology in combination with marketing practices may enable investigators to reach a larger and more diverse community of participants to take part in technology-based clinical trials, help maximize limited resources, and lead to more cost-effective and efficient clinical trial management of study participants as modes of communication evolve among the target population of participants. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Clinical Trials

MedlinePlus

Clinical trials are research studies that test how well new medical approaches work in people. Each study ... prevent, screen for, diagnose, or treat a disease. Clinical trials may also compare a new treatment to ...

Chronic hand eczema - self-management and prognosis: a study protocol for a randomised clinical trial

PubMed Central

2012-01-01

Background Hand eczema has a one-year prevalence of approximately 10 % in the general Danish population. Often the disease becomes chronic with numerous implications for the individual’s daily life, occupation and quality of life. However, no guidelines of self-management recommendations beyond the acute stage are given. Self-management of the disease is pivotal and involves self-monitoring of the condition, medication adherence, and preventive behaviour. Interventions best to support the individual in this ongoing process need to be developed. Methods/design This paper describes the design of a randomised clinical trial to test a newly developed intervention of individual counselling versus conventional information. 300 patients consecutively referred to dermatologic treatment at two different settings are individually randomised to either the intervention programme, named ‘The Healthy Skin Clinic’ or to the control group. Block-wise randomisation according to setting and gender is carried out. The intervention offers a tool for self-monitoring; basic and specific individual counselling; the possibility of asynchronous communication with the intervention team; and an electronic patient dialogue forum. Primary outcome variable is objective assessment of the hand eczema severity performed at baseline prior to randomisation, and repeated at six months follow-up. Secondary outcome variables are dermatology related life quality and perceived global burden of disease. Discussion The trial aims at evaluating a newly developed guidance programme which is expected to support self-management of patients referred to dermatology treatment due to chronic hand eczema. The design of the protocol is pragmatic with blinding of neither participants nor the investigator. Thus, in the interpretation of the results, the investigator takes into account effects that may be attributed to actors of the interventions rather than the intervention per se as well of potential observer

Quality of clinical trials: A moving target

PubMed Central

Bhatt, Arun

2011-01-01

Quality of clinical trials depends on data integrity and subject protection. Globalization, outsourcing and increasing complexicity of clinical trials have made the target of achieving global quality challenging. The quality, as judged by regulatory inspections of the investigator sites, sponsors/contract research organizations and Institutional Review Board, has been of concern to the US Food and Drug Administration, as there has been hardly any change in frequency and nature of common deficiencies. To meet the regulatory expectations, the sponsors need to improve quality by developing systems with specific standards for each clinical trial process. The quality systems include: personnel roles and responsibilities, training, policies and procedures, quality assurance and auditing, document management, record retention, and reporting and corrective and preventive action. With an objective to improve quality, the FDA has planned new inspection approaches such as risk-based inspections, surveillance inspections, real-time oversight, and audit of sponsor quality systems. The FDA has partnered with Duke University for Clinical Trials Transformation Initiative, which will conduct research projects on design principles, data quality and quantity including monitoring, study start-up, and adverse event reporting. These recent initiatives will go a long way in improving quality of clinical trials. PMID:22145122

Imaging and Data Acquisition in Clinical Trials for Radiation Therapy

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

FitzGerald, Thomas J., E-mail: Thomas.Fitzgerald@umassmed.edu; Bishop-Jodoin, Maryann; Followill, David S.

2016-02-01

Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy qualitymore » assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials.« less

Assessing the detection, reporting and investigation of adverse events in clinical trial protocols implemented in Cameroon: a documentary review of clinical trial protocols.

PubMed

Ebile, Akoh Walter; Ateudjieu, Jerome; Yakum, Martin Ndinakie; Djuidje, Marceline Ngounoue; Watcho, Pierre

2015-09-29

International guidelines recommend ethical and scientific quality standards for managing and reporting adverse events occurring during clinical trials to competent research ethics committees and regulatory authorities. The purpose of this study was to determine whether clinical trial protocols in Cameroon are developed in line with national requirements and international guidelines as far as detecting, reporting and investigating of adverse events is concerned. It was a documentary review of all approved clinical trial protocols that were submitted at the Cameroon National Ethics Committee for evaluation from 1997 through 2012. Data were extracted using a preconceived and validated grid. Protocol review process targeted the title, abstract, objectives, methodology, resources, and the chapter on safety. In total, 106 (4.9 %) clinical trial protocols were identified from 2173 protocols seen in the archive and 104 (4.8 %) included for review. Seventy six (73.1 %) trials did not include the surveillance of adverse events as part of their objective. A total of 91 (87.5 %) protocols did not budget for adverse event surveillance, 76 (73.1 %) did not have a data safety management board (DSMB), 11(10.6 %) included insurance for participants, 47 (45.2 %) did not include a case definition for serious adverse events, 33 (31.7 %) described procedures to detect adverse events, 33 (31.7 %) described procedure for reporting and 22 (21.2 %) described procedure for investigating adverse events. Most clinical trial protocols in Cameroon are developed to focus on benefits and pay little attention to harms. The development of national guidelines can improve the surveillance of adverse events in clinical trial research conducted in Cameroon. Adverse events surveillance tools and a budget are critical for an adequate planning for adverse event surveillance when developing trial protocols. Clinical trial protocols submitted in the Cameroon National Ethics Committee do not adequately plan

TERMTrial--terminology-based documentation systems for cooperative clinical trials.

PubMed

Merzweiler, A; Weber, R; Garde, S; Haux, R; Knaup-Gregori, P

2005-04-01

Within cooperative groups of multi-center clinical trials a standardized documentation is a prerequisite for communication and sharing of data. Standardizing documentation systems means standardizing the underlying terminology. The management and consistent application of terminology systems is a difficult and fault-prone task, which should be supported by appropriate software tools. Today, documentation systems for clinical trials are often implemented as so-called Remote-Data-Entry-Systems (RDE-systems). Although there are many commercial systems, which support the development of RDE-systems there is none offering a comprehensive terminological support. Therefore, we developed the software system TERMTrial which consists of a component for the definition and management of terminology systems for cooperative groups of clinical trials and two components for the terminology-based automatic generation of trial databases and terminology-based interactive design of electronic case report forms (eCRFs). TERMTrial combines the advantages of remote data entry with a comprehensive terminological control.

ClinicalTrials.gov

MedlinePlus

... Terms and Conditions Disclaimer ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted ... world. ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of ...

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov.

PubMed

Chen, Junchao; Huang, Jihan; Li, Jordan V; Lv, Yinghua; He, Yingchun; Zheng, Qingshan

2017-01-01

The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM.

Clinical Trial Electronic Portals for Expedited Safety Reporting: Recommendations from the Clinical Trials Transformation Initiative Investigational New Drug Safety Advancement Project.

PubMed

Perez, Raymond P; Finnigan, Shanda; Patel, Krupa; Whitney, Shanell; Forrest, Annemarie

2016-12-15

Use of electronic clinical trial portals has increased in recent years to assist with sponsor-investigator communication, safety reporting, and clinical trial management. Electronic portals can help reduce time and costs associated with processing paperwork and add security measures; however, there is a lack of information on clinical trial investigative staff's perceived challenges and benefits of using portals. The Clinical Trials Transformation Initiative (CTTI) sought to (1) identify challenges to investigator receipt and management of investigational new drug (IND) safety reports at oncologic investigative sites and coordinating centers and (2) facilitate adoption of best practices for communicating and managing IND safety reports using electronic portals. CTTI, a public-private partnership to improve the conduct of clinical trials, distributed surveys and conducted interviews in an opinion-gathering effort to record investigator and research staff views on electronic portals in the context of the new safety reporting requirements described in the US Food and Drug Administration's final rule (Code of Federal Regulations Title 21 Section 312). The project focused on receipt, management, and review of safety reports as opposed to the reporting of adverse events. The top challenge investigators and staff identified in using individual sponsor portals was remembering several complex individual passwords to access each site. Also, certain tasks are time-consuming (eg, downloading reports) due to slow sites or difficulties associated with particular operating systems or software. To improve user experiences, respondents suggested that portals function independently of browsers and operating systems, have intuitive interfaces with easy navigation, and incorporate additional features that would allow users to filter, search, and batch safety reports. Results indicate that an ideal system for sharing expedited IND safety information is through a central portal used by

The web of clinical trial registration obligations: have foreign clinical trials been caught?

PubMed

Hathaway, Carolyne R; Manthei, John R; Haas, J Ben; Meltzer, Elizabeth D

2009-01-01

The web of overlapping requirements, standards, recommendations and policies governing the conduct of clinical trials highlights the intense scrutiny of the ethical, data quality and public access issues raised by human trials that are conducted to demonstrate the safety and efficacy of medical products marketed in the United States. One relatively recent development is the requirement that sponsors register and make public information about their clinical trials and clinical trial results. These clinical trial registration requirements illustrate the interests of patients, providers and researchers in increased visibility, transparency and accessibility of clinical trials and the data they generate. These requirements, however, pose regulatory, logistical and practical hurdles for companies sponsoring clinical trials of drugs and medical devices.

Clinical Trials - Multiple Languages

MedlinePlus

... new window. Arabic (العربية) Expand Section Clinical Trials - English PDF Clinical Trials - العربية (Arabic) PDF American Cancer ... Traditional (Cantonese dialect) (繁體中文) Expand Section Clinical Trials - English PDF Clinical Trials - 繁體中文 (Chinese, Traditional (Cantonese dialect)) ...

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.

Patient reported outcomes (PROs) in clinical trials: is 'in-trial' guidance lacking? a systematic review.

PubMed

Kyte, Derek G; Draper, Heather; Ives, Jonathan; Liles, Clive; Gheorghe, Adrian; Calvert, Melanie

2013-01-01

Patient reported outcomes (PROs) are increasingly assessed in clinical trials, and guidelines are available to inform the design and reporting of such trials. However, researchers involved in PRO data collection report that specific guidance on 'in-trial' activity (recruitment, data collection and data inputting) and the management of 'concerning' PRO data (i.e., data which raises concern for the well-being of the trial participant) appears to be lacking. The purpose of this review was to determine the extent and nature of published guidelines addressing these areas. Systematic review of 1,362 articles identified 18 eligible papers containing 'in-trial' guidelines. Two independent authors undertook a qualitative content analysis of the selected papers. Guidelines presented in each of the articles were coded according to an a priori defined coding frame, which demonstrated reliability (pooled Kappa 0.86-0.97), and validity (<2% residual category coding). The majority of guidelines present were concerned with 'pre-trial' activities (72%), for example, outcome measure selection and study design issues, or 'post-trial' activities (16%) such as data analysis, reporting and interpretation. 'In-trial' guidelines represented 9.2% of all guidance across the papers reviewed, with content primarily focused on compliance, quality control, proxy assessment and reporting of data collection. There were no guidelines surrounding the management of concerning PRO data. The findings highlight there are minimal in-trial guidelines in publication regarding PRO data collection and management in clinical trials. No guidance appears to exist for researchers involved with the handling of concerning PRO data. Guidelines are needed, which support researchers to manage all PRO data appropriately and which facilitate unbiased data collection.

The Characteristics of TCM Clinical Trials: A Systematic Review of ClinicalTrials.gov

PubMed Central

Huang, Jihan; Li, Jordan V.; Lv, Yinghua; He, Yingchun

2017-01-01

Objective The aim of this review is to characterize current status of global TCM clinical trials registered in ClinicalTrials.gov. Methods We examined all the trials registered within ClinicalTrials.gov up to 25 September 2015, focusing on study interventions to identify TCM-related trials, and extracted 1,270 TCM trials from the data set. Results Overall, 691 (54.4%) trials were acupuncture, and 454 (35.8%) trials were herbal medicines. Differences in TCM trial intervention types were also evident among the specific therapeutic areas. Among all trials, 55.7% that were small studies enrolled <100 subjects, and only 8.7% of completed studies had reported results of trials. As for the location, the United States was second to China in conducting the most TCM trials. Conclusion This review is the first snapshot of the landscape of TCM clinical trials registered in ClinicalTrials.gov, providing the basis for treatment and prevention of diseases within TCM and offering useful information that will guide future research on TCM. PMID:29138646

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.

Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

PubMed

Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

2010-04-20

The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that

Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

PubMed Central

2010-01-01

Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The

Effect of Contract Research Organization Bureaucracy in Clinical Trial Management: A Model From Lung Cancer.

PubMed

Gobbini, Elisa; Pilotto, Sara; Pasello, Giulia; Polo, Valentina; Di Maio, Massimo; Arizio, Francesca; Galetta, Domenico; Petrillo, Patrizia; Chiari, Rita; Matocci, Roberta; Di Costanzo, Alessandro; Di Stefano, Teresa Severina; Aglietta, Massimo; Cagnazzo, Celeste; Sperduti, Isabella; Bria, Emilio; Novello, Silvia

2018-03-01

Contract research organization (CRO) support is largely included in clinical trial management, although its effect in terms of time savings and benefit has not yet been quantified. We performed a retrospective multicenter analysis of lung cancer trials to explore differences in term of trial activation timelines and accrual for studies with and without CRO involvement. Results regarding study timelines from feasibility data to first patient enrollment were collected from 7 Italian thoracic oncology departments. The final accruals (screened/enrolled patients) are reported. We considered CRO/sponsor-administered and CRO-free trials according to who was responsible for the management of the crucial setup phases. Of 113 trials, 62 (54.9%) were CRO-administered, 34 (30.1%) were sponsor-administered, and 17 (15.0%) were CRO-free. The median time from feasibility invitation to documentation obtainment was 151 days in the CRO-administered trials versus 128 in the sponsor-administered and 120 in the CRO-free trials. The time from document submission to contract signature was 142 days in the CRO-administered versus 128 in the sponsor-administered and 132 in the CRO-free trials. The time from global accrual opening to first patient enrollment was 247 days for the CRO-administered versus 194 in the sponsor-administered and 151 in the CRO-free trials. No significant differences were observed in terms of the median overall timeline: 21 months in the CRO-administered, 15 in the sponsor-administered, and 18 months in the CRO-free studies (P = .29). Although no statistically significant differences were identified, the results of our analysis support the idea that bureaucratic procedures might require more time in CRO-administered trials than in sponsor-administered and CRO-free studies. This bureaucratic delay could negatively affect Italian patients' screening and enrollment compared with other countries. Copyright © 2017 Elsevier Inc. All rights reserved.

Contribution of clinical trials to gross domestic product in Hungary

PubMed Central

Kaló, Zoltán; Antal, János; Pénzes, Miklós; Pozsgay, Csilla; Szepezdi, Zsuzsanna; Nagyjánosi, László

2014-01-01

Aim To determine the contribution of clinical trials to the gross domestic product (GDP) in Hungary. Methods An anonymous survey of pharmaceutical companies and clinical research organizations (CROs) was conducted to estimate their clinical trial-related employment and revenues. Clinical trial documents at the National Institute of Pharmacy (NIP) were analyzed to estimate trial-related revenues at health care institutions and the value of investigational medical products (IMPs) based on avoided drug costs. Financial benefits were calculated as 2010 US $ purchasing power parity (PPP) values. Results Clinical trials increased the revenue of Hungarian health care providers by US $165.6 million. The value of IMPs was US $67.0 million. Clinical trial operation and management activities generated 900 jobs and US $166.9 million in revenue among CROs and pharmaceutical companies. Conclusions The contribution of clinical trials to the Hungarian GDP in 2010 amounted to 0.2%. Participation in international clinical trials may result in health, financial, and intangible benefits that contribute to the sustainability of health care systems, especially in countries with severe resource constraints. Although a conservative approach was employed to estimate the economic benefits of clinical trials, further research is necessary to improve the generalizability of our findings. PMID:25358877

Effects of distance learning on clinical management of LUTS in primary care: a randomised trial.

PubMed

Wolters, René; Wensing, Michel; Klomp, Maarten; Lagro-Jansen, Toine; Weel, Chris van; Grol, Richard

2005-11-01

To determine the effect of a distance learning programme on general practice management of men with lower urinary tract symptoms (LUTS). A cluster randomised controlled trial was performed. General practitioners (GPs) were randomised to a distance learning programme accompanied with educational materials or to a control group only receiving mailed clinical guidelines on LUTS. Clinical management was considered as outcome. Sixty-three GPs registered care management of 187 patients older than 50 years attending the practice because of LUTS. The intervention group showed a lower referral rate to a urologist (OR: 0.08 (95% CI: 0.02-0.40)), but no effect on PSA testing or prescription of medication. PSA testing tended to be requested more frequently by intervention group GPs. Secondary analysis showed patients in the intervention group received more educational materials (OR: 75.6 (95% CI: 13.60-419.90)). The educational programme had impact on clinical management without changing PSA testing. Distance learning is an promising method for continuing education. Activating distance learning packages are a potentially effective method for improving professional performance. Emotional matters as PSA testing probably need a more complex approach.

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.

Organizational structure and communication strategies of the bypass angioplasty revascularization investigation: a multicenter clinical trial.

PubMed

Naydeck, B L; Sutton-Tyrrell, K; Burek, K; Sopko, G S

1996-06-01

Efficient communication is a challenge for the many operating components of a multicenter randomized clinical trial. Traditional management theory states that communications generally flow along a path established by a hierarchical organizational structure. A multicenter clinical trial does not fit traditional organizational models well and requires modification of traditional communication techniques. While the scientific community typically views a clinical trial as one large and cohesive enterprise, at each site the trial may actually be conducted as a small project related to the medical specialty of the investigator. Therefore overall trial management must be accomplished through collaboration rather than through direct management. In the Bypass Angioplasty Revascularization Investigation (BARI), the BARI clinical coordinating center has designed and utilized several mechanisms that facilitate effective communication and administrative control of a multicenter clinical trial. These mechanisms provide a framework of communication techniques that accommodate the specific needs of a complex organization.

Non-operative management of posterior tibialis tendon dysfunction: design of a randomized clinical trial [NCT00279630

PubMed Central

Kulig, Kornelia; Pomrantz, Amy B; Burnfield, Judith M; Reischl, Stephen F; Mais-Requejo, Susan; Thordarson, David B; Smith, Ronald W

2006-01-01

Background Posterior tibialis tendon dysfunction (PTTD) is a common cause of foot pain and dysfunction in adults. Clinical observations strongly suggest that the condition is progressive. There are currently no controlled studies evaluating the effectiveness of exercise, orthoses, or orthoses and exercise on Stage I or IIA PTTD. Our study will explore the effectiveness of an eccentric versus concentric strengthening intervention to results obtained with the use of orthoses alone. Findings from this study will guide the development of more efficacious PTTD intervention programs and contribute to enhanced function and quality of life in persons with posterior tibialis tendon dysfunction. Methods/design This paper presents the rationale and design for a randomized clinical trial evaluating the effectiveness of a treatment regime for the non-operative management of Stage I or IIA PTTD. Discussion We have presented the rationale and design for an RCT evaluating the effectiveness of a treatment regimen for the non-operative management of Stage I or IIA PTTD. The results of this trial will be presented as soon as they are available. PMID:16756656

Conducting qualitative research within Clinical Trials Units: avoiding potential pitfalls.

PubMed

Cooper, Cindy; O'Cathain, Alicia; Hind, Danny; Adamson, Joy; Lawton, Julia; Baird, Wendy

2014-07-01

The value of using qualitative research within or alongside randomised controlled trials (RCTs) is becoming more widely accepted. Qualitative research may be conducted concurrently with pilot or full RCTs to understand the feasibility and acceptability of the interventions being tested, or to improve trial conduct. Clinical Trials Units (CTUs) in the United Kingdom (UK) manage large numbers of RCTs and, increasingly, manage the qualitative research or collaborate with qualitative researchers external to the CTU. CTUs are beginning to explicitly manage the process, for example, through the use of standard operating procedures for designing and implementing qualitative research with trials. We reviewed the experiences of two UK Clinical Research Collaboration (UKCRC) registered CTUs of conducting qualitative research concurrently with RCTs. Drawing on experiences gained from 15 studies, we identify the potential for the qualitative research to undermine the successful completion or scientific integrity of RCTs. We show that potential problems can arise from feedback of interim or final qualitative findings to members of the trial team or beyond, in particular reporting qualitative findings whilst the trial is on-going. The problems include: We make recommendations for improving the management of qualitative research within CTUs. Copyright © 2014. Published by Elsevier Inc.

A novel drug management system in the Febuxostat versus Allopurinol Streamlined Trial: A description of a pharmacy system designed to supply medications directly to patients within a prospective multicenter randomised clinical trial.

PubMed

Rogers, Amy; Flynn, Robert Wv; McDonnell, Patrick; Mackenzie, Isla S; MacDonald, Thomas M

2016-12-01

Trials of investigational medicinal products are required to adhere to strict guidelines with regard to the handling and supply of medication. Information technology offers opportunities to approach clinical trial methodology in new ways. This report summarises a novel pharmacy system designed to supply trial medications directly to patients by post in the Febuxostat versus Allopurinol Streamlined Trial. A bespoke web-based software package was designed to facilitate the direct supply of trial medications to Febuxostat versus Allopurinol Streamlined Trial participants from a pharmacy based in the Medicines Monitoring Unit, University of Dundee. To date, 65,467 packs of medication have been dispensed using the system to 3978 patients. Up to 238 packs per day have been dispensed. The Medicines Monitoring Unit Febuxostat versus Allopurinol Streamlined Trial drug management system is an effective method of administering the complex drug supply requirements of a large-scale clinical trial with advantages over existing arrangements. A low rate of loss to follow-up in the Febuxostat versus Allopurinol Streamlined Trial may be attributable to the drug management system. © The Author(s) 2016.

The state of infectious diseases clinical trials: a systematic review of ClinicalTrials.gov.

PubMed

Goswami, Neela D; Pfeiffer, Christopher D; Horton, John R; Chiswell, Karen; Tasneem, Asba; Tsalik, Ephraim L

2013-01-01

There is a paucity of clinical trials informing specific questions faced by infectious diseases (ID) specialists. The ClinicalTrials.gov registry offers an opportunity to evaluate the ID clinical trials portfolio. We examined 40,970 interventional trials registered with ClinicalTrials.gov from 2007-2010, focusing on study conditions and interventions to identify ID-related trials. Relevance to ID was manually confirmed for each programmatically identified trial, yielding 3570 ID trials and 37,400 non-ID trials for analysis. The number of ID trials was similar to the number of trials identified as belonging to cardiovascular medicine (n = 3437) or mental health (n = 3695) specialties. Slightly over half of ID trials were treatment-oriented trials (53%, vs. 77% for non-ID trials) followed by prevention (38%, vs. 8% in non-ID trials). ID trials tended to be larger than those of other specialties, with a median enrollment of 125 subjects (interquartile range [IQR], 45-400) vs. 60 (IQR, 30-160) for non-ID trials. Most ID studies are randomized (73%) but nonblinded (56%). Industry was the funding source in 51% of ID trials vs. 10% that were primarily NIH-funded. HIV-AIDS trials constitute the largest subset of ID trials (n = 815 [23%]), followed by influenza vaccine (n = 375 [11%]), and hepatitis C (n = 339 [9%]) trials. Relative to U.S. and global mortality rates, HIV-AIDS and hepatitis C virus trials are over-represented, whereas lower respiratory tract infection trials are under-represented in this large sample of ID clinical trials. This work is the first to characterize ID clinical trials registered in ClinicalTrials.gov, providing a framework to discuss prioritization, methodology, and policy.

A centralized informatics infrastructure for the National Institute on Drug Abuse Clinical Trials Network.

PubMed

Pan, Jeng-Jong; Nahm, Meredith; Wakim, Paul; Cushing, Carol; Poole, Lori; Tai, Betty; Pieper, Carl F

2009-02-01

Clinical trial networks (CTNs) were created to provide a sustaining infrastructure for the conduct of multisite clinical trials. As such, they must withstand changes in membership. Centralization of infrastructure including knowledge management, portfolio management, information management, process automation, work policies, and procedures in clinical research networks facilitates consistency and ultimately research. In 2005, the National Institute on Drug Abuse (NIDA) CTN transitioned from a distributed data management model to a centralized informatics infrastructure to support the network's trial activities and administration. We describe the centralized informatics infrastructure and discuss our challenges to inform others considering such an endeavor. During the migration of a clinical trial network from a decentralized to a centralized data center model, descriptive data were captured and are presented here to assess the impact of centralization. We present the framework for the informatics infrastructure and evaluative metrics. The network has decreased the time from last patient-last visit to database lock from an average of 7.6 months to 2.8 months. The average database error rate decreased from 0.8% to 0.2%, with a corresponding decrease in the interquartile range from 0.04%-1.0% before centralization to 0.01-0.27% after centralization. Centralization has provided the CTN with integrated trial status reporting and the first standards-based public data share. A preliminary cost-benefit analysis showed a 50% reduction in data management cost per study participant over the life of a trial. A single clinical trial network comprising addiction researchers and community treatment programs was assessed. The findings may not be applicable to other research settings. The identified informatics components provide the information and infrastructure needed for our clinical trial network. Post centralization data management operations are more efficient and less

Towards building high performance medical image management system for clinical trials

NASA Astrophysics Data System (ADS)

Wang, Fusheng; Lee, Rubao; Zhang, Xiaodong; Saltz, Joel

2011-03-01

Medical image based biomarkers are being established for therapeutic cancer clinical trials, where image assessment is among the essential tasks. Large scale image assessment is often performed by a large group of experts by retrieving images from a centralized image repository to workstations to markup and annotate images. In such environment, it is critical to provide a high performance image management system that supports efficient concurrent image retrievals in a distributed environment. There are several major challenges: high throughput of large scale image data over the Internet from the server for multiple concurrent client users, efficient communication protocols for transporting data, and effective management of versioning of data for audit trails. We study the major bottlenecks for such a system, propose and evaluate a solution by using a hybrid image storage with solid state drives and hard disk drives, RESTfulWeb Services based protocols for exchanging image data, and a database based versioning scheme for efficient archive of image revision history. Our experiments show promising results of our methods, and our work provides a guideline for building enterprise level high performance medical image management systems.

[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.

Pediatric Clinical Trials Conducted in South Korea from 2006 to 2015: An Analysis of the South Korean Clinical Research Information Service, US ClinicalTrials.gov and European Clinical Trials Registries.

PubMed

Choi, Sheung-Nyoung; Lee, Ji-Hyun; Song, In-Kyung; Kim, Eun-Hee; Kim, Jin-Tae; Kim, Hee-Soo

2017-12-01

The status of pediatric clinical trials performed in South Korea in the last decade, including clinical trials of drugs with unapproved indications for children, has not been previously examined. The aim was to provide information regarding the current state of pediatric clinical trials and create a basis for future trials performed in South Korea by reviewing three databases of clinical trials registrations. We searched for pediatric clinical studies (participants <18 years old) conducted in South Korea between 2006 and 2015 registered on the Clinical Research Information Service (CRIS), ClinicalTrials.gov, and the European Clinical Trials Registry (EuCTR). Additionally, we reviewed whether unapproved indications were involved in each trial by comparing the trials with a list of authorized trials provided by the Ministry of Food and Drug Safety (MFDS). The primary and secondary outcomes were to determine the change in number of pediatric clinical trials with unapproved indications over time and to assess the status of unauthorized pediatric clinical trials from the MFDS and the publication of articles after these clinical trials, respectively. We identified 342 clinical studies registered in the CRIS (n = 81), ClinicalTrials.gov (n = 225), and EuCTR (n = 36), of which 306 were reviewed after excluding duplicate registrations. Among them, 181 studies were interventional trials dealing with drugs and biological agents, of which 129 (71.3%) involved unapproved drugs. Of these 129 trials, 107 (82.9%) were authorized by the MFDS. Pediatric clinical trials in South Korea aiming to establish the safety and efficacy of drugs in children are increasing; however, non-MFDS-authorized studies remain an issue.

[Non-commercial clinical trials--who will be the legal sponsor? Sponsorship of investigator-initiated clinical trials according to the German Drug Law].

PubMed

Benninger-Döring, G; Boos, J

2006-07-01

Non-commercial clinical trials may be of great benefit to the patients concerned. The 12th amendment to the German Drug Law (AMG) changed legal liability of the initiators of investigator-initiated clinical trials with extensive consequences for traditional project leaders. The central point under discussion is the sponsor's responsibility according to the AMG. Presently leading management divisions of university hospitals and universities are developing proceedings to assume sponsor responsibility by institutions (institutional sponsorship), which should enable investigator-initiated clinical trials to be conducted according to legal requirements in the future. Detailed problems and special questions can only be resolved in a single-minded fashion, and if necessary political processes should be catalyzed.

Performance of an Electronic Diary System for Intensive Insulin Management in Global Diabetes Clinical Trials

PubMed Central

Zhang, Shuyu; Mou, Jiani; Hackett, Andy P.; Raymond, Stephen A.; Chang, Annette M.

2015-01-01

Abstract Background: This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient–investigator interactions during intensive insulin management in diabetes clinical trials. Materials and Methods: We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report. Results: Patients (n=2,938) in 31 countries used e-diaries to transmit 2,439,087 blood glucose (BG) values, 96% of which were associated by the patient with a protocol time point during the 72-h response window. Of 208,192 hypoglycemia events captured, 96% had a BG value, and 95% had treatments and outcomes entered by patients within the 72-h window. Patients recorded administration of 1,964,477 insulin doses; 93% of basal insulin doses were adherent with the investigator prescription. Investigators adjusted 13 basal and 92 bolus insulin prescriptions per patient-year using the e-diary system. After 26 weeks of treatment and e-diary use in the combined study arms, hemoglobin A1c values decreased by 0.6% or 1.6% and fasting BG decreased by 7.8 or 28 mg/dL in patients with T1DM or T2DM, respectively. Conclusions: The e-diary system enabled comprehensive data collection and facilitated communication between investigators and patients for intensive insulin management in three global clinical trials testing basal insulins. PMID:25826466

Examining longitudinal stimulant use and treatment attendance as parallel outcomes in two contingency management randomized clinical trials

PubMed Central

McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

2015-01-01

The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one ‘parallel outcomes’ model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β = 0.060, p < 0.05). In the second trial, CM predicted negative urinalysis (−UA) over the 12-week treatment period (β = 0.069, p < 0.05). In both trials, there was a significant, positive relationship between attendance and −UA submission, but in the first trial a −UA at both baseline and over time was related to attendance over time (r = 0.117; r = 0.013, respectively) and in the second trial, a −UA submission at baseline was associated with increased attendance over time (r = 0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This ‘indirect reinforcement’ between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. PMID:26456717

Examining Longitudinal Stimulant Use and Treatment Attendance as Parallel Outcomes in Two Contingency Management Randomized Clinical Trials.

PubMed

McPherson, Sterling; Brooks, Olivia; Barbosa-Leiker, Celestina; Lederhos, Crystal; Lamp, Amanda; Murphy, Sean; Layton, Matthew; Roll, John

2016-02-01

The primary aim of this study was to examine stimulant use and longitudinal treatment attendance in one 'parallel outcomes' model in order to determine how these two outcomes are related to one another during treatment, and to quantify how the intervention impacts these two on- and off-target outcomes differently. Data came from two multi-site randomized clinical trials (RCTs) of contingency management (CM) that targeted stimulant use. We used parallel multilevel modeling to examine the impact of multiple pre-specified covariates, including selected Addiction Severity Index (ASI) scores, age and sex, in addition to CM on concurrent attendance and stimulant use in two separate analyses, i.e., one per trial. In one trial, CM was positively associated with attending treatment throughout the trial (β=0.060, p<0.05). In the second trial, CM predicted negative urinalysis ((-)UA) over the 12-week treatment period (β=0.069, p<0.05). In both trials, there was a significant, positive relationship between attendance and (-)UA submission, but in the first trial a (-)UA at both baseline and over time was related to attendance over time (r=0.117; r=0.013, respectively) and in the second trial, a (-)UA submission at baseline was associated with increased attendance over time (r=0.055). These findings indicate that stimulant use and treatment attendance over time are related but distinct outcomes that, when analyzed simultaneously, portray a more informative picture of their predictors and the separate trajectories of each. This 'indirect reinforcement' between two clinically meaningful on-target (directly reinforced behavior) and off-target (indirectly reinforced behavior) outcomes is in need of further examination in order to fully exploit the potential clinical benefits that could be realized in substance use disorder treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Optimization of protocol design: a path to efficient, lower cost clinical trial execution

PubMed Central

Malikova, Marina A

2016-01-01

Managing clinical trials requires strategic planning and efficient execution. In order to achieve a timely delivery of important clinical trials’ outcomes, it is useful to establish standardized trial management guidelines and develop robust scoring methodology for evaluation of study protocol complexity. This review will explore the challenges clinical teams face in developing protocols to ensure that the right patients are enrolled and the right data are collected to demonstrate that a drug is safe and efficacious, while managing study costs and study complexity based on proposed comprehensive scoring model. Key factors to consider when developing protocols and techniques to minimize complexity will be discussed. A methodology to identify processes at planning phase, approaches to increase fiscal return and mitigate fiscal compliance risk for clinical trials will be addressed. PMID:28031939

Ethics of clinical trials.

PubMed

Iyalomhe, G B S; Imomoh, P A

2007-01-01

Although clinical trials are conducted far more ethically and safer now than they were some decades ago, the elimination of gross abuses has tended to highlight more subtle ethical problems. Therefore, research in man, especially clinical drug trials, must now take into account ethical and legal requirements. This review examines the progress of clinical trial ethics, highlights the major ethical principles and challenges involved in the conduct of clinical trials, and suggests measures to ensure scientifically and ethically sound clinical trials. An internet search and a perusal of the literature on the history of clinical trials, medical ethics and good clinical practice, reveal that apart from laying a general principle, the Oath of Hippocrates did not provide a guide on the specific ethical problems involved in undertaking research, an important arm of advancement in medical knowledge. Hence, to avert continued ethical abuses of subjects during clinical research, the current reference guideliNe--the Helsinki Declaration of 1964 (revised in 1975), was adopted by the World Medical Assembly. It emphasized four major principles: autonomy, nonmaleficience, beneficence and justice. In applying these principles, the researcher must obtain a written free and well informed consent from patients who should be aware of their right to withdraw from trial at any moment. Where possible, a new drug should always first be compared to placebo in order to prove its superiority. He must ethically monitor and assess risks and benefits of the trial throughout its duration and use a fair procedure in selecting research subjects and must respect the concept of inviolability of the human person. Ethical challenges confronting clinical trials include the appropriateness of the proposed research, obtaining free informed consent, use of medications after completion of drug trials, drug toxicities and long-term side effects as well as the release and publication of research result. To

Development of a user customizable imaging informatics-based intelligent workflow engine system to enhance rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Martinez, Clarisa; Wang, Jing; Liu, Ye; Liu, Brent

2014-03-01

Clinical trials usually have a demand to collect, track and analyze multimedia data according to the workflow. Currently, the clinical trial data management requirements are normally addressed with custom-built systems. Challenges occur in the workflow design within different trials. The traditional pre-defined custom-built system is usually limited to a specific clinical trial and normally requires time-consuming and resource-intensive software development. To provide a solution, we present a user customizable imaging informatics-based intelligent workflow engine system for managing stroke rehabilitation clinical trials with intelligent workflow. The intelligent workflow engine provides flexibility in building and tailoring the workflow in various stages of clinical trials. By providing a solution to tailor and automate the workflow, the system will save time and reduce errors for clinical trials. Although our system is designed for clinical trials for rehabilitation, it may be extended to other imaging based clinical trials as well.

Advances in Clinical Cardiology 2016: A Summary of the Key Clinical Trials.

PubMed

Gray, Alastair; McQuillan, Conor; Menown, Ian B A

2017-07-01

The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA). Selection criteria were trials with a broad relevance to the cardiology community and those with potential to change current practice. A total of 57 key cardiology clinical trials were identified for inclusion. Here we describe and place in clinical context the key findings of new data relating to interventional and structural cardiology including delayed stenting following primary angioplasty, contrast-induced nephropathy, management of jailed wires, optimal duration of dual antiplatelet therapy (DAPT), stenting vs bypass for left main disease, new generation stents (BioFreedom, Orsiro, Absorb), transcatheter aortic valve implantation (Edwards Sapien XT, transcatheter embolic protection), and closure devices (Watchman, Amplatzer). New preventative cardiology data include trials of bariatric surgery, empagliflozin, liraglutide, semaglutide, PCSK9 inhibitors (evolocumab and alirocumab), and inclisiran. Antiplatelet therapy trials include platelet function monitoring and ticagrelor vs clopidogrel for peripheral vascular disease. New data are also presented in fields of heart failure (sacubitril/valsartan, aliskiren, spironolactone), atrial fibrillation (rivaroxaban in patients undergoing coronary intervention, edoxaban in DC cardioversion), cardiac devices (implantable cardioverter

Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of gastric cancer: a systematic review of phase II and III clinical trials.

PubMed

Mawalla, Brian; Yuan, Xianglin; Luo, Xiaoxiao; Chalya, Phillip L

2018-01-12

Advanced gastric cancer poses a therapeutic challenge worldwide. In randomised clinical trials, anti-VEGF has been reported as an essential agent for the treatment of advanced gastric cancer. This review aims at assessing the treatment outcome of anti-angiogenesis therapy through the VEGF pathway in the management of patients with advanced gastric cancer. During this review, 38 clinical trials were identified. Of these, 30 clinical trials were excluded, leaving eight trials of phase II and III. Ramucirumab, as a second line treatment of advanced gastric cancer, decreases the risk of disease progression (37-52%) and death (19-22%). Compare ramucirumab and bevacizumab in combination with traditional chemotherapy; ramucirumab has shown to improve progression-free survival and overall survival. Apatinib tyrosine kinase inhibitor combined with traditional chemotherapy has shown to improve overall response rate and progression-free survival with marginal improvements in overall survival. Chemotherapy, in combination with anti-VEGF drugs, in the management of advanced gastric cancer significantly improves the outcome of overall response rate, progression-free survival and overall survival when compared to chemotherapy alone. Therefore, we recommend that anti-VEGF drugs are the drugs of choice in the management of patients with advanced gastric cancer.

[Infrastructure and contents of clinical data management plan].

PubMed

Shen, Tong; Xu, Lie-dong; Fu, Hai-jun; Liu, Yan; He, Jia; Chen, Ping-yan; Song, Yu-fei

2015-11-01

Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.

Nurse-Led Multidisciplinary Heart Failure Group Clinic Appointments: Methods, Materials, and Outcomes Used in the Clinical Trial.

PubMed

Smith, Carol E; Piamjariyakul, Ubolrat; Dalton, Kathleen M; Russell, Christy; Wick, Jo; Ellerbeck, Edward F

2015-01-01

The Self-management and Care of Heart Failure through Group Clinics Trial evaluated the effects of multidisciplinary group clinic appointments on self-care skills and rehospitalizations in high-risk heart failure (HF) patients. The purpose of this article is to (1) describe key Self-management and Care of Heart Failure through Group Clinics Trial group clinic interactive learning strategies, (2) describe resources and materials used in the group clinic appointment, and (3) present results supporting this patient-centered group intervention. This clinical trial included 198 HF patients (randomized to either group clinical appointments or to standard care). Data were collected from 72 group clinic appointments via patients' (1) group clinic session evaluations, (2) HF self-care behaviors skills, (3) HF-related discouragement and quality of life scores, and (4) HF-related reshopitalizations during the 12-month follow-up. Also, the costs of delivery of the group clinical appointments were tabulated. Overall, patients rated group appointments as 4.8 of 5 on the "helpfulness" in managing HF score. The statistical model showed a 33% decrease in the rate of rehospitalizations (incidence rate ratio, 0.67) associated with the intervention over the 12-month follow-up period when compared with control patients (χ(2)1=3.9, P=.04). The total cost for implementing 5 group appointments was $243.58 per patient. The intervention was associated with improvements in HF self-care knowledge and home care behavior skills and managing their for HF care. In turn, better self-care was associated with reductions in HF-related hospitalizations.

Clinical Inertia in a Randomized Trial of Telemedicine-Based Chronic Disease Management: Lessons Learned.

PubMed

Barton, Anna Beth; Okorodudu, Daniel E; Bosworth, Hayden B; Crowley, Matthew J

2018-01-17

Treatment nonadherence and clinical inertia perpetuate poor cardiovascular disease (CVD) risk factor control. Telemedicine interventions may counter both treatment nonadherence and clinical inertia. We explored why a telemedicine intervention designed to reduce treatment nonadherence and clinical inertia did not improve CVD risk factor control, despite enhancing treatment adherence versus usual care. In this analysis of a randomized trial, we studied recipients of the 12-month telemedicine intervention. This intervention comprised two nurse-administered components: (1) monthly self-management education targeting improved treatment adherence; and (2) quarterly medication management facilitation designed to support treatment intensification by primary care (thereby reducing clinical inertia). For each medication management facilitation encounter, we ascertained whether patients met treatment goals, and if not, whether primary care recommended treatment intensification following the encounter. We assessed disease control associated with encounters, where intensification was/was not recommended. We examined 455 encounters across 182 intervention recipients (100% African Americans with type 2 diabetes). Even after accounting for valid reasons for deferring intensification (e.g., treatment nonadherence), intensification was not recommended in 67.5% of encounters in which hemoglobin A1c was above goal, 72.5% in which systolic blood pressure was above goal, and 73.9% in which low-density lipoprotein cholesterol was above goal. In each disease state, treatment intensification was more likely with poorer control. Despite enhancing treatment adherence, this intervention was unsuccessful in countering clinical inertia, likely explaining its lack of effect on CVD risk factors. We identify several lessons learned that may benefit investigators and healthcare systems.

Randomized Controlled Trial in Clinical Settings to Evaluate Effectiveness of Coping Skills Education Used with Progressive Tinnitus Management

ERIC Educational Resources Information Center

Henry, James A.; Thielman, Emily J.; Zaugg, Tara L.; Kaelin, Christine; Schmidt, Caroline J.; Griest, Susan; McMillan, Garnett P.; Myers, Paula; Rivera, Izel; Baldwin, Robert; Carlson, Kathleen

2017-01-01

Purpose: This randomized controlled trial evaluated, within clinical settings, the effectiveness of coping skills education that is provided with progressive tinnitus management (PTM). Method: At 2 Veterans Affairs medical centers, N = 300 veterans were randomized to either PTM intervention or 6-month wait-list control. The PTM intervention…

Clinical decision support tools for osteoporosis disease management: a systematic review of randomized controlled trials.

PubMed

Kastner, Monika; Straus, Sharon E

2008-12-01

Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management.

The Internet and Clinical Trials: Background, Online Resources, Examples and Issues

PubMed Central

Seib, Rachael; Prescott, Todd

2005-01-01

Both the Internet and clinical trials were significant developments in the latter half of the twentieth century: the Internet revolutionized global communications and the randomized controlled trial provided a means to conduct an unbiased comparison of two or more treatments. Large multicenter trials are often burdened with an extensive development time and considerable expense, as well as significant challenges in obtaining, backing up and analyzing large amounts of data. Alongside the increasing complexities of the modern clinical trial has grown the power of the Internet to improve communications, centralize and secure data as well as to distribute information. As more and more clinical trials are required to coordinate multiple trial processes in real time, centers are turning to the Internet for the tools to manage the components of a clinical trial, either in whole or in part, to produce lower costs and faster results. This paper reviews the historical development of the Internet and the randomized controlled trial, describes the Internet resources available that can be used in a clinical trial, reviews some examples of online trials and describes the advantages and disadvantages of using the Internet to conduct a clinical trial. We also extract the characteristics of the 5 largest clinical trials conducted using the Internet to date, which together enrolled over 26000 patients. PMID:15829477

Prevalence of clinical trial status discrepancies: A cross-sectional study of 10,492 trials registered on both ClinicalTrials.gov and the European Union Clinical Trials Register.

PubMed

Fleminger, Jessica; Goldacre, Ben

2018-01-01

Trial registries are a key source of information for clinicians and researchers. While building OpenTrials, an open database of public trial information, we identified errors and omissions in registries, including discrepancies between descriptions of the same trial in different registries. We set out to ascertain the prevalence of discrepancies in trial completion status using a cohort of trials registered on both the European Union Clinical Trials Register (EUCTR) and ClinicalTrials.gov. We used matching titles and registry IDs provided by both registries to build a cohort of dual-registered trials. Completion statuses were compared; we calculated descriptive statistics on the prevalence of discrepancies. 11,988 dual-registered trials were identified. 1,496 did not provide a comparable completion status, leaving 10,492 trials. 16.2% were discrepant on completion status. The majority of discrepancies (90.5%) were a 'completed' trial on ClinicalTrials.gov inaccurately marked as 'ongoing' on EUCTR. Overall, 33.9% of dual-registered trials described as 'ongoing' on EUCTR were listed as 'completed' on ClinicalTrials.gov. Completion status on registries is commonly inaccurate. Previous work on publication bias may underestimate non-reporting. We describe simple steps registry owners and trialists could take to improve accuracy.

Assessing the challenges of multi-scope clinical research sites: an example from NIH HIV/AIDS clinical trials networks.

PubMed

Rosas, Scott R; Cope, Marie T; Villa, Christie; Motevalli, Mahnaz; Utech, Jill; Schouten, Jeffrey T

2014-04-01

Large-scale, multi-network clinical trials are seen as a means for efficient and effective utilization of resources with greater responsiveness to new discoveries. Formal structures instituted within the National Institutes of Health (NIH) HIV/AIDS Clinical Trials facilitate collaboration and coordination across networks and emphasize an integrated approach to HIV/AIDS vaccine, prevention and therapeutics clinical trials. This study examines the joint usage of clinical research sites as means of gaining efficiency, extending capacity, and adding scientific value to the networks. A semi-structured questionnaire covering eight clinical management domains was administered to 74 (62% of sites) clinical site coordinators at single- and multi-network sites to identify challenges and efficiencies related to clinical trials management activities and coordination with multi-network units. Overall, respondents at multi-network sites did not report more challenges than single-network sites, but did report unique challenges to overcome including in the areas of study prioritization, community engagement, staff education and training, and policies and procedures. The majority of multi-network sites reported that such affiliations do allow for the consolidation and cost-sharing of research functions. Suggestions for increasing the efficiency or performance of multi-network sites included streamlining standards and requirements, consolidating protocol activation methods, using a single cross-network coordinating centre, and creating common budget and payment mechanisms. The results of this assessment provide important information to consider in the design and management of multi-network configurations for the NIH HIV/AIDS Clinical Trials Networks, as well as others contemplating and promoting the concept of multi-network settings. © 2013 John Wiley & Sons Ltd.

Clinical Trials in Benign Prostatic Hyperplasia: A Moving Target of Success.

PubMed

Thomas, Dominique; Chung, Caroline; Zhang, Yiye; Te, Alexis; Gratzke, Christian; Woo, Henry; Chughtai, Bilal

2018-05-24

Benign prostatic hyperplasia (BPH) affects over 50% of men above the age of 50 yr. With half of these men having bothersome lower urinary tract symptoms, this area represents a hot bed of novel treatments. Many BPH therapies have favorable short-term outcomes but lack durability or well-defined adverse events (AEs). Clinical trials are a gold standard for comparing treatments. We characterized all BPH clinical trials registered worldwide from inception to 2017. A total of 251 clinical trials were included. Of the studies, 30.1% used patient-reported outcomes such as the American Urological Association Symptom Score. Approximately 70% of clinical trials studied medical interventions, while the remaining trials investigated surgical approaches. Seventy-nine percent of trials were industry sponsored, while a minority were funded without commercial interest. Only 42% of trials had 12-mo follow-up, with the majority with <3 mo of follow-up. No trials evaluated prevention, diet, behavior, or alternative methods Overall, only 23% of trials reported results. Management options for BPH need unified benchmarks of success, AEs, durability, and standard reporting for all clinical trials, regardless of outcomes. We found that the majority of clinical trials were medical intervention, with very few trials evaluating prevention, diet, behavior, or alternative methods Furthermore, a few trials reported results in peer-reviewed journals. All clinical trials need to report results regardless of outcome, and in conclusion, standardized methods are needed in order to document the successes, adverse events, and durability for all clinical trials. Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

An analysis of registered clinical trials in otolaryngology from 2007 to 2010: ClinicalTrials.gov.

PubMed

Witsell, David L; Schulz, Kristine A; Lee, Walter T; Chiswell, Karen

2013-11-01

To describe the conditions studied, interventions used, study characteristics, and funding sources of otolaryngology clinical trials from the ClinicalTrials.gov database; compare this otolaryngology cohort of interventional studies to clinical visits in a health care system; and assess agreement between clinical trials and clinical activity. Database analysis. Trial registration data downloaded from ClinicalTrials.gov and administrative data from the Duke University Medical Center from October 1, 2007 to September 27, 2010. Data extraction from ClinicalTrials.gov was done using MeSH and non-MeSH disease condition terms. Studies were subcategorized to create the following groupings for descriptive analysis: ear, nose, allergy, voice, sleep, head and neck cancer, thyroid, and throat. Duke Health System visits were queried by using selected ICD-9 codes for otolaryngology and non-otolaryngology providers. Visits were grouped similarly to ClinicalTrials.gov for further analysis. Chi-square tests were used to explore differences between groups. A total of 1115 of 40,970 registered interventional trials were assigned to otolaryngology. Head and neck cancer trials predominated. Study models most frequently incorporated parallel design (54.6%), 2 study groups (46.6%), and randomization (69.1%). Phase 2 or 3 studies constituted 46.4% of the cohort. Comparison of the ClinicalTrials.gov database with administrative health system visit data by disease condition showed discordance between national research activity and clinical visit volume for patients with otolaryngology complaints. Analysis of otolaryngology-related clinical research as listed in ClinicalTrials.gov can inform patients, physicians, and policy makers about research focus areas. The relative burden of otolaryngology-associated conditions in our tertiary health system exceeds research activity within the field.

Re-Engineering Alzheimer Clinical Trials: Global Alzheimer's Platform Network.

PubMed

Cummings, J; Aisen, P; Barton, R; Bork, J; Doody, R; Dwyer, J; Egan, J C; Feldman, H; Lappin, D; Truyen, L; Salloway, S; Sperling, R; Vradenburg, G

2016-06-01

Alzheimer's disease (AD) drug development is costly, time-consuming, and inefficient. Trial site functions, trial design, and patient recruitment for trials all require improvement. The Global Alzheimer Platform (GAP) was initiated in response to these challenges. Four GAP work streams evolved in the US to address different trial challenges: 1) registry-to-cohort web-based recruitment; 2) clinical trial site activation and site network construction (GAP-NET); 3) adaptive proof-of-concept clinical trial design; and 4) finance and fund raising. GAP-NET proposes to establish a standardized network of continuously funded trial sites that are highly qualified to perform trials (with established clinical, biomarker, imaging capability; certified raters; sophisticated management system. GAP-NET will conduct trials for academic and biopharma industry partners using standardized instrument versions and administration. Collaboration with the Innovative Medicines Initiative (IMI) European Prevention of Alzheimer's Disease (EPAD) program, the Canadian Consortium on Neurodegeneration in Aging (CCNA) and other similar international initiatives will allow conduct of global trials. GAP-NET aims to increase trial efficiency and quality, decrease trial redundancy, accelerate cohort development and trial recruitment, and decrease trial costs. The value proposition for sites includes stable funding and uniform training and trial execution; the value to trial sponsors is decreased trial costs, reduced time to execute trials, and enhanced data quality. The value for patients and society is the more rapid availability of new treatments for AD.

Social media in clinical trials.

PubMed

Thompson, Michael A

2014-01-01

Social media has potential in clinical trials for pointing out trial issues, addressing barriers, educating, and engaging multiple groups involved in cancer clinical research. Social media is being used in clinical trials to highlight issues such as poor accrual and barriers; educate potential participants and physicians about clinical trial options; and is a potential indirect or direct method to improve accrual. We are moving from a passive "push" of information to patients to a "pull" of patients requesting information. Patients and advocates are often driving an otherwise reluctant health care system into communication. Online patient communities are creating new information repositories. Potential clinical trial participants are using the Twittersphere and other sources to learn about potential clinical trial options. We are seeing more organized patient-centric and patient-engaged forums with the potential to crowd source to improve clinical trial accrual and design. This is an evolving process that will meet many individual, institutional, and regulatory obstacles as we move forward in a changed research landscape.

Effect of health information technology interventions on lipid management in clinical practice: a systematic review of randomized controlled trials.

PubMed

Aspry, Karen E; Furman, Roy; Karalis, Dean G; Jacobson, Terry A; Zhang, Audrey M; Liptak, Gregory S; Cohen, Jerome D

2013-01-01

Large gaps in lipid treatment and medication adherence persist in high-risk outpatients in the United States. Health information technology (HIT) is being applied to close quality gaps in chronic illness care, but its utility for lipid management has not been widely studied. To perform a qualitative review of the impact of HIT interventions on lipid management processes of care (screening or testing; drug initiation, titration or adherence; or referrals) or clinical outcomes (percent at low density lipoprotein cholesterol goal; absolute lipid levels; absolute risk scores; or cardiac hospitalizations) in outpatients with coronary heart disease or at increased risk. PubMed and Google Scholar databases were searched using Medical Subject Headings related to clinical informatics and cholesterol or lipid management. English language articles that described a randomized controlled design, tested at least one HIT tool in high risk outpatients, and reported at least 1 lipid management process measure or clinical outcome, were included. Thirty-four studies that enrolled 87,874 persons were identified. Study ratings, outcomes, and magnitude of effects varied widely. Twenty-three trials reported a significant positive effect from a HIT tool on lipid management, but only 14 showed evidence that HIT interventions improve clinical outcomes. There was mixed evidence that provider-level computerized decision support improves outcomes. There was more evidence in support of patient-level tools that provide connectivity to the healthcare system, as well as system-level interventions that involve database monitoring and outreach by centralized care teams. Randomized controlled trials show wide variability in the effects of HIT on lipid management outcomes. Evidence suggests that multilevel HIT approaches that target not only providers but include patients and systems approaches will be needed to improve lipid treatment, adherence and quality. Copyright © 2013 National Lipid

Results of an Oncology Clinical Trial Nurse Role Delineation Study.

PubMed

Purdom, Michelle A; Petersen, Sandra; Haas, Barbara K

2017-09-01

To evaluate the relevance of a five-dimensional model of clinical trial nursing practice in an oncology clinical trial nurse population. 
. Web-based cross-sectional survey.
. Online via Qualtrics.
. 167 oncology nurses throughout the United States, including 41 study coordinators, 35 direct care providers, and 91 dual-role nurses who provide direct patient care and trial coordination.
. Principal components analysis was used to determine the dimensions of oncology clinical trial nursing practice.
. Self-reported frequency of 59 activities.
. The results did not support the original five-dimensional model of nursing care but revealed a more multidimensional model.
. An analysis of frequency data revealed an eight-dimensional model of oncology research nursing, including care, manage study, expert, lead, prepare, data, advance science, and ethics.
. This evidence-based model expands understanding of the multidimensional roles of oncology nurses caring for patients with cancer enrolled in clinical trials.

Clinical Trials in Dentistry: A Cross-sectional Analysis of World Health Organization-International Clinical Trial Registry Platform.

PubMed

Sivaramakrishnan, Gowri; Sridharan, Kannan

2016-06-01

Clinical trials are the back bone for evidence-based practice (EBP) and recently EBP has been considered the best source of treatment strategies available. Clinical trial registries serve as databases of clinical trials. As regards to dentistry in specific data on the number of clinical trials and their quality is lacking. Hence, the present study was envisaged. Clinical trials registered in WHO-ICTRP (http://apps.who.int/trialsearch/AdvSearch.aspx) in dental specialties were considered. The details assessed from the collected trials include: Type of sponsors; Health condition; Recruitment status; Study design; randomization, method of randomization and allocation concealment; Single or multi-centric; Retrospective or prospective registration; and Publication status in case of completed studies. A total of 197 trials were identified. Maximum trials were from United States (n = 30) and United Kingdom (n = 38). Seventy six trials were registered in Clinical Trials.gov, 54 from International Standards of Reporting Clinical Trials, 13 each from Australia and New Zealand Trial Register and Iranian Registry of Clinical Trials, 10 from German Clinical Trial Registry, eight each from Brazilian Clinical Trial Registry and Nederland's Trial Register, seven from Japan Clinical Trial Registry, six from Clinical Trial Registry of India and two from Hong Kong Clinical Trial Registry. A total of 78.7% studies were investigator-initiated and 64% were completed while 3% were terminated. Nearly four-fifths of the registered trials (81.7%) were interventional studies of which randomized were the large majority (94.4%) with 63.2% being open label, 20.4% using single blinding technique and 16.4% were doubled blinded. The number, methodology and the characteristics of clinical trials in dentistry have been noted to be poor especially in terms of being conducted multi-centrically, employing blinding and the method for randomization and allocation concealment. More emphasis has to be

Comparing clinical quality indicators for asthma management in children with outcome measures used in randomised controlled trials: a protocol.

PubMed

Choong, Miew Keen; Tsafnat, Guy; Hibbert, Peter; Runciman, William B; Coiera, Enrico

2015-09-08

Clinical quality indicators are necessary to monitor the performance of healthcare services. The development of indicators should, wherever possible, be based on research evidence to minimise the risk of bias which may be introduced during their development, because of logistic, ethical or financial constraints alone. The development of automated methods to identify the evidence base for candidate indicators should improve the process of indicator development. The objective of this study is to explore the relationship between clinical quality indicators for asthma management in children with outcome and process measurements extracted from randomised controlled clinical trial reports. National-level indicators for asthma management in children will be extracted from the National Quality Measures Clearinghouse (NQMC) database and the National Institute for Health and Care Excellence (NICE) quality standards. Outcome measures will be extracted from published English language randomised controlled trial (RCT) reports for asthma management in children aged below 12 years. The two sets of measures will be compared to assess any overlap. The study will provide insights into the relationship between clinical quality indicators and measurements in RCTs. This study will also yield a list of measurements used in RCTs for asthma management in children, and will find RCT evidence for indicators used in practice. Ethical approval is not necessary because this study will not include patient data. Findings will be disseminated through peer-reviewed publications. 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.

Depression care management for adults older than 60 years in primary care clinics in urban China: a cluster-randomised trial.

PubMed

Chen, Shulin; Conwell, Yeates; He, Jin; Lu, Naiji; Wu, Jiayan

2015-04-01

China's national health policy classifies depression as a chronic disease that should be managed in primary care settings. In some high-income countries use of chronic disease management principles and primary care-based collaborative-care models have improved outcomes for late-life depression; however, this approach has not yet been tested in China. We aimed to assess whether use of a collaborative-care depression care management (DCM) intervention could improve outcomes for Chinese adults with depression aged 60 years and older. Between Jan 17, 2011, [corrected] and Nov 30, 2013, we did a cluster-randomised trial in patients from primary care centre clinics in Shangcheng district of Hangzhou city in eastern China. We randomly assigned (1:1) clinics to either DCM (involving training for physicians in use of treatment guidelines, training for primary care nurses to function as care managers, and consultation with psychiatrists as support) or to give enhanced care as usual to all eligible patients aged 60 years and older with major depressive disorder. Clinics were chosen randomly for inclusion from all primary care clinics in the district by computer algorithm and then randomly allocated depression care interventions remotely by computer algorithm. Physicians, study personnel, and patients were not masked to clinic assignment. Our primary outcome was difference in Hamilton Depression Rating Scale (HAMD) score using data for clusters at baseline and 3, 6, and 12 month follow-up in a mixed-effects model of the intention-to-treat population. We originally aimed to analyse outcomes at 24 months, however the difference between groups at 12 months was large and funding was insufficient to continue to 24 months, therefore we decided to end the trial at 12 months. This trial is registered with ClinicalTrials.gov, number NCT01287494. Of 34 primary care clinics in Shangcheng district, 16 were randomly chosen. We randomly assigned eight clinics to the DCM intervention (164

Clinical Trials - Information for Participants

MedlinePlus

... Study Near You Learn More Share Clinical Trials – Information for Participants Overview Clinical research trials are at ... improved health in the future. Learn More Contact Information For more information about clinical trials conducted at ...

Clinical trials in dentistry in India: Analysis from trial registry.

PubMed

Gowri, S; Kannan, Sridharan

2017-01-01

Evidence-based practice requires clinical trials to be performed. In India, if any clinical trial has to be performed, it has to be registered with clinical trial registry of India. Studies have shown that the report of clinical trials is poor in dentistry. Hence, the present study has been conducted to assess the type and trends of clinical trials being undertaken in dentistry in India over a span of 6 years. All the clinical trials which were registered with the Central Trial Registry of India (CTRI) (www.ctri.nic.in) from January 1, 2007 to March 3, 2014 were evaluated using the keyword "dental." Following information were collected for each of the clinical trials obtained from the search; number of centres (single center/multicentric), type of the institution undertaking the research (government/private/combined), study (observational/interventional), study design (randomized/single blinded/double-blinded), type of health condition, type of participants (healthy/patients), sponsors (academia/commercial), phase of clinical trial (Phase 1/2/3/4), publication details (published/not published), whether it was a postgraduate thesis or not and prospective or retrospective registration of clinical trials, methodological quality (method of randomization, allocation concealment). Descriptive statistics was used for analysis of various categories. Trend analysis was done to assess the changes over a period of time. The search yielded a total of 84 trials of which majority of them were single centered. Considering the study design more than half of the registered clinical trials were double-blinded (47/84 [56%]). With regard to the place of conducting a trial, most of the trials were planned to be performed in private hospitals (56/84 [66.7%]). Most (79/84, 94.1%) of the clinical trials were interventional while only 5/84 (5.9%) were observational. Majority (65/84, 77.4%) of the registered clinical trials were recruiting patients while the rest were being done in healthy

Clinical trials in rheumatoid arthritis: a status report from the ClinicalTrials.gov website.

PubMed

Paul, Jisna R; Ranganathan, Prabha

2012-06-01

The aims of this study are to describe the characteristics of clinical trials in rheumatoid arthritis (RA) listed in ClinicalTrials.gov and examine existing trends in study design, funding sources, outcomes, and drugs under investigation. We conducted a survey of ongoing clinical trials in RA registered in the ClinicalTrials.gov website. We used the advanced search option and applied the following inclusion criteria, "rheumatoid arthritis", "open studies", "interventional", and "adults 18 years or older". Of 127 eligible trials, 53.5% of the studies were either phase 3 or 4, and 40.2% were phase 1, 2, and 2/3. Two-thirds of the trials were randomized (70.9%), and over half were, in addition, double-blinded (53.5%) and placebo-controlled (53.5%). Universities were listed as the primary sponsor for 18.9% of the trials and pharmaceutical industry for 73.2%. Majority of the trials were multi-center studies (93%) conducted outside the United States (54.3%). The most frequently used endpoint was drug efficacy (54.3%) followed by drug safety (25.2%). Most industry-funded trials were open for less than 12 months, whereas most university-funded trials were open for more than 24 months (58% each). Biologic therapies were the focus of most trials in the registry (78.5%). Randomized, double-blinded, placebo-controlled, phase 3 and 4 trials form the majority of ongoing clinical trials in RA. The preponderance of industry funding of RA trials and the short duration of such trials are troubling trends which need to be addressed.

Linking ClinicalTrials.gov and PubMed to Track Results of Interventional Human Clinical Trials

PubMed Central

Huser, Vojtech; Cimino, James J.

2013-01-01

Objective In an effort to understand how results of human clinical trials are made public, we analyze a large set of clinical trials registered at ClinicalTrials.gov, the world’s largest clinical trial registry. Materials and Methods We considered two trial result artifacts: (1) existence of a trial result journal article that is formally linked to a registered trial or (2) the deposition of a trial’s basic summary results within the registry. Results The study sample consisted of 8907 completed, interventional, phase 2-or-higher clinical trials that were completed in 2006-2009. The majority of trials (72.2%) had no structured trial-article link present. A total of 2367 trials (26.6%) deposited basic summary results within the registry. Of those , 969 trials (10.9%) were classified as trials with extended results and 1398 trials (15.7%) were classified as trials with only required basic results. The majority of the trials (54.8%) had no evidence of results, based on either linked result articles or basic summary results (silent trials), while a minimal number (9.2%) report results through both registry deposition and publication. Discussion Our study analyzes the body of linked knowledge around clinical trials (which we refer to as the “trialome”). Our results show that most trials do not report results and, for those that do, there is minimal overlap in the types of reporting. We identify several mechanisms by which the linkages between trials and their published results can be increased. Conclusion Our study shows that even when combining publications and registry results, and despite availability of several information channels, trial sponsors do not sufficiently meet the mandate to inform the public either via a linked result publication or basic results submission. PMID:23874614

Clinical trials finance and operations.

PubMed

O'Brien, Jennifer A

2007-01-01

The National Coverage Decision of 2000 was designed to enhance the participation in clinical trials for both patients and physicians by mandating the governmental coverage for services in a clinical trial that are considered "routine" regardless of the trial. Participation in clinical trials can be a practice builder as well as a contribution to the betterment of medical science. Without proper coverage analysis, study budgeting, accurate time estimates, and effective negotiation prior to signing the contract, participation in clinical trials can cost a practice rather than benefit it.

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics and their Environment

DTIC Science & Technology

2012-07-01

sites to assess their discussions with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about...with physicians, intentions and actual participation in prostate cancer clinical trials, attitudes and knowledge about such trials, and barriers to and...calculated and compared across race/ethnicity. Examination of major outcomes included willingness to participate in, knowledge of, and attitudes towards

Compliance with mandatory reporting of clinical trial results on ClinicalTrials.gov: cross sectional study.

PubMed

Prayle, Andrew P; Hurley, Matthew N; Smyth, Alan R

2012-01-03

To examine compliance with mandatory reporting of summary clinical trial results (within one year of completion of trial) on ClinicalTrials.gov for studies that fall under the recent Food and Drug Administration Amendments Act (FDAAA) legislation. Registry based study of clinical trial summaries. ClinicalTrials.gov, searched on 19 January 2011, with cross referencing with Drugs@FDA to determine for which trials mandatory reporting was required within one year. Selection criteria Studies registered on ClinicalTrials.gov with US sites which completed between 1 January and 31 December 2009. Proportion of trials for which results had been reported. The ClinicalTrials.gov registry contained 83,579 entries for interventional trials, of which 5642 were completed within the timescale of interest. We identified trials as falling within the mandatory reporting rules if they were covered by the FDAAA (trials of a drug, device, or biological agent, which have at least one US site, and are of phase II or later) and if they investigated a drug that already had approval from the Food and Drug Administration. Of these, 163/738 (22%) had reported results within one year of completion of the trial compared with 76/727 (10%) trials that were not subject to mandatory reporting (95% confidence interval for the difference in proportions 7.8% to 15.5%; χ(2) test, P = 2.6 × 10(-9)). Later phase trials were more likely to report results (P = 4.4 × 10(-11)), as were industry funded trials (P = 2.2 × 10(-16)). Most trials subject to mandatory reporting did not report results within a year of completion.

Clinical trials integrity: a CRO perspective.

PubMed

Beach, J E

2001-01-01

When contract research organizations (CROs) were first formed, pharmaceutical companies outsourced to them only certain aspects of the conduct of their clinical trials. At first CROs were highly specialized entities, providing, for example, either biostatistical advice, clinical research associates who monitored investigational sites for regulatory compliance, or regulatory support. Gradually, full service CROs emerged, offering a full range of services for clinical trials, including the selection of investigators and investigational sites, assistance with patient recruitment, safety surveillance and reporting, site audits, and data management and biostatistics. This evolving relationship between CROs and the pharmaceutical and medical device industries has resulted in CROs assuming more and more of the regulatory and ethical risks and responsibilities inherent in the conduct of clinical trials. In this full service role, CROs, unlike sponsors, are not interested in the outcome of study, but like sponsors, are subject to heavy regulation by the federal government, must follow applicable state laws, must respect international guidelines, and are obliged to follow their own operating procedures. Moreover, they are judged by the industry on the basis of the scope and quality of services provided, including the degree of adherence to the research protocol, regulatory requirements, and timelines; the quality of the professional working relationships with investigators and institutions, both academic and community-based; and the validity of the data. Further, CROs are subject to comprehensive audits by sponsoring companies, FDA, and other regulatory authorities. For all these reasons, CROs are being tasked with strict vigilance of all stages of the clinical trial process to ensure that the laws, regulations, and industry standards designed for the protection of human subjects and data integrity are maintained.

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.

Research Areas - Clinical Trials

Cancer.gov

Information about NCI programs and initiatives that sponsor, conduct, develop, or support clinical trials, including NCI’s Clinical Trial Network (NCTN) and NCI Community Oncology Research Program (NCORP) initiatives.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of rehabilitation interventions for osteoarthritis.

PubMed

Fitzgerald, G K; Hinman, R S; Zeni, J; Risberg, M A; Snyder-Mackler, L; Bennell, K L

2015-05-01

A Task Force of the Osteoarthritis Research Society International (OARSI) has previously published a set of guidelines for the conduct of clinical trials in osteoarthritis (OA) of the hip and knee. Limited material available on clinical trials of rehabilitation in people with OA has prompted OARSI to establish a separate Task Force to elaborate guidelines encompassing special issues relating to rehabilitation of OA. The Task Force identified three main categories of rehabilitation clinical trials. The categories included non-operative rehabilitation trials, post-operative rehabilitation trials, and trials examining the effectiveness of devices (e.g., assistive devices, bracing, physical agents, electrical stimulation, etc.) that are used in rehabilitation of people with OA. In addition, the Task Force identified two main categories of outcomes in rehabilitation clinical trials, which include outcomes related to symptoms and function, and outcomes related to disease modification. The guidelines for rehabilitation clinical trials provided in this report encompass these main categories. The report provides guidelines for conducting and reporting on randomized clinical trials. The topics include considerations for entering patients into trials, issues related to conducting trials, considerations for selecting outcome measures, and recommendations for statistical analyses and reporting of results. The focus of the report is on rehabilitation trials for hip, knee and hand OA, however, we believe the content is broad enough that it could be applied to rehabilitation trials for other regions as well. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

[Clinical trials in nursing journals].

PubMed

Di Giulio, Paola; Campagna, Sara; Dimonte, Valerio

2014-01-01

Clinical trials are pivotal for the development of nursing knowledge. To describe the clinical trials published in nursing journals in the last two years and propose some general reflections on nursing research. A search with the key-word trial was done on PubMed (2009-2013) on Cancer Nursing, European Journal of Oncology Nursing, International Journal of Nursing Studies, Journal of Advanced Nursing, Journal of Clinical Nursing and Nursing Research. Of 228 trials identified, 104 (45.8%) were published in the last 2 years. Nurses from Asian countries published the larger number of trials. Educational and supportive interventions were the most studied (61/104 trials), followed by clinical interventions (33/104). Samples were limited and most trials are monocentric. A growing number of trials is published, on issues relevant for the nursing profession, however larger samples and multicentric studies would be necessary.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the design and operation of multi-center clinical trials: a qualitative research study.

PubMed

Eisenstein, Eric L; Diener, Lawrence W; Nahm, Meredith; Weinfurt, Kevin P

2011-12-01

New technologies may be required to integrate the National Institutes of Health's Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies.

Impact of the Patient-Reported Outcomes Management Information System (PROMIS) upon the Design and Operation of Multi-center Clinical Trials: a Qualitative Research Study

PubMed Central

Diener, Lawrence W.; Nahm, Meredith; Weinfurt, Kevin P.

2013-01-01

New technologies may be required to integrate the National Institutes of Health’s Patient Reported Outcome Management Information System (PROMIS) into multi-center clinical trials. To better understand this need, we identified likely PROMIS reporting formats, developed a multi-center clinical trial process model, and identified gaps between current capabilities and those necessary for PROMIS. These results were evaluated by key trial constituencies. Issues reported by principal investigators fell into two categories: acceptance by key regulators and the scientific community, and usability for researchers and clinicians. Issues reported by the coordinating center, participating sites, and study subjects were those faced when integrating new technologies into existing clinical trial systems. We then defined elements of a PROMIS Tool Kit required for integrating PROMIS into a multi-center clinical trial environment. The requirements identified in this study serve as a framework for future investigators in the design, development, implementation, and operation of PROMIS Tool Kit technologies. PMID:20703765

Clinical trials in peripheral vascular disease: pipeline and trial designs: an evaluation of the ClinicalTrials.gov database.

PubMed

Subherwal, Sumeet; Patel, Manesh R; Chiswell, Karen; Tidemann-Miller, Beth A; Jones, W Schuyler; Conte, Michael S; White, Christopher J; Bhatt, Deepak L; Laird, John R; Hiatt, William R; Tasneem, Asba; Califf, Robert M

2014-11-11

Tremendous advances have occurred in therapies for peripheral vascular disease (PVD); until recently, however, it has not been possible to examine the entire clinical trial portfolio of studies for the treatment of PVD (both arterial and venous disease). We examined interventional trials registered in ClinicalTrials.gov from October 2007 through September 2010 (n=40,970) and identified 676 (1.7%) PVD trials (n=493 arterial only, n=170 venous only, n=13 both arterial and venous). Most arterial studies investigated lower-extremity peripheral artery disease and acute stroke (35% and 24%, respectively), whereas most venous studies examined deep vein thrombosis/pulmonary embolus prevention (42%) or venous ulceration (25%). A placebo-controlled trial design was used in 27% of the PVD trials, and 4% of the PVD trials excluded patients >65 years of age. Enrollment in at least 1 US site decreased from 51% of trials in 2007 to 41% in 2010. Compared with noncardiology disciplines, PVD trials were more likely to be double-blinded, to investigate the use of devices and procedures, and to have industry sponsorship and assumed funding source, and they were less likely to investigate drug and behavioral therapies. Geographic access to PVD clinical trials within the United States is limited to primarily large metropolitan areas. PVD studies represent a small group of trials registered in ClinicalTrials.gov, despite the high prevalence of vascular disease in the general population. This low number, compounded by the decreasing number of PVD trials in the United States, is concerning and may limit the ability to inform current clinical practice of patients with PVD. © 2014 American Heart Association, Inc.

Data management in clinical research: An overview

PubMed Central

Krishnankutty, Binny; Bellary, Shantala; Kumar, Naveen B.R.; Moodahadu, Latha S.

2012-01-01

Clinical Data Management (CDM) is a critical phase in clinical research, which leads to generation of high-quality, reliable, and statistically sound data from clinical trials. This helps to produce a drastic reduction in time from drug development to marketing. Team members of CDM are actively involved in all stages of clinical trial right from inception to completion. They should have adequate process knowledge that helps maintain the quality standards of CDM processes. Various procedures in CDM including Case Report Form (CRF) designing, CRF annotation, database designing, data-entry, data validation, discrepancy management, medical coding, data extraction, and database locking are assessed for quality at regular intervals during a trial. In the present scenario, there is an increased demand to improve the CDM standards to meet the regulatory requirements and stay ahead of the competition by means of faster commercialization of product. With the implementation of regulatory compliant data management tools, CDM team can meet these demands. Additionally, it is becoming mandatory for companies to submit the data electronically. CDM professionals should meet appropriate expectations and set standards for data quality and also have a drive to adapt to the rapidly changing technology. This article highlights the processes involved and provides the reader an overview of the tools and standards adopted as well as the roles and responsibilities in CDM. PMID:22529469

Impact of clinical trial findings on Bell's palsy management in general practice in the UK 2001-2012: interrupted time series regression analysis.

PubMed

Morales, Daniel R; Donnan, Peter T; Daly, Fergus; Staa, Tjeerd Van; Sullivan, Frank M

2013-01-01

To measure the incidence of Bell's palsy and determine the impact of clinical trial findings on Bell's palsy management in the UK. Interrupted time series regression analysis and incidence measures. General practices in the UK contributing to the Clinical Practice Research Datalink (CPRD). Patients ≥16 years with a diagnosis of Bell's palsy between 2001 and 2012. (1) Publication of the 2004 Cochrane reviews of clinical trials on corticosteroids and antivirals for Bell's palsy, which made no clear recommendation on their use and (2) publication of the 2007 Scottish Bell's Palsy Study (SBPS), which made a clear recommendation that treatment with prednisolone alone improves chances for complete recovery. Incidence of Bell's palsy per 100 000 person-years. Changes in the management of Bell's palsy with either prednisolone therapy, antiviral therapy, combination therapy (prednisolone with antiviral therapy) or untreated cases. During the 12-year period, 14 460 cases of Bell's palsy were identified with an overall incidence of 37.7/100 000 person-years. The 2004 Cochrane reviews were associated with immediate falls in prednisolone therapy (-6.3% (-11.0 to -1.6)), rising trends in combination therapy (1.1% per quarter (0.5 to 1.7)) and falling trends for untreated cases (-0.8% per quarter (-1.4 to -0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1% (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to 1.2)); falling trends in combination therapy (-1.7% per quarter (-2.2 to -1.3)); and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite improvements, 44% still remain untreated. SBPS was clearly associated with change in management, but a significant proportion of patients failed to receive effective treatment, which cannot be fully explained. Clarity and uncertainty in clinical trial recommendations may change clinical practice. However, better ways are needed to understand and circumvent

Patient retention gifts in clinical trials - undue inducement or justified motivational tools?

PubMed

Burgess, L J; Sulzer, N

2011-09-05

The use of retention gifts in clinical trials has been controversial, with some ethicists maintaining that such gifts represent undue inducement to the trial participants. A study was conducted at TREAD Research, a site-managed organisation based at Tygerberg Hospital, in which 302 participants completed a questionnaire that focused on their opinion with regard to such gifts. The results suggest that these gifts do not influence patients to participate in a clinical trial or influence them to remain on a trial should they wish to withdraw. However, they do act as a useful motivational tool and trial participants appreciate them.

Clinical Decision Support Tools for Osteoporosis Disease Management: A Systematic Review of Randomized Controlled Trials

PubMed Central

Straus, Sharon E.

2008-01-01

BACKGROUND Studies indicate a gap between evidence and clinical practice in osteoporosis management. Tools that facilitate clinical decision making at the point of care are promising strategies for closing these practice gaps. OBJECTIVE To systematically review the literature to identify and describe the effectiveness of tools that support clinical decision making in osteoporosis disease management. DATA SOURCES Medline, EMBASE, CINAHL, and EBM Reviews (CDSR, DARE, CCTR, and ACP J Club), and contact with experts in the field. REVIEW METHODS Randomized controlled trials (RCTs) in any language from 1966 to July 2006 investigating disease management interventions in patients at risk for osteoporosis. Outcomes included fractures and bone mineral density (BMD) testing. Two investigators independently assessed articles for relevance and study quality, and extracted data using standardized forms. RESULTS Of 1,246 citations that were screened for relevance, 13 RCTs met the inclusion criteria. Reported study quality was generally poor. Meta-analysis was not done because of methodological and clinical heterogeneity; 77% of studies included a reminder or education as a component of their intervention. Three studies of reminders plus education targeted to physicians and patients showed increased BMD testing (RR range 1.43 to 8.67) and osteoporosis medication use (RR range 1.60 to 8.67). A physician reminder plus a patient risk assessment strategy found reduced fractures [RR 0.58, 95% confidence interval (CI) 0.37 to 0.90] and increased osteoporosis therapy (RR 2.44, CI 1.43 to 4.17). CONCLUSION Multi-component tools that are targeted to physicians and patients may be effective for supporting clinical decision making in osteoporosis disease management. Electronic supplementary material The online version of this article (doi:10.1007/s11606-008-0812-9) contains supplementary material, which is available to authorized users. PMID:18836782

Informed Consent (Clinical Trials)

MedlinePlus

... Cancer Treatment Types of Cancer Treatment Side Effects Clinical Trials Information A to Z List of Cancer ... Staging Prognosis Treatment Types of Treatment Side Effects Clinical Trials Cancer Drugs Complementary & Alternative Medicine Coping Feelings & ...

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

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

OARSI Clinical Trials Recommendations: Soluble biomarker assessments in clinical trials in osteoarthritis.

PubMed

Kraus, V B; Blanco, F J; Englund, M; Henrotin, Y; Lohmander, L S; Losina, E; Önnerfjord, P; Persiani, S

2015-05-01

The objective of this work was to describe requirements for inclusion of soluble biomarkers in osteoarthritis (OA) clinical trials and progress toward OA-related biomarker qualification. The Guidelines for Biomarkers Working Group, representing experts in the field of OA biomarker research from both academia and industry, convened to discuss issues related to soluble biomarkers and to make recommendations for their use in OA clinical trials based on current knowledge and anticipated benefits. This document summarizes current guidance on use of biomarkers in OA clinical trials and their utility at five stages, including preclinical development and phase I to phase IV trials. As demonstrated by this summary, biomarkers can provide value at all stages of therapeutics development. When resources permit, we recommend collection of biospecimens in all OA clinical trials for a wide variety of reasons but in particular, to determine whether biomarkers are useful in identifying those individuals most likely to receive clinically important benefits from an intervention; and to determine whether biomarkers are useful for identifying individuals at earlier stages of OA in order to institute treatment at a time more amenable to disease modification. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Parents' perceived obstacles to pediatric clinical trial participation: Findings from the clinical trials transformation initiative.

PubMed

Greenberg, Rachel G; Gamel, Breck; Bloom, Diane; Bradley, John; Jafri, Hasan S; Hinton, Denise; Nambiar, Sumathi; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation. Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions. In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

A Paradox-based data collection and management system for multi-center randomized clinical trials.

PubMed

Abdellatif, Mazen; Reda, Domenic J

2004-02-01

We have developed a Paradox-based data collection and management system for large-scale multi-site randomized clinical trials. The system runs under Windows operating system and integrates Symantec pcAnywhere32 telecommunications software for data transmission and remote control sessions, PKZIP utility for the compression/decompression of transmitted data, and Stat/Transfer for exporting the centralized Paradox database for analyses. We initially developed this system for VA Cooperative Study #399 'The Effect of Antiarrhythmic Therapy in Maintaining Stability of Sinus Rhythm in Atrial Fibrillation', which collects over 1000 variables on 706 patients at 20 sites. Patient intake for this 5-year study began in March of 1998. We have also developed an enhanced version of this system, which is being used in the NIH-funded 'Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)' that collects over 1200 variables on 1588 patients at 13 sites. Patient intake for this 4-year study began in October of 2000.

From ClinicalTrials.gov trial registry to an analysis-ready database of clinical trial results.

PubMed

Cepeda, M Soledad; Lobanov, Victor; Berlin, Jesse A

2013-04-01

The ClinicalTrials.gov web site provides a convenient interface to look up study results, but it does not allow downloading data in a format that can be readily used for quantitative analyses. To develop a system that automatically downloads study results from ClinicalTrials.gov and provides an interface to retrieve study results in a spreadsheet format ready for analysis. Sherlock(®) identifies studies by intervention, population, or outcome of interest and in seconds creates an analytic database of study results ready for analyses. The outcome classification algorithms used in Sherlock were validated against a classification by an expert. Having a database ready for analysis that can be updated automatically, dramatically extends the utility of the ClinicalTrials.gov trial registry. It increases the speed of comparative research, reduces the need for manual extraction of data, and permits answering a vast array of questions.

Adaptive design clinical trials: a review of the literature and ClinicalTrials.gov

PubMed Central

Bothwell, Laura E; Avorn, Jerry; Khan, Nazleen F; Kesselheim, Aaron S

2018-01-01

Objectives This review investigates characteristics of implemented adaptive design clinical trials and provides examples of regulatory experience with such trials. Design Review of adaptive design clinical trials in EMBASE, PubMed, Cochrane Registry of Controlled Clinical Trials, Web of Science and ClinicalTrials.gov. Phase I and seamless Phase I/II trials were excluded. Variables extracted from trials included basic study characteristics, adaptive design features, size and use of independent data monitoring committees (DMCs) and blinded interim analyses. We also examined use of the adaptive trials in new drug submissions to the Food and Drug Administration (FDA) and European Medicines Agency (EMA) and recorded regulators’ experiences with adaptive designs. Results 142 studies met inclusion criteria. There has been a recent growth in publicly reported use of adaptive designs among researchers around the world. The most frequently appearing types of adaptations were seamless Phase II/III (57%), group sequential (21%), biomarker adaptive (20%), and adaptive dose-finding designs (16%). About one-third (32%) of trials reported an independent DMC, while 6% reported blinded interim analysis. We found that 9% of adaptive trials were used for FDA product approval consideration, and 12% were used for EMA product approval consideration. International regulators had mixed experiences with adaptive trials. Many product applications with adaptive trials had extensive correspondence between drug sponsors and regulators regarding the adaptive designs, in some cases with regulators requiring revisions or alterations to research designs. Conclusions Wider use of adaptive designs will necessitate new drug application sponsors to engage with regulatory scientists during planning and conduct of the trials. Investigators need to more consistently report protections intended to preserve confidentiality and minimise potential operational bias during interim analysis. PMID:29440155

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

Minorities and Clinical Trials: Patients, Physicians, Clinical Trial Characteristics, and Their Environment

DTIC Science & Technology

2011-07-01

cancer clinical trials, attitudes and knowledge about such trials, and barriers to and facilitators of participation, b) Conduct a self-administered...facilitate or hinder participation in prostate cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of...cancer trials by examining patients’ attitudes , physicians’ perceived barriers, characteristics of prostate trials and sites, and broader community

Patient engagement in clinical trials: The Clinical Trials Transformation Initiative's leadership from theory to practical implementation.

PubMed

Patrick-Lake, Bray

2018-02-01

Patient engagement is an increasingly important aspect of successful clinical trials. Over the past decade, as patient group involvement in clinical trials has continued to increase and diversify, the Clinical Trials Transformation Initiative has not only recognized the crucial role patients play in improving the clinical trial enterprise but also made a deep commitment to help grow and shape the emerging field of patient engagement. This article describes the evolution of patient engagement including the origins of the patient engagement movement; barriers to successful engagement and remaining challenges to full and valuable collaboration between patient groups and trial sponsors; and Clinical Trials Transformation Initiative's role in influencing the field through organizational practices, formal project work and resulting recommendations, and external advocacy efforts.

Transparency and public accessibility of clinical trial information in Croatia: how it affects patient participation in clinical trials.

PubMed

Šolić, Ivana; Stipčić, Ana; Pavličević, Ivančica; Marušić, Ana

2017-06-15

Despite increased visibility of clinical trials through international trial registries, patients often remain uninformed of their existence, especially if they do not have access to adequate information about clinical research, including the language of the information. The aim of this study was to describe the context for transparency of clinical trials in Croatia in relation to countries in Central and Eastern Europe, and to assess how informed Croatian patients are about clinical trials and their accessibility. We assessed the transparency of clinical trials from the data available in the public domain. We also conducted an anonymous survey on a convenience sample of 257 patients visiting two family medicine offices or an oncology department in south Croatia, and members of national patients' associations. Despite legal provisions for transparency of clinical trials in Croatia, they are still not sufficiently visible in the public domain. Among countries from Central and Eastern Europe, Croatia has the fewest number of registered trials in the EU Clinical Trials Registry. 66% of the patients in the survey were aware of the existence of clinical trials but only 15% were informed about possibilities of participating in a trial. Although 58% of the respondents were willing to try new treatments, only 6% actually participated in a clinical trial. Only 2% of the respondents were aware of publicly available trial registries. Our study demonstrates that there is low transparency of clinical trials in Croatia, and that Croatian patients are not fully aware of clinical trials and the possibilities of participating in them, despite reported availability of Internet resources and good communication with their physicians. There is a need for active policy measures to increase the awareness of and access to clinical trials to patients in Croatia, particularly in their own language.

Paying for Clinical Trials

Cancer.gov

Learn about the different types of costs related to taking part in a clinical trial, and who is expected to pay for which costs. This whiteboard animation from the National Cancer Insitute (NCI) is part of a video series about clinical trials.

Contemporary Aspects of Marketing in Clinical Trials Including Segments of IT and Technology Transfer

PubMed Central

Stamenovic, Milorad; Dobraca, Amra; Smajlovic, Mersiha

2018-01-01

Introduction: The aim of this paper is to present the marketing strategy and the application of management (marketing management) and advertising in order to increase the efficiency of innovative approach in clinical trials that include and involve the use of new technologies and transfer of technologies. Material and Methods: This paper has a descriptive character and represents a narrative review of the literature and new model implementation. Results: Marketing models are primarily used to improve the inclusion of a larger (and appropriate) number of patients, but they can be credited for the stay and monitoring of patients in the trial. Regulatory mechanisms play an important role in the application of various marketing strategies within clinical trials. The value for the patient as the most important stakeholder is defined in the field of clinical trials according to Kotler’s value model for the consumer. Conclusion: In order to achieve the best results it is important to adequately examine all the elements of clinical trials and apply this knowledge in creation of a marketing plan that will be made in accordance with the legal regulations defined globally and locally. In this paper, two challenges have been highlighted for the adequate application of marketing tools in the field of clinical trials, namely: defining business elements in order to provide an adequate marketing approach for clinical trials and technology transfer and ensuring uniformity and regulatory affirmation of marketing attitudes in clinical trials in all regions in which they are carried out in accordance with ICH-GCP and valid regulations. PMID:29719318

Contemporary Aspects of Marketing in Clinical Trials Including Segments of IT and Technology Transfer.

PubMed

Stamenovic, Milorad; Dobraca, Amra; Smajlovic, Mersiha

2018-01-01

The aim of this paper is to present the marketing strategy and the application of management (marketing management) and advertising in order to increase the efficiency of innovative approach in clinical trials that include and involve the use of new technologies and transfer of technologies. This paper has a descriptive character and represents a narrative review of the literature and new model implementation. Marketing models are primarily used to improve the inclusion of a larger (and appropriate) number of patients, but they can be credited for the stay and monitoring of patients in the trial. Regulatory mechanisms play an important role in the application of various marketing strategies within clinical trials. The value for the patient as the most important stakeholder is defined in the field of clinical trials according to Kotler's value model for the consumer. In order to achieve the best results it is important to adequately examine all the elements of clinical trials and apply this knowledge in creation of a marketing plan that will be made in accordance with the legal regulations defined globally and locally. In this paper, two challenges have been highlighted for the adequate application of marketing tools in the field of clinical trials, namely: defining business elements in order to provide an adequate marketing approach for clinical trials and technology transfer and ensuring uniformity and regulatory affirmation of marketing attitudes in clinical trials in all regions in which they are carried out in accordance with ICH-GCP and valid regulations.

Assessing Clinical Trial–Associated Workload in Community-Based Research Programs Using the ASCO Clinical Trial Workload Assessment Tool

PubMed Central

Hurley, Patricia; Woo, Kaitlin M.; Szczepanek, Connie; Stewart, Teresa; Robert, Nicholas; Lyss, Alan; Gönen, Mithat; Lilenbaum, Rogerio

2016-01-01

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:27006354

Digital management and regulatory submission of medical images from clinical trials: role and benefits of the core laboratory

NASA Astrophysics Data System (ADS)

Robbins, William L.; Conklin, James J.

1995-10-01

Medical images (angiography, CT, MRI, nuclear medicine, ultrasound, x ray) play an increasingly important role in the clinical development and regulatory review process for pharmaceuticals and medical devices. Since medical images are increasingly acquired and archived digitally, or are readily digitized from film, they can be visualized, processed and analyzed in a variety of ways using digital image processing and display technology. Moreover, with image-based data management and data visualization tools, medical images can be electronically organized and submitted to the U.S. Food and Drug Administration (FDA) for review. The collection, processing, analysis, archival, and submission of medical images in a digital format versus an analog (film-based) format presents both challenges and opportunities for the clinical and regulatory information management specialist. The medical imaging 'core laboratory' is an important resource for clinical trials and regulatory submissions involving medical imaging data. Use of digital imaging technology within a core laboratory can increase efficiency and decrease overall costs in the image data management and regulatory review process.

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials for hand osteoarthritis.

PubMed

Kloppenburg, M; Maheu, E; Kraus, V B; Cicuttini, F; Doherty, M; Dreiser, R-L; Henrotin, Y; Jiang, G-L; Mandl, L; Martel-Pelletier, J; Nelson, A E; Neogi, T; Pelletier, J-P; Punzi, L; Ramonda, R; Simon, L S; Wang, S

2015-05-01

Hand osteoarthritis (OA) is a very frequent disease, but yet understudied. However, a lot of works have been published in the past 10 years, and much has been done to better understand its clinical course and structural progression. Despite this new knowledge, few therapeutic trials have been conducted in hand OA. The last OARSI recommendations for the conduct of clinical trials in hand OA dates back to 2006. The present recommendations aimed at updating previous recommendations, by incorporating new data. The purpose of this expert opinion, consensus driven exercise is to provide evidence-based guidance on the design, execution and analysis of clinical trials in hand OA, where published evidence is available, supplemented by expert opinion, where evidence is lacking, to perform clinical trials in hand OA, both for symptom and for structure-modification. They indicate core outcome measurement sets for studies in hand OA, and list the methods and instruments that should be used to measure symptoms or structure. For both symptom- and structure-modification, at least pain, physical function, patient global assessment, HR-QoL, joint activity and hand strength should be assessed. In addition, for structure-modification trials, structural progression should be measured by radiographic changes. We also provide a research agenda listing many unsolved issues that seem to most urgently need to be addressed from the perspective of performing "good" clinical trials in hand OA. These updated OARSI recommendations should allow for better standardizing the conduct of clinical trials in hand OA in the next future. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Parents as Agents of Change (PAC) in pediatric weight management: The protocol for the PAC randomized clinical trial

PubMed Central

2012-01-01

Background There is an urgent need to develop and evaluate weight management interventions to address childhood obesity. Recent research suggests that interventions designed for parents exclusively, which have been named parents as agents of change (PAC) approaches, have yielded positive outcomes for managing pediatric obesity. To date, no research has combined a PAC intervention approach with cognitive behavioural therapy (CBT) to examine whether these combined elements enhance intervention effectiveness. This paper describes the protocol our team is using to examine two PAC-based interventions for pediatric weight management. We hypothesize that children with obesity whose parents complete a CBT-based PAC intervention will achieve greater reductions in adiposity and improvements in cardiometabolic risk factors, lifestyle behaviours, and psychosocial outcomes than children whose parents complete a psycho-education-based PAC intervention (PEP). Methods/Design This study is a pragmatic, two-armed, parallel, single-blinded, superiority, randomized clinical trial. The primary objective is to examine the differential effects of a CBT-based PAC vs PEP-based PAC intervention on children’s BMI z-score (primary outcome). Secondary objectives are to assess intervention-mediated changes in cardiometabolic, lifestyle, and psychosocial variables in children and parents. Both interventions are similar in frequency of contact, session duration, group facilitation, lifestyle behaviour goals, and educational content. However, the interventions differ insofar as the CBT-based intervention incorporates theory-based concepts to help parents link their thoughts, feelings, and behaviours; these cognitive activities are enabled by group leaders who possess formal training in CBT. Mothers and fathers of children (8–12 years of age; BMI ≥85th percentile) are eligible to participate if they are proficient in English (written and spoken) and agree for at least one parent to attend

Characteristics of oncology clinical trials: insights from a systematic analysis of ClinicalTrials.gov.

PubMed

Hirsch, Bradford R; Califf, Robert M; Cheng, Steven K; Tasneem, Asba; Horton, John; Chiswell, Karen; Schulman, Kevin A; Dilts, David M; Abernethy, Amy P

2013-06-10

Clinical trials are essential to cancer care, and data about the current state of research in oncology are needed to develop benchmarks and set the stage for improvement. To perform a comprehensive analysis of the national oncology clinical research portfolio. All interventional clinical studies registered on ClinicalTrials.gov between October 2007 and September 2010 were identified using Medical Subject Heading terms and submitted conditions. They were reviewed to validate classification, subcategorized by cancer type, and stratified by design characteristics to facilitate comparison across cancer types and with other specialties. Of 40 970 interventional studies registered between October 2007 and September 2010, a total of 8942 (21.8%) focused on oncology. Compared with other specialties, oncology trials were more likely to be single arm (62.3% vs 23.8%; P < .001), open label (87.8% vs 47.3%; P < .001), and nonrandomized (63.9% vs 22.7%; P < .001). There was moderate but significant correlation between number of trials conducted by cancer type and associated incidence and mortality (Spearman rank correlation coefficient, 0.56 [P = .04] and 0.77 [P = .001], respectively). More than one-third of all oncology trials were conducted solely outside North America. There are significant variations between clinical trials in oncology and other diseases, as well as among trials within oncology. The differences must be better understood to improve both the impact of cancer research on clinical practice and the use of constrained resources.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

PubMed

Zannad, Faiez; Pfeffer, Marc A; Bhatt, Deepak L; Bonds, Denise E; Borer, Jeffrey S; Calvo-Rojas, Gonzalo; Fiore, Louis; Lund, Lars H; Madigan, David; Maggioni, Aldo Pietro; Meyers, Catherine M; Rosenberg, Yves; Simon, Tabassome; Stough, Wendy Gattis; Zalewski, Andrew; Zariffa, Nevine; Temple, Robert

2017-08-01

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease. © 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.

eTACTS: a method for dynamically filtering clinical trial search results.

PubMed

Miotto, Riccardo; Jiang, Silis; Weng, Chunhua

2013-12-01

Information overload is a significant problem facing online clinical trial searchers. We present eTACTS, a novel interactive retrieval framework using common eligibility tags to dynamically filter clinical trial search results. eTACTS mines frequent eligibility tags from free-text clinical trial eligibility criteria and uses these tags for trial indexing. After an initial search, eTACTS presents to the user a tag cloud representing the current results. When the user selects a tag, eTACTS retains only those trials containing that tag in their eligibility criteria and generates a new cloud based on tag frequency and co-occurrences in the remaining trials. The user can then select a new tag or unselect a previous tag. The process iterates until a manageable number of trials is returned. We evaluated eTACTS in terms of filtering efficiency, diversity of the search results, and user eligibility to the filtered trials using both qualitative and quantitative methods. eTACTS (1) rapidly reduced search results from over a thousand trials to ten; (2) highlighted trials that are generally not top-ranked by conventional search engines; and (3) retrieved a greater number of suitable trials than existing search engines. eTACTS enables intuitive clinical trial searches by indexing eligibility criteria with effective tags. User evaluation was limited to one case study and a small group of evaluators due to the long duration of the experiment. Although a larger-scale evaluation could be conducted, this feasibility study demonstrated significant advantages of eTACTS over existing clinical trial search engines. A dynamic eligibility tag cloud can potentially enhance state-of-the-art clinical trial search engines by allowing intuitive and efficient filtering of the search result space. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

eTACTS: A Method for Dynamically Filtering Clinical Trial Search Results

PubMed Central

Miotto, Riccardo; Jiang, Silis; Weng, Chunhua

2013-01-01

Objective Information overload is a significant problem facing online clinical trial searchers. We present eTACTS, a novel interactive retrieval framework using common eligibility tags to dynamically filter clinical trial search results. Materials and Methods eTACTS mines frequent eligibility tags from free-text clinical trial eligibility criteria and uses these tags for trial indexing. After an initial search, eTACTS presents to the user a tag cloud representing the current results. When the user selects a tag, eTACTS retains only those trials containing that tag in their eligibility criteria and generates a new cloud based on tag frequency and co-occurrences in the remaining trials. The user can then select a new tag or unselect a previous tag. The process iterates until a manageable number of trials is returned. We evaluated eTACTS in terms of filtering efficiency, diversity of the search results, and user eligibility to the filtered trials using both qualitative and quantitative methods. Results eTACTS (1) rapidly reduced search results from over a thousand trials to ten; (2) highlighted trials that are generally not top-ranked by conventional search engines; and (3) retrieved a greater number of suitable trials than existing search engines. Discussion eTACTS enables intuitive clinical trial searches by indexing eligibility criteria with effective tags. User evaluation was limited to one case study and a small group of evaluators due to the long duration of the experiment. Although a larger-scale evaluation could be conducted, this feasibility study demonstrated significant advantages of eTACTS over existing clinical trial search engines. Conclusion A dynamic eligibility tag cloud can potentially enhance state-of-the-art clinical trial search engines by allowing intuitive and efficient filtering of the search result space. PMID:23916863

Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

DTIC Science & Technology

2007-05-01

competence of clinical trial staff, and outreach efforts. We have started to geographic, social and physical attributes of the communities surrounding the...aimed at clinical trial sites and that address specific barriers associated with the social or physical environment. 15. SUBJECT TERMS Clinical trials...and availability of trials, patient burden and benefit, site cultural competence, and outreach efforts. We will also examine the social and

Types of Cancer Clinical Trials

Cancer.gov

Information about the several types of cancer clinical trials, including treatment trials, prevention trials, screening trials, supportive and palliative care trials. Each type of trial is designed to answer different research questions.

The Geographical Distribution of Leadership in Globalized Clinical Trials

PubMed Central

Hoekman, Jarno; Frenken, Koen; de Zeeuw, Dick; Heerspink, Hiddo Lambers

2012-01-01

Background Pharmaceutical trials are mainly initiated by sponsors and investigators in the United States, Western Europe and Japan. However, more and more patients are enrolled in Central and Eastern Europe, Latin America and Asia. The involvement of patients in new geographical settings raises questions about scientific and ethical integrity, especially when experience with those settings is lacking at the level of trial management. We therefore studied to what extent the geographical shift in patient enrolment is anticipated in the composition of trial management teams using the author nationalities on the primary outcome publication as an indicator of leadership. Methods and Findings We conducted a cohort-study among 1,445 registered trials in www.clinicaltrials.gov that could be matched with a primary outcome publication using clinical trial registry numbers listed in publications. The name of the sponsor and the enrolment countries were extracted from all registrations. The author-addresses of all authors were extracted from the publications. We searched the author-address of all publications to determine whether enrolment countries and sponsors listed on registrations also appeared on a matched publication. Of all sponsors, 80.1% were listed with an author-address on the publication. Of all enrolment countries, 50.3% appeared with an author-address on the publication. The listing of enrolment countries was especially low for industry-funded trials (39.9%) as compared to government (90.4%) and not-for-profit funding (93.7%). We found that listing of enrolment countries in industry-funded trials was higher for traditional research locations such as the United States (98.2%) and Japan (72.0%) as compared to nontraditional research locations such as Poland (27.3%) and Mexico (14.1%). Conclusions Despite patient enrolment efforts, the involvement of researchers from nontraditional locations in trial management as measured by their contribution to manuscript

Dialogues on Diversifying Clinical Trials: Successful Strategies for Engaging Women and Minorities in Clinical Trials

PubMed Central

Fadiran, Emmanuel Olutayo; Parrish, L. Jo; Griffith, Rachel A.; Weiss, Eleanor; Carter, Christine

2012-01-01

Abstract There is mounting scientific evidence pointing to genetic or physiologic distinctions between genders and among racial and ethnic groups that influence disease risk and severity and response to treatment. The diverse enrollment of subjects engaged in clinical trials research is, thus, critical to developing safer and more effective drugs and medical devices. However, in the United States, there are striking disparities in clinical trial participation. To address this problem, the Food and Drug Administration (FDA) Office of Women's Health and the Society for Women's Health Research (SWHR) together convened the 2-day meeting, Dialogues on Diversifying Clinical Trials. The conference was held in Washington, DC, on September 22–23, 2011, and brought together a wide range of speakers from clinical research, industry, and regulatory agencies. Here, we present the major findings discussed at this meeting about female and minority patients and physicians and their willingness to participate in clinical trials and the barriers that sponsors face in recruiting a diverse trial population. We also discuss some recommendations for improving trial diversity through new technologies and greater efficiency in trial regulation and review. PMID:22747427

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.

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

Medication Therapy Management after Hospitalization in CKD: A Randomized Clinical Trial.

PubMed

Tuttle, Katherine R; Alicic, Radica Z; Short, Robert A; Neumiller, Joshua J; Gates, Brian J; Daratha, Kenn B; Barbosa-Leiker, Celestina; McPherson, Sterling M; Chaytor, Naomi S; Dieter, Brad P; Setter, Stephen M; Corbett, Cynthia F

2018-02-07

CKD is characterized by remarkably high hospitalization and readmission rates. Our study aim was to test a medication therapy management intervention to reduce subsequent acute care utilization. The CKD Medication Intervention Trial was a single-blind (investigators), randomized clinical trial conducted at Providence Health Care in Spokane, Washington. Patients with CKD stages 3-5 not treated by dialysis who were hospitalized for acute illness were recruited. The intervention was designed to improve posthospitalization care by medication therapy management. A pharmacist delivered the intervention as a single home visit within 7 days of discharge. The intervention included these fundamental elements: comprehensive medication review, medication action plan, and a personal medication list. The primary outcome was a composite of acute care utilization (hospital readmissions and emergency department and urgent care visits) for 90 days after hospitalization. Baseline characteristics of participants ( n =141) included the following: age, 69±11 (mean±SD) years old; women, 48% (67 of 141); diabetes, 56% (79 of 141); hypertension, 83% (117 of 141); eGFR, 41±14 ml/min per 1.73 m 2 (serum creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation); and urine albumin-to-creatinine ratio median, 43 mg/g (interquartile range, 8-528) creatinine. The most common primary diagnoses for hospitalization were the following: cardiovascular events, 36% (51 of 141); infections, 18% (26 of 141); and kidney diseases, 12% (17 of 141). The primary outcome occurred in 32 of 72 (44%) of the medication intervention group and 28 of 69 (41%) of those in usual care (log rank P =0.72). For only hospital readmission, the rate was 19 of 72 (26%) in the medication intervention group and 18 of 69 (26%) in the usual care group (log rank P =0.95). There was no between-group difference in achievement of guideline-based goals for use of renin-angiotensin system inhibition or for BP

Clinical trials. A pending subject.

PubMed

Gil-Extremera, B; Jiménez-López, P; Mediavilla-García, J D

2018-04-01

Clinical trials are essential tools for the progress of clinical medicine in its diagnostic and therapeutic aspects. Since the first trial in 1948, which related tobacco use with lung cancer, there have been more than 150,000 clinical trials to date in various areas (paediatrics, cardiology, oncology, endocrinology, etc.). This article highlights the importance for all physicians to participate, over the course of their professional career, in a clinical trial, due to the inherent benefits for patients, the progress of medicine and for curricular prestige. The authors have created a synthesis of their experience with clinical trials on hypertension, diabetes, dyslipidaemia and ischaemic heart disease over the course of almost 3 decades. Furthermore, a brief reference has been made to the characteristics of a phase I unit, as well as to a number of research studies currently underway. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Women in Clinical Trials

MedlinePlus

... your healthcare provider if a clinical trial is right for you. Are Women in Clinical Trials? Yes. Women are already in ... how drugs and devices work. FDA Office of Women’s ... should not feel pressured to join. You have the right to quit at any time. There are rules ...

Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov.

PubMed

Lebensburger, Jeffrey D; Hilliard, Lee M; Pair, Lauren E; Oster, Robert; Howard, Thomas H; Cutter, Gary R

2015-12-01

The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials. To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 "closed," "interventional" sickle cell trials registered at ClinicalTrials.gov was completed in January 2015. The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript. ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results. © The Author(s) 2015.

[Failure mode and effects analysis to improve quality in clinical trials].

PubMed

Mañes-Sevilla, M; Marzal-Alfaro, M B; Romero Jiménez, R; Herranz-Alonso, A; Sanchez Fresneda, M N; Benedi Gonzalez, J; Sanjurjo-Sáez, M

The failure mode and effects analysis (FMEA) has been used as a tool in risk management and quality improvement. The objective of this study is to identify the weaknesses in processes in the clinical trials area, of a Pharmacy Department (PD) with great research activity, in order to improve the safety of the usual procedures. A multidisciplinary team was created to analyse each of the critical points, identified as possible failure modes, in the development of clinical trial in the PD. For each failure mode, the possible cause and effect were identified, criticality was calculated using the risk priority number and the possible corrective actions were discussed. Six sub-processes were defined in the development of the clinical trials in PD. The FMEA identified 67 failure modes, being the dispensing and prescription/validation sub-processes the most likely to generate errors. All the improvement actions established in the AMFE were implemented in the Clinical Trials area. The FMEA is a useful tool in proactive risk management because it allows us to identify where we are making mistakes and analyze the causes that originate them, to prioritize and to adopt solutions to risk reduction. The FMEA improves process safety and quality in PD. Copyright © 2018 SECA. Publicado por Elsevier España, S.L.U. All rights reserved.

The National Clinical Trials Network: Conducting Successful Clinical Trials of New Therapies for Rare Cancers

PubMed Central

Schott, Anne F.; Welch, John J.; Verschraegen, Claire F.; Kurzrock, Razelle

2015-01-01

Rare cancers account for 27% of neoplasms diagnosed each year, and 25% of cancer-related deaths in the United States. However, rare cancers show some of the highest response rates to targeted therapies, probably due to identification of oncogenic drivers with little inter-patient variability. Although the low incidence of rare cancers make large scale randomized trials involving single histologies difficult to perform, drugs have been successfully developed in rare cancers utilizing clinical trial designs that combine microscopic anatomies. Such trials are being pursued within the National Clinical Trials Network (NCTN), which possesses unique qualifications to perform widespread molecular screening of tumors for patient enrollment onto therapeutic clinical trials. When larger clinical trials are needed to determine optimum treatment strategies in rare cancers, the NCTN's broad reach in North America and internationally, and ability to partner with both US-based and international research organizations, can make these challenging studies feasible. PMID:26433554

Awareness and attitudes towards clinical trials among Polish oncological patients who had never participated in a clinical trial.

PubMed

Staniszewska, Anna; Lubiejewska, Adriana; Czerw, Aleksandra; Dąbrowska-Bender, Marta; Duda-Zalewska, Aneta; Olejniczak, Dominik; Juszczyk, Grzegorz; Bujalska-Zadrożny, Magdalena

2018-03-21

Participation in a clinical trial significantly shortens waiting time associated with receiving specialist care. Furthermore, it may be the case that, through clinical trials, subjects can access medicines that are not typically available in Poland. The aim of this study was to determine the opinions of oncological patients about clinical trials. The research has been carried out during the years 2014-2016. A proprietary questionnaire consisting of 10 closed, single and multiple choice questions about awareness and perceptions of clinical trials, and 5 questions concerning demographic information was used. A group of 256 patients with cancer (54% women, 46% men), aged 21-77 years, was surveyed. Respondents were statistically more likely to decide to participate in a clinical trial as oncological patients than the healthy volunteers (Pearson's χ2 test p = 0.00006). The desire to qualify for clinical trials in no way depends on the knowledge of side effects (Pearson's χ2 test p = 0.16796). Our study found that the patients' awareness about clinical trials varied. However, a positive attitude towards research was visible. The main identified barriers to clinical trial participation were fear of possible side effects. Most patients regarded clinical trials as useful, and considered that they are conducted to introduce new treatment/new drug.

MEDUCATE trial: effectiveness of an intensive EDUCATional intervention for IT-mediated MEDication management in the outpatient clinic - study protocol for a cluster randomized controlled trial.

PubMed

van Stiphout, F; Zwart-van Rijkom, J E F; Aarts, J E C M; Koffijberg, H; Klarenbeek-deJonge, E; Krulder, M; Roes, K C B; Egberts, A C G; ter Braak, E W M T

2015-05-22

Using information technology for medication management is an opportunity to help physicians to improve the quality of their documentation and communication and ultimately to improve patient care and patient safety. Physician education is necessary to take full advantage of information technology systems. In this trial, we seek to determine the effectiveness of an intensive educational intervention compared with the standard approach in improving information technology-mediated medication management and in reducing potential adverse drug events in the outpatient clinic. We are conducting a multicenter, cluster randomized controlled trial. The participants are specialists and residents working in the outpatient clinic of internal medicine, cardiology, pulmonology, geriatrics, gastroenterology and rheumatology. The intensive educational intervention is composed of a small-group session and e-learning. The primary outcome is discrepancies between registered medication (by physicians) and actually used medication (by patients). The key secondary outcomes are potential adverse events caused by missed drug-drug interactions. The primary and key secondary endpoints are being assessed shortly after the educational intervention is completed. Sample size will be calculated to ensure sufficient power. A sample size of 40 physicians per group and 20 patients per physician will ensure a power of >90 %, which means we will need a total of 80 physicians and 1,600 patients. We performed an exploratory trial wherein we tested the recruitment process, e-learning, time schedule, and methods for data collection, data management and data analysis. Accordingly, we refined the processes and content: the recruitment strategy was intensified, extra measures were taken to facilitate smooth conductance of the e-learning and parts were made optional. First versions of the procedures for data collection were determined. Data entry and analysis was further standardized by using the G

Randomization in cancer clinical trials: permutation test and development of a computer program.

PubMed Central

Ohashi, Y

1990-01-01

When analyzing cancer clinical trial data where the treatment allocation is done using dynamic balancing methods such as the minimization method for balancing the distribution of important prognostic factors in each arm, conservativeness occurs if such a randomization scheme is ignored and a simple unstratified analysis is carried out. In this paper, the above conservativeness is demonstrated by computer simulation, and the development of a computer program that carries out permutation tests of the log-rank statistics for clinical trial data where the allocation is done by the minimization method or a stratified permuted block design is introduced. We are planning to use this program in practice to supplement a usual stratified analysis and model-based methods such as the Cox regression. The most serious problem in cancer clinical trials in Japan is how to carry out the quality control or data management in trials that are initiated and conducted by researchers without support from pharmaceutical companies. In the final section of this paper, one international collaborative work for developing international guidelines on data management in clinical trials of bladder cancer is briefly introduced, and the differences between the system adopted in US/European statistical centers and the Japanese system is described. PMID:2269216

Feasibility of feature-based indexing, clustering, and search of clinical trials: A case study of breast cancer trials from ClinicalTrials.gov

PubMed Central

Boland, Mary Regina; Miotto, Riccardo; Gao, Junfeng; Weng, Chunhua

2013-01-01

Summary Background When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. Objectives This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. Methods We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. Results We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. Conclusions It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency. PMID:23666475

Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.

PubMed

Boland, M R; Miotto, R; Gao, J; Weng, C

2013-01-01

When standard therapies fail, clinical trials provide experimental treatment opportunities for patients with drug-resistant illnesses or terminal diseases. Clinical Trials can also provide free treatment and education for individuals who otherwise may not have access to such care. To find relevant clinical trials, patients often search online; however, they often encounter a significant barrier due to the large number of trials and in-effective indexing methods for reducing the trial search space. This study explores the feasibility of feature-based indexing, clustering, and search of clinical trials and informs designs to automate these processes. We decomposed 80 randomly selected stage III breast cancer clinical trials into a vector of eligibility features, which were organized into a hierarchy. We clustered trials based on their eligibility feature similarities. In a simulated search process, manually selected features were used to generate specific eligibility questions to filter trials iteratively. We extracted 1,437 distinct eligibility features and achieved an inter-rater agreement of 0.73 for feature extraction for 37 frequent features occurring in more than 20 trials. Using all the 1,437 features we stratified the 80 trials into six clusters containing trials recruiting similar patients by patient-characteristic features, five clusters by disease-characteristic features, and two clusters by mixed features. Most of the features were mapped to one or more Unified Medical Language System (UMLS) concepts, demonstrating the utility of named entity recognition prior to mapping with the UMLS for automatic feature extraction. It is feasible to develop feature-based indexing and clustering methods for clinical trials to identify trials with similar target populations and to improve trial search efficiency.

Decrease in Urinary Incontinence Management Costs in Women Enrolled in a Clinical Trial of Weight Loss to Treat Urinary Incontinence

PubMed Central

Subak, Leslee L.; Pinto, Angela Marinilli; Wing, Rena R.; Nakagawa, Sanae; Kusek, John W.; Herman, William H.; Kuppermann, Miriam

2012-01-01

Objective To estimate the effect of a decrease in urinary incontinence frequency on urinary incontinence management costs among women enrolled in a clinical trial of a weight loss intervention and to identify factors that predict change in cost. Methods This is a secondary cohort analysis of 338 obese and overweight women with ≥ 10 weekly episodes of urinary incontinence enrolled in an 18-month randomized clinical trial of a weight loss intervention compared to a structured education program to treat urinary incontinence. Quantities of resources used for incontinence management, including pads, additional laundry, and dry cleaning were reported by participants. Direct costs for urinary incontinence management (“cost”) were calculated by multiplying resources used by national resource costs (in 2006 U.S. dollars). Randomized groups were combined to examine the effects of change in incontinence frequency on cost. Possible predictors of change in cost were examined using generalized estimating equations controlling for factors associated with change in cost in univariable analyses. Results Mean (±SD) age was 53±10 years and baseline weight was 97+17 kg. Mean weekly urinary incontinence frequency was 24+18 at baseline and decreased by 37% at 6 months and 60% at 18 months follow-up (both P<0.001). At baseline, adjusted mean cost was $7.76±$14 per week, with costs increasing significantly with greater incontinence frequency. Mean cost decreased by 54% at 6 months and 81% at 18 months (both P<0.001). In multivariable analyses, cost independently decreased by 23% for each decrease of seven urinary incontinence episodes per week and 21% for each 5 kg of weight lost (P<0.001 for both). Conclusion In obese and overweight women enrolled in a clinical trial of weight loss for urinary incontinence, incontinence management cost decreased by 81% at 18 months ($327 per woman per year) and was strongly and independently associated with decreasing incontinence frequency

Safety and tolerability review of lorcaserin in clinical trials.

PubMed

Greenway, F L; Shanahan, W; Fain, R; Ma, T; Rubino, D

2016-10-01

Lorcaserin is a novel selective serotonin 2C receptor agonist indicated by the US Food and Drug Administration for chronic weight management in adults with obesity or overweight with ≥1 comorbidity. The safety and efficacy of lorcaserin were established during two Phase III clinical trials in patients without diabetes (BLOOM and BLOSSOM) and one Phase III clinical trial in patients with type 2 diabetes (BLOOM-DM). Headache was the most common adverse event experienced by patients during all Phase III trials. Additional adverse events occurring in >5% of patients receiving lorcaserin included dizziness, fatigue, nausea, dry mouth and constipation in patients without diabetes, and hypoglycaemia, back pain, cough and fatigue in patients with diabetes. In a pooled analysis of echocardiographic data collected during the three lorcaserin Phase III trials, the incidence of FDA-defined valvulopathy was similar in patients taking lorcaserin and the placebo. Here, the safety profile of lorcaserin at the FDA-approved dose of 10 mg twice daily is reviewed using data from the lorcaserin Phase III programme, with a focus on theoretical adverse events commonly associated with agonists of the serotonin receptor family. Based on the lorcaserin Phase III clinical trial data, lorcaserin is safe and well tolerated in the indicated patient populations. © 2016 World Obesity.

Adaptive clinical trial design.

PubMed

Chow, Shein-Chung

2014-01-01

In recent years, the use of adaptive design methods in clinical trials based on accumulated data at interim has received much attention because of its flexibility and efficiency in pharmaceutical/clinical development. In practice, adaptive design may provide the investigators a second chance to modify or redesign the trial while the study is still ongoing. However, it is a concern that a shift in target patient population may occur after significant adaptations are made. In addition, the overall type I error rate may not be preserved. Moreover, the results may not be reliable and hence are difficult to interpret. As indicated by the US Food and Drug Administration draft guidance on adaptive design clinical trials, the adaptive design has to be a prospectively planned opportunity and should be based on information collected within the study, with or without formal statistical hypothesis testing. This article reviews the relative advantages, limitations, and feasibility of commonly considered adaptive designs in clinical trials. Statistical concerns when implementing adaptive designs are also discussed.

Challenges and opportunities in SLE clinical trials.

PubMed

van Vollenhoven, Ronald F

2013-09-01

To provide an update on the field of clinical trials in systemic lupus erythematosus (SLE). This review will examine failed and successful clinical trials in SLE in order to draw lessons and determine the optimal ways forward. Over the past decade, many clinical trials in SLE met with limited success, but in the past 2 years several SLE clinical trials have been successful. The two large phase III randomized controlled trials (RCTs) of belimumab achieved their primary endpoints and resulted in food and drug administration and European medicines agency approval of the drug. Characteristics of these trials were, among other things, a very large number of patients (>800 each), compound clinical endpoints, and a flexible design with regards to concomitant medication use. Likewise, large randomized controlled trials with mycophenolate mofetil, although nominally unsuccessful, clearly demonstrated the clinical benefit of this drug in lupus nephritis. Posthoc analyses of several failed trials involving abatacept and rituximab revealed design elements and/or outcomes that might have changed the outcomes of these studies. Many smaller trials have also been reported, in some instances with surprisingly positive results. An improved understanding of specific design features in SLE clinical trials combined with robust outcomes will make it possible more effectively to design and conduct clinical trials in SLE.

From clinical trial to prescription.

PubMed

Carpenter, William T

2002-03-01

There are many steps between drug discovery and prescribing for a patient. Each step has problems. In this issue of ARCHIVES, Klein and colleagues propose changes in clinical trials that would result in more meaningful information for the treating physician. Of particular importance is the gap between what a physician needs to know and what is produced in the clinical trials that leads to approval of a new drug by the US Food and Drug Administration (FDA). Their recommendations for improving clinical trials are cogent, but broad-based implementation depends on an organizational structure and political effectiveness not presently in place. Most important, as the authors note, is an effective work group representing industry, regulatory agencies, and academic and federal science, addressing clinical trials issues with public participation. While improved quality and relevance of data from clinical trials will strengthen the scientific foundation of pharmacotherapy, other problems impede the delivery of objective information to the treating physician. Most hotly debated is the role of money in the creation and dissemination of knowledge.

CRC Clinical Trials Management System (CTMS): An Integrated Information Management Solution for Collaborative Clinical Research

PubMed Central

Payne, Philip R.O.; Greaves, Andrew W.; Kipps, Thomas J.

2003-01-01

The Chronic Lymphocytic Leukemia (CLL) Research Consortium (CRC) consists of 9 geographically distributed sites conducting a program of research including both basic science and clinical components. To enable the CRC’s clinical research efforts, a system providing for real-time collaboration was required. CTMS provides such functionality, and demonstrates that the use of novel data modeling, web-application platforms, and management strategies provides for the deployment of an extensible, cost effective solution in such an environment. PMID:14728471

Building trust and diversity in patient-centered oncology clinical trials: An integrated model.

PubMed

Hurd, Thelma C; Kaplan, Charles D; Cook, Elise D; Chilton, Janice A; Lytton, Jay S; Hawk, Ernest T; Jones, Lovell A

2017-04-01

contract. Contract renegotiation occurs in response to cyclical changes within the trust relationship throughout trial participation. The Integrated Model of Trust offers a novel framework to interrogate the process by which diverse populations and clinical trial teams build trust. To our knowledge, this is the first model of trust-building in clinical trials that frames trust development through integrated clinical and business perspectives. By focusing on the process, rather than outcomes of trust-building diverse trial participants, clinical trials teams, participants, and cancer centers may be able to better understand, measure, and manage their trust relationships in real time. Ultimately, this may foster increased recruitment and retention of diverse populations to clinical trials.

Radiological clinical trials: Proposal of a problem-finding questionnaire to improve study success.

PubMed

Valdora, Francesca; Bignotti, Bianca; Calabrese, Massimo; Houssami, Nehmat; Tagliafico, Alberto

2016-12-26

To develop a survey to help define the main problems in radiological clinical trials. Since 2006, we have managed seven different radiological clinical trials recruiting patients in academic and non-academic centres. We developed a preliminary questionnaire using a four-round Delphi approach to identify problems occurring in radiological clinical trials run at our centre. We investigated the recruitment experience, involvement of all multi-disciplinary team members and main obstacles to completing the projects. A final round of Delphi processes elucidated solutions to the identified problems. Among 19/20 (95%) respondents, 10 (53%) were young physicians (under 35 years old), and the respondents included non-faculty members, fellows, residents, and undergraduate students. Ninety-four percent (18/19) of respondents showed interest in conducting clinical trials. On a scale of 1 to 10, the problems with higher/worse scores (8-9) were related to technical or communication problems. The most frequent problems across all studies were technical problems related to clinical trial equipment, insufficient willingness to participate, obstacles to understanding the design of electronic-case report form and extra work. The developed questionnaire identified the main recurring problems in radiological clinical trials as perceived by end-users and helped define possible solutions that are mostly related to having dedicated clinical trial research staff.

Mortality Rates Among Substance Use Disorder Participants in Clinical Trials: Pooled Analysis of Twenty-Two Clinical Trials Within the National Drug Abuse Treatment Clinical Trials Network.

PubMed

Lindblad, Robert; Hu, Lian; Oden, Neal; Wakim, Paul; Rosa, Carmen; VanVeldhuisen, Paul

2016-11-01

Most substance use disorders (SUD) treatment clinical trials are too short and small to reliably estimate the incidence of rare events like death. The aim of this study is to estimate the overall mortality rates among a SUD treatment-seeking population by pooling participants from multiple clinical trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN). Drug and or alcohol users (N=9866) who sought treatment and participated in one of the twenty-two CTN trials. Data were collected through randomized clinical trials in national community treatment programs for SUD. Pooled analysis was performed to assess age- and gender-standardized mortality rate(s) (SM rate(s)), and mortality ratio(s) (SM ratio(s)) of CTN trial participants compared to the U.S. general population. The age- and gender-SM rate among CTN trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY) compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general population in 2005. By gender, age-adjusted SM ratio for female CTN trial participants was over five times (SM ratio=5.35, 95% CI: 3.31-8.19)), and for male CTN trial participants, it was over three times (SM ratio=3.39, 95% CI: 2.25-4.90) higher than their gender comparable peers in the U.S. general population. Age and gender-standardized mortality rates and ratios among NIDA CTN SUD treatment-seeking clinical trial participants are higher than the age and gender comparable U.S. general population. The overall mortality rates of CTN trial participants are similar to in-treatment mortality reported in large U.S. and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial participants and risk times will improve the stability of estimates, especially within subgroups based on primary substance of abuse. These SUD mortality rates can be used to facilitate safety monitoring within SUD clinical trials. Copyright © 2016

The current status of clinical trials focusing on nasopharyngeal carcinoma: A comprehensive analysis of ClinicalTrials.gov database.

PubMed

Peng, Hao; Chen, Lei; Chen, Yu-Pei; Li, Wen-Fei; Tang, Ling-Long; Lin, Ai-Hua; Sun, Ying; Ma, Jun

2018-01-01

Clinical Trials have emerged as the main force in driving the development of medicine. However, little is known about the current status of clinical trials regarding nasopharyngeal carcinoma (NPC). This study aimed at providing a comprehensive landscape of NPC-related trials on the basis of ClinicalTrials.gov database. We used the keyword "nasopharyngeal carcinoma" to search the ClinicalTrials.gov database and assessed the characteristics of these trials. Up to December 30, 2016, 462 eligible trials in total were identified, of which 222 (48.0%) recruited only NPC (NPC trials) and the other 240 (52.0%) recruited both NPC and other cancers (multiple cancer trials). Moreover, 47 (10.2%) were Epstein-Barr virus (EBV)-related trials and 267 (57.8%) focused on metastatic/recurrent disease. Compared with NPC trials, the multiple cancer trials had a higher percentage of phase 1 (26.7% vs. 6.7%, P < 0.001) studies and more patients with metastatic/recurrent disease (72.5% vs. 41.9%, P < 0.001). Notably, non-EBV trials had more phase 2 or 3 (78.4% vs. 48.8%, P < 0.001) and interventional studies (89.5% vs. 70.7%, P = 0.002) than EBV trials. Obviously, more phase 2/3 or 3 trials were conducted in patients with non-metastatic/recurrent disease (29.4% vs. 4.9%, P < 0.001); however, metastatic/recurrent trials were more likely to be anticancer (94.6% vs. 63.6%, P < 0.001). The role of plasma EBV DNA in clinical trials is underestimated, and high-level randomized clinical trials should be performed for patients with metastatic/recurrent disease.

Developing translational research infrastructure and capabilities associated with cancer clinical trials.

PubMed

Hall, Jacqueline A; Brown, Robert

2013-09-27

The integration of molecular information in clinical decision making is becoming a reality. These changes are shaping the way clinical research is conducted, and as reality sets in, the challenges in conducting, managing and organising multi-disciplinary research become apparent. Clinical trials provide a platform to conduct translational research (TR) within the context of high quality clinical data accrual. Integrating TR objectives in trials allows the execution of pivotal studies that provide clinical evidence for biomarker-driven treatment strategies, targeting early drug development trials to a homogeneous and well defined patient population, supports the development of companion diagnostics and provides an opportunity for deepening our understanding of cancer biology and mechanisms of drug action. To achieve these goals within a clinical trial, developing translational research infrastructure and capabilities (TRIC) plays a critical catalytic role for translating preclinical data into successful clinical research and development. TRIC represents a technical platform, dedicated resources and access to expertise promoting high quality standards, logistical and operational support and unified streamlined procedures under an appropriate governance framework. TRIC promotes integration of multiple disciplines including biobanking, laboratory analysis, molecular data, informatics, statistical analysis and dissemination of results which are all required for successful TR projects and scientific progress. Such a supporting infrastructure is absolutely essential in order to promote high quality robust research, avoid duplication and coordinate resources. Lack of such infrastructure, we would argue, is one reason for the limited effect of TR in clinical practice beyond clinical trials.

Types of Treatment: Clinical Trials

MedlinePlus

... or kidney disease Who's on the Clinical Trial Team? A clinical trial team is made up of doctors, nurses, social workers and other healthcare professionals. The team members: Check each participant's health at the beginning ...

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.

Asthma Self-Management Model: Randomized Controlled Trial

ERIC Educational Resources Information Center

Olivera, Carolina M. X.; Vianna, Elcio Oliveira; Bonizio, Roni C.; de Menezes, Marcelo B.; Ferraz, Erica; Cetlin, Andrea A.; Valdevite, Laura M.; Almeida, Gustavo A.; Araujo, Ana S.; Simoneti, Christian S.; de Freitas, Amanda; Lizzi, Elisangela A.; Borges, Marcos C.; de Freitas, Osvaldo

2016-01-01

Information for patients provided by the pharmacist is reflected in adhesion to treatment, clinical results and patient quality of life. The objective of this study was to assess an asthma self-management model for rational medicine use. This was a randomized controlled trial with 60 asthmatic patients assigned to attend five modules presented by…

Improving clinical trials in the critically ill.

PubMed

Angus, Derek C; Mira, Jean-Paul; Vincent, Jean-Louis

2010-02-01

To propose ways in which clinical trials in intensive care can be improved. An international roundtable conference was convened focused on improvement in three broad areas: translation of new knowledge from bench to bedside; design and conduct of clinical trials; and clinical trial infrastructure and environment. The roundtable recommendations were: improvement in clinical trials is a multistep process from better preclinical studies to better clinical trial methodology; new technologies should be used to improve models of critical illness; diseasomes and theragnostics will aid inpatient population selection and more appropriate targeting of interventions; broader study end points should include morbidity as well as mortality; more multicenter studies should be conducted by national and international networks or clinical trials groups; and better collaboration is needed with the industry. There was broad agreement among the roundtable participants regarding a number of explicit opportunities for the improvement of clinical trials in critical care.

Clinical Case Management versus Case Management with Problem-Solving Therapy in Low-Income, Disabled Elders with Major Depression: A Randomized Clinical Trial

PubMed Central

Alexopoulos, George S.; Raue, Patrick J.; McCulloch, Charles; Kanellopoulos, Dora; Seirup, Joanna K.; Sirey, Jo Anne; Banerjee, Samprit; Kiosses, Dimitris N.; Areán, Patricia A.

2015-01-01

Objective To test the hypotheses that (1) clinical case management integrated with problem-solving therapy (CM-PST) is more effective than clinical case management alone (CM) in reducing depressive symptoms of depressed, disabled, impoverished patients and that (2) development of problem-solving skills mediates improvement of depression. Methods This randomized clinical trial with a parallel design allocated participants to CM or CM-PST at 1:1 ratio. Raters were blind to patients’ assignments. Two hundred seventy-one individuals were screened and 171 were randomized to 12 weekly sessions of either CM or CM-PST. Participants were at least 60 years old with major depression measured with the 24-item Hamilton Depression Rating Scale (HAM-D), had at least one disability, were eligible for home-based meals services, and had income no more than 30% of their counties’ median. Results CM and CM-PST led to similar declines in HAM-D over 12 weeks (t = 0.37, df = 547, p = 0.71); CM was noninferior to CM-PST. The entire study group (CM plus CM-PST) had a 9.6-point decline in HAM-D (t = 18.7, df = 547, p <0.0001). The response (42.5% versus 33.3%) and remission (37.9% versus 31.0%) rates were similar (χ2 = 1.5, df = 1, p = 0.22 and χ2 = 0.9, df = 1, p = 0.34, respectively). Development of problem-solving skills did not mediate treatment outcomes. There was no significant increase in depression between the end of interventions and 12 weeks later (0.7 HAM-D point increase) (t = 1.36, df = 719, p = 0.17). Conclusion Organizations offering CM are available across the nation. With training in CM, their social workers can serve the many depressed, disabled, low-income patients, most of whom have poor response to antidepressants even when combined with psychotherapy. PMID:25794636

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.

Impact of clinical trial findings on Bell's palsy management in general practice in the UK 2001–2012: interrupted time series regression analysis

PubMed Central

Morales, Daniel R; Donnan, Peter T; Daly, Fergus; Staa, Tjeerd Van; Sullivan, Frank M

2013-01-01

Objectives To measure the incidence of Bell's palsy and determine the impact of clinical trial findings on Bell's palsy management in the UK. Design Interrupted time series regression analysis and incidence measures. Setting General practices in the UK contributing to the Clinical Practice Research Datalink (CPRD). Participants Patients ≥16 years with a diagnosis of Bell's palsy between 2001 and 2012. Interventions (1) Publication of the 2004 Cochrane reviews of clinical trials on corticosteroids and antivirals for Bell's palsy, which made no clear recommendation on their use and (2) publication of the 2007 Scottish Bell's Palsy Study (SBPS), which made a clear recommendation that treatment with prednisolone alone improves chances for complete recovery. Main outcome measures Incidence of Bell's palsy per 100 000 person-years. Changes in the management of Bell's palsy with either prednisolone therapy, antiviral therapy, combination therapy (prednisolone with antiviral therapy) or untreated cases. Results During the 12-year period, 14 460 cases of Bell's palsy were identified with an overall incidence of 37.7/100 000 person-years. The 2004 Cochrane reviews were associated with immediate falls in prednisolone therapy (−6.3% (−11.0 to −1.6)), rising trends in combination therapy (1.1% per quarter (0.5 to 1.7)) and falling trends for untreated cases (−0.8% per quarter (−1.4 to −0.3)). SBPS was associated with immediate increases in prednisolone therapy (5.1% (0.9 to 9.3)) and rising trends in prednisolone therapy (0.7% per quarter (0.4 to 1.2)); falling trends in combination therapy (−1.7% per quarter (−2.2 to −1.3)); and rising trends for untreated cases (1.2% per quarter (0.8 to 1.6)). Despite improvements, 44% still remain untreated. Conclusions SBPS was clearly associated with change in management, but a significant proportion of patients failed to receive effective treatment, which cannot be fully explained. Clarity and uncertainty in

Clinical Trials

MedlinePlus

... pill that has no medicine in it. Most times participants do not know which they are receiving. Other clinical trials involve a crossover design, where participants are randomly assigned to take a ...

Electronic data collection for clinical trials using tablet and handheld PCs

NASA Astrophysics Data System (ADS)

Alaoui, Adil; Vo, Minh; Patel, Nikunj; McCall, Keith; Lindisch, David; Watson, Vance; Cleary, Kevin

2005-04-01

This paper describes a system that uses electronic forms to collect patient and procedure data for clinical trials. During clinical trials, patients are typically required to provide background information such as demographics and medical history, as well as review and complete any consent forms. Physicians or their assistants then usually have additional forms for recording technical data from the procedure and for gathering follow-up information from patients after completion of the procedure. This approach can lead to substantial amounts of paperwork to collect and manage over the course of a clinical trial with a large patient base. By using e-forms instead, data can be transmitted to a single, centralized database, reducing the problem of managing paper forms. Additionally, the system can provide a means for relaying information from the database to the physician on his/her portable wireless device, such as to alert the physician when a patient has completed the pre-procedure forms and is ready to begin the procedure. This feature could improve the workflow in busy clinical practices. In the future, the system could be expanded so physicians could use their portable wireless device to pull up entire hospital records and view other pre-procedure data and patient images.

Birth Control in Clinical Trials

PubMed Central

Stewart, J.; Beyer, B. K.; Chadwick, K.; De Schaepdrijver, L.; Desai, M.; Enright, B.; Foster, W.; Hui, J. Y.; Moffat, G. J.; Tornesi, B.; Van Malderen, K.; Wiesner, L.; Chen, C. L.

2015-01-01

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception requirements in clinical trials, the governance processes set up to promote consistency and/or compliance with contraception requirements, and the effectiveness of current contraception practices in preventing pregnancies during clinical trials. Opportunities for improvements in current practices were also considered. The survey results from 12 pharmaceutical companies identified significant variability among companies with regard to contraception practices and governance during clinical trials. This variability was due primarily to differences in definitions, areas of scientific uncertainty or misunderstanding, and differences in company approaches to enrollment in clinical trials. The survey also revealed that few companies collected data in a manner that would allow a retrospective understanding of the reasons for failure of birth control during clinical trials. In this article, suggestions are made for topics where regulatory guidance or scientific publications could facilitate best practice. These include provisions for a pragmatic definition of women of childbearing potential, guidance on how animal data can influence the requirements for male and female birth control, evidence-based guidance on birth control and pregnancy testing regimes suitable for low- and high-risk situations, plus practical methods to ascertain the risk of drug-drug interactions with hormonal contraceptives. PMID:27042398

Ethics of clinical trials in Nigeria.

PubMed

Okonta, Patrick I

2014-05-01

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria.

Ethics of clinical trials in Nigeria

PubMed Central

Okonta, Patrick I.

2014-01-01

The conduct of clinical trials for the development and licensing of drugs is a very important aspect of healthcare. Drug research, development and promotion have grown to a multi-billion dollar global business. Like all areas of human endeavour involving generation and control of huge financial resources, it could be subject to deviant behaviour, sharp business practices and unethical practices. The main objective of this review is to highlight potential ethical challenges in the conduct of clinical trials in Nigeria and outline ways in which these can be avoided. Current international and national regulatory and ethical guidelines are reviewed to illustrate the requirements for ethical conduct of clinical trials. Past experiences of unethical conduct of clinical trials especially in developing countries along with the increasing globalisation of research makes it imperative that all players should be aware of the ethical challenges in clinical trials and the benchmarks for ethical conduct of clinical research in Nigeria. PMID:25013247

The quality of registration of clinical trials.

PubMed

Viergever, Roderik F; Ghersi, Davina

2011-02-24

Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records.

Mortality Rates among Substance Use Disorder Participants in Clinical Trials: Pooled Analysis of Twenty-two Clinical Trials within the National Drug Abuse Treatment Clinical Trials Network

PubMed Central

Lindblad, Robert; Hu, Lian; Oden, Neal; Wakim, Paul; Rosa, Carmen; VanVeldhuisen, Paul

2016-01-01

Background Most substance use disorders (SUD) treatment clinical trials are too short and small to reliably estimate the incidence of rare events like death. Objective The aim of this study is to estimate the overall mortality rates among a SUD treatment-seeking population by pooling participants from multiple clinical trials conducted through the National Institute on Drug Abuse (NIDA)-sponsored National Drug Abuse Treatment Clinical Trials Network (CTN). Participants Drug and or alcohol users (N=9,866) who sought treatment and participated in one of the twenty-two CTN trials. Measurements Data were collected through randomized clinical trials in national community treatment programs (CTPs) for SUD. Pooled analysis was performed to assess age- and gender-standardized mortality rate(s) (SM rate(s)), and mortality ratio(s) (SM ratio(s)) of CTN trial participants compared to the U.S. general population. We also assessed if there were differences in mortality rates across different types of substance of abuse. Results The age- and gender-SM rate among CTN trials participants was 1403 (95% CI: 862-2074) per 100,000 person years (PY) compared to 542 (95% CI: 541-543) per 100,000 PY among the U.S. general population in 2005. By gender, age-adjusted SM ratio for female CTN trial participants was over five times (SM ratio=5.35, 95% CI: 3.31-8.19)), and for male CTN trial participants was over three times (SM ratio=3.39, 95% CI: 2.25-4.90) higher than their gender comparable peers in the U.S. general population. Conclusions Age and gender-standardized mortality rates and ratios among NIDA CTN SUD treatment-seeking clinical trial participants are higher than the age and gender comparable U.S. general population. The overall mortality rates of CTN trial participants are similar to in-treatment mortality reported in large U.S. and non-U.S. cohorts of opioid users. Future analysis with additional CTN trial participants and risk times will improve the stability of estimates

DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

PubMed Central

2012-01-01

Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa. PMID:23046944

Design and implementation of a fault-tolerant and dynamic metadata database for clinical trials

NASA Astrophysics Data System (ADS)

Lee, J.; Zhou, Z.; Talini, E.; Documet, J.; Liu, B.

2007-03-01

In recent imaging-based clinical trials, quantitative image analysis (QIA) and computer-aided diagnosis (CAD) methods are increasing in productivity due to higher resolution imaging capabilities. A radiology core doing clinical trials have been analyzing more treatment methods and there is a growing quantity of metadata that need to be stored and managed. These radiology centers are also collaborating with many off-site imaging field sites and need a way to communicate metadata between one another in a secure infrastructure. Our solution is to implement a data storage grid with a fault-tolerant and dynamic metadata database design to unify metadata from different clinical trial experiments and field sites. Although metadata from images follow the DICOM standard, clinical trials also produce metadata specific to regions-of-interest and quantitative image analysis. We have implemented a data access and integration (DAI) server layer where multiple field sites can access multiple metadata databases in the data grid through a single web-based grid service. The centralization of metadata database management simplifies the task of adding new databases into the grid and also decreases the risk of configuration errors seen in peer-to-peer grids. In this paper, we address the design and implementation of a data grid metadata storage that has fault-tolerance and dynamic integration for imaging-based clinical trials.

The Cooperative Landscape of Multinational Clinical Trials

PubMed Central

Hsiehchen, David; Espinoza, Magdalena; Hsieh, Antony

2015-01-01

The scale and nature of cooperative efforts spanning geopolitical borders in clinical research have not been elucidated to date. In a cross-sectional study of 110,428 interventional trials registered in Clinicaltrials.gov, we characterized the evolution, trial demographics, and network properties of multinational clinical research. We reveal that the relative growth of international collaboratives has remained stagnant in the last two decades, although clinical trials have evolved to become much larger in scale. Multinational clinical trials are also characterized by higher patient enrollments, industry funding, and specific clinical disciplines including oncology and infectious disease. Network analyses demonstrate temporal shifts in collaboration patterns between countries and world regions, with developing nations now collaborating more within themselves, although Europe remains the dominant contributor to multinational clinical trials worldwide. Performances in network centrality measures also highlight the differential contribution of nations in the global research network. A city-level clinical trial network analysis further demonstrates how collaborative ties decline with physical distance. This study clarifies evolving themes and highlights potential growth mechanisms and barriers in multinational clinical trials, which may be useful in evaluating the role of national and local policies in organizing transborder efforts in clinical endeavors. PMID:26103155

Factors influencing clinical trial site selection in Europe: the Survey of Attitudes towards Trial sites in Europe (the SAT-EU Study).

PubMed

Gehring, Marta; Taylor, Rod S; Mellody, Marie; Casteels, Brigitte; Piazzi, Angela; Gensini, Gianfranco; Ambrosio, Giuseppe

2013-11-15

Applications to run clinical trials in Europe fell 25% between 2007 and 2011. Costs, speed of approvals and shortcomings of European Clinical Trial Directive are commonly invoked to explain this unsatisfactory performance. However, no hard evidence is available on the actual weight of these factors or has it been previously investigated whether other criteria may also impact clinical trial site selection. The Survey of Attitudes towards Trial sites in Europe (SAT-EU Study) was an anonymous, cross-sectional web-based survey that systematically assessed factors impacting European clinical trial site selection. It explored 19 factors across investigator-driven, hospital-driven and environment-driven criteria, and costs. It also surveyed perceptions of the European trial environment. Clinical research organisations (CROs), academic clinical trial units (CTUs) and industry invited to respond. weight assigned to each factor hypothesised to impact trial site selection and trial incidence. Secondary outcome: desirability of European countries to run clinical trials. Responses were obtained from 485 professionals in 34 countries: 49% from BioPharma, 40% from CTUs or CROs. Investigator-dependent, environment-dependent and hospital-dependent factors were rated highly important, costs being less important (p<0.0001). Within environment-driven criteria, pool of eligible patients, speed of approvals and presence of disease-management networks were significantly more important than costs or government financial incentives (p<0.0001). The pattern of response was consistent across respondent groupings (CTU vs CRO vs industry). Considerable variability was demonstrated in the perceived receptivity of countries to undertake clinical trials, with Germany, the UK and the Netherlands rated the best trial markets (p<0.0001). Investigator-dependent factors and ease of approval dominate trial site selection, while costs appear less important. Fostering competitiveness of European clinical

Transparency in ovarian cancer clinical trial results: ClinicalTrials.gov versus PubMed, Embase and Google scholar.

PubMed

Roberto, Anna; Radrezza, Silvia; Mosconi, Paola

2018-04-10

In recent years the question of the lack of transparency in clinical research has been debated by clinicians, researchers, citizens and their representatives, authors and publishers. This is particularly important for infrequent cancers such as ovarian cancer, where treatment still gives disappointing results in the majority of cases. Our aim was to assess the availability to the public of results in ClinicalTrials.gov, and the frequency of non-publication of results in ClinicalTrials.gov and in PubMed, Embase and Google Scholar. We collected all trials on ovarian cancer identified as "completed status" in the ClinicalTrials.gov registry on 17 January 2017. We checked the availability of the results in ClinicalTrials.gov and systematically identified published manuscripts on results. Out of 2725 trials on ovarian cancer identified, 752 were classified as "completed status". In those closed between 2008 and 2015, excluding phase I, the frequency of results in ClinicalTrials.gov was 35%. Of the 752 completed studies the frequency of published results in PubMed, Embase or Google Scholar ranged from 57.9% to 69.7% in the last years. These findings show a lack of transparency and credibility of research. Citizens or patients' representatives, with the medical community, should continuously support initiatives to improve the publication and dissemination of clinical study results.

Emerging innovations in clinical trial design.

PubMed

Berry, D A

2016-01-01

Designs of clinical trials have changed little since the advent of randomization in the 1940s. Modern innovations in designs are being driven by the increasing recognition in clinical research that diseases are heterogeneous and patients who apparently have the same disease require different therapies. This article describes some innovations in clinical trial design across therapeutic areas but with a focus on oncology. No one knows what the future holds for clinical trial design but the status quo of large trials that pretend the patient population is homogeneous is not sustainable, either economically or scientifically/medically. No one knows what the eventual business model and regulatory model will be, but they will be very different from today's. © 2015 American Society for Clinical Pharmacology and Therapeutics.

The Quality of Registration of Clinical Trials

PubMed Central

Viergever, Roderik F.; Ghersi, Davina

2011-01-01

Background Lack of transparency in clinical trial conduct, publication bias and selective reporting bias are still important problems in medical research. Through clinical trials registration, it should be possible to take steps towards resolving some of these problems. However, previous evaluations of registered records of clinical trials have shown that registered information is often incomplete and non-meaningful. If these studies are accurate, this negates the possible benefits of registration of clinical trials. Methods and Findings A 5% sample of records of clinical trials that were registered between 17 June 2008 and 17 June 2009 was taken from the International Clinical Trials Registry Platform (ICTRP) database and assessed for the presence of contact information, the presence of intervention specifics in drug trials and the quality of primary and secondary outcome reporting. 731 records were included. More than half of the records were registered after recruitment of the first participant. The name of a contact person was available in 94.4% of records from non-industry funded trials and 53.7% of records from industry funded trials. Either an email address or a phone number was present in 76.5% of non-industry funded trial records and in 56.5% of industry funded trial records. Although a drug name or company serial number was almost always provided, other drug intervention specifics were often omitted from registration. Of 3643 reported outcomes, 34.9% were specific measures with a meaningful time frame. Conclusions Clinical trials registration has the potential to contribute substantially to improving clinical trial transparency and reducing publication bias and selective reporting. These potential benefits are currently undermined by deficiencies in the provision of information in key areas of registered records. PMID:21383991

Data fraud in clinical trials

PubMed Central

George, Stephen L; Buyse, Marc

2015-01-01

Highly publicized cases of fabrication or falsification of data in clinical trials have occurred in recent years and it is likely that there are additional undetected or unreported cases. We review the available evidence on the incidence of data fraud in clinical trials, describe several prominent cases, present information on motivation and contributing factors and discuss cost-effective ways of early detection of data fraud as part of routine central statistical monitoring of data quality. Adoption of these clinical trial monitoring procedures can identify potential data fraud not detected by conventional on-site monitoring and can improve overall data quality. PMID:25729561

Transforming the Activation of Clinical Trials.

PubMed

Watters, Julie T; Pitzen, Jason H; Sanders, Linda J; Bruce, Virginia Nickie M; Cornell, Alissa R; Cseko, Gary C; Grace, Janice S; Kwon, Pamela S; Kukla, Andrea K; Lee, Michael S; Monosmith, Michelle D; Myren, John D; Kottschade, Rebecca S; Shaft, Marc N; Weis, Jennifer Jenny A; Welter, Jane C; Bharucha, Adil E

2018-01-01

The Institute of Medicine and US Food and Drug Administration (FDA) recognize that activating clinical trials in the United States is lengthy and inefficient. Downstream consequences include increased expense, suboptimal accrual, move of clinical trials overseas, and delayed availability of treatments for patients. An in-tandem processing initiative is here highlighted that transformed the activation of clinical trials (TACT), reduced the activation time by 70%, and offers a paradigm for enhanced translational readiness. © 2017 American Society for Clinical Pharmacology and Therapeutics.

Evaluating the financial impact of clinical trials in oncology: results from a pilot study from the Association of American Cancer Institutes/Northwestern University clinical trials costs and charges project.

PubMed

Bennett, C L; Stinson, T J; Vogel, V; Robertson, L; Leedy, D; O'Brien, P; Hobbs, J; Sutton, T; Ruckdeschel, J C; Chirikos, T N; Weiner, R S; Ramsey, M M; Wicha, M S

2000-08-01

Medical care for clinical trials is often not reimbursed by insurers, primarily because of concern that medical care as part of clinical trials is expensive and not part of standard medical practice. In June 2000, President Clinton ordered Medicare to reimburse for medical care expenses incurred as part of cancer clinical trials, although many private insurers are concerned about the expense of this effort. To inform this policy debate, the costs and charges of care for patients on clinical trials are being evaluated. In this Association of American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study, we describe the results and operational considerations of one of the first completed multisite economic analyses of clinical trials. Our pilot effort included assessment of total direct medical charges for 6 months of care for 35 case patients who received care on phase II clinical trials and for 35 matched controls (based on age, sex, disease, stage, and treatment period) at five AACI member cancer centers. Charge data were obtained for hospital and ancillary services from automated claims files at individual study institutions. The analyses were based on the perspective of a third-party payer. The mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years for control patients. The study population included persons with cancer of the breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of patients having stage III to IV disease. Total mean charges for treatment from the time of study enrollment through 6 months were similar: $57,542 for clinical trial patients and $63,721 for control patients (1998 US$; P =.4) Multisite economic analyses of oncology clinical trials are in progress. Strategies that are not likely to overburden data managers and clinicians are possible to devise. However, these studies require careful planning

Nurse-led Multidisciplinary Heart Failure Group Clinic Appointments: Methods, Materials and Outcomes Used in the Clinical Trial

PubMed Central

Smith, C. E.; Piamjariyakul, U.; Dalton, K. M.; Russell, C.; Wick, J.; Ellerbeck, E.F.

2015-01-01

Background The Self-Management and Care of Heart Failure through Group Clinics Trial (SMAC-HF) evaluated the effects of multidisciplinary group clinic appointments on self-care skills and rehospitalizations in high risk heart failure (HF) patients. Objective The purpose of this article is to: (1) describe key SMAC-HF group clinic interactive learning strategies; (2) describe resources and materials used in the group clinic appointment; and (3) present results supporting this patient-centered group intervention. Methods This clinical trial included 198 HF patients (randomized to either group clinical appointments or to standard care). Data were collected from 72 group clinic appointments via patients’: (1) group clinic session evaluations; (2) HF Self-Care Behaviors Skills; (3) HF related discouragement and quality of life scores and (4) HF related reshopitalizations during the 12 month follow-up. Also the costs of delivery of the group clinical appointments were tabulated. Results Overall, patients rated group appointments as 4.8 out of 5 on the “helpfulness” in managing HF score. The statistical model showed a 33% decrease in the rate of rehospitalizations (incidence rate ratio (IRR) = 0.67) associated with the intervention over the 12-month follow-up period when compared with control patients (χ2(1) = 3.9, p = 0.04). The total cost for implementing five group appointments was $243.58 per patient. Conclusion The intervention was associated with improvements in HF self-care knowledge and home care behavior skills and managing their for HF care. In turn, better self-care was associated with reductions in HF related hospitalizations. PMID:25774836

Managing side effects of JAK inhibitors for myelofibrosis in clinical practice.

PubMed

Saeed, Iram; McLornan, Donal; Harrison, Claire N

2017-07-01

Myelofibrosis (MF) is characterized by bone marrow fibrosis, abnormalities in peripheral counts, extramedullary hematopoiesis, splenomegaly and an increased risk of transformation to acute myeloid leukaemia. The disease course is often heterogeneous and management can range from observation alone through to allogeneic stem cell transplantation. As of 2017, the only approved medication for MF remains the JAK Inhibitor (JAKi), ruxolitinib (Novartis Pharmaceuticals, Basel, Switzerland; Incyte, Wilmington, Detroit, USA) although several others have reached advanced stages of clinical trials. Areas covered: In this review, we focus on the management of both common and uncommon side effects arising from the use of currently approved and clinical trial JAKi. Most of the discussion concerns ruxolitinib although we also cover both pacritinib (CTI BioPharma) and momelotinib (Gilead Sciences, Foster City, California) which have been in recent large, multinational phase III trials. The various approaches to management of JAKi-related side effects are discussed - with particular emphasis to anaemia, thrombocytopaenia and infection risk. Expert commentary: JAK inhibitors are effective in many individuals with MF and have revolutionized the current treatment paradigm. The side effect profile, in the most, is predictable and manageable with high degrees of clinical surveillance and dose modifications.

Type 1 Diabetes TrialNet--an international collaborative clinical trials network.

PubMed

Skyler, Jay S; Greenbaum, Carla J; Lachin, John M; Leschek, Ellen; Rafkin-Mervis, Lisa; Savage, Peter; Spain, Lisa

2008-12-01

Type 1 Diabetes TrialNet is an international consortium of clinical research centers aimed at the prevention or delay of type 1 diabetes (T1D). The fundamental goal of TrialNet is to counter the T1D disease process by immune modulation and/or enhancement of beta cell proliferation and regeneration. To achieve this goal, TrialNet researchers are working to better understand the natural history of the disease, to identify persons at risk, and to clinically evaluate novel therapies that balance potential risks and benefits. The particular focus is on studies of preventive measures. In addition, TrialNet evaluates therapies in individuals with newly diagnosed T1D with preserved beta cell function to help determine the risk/benefit profile and gain an initial assessment of potential efficacy in preservation of beta cell function, so that promising agents can be studied in prevention trials. In addition, TrialNet evaluates methodologies that enhance the conduct of its clinical trials, which includes tests of outcome assessment methodology, the evaluation of surrogate markers, and mechanistic studies laying the foundation for future clinical trials.

Patient-reported outcomes (PROs): the significance of using humanistic measures in clinical trial and clinical practice.

PubMed

Refolo, P; Minacori, R; Mele, V; Sacchini, D; Spagnolo, A G

2012-10-01

Patient-reported outcome (PRO) is an "umbrella term" that covers a whole range of potential types of measurement but it is used specifically to refer to all measures quantifying the state of health through the evaluation of outcomes reported by the patient himself/herself. PROs are increasingly seen as complementary to biomedical measures and they are being incorporated more frequently into clinical trials and clinical practice. After considering the cultural background of PROs - that is the well known patient-centered model of medicine -, their historical profile (since 1914, the year of the first outcome measure) and typologies, the paper aims at debating their methodological complexity and implementation into practice. Some clinical trials and therapeutic managements utilizing patient-centered measures will be also analyzed.

Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

PubMed

Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

2013-01-01

PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

A comparison of interventional clinical trials in rare versus non-rare diseases: an analysis of ClinicalTrials.gov.

PubMed

Bell, Stuart A; Tudur Smith, Catrin

2014-11-26

To provide a comprehensive characterisation of rare disease clinical trials registered in ClinicalTrials.gov, and compare against characteristics of trials in non-rare diseases. Registry based study of ClinicalTrials.gov registration entries. The ClinicalTrials.gov registry comprised 133,128 studies registered to September 27, 2012. By annotating medical subject heading descriptors to condition terms we could identify rare and non-rare disease trials. A total of 24,088 Interventional trials registered after January 1, 2006, conducted in the United States, Canada and/or the European Union were categorised as rare or non-rare. Characteristics of the respective trials were extracted and summarised with comparative statistics calculated where appropriate. Characteristics of interventional trials reported in the database categorised by rare and non-rare conditions to allow comparison. Of the 24,088 trials categorised 2,759 (11.5%) were classified as rare disease trials and 21,329 (88.5%) related to non-rare conditions. Despite the limitations of the database we found that rare disease trials differed to non-rare disease trials across all characteristics that we examined. Rare disease trials enrolled fewer participants (median 29 vs. 62), were more likely to be single arm (63.0% vs. 29.6%), non-randomised (64.5% vs. 36.1%) and open label (78.7% vs. 52.2%). A higher proportion of rare disease trials were terminated early (13.7% vs. 6.3%) and proportionally fewer rare disease studies were actively pursuing, or waiting to commence, enrolment (15.9% vs. 38.5%). Rare disease interventional trials differ from those in non-rare conditions with notable differences in enrolment, design, blinding and randomisation. However, clinical trials should aim to implement the highest trial design standards possible, regardless of whether diseases are rare or not.

Failure mode and effects analysis drastically reduced potential risks in clinical trial conduct.

PubMed

Lee, Howard; Lee, Heechan; Baik, Jungmi; Kim, Hyunjung; Kim, Rachel

2017-01-01

Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. A total of 114 failure modes were identified with an RPN score ranging 3-378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes.

Failure mode and effects analysis drastically reduced potential risks in clinical trial conduct

PubMed Central

Baik, Jungmi; Kim, Hyunjung; Kim, Rachel

2017-01-01

Background Failure mode and effects analysis (FMEA) is a risk management tool to proactively identify and assess the causes and effects of potential failures in a system, thereby preventing them from happening. The objective of this study was to evaluate effectiveness of FMEA applied to an academic clinical trial center in a tertiary care setting. Methods A multidisciplinary FMEA focus group at the Seoul National University Hospital Clinical Trials Center selected 6 core clinical trial processes, for which potential failure modes were identified and their risk priority number (RPN) was assessed. Remedial action plans for high-risk failure modes (RPN >160) were devised and a follow-up RPN scoring was conducted a year later. Results A total of 114 failure modes were identified with an RPN score ranging 3–378, which was mainly driven by the severity score. Fourteen failure modes were of high risk, 11 of which were addressed by remedial actions. Rescoring showed a dramatic improvement attributed to reduction in the occurrence and detection scores by >3 and >2 points, respectively. Conclusions FMEA is a powerful tool to improve quality in clinical trials. The Seoul National University Hospital Clinical Trials Center is expanding its FMEA capability to other core clinical trial processes. PMID:29089745

Managing Attribute—Value Clinical Trials Data Using the ACT/DB Client—Server Database System

PubMed Central

Nadkarni, Prakash M.; Brandt, Cynthia; Frawley, Sandra; Sayward, Frederick G.; Einbinder, Robin; Zelterman, Daniel; Schacter, Lee; Miller, Perry L.

1998-01-01

ACT/DB is a client—server database application for storing clinical trials and outcomes data, which is currently undergoing initial pilot use. It stores most of its data in entity—attribute—value form. Such data are segregated according to data type to allow indexing by value when possible, and binary large object data are managed in the same way as other data. ACT/DB lets an investigator design a study rapidly by defining the parameters (or attributes) that are to be gathered, as well as their logical grouping for purposes of display and data entry. ACT/DB generates customizable data entry. The data can be viewed through several standard reports as well as exported as text to external analysis programs. ACT/DB is designed to encourage reuse of parameters across multiple studies and has facilities for dictionary search and maintenance. It uses a Microsoft Access client running on Windows 95 machines, which communicates with an Oracle server running on a UNIX platform. ACT/DB is being used to manage the data for seven studies in its initial deployment. PMID:9524347

Methodology Series Module 4: Clinical Trials.

PubMed

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an "open trial." However, many of the trials are not open - they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.

Clinical Perspectives from Randomized Phase 3 Trials on Prostate Cancer: An Analysis of the ClinicalTrials.gov Database.

PubMed

Tsikkinis, Alexandros; Cihoric, Nikola; Giannarini, Gianluca; Hinz, Stefan; Briganti, Alberto; Wust, Peter; Ost, Piet; Ploussard, Guillaume; Massard, Christophe; Surcel, Cristian I; Sooriakumaran, Prasanna; Isbarn, Hendrik; De Visschere, Peter J L; Futterer, Jurgen J; van der Bergh, Roderick C N; Dal Pra, Alan; Aebersold, Daniel M; Budach, Volker; Ghadjar, Pirus

2015-09-01

It is not easy to overview pending phase 3 trials on prostate cancer (PCa), and awareness of these trials would benefit clinicians. To identify all phase 3 trials on PCa registered in the ClinicalTrials.gov database with pending results. On September 29, 2014, a database was established from the records for 175 538 clinical trials registered on ClinicalTrials.gov. A search of this database for the substring "prostat" identified 2951 prostate trials. Phase 3 trials accounted for 441 studies, of which 333 concerned only PCa. We selected only ongoing or completed trials with pending results, that is, for which the primary endpoint had not been published in a peer-reviewed medical journal. We identified 123 phase 3 trials with pending results. Trials were conducted predominantly in North America (n=63; 51%) and Europe (n=47; 38%). The majority were on nonmetastatic disease (n=82; 67%), with 37 (30%) on metastatic disease and four trials (3%) including both. In terms of intervention, systemic treatment was most commonly tested (n=71; 58%), followed by local treatment 34 (28%), and both systemic and local treatment (n=11; 9%), with seven (6%) trials not classifiable. The 71 trials on systemic treatment included androgen deprivation therapy (n=34; 48%), chemotherapy (n=15; 21%), immunotherapy (n=9; 13%), other systemic drugs (n=9; 13%), radiopharmaceuticals (n=2; 3%), and combinations (n=2; 3%). Local treatments tested included radiation therapy (n=27; 79%), surgery (n=5; 15%), and both (n=2; 2%). A limitation is that not every clinical trial is registered on ClinicalTrials.gov. There are many PCa phase 3 trials with pending results, most of which address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively. This report describes all phase 3 trials on prostate cancer registered in the ClinicalTrials

[Clinical trials registry].

PubMed

Ryder, Elena

2004-12-01

Authors and journals are more enthusiastic about the publication of trials with positive results than those negative or inconclusive trials. The International Committee of Medical Journal Editors proposed comprehensive trials registration as a solution to the problem of selective awareness and announces that the ICMJE member journals will adopt a trial-registration policy to promote this goal. They establish as a condition of consideration for publication, registration in a public trials registry. They recommend registries that meet certain criteria as www.clinicaltrials.com. Among those criteria is that the registry must be supported by a non-profit organization. On the other hand, people from Current Controlled Trials Ltd. being a commercial company, but meeting all the other criteria established by the ICMJE, feel that is being put aside. We wonder if clinical trials in our country are being registered in some of these International Registries. If not, would it be time to do so?

Spine device clinical trials: design and sponsorship.

PubMed

Cher, Daniel J; Capobianco, Robyn A

2015-05-01

Multicenter prospective randomized clinical trials represent the best evidence to support the safety and effectiveness of medical devices. Industry sponsorship of multicenter clinical trials is purported to lead to bias. To determine what proportion of spine device-related trials are industry-sponsored and the effect of industry sponsorship on trial design. Analysis of data from a publicly available clinical trials database. Clinical trials of spine devices registered on ClinicalTrials.gov, a publicly accessible trial database, were evaluated in terms of design, number and location of study centers, and sample size. The relationship between trial design characteristics and study sponsorship was evaluated using logistic regression and general linear models. One thousand six hundred thrity-eight studies were retrieved from ClinicalTrials.gov using the search term "spine." Of the 367 trials that focused on spine surgery, 200 (54.5%) specifically studied devices for spine surgery and 167 (45.5%) focused on other issues related to spine surgery. Compared with nondevice trials, device trials were far more likely to be sponsored by the industry (74% vs. 22.2%, odds ratio (OR) 9.9 [95% confidence interval 6.1-16.3]). Industry-sponsored device trials were more likely multicenter (80% vs. 29%, OR 9.8 [4.8-21.1]) and had approximately four times as many participating study centers (p<.0001) and larger sample sizes. There were very few US-based multicenter randomized trials of spine devices not sponsored by the industry. Most device-related spine research is industry-sponsored. Multicenter trials are more likely to be industry-sponsored. These findings suggest that previously published studies showing larger effect sizes in industry-sponsored vs. nonindustry-sponsored studies may be biased as a result of failure to take into account the marked differences in design and purpose. Copyright © 2015 Elsevier Inc. All rights reserved.

Best clinical trials reported in 2010.

PubMed

Garner, John B; Grayburn, Paul A; Yancy, Clyde W

2011-07-01

Each year, a number of clinical trials emerge with data sufficient to change clinical practice. Determining which findings will result in practice change and which will provide only incremental benefit can be a dilemma for clinicians. The authors review selected clinical trials reported in 2010 in journals, at society meetings, and at conferences, focusing on those studies that have the potential to change clinical practice. This review offers 3 separate means of analysis: an abbreviated text summary, organized by subject area; a comprehensive table of relevant clinical trials that provides a schematic review of the hypotheses, interventions, methods, primary end points, results, and implications; and a complete bibliography for further reading as warranted. It is hoped that this compilation of relevant clinical trials and their important findings released in 2010 will be of benefit in the everyday practice of cardiovascular medicine. Copyright © 2011 Elsevier Inc. All rights reserved.

Inclusion of Minority Patients in Breast Cancer Clinical Trials: The Role of the Clinical Trial Environment

DTIC Science & Technology

2008-05-01

trials, site cultural competence, and outreach efforts. We will also examine the social and physical characteristics of the community surrounding the...clinical trial sites and those that address specific barriers associated with the social or physical environment. 2 Body This annual report...indicators. Data will be collected to characterize both the physical environment and the social environment surrounding clinical trials. The

Designing clinical trials for amblyopia

PubMed Central

Holmes, Jonathan M.

2015-01-01

Randomized clinical trial (RCT) study design leads to one of the highest levels of evidence, and is a preferred study design over cohort studies, because randomization reduces bias and maximizes the chance that even unknown confounding factors will be balanced between treatment groups. Recent randomized clinical trials and observational studies in amblyopia can be taken together to formulate an evidence-based approach to amblyopia treatment, which is presented in this review. When designing future clinical studies of amblyopia treatment, issues such as regression to the mean, sample size and trial duration must be considered, since each may impact study results and conclusions. PMID:25752747

Guidance for Researchers Developing and Conducting Clinical Trials in Practice-based Research Networks (PBRNs)

PubMed Central

Dolor, Rowena J.; Schmit, Kristine M.; Graham, Deborah G.; Fox, Chester H.; Baldwin, Laura Mae

2015-01-01

Background There is increased interest nationally in multicenter clinical trials to answer questions about clinical effectiveness, comparative effectiveness, and safety in real-world community settings. Primary care practice-based research networks (PBRNs), comprising community- and/or academically affiliated practices committed to improving medical care for a range of health problems, offer ideal settings for these trials, especially pragmatic clinical trials. However, many researchers are not familiar with working with PBRNs. Methods Experts in practice-based research identified solutions to challenges that researchers and PBRN personnel experience when collaborating on clinical trials in PBRNs. These were organized as frequently asked questions in a draft document presented at a 2013 Agency for Health care Research and Quality PBRN conference workshop, revised based on participant feedback, then shared with additional experts from the DARTNet Institute, Clinical Translational Science Award PBRN, and North American Primary Care Research Group PBRN workgroups for further input and modification. Results The “Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice-Based Research Networks” offers guidance in the areas of recruiting and engaging practices, budgeting, project management, and communication, as well as templates and examples of tools important in developing and conducting clinical trials. Conclusion Ensuring the successful development and conduct of clinical trials in PBRNs requires a highly collaborative approach between academic research and PBRN teams. PMID:25381071

Randomised controlled trial of the clinical and cost-effectiveness of a peer-delivered self-management intervention to prevent relapse in crisis resolution team users: study protocol

PubMed Central

Mason, Oliver; Osborn, David; Henderson, Claire; Marston, Louise; Ambler, Gareth; Pilling, Stephen; Morant, Nicola; Gray, Richard; Weaver, Tim; Nolan, Fiona; Lloyd-Evans, Brynmor

2017-01-01

Introduction Crisis resolution teams (CRTs) provide assessment and intensive home treatment in a crisis, aiming to offer an alternative for people who would otherwise require a psychiatric inpatient admission. They are available in most areas in England. Despite some evidence for their clinical and cost-effectiveness, recurrent concerns are expressed regarding discontinuity with other services and lack of focus on preventing future relapse and readmission to acute care. Currently evidence on how to prevent readmissions to acute care is limited. Self-management interventions, involving supporting service users in recognising and managing signs of their own illness and in actively planning their recovery, have some supporting evidence, but have not been tested as a means of preventing readmission to acute care in people leaving community crisis care. We thus proposed the current study to test the effectiveness of such an intervention. We selected peer support workers as the preferred staff to deliver such an intervention, as they are well-placed to model and encourage active and autonomous recovery from mental health problems. Methods and analysis The CORE (CRT Optimisation and Relapse Prevention) self-management trial compares the effectiveness of a peer-provided self-management intervention for people leaving CRT care, with treatment as usual supplemented by a booklet on self-management. The planned sample is 440 participants, including 40 participants in an internal pilot. The primary outcome measure is whether participants are readmitted to acute care over 1 year of follow-up following entry to the trial. Secondary outcomes include self-rated recovery at 4 and at 18 months following trial entry, measured using the Questionnaire on the Process of Recovery. Analysis will follow an intention to treatment principle. Random effects logistic regression modelling with adjustment for clustering by peer support worker will be used to test the primary hypothesis. Ethics

[Features of Clinical Register of Chinese Medicine and Pharmacy Based on ClinicalTrials.gov. (USA)].

PubMed

Lu, Peng-fei; Liao, Xing; Xie, Yan-ming; Wang, Zhi-guo

2015-11-01

In recent 10 years, clinical trials of Chinese medicine and pharmacy (cMP) at clinicalTrials.gov.(USA) are gradually increasing. In order to analyze features of CMP clinical register, ClinicalTrials.gov register database were comprehensively retrieved in this study. Included clinical trials were input one item after another using EXCEL. A final of 348 CMP clinical trials were included. Results showed that China occupied the first place in CMP clinical register, followed by USA. CMP clinical trials, sponsored mainly by colleges/universities and hospitals, mostly covered interventional studies on evaluating safety/effectiveness of CMP. The proportions of studies, sponsored by mainland China and companies, recruitment trials and multi-center clinical trials in interventional trials were increasing. The proportions of studies sponsored by Hong Kong and Taiwan, research completed trials, unclear research status, phase III clinical trials, and published research trials in interventional trials were decreasing. Published ratios of CMP clinical trials were quite low. There were more missing types and higher proportions in trial register information.

Impact of the European Clinical Trials Directive on academic clinical research.

PubMed

Baeyens, A J

2004-01-01

With the adoption of the Clinical Trials Directive it was Europe's intention to make the performance of multi-national clinical trials in Europe easier through the harmonization of the regulatory procedures. As the Directive was mainly conceived to facilitate the performance of multi-national clinical trials to develop new drugs, it is to be determined to what extent academic clinical trials will be concerned by the Directive and more importantly what will be its impact on daily academic clinical research. Contrary to several national regulations the scope of the Directive is very large only excluding non-interventional trials. This implies that most of the academic clinical trials will be concerned by the Directive. Besides the handling of the regulatory procedures in the different countries, issues related to insurance, labeling requirements and provision of the investigational medical products will expose the academic sponsor to additional administrative and financial challenges that will have to be handled appropriately, as the academic sponsors will be controlled by Inspectors regarding their compliance with the new regulations to come.

Achieving consensus for clinical trials

PubMed Central

Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. Oliver; Walsh, Karin S.; Wolters, Pamela L.; Widemann, Brigitte C.

2013-01-01

The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

Nursing Case Management and Glycemic Control Among Brazilians With Type 2 Diabetes: Pragmatic Clinical Trial.

PubMed

Moreira, Ricardo Castanho; Mantovani, Maria de Fátima; Soriano, José Verdú

2015-01-01

Type 2 diabetes mellitus is a chronic condition that requires ongoing, life-long care in order to be controlled. The aims of the study were to assess the effect of nursing case management on glycated hemoglobin (HbA1c) levels compared to usual care in people with type 2 diabetes mellitus and to determine if effects of nursing case management varied by gender, age, duration of disease, education, and income. This is a pragmatic clinical trial, conducted in the municipality of Bandeirantes, Paraná, Brazil, in 2011 and 2012. Eighty individuals were recruited and randomized equally to receive nursing case management or usual care. Covariates were sociodemographic and clinical factors. The outcome was HbA1c measured at baseline, 6 months, and 12 months. The sample consisted predominately of women; most had been diagnosed with type 2 diabetes mellitus within the previous 5 years. Mean age was 50.14 (SD = 7.00), with 5.27 (SD = 4.39) years of schooling and an average HbA1c of 9.90% (SD = 2.49). Hemoglobin A1c was reduced from an average of 10.33% to 9.0% (p < .01) in the nursing case management group and from 9.57% to 8.93% (p = .05) in the usual care group; the group by time effect was not significant. Case management effects varied by younger age (p = .05), duration of type 2 diabetes less than 5 years (p = .03), up to 4 years of schooling (p = .04), and being in the lowest-income stratum (p = .02). Both groups showed a statistically significant reduction of HbA1c at 6 and 12 months following baseline. The difference in proportional reduction of HbA1c between groups was not statistically significant.

Clinical trials attitudes and practices of Latino physicians.

PubMed

Ramirez, Amelie G; Wildes, Kimberly; Talavera, Greg; Nápoles-Springer, Anna; Gallion, Kipling; Pérez-Stable, Eliseo J

2008-07-01

Ethnic differences in physicians' attitudes and behaviors related to clinical trials might partially account for disparities in clinical trial participation among Latino patients. Literature regarding Latino physicians' clinical trials attitudes and practices, in comparison to White physicians, was lacking. Cross-sectional data from randomly selected physicians (N=695), stratified by ethnicity, were analyzed to test associations of ethnicity with physicians' participation in and attitudes toward referral of patients to clinical trials. Chi-square analyses showed significant (p<0.05) associations of physician race/ethnicity and clinical trials involvement, type of trial for which the physician is likely to recommend a patient, belief in scientific value, and factors that would influence recommendation for a patient to participate. Multivariate analyses resulted in several significant (p<0.05) predictors of clinical trials outcomes, including physician race/ethnicity. Latino physicians were significantly less involved in clinical trials than White physicians and found less scientific value in them, highlighting areas for future education and intervention.

How Can the Evidence from Global Large-scale Clinical Trials for Cardiovascular Diseases be Improved?

PubMed

Sawata, Hiroshi; Tsutani, Kiichiro

2011-06-29

Clinical investigations are important for obtaining evidence to improve medical treatment. Large-scale clinical trials with thousands of participants are particularly important for this purpose in cardiovascular diseases. Conducting large-scale clinical trials entails high research costs. This study sought to investigate global trends in large-scale clinical trials in cardiovascular diseases. We searched for trials using clinicaltrials.gov (URL: http://www.clinicaltrials.gov/) using the key words 'cardio' and 'event' in all fields on 10 April, 2010. We then selected trials with 300 or more participants examining cardiovascular diseases. The search revealed 344 trials that met our criteria. Of 344 trials, 71% were randomized controlled trials, 15% involved more than 10,000 participants, and 59% were funded by industry. In RCTs whose results were disclosed, 55% of industry-funded trials and 25% of non-industry funded trials reported statistically significant superiority over control (p = 0.012, 2-sided Fisher's exact test). Our findings highlighted concerns regarding potential bias related to funding sources, and that researchers should be aware of the importance of trial information disclosures and conflicts of interest. We should keep considering management and training regarding information disclosures and conflicts of interest for researchers. This could lead to better clinical evidence and further improvements in the development of medical treatment worldwide.

[Standard Cancer Therapy Are Established by the Investigator-Initiated Post-Marketing Clinical Trials, Not by the Indication-Directed Clinical Trials].

PubMed

Shimada, Yasuhiro

2016-04-01

The financial supports for investigator-initiated post-marketing clinical trial in clinical oncology are reduced after scandals related to the other fields of clinical trials in Japan. These clinical trials are the essential final steps of clinical development in newer cancer therapy, which should be conducted in the investigator-initiated clinical trial groups with well-organized infrastructure and continuous financial supports. The present problems are discussed and summarized. Future perspectives with the national viewpoints needed to be included the idea of "health technology assessment".

Maintaining data integrity in a rural clinical trial.

PubMed

Van den Broeck, Jan; Mackay, Melanie; Mpontshane, Nontobeko; Kany Kany Luabeya, Angelique; Chhagan, Meera; Bennish, Michael L

2007-01-01

Clinical trials conducted in rural resource-poor settings face special challenges in ensuring quality of data collection and handling. The variable nature of these challenges, ways to overcome them, and the resulting data quality are rarely reported in the literature. To provide a detailed example of establishing local data handling capacity for a clinical trial conducted in a rural area, highlight challenges and solutions in establishing such capacity, and to report the data quality obtained by the trial. We provide a descriptive case study of a data system for biological samples and questionnaire data, and the problems encountered during its implementation. To determine the quality of data we analyzed test-retest studies using Kappa statistics of inter- and intra-observer agreement on categorical data. We calculated Technical Errors of Measurement of anthropometric measurements, audit trail analysis was done to assess error correction rates, and residual error rates were calculated by database-to-source document comparison. Initial difficulties included the unavailability of experienced research nurses, programmers and data managers in this rural area and the difficulty of designing new software tools and a complex database while making them error-free. National and international collaboration and external monitoring helped ensure good data handling and implementation of good clinical practice. Data collection, fieldwork supervision and query handling depended on streamlined transport over large distances. The involvement of a community advisory board was helpful in addressing cultural issues and establishing community acceptability of data collection methods. Data accessibility for safety monitoring required special attention. Kappa values and Technical Errors of Measurement showed acceptable values. Residual error rates in key variables were low. The article describes the experience of a single-site trial and does not address challenges particular to multi

[Optimizing the managment of patients with diabetes mellitus: selected clinical trials from the 2004 Congress of the American Diabetes Association].

PubMed

Scheen, A J; Radermecker, R P; Philips, J C

2004-06-01

The 64th scientific congress of the American Diabetes Association had a special session devoted to the presentation of the results from three clinical trials: 1) the first multicentre international trial of pancreatic islet transplantation according to the so-called Edmonton protocol with the primary endpoint of restoring insulin independence in type 1 diabetic patients; 2) three pivotal studies of 30 weeks testing both the efficacy and safety of exenatide (exendin-4), a new insulin secretagogue that is a long-acting analogue of glucagon-like peptide-1, in patients with type 2 diabetes treated with either metformin, or a sulfonylurea, or a metformin-sulfonylurea combination; and 3) the "Collaborative AtoRvastatin Diabetes Study" (CARDS), a placebo-controlled primary prevention trial of cardiovascular complications using atorvastatin 10 mg in 2 838 at risk patients with type 2 diabetes. The main results and conclusions of these trials are briefly presented as they open new perspectives in the management of patients with type 1 or type 2 diabetes mellitus.

Trial Registration at ClinicalTrials.gov between May and October 2005

PubMed Central

Zarin, Deborah A.; Tse, Tony; Ide, Nicholas C.

2006-01-01

BACKGROUND Clinical trial registration allows interested parties to obtain information about ongoing and completed trials, but there are few data indicating the quality of the information provided during the registration process. We used information in the publicly available ClinicalTrials.gov database to describe patterns of trial registration before and after the implementation by journal editors of a new policy requiring registration as a prerequisite for publication. METHODS We reviewed ClinicalTrials.gov records to determine patterns of completion of the “Intervention Name” and “Primary Outcome Measure” data fields for trials registered on May 20 and October 11, 2005, and for trials registered during the interval between these two dates, inclusively. RESULTS During the interval studied, the number of registrations in ClinicalTrials.gov increased by 73 percent from 13,153 to 22,714. The percentage of interventional trials registered by industry with nonspecific Intervention Name entries (attributable to four drug companies) decreased from 10 percent to 2 percent; all other industry and nonindustry records contained specific entries in this field. Of the 2670 studies registered by industry between the two dates, 76 percent provided information in the Primary Outcome Measure field, although these entries varied markedly in their degree of specificity. In the remaining 24 percent of the records, this field was blank. CONCLUSIONS During the summer of 2005, there were large increases in the number of clinical trial registrations. Overall, the data contained in records were more complete in October than they were in May, but there still is room for substantial improvement. PMID:16382064

Improvements in Clinical Trials Information Will Improve the Reproductive Health and Fertility of Cancer Patients.

PubMed

Dauti, Angela; Gerstl, Brigitte; Chong, Serena; Chisholm, Orin; Anazodo, Antoinette

2017-06-01

There are a number of barriers that result in cancer patients not being referred for oncofertility care, which include knowledge about reproductive risks of antineoplastic agents. Without this information, clinicians do not always make recommendations for oncofertility care. The objective of this study was to describe the level of reproductive information and recommendations that clinicians have available in clinical trial protocols regarding oncofertility management and follow-up, and the information that patients may receive in clinical trials patient information sheets or consent forms. A literature review of the 71 antineoplastic drugs included in the 68 clinical trial protocols showed that 68% of the antineoplastic drugs had gonadotoxic animal data, 32% had gonadotoxic human data, 83% had teratogenic animal data, and 32% had teratogenic human data. When the clinical trial protocols were reviewed, only 22% of the protocols reported the teratogenic risks and 32% of the protocols reported the gonadotoxic risk. Only 56% of phase 3 protocols had gonadotoxic information and 13% of phase 3 protocols had teratogenic information. Nine percent of the protocols provided fertility preservation recommendations and 4% provided reproductive information in the follow-up and survivorship period. Twenty-six percent had a section in the clinical trials protocol, which identified oncofertility information easily. When gonadotoxic and teratogenic effects of treatment were known, they were not consistently included in the clinical trial protocols and the lack of data for new drugs was not reported. Very few protocols gave recommendations for oncofertility management and follow-up following the completion of cancer treatment. The research team proposes a number of recommendations that should be required for clinicians and pharmaceutical companies developing new 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.

Methodology Series Module 4: Clinical Trials

PubMed Central

Setia, Maninder Singh

2016-01-01

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India. PMID:27512184

77 FR 24984 - Importer of Controlled Substances; Notice of Application; Clinical Supplies Management, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-26

... Application; Clinical Supplies Management, Inc. Pursuant to 21 U.S.C. 958(i), the Attorney General shall... on November 13, 2011, Clinical Supplies Management, Inc., 342 42nd Street South, Fargo, North Dakota... distributing to customers which are qualified clinical sites conducting clinical trials under the auspices of...

77 FR 38084 - Importer of Controlled Substances; Notice of Registration; Clinical Supplies Management, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-26

... Registration; Clinical Supplies Management, Inc. By Notice dated April 17, 2012, and published in the Federal Register on April 26, 2012, 77 FR 24984, Clinical Supplies Management, Inc., 342 42nd Street South, Fargo..., labeling, and distributing to customers which are qualified clinical sites conducting clinical trials under...

Qualitative analysis of clinical research coordinators' role in phase I cancer clinical trials.

PubMed

Fujiwara, Noriko; Ochiai, Ryota; Shirai, Yuki; Saito, Yuko; Nagamura, Fumitaka; Iwase, Satoru; Kazuma, Keiko

2017-12-01

Clinical research coordinators play a pivotal role in phase I cancer clinical trials. We clarified the care coordination and practice for patients provided by clinical research coordinators in phase I cancer clinical trials in Japan and elucidated clinical research coordinators' perspective on patients' expectations and understanding of these trials. Fifteen clinical research coordinators participated in semi-structured interviews regarding clinical practices; perceptions of patients' expectations; and the challenges that occur before, during, and after phase I cancer clinical trials. Qualitative content analysis showed that most clinical research coordinators observed that patients have high expectations from the trials. Most listened to patients to confirm patients' understanding and reflected on responses to maintain hope, but to avoid excessive expectations; clinical research coordinators considered avoiding unplanned endings; and they aimed to establish good relationships between patients, medical staff, and among the professional team. Clinical research coordinators were insightful about the needs of patients and took a meticulous approach to the phase I cancer clinical trial process, allowing time to connect with patients and to coordinate the inter-professional research team. Additionally, education in advanced oncology care was valuable for comforting participants in cancer clinical trials.

TU-C-9A-01: IROC Organization and Clinical Trial Credentialing

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

Followill, D; Molineu, A; Xiao, Y

2014-06-15

As a response to recommendations from a report from the Institute of Medicine, NCI is reorganizing it clinical trial groups into a National Clinical Trial Network (NCTN) that consists of four adult groups (Alliance, ECOGACRIN, NRG, and SWOG) and one children’s group (COG). NRG will house CIRO, a center to promote innovative radiation therapy research and intergroup collaboration in radiation. The quality assurance groups that support clinical trials have also been restructured. ITC, OSU Imaging corelab, Philadelphia Imaging core-lab, QARC, RPC, and RTOGQA have joined together to create the Imaging and Radiation Oncology Core (IROC) Group. IROC’s mission is tomore » provide integrated radiation oncology and diagnostic imaging quality control programs in support of the NCI’s NCTN thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide. This will be accomplished through five core services: site qualification, trial design support, credentialing, data management, case review.These changes are important for physicist participating in NCI clinical trials to understand. We will describe in detail the IROC’s activities and five core services so that as a user, the medical physicist can learn how to efficiently utilize this group. We will describe common pitfalls encountered in credentialing for current protocols and present methods to avoid them. These may include the which benchmarks are required for NSABP B-51/RTOG 1304 and how to plan them as well as tips for phantom planning. We will explain how to submit patient and phantom cases in the TRIAD system used by IROC. Learning Objectives: To understand the basic organization of IROC, its mission and five core services To learn how to use TRIAD for patient and phantom data submission To learn how to avoid common pitfalls in credentialing for current trials.« less

Comparison of reporting phase I trial results in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Goldvaser, H; Wang, L; Abdul Razak, A R; Bedard, P L

2017-12-01

Background Data on completeness of reporting of phase I cancer clinical trials in publications are lacking. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching primary publications published prior to November 1, 2016. Reporting in primary publications was compared with the ClinicalTrials.gov database using a 28-point score (2=complete; 1=partial; 0=no reporting) for 14 items related to study design, outcome measures and safety profile. Inconsistencies between primary publications and ClinicalTrials.gov were recorded. Linear regression was used to identify factors associated with incomplete reporting. Results After a review of 583 trials in ClinicalTrials.gov , 163 matching primary publications were identified. Publications reported outcomes that did not appear in ClinicalTrials.gov in 25% of trials. Outcomes were upgraded, downgraded or omitted in publications in 47% of trials. The overall median reporting score was 23/28 (interquartile range 21-25). Incompletely reported items in >25% publications were: inclusion criteria (29%), primary outcome definition (26%), secondary outcome definitions (53%), adverse events (71%), serious adverse events (80%) and dates of study start and database lock (91%). Higher reporting scores were associated with phase I (vs phase I/II) trials (p<0.001), multicenter trials (p<0.001) and publication in journals with lower impact factor (p=0.004). Conclusions Reported results in primary publications for early phase cancer trials are frequently inconsistent or incomplete compared with ClinicalTrials.gov entries. ClinicalTrials.gov may provide more comprehensive data from new cancer drug trials.

Building clinical trial capacity to develop a new treatment for multidrug-resistant tuberculosis.

PubMed

Tupasi, Thelma; Gupta, Rajesh; Danilovits, Manfred; Cirule, Andra; Sanchez-Garavito, Epifanio; Xiao, Heping; Cabrera-Rivero, Jose L; Vargas-Vasquez, Dante E; Gao, Mengqiu; Awad, Mohamed; Gentry, Leesa M; Geiter, Lawrence J; Wells, Charles D

2016-02-01

New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.

Disease-mongering through clinical trials.

PubMed

González-Moreno, María; Saborido, Cristian; Teira, David

2015-06-01

Our goal in this paper is to articulate a precise concept of at least a certain kind of disease-mongering, showing how pharmaceutical marketing can commercially exploit certain diseases when their best definition is given through the success of a treatment in a clinical trial. We distinguish two types of disease-mongering according to the way they exploit the definition of the trial population for marketing purposes. We argue that behind these two forms of disease-mongering there are two well-known problems in the statistical methodology of clinical trials (the reference class problem and the distinction between statistical and clinical significance). Overcoming them is far from simple. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development and Application of Direct Data Capture for Monitoring Medication Compliance in Clinical Trials.

PubMed

Kim, Eun-Young

2017-10-01

The monitoring of medication compliance in clinical trials is important but labor intensive. To check medication compliance in clinical trials, a system was developed, and its technical feasibility evaluated. The system consisted of three parts: a management part (clinical trial center database and a developed program), clinical trial investigator part (monitoring), and clinical trial participant part (personal digital assistant [PDA] with a barcode scanner). The system was tested with 20 participants for 2 weeks, and compliance was evaluated. This study developed a medication compliance monitoring system that used a PDA with a barcode scanner, which sent reminder/warning messages, logged medication barcode data, and provided compliance information to investigators. Registered participants received short message service (SMS) reminder/warning messages on their PDA and sent barcode data at the dosing time. The age range of the participants was 29 to 73 years. Five participants were <50 years old and 8 were ≥65 years old. The total mean compliance rate was 82.3%. The mean compliance rate was 83.1% in participants <65 years old and 81.1% in those ≥65 years old. The system was feasible, usable, and effective, even with elderly participants, for monitoring medication compliance in clinical trials using a PDA with a barcode scanner, and may improve the quality of clinical trials.

Impact of the European clinical trials directive on prospective academic clinical trials associated with BMT.

PubMed

Frewer, L J; Coles, D; van der Lans, I A; Schroeder, D; Champion, K; Apperley, J F

2011-03-01

The European Clinical Trials Directive (EU 2001; 2001/20/EC) was introduced to improve the efficiency of commercial and academic clinical trials. Concerns have been raised by interested organizations and institutions regarding the potential for negative impact of the Directive on non-commercial European clinical research. Interested researchers within the European Group for Blood and Marrow Transplantation (EBMT) were surveyed to determine whether researcher experiences confirmed this view. Following a pilot study, an internet-based questionnaire was distributed to individuals in key research positions in the European haemopoietic SCT community. Seventy-one usable questionnaires were returned from participants in different EU member states. The results indicate that the perceived impact of the European Clinical Trials Directive has been negative, at least in the research areas of interest to the EBMT.

Perceived barriers to pediatrician and family practitioner participation in pediatric clinical trials: Findings from the Clinical Trials Transformation Initiative.

PubMed

Greenberg, Rachel G; Corneli, Amy; Bradley, John; Farley, John; Jafri, Hasan S; Lin, Li; Nambiar, Sumathi; Noel, Gary J; Wheeler, Chris; Tiernan, Rosemary; Smith, P Brian; Roberts, Jamie; Benjamin, Daniel K

2018-03-01

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials. Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.

Tools in a clinical information system supporting clinical trials at a Swiss University Hospital.

PubMed

Weisskopf, Michael; Bucklar, Guido; Blaser, Jürg

2014-12-01

Issues concerning inadequate source data of clinical trials rank second in the most common findings by regulatory authorities. The increasing use of electronic clinical information systems by healthcare providers offers an opportunity to facilitate and improve the conduct of clinical trials and the source documentation. We report on a number of tools implemented into the clinical information system of a university hospital to support clinical research. In 2011/2012, a set of tools was developed in the clinical information system of the University Hospital Zurich to support clinical research, including (1) a trial registry for documenting metadata on the clinical trials conducted at the hospital, (2) a patient-trial-assignment-tool to tag patients in the electronic medical charts as participants of specific trials, (3) medical record templates for the documentation of study visits and trial-related procedures, (4) online queries on trials and trial participants, (5) access to the electronic medical records for clinical monitors, (6) an alerting tool to notify of hospital admissions of trial participants, (7) queries to identify potentially eligible patients in the planning phase as trial feasibility checks and during the trial as recruitment support, and (8) order sets to facilitate the complete and accurate performance of study visit procedures. The number of approximately 100 new registrations per year in the voluntary trial registry in the clinical information system now matches the numbers of the existing mandatory trial registry of the hospital. Likewise, the yearly numbers of patients tagged as trial participants as well as the use of the standardized trial record templates increased to 2408 documented trial enrolments and 190 reports generated/month in the year 2013. Accounts for 32 clinical monitors have been established in the first 2 years monitoring a total of 49 trials in 16 clinical departments. A total of 15 months after adding the optional feature of

NCI National Clinical Trials Network Structure

Cancer.gov

Learn about how the National Clinical Trials Network (NCTN) is structured. The NCTN is a program of the National Cancer Institute that gives funds and other support to cancer research organizations to conduct cancer clinical trials.

Clinical Research and Clinical Trials

MedlinePlus

... NICHD News Videos OUTREACH Safe to Sleep® National Child & Maternal Health Education Program RELATED WEBSITES NIH.gov HHS.gov USA.gov ClinicalTrials.gov WEBSITE POLICIES Disclaimer FOIA Privacy Policy Accessibility NIH...Turning Discovery Into Health ®

Mind the gap in clinical trials: A participatory action analysis with citizen collaborators.

PubMed

Price, Amy; Liew, Su May; Kirkpatrick, Jo; Price, Jazmin; Lopreto, Taylor; Nelken, Yasmin

2017-02-01

What are the strengths, gaps, expectations, and barriers to research engagement in clinical trials as communicated through social media? Clinical trials test treatments to provide reliable information for safety and effectiveness. Trials are building blocks in which what is learned in earlier research can be used to improve treatments, compare alternatives, and improve quality of life. For 20 years, the percentages of clinical trials volunteers have decreased whereas the costs of running clinical trials have multiplied. Participants enroll in trials to access latest treatments, to help others, and to advance science, but there is growing unrest. The priorities of those running the trials differ from those of the participants, and the roles for public research involvement lack clarity. Changes to bridge these gaps in the research culture are proposed through the use of participatory action research (PAR) in which stakeholders collaborate to improve research methodology, galvanize citizen participation, multiply health knowledge, problem-solve barriers to access, and explore the value of research volunteers as collaborators. PAR enabled the inclusion of citizens as full collaborators. Social media data were gathered for 120 days until saturation was reached. De-identified data were organized into a Strengths Weaknesses, Opportunities and Threats framework and coded into themes for analysis. After the analysis, the authors prioritized potential solutions for improving research engagement. Strengths and opportunities remained constant through trial phases, disease burdens, and interventions. Threats included alienation, litigation, disparity, and shaming. Poor management and barriers to inclusion were identified as weaknesses. Opportunities included improving resource management and information quality. Barriers were minimized when relationships between staff and participants were inclusive, respectful, tolerant, and open to change. Participants' communications

Overview of phase IV clinical trials for postmarket drug safety surveillance: a status report from the ClinicalTrials.gov registry.

PubMed

Zhang, Xinji; Zhang, Yuan; Ye, Xiaofei; Guo, Xiaojing; Zhang, Tianyi; He, Jia

2016-11-23

Phase IV trials are often used to investigate drug safety after approval. However, little is known about the characteristics of contemporary phase IV clinical trials and whether these studies are of sufficient quality to advance medical knowledge in pharmacovigilance. We aimed to determine the fundamental characteristics of phase IV clinical trials that evaluated drug safety using the ClinicalTrials.gov registry data. A data set of 19 359 phase IV clinical studies registered in ClinicalTrials.gov was downloaded. The characteristics of the phase IV trials focusing on safety only were compared with those evaluating both safety and efficacy. We also compared the characteristics of the phase IV trials in three major therapeutic areas (cardiovascular diseases, mental health and oncology). Multivariable logistic regression was used to evaluate factors associated with the use of blinding and randomisation. A total of 4772 phase IV trials were identified, including 330 focusing on drug safety alone and 4392 evaluating both safety and efficacy. Most of the phase IV trials evaluating drug safety (75.9%) had enrolment <300 with 96.5% <3000. Among these trials, 8.2% were terminated or withdrawn. Factors associated with the use of blinding and randomisation included the intervention model, clinical specialty and lead sponsor. Phase IV trials evaluating drug safety in the ClinicalTrials.gov registry were dominated by small trials that might not have sufficient power to detect less common adverse events. An adequate sample size should be emphasised for phase IV trials with safety surveillance as main task. 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/.

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.

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

PubMed

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical

Facilitating large-scale clinical trials: in Asia.

PubMed

Choi, Han Yong; Ko, Jae-Wook

2010-01-01

The number of clinical trials conducted in Asian countries has started to increase as a result of expansion of the pharmaceutical market in this area. There is a growing opportunity for large-scale clinical trials because of the large number of patients, significant market potential, good quality of data, and the cost effective and qualified medical infrastructure. However, for carrying out large-scale clinical trials in Asia, there are several major challenges, including the quality control of data, budget control, laboratory validation, monitoring capacity, authorship, staff training, and nonstandard treatment that need to be considered. There are also several difficulties in collaborating on international trials in Asia because Asia is an extremely diverse continent. The major challenges are language differences, diversity of patterns of disease, and current treatments, a large gap in the experience with performing multinational trials, and regulatory differences among the Asian countries. In addition, there are also differences in the understanding of global clinical trials, medical facilities, indemnity assurance, and culture, including food and religion. To make regional and local data provide evidence for efficacy through the standardization of these differences, unlimited effort is required. At this time, there are no large clinical trials led by urologists in Asia, but it is anticipated that the role of urologists in clinical trials will continue to increase. Copyright © 2010 Elsevier Inc. All rights reserved.

"You can save time if…"-A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa.

PubMed

Vischer, Nerina; Pfeiffer, Constanze; Limacher, Manuela; Burri, Christian

2017-01-01

The costs, complexity, legal requirements and number of amendments associated with clinical trials are rising constantly, which negatively affects the efficient conduct of trials. In Sub-Saharan Africa, this situation is exacerbated by capacity and funding limitations, which further increase the workload of clinical trialists. At the same time, trials are critically important for improving public health in these settings. The aim of this study was to identify the internal factors that slow down clinical trials in Sub-Saharan Africa. Here, factors are limited to those that exclusively relate to clinical trial teams and sponsors. These factors may be influenced independently of external conditions and may significantly increase trial efficiency if addressed by the respective teams. We conducted sixty key informant interviews with clinical trial staff working in different positions in two clinical research centres in Kenya, Ghana, Burkina Faso and Senegal. The study covered English- and French-speaking, and Eastern and Western parts of Sub-Saharan Africa. We performed thematic analysis of the interview transcripts. We found various internal factors associated with slowing down clinical trials; these were summarised into two broad themes, "planning" and "site organisation". These themes were consistently mentioned across positions and countries. "Planning" factors related to budget feasibility, clear project ideas, realistic deadlines, understanding of trial processes, adaptation to the local context and involvement of site staff in planning. "Site organisation" factors covered staff turnover, employment conditions, career paths, workload, delegation and management. We found that internal factors slowing down clinical trials are of high importance to trial staff. Our data suggest that adequate and coherent planning, careful assessment of the setting, clear task allocation and management capacity strengthening may help to overcome the identified internal factors and

A cluster randomised trial to assess the impact of clinical pathways on AMI management in rural Australian emergency departments.

PubMed

Kinsman, Leigh D; Buykx, Penny; Humphreys, John S; Snow, Pamela C; Willis, Jon

2009-05-25

People living in rural Australia are more likely to die in hospital following an acute myocardial infarction than those living in major cities. While several factors, including time taken to access hospital care, contribute to this risk, it is also partially attributable to the lower uptake of evidence-based guidelines for the administration of thrombolytic drugs in rural emergency departments where up to one-third of eligible patients do not receive this life-saving intervention. Clinical pathways have the potential to link evidence to practice by integrating guidelines into local systems, but their impact has been hampered by variable implementation strategies and sub-optimal research designs. The purpose of this study is to determine the impact of a five-step clinical pathways implementation process on the timely and efficient administration of thrombolytic drugs for acute myocardial infarctions managed in rural Australian emergency departments. The design is a two-arm, cluster-randomised trial with rural hospital emergency departments that treat and do not routinely transfer acute myocardial infarction patients. Six rural hospitals in the state of Victoria will participate, with three in the intervention group and three in the control group. Intervention hospitals will participate in a five-step clinical pathway implementation process: engagement of clinicians, pathway development according to local resources and systems, reminders, education, and audit and feedback. Hospitals in the control group will each receive a hard copy of Australian national guidelines for chest pain and acute myocardial infarction management. Each group will include 90 cases to give a power of 80% at 5% significance level for the two primary outcome measures: proportion of those eligible for thrombolysis receiving the drug and time to delivery of thrombolytic drug. Improved compliance with thrombolytic guidelines via clinical pathways will increase acute myocardial infarction survival

Cost-effectiveness of a nurse-led internet-based vascular risk factor management programme: economic evaluation alongside a randomised controlled clinical trial

PubMed Central

Greving, J P; Kaasjager, H A H; Vernooij, J W P; Hovens, M M C; Wierdsma, J; Grandjean, H M H; van der Graaf, Y; de Wit, G A; Visseren, F L J

2015-01-01

Objective To assess the cost-effectiveness of an internet-based, nurse-led vascular risk factor management programme in addition to usual care compared with usual care alone in patients with a clinical manifestation of a vascular disease. Design Cost-effectiveness analysis alongside a randomised controlled trial (the Internet-based vascular Risk factor Intervention and Self-management (IRIS) study). Setting Multicentre trial in a secondary and tertiary healthcare setting. Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary, cerebral, or peripheral arteries and with ≥2 treatable vascular risk factors not at goal. Intervention The intervention consisted of a personalised website with an overview and actual status of patients’ vascular risk factors, and mail communication with a nurse practitioner via the website for 12 months. The intervention combined self-management support, monitoring of disease control and pharmacotherapy. Main outcome measures Societal costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness. Results Patients experienced equal health benefits, that is, 0.86 vs 0.85 QALY (intervention vs usual care) at 1 year. Adjusting for baseline differences, the incremental QALY difference was −0.014 (95% CI −0.034 to 0.007). The intervention was associated with lower total costs (€4859 vs €5078, difference €219, 95% CI −€2301 to €1825). The probability that the intervention is cost-effective at a threshold value of €20 000/QALY, is 65%. At mean annual cost of €220 per patient, the intervention is relatively cheap. Conclusions An internet-based, nurse-led intervention in addition to usual care to improve vascular risk factors in patients with a clinical manifestation of a vascular disease does not result in a QALY gain at 1 year, but has a small effect on vascular risk factors and is associated with lower costs. Trial registration number NCT00785031. PMID

What Are Clinical Trials? | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn Javascript on. Feature: Clinical Trials What Are Clinical Trials? Past Issues / Fall 2010 Table of Contents ... conducted all the time. The Different Phases of Clinical Trials Clinical trials related to drugs are classified ...

Compliance with results reporting at ClinicalTrials.gov.

PubMed

Anderson, Monique L; Chiswell, Karen; Peterson, Eric D; Tasneem, Asba; Topping, James; Califf, Robert M

2015-03-12

The Food and Drug Administration Amendments Act (FDAAA) mandates timely reporting of results of applicable clinical trials to ClinicalTrials.gov. We characterized the proportion of applicable clinical trials with publicly available results and determined independent factors associated with the reporting of results. Using an algorithm based on input from the National Library of Medicine, we identified trials that were likely to be subject to FDAAA provisions (highly likely applicable clinical trials, or HLACTs) from 2008 through 2013. We determined the proportion of HLACTs that reported results within the 12-month interval mandated by the FDAAA or at any time during the 5-year study period. We used regression models to examine characteristics associated with reporting at 12 months and throughout the 5-year study period. From all the trials at ClinicalTrials.gov, we identified 13,327 HLACTs that were terminated or completed from January 1, 2008, through August 31, 2012. Of these trials, 77.4% were classified as drug trials. A total of 36.9% of the trials were phase 2 studies, and 23.4% were phase 3 studies; 65.6% were funded by industry. Only 13.4% of trials reported summary results within 12 months after trial completion, whereas 38.3% reported results at any time up to September 27, 2013. Timely reporting was independently associated with factors such as FDA oversight, a later trial phase, and industry funding. A sample review suggested that 45% of industry-funded trials were not required to report results, as compared with 6% of trials funded by the National Institutes of Health (NIH) and 9% of trials that were funded by other government or academic institutions. Despite ethical and legal obligations to disclose findings promptly, most HLACTs did not report results to ClinicalTrials.gov in a timely fashion during the study period. Industry-funded trials adhered to legal obligations more often than did trials funded by the NIH or other government or academic

Sharing and reuse of individual participant data from clinical trials: principles and recommendations

PubMed Central

Ohmann, Christian; Banzi, Rita; Canham, Steve; Battaglia, Serena; Matei, Mihaela; Ariyo, Christopher; Becnel, Lauren; Bierer, Barbara; Bowers, Sarion; Clivio, Luca; Dias, Monica; Druml, Christiane; Faure, Hélène; Fenner, Martin; Galvez, Jose; Ghersi, Davina; Gluud, Christian; Houston, Paul; Karam, Ghassan; Kalra, Dipak; Krleža-Jerić, Karmela; Kubiak, Christine; Kuchinke, Wolfgang; Kush, Rebecca; Lukkarinen, Ari; Marques, Pedro Silverio; Newbigging, Andrew; O’Callaghan, Jennifer; Ravaud, Philippe; Schlünder, Irene; Shanahan, Daniel; Sitter, Helmut; Spalding, Dylan; Tudur-Smith, Catrin; van Reusel, Peter; van Veen, Evert-Ben; Visser, Gerben Rienk; Wilson, Julia; Demotes-Mainard, Jacques

2017-01-01

Objectives We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. Design and methods This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. Outcome We developed principles and practical recommendations on how to share data from clinical trials. Results The task force reached consensus on 10 principles and 50 recommendations, representing the fundamental requirements of any framework used for the sharing of clinical trials data. The document covers the following main areas: making data sharing a reality (eg, cultural change, academic incentives, funding), consent for data sharing, protection of trial participants (eg, de-identification), data standards, rights, types and management of access (eg, data request and access models), data management and repositories, discoverability, and metadata. Conclusions The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide

Sharing and reuse of individual participant data from clinical trials: principles and recommendations.

PubMed

Ohmann, Christian; Banzi, Rita; Canham, Steve; Battaglia, Serena; Matei, Mihaela; Ariyo, Christopher; Becnel, Lauren; Bierer, Barbara; Bowers, Sarion; Clivio, Luca; Dias, Monica; Druml, Christiane; Faure, Hélène; Fenner, Martin; Galvez, Jose; Ghersi, Davina; Gluud, Christian; Groves, Trish; Houston, Paul; Karam, Ghassan; Kalra, Dipak; Knowles, Rachel L; Krleža-Jerić, Karmela; Kubiak, Christine; Kuchinke, Wolfgang; Kush, Rebecca; Lukkarinen, Ari; Marques, Pedro Silverio; Newbigging, Andrew; O'Callaghan, Jennifer; Ravaud, Philippe; Schlünder, Irene; Shanahan, Daniel; Sitter, Helmut; Spalding, Dylan; Tudur-Smith, Catrin; van Reusel, Peter; van Veen, Evert-Ben; Visser, Gerben Rienk; Wilson, Julia; Demotes-Mainard, Jacques

2017-12-14

We examined major issues associated with sharing of individual clinical trial data and developed a consensus document on providing access to individual participant data from clinical trials, using a broad interdisciplinary approach. This was a consensus-building process among the members of a multistakeholder task force, involving a wide range of experts (researchers, patient representatives, methodologists, information technology experts, and representatives from funders, infrastructures and standards development organisations). An independent facilitator supported the process using the nominal group technique. The consensus was reached in a series of three workshops held over 1 year, supported by exchange of documents and teleconferences within focused subgroups when needed. This work was set within the Horizon 2020-funded project CORBEL (Coordinated Research Infrastructures Building Enduring Life-science Services) and coordinated by the European Clinical Research Infrastructure Network. Thus, the focus was on non-commercial trials and the perspective mainly European. We developed principles and practical recommendations on how to share data from clinical trials. The task force reached consensus on 10 principles and 50 recommendations, representing the fundamental requirements of any framework used for the sharing of clinical trials data. The document covers the following main areas: making data sharing a reality (eg, cultural change, academic incentives, funding), consent for data sharing, protection of trial participants (eg, de-identification), data standards, rights, types and management of access (eg, data request and access models), data management and repositories, discoverability, and metadata. The adoption of the recommendations in this document would help to promote and support data sharing and reuse among researchers, adequately inform trial participants and protect their rights, and provide effective and efficient systems for preparing, storing and

Foot orthoses and physiotherapy in the treatment of patellofemoral pain syndrome: A randomised clinical trial

PubMed Central

Vicenzino, Bill; Collins, Natalie; Crossley, Kay; Beller, Elaine; Darnell, Ross; McPoil, Thomas

2008-01-01

Background Patellofemoral pain syndrome is a highly prevalent musculoskeletal overuse condition that has a significant impact on participation in daily and physical activities. A recent systematic review highlighted the lack of high quality evidence from randomised controlled trials for the conservative management of patellofemoral pain syndrome. Although foot orthoses are a commonly used intervention for patellofemoral pain syndrome, only two pilot studies with short term follow up have been conducted into their clinical efficacy. Methods/design A randomised single-blinded clinical trial will be conducted to investigate the clinical efficacy and cost effectiveness of foot orthoses in the management of patellofemoral pain syndrome. One hundred and seventy-six participants aged 18–40 with anterior or retropatellar knee pain of non-traumatic origin and at least six weeks duration will be recruited from the greater Brisbane area in Queensland, Australia through print, radio and television advertising. Suitable participants will be randomly allocated to receive either foot orthoses, flat insoles, physiotherapy or a combined intervention of foot orthoses and physiotherapy, and will attend six visits with a physiotherapist over a 6 week period. Outcome will be measured at 6, 12 and 52 weeks using primary outcome measures of usual and worst pain visual analogue scale, patient perceived treatment effect, perceived global effect, the Functional Index Questionnaire, and the Anterior Knee Pain Scale. Secondary outcome measures will include the Lower Extremity Functional Scale, McGill Pain Questionnaire, 36-Item Short-Form Health Survey, Hospital Anxiety and Depression Scale, Patient-Specific Functional Scale, Physical Activity Level in the Previous Week, pressure pain threshold and physical measures of step and squat tests. Cost-effectiveness analysis will be based on treatment effectiveness against resource usage recorded in treatment logs and self-reported diaries

SMART: self-management of anticoagulation, a randomised trial [ISRCTN19313375].

PubMed

McCahon, Deborah; Fitzmaurice, David A; Murray, Ellen T; Fuller, Christopher J; Hobbs, Richard F D; Allan, Teresa F; Raftery, James P

2003-09-18

Oral anticoagulation monitoring has traditionally taken place in secondary care because of the need for a laboratory blood test, the international normalised ratio (INR). The development of reliable near patient testing (NPT) systems for INR estimation has facilitated devolution of testing to primary care. Patient self-management is a logical progression from the primary care model. This study will be the first to randomise non-selected patients in primary care, to either self-management or standard care. The study was a multi-centred randomised controlled trial with patients from 49 general practices recruited. Those suitable for inclusion were aged 18 or over, with a long term indication for oral anticoagulation, who had taken warfarin for at least six months. Patients randomised to the intervention arm attended at least two training sessions which were practice-based, 1 week apart. Each patient was assessed on their capability to undertake self management. If considered capable, they were given a near patient INR testing monitor, test strips and quality control material for home testing. Patients managed their own anticoagulation for a period of 12 months and performed their INR test every 2 weeks. Control patients continued with their pre-study care either attending hospital or practice based anticoagulant clinics. The methodology used in this trial will overcome concerns from previous trials of selection bias and relevance to the UK health service. The study will give a clearer understanding of the benefits of self-management in terms of clinical and cost effectiveness and patient preference.

Statistical controversies in clinical research: comparison of primary outcomes in protocols, public clinical-trial registries and publications: the example of oncology trials.

PubMed

Perlmutter, A S; Tran, V-T; Dechartres, A; Ravaud, P

2017-04-01

Protocols are often unavailable to peer-reviewers and readers. To detect outcome reporting bias (ORB), readers usually have to resort to publicly available descriptions of study design such as public clinical trial registries. We compared primary outcomes in protocols, ClinicalTrials.gov and publications of oncology trials and evaluated the use of ClinicalTrials.gov as compared with protocols in detecting discrepancies between planned and published outcomes. We searched for phase III oncology trials registered in ClinicalTrials.gov and published in the Journal of Clinical Oncology and New England Journal of Medicine between January 2014 and June 2015. We extracted primary outcomes reported in the protocol, ClinicalTrials.gov and the publication. First, we assessed the quality of primary outcome descriptions by using a published framework. Second, we evaluated modifications of primary outcomes between each source. Finally, we evaluated the agreement, specificity and sensitivity of detecting modifications between planned and published outcomes by using protocols or ClinicalTrials.gov. We included 65 trials, with 81 primary outcomes common among the 3 sources. The proportion of primary outcomes reporting all items from the framework was 73%, 22%, and 75% for protocols, ClinicalTrials.gov and publications, respectively. Eight (12%) trials presented a discrepancy between primary outcomes reported in the protocol and in the publication. Twelve (18.5%) trials presented a discrepancy between primary outcomes registered at ClinicalTrials.gov and in publications. We found a moderate agreement in detecting discrepant reporting of outcomes by using protocols or ClinicalTrials.gov [κ = 0.53, 95% confidence interval (0.25-0.81)]. Using ClinicalTrials.gov to detect discrepant reporting of outcomes showed high specificity (89.5%) but lacked sensitivity (75%) as compared with use of protocols. In oncology trials, primary outcome descriptions in ClinicalTrials.gov are often of

Adaptive designs in clinical trials.

PubMed

Bowalekar, Suresh

2011-01-01

In addition to the expensive and lengthy process of developing a new medicine, the attrition rate in clinical research was on the rise, resulting in stagnation in the development of new compounds. As a consequence to this, the US Food and Drug Administration released a critical path initiative document in 2004, highlighting the need for developing innovative trial designs. One of the innovations suggested the use of adaptive designs for clinical trials. Thus, post critical path initiative, there is a growing interest in using adaptive designs for the development of pharmaceutical products. Adaptive designs are expected to have great potential to reduce the number of patients and duration of trial and to have relatively less exposure to new drug. Adaptive designs are not new in the sense that the task of interim analysis (IA)/review of the accumulated data used in adaptive designs existed in the past too. However, such reviews/analyses of accumulated data were not necessarily planned at the stage of planning clinical trial and the methods used were not necessarily compliant with clinical trial process. The Bayesian approach commonly used in adaptive designs was developed by Thomas Bayes in the 18th century, about hundred years prior to the development of modern statistical methods by the father of modern statistics, Sir Ronald A. Fisher, but the complexity involved in Bayesian approach prevented its use in real life practice. The advances in the field of computer and information technology over the last three to four decades has changed the scenario and the Bayesian techniques are being used in adaptive designs in addition to other sequential methods used in IA. This paper attempts to describe the various adaptive designs in clinical trial and views of stakeholders about feasibility of using them, without going into mathematical complexities.

Enhancing Cardiac Rehabilitation With Stress Management Training: A Randomized Clinical Efficacy Trial

PubMed Central

Blumenthal, James A.; Sherwood, Andrew; Smith, Patrick J.; Watkins, Lana; Mabe, Stephanie; Kraus, William E.; Ingle, Krista; Miller, Paula; Hinderliter, Alan

2016-01-01

Background Cardiac rehabilitation (CR) is the standard of care for patients with coronary heart disease (CHD). Despite considerable epidemiologic evidence that high stress is associated with worse health outcomes, stress management training (SMT) is not included routinely as a component of CR. Methods and Results 151 outpatients with CHD aged 36 to 84 years were randomized to 12-weeks of comprehensive CR or comprehensive CR combined with SMT (CR+SMT), with assessments of stress and CHD biomarkers obtained before and after treatment. A matched sample of CR-eligible patients who did not receive CR comprised a No-CR comparison group. All participants were followed for up to 5.3 years (median = 3.2 years) for clinical events. Patients randomized to CR+SMT exhibited greater reductions in composite stress levels compared with those randomized to CR alone (P = 0.022), an effect that was driven primarily by improvements in anxiety, distress, and perceived stress. Both CR groups achieved significant, and comparable, improvements in CHD biomarkers. Participants in the CR+SMT group exhibited lower rates of clinical events compared with CR alone (18% vs. 33%, HR = 0.49 [0.25, 0.95], P = 0.035) and both CR groups had lower event rates compared to the No-CR group (47%, HR = 0.44 [0.27, 0.71], P < .001). Conclusions CR enhanced by SMT produced significant reductions in stress and greater improvements in medical outcomes compared with standard CR. Our findings indicate that SMT may provide incremental benefit when combined with comprehensive CR and suggest that SMT should be incorporated routinely into CR. Clinical Trial Registration Information www.Clinicaltrials.gov. Identifier: NCT00981253. PMID:27045127

EXERCISE AND STRESS MANAGEMENT TRAINING PRIOR TO HEMATOPOIETIC CELL TRANSPLANTATION: BLOOD AND MARROW TRANSPLANT CLINICAL TRIALS NETWORK (BMT CTN) 0902

PubMed Central

Jacobsen, Paul B.; Le-Rademacher, Jennifer; Jim, Heather; Syrjala, Karen; Wingard, John R.; Logan, Brent; Wu, Juan; Majhail, Navneet S.; Wood, William; Rizzo, J. Douglas; Geller, Nancy L.; Kitko, Carrie; Faber, Edward; Abidi, Muneer H.; Slater, Susan; Horowitz, Mary M.; Lee, Stephanie J.

2014-01-01

Studies show that engaging patients in exercise and/or stress management techniques during hematopoietic cell transplantation (HCT) improves quality of life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy of training patients to engage in self-directed exercise and stress management during their HCTs. The study randomized 711 patients at 21 centers to receive one of four training interventions before HCT: a self-directed exercise program, a self-administered stress management program, both or neither. Participants completed self-reported assessments at enrollment and up to 180 days after transplant. Randomization was stratified by center and transplant type. There were no differences in the primary endpoints of the physical (PCS) and mental (MCS) component scales of the SF36 at day 100 among the groups based on an intention-to-treat analysis. There were no differences observed in overall survival, hospital days through day 100 post-HCT, or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea. Patient randomized to training in stress management reported more use of those techniques; patients randomized to training in exercise did not report more physical activity. Although other studies have reported efficacy of more intensive interventions, brief training in an easy-to-disseminate format for either self-directed exercise or stress management was not effective in our trial. PMID:24910380

Impact of a cancer clinical trials web site on discussions about trial participation: a cluster randomized trial.

PubMed

Dear, R F; Barratt, A L; Askie, L M; Butow, P N; McGeechan, K; Crossing, S; Currow, D C; Tattersall, M H N

2012-07-01

Cancer patients want access to reliable information about currently recruiting clinical trials. Oncologists and their patients were randomly assigned to access a consumer-friendly cancer clinical trials web site [Australian Cancer Trials (ACT), www.australiancancertrials.gov.au] or to usual care in a cluster randomized controlled trial. The primary outcome, measured from audio recordings of oncologist-patient consultations, was the proportion of patients with whom participation in any clinical trial was discussed. Analysis was by intention-to-treat accounting for clustering and stratification. Thirty medical oncologists and 493 patients were recruited. Overall, 46% of consultations in the intervention group compared with 34% in the control group contained a discussion about clinical trials (P=0.08). The mean consultation length in both groups was 29 min (P=0.69). The proportion consenting to a trial was 10% in both groups (P=0.65). Patients' knowledge about randomized trials was lower in the intervention than the control group (mean score 3.0 versus 3.3, P=0.03) but decisional conflict scores were similar (mean score 42 versus 43, P=0.83). Good communication between patients and physicians is essential. Within this context, a web site such as Australian Cancer Trials may be an important tool to encourage discussion about clinical trial participation.

Randomized Trial of a Web-Based Intervention to Address Barriers to Clinical Trials.

PubMed

Meropol, Neal J; Wong, Yu-Ning; Albrecht, Terrance; Manne, Sharon; Miller, Suzanne M; Flamm, Anne Lederman; Benson, Al Bowen; Buzaglo, Joanne; Collins, Michael; Egleston, Brian; Fleisher, Linda; Katz, Michael; Kinzy, Tyler G; Liu, Tasnuva M; Margevicius, Seunghee; Miller, Dawn M; Poole, David; Roach, Nancy; Ross, Eric; Schluchter, Mark D

2016-02-10

Lack of knowledge and negative attitudes have been identified as barriers to participation in clinical trials by patients with cancer. We developed Preparatory Education About Clinical Trials (PRE-ACT), a theory-guided, Web-based, interactive computer program, to deliver tailored video educational content to patients in an effort to overcome barriers to considering clinical trials as a treatment option. A prospective, randomized clinical trial compared PRE-ACT with a control condition that provided general clinical trials information produced by the National Cancer Institute (NCI) in text format. One thousand two hundred fifty-five patients with cancer were randomly allocated before their initial visit with an oncologist to PRE-ACT (n = 623) or control (n = 632). PRE-ACT had three main components: assessment of clinical trials knowledge and attitudinal barriers, values assessment with clarification back to patients, and provision of a video library tailored to address each patient's barriers. Outcomes included knowledge and attitudes and preparation for decision making about clinical trials. Both PRE-ACT and control interventions improved knowledge and attitudes (all P < .001) compared with baseline. Patients randomly allocated to PRE-ACT showed a significantly greater increase in knowledge (P < .001) and a significantly greater decrease in attitudinal barriers (P < .001) than did their control (text-only) counterparts. Participants in both arms significantly increased their preparedness to consider clinical trials (P < .001), and there was a trend favoring the PRE-ACT group (P < .09). PRE-ACT was also associated with greater patient satisfaction than was NCI text alone. These data show that patient education before the first oncologist visit improves knowledge, attitudes, and preparation for decision making about clinical trials. Both text and tailored video were effective. The PRE-ACT interactive video program was more effective than NCI text in improving

Contemporary Clinical Management of Endometrial Cancer

PubMed Central

Dinkelspiel, Helen E.; Wright, Jason D.; Lewin, Sharyn N.; Herzog, Thomas J.

2013-01-01

Although the contemporary management of endometrial cancer is straightforward in many ways, novel data has emerged over the past decade that has altered the clinical standards of care while generating new controversies that will require further investigation. Fortunately most cases are diagnosed at early stages, but high-risk histologies and poorly differentiated tumors have high metastatic potential with a significantly worse prognosis. Initial management typically requires surgery, but the role and extent of lymphadenectomy are debated especially with well-differentiated tumors. With the changes in surgical staging, prognosis correlates more closely with stage, and the importance of cytology has been questioned and is under evaluation. The roles of radiation in intermediate-risk patients and chemotherapy in high-risk patients are emerging. The therapeutic index of brachytherapy needs to be considered, and the best sequencing of combined modalities needs to balance efficacy and toxicities. Additionally novel targeted therapies show promise, and further studies are needed to determine the appropriate use of these new agents. Management of endometrial cancer will continue to evolve as clinical trials continue to answer unsolved clinical questions. PMID:23864861

Review of ongoing clinical trials in non-small cell lung cancer: a status report for 2009 from the ClinicalTrials.gov website.

PubMed

Subramanian, Janakiraman; Madadi, Anusha R; Dandona, Monica; Williams, Kristina; Morgensztern, Daniel; Govindan, Ramaswamy

2010-08-01

Several new agents are being tested in clinical trials for patients with non-small cell lung cancer (NSCLC). A survey of ongoing clinical trials in NSCLC in the ClinicalTrials.gov website would help identify areas that require further attention in the future. We conducted a survey of ongoing clinical trials on NSCLC registered in the ClinicalTrials.gov website. The advanced search option was applied using the terms "non small cell lung cancer," "open studies," "interventional," and "adults 18 years or older." Of the 493 eligible trials, 77 (15.6%) were phase III, 92 (18.7%) were phase I, and 240 (48.7%) were phase II trials. Universities were listed as the primary sponsor for 224 (45.4%) trials and pharmaceutical industry for 166 (33.7%) trials. Majority of the trials were multicenter studies (56.8%) and were being conducted exclusively within the United States (51.3%). A large proportion of phase II and III clinical trials (77.2%) were focused on patients with advanced-stage disease. The most frequently used end points were progression-free survival (27.1%) followed by tumor response rate (22.9%) and overall survival (16.6%). Although biomarker analysis was included in 185 (37.5%) trials, only 39 (7.9%) trials used biomarkers for patient selection. Progression-free survival is the end point most commonly used to assess the effectiveness of experimental regimens, and biomarker-based patient selection is rarely used in ongoing clinical trials for NSCLC.

Adherence in single-parent households in a long-term asthma clinical trial.

PubMed

Spicher, Mary; Bollers, Nancy; Chinn, Tamara; Hall, Anita; Plunkett, Anne; Rodgers, Denise; Sundström, D A; Wilson, Laura

2012-01-01

Adherence of participants in a long-term clinical trial is necessary to assure validity of findings. This article examines adherence differences between single-parent and two-parent families in the Childhood Asthma Management Program (CAMP). Adherence was defined as the percentage of completed daily diary cards and scheduled study visits during the course of the trial. Logistic regression and ordinal logistic regression analyses were used. Children from single-parent families had a lower percentage of completed diary cards (72% vs. 84%) than two-parent families. Single-parent families were also more likely to reschedule visits (62% vs. 45%) and miss more clinic visits (23% vs. 17%) than two-parent families. Suggestions are given for study coordinators to assist participants in completing a long-term clinical trial. Many suggestions may be adapted for nurses in inpatient or outpatient settings for assisting parents of patients with chronic diseases.

Coordination and Management of Multisite Complementary and Alternative Medicine (CAM) Therapies: Experience from a Multisite Reflexology Intervention Trial

PubMed Central

Rahbar, Mohammad H.; Wyatt, Gwen; Sikorskii, Alla; Victorson, David; Ardjomand-Hessabi, Manouchehr

2011-01-01

Background Multisite randomized clinical trials allow for increased research collaboration among investigators and expedite data collection efforts. As a result, government funding agencies typically look favorably upon this approach. As the field of complementary and alternative medicine (CAM) continues to evolve, so do increased calls for the use of more rigorous study design and trial methodologies, which can present challenges for investigators. Purpose To describe the processes involved in the coordination and management of a multisite randomized clinical trial of a CAM intervention. Methods Key aspects related to the coordination and management of a multisite CAM randomized clinical trial are presented, including organizational and site selection considerations, recruitment concerns and issues related to data collection and randomization to treatment groups. Management and monitoring of data, as well as quality assurance procedures are described. Finally, a real world perspective is shared from a recently conducted multisite randomized clinical trial of reflexology for women diagnosed with advanced breast cancer. Results The use of multiple sites in the conduct of CAM-based randomized clinical trials can provide an efficient, collaborative and robust approach to study coordination and data collection that maximizes efficiency and ensures the quality of results. Conclusions Multisite randomized clinical trial designs can offer the field of CAM research a more standardized and efficient approach to examine the effectiveness of novel therapies and treatments. Special attention must be given to intervention fidelity, consistent data collection and ensuring data quality. Assessment and reporting of quantitative indicators of data quality should be required. PMID:21664296

Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

2017-01-03

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

Clinical Trial Basics

MedlinePlus

... participate, in a study. These guidelines are called Inclusion/Exclusion Criteria . Factors that allow you to take part in a clinical trial are called "inclusion criteria." Those that exclude or prevent participation are " ...

OARSI Clinical Trials Recommendations: Design and conduct of clinical trials of lifestyle diet and exercise interventions for osteoarthritis.

PubMed

Messier, S P; Callahan, L F; Golightly, Y M; Keefe, F J

2015-05-01

The objective was to develop a set of "best practices" for use as a primer for those interested in entering the clinical trials field for lifestyle diet and/or exercise interventions in osteoarthritis (OA), and as a set of recommendations for experienced clinical trials investigators. A subcommittee of the non-pharmacologic therapies committee of the OARSI Clinical Trials Working Group was selected by the Steering Committee to develop a set of recommended principles for non-pharmacologic diet/exercise OA randomized clinical trials. Topics were identified for inclusion by co-authors and reviewed by the subcommittee. Resources included authors' expert opinions, traditional search methods including MEDLINE (via PubMed), and previously published guidelines. Suggested steps and considerations for study methods (e.g., recruitment and enrollment of participants, study design, intervention and assessment methods) were recommended. The recommendations set forth in this paper provide a guide from which a research group can design a lifestyle diet/exercise randomized clinical trial in patients with OA. Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Clinical Trials in Noninfectious Uveitis

PubMed Central

Kim, Jane S.; Knickelbein, Jared E.; Nussenblatt, Robert B.; Sen, H. Nida

2015-01-01

The treatment of noninfectious uveitis continues to remain a challenge for many ophthalmologists. Historically, clinical trials in uveitis have been sparse, and thus, most treatment decisions have largely been based on clinical experience and consensus guidelines. The current treatment paradigm favors initiation then tapering of corticosteroids with addition of steroid-sparing immunosuppressive agents for persistence or recurrence of disease. Unfortunately, in spite of a multitude of highly unfavorable systemic effects, corticosteroids are still regarded as the mainstay of treatment for many patients with chronic and refractory noninfectious uveitis. However, with the success of other conventional and biologic immunomodulatory agents in treating systemic inflammatory and autoimmune conditions, interest in targeted treatment strategies for uveitis has been renewed. Multiple clinical trials on steroid-sparing immunosuppressive agents, biologic agents, intraocular corticosteroid implants, and topical ophthalmic solutions have already been completed, and many more are ongoing. This review discusses the results and implications of these clinical trials investigating both alternative and novel treatment options for noninfectious uveitis. PMID:26035763

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.

Haphazard reporting of deaths in clinical trials: a review of cases of ClinicalTrials.gov records and matched publications-a cross-sectional study.

PubMed

Earley, Amy; Lau, Joseph; Uhlig, Katrin

2013-01-18

A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. To examine (1) how often and how numbers of deaths are reported in ClinicalTrials.gov records; (2) how often total deaths can be determined per arm within a ClinicalTrials.gov results record and its corresponding publication and (3) whether counts may be discordant. Registry-based study of clinical trial results reporting. ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. ClinicalTrials.gov records reporting number of deaths under participant flow, primary or secondary outcome or serious adverse events. Consistency in reporting of number of deaths between ClinicalTrials.gov records and corresponding publications. In 500 randomly selected ClinicalTrials.gov records, only 123 records (25%) reported a number for deaths. Reporting of deaths across data modules for participant flow, primary or secondary outcomes and serious adverse events was variable. In a sample of 27 pairs of ClinicalTrials.gov records with number of deaths and corresponding publications, total deaths per arm could only be determined in 56% (15/27 pairs) but were discordant in 19% (5/27). In 27 pairs of ClinicalTrials.gov records without any information on number of deaths, 48% (13/27) were discordant since the publications reported absence of deaths in 33% (9/27) and positive death numbers in 15% (4/27). Deaths are variably reported in ClinicalTrials.gov records. A reliable total number of deaths per arm cannot always be determined with certainty or can be discordant with number reported in corresponding trial publications. This highlights a need for unambiguous and complete reporting of the number of deaths in trial registries and publications.

Clinical trial designs incorporating predictive biomarkers☆

PubMed Central

Renfro, Lindsay A.; Mallick, Himel; An, Ming-Wen; Sargent, Daniel J.; Mandrekar, Sumithra J.

2016-01-01

Development of oncologic therapies has traditionally been performed in a sequence of clinical trials intended to assess safety (phase I), preliminary efficacy (phase II), and improvement over the standard of care (phase III) in homogeneous (in terms of tumor type and disease stage) patient populations. As cancer has become increasingly understood on the molecular level, newer “targeted” drugs that inhibit specific cancer cell growth and survival mechanisms have increased the need for new clinical trial designs, wherein pertinent questions on the relationship between patient biomarkers and response to treatment can be answered. Herein, we review the clinical trial design literature from initial to more recently proposed designs for targeted agents or those treatments hypothesized to have enhanced effectiveness within patient subgroups (e.g., those with a certain biomarker value or who harbor a certain genetic tumor mutation). We also describe a number of real clinical trials where biomarker-based designs have been utilized, including a discussion of their respective advantages and challenges. As cancers become further categorized and/or reclassified according to individual patient and tumor features, we anticipate a continued need for novel trial designs to keep pace with the changing frontier of clinical cancer research. PMID:26827695

Current status and future prospects of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) clinical trials in ovarian cancer.

PubMed

Cowan, Renee A; O'Cearbhaill, Roisin E; Zivanovic, Oliver; Chi, Dennis S

2017-08-01

The natural history of advanced-stage epithelial ovarian cancer is one of clinical remission after surgery and platinum/taxane-based intravenous (IV) and/or intraperitoneal (IP) chemotherapy followed by early or late recurrence in the majority of patients. Prevention of progression and recurrence remains a major hurdle in the management of ovarian cancer. Recently, many investigators have evaluated the use of normothermic and hyperthermic intraoperative IP drug delivery as a management strategy. This is a narrative review of the current status of clinical trials of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in ovarian cancer and the future directions for this treatment strategy. The existing studies on HIPEC in patients with epithelial ovarian cancer are mostly retrospective in nature, are heterogeneous with regards to combined inclusion of primary and recurrent disease and lack unbiased data. Until data are available from evidence-based trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is a rational and interesting, though still investigative, approach in the management of epithelial ovarian cancer, whose use should be employed within prospective clinical trials.

Laboratory and software applications for clinical trials: the global laboratory environment.

PubMed

Briscoe, Chad

2011-11-01

The Applied Pharmaceutical Software Meeting is held annually. It is sponsored by The Boston Society, a not-for-profit organization that coordinates a series of meetings within the global pharmaceutical industry. The meeting generally focuses on laboratory applications, but in recent years has expanded to include some software applications for clinical trials. The 2011 meeting emphasized the global laboratory environment. Global clinical trials generate massive amounts of data in many locations that must be centralized and processed for efficient analysis. Thus, the meeting had a strong focus on establishing networks and systems for dealing with the computer infrastructure to support such environments. In addition to the globally installed laboratory information management system, electronic laboratory notebook and other traditional laboratory applications, cloud computing is quickly becoming the answer to provide efficient, inexpensive options for managing the large volumes of data and computing power, and thus it served as a central theme for the meeting.

The NKF-NUS hemodialysis trial protocol - a randomized controlled trial to determine the effectiveness of a self management intervention for hemodialysis patients

PubMed Central

2011-01-01

Background Poor adherence to treatment is common in patients on hemodialysis which may increase risk for poor clinical outcomes and mortality. Self management interventions have been shown to be effective in improving compliance in other chronic populations. The aim of this trial is to evaluate the effectiveness of a recently developed group based self management intervention for hemodialysis patients compared to standard care. Methods/Design This is a multicentre parallel arm block randomized controlled trial (RCT) of a four session group self management intervention for hemodialysis patients delivered by health care professionals compared to standard care. A total of 176 consenting adults maintained on hemodialysis for a minimum of 6 months will be randomized to receive the self management intervention or standard care. Primary outcomes are biochemical markers of clinical status and adherence. Secondary outcomes include general health related quality of life, disease-specific quality of life, mood, self efficacy and self-reported adherence. Outcomes will be measured at baseline, immediately post-intervention and at 3 and 9 months post-intervention by an independent assessor and analysed on intention to treat principles with linear mixed-effects models across all time points. A qualitative component will examine which aspects of program participants found particularly useful and any barriers to change. Discussion The NKF-NUS intervention builds upon previous research emphasizing the importance of empowering patients in taking control of their treatment management. The trial design addresses weaknesses of previous research by use of an adequate sample size to detect clinically significant changes in biochemical markers, recruitment of a sufficiently large representative sample, a theory based intervention and careful assessment of both clinical and psychological endpoints at various follow up points. Inclusion of multiple dependent variables allows us to assess the

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

"You can save time if…"—A qualitative study on internal factors slowing down clinical trials in Sub-Saharan Africa

PubMed Central

Pfeiffer, Constanze; Limacher, Manuela; Burri, Christian

2017-01-01

Background The costs, complexity, legal requirements and number of amendments associated with clinical trials are rising constantly, which negatively affects the efficient conduct of trials. In Sub-Saharan Africa, this situation is exacerbated by capacity and funding limitations, which further increase the workload of clinical trialists. At the same time, trials are critically important for improving public health in these settings. The aim of this study was to identify the internal factors that slow down clinical trials in Sub-Saharan Africa. Here, factors are limited to those that exclusively relate to clinical trial teams and sponsors. These factors may be influenced independently of external conditions and may significantly increase trial efficiency if addressed by the respective teams. Methods We conducted sixty key informant interviews with clinical trial staff working in different positions in two clinical research centres in Kenya, Ghana, Burkina Faso and Senegal. The study covered English- and French-speaking, and Eastern and Western parts of Sub-Saharan Africa. We performed thematic analysis of the interview transcripts. Results We found various internal factors associated with slowing down clinical trials; these were summarised into two broad themes, “planning” and “site organisation”. These themes were consistently mentioned across positions and countries. “Planning” factors related to budget feasibility, clear project ideas, realistic deadlines, understanding of trial processes, adaptation to the local context and involvement of site staff in planning. “Site organisation” factors covered staff turnover, employment conditions, career paths, workload, delegation and management. Conclusions We found that internal factors slowing down clinical trials are of high importance to trial staff. Our data suggest that adequate and coherent planning, careful assessment of the setting, clear task allocation and management capacity strengthening may