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 hospital admission alerts of trial participants, 107 running trials have activated this option, including 48 out of 97 studies (49.5%) registered in the year 2013, generating approximately 85 alerts per month. The popularity of the presented tools in the clinical information system illustrates their potential to facilitate the conduct of clinical trials. The tools also allow for enhanced transparency on trials conducted at the hospital. Future studies on monitoring and inspection findings will have to evaluate their impact on quality and safety. © The Author(s) 2014.

Prevalence of primary outcome changes in clinical trials registered on ClinicalTrials.gov: a cross-sectional study.

PubMed

Ramagopalan, Sreeram; Skingsley, Andrew P; Handunnetthi, Lahiru; Klingel, Michelle; Magnus, Daniel; Pakpoor, Julia; Goldacre, Ben

2014-01-01

An important principle in the good conduct of clinical trials is that a summary of the trial protocol, with a pre-defined primary outcome, should be freely available before the study commences. The clinical trials registry ClinicalTrials.gov provides one method of doing this, and once the trial is registered, any changes made to the primary outcome are documented. The objectives of this study were: to assess the proportion of registered trials on ClinicalTrials.gov that had the primary outcome changed; to assess when the primary outcome was changed in relation to the listed study start and end dates and to assess whether the primary outcome change had any relation to the study sponsor. A cross-sectional analysis of all interventional clinical trials registered on ClinicalTrials.gov as of 25 October 2012 was performed. The main outcome was any change made to the initially listed primary outcome and the time of the change in relation to the trial start and end date. Our analysis showed that 28229 of 89204 (31.7%) registered studies had their primary outcome changed.  Industry funding was associated with all primary outcome changes, odds ratio (OR)= 1.36, 95% confidence interval (CI)=1.31-1.41, p<0.001; with primary outcome changes after study start date OR=1.37, 95% CI=1.32-1.42, p<0.001; with primary outcome changes after primary completion date OR=1.84, 95% CI=1.75-1.94, p<0.001 and with primary outcome changes after study completion date OR=1.82, 95% CI=1.73-1.91, p<0.001.  Conclusions A significant proportion of interventional trials registered on ClinicalTrials.gov have their primary outcomes altered after the listed study start and completion dates. These changes are associated with funding source.

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PubMed

da Silva, Ricardo Eccard; Amato, Angélica Amorim; Sousa, Thiago do Rego; de Carvalho, Marta Rodrigues; Novaes, Maria Rita Carvalho Garbi

2018-05-12

Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

Physician compensation for industry-sponsored clinical trials in multiple sclerosis influences patient trust.

PubMed

Klein, E; Solomon, A J; Corboy, J; Bernat, J

2016-07-01

Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust. To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials. An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials. Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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 ...

Limited accessibility to designs and results of Japanese large-scale clinical trials for cardiovascular diseases.

PubMed

Sawata, Hiroshi; Ueshima, Kenji; Tsutani, Kiichiro

2011-04-14

Clinical evidence is important for improving the treatment of patients by health care providers. In the study of cardiovascular diseases, large-scale clinical trials involving thousands of participants are required to evaluate the risks of cardiac events and/or death. The problems encountered in conducting the Japanese Acute Myocardial Infarction Prospective (JAMP) study highlighted the difficulties involved in obtaining the financial and infrastructural resources necessary for conducting large-scale clinical trials. The objectives of the current study were: 1) to clarify the current funding and infrastructural environment surrounding large-scale clinical trials in cardiovascular and metabolic diseases in Japan, and 2) to find ways to improve the environment surrounding clinical trials in Japan more generally. We examined clinical trials examining cardiovascular diseases that evaluated true endpoints and involved 300 or more participants using Pub-Med, Ichushi (by the Japan Medical Abstracts Society, a non-profit organization), websites of related medical societies, the University Hospital Medical Information Network (UMIN) Clinical Trials Registry, and clinicaltrials.gov at three points in time: 30 November, 2004, 25 February, 2007 and 25 July, 2009. We found a total of 152 trials that met our criteria for 'large-scale clinical trials' examining cardiovascular diseases in Japan. Of these, 72.4% were randomized controlled trials (RCTs). Of 152 trials, 9.2% of the trials examined more than 10,000 participants, and 42.8% examined between 1,000 and 10,000 participants. The number of large-scale clinical trials markedly increased from 2001 to 2004, but suddenly decreased in 2007, then began to increase again. Ischemic heart disease (39.5%) was the most common target disease. Most of the larger-scale trials were funded by private organizations such as pharmaceutical companies. The designs and results of 13 trials were not disclosed. To improve the quality of clinical trials, all sponsors should register trials and disclose the funding sources before the enrolment of participants, and publish their results after the completion of each study.

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.

Does information from ClinicalTrials.gov increase transparency and reduce bias? Results from a five-report case series.

PubMed

Adam, Gaelen P; Springs, Stacey; Trikalinos, Thomas; Williams, John W; Eaton, Jennifer L; Von Isenburg, Megan; Gierisch, Jennifer M; Wilson, Lisa M; Robinson, Karen A; Viswanathan, Meera; Middleton, Jennifer Cook; Forman-Hoffman, Valerie L; Berliner, Elise; Kaplan, Robert M

2018-04-16

We investigated whether information in ClinicalTrials.gov would impact the conclusions of five ongoing systematic reviews. We considered five reviews that included 495 studies total. Each review team conducted a search of ClinicalTrials.gov up to the date of the review's last literature search, screened the records using the review's eligibility criteria, extracted information, and assessed risk of bias and applicability. Each team then evaluated the impact of the evidence found in ClinicalTrials.gov on the conclusions in the review. Across the five reviews, the number of studies that had both a registry record and a publication varied widely, from none in one review to 43% of all studies identified in another. Among the studies with both a record and publication, there was also wide variability in the match between published outcomes and those listed in ClinicalTrials.gov. Of the 173 total ClinicalTrials.gov records identified across the five projects, between 11 and 43% did not have an associated publication. In the 14% of records that contained results, the new data provided in the ClinicalTrials.gov records did not change the results or conclusions of the reviews. Finally, a large number of published studies were not registered in ClinicalTrials.gov, but many of these were published before ClinicalTrials.gov's inception date of 2000. Improved prospective registration of trials and consistent reporting of results in ClinicalTrials.gov would help make ClinicalTrials.gov records more useful in finding unpublished information and identifying potential biases. In addition, consistent indexing in databases, such as MEDLINE, would allow for better matching of records and publications, leading to increased utility of these searches for systematic review projects.

Challenges in translating endpoints from trials to observational cohort studies in oncology

PubMed Central

Ording, Anne Gulbech; Cronin-Fenton, Deirdre; Ehrenstein, Vera; Lash, Timothy L; Acquavella, John; Rørth, Mikael; Sørensen, Henrik Toft

2016-01-01

Clinical trials are considered the gold standard for examining drug efficacy and for approval of new drugs. Medical databases and population surveillance registries are valuable resources for post-approval observational research, which are increasingly used in studies of benefits and risk of new cancer drugs. Here, we address the challenges in translating endpoints from oncology trials to observational studies. Registry-based cohort studies can investigate real-world safety issues – including previously unrecognized concerns – by examining rare endpoints or multiple endpoints at once. In contrast to clinical trials, observational cohort studies typically do not exclude real-world patients from clinical practice, such as old and frail patients with comorbidity. The observational cohort study complements the clinical trial by examining the effectiveness of interventions applied in clinical practice and by providing evidence on long-term clinical outcomes, which are often not feasible to study in a clinical trial. Various endpoints can be included in clinical trials, such as hard endpoints, soft endpoints, surrogate endpoints, and patient-reported endpoints. Each endpoint has it strengths and limitations for use in research studies. Endpoints used in oncology trials are often not applicable in observational cohort studies which are limited by the setting of standard clinical practice and by non-standardized endpoint determination. Observational studies can be more helpful moving research forward if they restrict focus to appropriate and valid endpoints. PMID:27354827

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 institutions. (Funded by the Clinical Trials Transformation Initiative and the NIH.).

Explanatory Versus Pragmatic Trials: An Essential Concept in Study Design and Interpretation.

PubMed

Merali, Zamir; Wilson, Jefferson R

2017-11-01

Randomized clinical trials often represent the highest level of clinical evidence available to evaluate the efficacy of an intervention in clinical medicine. Although the process of randomization serves to maximize internal validity, the external validity, or generalizability, of such studies depends on several factors determined at the design phase of the trial including eligibility criteria, study setting, and outcomes of interest. In general, explanatory trials are optimized to demonstrate the efficacy of an intervention in a highly selected patient group; however, findings from these studies may not be generalizable to the larger clinical problem. In contrast, pragmatic trials attempt to understand the real-world benefit of an intervention by incorporating design elements that allow for greater generalizability and clinical applicability of study results. In this article we describe the explanatory-pragmatic continuum for clinical trials in greater detail. Further, a well-accepted tool for grading trials on this continuum is described, and applied, to 2 recently published trials pertaining to the surgical management of lumbar degenerative spondylolisthesis.

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 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.

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.

Temporal Trends and Predictors for Cancer Clinical Trial Availability for Medically Underserved Populations

PubMed Central

Lakoduk, Ashley M.; Priddy, Laurin L.; Yan, Jingsheng; Xie, Xian-Jin

2015-01-01

Background. Lack of access to available cancer clinical trials has been cited as a key factor limiting trial accrual, particularly among medically underserved populations. We examined the trends and factors in clinical trial availability within a major U.S. safety-net hospital system. Materials and Methods. We identified cancer clinical trials activated at the Harold C. Simmons Cancer from 1991 to 2014 and recorded the characteristics of the trials that were and were not activated at the Parkland Health and Hospital System satellite site. We used univariate and multivariate logistic regression to determine the association between trial characteristics and nonactivation status, and chi-square analysis to determine the association between the trial characteristics and the reasons for nonactivation. Results. A total of 773 trials were identified, of which 152 (20%) were not activated at Parkland. In multivariable analysis, nonactivation at Parkland was associated with trial year, sponsor, and phase. Compared with the 1991–2006 period, clinical trials in the 2007–2014 period were almost eightfold more likely not to be activated at Parkland. The most common reasons for nonactivation at Parkland were an inability to perform the study procedures (27%) and the startup costs (15%). Conclusion. Over time, in this single-center setting, a decreasing proportion of cancer clinical trials were available to underserved populations. Trial complexity and costs appeared to account for much of this trend. Efforts to overcome these barriers will be key to equitable access to clinical trials, efficient accrual, and the generalizability of the results. Implications for Practice: Despite numerous calls to increase and diversify cancer clinical trial accrual, the present study found that cancer clinical trial activation rates in a safety-net setting for medically underserved populations have decreased substantially in recent years. The principal reasons for study nonactivation were expenses and an inability to perform the study-related procedures, reflecting the increasing costs and complexity of cancer clinical trials. Future efforts need to focus on strategies to mitigate the increasing disparity in access to clinical research and cutting-edge therapies, which also threatens to hinder study accrual, completion rates, and generalizability. PMID:26018661

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 ...

Conducting feasibilities in clinical trials: an investment to ensure a good study.

PubMed

Rajadhyaksha, Viraj

2010-07-01

Conducting clinical trial feasibility is one of the first steps in clinical trial conduct. This process includes assessing internal and environmental capacity, alignment of the clinical trial in terms of study design, dose of investigational product, comparator, patient type, with the local environment and assessing potential of conducting clinical trial in a specific country. A robust feasibility also ensures a realistic assessment and capability to conduct the clinical trial. For local affiliates of pharmaceutical organizations, and contract research organizations, this is a precursor to study placement and influences the decision of study placement. This article provides details on different types of feasibilities, information which is to be included and relevance of each. The article also aims to provide practical hands-on suggestions to make feasibilities more realistic and informative.

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.

Searching ClinicalTrials.gov and the International Clinical Trials Registry Platform to inform systematic reviews: what are the optimal search approaches?

PubMed

Glanville, Julie M; Duffy, Steven; McCool, Rachael; Varley, Danielle

2014-07-01

Since 2005, International Committee of Medical Journal Editors (ICMJE) member journals have required that clinical trials be registered in publicly available trials registers before they are considered for publication. The research explores whether it is adequate, when searching to inform systematic reviews, to search for relevant clinical trials using only public trials registers and to identify the optimal search approaches in trials registers. A search was conducted in ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP) for research studies that had been included in eight systematic reviews. Four search approaches (highly sensitive, sensitive, precise, and highly precise) were performed using the basic and advanced interfaces in both resources. On average, 84% of studies were not listed in either resource. The largest number of included studies was retrieved in ClinicalTrials.gov and ICTRP when a sensitive search approach was used in the basic interface. The use of the advanced interface maintained or improved sensitivity in 16 of 19 strategies for Clinicaltrials.gov and 8 of 18 for ICTRP. No single search approach was sensitive enough to identify all studies included in the 6 reviews. Trials registers cannot yet be relied upon as the sole means to locate trials for systematic reviews. Trials registers lag behind the major bibliographic databases in terms of their search interfaces. For systematic reviews, trials registers and major bibliographic databases should be searched. Trials registers should be searched using sensitive approaches, and both the registers consulted in this study should be searched.

State-of-the-science of patient navigation as a strategy for enhancing minority clinical trial accrual.

PubMed

Ghebre, Rahel G; Jones, Lovell A; Wenzel, Jennifer A; Martin, Michelle Y; Durant, Raegan W; Ford, Jean G

2014-04-01

Patient navigation programs are emerging that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process as well as outcome measures to evaluate program effectiveness. A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. The eligible studies reported on the development of programs for patient navigation in cancer clinical trials, including training and implementation among African Americans, American Indians, and Native Hawaiians. A low rate of clinical trial refusal (range, 4%-6%) was reported among patients enrolled in patient navigation programs. However, few studies reported on the efficacy of patient navigation in increasing clinical treatment trial enrollment. Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients. © 2014 American Cancer Society.

State-of-the-Science of Patient Navigation as a Strategy for Enhancing Minority Clinical Trial Accrual

PubMed Central

Ghebre, Rahel G.; Jones, Lovell A.; Wenzel, Jennifer; Martin, Michelle Y.; Durant, Raegan; Ford, Jean G.

2014-01-01

Background Patient navigation programs are emerging, that aim to address disparities in clinical trial participation among medically underserved populations, including racial/ethnic minorities. However, there is a lack of consensus on the role of patient navigators within the clinical trial process, as well as outcome measures to evaluate program effectiveness. Methods A review of the literature was conducted of PubMed, Medline, CINHAL, and other sources to identify qualitative and quantitative studies on patient navigation in clinical trials. The search yielded 212 studies, of which only 12 were eligible for this review. Results The eligible studies reported on development of programs for patient navigation in cancer clinical trials, including training and implementation among African American, American Indian and Native Hawaiians. Low clinical trial refusal, 4% to 6%, was reported among patients enrolled in patient navigation program. However, few studies reported on the efficacy of patient navigation on increasing clinical treatment trial enrollment. Conclusion Outcome measures are proposed to assist in developing and evaluating the efficacy and/or effectiveness of patient navigation programs that aim to increase participation in cancer clinical trials. Future research is needed to evaluate the efficacy of patient navigators in addressing barriers to clinical trial participation and increasing enrollment among medically underserved cancer patients. PMID:24643650

Discrepancies between ClinicalTrials.gov recruitment status and actual trial status: a cross-sectional analysis.

PubMed

Jones, Christopher W; Safferman, Michelle R; Adams, Amanda C; Platts-Mills, Timothy F

2017-10-11

To determine the accuracy of the recruitment status listed on ClinicalTrials.gov as compared with the actual trial status. Cross-sectional analysis. Random sample of interventional phase 2-4 clinical trials registered between 2010 and 2012 on ClinicalTrials.gov. For each trial which was listed within ClinicalTrials.gov as ongoing, two investigators performed a comprehensive literature search for evidence that the trial had actually been completed. For each trial listed as completed or terminated early by ClinicalTrials.gov, we compared the date that the trial was actually concluded with the date the registry was updated to reflect the study's conclusion status. Among the 405 included trials, 92 had a registry status indicating that study activity was either ongoing or the recruitment status was unknown. Of these, published results were available for 34 (37%). Among the 313 concluded trials, the median delay between study completion and a registry update reflecting that the study had ended was 141 days (IQR 48-419), with delays of over 1 year present for 29%. In total, 125 trials (31%) either had a listed recruitment status which was incorrect or had a delay of more than 1 year between the time the study was concluded and the time the registry recruitment status was updated. At present, registry recruitment status information in ClinicalTrials.gov is often outdated or wrong. This inaccuracy has implications for the ability of researchers to identify completed trials and accurately characterise all available medical knowledge on a given subject. © 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.

Establishing Evidence-Based Indications for Proton Therapy: An Overview of Current Clinical Trials

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

Mishra, Mark V., E-mail: mmishra@umm.edu; Aggarwal, Sameer; Bentzen, Soren M.

Purpose: To review and assess ongoing proton beam therapy (PBT) clinical trials and to identify major gaps. Methods and Materials: Active PBT clinical trials were identified from (clinicaltrials.gov) and the World Health Organization International Clinical Trials Platform Registry. Data on clinical trial disease site, age group, projected patient enrollment, expected start and end dates, study type, and funding source were extracted. Results: A total of 122 active PBT clinical trials were identified, with target enrollment of >42,000 patients worldwide. Ninety-six trials (79%), with a median planned sample size of 68, were classified as interventional studies. Observational studies accounted for 21% ofmore » trials but 71% (n=29,852) of planned patient enrollment. The most common PBT clinical trials focus on gastrointestinal tract tumors (21%, n=26), tumors of the central nervous system (15%, n=18), and prostate cancer (12%, n=15). Five active studies (lung, esophagus, head and neck, prostate, breast) will randomize patients between protons and photons, and 3 will randomize patients between protons and carbon ion therapy. Conclusions: The PBT clinical trial portfolio is expanding rapidly. Although the majority of ongoing studies are interventional, the majority of patients will be accrued to observational studies. Future efforts should focus on strategies to encourage optimal patient enrollment and retention, with an emphasis on randomized, controlled trials, which will require support from third-party payers. Results of ongoing PBT studies should be evaluated in terms of comparative effectiveness, as well as incremental effectiveness and value offered by PBT in comparison with conventional radiation modalities.« less

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians' Patient Care Decisions.

PubMed

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians.

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.

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.

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.

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.

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

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, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

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.

Non-commercial vs. commercial clinical trials: a retrospective study of the applications submitted to a research ethics committee.

PubMed

Fuentes Camps, Inmaculada; Rodríguez, Alexis; Agustí, Antonia

2018-06-01

There are many difficulties in undertaking independent clinical research without support from the pharmaceutical industry. In this retrospective observational study, some design characteristics, the clinical trial public register and the publication rate of noncommercial clinical trials were compared to those of commercial clinical trials. A total of 809 applications of drug-evaluation clinical trials were submitted from May 2004 to May 2009 to the research ethics committee of a tertiary hospital, and 16.3% of trials were noncommercial. They were mainly phase IV, multicentre national, and unmasked controlled trials, compared to the commercial trials that were mainly phase II or III, multicentre international, and double-blind masked trials. The commercial trials were registered and published more often than noncommercial trials. More funding for noncommercial research is still needed. The results of the research, commercial or noncommercial, should be disseminated in order not to compromise either its scientific or its social value. © 2018 The British Pharmacological Society.

Characteristics of NIH- and industry-sponsored head and neck cancer clinical trials.

PubMed

Devaiah, Anand; Murchison, Charles

2016-09-01

Compare U.S. clinical trials sponsored by the National Institutes of Health (NIH) and industry, especially with regard to trial design, interventions studied, and results reporting rates. U.S. head and neck cancer clinical trials. We used information from ClinicalTrials.gov to compare NIH- and industry-sponsored head and neck cancer clinical trials, specifically analyzing differences in trial design and interventions studied. We examined publication rates and positive results rates using PubMed.gov. About 50% of NIH- and industry-sponsored clinical trials have their results reported in peer-reviewed literature. Industry-sponsored trials had higher rates of positive results than NIH-sponsored trials. NIH- and industry-sponsored clinical trials had similar trial designs, although industry-sponsored trials had significantly lower rates of randomization. Industry trials utilized radiation in 19% of trials and surgery in 2% of trials. NIH trials also had low utilization of both radiation and surgery (27% and 12% of trials, respectively). NIH- and industry-sponsored trials published their results in journals with comparable impact factors. There is significant underreporting of results in U.S. head and neck cancer clinical trials, whether sponsored by NIH or industry. Industry trials have significantly higher rates of positive results, although it is unclear what contributes to this. Both NIH- and industry-sponsored trials underutilize surgery and radiation as treatment modalities, despite the fact that these are standard-of-care therapies for head and neck cancer. We recommend that the NIH and industry report all results from clinical trials and use surgery and radiation as treatment arms in order to arrive at more balanced therapeutic recommendations. N/A. Laryngoscope, 126:E300-E303, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries.

PubMed

Ito, Tatsuya

2016-01-01

Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. Using Thomson Reuters Pharma™, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan.

Attitudes toward placebo-controlled clinical trials among depressed patients in Japan.

PubMed

Sugawara, Norio; Ishioka, Masamichi; Tsuchimine, Shoko; Tsuruga, Koji; Sato, Yasushi; Tarakita, Natsumi; Furukori, Hanako; Kudo, Shuhei; Tomita, Tetsu; Nakagami, Taku; Yasui-Furukori, Norio

2018-01-01

Placebo-controlled clinical trials are the standard in the design of clinical studies for the licensing of new drugs. Medical and ethical concerns regarding placebo use still exist in clinical trials of depressed patients. The aim of this study was to investigate the attitudes toward placebo-controlled clinical trials and to assess factors related to the willingness to participate in such trials among depressed patients in Japan. A total of 206 depressed patients aged 49.5 ± 15.7 years (mean ± SD) who were admitted to three psychiatric hospitals were recruited for a cross-sectional study from June 2015 to March 2016. After a thorough explanation of the placebo, the study participants completed a brief 14-item questionnaire developed to evaluate patients' attitudes regarding possible participation in placebo-controlled clinical trials. The Quick Inventory of Depressive Symptomatology was also administered to assess depressive symptoms. The results indicated that 47% of the patients would be willing to participate in a placebo-controlled clinical trial. Expectations for the improvement of disease, desire to receive more medical care, encouragement by family or friends, and desire to support the development of new drugs were associated with the willingness to participate in such trials, whereas a belief that additional time would be required for medical examinations and fear of exacerbation of symptoms due to placebo use were associated with non-participation. Patients were asked about possible participation in placebo-controlled clinical trials. Less than half of the respondents were willing to participate in placebo-controlled clinical trials. Attitudes toward participation in a placebo-controlled clinical trial need to be considered when deciding whether to conduct such a trial. Copyright © 2017. Published by Elsevier B.V.

A Pilot Study to Determine the Effect of an Educational DVD in Philippine Languages on Cancer Clinical Trial Participation among Filipinos in Hawai'i.

PubMed

Felicitas-Perkins, Jamie Q; Palalay, Melvin Paul; Cuaresma, Charlene; Ho, Reginald Cs; Chen, Moon S; Dang, Julie; Loui, William S

2017-07-01

We conducted an experimental pilot study in an oncology clinic in Honolulu, Hawai'i to determine the effect of a culturally-tailored educational DVD on cancer clinical trial participation among Filipino cancer patients. Thirty-seven patients participated in the study, with 17 randomized into the control group (ie, usual education) and 20 into the intervention group (ie, usual education plus educational DVD). Participants completed pre- and post-educational questionnaires with items asking about understanding of several cancer topics, behavioral outcomes, and attitudes regarding several treatment and physician related topics. A Fisher's exact test was conducted to explore the association between enrollment into a clinical trial and group assignment. General linear models were created to determine significant differences between study groups in post-education response scores for each questionnaire item after controlling for age, gender, education, and pre-education response scores. Two participants from the control group and three participants from the intervention group enrolled into clinical trials. Results showed no significant association between clinical trial enrollment and study group assignment ( P > .99). A significant difference was found between study groups on surety of joining the clinical trial suggested to them ( P = .013). A multilingual educational DVD to supplement clinical trial education may positively influence Filipino cancer patients to move forward with the decision to join a cancer clinical trial. However, health literacy may serve as a major barrier to actual enrollment into the particular clinical trial available to a patient.

The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated protein C?*.

PubMed

Opal, Steven M; Dellinger, R Phillip; Vincent, Jean-Louis; Masur, Henry; Angus, Derek C

2014-07-01

The developmental pipeline for novel therapeutics to treat sepsis has diminished to a trickle compared to previous years of sepsis research. While enormous strides have been made in understanding the basic molecular mechanisms that underlie the pathophysiology of sepsis, a long list of novel agents have now been tested in clinical trials without a single immunomodulating therapy showing consistent benefit. The only antisepsis agent to successfully complete a phase III clinical trial was human recumbent activated protein C. This drug was taken off the market after a follow-up placebo-controlled trial (human recombinant activated Protein C Worldwide Evaluation of Severe Sepsis and septic Shock [PROWESS SHOCK]) failed to replicate the favorable results of the initial registration trial performed ten years earlier. We must critically reevaluate our basic approach to the preclinical and clinical evaluation of new sepsis therapies. We selected the major clinical studies that investigated interventional trials with novel therapies to treat sepsis over the last 30 years. Phase II and phase III trials investigating new treatments for sepsis and editorials and critiques of these studies. Selected manuscripts and clinical study reports were analyzed from sepsis trials. Specific shortcomings and potential pit falls in preclinical evaluation and clinical study design and analysis were reviewed and synthesized. After review and discussion, a series of 12 recommendations were generated with suggestions to guide future studies with new treatments for sepsis. We need to improve our ability to define appropriate molecular targets for preclinical development and develop better methods to determine the clinical value of novel sepsis agents. Clinical trials must have realistic sample sizes and meaningful endpoints. Biomarker-driven studies should be considered to categorize specific "at risk" populations most likely to benefit from a new treatment. Innovations in clinical trial design such as parallel crossover design, alternative endpoints, or adaptive trials should be pursued to improve the outlook for future interventional trials in sepsis.

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.

The application of disease management to clinical trial designs.

PubMed

Puterman, Jared; Alter, David A

2009-08-01

The utilization of disease management (DM) as a minimum standard of care is believed to facilitate pronounced benefits in overall patient outcome and cost management. Randomized clinical trials remain the gold standard evaluative tool in clinical medicine. However, the extent to which contemporary cardiovascular clinical trials incorporate DM components into their treatment or control arms is unknown. Our study is the first to evaluate the extent to which clinical trials incorporate DM as a minimum standard of care for both the intervention and control groups. In total, 386 clinical trials published in 3 leading medical journals between 2003 and 2006 were evaluated. For each study, elements related to DM care, as defined using the American Heart Association Taxonomy, were abstracted and characterized. Our results demonstrate that while the application of DM has increased over time, only 3.4% of the clinical trials examined incorporated all 8 DM elements (and only 11% of such trials incorporated 4 DM elements). A significant association was found between study year and the inclusion of more than 3 elements of DM (chi(2) = 10.10 (3); p = 0.018). In addition, associations were found between study objective and DM criteria, as well as between cohort type and domains described. Our study serves as a baseline reference for the tracking of DM within, and its application to, randomized clinical trials. Moreover, our results underscore the need for broader implementation and evaluation of DM as a minimum care standard within clinical trial research.

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 and coordination among cancer center directors, finance department personnel, economists, and health services researchers.

Challenges in recruitment and retention of clinical trial subjects.

PubMed

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

2016-01-01

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

Feasibility of Extracting Key Elements from ClinicalTrials.gov to Support Clinicians’ Patient Care Decisions

PubMed Central

Kim, Heejun; Bian, Jiantao; Mostafa, Javed; Jonnalagadda, Siddhartha; Del Fiol, Guilherme

2016-01-01

Motivation: Clinicians need up-to-date evidence from high quality clinical trials to support clinical decisions. However, applying evidence from the primary literature requires significant effort. Objective: To examine the feasibility of automatically extracting key clinical trial information from ClinicalTrials.gov. Methods: We assessed the coverage of ClinicalTrials.gov for high quality clinical studies that are indexed in PubMed. Using 140 random ClinicalTrials.gov records, we developed and tested rules for the automatic extraction of key information. Results: The rate of high quality clinical trial registration in ClinicalTrials.gov increased from 0.2% in 2005 to 17% in 2015. Trials reporting results increased from 3% in 2005 to 19% in 2015. The accuracy of the automatic extraction algorithm for 10 trial attributes was 90% on average. Future research is needed to improve the algorithm accuracy and to design information displays to optimally present trial information to clinicians. PMID:28269867

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.

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.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design.

PubMed

Goswami, Neela D; Tsalik, Ephraim L; Naggie, Susanna; Miller, William C; Horton, John R; Pfeiffer, Christopher D; Hicks, Charles B

2014-01-22

The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology.

A cross-sectional analysis of HIV and hepatitis C clinical trials 2007 to 2010: the relationship between industry sponsorship and randomized study design

PubMed Central

2014-01-01

Background The proportion of clinical research sponsored by industry will likely continue to expand as federal funds for academic research decreases, particularly in the fields of HIV/AIDS and hepatitis C (HCV). While HIV and HCV continue to burden the US population, insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases. Debate exists about whether pharmaceutical companies undertake more market-driven research practices to promote therapeutics, or instead conduct more rigorous trials than their non-industry counterparts because of increased resources and scrutiny. The ClinicalTrials.gov registry, which allows investigators to fulfill a federal mandate for public trial registration, provides an opportunity for critical evaluation of study designs for industry-sponsored trials, independent of publication status. As part of a large public policy effort, the Clinical Trials Transformation Initiative (CTTI) recently transformed the ClinicalTrials.gov registry into a searchable dataset to facilitate research on clinical trials themselves. Methods We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials, registered with ClinicalTrials.gov from 1 October 2007 to 27 September 2010, to study the relationship of study sponsorship with randomized study design. The likelihood of using randomization given industry (versus non-industry) sponsorship was reported with prevalence ratios (PR). PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee, enrollment size, study phase, number of study sites, inclusion of foreign study sites, exclusion of persons older than age 65, and disease condition. Results The crude PR was 1.17 (95% CI 0.94, 1.45). Adjusted Poisson models produced a PR of 1.13 (95% CI 0.82, 1.56). There was a trend toward mild effect measure modification by study phase, but this was not statistically significant. In stratified tabular analysis the adjusted PR was 1.14 (95% CI 0.78, 1.68) among phase 2/3 trials and 1.06 (95% CI 0.50, 2.22) among phase 4 trials. Conclusions No significant relationship was found between industry sponsorship and use of randomization in trial design in this cross-sectional study. Prospective studies evaluating other aspects of trial design may shed further light on the relationship between industry sponsorship and appropriate trial methodology. PMID:24450313

How many research nurses for how many clinical trials in an oncology setting? Definition of the Nursing Time Required by Clinical Trial-Assessment Tool (NTRCT-AT).

PubMed

Milani, Alessandra; Mazzocco, Ketti; Stucchi, Sara; Magon, Giorgio; Pravettoni, Gabriella; Passoni, Claudia; Ciccarelli, Chiara; Tonali, Alessandra; Profeta, Teresa; Saiani, Luisa

2017-02-01

Few resources are available to quantify clinical trial-associated workload, needed to guide staffing and budgetary planning. The aim of the study is to describe a tool to measure clinical trials nurses' workload expressed in time spent to complete core activities. Clinical trials nurses drew up a list of nursing core activities, integrating results from literature searches with personal experience. The final 30 core activities were timed for each research nurse by an outside observer during daily practice in May and June 2014. Average times spent by nurses for each activity were calculated. The "Nursing Time Required by Clinical Trial-Assessment Tool" was created as an electronic sheet that combines the average times per specified activities and mathematic functions to return the total estimated time required by a research nurse for each specific trial. The tool was tested retrospectively on 141 clinical trials. The increasing complexity of clinical research requires structured approaches to determine workforce requirements. This study provides a tool to describe the activities of a clinical trials nurse and to estimate the associated time required to deliver individual trials. The application of the proposed tool in clinical research practice could provide a consistent structure for clinical trials nursing workload estimation internationally. © 2016 John Wiley & Sons Australia, Ltd.

"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 allow clinical trials to proceed more efficiently.

Clinical trials and the new good clinical practice guideline in Japan. An economic perspective.

PubMed

Ono, S; Kodama, Y

2000-08-01

Japanese clinical trials have been drastically changing in response to the implementation of the International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guideline in 1997. The most important aim of the new guideline is to standardise the quality of clinical trials in the US, European Union and Japan, but it inevitably imposes substantial costs on investigators, sponsors and even patients in Japan. The study environment in Japan differs from that in the US in several ways: (i) historical lack of a formal requirement for informed consent; (ii) patients' attitudes to clinical trials in terms of expectation of positive outcomes; (iii) the implications of universal health insurance for trial participation; (iv) the historical absence of on-site monitoring by the sponsor, with the attendant effects on study quality; and (v) the lack of adequate financial and personnel support for the conduct of trials. Implementation of the new GCP guideline will improve the ethical and scientific quality of trials conducted in Japan. It may also lead to an improved relationship between medical professionals and patients if the requirement for explicit informed consent in clinical trials leads to the provision of a similar level of patient information in routine care and changes the traditional paternalistic attitude of physicians to patients. The initial response of the Japanese 'market' for clinical trials to the implementation of the ICH-GCP guideline has been clinical trial price increases and a decrease in the number of study contracts. These changes can be explained by applying a simple demand-supply scheme. Whether clinical trials undertaken in Japan become more or less attractive to the industry in the long term will depend on other factors such as international regulations on the acceptability of foreign clinical trials and the reform of domestic healthcare policies.

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.

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

PubMed Central

Earley, Amy; Lau, Joseph; Uhlig,, Katrin

2013-01-01

Context A participant death is a serious event in a clinical trial and needs to be unambiguously and publicly reported. Objective 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. Design Registry-based study of clinical trial results reporting. Setting ClinicalTrials.gov results database searched in July 2011 and matched PubMed publications. Selection criteria A random sample of ClinicalTrials.gov results records. Detailed review of records with a single corresponding publication. Main outcome measure 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. Results 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). Conclusions 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. PMID:23335556

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.

Clinical trial participation. Viewpoints from racial/ethnic groups.

PubMed

Roberson, N L

1994-11-01

Racial/ethnic groups' participation in clinical trials is a relatively new area of research that warrants attention. Although racial/ethnic groups have been included in experimental studies since the 1940s, they were not included in significant numbers in clinical trials for cancer. Clinical trials play a dominant role in clinical oncology. Despite this state-of-the-art cancer treatment, however, there is mounting concern that this scientific progress is not being shared equitably by all segments of the U.S. population. There is underrepresentation of members of racial/ethnic groups in cancer clinical trials, which suggests that participation may be a critical issue. Unfortunately, little is known or documented about these groups' participation in clinical trials. This paper discusses racial/ethnic groups' views and opinions about clinical trial participation. Diagnostic research was conducted as a beginning phase to investigate this new area of research. African Americans, Hispanics, and Native Americans in three Buffalo, New York, communities were selected as study subjects. Data were collected via telephone surveys. Qualitative methods were employed for data analysis and reporting. Findings showed that study subjects knew little about cancer clinical trials and basically had no opportunity to participate. They believed that participation in clinical trials could be beneficial. In each of the three groups, however, there were cultural factors believed to influence participation. A primary concern was "mistrust of white people" and the feeling of being treated like "guinea pigs." Based on study findings, it was evident that recruitment for improving participation requires strategic planning that involves participants representative of the study population. To yield results, the plan should be tailored to the target group, presented as a credible study, designed to reflect trust in the medical care team, and implemented through a continuous educational process.

77 FR 35407 - Proposed Collection; Comment Request: Clinical Mythteries: A Video Game About Clinical Trials

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-13

... Request: Clinical Mythteries: A Video Game About Clinical Trials SUMMARY: In compliance with the... review and approval. Proposed Collection: Title: Clinical Mythteries: A Video Game About Clinical Trials... an engaging, informational ``serious video game'' for adolescents about clinical studies which: (1...

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.

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.

Comparison of Data on Serious Adverse Events and Mortality in ClinicalTrials.gov, Corresponding Journal Articles, and FDA Medical Reviews: Cross-Sectional Analysis.

PubMed

Pradhan, Richeek; Singh, Sonal

2018-04-11

Inconsistencies in data on serious adverse events (SAEs) and mortality in ClinicalTrials.gov and corresponding journal articles pose a challenge to research transparency. The objective of this study was to compare data on SAEs and mortality from clinical trials reported in ClinicalTrials.gov and corresponding journal articles with US Food and Drug Administration (FDA) medical reviews. We conducted a cross-sectional study of a randomly selected sample of new molecular entities approved during the study period 1 January 2013 to 31 December 2015. We extracted data on SAEs and mortality from 15 pivotal trials from ClinicalTrials.gov and corresponding journal articles (the two index resources), and FDA medical reviews (reference standard). We estimated the magnitude of deviations in rates of SAEs and mortality between the index resources and the reference standard. We found deviations in rates of SAEs (30% in ClinicalTrials.gov and 30% in corresponding journal articles) and mortality (72% in ClinicalTrials.gov and 53% in corresponding journal articles) when compared with the reference standard. The intra-class correlation coefficient between the three resources was 0.99 (95% confidence interval [CI] 0.98-0.99) for SAE rates and 0.99 (95% CI 0.97-0.99) for mortality rates. There are differences in data on rates of SAEs and mortality in randomized clinical trials in both ClinicalTrials.gov and journal articles compared with FDA reviews. Further efforts should focus on decreasing existing discrepancies to enhance the transparency and reproducibility of data reporting in clinical trials.

Participation in clinical trials among women living with HIV in Canada

PubMed Central

Hankins, C; Lapointe, N; Walmsley, S

1998-01-01

BACKGROUND: To describe participation in clinical trials among HIV-positive women enrolled since 1993 in the Canadian Women's HIV Study, a prospective open cohort study. METHODS: All HIV-positive women being followed at hospital-based or community-based clinics at 28 sites in 11 Canadian cities were eligible to participate in the Canadian Women's HIV Study. Baseline and follow-up information was collected for 413 women every 6 months by study nurses using standardized questionnaires. Data included sociodemographic variables, HIV exposure group, CD4 count, disease classification, use of antiretroviral therapies and participation in clinical trials. RESULTS: At study intake 15.0% (62/413) of the women had participated in a clinical trial; an additional 8.5% (35/413) participated during a median follow-up of 18 months. Multivariate analysis revealed that the following factors were independently associated with participation in a clinical trial: white race (adjusted odds ratio [OR] 3.38, p = 0.001), current use of antiretroviral therapy (adjusted OR 2.01, p = 0.008), completion of secondary school (adjusted OR 1.97, p = 0.024) and residence in the Prairies or Atlantic provinces (adjusted OR 1.98, p = 0.043). INTERPRETATION: Although the overall clinical trial participation rate of 23.5% was relatively high among HIV-positive women, injection drug users were underrepresented in this study population, and non-white women, women who did not complete high school and women not receiving antiretroviral therapy were less likely than white women, women of higher education and women receiving antiretroviral therapy to participate in clinical trials in Canada. Because of the importance of trial participants being representative of the population for which therapeutic agents are intended, HIV clinical trials must recruit women with lower literacy levels, non-white women, women not receiving antiretroviral therapy and women who are injection drug users to ensure generalizability of research findings. Further study is needed to assess factors that act as barriers and motivators to women's participation in HIV clinical trials. PMID:9861204

Managing multicentre clinical trials with open source.

PubMed

Raptis, Dimitri Aristotle; Mettler, Tobias; Fischer, Michael Alexander; Patak, Michael; Lesurtel, Mickael; Eshmuminov, Dilmurodjon; de Rougemont, Olivier; Graf, Rolf; Clavien, Pierre-Alain; Breitenstein, Stefan

2014-03-01

Multicentre clinical trials are challenged by high administrative burden, data management pitfalls and costs. This leads to a reduced enthusiasm and commitment of the physicians involved and thus to a reluctance in conducting multicentre clinical trials. The purpose of this study was to develop a web-based open source platform to support a multi-centre clinical trial. We developed on Drupal, an open source software distributed under the terms of the General Public License, a web-based, multi-centre clinical trial management system with the design science research approach. This system was evaluated by user-testing and well supported several completed and on-going clinical trials and is available for free download. Open source clinical trial management systems are capable in supporting multi-centre clinical trials by enhancing efficiency, quality of data management and collaboration.

South Asian patients' views and experiences of clinical trial participation.

PubMed

Hussain-Gambles, Mah

2004-12-01

This paper explores South Asian patients' views and experiences of clinical trial participation, as part of a larger study which sought to assess British South Asian under-representation in clinical trials. The study was based on semi-structured interviews with South Asian trial participants in primary care and specialist treatment centres in the north of England. Fifteen South Asian patients who had participated in one of six different clinical trials to test pharmaceutical products comprised the study cohort. South Asian motivations to participate in clinical trials are similar to those of the majority 'White' population. Clear and concise trial information (provided by caring and understanding trial staff) was considered an important aspect of the respondents' experiences. Appealing to South Asian peoples' altruistic nature by making them aware of South Asian under-representation (especially in clinical trials that investigate illnesses prevalent in their community) was also identified as a strong motivational factor. Potential barriers to their participation included: trial burden (which bears heavily on the poor), language, and discriminatory practices in the NHS, which can lead to mistrust of health professionals. In addition, female modesty and preference for female trial staff was recognized as a 'cultural' barrier to participation. There are more similarities than differences between the experiences of British South Asians and 'White' trial participants. Present findings suggest that ethnicity operates at different levels. In addition to South Asian trial participants' culture, social class and gender are also as likely to affect their participation in clinical trials. To improve South Asian accrual rates, strategies should be designed to take into consideration linguistic differences and improving overall trust in the clinical trial team.

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

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.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting

PubMed Central

Wang, Ruibin; Prasad, Vinay; Bates, Susan E.; Fojo, Tito

2016-01-01

Background. Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Materials and Methods. Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4−6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. Results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11–1.36], p < .001; and 1.64 [1.15–2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38–1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61–1.29]; p = .532). Conclusion. This is the largest reported study examining why oncology trials are not published. The data show that 4−6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. Implications for Practice: The Declaration of Helsinki Ethical Principles for Medical Research Involving Human Subjects notes the ethical obligation to report clinical trial data, whether positive or negative. This obligation is listed alongside requirements for risk minimization, access, confidentiality, and informed consent, all bedrocks of the clinical trial system, yet clinical trials are often not published, particularly if negative or difficult to complete. This study found that among American Society for Clinical Oncology (ASCO) Annual Meeting abstracts, 2009–2011, only 61% were published 4–6 years later: 75% of randomized trials and 54% of nonrandomized trials. Clinicians need to insist that every study in which they participate is published. PMID:26888691

Orthodontic treatment in periodontitis‐susceptible subjects: a systematic literature review

PubMed Central

Lindsten, Rune; Slotte, Christer; Bjerklin, Krister

2016-01-01

Abstract The aim is to evaluate the literature for clinical scientific data on possible effects of orthodontic treatment on periodontal status in periodontitis‐susceptible subjects. A systematic literature review was performed on studies in English using PubMed, MEDLINE, and Cochrane Library central databases (1965‐2014). By manually searching reference lists of selected studies, we identified additional articles; then we searched these publications: Journal of Periodontology, Periodontology 2000, Journal of Clinical Periodontology, American Journal of Orthodontics and Dentofacial Orthopedics, Angle Orthodontist, International Journal of Periodontics & Restorative Dentistry, and European Journal of Orthodontics. Search terms included randomized clinical trials, controlled clinical trials, prospective and retrospective clinical studies, case series >5 patients, periodontitis, orthodontics, alveolar bone loss, tooth migration, tooth movement, orthodontic extrusion, and orthodontic intrusion. Only studies on orthodontic treatment in periodontally compromised dentitions were included. One randomized controlled clinical trial, one controlled clinical trial, and 12 clinical studies were included. No evidence currently exists from controlled studies and randomized controlled clinical trials, which shows that orthodontic treatment improves or aggravates the status of periodontally compromised dentitions. PMID:29744163

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

PubMed

Cooper, Stephen A; Desjardins, Paul J; Turk, Dennis C; Dworkin, Robert H; Katz, Nathaniel P; Kehlet, Henrik; Ballantyne, Jane C; Burke, Laurie B; Carragee, Eugene; Cowan, Penney; Croll, Scott; Dionne, Raymond A; Farrar, John T; Gilron, Ian; Gordon, Debra B; Iyengar, Smriti; Jay, Gary W; Kalso, Eija A; Kerns, Robert D; McDermott, Michael P; Raja, Srinivasa N; Rappaport, Bob A; Rauschkolb, Christine; Royal, Mike A; Segerdahl, Märta; Stauffer, Joseph W; Todd, Knox H; Vanhove, Geertrui F; Wallace, Mark S; West, Christine; White, Richard E; Wu, Christopher

2016-02-01

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.

Patient Navigation As a Model to Increase Participation of African Americans in Cancer Clinical Trials.

PubMed

Fouad, Mona N; Acemgil, Aras; Bae, Sejong; Forero, Andres; Lisovicz, Nedra; Martin, Michelle Y; Oates, Gabriela R; Partridge, Edward E; Vickers, Selwyn M

2016-06-01

Less than 10% of patients enrolled in clinical trials are minorities. The patient navigation model has been used to improve access to medical care but has not been evaluated as a tool to increase the participation of minorities in clinical trials. The Increasing Minority Participation in Clinical Trials project used patient navigators (PNs) to enhance the recruitment of African Americans for and their retention in therapeutic cancer clinical trials in a National Cancer Institute-designated comprehensive cancer center. Lay individuals were hired and trained to serve as PNs for clinical trials. African American patients potentially eligible for clinical trials were identified through chart review or referrals by clinic nurses, physicians, and social workers. PNs provided two levels of services: education about clinical trials and tailored support for patients who enrolled in clinical trials. Between 2007 and 2014, 424 African American patients with cancer were referred to the Increasing Minority Participation in Clinical Trials project. Of those eligible for a clinical trial (N = 378), 304 (80.4%) enrolled in a trial and 272 (72%) consented to receive patient navigation support. Of those receiving patient navigation support, 74.5% completed the trial, compared with 37.5% of those not receiving patient navigation support. The difference in retention rates between the two groups was statistically significant (P < .001). Participation of African Americans in therapeutic cancer clinical trials increased from 9% to 16%. Patient navigation for clinical trials successfully retained African Americans in therapeutic trials compared with non-patient navigation trial participation. The model holds promise as a strategy to reduce disparities in cancer clinical trial participation. Future studies should evaluate it with racial/ethnic minorities across cancer centers. Copyright © 2016 by American Society of Clinical Oncology.

Characteristics of antimicrobial studies registered in the USA through ClinicalTrials.Gov

PubMed Central

Stockmann, Chris; Sherwin, Catherine M.T.; Ampofo, Krow; Hersh, Adam L.; Pavia, Andrew T.; Byington, Carrie L.; Ward, Robert M.; Spigarelli, Michael G.

2013-01-01

Increasing rates of antimicrobial-resistant infections and the dwindling pipeline of new agents necessitate judicious, evidence-based antimicrobial prescribing. Clinical trials represent a vital resource for establishing evidence of safety and efficacy, which are crucial to guiding antimicrobial treatment decisions. The objective of this study was to comprehensively evaluate the characteristics of antimicrobial research studies registered in ClinicalTrials.gov. Primary outcome measures, funding sources, inclusion criteria and the reporting of study results were evaluated for 16 055 antimicrobial studies registered in ClinicalTrials.gov as of mid 2012. Interventional studies accounted for 93% of registered antimicrobial studies. Clinical trials of drugs (82%) and biologics (9%) were most common. Antibacterial, antiviral and antifungal studies accounted for 43%, 41% and 16% of drug trials, respectively. Among interventional drug trials, 73% featured randomised allocation to study arms and 71% included measures of safety and/or efficacy as primary endpoints. Children were eligible for enrolment in 26% of studies. Among the studies, 60% were sponsored primarily by non-profit organisations, 30% by industry and 10% by the federal government. Only 7% of studies reported results; however, 71% of these were sponsored primarily by industry. Antimicrobial studies commonly incorporated elements of high-quality trial design, including randomisation and safety/efficacy endpoints. Publication of study results and updating of ClinicalTrials.gov should be encouraged for all studies, with particular attention paid to research sponsored by non-profit organisations and governmental agencies. Leveraging the application of these data to guide the careful selection of antimicrobial agents will be essential to preserve their utility for years to come. PMID:23726436

The nature of placebo response in clinical studies of major depressive disorder.

PubMed

Papakostas, George I; Østergaard, Søren D; Iovieno, Nadia

2015-04-01

To review factors influencing placebo response and clinical trial outcome in depression, and suggest ways to optimize trial success in mood disorders. PubMed searches were conducted by cross-referencing the terms depression, depressive with placebo, clinical trial, and clinical trials for studies published in English between 1970 and September 2013. Relevant abstracts were identified in PubMed, including clinical trials, quantitative studies, and qualitative research. We obtained and reviewed relevant articles and utilized their information to synthesize the present review. Included articles were grouped in the following areas of relevance: (1) biological validity of illness, (2) baseline severity of illness, (3) chronicity of the index episode of depression, (4) age of participants, (5) medical and psychiatric comorbidity, (6) probability of receiving placebo, (7) use of prospective treatment phases (lead-in) (8) dosing schedule, (9) trial duration, (10) frequency of follow-up assessments, and (11) study outcome measure. Several key elements emerge as critical to the ultimate success of a clinical trial, including the probability of receiving placebo, study duration, dosing schedule, visit frequency, the use of blinded lead-in phases, the use of centralized raters, illness severity and duration, and comorbid anxiety. Our increasing understanding of the placebo response in clinical trials of major depressive disorder lends to a, gradually, more predictable phenomenon and, hopefully, to one that becomes lesser in magnitude and variability. Several elements have emerged that seem to play a critical role in trial success, gradually reshaping the design of clinical, translational, as well as mechanistic studies in depression. © Copyright 2015 Physicians Postgraduate Press, Inc.

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

Remune trial will stop; new trials planned.

PubMed

James, J S

1999-05-21

A clinical trial using remune, the anti-HIV vaccine developed by the late Dr. Jonas Salk, has been ended. The study is a clinical-endpoint trial which looks for statistically significant differences in AIDS sickness or death between patients who add remune to their treatment regimens versus those who use a placebo. Agouron Pharmaceuticals and the Immune Response Corporation who were conducting the trial announced their decision to stop it after an analysis by the Data Safety Monitoring Board. No differences in clinical endpoints were found and it was projected that continuing the trial would likely not find any. The companies are now planning two new Phase III trials using viral load testing rather than clinical endpoints as study criteria.

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.

The Effect of Sodium Hypochlorite and Chlorhexidine as Irrigant Solutions for Root Canal Disinfection: A Systematic Review of Clinical Trials.

PubMed

Gonçalves, Lucio Souza; Rodrigues, Renata Costa Val; Andrade Junior, Carlos Vieira; Soares, Renata G; Vettore, Mario Vianna

2016-04-01

This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. A literature search for clinical trials was made on the PubMed (MEDLINE), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was performed according to the Consolidated Standards of Reporting Trials statement. One clinical trial and 4 randomized clinical trials were selected from the 172 articles initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine in reducing microorganisms in 1 study, and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in 1 study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. The available evidence on this topic is scarce, and the findings of studies were not consistent. Additional randomized clinical trials using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Clinical trial transparency: an assessment of the disclosure of results of company-sponsored trials associated with new medicines approved recently in Europe.

PubMed

Rawal, Bina; Deane, Bryan R

2014-03-01

Previous studies have raised concerns around the transparency and disclosure rates of clinical trial results on clinical trial registries and in the scientific literature. The objective of this study was to assess the timely disclosure in the public domain of results of company-sponsored clinical trials related to all new medicines approved by the European Medicines Agency (EMA) over a recent 3 year period. The study surveyed various publicly available information sources for both clinical trial registration and disclosure of results (including clinical trial registries, the International Federation of Pharmaceutical Manufacturers and Associations [IFPMA] Clinical Trials Portal, EMA European Public Assessment Reports and PubMed), searched from 27 December 2012 to 31 January 2013. The study covered all 53 new medicines (except vaccines and fixed-dose combinations) approved for marketing by 34 pharmaceutical companies by the EMA in 2009, 2010 and 2011. It included all completed company-sponsored clinical trials conducted in patients and recorded on a clinical trial registry and/or included in an EPAR. OUTCOME MEASURE AND RESULTS: The main outcome measure was the proportion of trials for which results had been disclosed on a registry or in the scientific literature either within 12 months of the later of either first regulatory approval or trial completion, or by 31 January 2013 (end of survey). Of the completed clinical trials associated with all 53 new medicines approved by the EMA between 2009 and 2011, 77% had results disclosed within 12 months. By 31 January 2013, this had increased to 89%. Rates of results disclosure within 12 months were 71%, 81% and 86% for new medicines approved in 2009, 2010 and 2011 respectively. Disclosure increased to 86%, 93% and 91% respectively by 31 January 2013. Although this was a purely quantitative study which did not aim to assess the content of disclosure against any specific requirements, limitations relating to a number of difficulties in finding all relevant data from multiple sources in the public domain were captured. Results of over three-quarters of all company-sponsored clinical trials related to new medicines recently approved by the EMA were disclosed within a year of completion or regulatory approval, and almost 90% were disclosed by 31 January 2013, suggesting transparency is now better than has sometimes been reported previously.

The Database for Aggregate Analysis of ClinicalTrials.gov (AACT) and Subsequent Regrouping by Clinical Specialty

PubMed Central

Tasneem, Asba; Aberle, Laura; Ananth, Hari; Chakraborty, Swati; Chiswell, Karen; McCourt, Brian J.; Pietrobon, Ricardo

2012-01-01

Background The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. Methods/Principal Results The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. Conclusions/Significance The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups. PMID:22438982

The database for aggregate analysis of ClinicalTrials.gov (AACT) and subsequent regrouping by clinical specialty.

PubMed

Tasneem, Asba; Aberle, Laura; Ananth, Hari; Chakraborty, Swati; Chiswell, Karen; McCourt, Brian J; Pietrobon, Ricardo

2012-01-01

The ClinicalTrials.gov registry provides information regarding characteristics of past, current, and planned clinical studies to patients, clinicians, and researchers; in addition, registry data are available for bulk download. However, issues related to data structure, nomenclature, and changes in data collection over time present challenges to the aggregate analysis and interpretation of these data in general and to the analysis of trials according to clinical specialty in particular. Improving usability of these data could enhance the utility of ClinicalTrials.gov as a research resource. The purpose of our project was twofold. First, we sought to extend the usability of ClinicalTrials.gov for research purposes by developing a database for aggregate analysis of ClinicalTrials.gov (AACT) that contains data from the 96,346 clinical trials registered as of September 27, 2010. Second, we developed and validated a methodology for annotating studies by clinical specialty, using a custom taxonomy employing Medical Subject Heading (MeSH) terms applied by an NLM algorithm, as well as MeSH terms and other disease condition terms provided by study sponsors. Clinical specialists reviewed and annotated MeSH and non-MeSH disease condition terms, and an algorithm was created to classify studies into clinical specialties based on both MeSH and non-MeSH annotations. False positives and false negatives were evaluated by comparing algorithmic classification with manual classification for three specialties. The resulting AACT database features study design attributes parsed into discrete fields, integrated metadata, and an integrated MeSH thesaurus, and is available for download as Oracle extracts (.dmp file and text format). This publicly-accessible dataset will facilitate analysis of studies and permit detailed characterization and analysis of the U.S. clinical trials enterprise as a whole. In addition, the methodology we present for creating specialty datasets may facilitate other efforts to analyze studies by specialty groups.

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/.

EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti‐neutrophil cytoplasm antibody‐associated vasculitis

PubMed Central

Hellmich, Bernhard; Flossmann, Oliver; Gross, Wolfgang L; Bacon, Paul; Cohen‐Tervaert, Jan Willem; Guillevin, Loic; Jayne, David; Mahr, Alfred; Merkel, Peter A; Raspe, Heiner; Scott, David G I; Witter, James; Yazici, Hasan; Luqmani, Raashid A

2007-01-01

Objectives To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence‐based and expert opinion‐based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti‐neutrophil cytoplasm antibody‐associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis‐specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well‐designed research in non‐AAV systemic vasculitides. PMID:17170053

Randomized clinical trials and observational studies in the assessment of drug safety.

PubMed

Sawchik, J; Hamdani, J; Vanhaeverbeek, M

2018-05-01

Randomized clinical trials are considered as the preferred design to assess the potential causal relationships between drugs or other medical interventions and intended effects. For this reason, randomized clinical trials are generally the basis of development programs in the life cycle of drugs and the cornerstone of evidence-based medicine. Instead, randomized clinical trials are not the design of choice for the detection and assessment of rare, delayed and/or unexpected effects related to drug safety. Moreover, the highly homogeneous populations resulting from restrictive eligibility criteria make randomized clinical trials inappropriate to describe comprehensively the safety profile of drugs. In that context, observational studies have a key added value when evaluating the benefit-risk balance of the drugs. However, observational studies are more prone to bias than randomized clinical trials and they have to be designed, conducted and reported judiciously. In this article, we discuss the strengths and limitations of randomized clinical trials and of observational studies, more particularly regarding their contribution to the knowledge of medicines' safety profile. In addition, we present general recommendations for the sensible use of observational data. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Public availability of results of observational studies evaluating an intervention registered at ClinicalTrials.gov.

PubMed

Baudart, Marie; Ravaud, Philippe; Baron, Gabriel; Dechartres, Agnes; Haneef, Romana; Boutron, Isabelle

2016-01-28

Observational studies are essential for assessing safety. The aims of this study were to evaluate whether results of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov were published and, if not, whether they were available through posting on ClinicalTrials.gov or the sponsor website. We identified a cohort of observational studies with safety outcome(s) registered on ClinicalTrials.gov after October 1, 2007, and completed between October 1, 2007, and December 31, 2011. We systematically searched PubMed for a publication, as well as ClinicalTrials.gov and the sponsor website for results. The main outcomes were the time to the first publication in journals and to the first public availability of the study results (i.e. published or posted on ClinicalTrials.gov or the sponsor website). For all studies with results publicly available, we evaluated the completeness of reporting (i.e. reported with the number of events per arm) of safety outcomes. We identified 489 studies; 334 (68%) were partially or completely funded by industry. Results for only 189 (39%, i.e. 65% of the total target number of participants) were published at least 30 months after the study completion. When searching other data sources, we obtained the results for 53% (n = 158; i.e. 93% of the total target number of participants) of unpublished studies; 31% (n = 94) were posted on ClinicalTrials.gov and 21% (n = 64) on the sponsor website. As compared with non-industry-funded studies, industry-funded study results were less likely to be published but not less likely to be publicly available. Of the 242 studies with a primary outcome recorded as a safety issue, all these outcomes were adequately reported in 86% (114/133) when available in a publication, 91% (62/68) when available on ClinicalTrials.gov, and 80% (33/41) when available on the sponsor website. Only 39% of observational studies evaluating an intervention with safety outcome(s) registered at ClinicalTrials.gov had their results published at least 30 months after study completion. The registration of these observational studies allowed searching other sources (results posted at ClinicalTrials.gov and sponsor website) and obtaining results for half of unpublished studies and 93% of the total target number of participants.

Effect of European Clinical Trials Directive on academic drug trials in Denmark: retrospective study of applications to the Danish Medicines Agency 1993-2006.

PubMed

Berendt, Louise; Håkansson, Cecilia; Bach, Karin Friis; Dalhoff, Kim; Andreasen, Per Buch; Petersen, Lene Grejs; Andersen, Elin; Poulsen, Henrik Enghusen

2008-01-05

To determine the impact of the European Union's Clinical Trials Directive on the number of academic drug trials carried out in Denmark. Retrospective review of applications for drug trials to the Danish Medicines Agency, 1993-2006. Applications for drug trials for alternate years were classified as academic or commercial trials. A random subset of academic trials was reviewed for number of participants in and intended monitoring of the trials. Academic and commercial drug trials showed an identical steady decline from 1993 to 2006 and no noticeable change after 2004 when good clinical practice became mandatory for academic trials. The Clinical Trials Directive introduced in May 2004 to ensure good clinical practice for academic drug trials was not associated with a decline in research activity in Denmark; presumably because good clinical practice units had already been in place in Danish universities since 1999. With such an infrastructure academic researchers can do drug trials under the same regulations as drug companies.

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.

Availability and Use of Shared Data From Cardiometabolic Clinical Trials.

PubMed

Vaduganathan, Muthiah; Nagarur, Amulya; Qamar, Arman; Patel, Ravi B; Navar, Ann Marie; Peterson, Eric D; Bhatt, Deepak L; Fonarow, Gregg C; Yancy, Clyde W; Butler, Javed

2018-02-27

Sharing of patient-level clinical trial data has been widely endorsed. Little is known about how extensively these data have been used for cardiometabolic diseases. We sought to evaluate the availability and use of shared data from cardiometabolic clinical trials. We extracted data from ClinicalStudyDataRequest.com, a large, multisponsor data-sharing platform hosting individual patient-level data from completed studies sponsored by 13 pharmaceutical companies. From January 2013 to May 2017, the platform had data from 3374 clinical trials, of which 537 (16%) evaluated cardiometabolic therapeutics (phase 1, 36%; phase 2, 17%; phase 2/3, 1%; phase 3, 42%; phase 4, 4%). They covered 74 therapies and 398 925 patients. Diabetes mellitus (60%) and hypertension (15%) were the most common study topics. Median time from study completion to data availability was 79 months. As of May 2017, ClinicalStudyDataRequest.com had received 318 submitted proposals, of which 163 had signed data-sharing agreements. Thirty of these proposals were related to cardiometabolic therapies and requested data from 79 unique studies (15% of all trials, 29% of phase 3/4 trials). Most (96%) data requesters of cardiometabolic clinical trial data were from academic centers in North America and Western Europe, and half the proposals were unfunded. Most proposals were for secondary hypothesis-generating questions, with only 1 proposed reanalysis of the original study primary hypothesis. To date, 3 peer-reviewed articles have been published after a median of 19 months (9-32 months) from the data-sharing agreement. Despite availability of data from >500 cardiometabolic trials in a multisponsor data-sharing platform, only 15% of these trials and 29% of phase 3/4 trials have been accessed by investigators thus far, and a negligible minority of analyses have reached publication. © 2017 American Heart Association, Inc.

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.

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

PubMed

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

2007-01-01

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

The design and methodology of premature ejaculation interventional studies

PubMed Central

2016-01-01

Large well-designed clinical efficacy and safety randomized clinical trials (RCTs) are required to achieve regulatory approval of new drug treatments. The objective of this article is to make recommendations for the criteria for defining and selecting the clinical trial study population, design and efficacy outcomes measures which comprise ideal premature ejaculation (PE) interventional trial methodology. Data on clinical trial design, epidemiology, definitions, dimensions and psychological impact of PE was reviewed, critiqued and incorporated into a series of recommendations for standardisation of PE clinical trial design, outcome measures and reporting using the principles of evidence based medicine. Data from PE interventional studies are only reliable, interpretable and capable of being generalised to patients with PE, when study populations are defined by the International Society for Sexual Medicine (ISSM) multivariate definition of PE. PE intervention trials should employ a double-blind RCT methodology and include placebo control, active standard drug control, and/or dose comparison trials. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. The ISSM definition of PE reflects the contemporary understanding of PE and represents the state-of-the-art multi-dimensional definition of PE and is recommended as the basis of diagnosis of PE for all PE clinical trials. PMID:27652224

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 research may not require additional government spending/incentives. Rather, harmonisation of approval processes, greater visibility of centres of excellence and reduction of 'hidden' indirect costs, may bring significantly more clinical trials to Europe.

Efficient design of clinical trials and epidemiological research: is it possible?

PubMed

Lauer, Michael S; Gordon, David; Wei, Gina; Pearson, Gail

2017-08-01

Randomized clinical trials and large-scale, cohort studies continue to have a critical role in generating evidence in cardiovascular medicine; however, the increasing concern is that ballooning costs threaten the clinical trial enterprise. In this Perspectives article, we discuss the changing landscape of clinical research, and clinical trials in particular, focusing on reasons for the increasing costs and inefficiencies. These reasons include excessively complex design, overly restrictive inclusion and exclusion criteria, burdensome regulations, excessive source-data verification, and concerns about the effect of clinical research conduct on workflow. Thought leaders have called on the clinical research community to consider alternative, transformative business models, including those models that focus on simplicity and leveraging of digital resources. We present some examples of innovative approaches by which some investigators have successfully conducted large-scale, clinical trials at relatively low cost. These examples include randomized registry trials, cluster-randomized trials, adaptive trials, and trials that are fully embedded within digital clinical care or administrative platforms.

"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 help to overcome the identified internal factors and allow clinical trials to proceed more efficiently. PMID:28301530

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination

PubMed Central

Williams, Rebecca J.; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A.

2015-01-01

Background Clinical trials that end prematurely (or “terminate”) raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. Methods and Findings A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Conclusions Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study. PMID:26011295

Terminated Trials in the ClinicalTrials.gov Results Database: Evaluation of Availability of Primary Outcome Data and Reasons for Termination.

PubMed

Williams, Rebecca J; Tse, Tony; DiPiazza, Katelyn; Zarin, Deborah A

2015-01-01

Clinical trials that end prematurely (or "terminate") raise financial, ethical, and scientific concerns. The extent to which the results of such trials are disseminated and the reasons for termination have not been well characterized. A cross-sectional, descriptive study of terminated clinical trials posted on the ClinicalTrials.gov results database as of February 2013 was conducted. The main outcomes were to characterize the availability of primary outcome data on ClinicalTrials.gov and in the published literature and to identify the reasons for trial termination. Approximately 12% of trials with results posted on the ClinicalTrials.gov results database (905/7,646) were terminated. Most trials were terminated for reasons other than accumulated data from the trial (68%; 619/905), with an insufficient rate of accrual being the lead reason for termination among these trials (57%; 350/619). Of the remaining trials, 21% (193/905) were terminated based on data from the trial (findings of efficacy or toxicity) and 10% (93/905) did not specify a reason. Overall, data for a primary outcome measure were available on ClinicalTrials.gov and in the published literature for 72% (648/905) and 22% (198/905) of trials, respectively. Primary outcome data were reported on the ClinicalTrials.gov results database and in the published literature more frequently (91% and 46%, respectively) when the decision to terminate was based on data from the trial. Trials terminate for a variety of reasons, not all of which reflect failures in the process or an inability to achieve the intended goals. Primary outcome data were reported most often when termination was based on data from the trial. Further research is needed to identify best practices for disseminating the experience and data resulting from terminated trials in order to help ensure maximal societal benefit from the investments of trial participants and others involved with the study.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database.

PubMed

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials.

The Landscape of Clinical Trials Evaluating the Theranostic Role of PET Imaging in Oncology: Insights from an Analysis of ClinicalTrials.gov Database

PubMed Central

Chen, Yu-Pei; Lv, Jia-Wei; Liu, Xu; Zhang, Yuan; Guo, Ying; Lin, Ai-Hua; Sun, Ying; Mao, Yan-Ping; Ma, Jun

2017-01-01

In the war on cancer marked by personalized medicine, positron emission tomography (PET)-based theranostic strategy is playing an increasingly important role. Well-designed clinical trials are of great significance for validating the PET applications and ensuring evidence-based cancer care. This study aimed to provide a comprehensive landscape of the characteristics of PET clinical trials using the substantial resource of ClinicalTrials.gov database. We identified 25,599 oncology trials registered with ClinicalTrials.gov in the last ten-year period (October 2005-September 2015). They were systematically reviewed to validate classification into 519 PET trials and 25,080 other oncology trials used for comparison. We found that PET trials were predominantly phase 1-2 studies (86.2%) and were more likely to be single-arm (78.9% vs. 57.9%, P <0.001) using non-randomized assignment (90.1% vs. 66.7%, P <0.001) than other oncology trials. Furthermore, PET trials were small in scale, generally enrolling fewer than 100 participants (20.3% vs. 25.7% for other oncology trials, P = 0.014), which might be too small to detect a significant theranostic effect. The funding support from industry or National Institutes of Health shrunk over time (both decreased by about 5%), and PET trials were more likely to be conducted in only one region lacking international collaboration (97.0% vs. 89.3% for other oncology trials, P <0.001). These findings raise concerns that clinical trials evaluating PET imaging in oncology are not receiving the attention or efforts necessary to generate high-quality evidence. Advancing the clinical application of PET imaging will require a concerted effort to improve the quality of trials. PMID:28042342

Participants with schizophrenia retain the information necessary for informed consent during clinical trials

PubMed Central

Fischer, Bernard A.; McMahon, Robert P.; Meyer, Walter A.; Slack, Daniel J.; Appelbaum, Paul S.; Carpenter, William T.

2015-01-01

Objective Cognitive impairment is a characteristic of schizophrenia. This impairment may affect the retention of information required for ongoing knowledgeable participation in clinical trials. This study monitored retention of study-related knowledge--including assessment of therapeutic misconception--in people with stable, DSM-IV schizophrenia during participation in placebo-controlled clinical trials of adjunctive agents. Stability was defined as being on an antipsychotic with no change in medication or dose over the previous 4 weeks. Method Individuals enrolling in one of seven clinical trials were approached for participation. Participants came from research clinics and community mental health centers. At baseline, clinical trial consent forms were reviewed and study knowledge assessed. Participants were randomized to follow-up assessments at weeks 1, 4, and 8; weeks 4 and 8; or at week 8 only. Clinical trial consent forms were not re-reviewed at any follow-up visit. Results Fifty-nine participants were enrolled; analysis included 52 participants with at least one follow-up visit. Study knowledge did not decrease meaningfully in any group. Therapeutic misconception was not observed in participants during the study. The group assessed most frequently demonstrated significant improvement over baseline (t44= 3.43, p= 0.001). Retention of study knowledge was not related to symptoms, but had a weak correlation with cognitive capacity (R= 0.28, p= 0.07). Performance did not differ between participants from research clinics and those from community mental health centers. Conclusions Clinically-stable people with schizophrenia enrolling in a placebo-controlled adjunctive medication study, once determined to have capacity to consent to a clinical trial, retained appropriate study knowledge for at least 8 weeks. In the absence of a specific reason to suspect a loss of decisional capacity, there appears to be no need to routinely re-evaluate participants during this type of clinical trial. PMID:23842013

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Taylor, Jakeisha; Dickersin, Kay

2013-06-18

The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the "Primary Outcome" field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required.

ClinicalTrials.gov registration can supplement information in abstracts for systematic reviews: a comparison study

PubMed Central

2013-01-01

Background The inclusion of randomized controlled trials (RCTs) reported in conference abstracts in systematic reviews is controversial, partly because study design information and risk of bias is often not fully reported in the abstract. The Association for Research in Vision and Ophthalmology (ARVO) requires trial registration of abstracts submitted for their annual conference as of 2007. Our goal was to assess the feasibility of obtaining study design information critical to systematic reviews, but not typically included in conference abstracts, from the trial registration record. Methods We reviewed all conference abstracts presented at the ARVO meetings from 2007 through 2009, and identified 496 RCTs; 154 had a single matching registration record in ClinicalTrials.gov. Two individuals independently extracted information from the abstract and the ClinicalTrials.gov record, including study design, sample size, inclusion criteria, masking, interventions, outcomes, funder, and investigator name and contact information. Discrepancies were resolved by consensus. We assessed the frequencies of reporting variables appearing in the abstract and the trial register and assessed agreement of information reported in both sources. Results We found a substantial amount of study design information in the ClinicalTrials.gov record that was unavailable in the corresponding conference abstract, including eligibility criteria associated with gender (83%; 128/154); masking or blinding of study participants (53%, 82/154), persons administering treatment (30%, 46/154), and persons measuring the outcomes (40%, 61/154)); and number of study centers (58%; 90/154). Only 34% (52/154) of abstracts explicitly described a primary outcome, but a primary outcome was included in the “Primary Outcome” field in the ClinicalTrials.gov record for 82% (126/154) of studies. One or more study interventions were reported in each abstract, but agreed exactly with those reported in ClinicalTrials.gov only slightly more than half the time (88/154, 56%). We found no contact information for study investigators in the abstract, but this information was available in less than one quarter of ClinicalTrial.gov records (17%; 26/154). Conclusion RCT design information not reported in conference abstracts is often available in the corresponding ClinicalTrials.gov registration record. Sometimes there is conflicting information reported in the two sources and further contact with the trial investigators may still be required. PMID:23773868

Standardized patient walkthroughs in the National Drug Abuse Treatment Clinical Trials Network: common challenges to protocol implementation.

PubMed

Fussell, Holly E; Kunkel, Lynn E; McCarty, Dennis; Lewy, Colleen S

2011-09-01

Training research staff to implement clinical trials occurring in community-based addiction treatment programs presents unique challenges. Standardized patient walkthroughs of study procedures may enhance training and protocol implementation. Examine and discuss cross-site and cross-study challenges of participant screening and data collection procedures identified during standardized patient walkthroughs of multi-site clinical trials. Actors portrayed clients and "walked through" study procedures with protocol research staff. The study completed 57 walkthroughs during implementation of 4 clinical trials. Observers and walkthrough participants identified three areas of concern (consent procedures, screening and assessment processes, and protocol implementation) and made suggestions for resolving the concerns. Standardized patient walkthroughs capture issues with study procedures previously unidentified with didactic training or unscripted rehearsals. Clinical trials within the National Drug Abuse Treatment Clinical Trials Network are conducted in addiction treatment centers that vary on multiple dimensions. Based on walkthrough observations, the national protocol team and local site leadership modify standardized operating procedures and resolve cross-site problems prior to recruiting study participants. The standardized patient walkthrough improves consistency across study sites and reduces potential site variation in study outcomes.

“Entering a Clinical Trial: Is it Right For You?"-- A Randomized Study of The Clinical Trials Video and Its Impact on the Informed Consent Process

PubMed Central

Hoffner, Brianna; Bauer-Wu, Susan; Hitchcock-Bryan, Suzanne; Powell, Mark; Wolanski, Andrew; Joffe, Steven

2011-01-01

PURPOSE This randomized study was designed to assess the utility of an educational video in preparing cancer patients for decisions about clinical trial participation. The study assessed the effect of the video on patients’ understanding and perceptions of clinical trials, its impact on decision making and patient-provider communication, and patients’ satisfaction with the video. METHODS Ninety adults considering cancer clinical trials were randomized to receive (n=45) or not receive (n=45) the video. Using the validated Quality of Informed Consent (QuIC), respondents’ knowledge about clinical trial participation was assessed. All subjects completed additional questions about satisfaction with the video, decision making, and patient-provider communication. Data were analyzed using the Wilcoxon rank-sum test, regression model and descriptive statistics. RESULTS Although intent-to-treat analysis found no significant group differences in objective understanding between those randomized to view or not view the video, the majority of participants reported favorable experiences with regard to watching the video: 85% found the video was an important source of information about clinical trials; 81% felt better prepared to discuss the trial with their physician; 89% of those who watched the video with family indicated that it helped family better understand clinical trials; and 73% indicated it helped family accept their decision about participation. CONCLUSIONS Although the video did not measurably improve patients’ knowledge about clinical trials, it was an important source of information, helped educate families, and enhanced patient communication with their oncology providers. PMID:22009665

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States

PubMed Central

McClure, Erin A.; King, Jacqueline S.; Wahle, Aimee; Matthews, Abigail G.; Sonne, Susan C.; Lofwall, Michelle R.; McRae-Clark, Aimee L.; Ghitza, Udi E.; Martinez, Melissa; Cloud, Kasie; Virk, Harvir S.; Gray, Kevin M.

2017-01-01

Background Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment Episodes Data Set – Admissions. Methods Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. Results Results showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. Conclusions These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings. PMID:28511033

Comparing adult cannabis treatment-seekers enrolled in a clinical trial with national samples of cannabis users in the United States.

PubMed

McClure, Erin A; King, Jacqueline S; Wahle, Aimee; Matthews, Abigail G; Sonne, Susan C; Lofwall, Michelle R; McRae-Clark, Aimee L; Ghitza, Udi E; Martinez, Melissa; Cloud, Kasie; Virk, Harvir S; Gray, Kevin M

2017-07-01

Cannabis use rates are increasing among adults in the United States (US) while the perception of harm is declining. This may result in an increased prevalence of cannabis use disorder and the need for more clinical trials to evaluate efficacious treatment strategies. Clinical trials are the gold standard for evaluating treatment, yet study samples are rarely representative of the target population. This finding has not yet been established for cannabis treatment trials. This study compared demographic and cannabis use characteristics of a cannabis cessation clinical trial sample (run through National Drug Abuse Treatment Clinical Trials Network) with three nationally representative datasets from the US; 1) National Survey on Drug Use and Health, 2) National Epidemiologic Survey on Alcohol and Related Conditions-III, and 3) Treatment: Episodes Data Set - Admissions. Comparisons were made between the clinical trial sample and appropriate cannabis using sub-samples from the national datasets, and propensity scores were calculated to determine the degree of similarity between samples. showed that the clinical trial sample was significantly different from all three national datasets, with the clinical trial sample having greater representation among older adults, African Americans, Hispanic/Latinos, adults with more education, non-tobacco users, and daily and almost daily cannabis users. These results are consistent with previous studies of other substance use disorder populations and extend sample representation issues to a cannabis use disorder population. This illustrates the need to ensure representative samples within cannabis treatment clinical trials to improve the generalizability of promising findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov.

PubMed

Stockmann, Chris; Sherwin, Catherine M T; Koren, Gideon; Campbell, Sarah C; Constance, Jonathan E; Linakis, Matthew; Balch, Alfred; Varner, Michael W; Spigarelli, Michael G

2014-04-01

Physiologic changes during pregnancy alter the pharmacokinetics, safety, and efficacy of many drugs. For clinicians, there is often uncertainty regarding the safety of these drugs due to a scarcity of published data. This study aimed to comprehensively evaluate the characteristics and publication patterns of obstetric studies registered in ClinicalTrials.gov from 2007 to 2012. Primary outcome measures, funding sources, inclusion criteria, and the reporting of study results were evaluated. A manual review of Medline/PubMed was performed to identify publications associated with studies registered in ClinicalTrials.gov. Of 93,709 total studies, there were 5,203 (6%) obstetric studies registered in ClinicalTrials.gov. Interventional studies accounted for 70% and 30% were observational. Clinical trials of drugs (49%), procedures (13%), and behavioral interventions (12%) were most common. Among interventional drug trials, 84% featured randomized allocation to study arms and 93% included measures of safety and/or efficacy as primary endpoints. Of 946 (18%) studies completed more than 2 years ago, only 11% had reported results and <7% had been published. In an area with a great need for evidence of safe and effective therapies, the low publication rate of completed studies incorporating elements of high-quality trial design is concerning. The sources of this trend should be closely investigated. © 2013, The American College of Clinical Pharmacology.

Poor reporting of scientific leadership information in clinical trial registers.

PubMed

Sekeres, Melanie; Gold, Jennifer L; Chan, An-Wen; Lexchin, Joel; Moher, David; Van Laethem, Marleen L P; Maskalyk, James; Ferris, Lorraine; Taback, Nathan; Rochon, Paula A

2008-02-20

In September 2004, the International Committee of Medical Journal Editors (ICMJE) issued a Statement requiring that all clinical trials be registered at inception in a public register in order to be considered for publication. The World Health Organization (WHO) and ICMJE have identified 20 items that should be provided before a trial is considered registered, including contact information. Identifying those scientifically responsible for trial conduct increases accountability. The objective is to examine the proportion of registered clinical trials providing valid scientific leadership information. We reviewed clinical trial entries listing Canadian investigators in the two largest international and public trial registers, the International Standard Randomized Controlled Trial Number (ISRCTN) register, and ClinicalTrials.gov. The main outcome measures were the proportion of clinical trials reporting valid contact information for the trials' Principal Investigator (PI)/Co-ordinating Investigator/Study Chair/Site PI, and trial e-mail contact address, stratified by funding source, recruiting status, and register. A total of 1388 entries (142 from ISRCTN and 1246 from ClinicalTrials.gov) comprised our sample. We found non-compliance with mandatory registration requirements regarding scientific leadership and trial contact information. Non-industry and partial industry funded trials were significantly more likely to identify the individual responsible for scientific leadership (OR = 259, 95% CI: 95-701) and to provide a contact e-mail address (OR = 9.6, 95% CI: 6.6-14) than were solely industry funded trials. Despite the requirements set by WHO and ICMJE, data on scientific leadership and contact e-mail addresses are frequently omitted from clinical trials registered in the two leading public clinical trial registers. To promote accountability and transparency in clinical trials research, public clinical trials registers should ensure adequate monitoring of trial registration to ensure completion of mandatory contact information fields identifying scientific leadership.

A case study of SMART attributes: a qualitative assessment of generalizability, retention rate, and trial quality.

PubMed

Moodie, Erica E M; Karran, James C; Shortreed, Susan M

2016-05-14

Personalizing medical care is becoming increasingly popular, particularly mental health care. There is growing interest in formalizing medical decision making based on evolving patient symptoms in an evidence-based manner. To determine optimal sequencing of treatments, the sequences themselves must be studied; this may be accomplished by using a sequential multiple assignment randomized trial (SMART). It has been hypothesized that SMART studies may improve participant retention and generalizability. We examine the hypotheses that SMART studies are more generalizable and have better retention than traditional randomized clinical trials via a case study of a SMART study of antipsychotic medications. We considered the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study, comparing the trial participant characteristics and overall retention to those of comparable trials found via a review of all related trials conducted from 2000 onwards. A MEDLINE search returned 6435 results for primary screening; ultimately, 48 distinct trials were retained for analysis. The study population in CATIE was similar to, although perhaps less symptomatic than, the study populations of traditional randomized clinical trials (RCTs), suggesting no large gains in generalizability despite the pragmatic nature of the trial. However, CATIE did see good month-by-month retention. SMARTs offer the possibility of studying treatment sequences in a way that a series of traditional RCTs cannot. SMARTs may offer improved retention; however, this case study did not find evidence to suggest greater generalizability using this trial design. ClinicalTrials.gov NCT00014001 . Registered on 6 April 2001.

Trial Prospector: Matching Patients with Cancer Research Studies Using an Automated and Scalable Approach

PubMed Central

Sahoo, Satya S; Tao, Shiqiang; Parchman, Andrew; Luo, Zhihui; Cui, Licong; Mergler, Patrick; Lanese, Robert; Barnholtz-Sloan, Jill S; Meropol, Neal J; Zhang, Guo-Qiang

2014-01-01

Cancer is responsible for approximately 7.6 million deaths per year worldwide. A 2012 survey in the United Kingdom found dramatic improvement in survival rates for childhood cancer because of increased participation in clinical trials. Unfortunately, overall patient participation in cancer clinical studies is low. A key logistical barrier to patient and physician participation is the time required for identification of appropriate clinical trials for individual patients. We introduce the Trial Prospector tool that supports end-to-end management of cancer clinical trial recruitment workflow with (a) structured entry of trial eligibility criteria, (b) automated extraction of patient data from multiple sources, (c) a scalable matching algorithm, and (d) interactive user interface (UI) for physicians with both matching results and a detailed explanation of causes for ineligibility of available trials. We report the results from deployment of Trial Prospector at the National Cancer Institute (NCI)-designated Case Comprehensive Cancer Center (Case CCC) with 1,367 clinical trial eligibility evaluations performed with 100% accuracy. PMID:25506198

Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.

PubMed

Perlis, Roy H; Perlis, Clifford S; Wu, Yelena; Hwang, Cindy; Joseph, Megan; Nierenberg, Andrew A

2005-10-01

Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge. The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo.

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.

Type 1 Diabetes TrialNet: A Multifaceted Approach to Bringing Disease-Modifying Therapy to Clinical Use in Type 1 Diabetes.

PubMed

Bingley, Polly J; Wherrett, Diane K; Shultz, Ann; Rafkin, Lisa E; Atkinson, Mark A; Greenbaum, Carla J

2018-04-01

What will it take to bring disease-modifying therapy to clinical use in type 1 diabetes? Coordinated efforts of investigators involved in discovery, translational, and clinical research operating in partnership with funders and industry and in sync with regulatory agencies are needed. This Perspective describes one such effort, Type 1 Diabetes TrialNet, a National Institutes of Health-funded and JDRF-supported international clinical trials network that emerged from the Diabetes Prevention Trial-Type 1 (DPT-1). Through longitudinal natural history studies, as well as trials before and after clinical onset of disease combined with mechanistic and ancillary investigations to enhance scientific understanding and translation to clinical use, TrialNet is working to bring disease-modifying therapies to individuals with type 1 diabetes. Moreover, TrialNet uses its expertise and experience in clinical studies to increase efficiencies in the conduct of trials and to reduce the burden of participation on individuals and families. Herein, we highlight key contributions made by TrialNet toward a revised understanding of the natural history of disease and approaches to alter disease course and outline the consortium's plans for the future. © 2018 by the American Diabetes Association.

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 trial design for women. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

ClinicalTrials.gov as a data source for semi-automated point-of-care trial eligibility screening.

PubMed

Pfiffner, Pascal B; Oh, JiWon; Miller, Timothy A; Mandl, Kenneth D

2014-01-01

Implementing semi-automated processes to efficiently match patients to clinical trials at the point of care requires both detailed patient data and authoritative information about open studies. To evaluate the utility of the ClinicalTrials.gov registry as a data source for semi-automated trial eligibility screening. Eligibility criteria and metadata for 437 trials open for recruitment in four different clinical domains were identified in ClinicalTrials.gov. Trials were evaluated for up to date recruitment status and eligibility criteria were evaluated for obstacles to automated interpretation. Finally, phone or email outreach to coordinators at a subset of the trials was made to assess the accuracy of contact details and recruitment status. 24% (104 of 437) of trials declaring on open recruitment status list a study completion date in the past, indicating out of date records. Substantial barriers to automated eligibility interpretation in free form text are present in 81% to up to 94% of all trials. We were unable to contact coordinators at 31% (45 of 146) of the trials in the subset, either by phone or by email. Only 53% (74 of 146) would confirm that they were still recruiting patients. Because ClinicalTrials.gov has entries on most US and many international trials, the registry could be repurposed as a comprehensive trial matching data source. Semi-automated point of care recruitment would be facilitated by matching the registry's eligibility criteria against clinical data from electronic health records. But the current entries fall short. Ultimately, improved techniques in natural language processing will facilitate semi-automated complex matching. As immediate next steps, we recommend augmenting ClinicalTrials.gov data entry forms to capture key eligibility criteria in a simple, structured format.

Reporting of statistically significant results at ClinicalTrials.gov for completed superiority randomized controlled trials.

PubMed

Dechartres, Agnes; Bond, Elizabeth G; Scheer, Jordan; Riveros, Carolina; Atal, Ignacio; Ravaud, Philippe

2016-11-30

Publication bias and other reporting bias have been well documented for journal articles, but no study has evaluated the nature of results posted at ClinicalTrials.gov. We aimed to assess how many randomized controlled trials (RCTs) with results posted at ClinicalTrials.gov report statistically significant results and whether the proportion of trials with significant results differs when no treatment effect estimate or p-value is posted. We searched ClinicalTrials.gov in June 2015 for all studies with results posted. We included completed RCTs with a superiority hypothesis and considered results for the first primary outcome with results posted. For each trial, we assessed whether a treatment effect estimate and/or p-value was reported at ClinicalTrials.gov and if yes, whether results were statistically significant. If no treatment effect estimate or p-value was reported, we calculated the treatment effect and corresponding p-value using results per arm posted at ClinicalTrials.gov when sufficient data were reported. From the 17,536 studies with results posted at ClinicalTrials.gov, we identified 2823 completed phase 3 or 4 randomized trials with a superiority hypothesis. Of these, 1400 (50%) reported a treatment effect estimate and/or p-value. Results were statistically significant for 844 trials (60%), with a median p-value of 0.01 (Q1-Q3: 0.001-0.26). For the 1423 trials with no treatment effect estimate or p-value posted, we could calculate the treatment effect and corresponding p-value using results reported per arm for 929 (65%). For 494 trials (35%), p-values could not be calculated mainly because of insufficient reporting, censored data, or repeated measurements over time. For the 929 trials we could calculate p-values, we found statistically significant results for 342 (37%), with a median p-value of 0.19 (Q1-Q3: 0.005-0.59). Half of the trials with results posted at ClinicalTrials.gov reported a treatment effect estimate and/or p-value, with significant results for 60% of these. p-values could be calculated from results reported per arm at ClinicalTrials.gov for only 65% of the other trials. The proportion of significant results was much lower for these trials, which suggests a selective posting of treatment effect estimates and/or p-values when results are statistically significant.

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.

African American women's perceptions of cancer clinical trials

PubMed Central

Haynes-Maslow, Lindsey; Godley, Paul; Dimartino, Lisa; White, Brandolyn; Odom, Janice; Richmond, Alan; Carpenter, William

2014-01-01

Cancer clinical trials are important for resolving cancer health disparities for several reasons; however, clinical trial participation among African Americans is significantly lower than Caucasians. This study engaged focus groups of 82 female African American cancer survivors or cancer caregivers, including those in better resourced, more urban areas and less resourced, more rural areas. Informed by an integrated conceptual model, the focus groups examined perceptions of cancer clinical trials and identified leverage points that future interventions may use to improve enrollment rates. Study findings highlight variation in community knowledge regarding cancer clinical trials, and the importance of community education regarding clinical trials and overcoming historical stigma associated with clinical research specifically and the health care system more generally. Study participants commented on the centrality of churches in their communities, and thus the promise of the church as loci of such education. Findings also suggested the value of informed community leaders as community information sources, including community members who have a previous diagnosis of cancer and clinical trial experience. The sample size and location of the focus groups may limit the generalizability of the results. Since the women in the focus groups were either cancer survivors or caregivers, they may have different experiences than nonparticipants who lack the close connection with cancer. Trust in the health system and in one's physician was seen as important factors associated with patient willingness to enroll in clinical trials, and participants suggested that physicians who were compassionate and who engaged and educated their patients would build important trust requisite for patient participation in clinical trials. PMID:24905181

Reporting discrepancies between the ClinicalTrials.gov results database and peer-reviewed publications.

PubMed

Hartung, Daniel M; Zarin, Deborah A; Guise, Jeanne-Marie; McDonagh, Marian; Paynter, Robin; Helfand, Mark

2014-04-01

ClinicalTrials.gov requires reporting of result summaries for many drug and device trials. To evaluate the consistency of reporting of trials that are registered in the ClinicalTrials.gov results database and published in the literature. ClinicalTrials.gov results database and matched publications identified through ClinicalTrials.gov and a manual search of 2 electronic databases. 10% random sample of phase 3 or 4 trials with results in the ClinicalTrials.gov results database, completed before 1 January 2009, with 2 or more groups. One reviewer extracted data about trial design and results from the results database and matching publications. A subsample was independently verified. Of 110 trials with results, most were industry-sponsored, parallel-design drug studies. The most common inconsistency was the number of secondary outcome measures reported (80%). Sixteen trials (15%) reported the primary outcome description inconsistently, and 22 (20%) reported the primary outcome value inconsistently. Thirty-eight trials inconsistently reported the number of individuals with a serious adverse event (SAE); of these, 33 (87%) reported more SAEs in ClinicalTrials.gov. Among the 84 trials that reported SAEs in ClinicalTrials.gov, 11 publications did not mention SAEs, 5 reported them as zero or not occurring, and 21 reported a different number of SAEs. Among 29 trials that reported deaths in ClinicalTrials.gov, 28% differed from the matched publication. Small sample that included earliest results posted to the database. Reporting discrepancies between the ClinicalTrials.gov results database and matching publications are common. Which source contains the more accurate account of results is unclear, although ClinicalTrials.gov may provide a more comprehensive description of adverse events than the publication. Agency for Healthcare Research and Quality.

First-in-human Phase 1 CRISPR Gene Editing Cancer Trials: Are We Ready?

PubMed

Baylis, Francoise; McLeod, Marcus

2017-01-01

A prospective first-in-human Phase 1 CRISPR gene editing trial in the United States for patients with melanoma, synovial sarcoma, and multiple myeloma offers hope that gene editing tools may usefully treat human disease. An overarching ethical challenge with first-in-human Phase 1 clinical trials, however, is knowing when it is ethically acceptable to initiate such trials on the basis of safety and efficacy data obtained from pre-clinical studies. If the pre-clinical studies that inform trial design are themselves poorly designed - as a result of which the quality of pre-clinical evidence is deficient - then the ethical requirement of scientific validity for clinical research may not be satisfied. In turn, this could mean that the Phase 1 clinical trial will be unsafe and that trial participants will be exposed to risk for no potential benefit. To assist sponsors, researchers, clinical investigators and reviewers in deciding when it is ethically acceptable to initiate first-in-human Phase 1 CRISPR gene editing clinical trials, structured processes have been developed to assess and minimize translational distance between pre-clinical and clinical research. These processes draw attention to various features of internal validity, construct validity, and external validity. As well, the credibility of supporting evidence is to be critically assessed with particular attention to optimism bias, financial conflicts of interest and publication bias. We critically examine the pre-clinical evidence used to justify the first-inhuman Phase 1 CRISPR gene editing cancer trial in the United States using these tools. We conclude that the proposed trial cannot satisfy the ethical requirement of scientific validity because the supporting pre-clinical evidence used to inform trial design is deficient. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006–2015

PubMed Central

Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

2017-01-01

Objectives To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. Setting The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. Design The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Results Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Conclusions Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. PMID:28619765

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho

2018-01-01

Background Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. Objective The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. Methods This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. Results In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. Conclusions The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws. PMID:29691212

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

Linear Combinations of Multiple Outcome Measures to Improve the Power of Efficacy Analysis ---Application to Clinical Trials on Early Stage Alzheimer Disease

PubMed Central

Xiong, Chengjie; Luo, Jingqin; Morris, John C; Bateman, Randall

2018-01-01

Modern clinical trials on Alzheimer disease (AD) focus on the early symptomatic stage or even the preclinical stage. Subtle disease progression at the early stages, however, poses a major challenge in designing such clinical trials. We propose a multivariate mixed model on repeated measures to model the disease progression over time on multiple efficacy outcomes, and derive the optimum weights to combine multiple outcome measures by minimizing the sample sizes to adequately power the clinical trials. A cross-validation simulation study is conducted to assess the accuracy for the estimated weights as well as the improvement in reducing the sample sizes for such trials. The proposed methodology is applied to the multiple cognitive tests from the ongoing observational study of the Dominantly Inherited Alzheimer Network (DIAN) to power future clinical trials in the DIAN with a cognitive endpoint. Our results show that the optimum weights to combine multiple outcome measures can be accurately estimated, and that compared to the individual outcomes, the combined efficacy outcome with these weights significantly reduces the sample size required to adequately power clinical trials. When applied to the clinical trial in the DIAN, the estimated linear combination of six cognitive tests can adequately power the clinical trial. PMID:29546251

So different, yet so similar: meta-analysis and policy modeling of willingness to participate in clinical trials among Brazilians and Indians.

PubMed

Zammar, Guilherme; Meister, Henrique; Shah, Jatin; Phadtare, Amruta; Cofiel, Luciana; Pietrobon, Ricardo

2010-12-16

With the global expansion of clinical trials and the expectations of the rise of the emerging economies known as BRICs (Brazil, Russia, India and China), the understanding of factors that affect the willingness to participate in clinical trials of patients from those countries assumes a central role in the future of health research. We conducted a systematic review and meta-analysis (SRMA) of willingness to participate in clinical trials among Brazilian patients and then we compared it with Indian patients (with results of another SRMA previously conducted by our group) through a system dynamics model. Five studies were included in the SRMA of Brazilian patients. Our main findings are 1) the major motivation for Brazilian patients to participate in clinical trials is altruism, 2) monetary reimbursement is the least important factor motivating Brazilian patients, 3) the major barrier for Brazilian patients to not participate in clinical trials is the fear of side effects, and 4) Brazilian patients are more likely willing to participate in clinical trials than Indians. Our study provides important insights for investigators and sponsors for planning trials in Brazil (and India) in the future. Ignoring these results may lead to unnecessary fund/time spending. More studies are needed to validate our results and for better understanding of this poorly studied theme.

Methodological considerations in the design and implementation of clinical trials.

PubMed

Cirrincione, Constance T; Lavoie Smith, Ellen M; Pang, Herbert

2014-02-01

To review study design issues related to clinical trials led by oncology nurses, with special attention to those conducted within the cooperative group setting; to emphasize the importance of the statistician's role in the process of clinical trials. Studies available at clinicaltrials.gov using experimental designs that have been published in peer-reviewed journals; cooperative group trials are highlighted. The clinical trial is a primary means to test intervention efficacy. A properly designed and powered study with clear and measurable objectives is as important as the intervention itself. Collaboration among the study team, including the statistician, is central in developing and conducting appropriately designed studies. For optimal results, collaboration is an ongoing process that should begin early on. Copyright © 2014 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.

Parent satisfaction in a multi-site acute trial of risperidone in children with autism: a social validity study.

PubMed

Tierney, Elaine; Aman, Michael; Stout, David; Pappas, Krista; Arnold, L Eugene; Vitiello, Benedetto; Scahill, Lawrence; McDougle, Christopher; McCracken, James; Wheeler, Courtney; Martin, Andres; Posey, David; Shah, Bhavik

2007-03-01

Subjects who view experimental procedures as worthwhile are more likely to participate in clinical trials and comply with study procedures. Designing studies that consider the consumer's perspective will help to forge a better alliance between participants and researchers. Participant satisfaction is seldom assessed in pharmacological research. In this paper, we report on parent satisfaction in a randomized clinical trial in children with autistic disorder and severely disruptive behavior. Parents of 101 children with autism who had participated in a multi-site 8-week double-blind clinical trial of risperidone were given a questionnaire at the end to elicit their perceptions of the appropriateness and acceptability of clinical trial procedures. Ninety-six (95.0%) parents returned the questionnaire. Of these, 80.0 to 96.8%, depending on the question, expressed satisfaction with their child's research participation regardless of treatment outcome or assignment to active drug or placebo. In all, 90.5% of parents indicated that they would "definitely" recommend the clinical trial to other families with similar children. A total of 92.7% indicated that they would rejoin the clinical trial if they had to do it all over again. Ethnic minority subjects were more satisfied than white participants with the use of "learning tests". Parents of children participating in this trial were highly satisfied and supportive of the clinical trial procedures. Random assignment to drug or placebo and the clinical response of their children did not appear to influence their views. Further satisfaction studies of this sort are encouraged.

Using "clinical trial diaries" to track patterns of participation for serial healthy volunteers in U.S. phase I studies.

PubMed

Edelblute, Heather B; Fisher, Jill A

2015-02-01

Phase I testing of investigational drugs relies on healthy volunteers as research participants. Many U.S. healthy volunteers enroll repeatedly in clinical trials for the financial compensation. Serial participants are incentivized to ignore restrictions on their participation, and no centralized clinical trial registry prevents dual enrollment. Little is currently known about how healthy volunteers participate in studies over time, hampering the development of policies to protect this group. We detail a methodology developed as part of a longitudinal study to track in real-time healthy volunteers' Phase I participation. Illustrating these data through three case studies, we document how healthy volunteers use strategies, such as qualifying for studies at more than one clinic and traveling significant distances, to maximize their participation. Our findings suggest that "clinical trial diaries" can generate critical information about serial research participation and point to ethical issues unique to healthy volunteers' involvement in Phase I clinical trials. © The Author(s) 2015.

An assessment of the utilization of the preclinical rodent model literature in clinical trials of putative therapeutics for the treatment of alcohol use disorders.

PubMed

Barajaz, Ashley M; Kliethermes, Christopher L

2017-12-01

Rodent models of Alcohol Use Disorders (AUD) are used extensively by preclinical researchers to develop new therapeutics for the treatment of AUD. Although these models play an important role in the development of novel, targeted therapeutics, their role in bringing therapeutics to clinical trials is unclear, as off-label use of existing medications not approved for the treatment of AUD is commonly seen in the clinic and clinical trials. In the current study, we used the Clinicaltrials.gov database to obtain a list of drugs that have been tested for efficacy in a clinical trial between 1997 and 2017. We then conducted a set of literature searches to determine which of the 98 unique drugs we identified had shown efficacy in a rodent model of an AUD prior to being tested in a clinical trial. We found that slightly less than half of the drugs tested in clinical trials (48%) had shown prior efficacy in any rodent model of an AUD, while the remaining 52% of drugs were used off-label, or in some cases, following non-published studies. This study raises the question of how clinical researchers incorporate results from preclinical studies in the decision to bring a drug to a clinical trial. Our results underscore the need for ongoing communication among preclinical and clinical researchers. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

Bovaira-García, M J; Soler-Company, E

2012-01-01

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

The fate of prospective spine studies registered on www.ClinicalTrials.gov.

PubMed

Ohnmeiss, Donna D

2015-03-01

There has been concern expressed about research ethics with respect to not fully reporting data collected during clinical studies. One site available for all clinical trials is ClinicalTrials.gov. The original purpose of this site was to facilitate patients seeking a trial for the treatment of their particular condition. The internationally available site offers general information about the study, sponsor name, principal investigator, patient selection criteria, enrollment goal, study design, outcome measures, participating centers, initiation date, date posted, date completed, and other pertinent data. The site can be used to identify studies conducted for a particular condition or intervention. The purpose of this study was to investigate the fate of spine-related studies registered on www.ClinicalTrials.gov, with particular focus on the publication rate of completed trials. Analysis and classification of clinical studies posted on an international research registry Web page and literature search for related publications. Not applicable. The primary outcome measure was publication of the study registered on ClinicalTrials.gov. Multiple searches were conducted on ClinicalTrials.gov Web site to identify studies related to commonly treated spinal conditions, including herniated disc, degenerative disc disease, stenosis, and spondylolisthesis. Studies related to tumors, fractures, or that included nonspine conditions were not included. For studies classified as completed more than 18 months before this review, literature searches were conducted to determine if the results of the study had been published and factors related to publication. The author has no financial conflict related to this work. There were 263 spine-related studies identified from searches on the ClinicalTrials.gov site. Data on the site had the studies classified as follows: 72 completed, 70 active, not recruiting (generally indicates collecting follow-up data), 74 recruiting, 11 recruiting by invitation, 13 not yet recruiting, 18 terminated, 4 withdrawn, and 1 suspended. Among the 72 studies indicated to be completed, 28 (38.9%) have been published. The mean time to publish was 27.9 months from the date of completion. Among unpublished studies, the mean length of time from study completion to the preparation of this article was 62.0 months. There was no difference in the likelihood of publication based on the geographic region of study origin or whether the study was registered before or after initiation. There were statistically significant relationships between the publication rate and the funding type as well as the research type (p<.05) with industrial-funded studies and those evaluating devices having a lower publication rate and those that were funded by a federal agency and comparing surgery to nonoperative care had the highest publication rates. Although the 38.9% publication rate for spine-related studies found in this study appears low, it is in line with other studies reporting a 22.8% publication rate for arthroplasty trials and 43.2% for orthopedic trauma trials. In addition to ClinicalTrials.gov Web site fulfilling its original goal of providing patients information about clinical studies, it can also provide a means of tracking publication of prospective studies, changes to protocols, matching publication content to posted study design, and others and raise queries concerning the reasons for not publishing what appear to be well-designed studies. The posting of spine studies before initiation can increase transparency and ability to evaluate clinical trials in spine. Copyright © 2015 Elsevier Inc. All rights reserved.

Assessing the Eventual Publication of Clinical Trial Abstracts Submitted to a Large Annual Oncology Meeting.

PubMed

Massey, Paul R; Wang, Ruibin; Prasad, Vinay; Bates, Susan E; Fojo, Tito

2016-03-01

Despite the ethical imperative to publish clinical trials when human subjects are involved, such data frequently remain unpublished. The objectives were to tabulate the rate and ascertain factors associated with eventual publication of clinical trial results reported as abstracts in the Proceedings of the American Society of Clinical Oncology (American Society of Clinical Oncology). Abstracts describing clinical trials for patients with breast, lung, colorectal, ovarian, and prostate cancer from 2009 to 2011 were identified by using a comprehensive online database (http://meetinglibrary.asco.org/abstracts). Abstracts included reported results of a treatment or intervention assessed in a discrete, prospective clinical trial. Publication status at 4-6 years was determined by using a standardized search of PubMed. Primary outcomes were the rate of publication for abstracts of randomized and nonrandomized clinical trials. Secondary outcomes included factors influencing the publication of results. A total of 1,075 abstracts describing 378 randomized and 697 nonrandomized clinical trials were evaluated. Across all years, 75% of randomized and 54% of nonrandomized trials were published, with an overall publication rate of 61%. Sample size was a statistically significant predictor of publication for both randomized and nonrandomized trials (odds ratio [OR] per increase of 100 participants = 1.23 [1.11-1.36], p < .001; and 1.64 [1.15-2.34], p = .006, respectively). Among randomized studies, an industry coauthor or involvement of a cooperative group increased the likelihood of publication (OR 2.37, p = .013; and 2.21, p = .01, respectively). Among nonrandomized studies, phase II trials were more likely to be published than phase I (p < .001). Use of an experimental agent was not a predictor of publication in randomized (OR 0.76 [0.38-1.52]; p = .441) or nonrandomized trials (OR 0.89 [0.61-1.29]; p = .532). This is the largest reported study examining why oncology trials are not published. The data show that 4-6 years after appearing as abstracts, 39% of oncology clinical trials remain unpublished. Larger sample size and advanced trial phase were associated with eventual publication; among randomized trials, an industry-affiliated author or a cooperative group increased likelihood of publication. Unfortunately, we found that, despite widespread recognition of the problem and the creation of central data repositories, timely publishing of oncology clinical trials results remains unsatisfactory. ©AlphaMed Press.

Feasibility trial of a Spanish-language multimedia educational intervention.

PubMed

Wells, Kristen J; McIntyre, Jessica; Gonzalez, Luis E; Lee, Ji-Hyun; Fisher, Kate J; Jacobsen, Paul B; Meade, Cathy; Muñoz-Antonia, Teresita; Quinn, Gwendolyn P

2013-10-01

Hispanic cancer patients are underrepresented in clinical trials; research suggests lack of knowledge and language barriers contribute to low accrual. Multimedia materials offer advantages to Hispanic populations because they have high acceptability, are easy to disseminate, and can be viewed with family. Hispanic cancer patients and caregivers participated in focus groups to aid in developing a Spanish-language multimedia intervention to educate Hispanic cancer patients about clinical trials. We explored the feasibility of delivering the intervention in medical oncology clinics. A total of 35 patients were randomized to either the multimedia intervention group (n = 18) or a control group (n = 17) who were asked to read the National Cancer Institute's Spanish-language clinical trials brochure. Self-reported data on knowledge about and attitudes toward clinical trials, self-efficacy for participating in a clinical trial, intention to participate in a clinical trial if asked, and receptivity to information about a clinical trial were collected at baseline and 10 days later. Delivery of the multimedia presentation in oncology clinics was feasible. The intervention group had more knowledge about clinical trials at follow-up than the control group; scores for intention to participate in a clinical trial by participants in the intervention group increased from 3.8 to 4.0 of a possible 5, but declined in the control group from 4.5 to 4.1. No statistically significant difference was detected between groups in scores for attitudes or self-efficacy for making a decision to participate in a clinical trial. Our sample size was inadequate to identify differences between the informational methods. Although all patients were asked about their willingness to participate in a clinical trial, this decision was hypothetical. In addition, the study was conducted with a sample of Spanish-speaking Hispanic cancer patients at a comprehensive cancer center in Florida. Thus, the results may not generalize to other Hispanic populations. In the pilot project, we demonstrated the feasibility of delivering multimedia information to patients in medical oncology clinics. Because delivery in a clinical setting was found to be feasible, a larger study should be conducted to evaluate the efficacy of the multimedia intervention with respect to promoting accrual of Hispanic patients to clinical trials.

The case for introducing pre-registered confirmatory pharmacological pre-clinical studies.

PubMed

Kiwanuka, Olivia; Bellander, Bo-Michael; Hånell, Anders

2018-05-01

When evaluating the design of pre-clinical studies in the field of traumatic brain injury, we found substantial differences compared to phase III clinical trials, which in part may explain the difficulties in translating promising experimental drugs into approved treatments. By using network analysis, we also found cases where a large proportion of the studies evaluating a pre-clinical treatment was performed by inter-related researchers, which is potentially problematic. Subjecting all pre-clinical trials to the rigor of a phase III clinical trial is, however, likely not practically achievable. Instead, we repeat the call for a distinction to be made between exploratory and confirmatory pre-clinical studies.

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.

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: 0.51-0.83)). Conclusion A total of 15% of pulmonary clinical highly likely applicable clinical trials report basic summary results to ClinicalTrials.gov within 1 year of trial completion. Strategies to improve reporting are needed within the pulmonary community.

An educational video to increase clinical trials enrollment among breast cancer patients.

PubMed

Du, Wei; Mood, Darlene; Gadgeel, Shirish; Simon, Michael S

2009-09-01

Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients' attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment.

An educational video to increase clinical trials enrollment among breast cancer patients

PubMed Central

Du, Wei; Mood, Darlene; Gadgeel, Shirish; Simon, Michael S.

2013-01-01

Only 3% of women with breast cancer participate in cancer clinical trials nationwide. The lack of awareness about clinical trials is a significant barrier towards clinical trials participation. A study was conducted at a large urban Comprehensive Cancer Center to test (1) the effectiveness of an 18-min educational video on improving attitudes toward clinical trials and trials enrollment among new breast cancer patients seen at the Karmanos Cancer Institute, and (2) to assess racial differences in attitudes regarding clinical trials. Participants were randomized to either the educational intervention prior to their first oncology clinic appointment or to standard care. A baseline and 2-week post-intervention survey to assess attitudes toward clinical trials participation was completed by participants. Of 218 subjects recruited, 196 (55% white vs. 45% African American (AA)) eligible patients were included in the analysis. A small increase in therapeutic clinical trial enrollment was observed in the intervention arm but was not statistically significant (10.4% vs. 6.1%; P = 0.277). The intervention also did not result in a clear improvement in patients’ attitudes toward clinical trials at posttest. However, a lower enrollment rate for the AA women was noted after adjusting for stage (OR = 0.282, P = 0.049). Significantly more negative scores were noted in 3 out of the 5 baseline attitudinal scales for AA women. The educational video did not significantly increase enrollment in breast cancer clinical trials. The findings that AA women had significantly more negative attitudes toward clinical trials than white women may partially explain the racial disparity in enrollment. An educational video remains a simple and cost-effective way to educate patients. Future studies should focus on designing a new educational video to specifically target cultural and attitudinal barriers in the AA population to more effectively change attitudes and increase trial enrollment. PMID:19152024

Standards for Clinical Trials in Male and Female Sexual Dysfunction: III. Unique Aspects of Clinical Trials in Male Sexual Dysfunction.

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

2017-01-01

This series of articles, Standards for Clinical Trials in Male and Female Sexual Dysfunction, began with the discussion of 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 the selection of study population and study duration in male and female sexual dysfunction. The second article in this series discussed fundamental principles in development, validation, and selection of patient- (and partner-) reported outcome assessment. The third and present article in this series discusses selected aspects of sexual dysfunction that are that are unique to male sexual dysfunctions and relevant to the conduct of clinical trials of candidate treatments for men. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Critical appraisal of clinical trials in multiple system atrophy: Toward better quality.

PubMed

Castro Caldas, Ana; Levin, Johannes; Djaldetti, Ruth; Rascol, Olivier; Wenning, Gregor; Ferreira, Joaquim J

2017-10-01

Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

The correlation between the number of eligible patients in routine clinical practice and the low recruitment level in clinical trials: a retrospective study using electronic medical records.

PubMed

Sumi, Eriko; Teramukai, Satoshi; Yamamoto, Keiichi; Satoh, Motohiko; Yamanaka, Kenya; Yokode, Masayuki

2013-12-11

A number of clinical trials have encountered difficulties enrolling a sufficient number of patients upon initiating the trial. Recently, many screening systems that search clinical data warehouses for patients who are eligible for clinical trials have been developed. We aimed to estimate the number of eligible patients using routine electronic medical records (EMRs) and to predict the difficulty of enrolling sufficient patients prior to beginning a trial. Investigator-initiated clinical trials that were conducted at Kyoto University Hospital between July 2004 and January 2011 were included in this study. We searched the EMRs for eligible patients and calculated the eligible EMR patient index by dividing the number of eligible patients in the EMRs by the target sample size. Additionally, we divided the trial eligibility criteria into corresponding data elements in the EMRs to evaluate the completeness of mapping clinical manifestation in trial eligibility criteria into structured data elements in the EMRs. We evaluated the correlation between the index and the accrual achievement with Spearman's rank correlation coefficient. Thirteen of 19 trials did not achieve their original target sample size. Overall, 55% of the trial eligibility criteria were mapped into data elements in EMRs. The accrual achievement demonstrated a significant positive correlation with the eligible EMR patient index (r = 0.67, 95% confidence interval (CI), 0.42 to 0.92). The receiver operating characteristic analysis revealed an eligible EMR patient index cut-off value of 1.7, with a sensitivity of 69.2% and a specificity of 100.0%. Our study suggests that the eligible EMR patient index remains exploratory but could be a useful component of the feasibility study when planning a clinical trial. Establishing a step to check whether there are likely to be a sufficient number of eligible patients enables sponsors and investigators to concentrate their resources and efforts on more achievable trials.

Barriers to participation in clinical trials: a physician survey.

PubMed

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

2018-04-01

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

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.

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.

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

The challenge of comorbidity in clinical trials for multiple sclerosis.

PubMed

Marrie, Ruth Ann; Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A

2016-04-12

We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to "real world" settings where the MS population commonly has comorbid conditions. © 2016 American Academy of Neurology.

The challenge of comorbidity in clinical trials for multiple sclerosis

PubMed Central

Miller, Aaron; Sormani, Maria Pia; Thompson, Alan; Waubant, Emmanuelle; Trojano, Maria; O'Connor, Paul; Reingold, Stephen; Cohen, Jeffrey A.

2016-01-01

Objective: We aimed to provide recommendations for addressing comorbidity in clinical trial design and conduct in multiple sclerosis (MS). Methods: We held an international workshop, informed by a systematic review of the incidence and prevalence of comorbidity in MS and an international survey about research priorities for studying comorbidity including their relation to clinical trials in MS. Results: We recommend establishing age- and sex-specific incidence estimates for comorbidities in the MS population, including those that commonly raise concern in clinical trials of immunomodulatory agents; shifting phase III clinical trials of new therapies from explanatory to more pragmatic trials; describing comorbidity status of the enrolled population in publications reporting clinical trials; evaluating treatment response, tolerability, and safety in clinical trials according to comorbidity status; and considering comorbidity status in the design of pharmacovigilance strategies. Conclusion: Our recommendations will help address knowledge gaps regarding comorbidity that interfere with the ability to interpret safety in monitored trials and will enhance the generalizability of findings from clinical trials to “real world” settings where the MS population commonly has comorbid conditions. PMID:26888986

Comparison of Survival Outcomes Among Cancer Patients Treated In and Out of Clinical Trials

PubMed Central

2014-01-01

Background Clinical trials test the efficacy of a treatment in a select patient population. We examined whether cancer clinical trial patients were similar to nontrial, “real-world” patients with respect to presenting characteristics and survival. Methods We reviewed the SWOG national clinical trials consortium database to identify candidate trials. Demographic factors, stage, and overall survival for patients in the standard arms were compared with nontrial control subjects selected from the Surveillance, Epidemiology, and End Results program. Multivariable survival analyses using Cox regression were conducted. The survival functions from aggregate data across all studies were compared separately by prognosis (≥50% vs <50% average 2-year survival). All statistical tests were two-sided. Results We analyzed 21 SWOG studies (11 good prognosis and 10 poor prognosis) comprising 5190 patients enrolled from 1987 to 2007. Trial patients were younger than nontrial patients (P < .001). In multivariable analysis, trial participation was not associated with improved overall survival for all 11 good-prognosis studies but was associated with better survival for nine of 10 poor-prognosis studies (P < .001). The impact of trial participation on overall survival endured for only 1 year. Conclusions Trial participation was associated with better survival in the first year after diagnosis, likely because of eligibility criteria that excluded higher comorbidity patients from trials. Similar survival patterns between trial and nontrial patients after the first year suggest that trial standard arm outcomes are generalizable over the long term and may improve confidence that trial treatment effects will translate to the real-world setting. Reducing eligibility criteria would improve access to clinical trials. PMID:24627276

Searching ClinicalTrials.gov did not change the conclusions of a systematic review.

PubMed

Wilson, Lisa M; Sharma, Ritu; Dy, Sydney M; Waldfogel, Julie M; Robinson, Karen A

2017-10-01

We assessed the effect of searching ClinicalTrials.gov on the conclusions of a systematic review. We conducted this case study concurrently with a systematic review. We searched ClinicalTrials.gov on March 9, 2016, to identify trial records eligible for inclusion in the review. Two independent reviewers screened ClinicalTrials.gov records. We compared conclusions and strength of evidence grade with and without ClinicalTrials.gov records for 31 comparisons and 2 outcomes. We identified 106 trials (53 in the peer-reviewed literature only, 23 in ClinicalTrials.gov only, and 30 in both sources). For one comparison, the addition of results identified through ClinicalTrials.gov reduced the pooled effect size. We found evidence of selective outcome reporting for two comparisons and suspected publication bias for another two comparisons. For all other comparisons, searching ClinicalTrials.gov did not change conclusions or the strength of evidence grading for the two outcomes. Our search of ClinicalTrials.gov bolstered suspicions of reporting biases but did not change either the conclusions or the strength of evidence grading. Further research is needed to determine the effect of searching ClinicalTrials.gov on the conclusions of systematic reviews in different topic areas and as the new rules for registration of trial results take effect. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of the Study Characteristics Affecting Clinical Trial Quality Using the Protocol Deviations Leading to Exclusion of Subjects From the Per Protocol Set Data in Studies for New Drug Application: A Retrospective Analysis.

PubMed

Kohara, Norihito; Kaneko, Masayuki; Narukawa, Mamoru

2018-01-01

The concept of the risk-based approach has been introduced as an effort to secure the quality of clinical trials. In the risk-based approach, identification and evaluation of risk in advance are considered important. For recently completed clinical trials, we investigated the relationship between study characteristics and protocol deviations leading to the exclusion of subjects from Per Protocol Set (PPS) efficacy analysis. New drugs approved in Japan in the fiscal year 2014-2015 were targeted in the research. The reasons for excluding subjects from the PPS efficacy analysis were described in 102 trials out of 492 in the summary of new drug application documents, which was publicly disclosed after the drug's regulatory approval. The author extracted these reasons along with the numbers of the cases and the study characteristics of each clinical trial. Then, the direct comparison, univariate regression analysis, and multivariate regression analysis was carried out based on the exclusion rate. The study characteristics for which exclusion of subjects from the PPS efficacy analysis were frequently observed was multiregional clinical trials in study region; inhalant and external use in administration route; Anti-infective for systemic use; Respiratory system, Dermatologicals, and Nervous system in therapeutic drug under the Anatomical Therapeutic Chemical Classification. In the multivariate regression analysis, the clinical trial variables of inhalant, Respiratory system, or Dermatologicals were selected as study characteristics leading to a higher exclusion rate. The characteristics of the clinical trial that is likely to cause protocol deviations that will affect efficacy analysis were suggested. These studies should be considered for specific attention and priority observation in the trial protocol or its monitoring plan and execution, such as a clear description of inclusion/exclusion criteria in the protocol, development of training materials to site staff, and/or trial subjects as specific risk-alleviating measures.

Clinical Trials of Precision Medicine through Molecular Profiling: Focus on Breast Cancer.

PubMed

Zardavas, Dimitrios; Piccart-Gebhart, Martine

2015-01-01

High-throughput technologies of molecular profiling in cancer, such as gene-expression profiling and next-generation sequencing, are expanding our knowledge of the molecular landscapes of several cancer types. This increasing knowledge coupled with the development of several molecularly targeted agents hold the promise for personalized cancer medicine to be fully realized. Moreover, an expanding armamentarium of targeted agents has been approved for the treatment of specific molecular cancer subgroups in different diagnoses. According to this paradigm, treatment selection should be dictated by the specific molecular aberrations found in each patient's tumor. The classical clinical trials paradigm of patients' eligibility being based on clinicopathologic parameters is being abandoned, with current clinical trials enrolling patients on the basis of specific molecular aberrations. New, innovative trial designs have been generated to better tackle the multiple challenges induced by the increasing molecular fragmentation of cancer, namely: (1) longitudinal cohort studies with or without downstream trials, (2) studies assessing the clinical utility of molecular profiling, (3) master or umbrella trials, (4) basket trials, (5) N-of-1 trials, and (6) adaptive design trials. This article provides an overview of the challenges for clinical trials in the era of molecular profiling of cancer. Subsequently, innovative trial designs with respective examples and their potential to expedite efficient clinical development of targeted anticancer agents is discussed.

Clinical trials transparency and the Trial and Experimental Studies Transparency (TEST) act.

PubMed

Logvinov, Ilana

2014-03-01

Clinical trial research is the cornerstone for successful advancement of medicine that provides hope for millions of people in the future. Full transparency in clinical trials may allow independent investigators to evaluate study designs, perform additional analysis of data, and potentially eliminate duplicate studies. Current regulatory system and publishers rely on investigators and pharmaceutical industries for complete and accurate reporting of results from completed clinical trials. Legislation seems to be the only way to enforce mandatory disclosure of results. The Trial and Experimental Studies Transparency (TEST) Act of 2012 was introduced to the legislators in the United States to promote greater transparency in research industry. Public safety and advancement of science are the driving forces for the proposed policy change. The TEST Act may benefit the society and researchers; however, there are major concerns with participants' privacy and intellectual property protection. Copyright © 2014 Elsevier Inc. All rights reserved.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?

PubMed

Hamaker, M E; Stauder, R; van Munster, B C

2014-03-01

Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?†

PubMed Central

Hamaker, M. E.; Stauder, R.; van Munster, B. C.

2014-01-01

Background Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. Method The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Conclusion Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population. PMID:24458474

Automated matching software for clinical trials eligibility: measuring efficiency and flexibility.

PubMed

Penberthy, Lynne; Brown, Richard; Puma, Federico; Dahman, Bassam

2010-05-01

Clinical trials (CT) serve as the media that translates clinical research into standards of care. Low or slow recruitment leads to delays in delivery of new therapies to the public. Determination of eligibility in all patients is one of the most important factors to assure unbiased results from the clinical trials process and represents the first step in addressing the issue of under representation and equal access to clinical trials. This is a pilot project evaluating the efficiency, flexibility, and generalizibility of an automated clinical trials eligibility screening tool across 5 different clinical trials and clinical trial scenarios. There was a substantial total savings during the study period in research staff time spent in evaluating patients for eligibility ranging from 165h to 1329h. There was a marked enhancement in efficiency with the automated system for all but one study in the pilot. The ratio of mean staff time required per eligible patient identified ranged from 0.8 to 19.4 for the manual versus the automated process. The results of this study demonstrate that automation offers an opportunity to reduce the burden of the manual processes required for CT eligibility screening and to assure that all patients have an opportunity to be evaluated for participation in clinical trials as appropriate. The automated process greatly reduces the time spent on eligibility screening compared with the traditional manual process by effectively transferring the load of the eligibility assessment process to the computer. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Embedding clinical interventions into observational studies

PubMed Central

Newman, Anne B.; Avilés-Santa, M. Larissa; Anderson, Garnet; Heiss, Gerardo; Howard, Wm. James; Krucoff, Mitchell; Kuller, Lewis H.; Lewis, Cora E.; Robinson, Jennifer G.; Taylor, Herman; Treviño, Roberto P.; Weintraub, William

2017-01-01

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed. PMID:26611435

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.

Ethical challenges in preclinical Alzheimer’s disease observational studies and trials: results of the Barcelona summit

PubMed Central

Molinuevo, José L.; Cami, Jordi; Carné, Xavier; Carrillo, Maria C.; Georges, Jean; Isaac, Maria B.; Khachaturian, Zaven; Kim, Scott Y. H.; Morris, John C.; Pasquier, Florence; Ritchie, Craig; Sperling, Reisa; Karlawish, Jason

2016-01-01

Alzheimer’s disease (AD) is among the most significant healthcare burdens. Disappointing results from clinical trials in late-stage AD persons combined with hopeful results from trials in persons with early-stage suggest that research in the preclinical stage of AD is necessary to define an optimal therapeutic success window. We review the justification for conducting trials in the preclinical stage and highlight novel ethical challenges that arise and are related to determining appropriate risk-benefit ratios and disclosing individuals’ biomarker status. We propose that to conduct clinical trials with these participants, we need to improve public understanding of AD using unified vocabulary, resolve the acceptable risk-benefit ratio in asymptomatic participants and disclose or not biomarker status with attention to study type (observational studies versus clinical trials). Overcoming these challenges will justify clinical trials in preclinical AD at the societal level and aid to the development of societal and legal support for trial participants. PMID:26988427

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.

The effect of the European Clinical Trials Directive on published drug research in anaesthesia.

PubMed

Walker, E; Hankins, M C; White, S M

2009-09-01

The clinical indications for anaesthetic drugs are developed through peer-reviewed publication of clinical trials. We performed a bibliometric analysis of all human research papers reported in nine general anaesthesia journals over 6 years (n = 6489), to determine any effects of the 2004 European Clinical Trials Directive on reported drug research in anaesthesia originating from Europe and the United Kingdom. We found 89% studies involved patients and 11% volunteers. Of 3234 (50%) drug studies, 96% were phase IV (post-marketing) trials. Worldwide, the number of research papers fell by 3.6% (p < 0.004) in the 3 years following introduction of the European Clinical Trials Directive (5% Europe, 18% United Kingdom), and drug research papers fell by 12% (p < 0.001; 15% Europe, 29% United Kingdom). The introduction of the Clinical Trials Directive has therefore coincided with a decline in European drug research, particularly that originating from the United Kingdom. We suggest a number of measures researchers could take in response, and we propose a simplification of the application process for phase IV clinical trials, emphasising patient risk assessment.

Reporting of harms outcomes: a comparison of journal publications with unpublished clinical study reports of orlistat trials.

PubMed

Hodkinson, Alex; Gamble, Carrol; Smith, Catrin Tudur

2016-04-22

The quality of harms reporting in journal publications is often poor, which can impede the risk-benefit interpretation of a clinical trial. Clinical study reports can provide more reliable, complete, and informative data on harms compared to the corresponding journal publication. This case study compares the quality and quantity of harms data reported in journal publications and clinical study reports of orlistat trials. Publications related to clinical trials of orlistat were identified through comprehensive literature searches. A request was made to Roche (Genentech; South San Francisco, CA, USA) for clinical study reports related to the orlistat trials identified in our search. We compared adverse events, serious adverse events, and the reporting of 15 harms criteria in both document types and compared meta-analytic results using data from the clinical study reports against the journal publications. Five journal publications with matching clinical study reports were available for five independent clinical trials. Journal publications did not always report the complete list of identified adverse events and serious adverse events. We found some differences in the magnitude of the pooled risk difference between both document types with a statistically significant risk difference for three adverse events and two serious adverse events using data reported in the clinical study reports; these events were of mild intensity and unrelated to the orlistat. The CONSORT harms reporting criteria were often satisfied in the methods section of the clinical study reports (70-90 % of the methods section criteria satisfied in the clinical study reports compared to 10-50 % in the journal publications), but both document types satisfied 80-100 % of the results section criteria, albeit with greater detail being provided in the clinical study reports. In this case study, journal publications provided insufficient information on harms outcomes of clinical trials and did not specify that a subset of harms data were being presented. Clinical study reports often present data on harms, including serious adverse events, which are not reported or mentioned in the journal publications. Therefore, clinical study reports could support a more complete, accurate, and reliable investigation, and researchers undertaking evidence synthesis of harm outcomes should not rely only on incomplete published data that are presented in the journal publications.

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

PubMed Central

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

2018-01-01

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

Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study

PubMed Central

Carter, Rickey E; Sonne, Susan C; Brady, Kathleen T

2005-01-01

Background Adequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated. Methods This report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development. Results Incorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trial's planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period. Conclusion The accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial. PMID:15796782

Participant verification: prevention of co-enrolment in clinical trials in South Africa.

PubMed

Harichund, C; Haripersad, K; Ramjee, R

2013-05-15

As KwaZulu-Natal Province is the epicentre of the HIV epidemic in both South Africa (SA) and globally, it is an ideal location to conduct HIV prevention and therapeutic trials. Numerous prevention trials are currently being conducted here; the potential for participant co-enrolment may compromise the validity of these studies and is therefore of great concern. To report the development and feasibility of a digital, fingerprint-based participant identification method to prevent co-enrolment at multiple clinical trial sites. The Medical Research Council (MRC) HIV Prevention Research Unit (HPRU) developed the Biometric Co-enrolment Prevention System (BCEPS), which uses fingerprint-based biometric technology to identify participants. A trial website was used to determine the robustness and usability of the system. After successful testing, the BCEPS was piloted in July 2010 across 7 HPRU clinical research sites. The BCEPS was pre-loaded with study names and clinical trial sites, with new participant information loaded at first visit to a trial site. We successfully implemented the BCEPS at the 7 HPRU sites. Using the BCEPS, we performed real-time 'flagging' of women who were already enrolled in another study as they entered a trial at an HPRU site and, where necessary, excluded them from participation on site. This system has promise in reducing co-enrolment in clinical trials and represents a valuable tool for future implementation by all groups conducting trials. The MRC is currently co-ordinating this effort with clinical trial sites nationally.

Perceptions of cancer clinical research among African American men in North Carolina

PubMed Central

Trantham, Laurel C.; Carpenter, William R; DiMartino, Lisa D.; White, Brandolyn; Green, Melissa; Teal, Randall; Corbie-Smith, Giselle; Godley, Paul A.

2015-01-01

Objective The problem of cancer health disparities is substantial. Clinical trials are widely advocated as a means of reducing disparities and bringing state-of-the-art care to the broader community, where most cancer care is delivered. This study sought to develop a better understanding of why disproportionately few African American men enroll in clinical trials given their substantial cancer burden. Design This study applied community-based participatory research (CBPR) methods to design and conduct four focus groups of African American male cancer survivors and their caregivers in North Carolina. Results Among major themes, participants expressed confusion about the relationship between clinical trials, treatment, and research, signifying patient confusion and misinterpretation of common clinical trial terminology. Social norms including gender barriers and generational differences remain problematic; participants often reported that men do not talk about health issues, are unwilling to go to the doctor, and exhibit misapprehension and distrust regarding trials. Participants perceived this as detrimental to community health and expressed the need for more clarity in clinical trials information and a more fundamental social openness and communication about cancer detection and treatment. Conclusion Findings indicate the importance of clinical trials education in both traditional provider referral to trials and also in general patient navigation. To dispel pervasive misapprehension regarding placebos, clinical trials information should emphasize the role of standard care in modern cancer treatment trials. Many participants described willingness to participate in a trial upon physician recommendation, suggesting merit in improving patient-physician communication through culturally competent terminology and trial referral systems. PMID:26113749

Consent for participating in clinical trials - Is it really informed?

PubMed

Alexa-Stratulat, Teodora; Neagu, Marius; Neagu, Anca-Iulia; Alexa, Ioana Dana; Ioan, Beatrice Gabriela

2018-06-22

The article explores the challenges of ensuring voluntary and informed consent which is obtained from potential research subjects in the north-eastern part of Romania. This study is one of the first empirical papers of this nature in Romania. The study used a quantitative survey design using the adapted Quality of Informed Consent (QuIC) questionnaire. The target population consisted of 100 adult persons who voluntarily enrolled in clinical trials. The informed consent form must contain details regarding the potential risks and benefits, the aim of the clinical trial, study design, confidentiality, insurance and contact details in case of additional questions. Our study confirmed that although all required information was included in the ICF, few clinical trial participants truly understood it. We also found that the most important predictive factor for a good subjective and objective understanding of the clinical trial was the level of education. Our study suggests that researchers should consider putting more effort in order to help clinical trials participants achieve a better understanding of the informed consent. In this way they will ensure that participants' decision-making is meaningful and that their interests are protected. © 2018 John Wiley & Sons Ltd.

Development of Pain Endpoint Models for Use in Prostate Cancer Clinical Trials and Drug Approval

DTIC Science & Technology

2016-10-01

consensus meeting, with input from investigators in the Prostate Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study...Cancer Clinical Trials Consortium, FDA Office of Oncology Drug Products, FDA Study Endpoint and Label Development Team, and FDA Division of...Abstract. American Society of Clinical Oncology . Chicago IL, June 1-5, 2013. INVENTIONS, PATENTS AND LICENSES None 11 REPORTABLE OUTCOMES

Early termination of cardiovascular trials as a consequence of poor accrual: analysis of ClinicalTrials.gov 2006-2015.

PubMed

Baldi, Ileana; Lanera, Corrado; Berchialla, Paola; Gregori, Dario

2017-06-15

To present a snapshot of experimental cardiovascular research with a focus on geographical and temporal patterns of early termination due to poor accrual. The Aggregate Analysis of ClinicalTrials.gov (AACT) database, reflecting ClinicalTrials.gov as of 27 March 2016. The AACT database was searched for all cardiovascular clinical trials that started from January 2006 up to December 2015. Thirteen thousand and seven hundred twenty-nine cardiovascular trials were identified. Of these, 8900 (65%) were classified as closed studies. Globally, 11% of closed trials were terminated. This proportion varied from 9.6% to 14% for trials recruiting from Europe and Americas, respectively, with a slightly decreasing trend (p=0.02) over the study period. The most common reason for trials failing to complete was poor accrual (41%). Intercontinental trials exhibited lower figures of poor accrual as the reason for their early stopping, as compared with trials recruiting in a single continent (28% vs 44%, p=0.002). Poor accrual significantly challenges the successful completion of cardiovascular clinical trials. Findings are suggestive of a positive effect of globalisation of cardiovascular clinical research on the achievement of enrolment goals within a reasonable time frame. © 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.

Insufficient recruitment and premature discontinuation of clinical trials in Switzerland: qualitative study with trialists and other stakeholders.

PubMed

Briel, Matthias; Elger, Bernice; von Elm, Erik; Satalkar, Priya

2017-11-29

Premature discontinuation occurs in about 25% of randomised clinical trials in Switzerland; it mainly affects investigator-initiated trials and is mostly due to problems with recruitment of patients. The aim of this study was to qualitatively investigate reasons for trial discontinuation due to poor patient recruitment and suggestions to address those reasons in the Swiss context. We conducted semi-structured interviews with trialists whose trials were discontinued because of recruitment problems, other experienced trialists, and stakeholders in clinical research in Switzerland. Interviews were audio-recorded, transcribed verbatim, and anonymised. We analysed the transcripts using deductive coding and built up themes that were continuously discussed within the research team. Of 65 invited Swiss trialists and stakeholders, 39 (60%) agreed to be interviewed and contributed to this analysis. We identified four main themes of reasons for poor recruitment: (1) Switzerland has a decentralised healthcare system with many small hospitals and few patients per hospital, many research regulations, no standardisation of medical records across hospitals, and a heterogeneous ethics assessment of study protocols. There is little collaboration of different stakeholders in clinical research and a lack of prioritisation of projects. (2) Limited human and financial resources, especially in the academic setting, compromise research questions and size of clinical trials. When funding is used up this typically triggers discontinuation of already delayed clinical trials. (3) Investigators face underdeveloped research networks and a limited collaborative attitude among clinical researchers. They typically embark on clinical studies with a great deal of optimism but insufficient preparation. (4) Swiss patients have universal health coverage and many treatment options. Negative media coverage of clinical research and a lack of accessible information for patients about ongoing clinical studies frequently make participation in clinical trials less attractive. More interactive structures and collaboration across stakeholders were mentioned as potential solutions to tackle the problems. Recruitment of participants into clinical trials in Switzerland is challenging because of various, often interlinked factors related to the Swiss health system, available funding, investigators, and patients. Common goals and concerted efforts by involved stakeholders appear necessary to achieve improvement.

Comparison of reporting phase III randomized controlled trials of antibiotic treatment for common bacterial infections in ClinicalTrials.gov and matched publications.

PubMed

Shepshelovich, D; Yelin, D; Gafter-Gvili, A; Goldman, S; Avni, T; Yahav, D

2018-02-15

Discrepancies between ClinicalTrials.gov entries and matching publications were previously described in general medicine. We aimed to evaluate the consistency of reporting in trials addressing systemic antibiotic therapy. We searched ClinicalTrials.gov for completed phase III trials comparing antibiotic regimens until May 2017. Matched publications were identified in PubMed. Two independent reviewers extracted data and identified inconsistencies. Reporting was assessed among studies started before and after 1 July 2005, when the International Committee of Medical Journal Editors (ICMJE) required mandatory registration as a prerequisite for considering a trial for publication. Matching publications were identified for 75 (70%) of 107 ClinicalTrials.gov entries. Median time from study completion to publication was 26 months (interquartile range 19-42). Primary outcome definition was inconsistent between ClinicalTrials.gov and publications in seven trials (7/72, 10%) and reporting of the primary outcome timeframe was inconsistent in 14 (14/71, 20%). Secondary outcomes definitions were inconsistent in 36 trials (36/66, 55%). Reporting of inclusion criteria and study timeline were inconsistent in 17% (13/65) and 3% (2/65), respectively. Trials started after July 2005 were significantly less likely to have reporting inconsistencies and were published in higher impact factor journals. We found a lower inconsistency rate of outcome reporting compared with other medical disciplines. Reporting completeness and consistency were significantly better after July 2005. The ICMJE requirement for mandatory registration was associated with significant improvement in reporting quality in infectious diseases trials. Prolonged time lag to publication and missing data from unpublished trials should raise a discussion on current reporting and publishing procedures. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

A prospective analysis of the influence of older age on physician and patient decision-making when considering enrollment in breast cancer clinical trials (SWOG S0316).

PubMed

Javid, Sara H; Unger, Joseph M; Gralow, Julie R; Moinpour, Carol M; Wozniak, Antoinette J; Goodwin, J Wendall; Lara, Primo N; Williams, Pamela A; Hutchins, Laura F; Gotay, Carolyn C; Albain, Kathy S

2012-01-01

Patients older than 65 years are underrepresented in clinical trials. We conducted a prospective study (SWOG S0316) to determine physician- and patient-perceived barriers to breast cancer clinical trial enrollment for older patients. Eight geographically diverse SWOG institutions participated. The study assessed patients' and physicians' decisions to enroll in or decline clinical treatment trials, including demographics, trial availability, and eligibility. Patient and physician questionnaires elicited concerns related to treatment, medical status, age, family, and financial or transportation concerns. A total of 1,079 patients were registered and eligible and 909 (84%) returned for follow-up. The major reason for nonaccrual was either trial unavailability or ineligibility (60%). Older patients were less likely to be eligible for trials (65% for age ≥65 years vs. 78% for age <65 years). If eligible, trial participation rates did not differ significantly by age (34% for age ≥65 years vs. 40% for age <65 years). Patients ≥65 years more often were concerned about side effects, had friends opposed to participation, or believed that participation would not benefit other generations. When trials were available and patients were eligible, physicians discussed trial participation with 76% of patients <65 years versus 58% of patients ≥65 years of age. For patients ≥65 years, 11% of physicians indicated age as a reason they did not enroll a patient in a clinical trial. Trial unavailability or patient ineligibility were the major reasons for lack of enrollment in breast cancer clinical trials for patients of all ages in this prospective study. Older patients were less likely to be eligible for trials, but if eligible they participated at similar rates to younger patients.

Caffeine, Adenosine Receptors and Estrogen in Toxin Models of Parkinson’s Disease

DTIC Science & Technology

2008-10-30

these have advanced molecules to clinical studies.2,3 Thus, the NIH clinical trial registry lists over a dozen actively recruiting or completed trials ...into clinical trials ,4 and multiple other preclinical programs are apparently progressing (including publicly announced programs at Neurocrine5 and...unpublished results). Adenosine A2AR antagonists are currently in clinical trials for PD because of their symptom- improving abilities. The

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.

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

Evaluation of eligibility and recruitment in breast cancer clinical trials.

PubMed

Lemieux, Julie; Forget, Geneviève; Brochu, Olyvia; Provencher, Louise; Cantin, Guy; Desbiens, Christine; Doyle, Catherine; Poirier, Brigitte; Camden, Stéphanie; Durocher, Martin

2014-08-01

Objectives of the study were to measure recruitment rates in clinical trials and to identify patients, physicians or trials characteristics associated with higher recruitment rates. Among patients who had a clinical trial available for their cancer, 83.5% (345/413) met the eligibility criteria to at least one clinical trial. At least one trial was proposed to 33.1% (113/341) of the eligible patients and 19.7% (68/345) were recruited. Overall recruitment was 16.5% (68/413). In multivariate analyses, trial proposal and enrollment were lower for elderly patients and higher in high cancer stages. Trials from pharmaceutical industry had higher recruitment rates and trials testing hormonal therapy enrolled more patients. Breast cancer patients' accrual to a clinical trial could be improved by trying to systematically identify all eligible patients and propose a trial to those eligible and to whom the treatment is planned to be equivalent to the standard arm of the trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Patients' attitudes and preferences about participation and recruitment strategies in clinical trials.

PubMed

Sood, Amit; Prasad, Kavita; Chhatwani, Laveena; Shinozaki, Eri; Cha, Stephen S; Loehrer, Laura L; Wahner-Roedler, Dietlind L

2009-03-01

To assess attitudes of patients about participation in clinical trials. This is a self-report survey of 400 patients who underwent general medical evaluations between September and November 2006 at a tertiary care academic medical center in Rochester, MN. We measured knowledge of access to clinical trials, attitudes toward participation, recruitment preferences, and beliefs about research integrity. Of 485 consecutive patients, 400 (82%) completed the survey. Previous participation in clinical trials was reported by 112 patients (28%). Most were unaware of online information about clinical trials (330 [82%]), were satisfied with their current knowledge (233 [58%]), expected their treating physician to inform them about current trials (304 [76%]), and showed equal interest in participating in conventional or complementary intervention trials (174 [44%]). Of the 400 respondents, 321 (80%) found it appropriate to be contacted by mail and 253 (63%) by telephone regarding study participation. Most patients (364 [91%]) wanted to be informed about research findings or else would not participate in future clinical trials (272 [68%]). The most frequently expected compensation was free parking (234 [58%]). Most thought that their safety (373 [93%]) and privacy (376 [94%]) would be guarded. Patients are interested in participating in clinical trials but commonly lack adequate information. If patients received more information (through their treating physicians), enrollment might improve. This single-site study has limited generalizability. Future studies involving a diverse group of patients from a broader geographic distribution will help provide more definitive results.

Patients' Attitudes and Preferences About Participation and Recruitment Strategies in Clinical Trials

PubMed Central

Sood, Amit; Prasad, Kavita; Chhatwani, Laveena; Shinozaki, Eri; Cha, Stephen S.; Loehrer, Laura L.; Wahner-Roedler, Dietlind L.

2009-01-01

OBJECTIVE: To assess attitudes of patients about participation in clinical trials. PATIENTS AND METHODS: This is a self-report survey of 400 patients who underwent general medical evaluations between September and November 2006 at a tertiary care academic medical center in Rochester, MN. We measured knowledge of access to clinical trials, attitudes toward participation, recruitment preferences, and beliefs about research integrity. RESULTS: Of 485 consecutive patients, 400 (82%) completed the survey. Previous participation in clinical trials was reported by 112 patients (28%). Most were unaware of online information about clinical trials (330 [82%]), were satisfied with their current knowledge (233 [58%]), expected their treating physician to inform them about current trials (304 [76%]), and showed equal interest in participating in conventional or complementary intervention trials (174 [44%]). Of the 400 respondents, 321 (80%) found it appropriate to be contacted by mail and 253 (63%) by telephone regarding study participation. Most patients (364 [91%]) wanted to be informed about research findings or else would not participate in future clinical trials (272 [68%]). The most frequently expected compensation was free parking (234 [58%]). Most thought that their safety (373 [93%]) and privacy (376 [94%]) would be guarded. CONCLUSION: Patients are interested in participating in clinical trials but commonly lack adequate information. If patients received more information (through their treating physicians), enrollment might improve. This single-site study has limited generalizability. Future studies involving a diverse group of patients from a broader geographic distribution will help provide more definitive results. PMID:19252111

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

METHODOLOGICAL QUALITY OF ECONOMIC EVALUATIONS ALONGSIDE TRIALS OF KNEE PHYSIOTHERAPY.

PubMed

García-Pérez, Lidia; Linertová, Renata; Arvelo-Martín, Alejandro; Guerra-Marrero, Carolina; Martínez-Alberto, Carlos Enrique; Cuéllar-Pompa, Leticia; Escobar, Antonio; Serrano-Aguilar, Pedro

2017-01-01

The methodological quality of an economic evaluation performed alongside a clinical trial can be underestimated if the paper does not report key methodological features. This study discusses methodological assessment issues on the example of a systematic review on cost-effectiveness of physiotherapy for knee osteoarthritis. Six economic evaluation studies included in the systematic review and related clinical trials were assessed using the 10-question check-list by Drummond and the Physiotherapy Evidence Database (PEDro) scale. All economic evaluations were performed alongside a clinical trial but the studied interventions were too heterogeneous to be synthesized. Methodological quality of the economic evaluations reported in the papers was not free of drawbacks, and in some cases, it improved when information from the related clinical trial was taken into account. Economic evaluation papers dedicate little space to methodological features of related clinical trials; therefore, the methodological quality can be underestimated if evaluated separately from the trials. Future economic evaluations should follow more strictly the recommendations about methodology and the authors should pay special attention to the quality of reporting.

Systematic Reviews Published in Emergency Medicine Journals Do Not Routinely Search Clinical Trials Registries: A Cross-Sectional Analysis.

PubMed

Keil, Lukas G; Platts-Mills, Timothy F; Jones, Christopher W

2015-10-01

Publication bias compromises the validity of systematic reviews. This problem can be addressed in part through searching clinical trials registries to identify unpublished studies. This study aims to determine how often systematic reviews published in emergency medicine journals include clinical trials registry searches. We identified all systematic reviews published in the 6 highest-impact emergency medicine journals between January 1 and December 31, 2013. Systematic reviews that assessed the effects of an intervention were further examined to determine whether the authors described searching a clinical trials registry and whether this search identified relevant unpublished studies. Of 191 articles identified through PubMed search, 80 were confirmed to be systematic reviews. Our sample consisted of 41 systematic reviews that assessed a specific intervention. Eight of these 41 (20%) searched a clinical trials registry. For 4 of these 8 reviews, the registry search identified at least 1 relevant unpublished study. Systematic reviews published in emergency medicine journals do not routinely include searches of clinical trials registries. By helping authors identify unpublished trial data, the addition of registry searches may improve the validity of systematic reviews. Copyright © 2014 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

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

Phase 3 Oncology Clinical Trials in South Africa: Experimentation or Therapeutic Misconception?

PubMed

Malan, Tina; Moodley, Keymanthri

2016-02-01

Although clinical research in oncology is vital to improve current understanding of cancer and to validate new treatment options, voluntary informed consent is a critical component. Oncology research participants are a particularly vulnerable population; hence, therapeutic misconception often leads to ethical and legal challenges. We conducted a qualitative study administering semi-structured questionnaires on 29 adult, Phase 3, oncology clinical trial participants at three different private oncology clinical trial sites in South Africa. A descriptive content analysis was performed to identify perceptions of these participants regarding Phase 3 clinical trials. We found that most participants provided consent to be included in the trial for self-benefit. More than half of the participants had a poor understanding of Phase 3 clinical trials, and almost half the participants believed the clinical trial did not pose any significant risk to them. The word "hope" was used frequently by participants, displaying clear optimism with regard to the clinical trial and its outcome. This indicated that therapeutic misconception does occur in the South African oncology research setting and has the potential to lead to underestimation of the risks of a Phase 3 clinical trial. Emphasizing the experimental nature of a clinical trial during the consent process is critical to address therapeutic misconception in oncology research. © The Author(s) 2016.

Utilization of a Clinical Trial Management System for the Whole Clinical Trial Process as an Integrated Database: System Development.

PubMed

Park, Yu Rang; Yoon, Young Jo; Koo, HaYeong; Yoo, Soyoung; Choi, Chang-Min; Beck, Sung-Ho; Kim, Tae Won

2018-04-24

Clinical trials pose potential risks in both communications and management due to the various stakeholders involved when performing clinical trials. The academic medical center has a responsibility and obligation to conduct and manage clinical trials while maintaining a sufficiently high level of quality, therefore it is necessary to build an information technology system to support standardized clinical trial processes and comply with relevant regulations. The objective of the study was to address the challenges identified while performing clinical trials at an academic medical center, Asan Medical Center (AMC) in Korea, by developing and utilizing a clinical trial management system (CTMS) that complies with standardized processes from multiple departments or units, controlled vocabularies, security, and privacy regulations. This study describes the methods, considerations, and recommendations for the development and utilization of the CTMS as a consolidated research database in an academic medical center. A task force was formed to define and standardize the clinical trial performance process at the site level. On the basis of the agreed standardized process, the CTMS was designed and developed as an all-in-one system complying with privacy and security regulations. In this study, the processes and standard mapped vocabularies of a clinical trial were established at the academic medical center. On the basis of these processes and vocabularies, a CTMS was built which interfaces with the existing trial systems such as the electronic institutional review board health information system, enterprise resource planning, and the barcode system. To protect patient data, the CTMS implements data governance and access rules, and excludes 21 personal health identifiers according to the Health Insurance Portability and Accountability Act (HIPAA) privacy rule and Korean privacy laws. Since December 2014, the CTMS has been successfully implemented and used by 881 internal and external users for managing 11,645 studies and 146,943 subjects. The CTMS was introduced in the Asan Medical Center to manage the large amounts of data involved with clinical trial operations. Inter- and intraunit control of data and resources can be easily conducted through the CTMS system. To our knowledge, this is the first CTMS developed in-house at an academic medical center side which can enhance the efficiency of clinical trial management in compliance with privacy and security laws. ©Yu Rang Park, Young Jo Yoon, HaYeong Koo, Soyoung Yoo, Chang-Min Choi, Sung-Ho Beck, Tae Won Kim. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.04.2018.

Motivation for health information seeking and processing about clinical trial enrollment.

PubMed

Yang, Z Janet; McComas, Katherine; Gay, Geri; Leonard, John P; Dannenberg, Andrew J; Dillon, Hildy

2010-07-01

Low patient accrual in clinical trials poses serious concerns for the advancement of medical science in the United States. Past research has identified health communication as a crucial step in overcoming barriers to enrollment. However, few communication scholars have studied this problem from a sociopsychological perspective to understand what motivates people to look for or pay attention to information about clinical trial enrollment. This study applies the model of Risk Information Seeking and Processing (RISP) to this context of health decision making. By recognizing the uncertainties embedded in clinical trials, we view clinical trial enrollment as a case study of risk. With data from a random-digit-dial telephone survey of 500 adults living in the United States, we used structural equation modeling to test the central part of the RISP model. In particular, we examined the role of optimistic feelings, as a type of positive affect, in motivating information seeking and processing. Our results indicated that rather than exerting an indirect influence on information seeking through motivating a psychological need for more information, optimistic feelings have more direct relationships with information seeking and processing. Similarly, informational subjective norms also exhibit a more direct relationship with information seeking and processing. These results suggest merit in applying the RISP model to study health decision making related to clinical trial enrollment. Our findings also render practical implications on how to improve communication about clinical trial enrollment.

Ticagrelor for the treatment of atherosclerotic disease: insights from the PARTHENON clinical development program.

PubMed

Held, Peter; Himmelmann, Anders; Ditmarsch, Marc

2016-07-01

Ticagrelor (P2Y12 receptor antagonist) is presently indicated for preventing atherothrombotic events in patients with acute coronary syndrome and patients with a history of myocardial infarction. The PARTHENON clinical development program comprises five randomized, controlled, cardiovascular, indication-seeking outcome studies, aiming to evaluate ticagrelor across the spectrum of patients with atherothrombotic disease. Results of two large-scale trials support a benefit for ticagrelor in patients with acute coronary syndrome (PLATO; ClinicalTrials.gov: NCT00391872) and in patients with a history of myocardial infarction (PEGASUS-TIMI 54; ClinicalTrials.gov: NCT01225562). Ongoing trials will provide information on the efficacy and safety of ticagrelor in patients with acute ischemic stroke or transient ischemic attack (SOCRATES; ClinicalTrials.gov: NCT01994720), peripheral artery disease (EUCLID; ClinicalTrials.gov: NCT01732822) and coronary artery disease in patients with Type 2 diabetes mellitus (THEMIS: ClinicalTrials.gov: NCT01991795).

Changes in clinical trials methodology over time: a systematic review of six decades of research in psychopharmacology.

PubMed

Brunoni, André R; Tadini, Laura; Fregni, Felipe

2010-03-03

There have been many changes in clinical trials methodology since the introduction of lithium and the beginning of the modern era of psychopharmacology in 1949. The nature and importance of these changes have not been fully addressed to date. As methodological flaws in trials can lead to false-negative or false-positive results, the objective of our study was to evaluate the impact of methodological changes in psychopharmacology clinical research over the past 60 years. We performed a systematic review from 1949 to 2009 on MEDLINE and Web of Science electronic databases, and a hand search of high impact journals on studies of seven major drugs (chlorpromazine, clozapine, risperidone, lithium, fluoxetine and lamotrigine). All controlled studies published 100 months after the first trial were included. Ninety-one studies met our inclusion criteria. We analyzed the major changes in abstract reporting, study design, participants' assessment and enrollment, methodology and statistical analysis. Our results showed that the methodology of psychiatric clinical trials changed substantially, with quality gains in abstract reporting, results reporting, and statistical methodology. Recent trials use more informed consent, periods of washout, intention-to-treat approach and parametric tests. Placebo use remains high and unchanged over time. Clinical trial quality of psychopharmacological studies has changed significantly in most of the aspects we analyzed. There was significant improvement in quality reporting and internal validity. These changes have increased study efficiency; however, there is room for improvement in some aspects such as rating scales, diagnostic criteria and better trial reporting. Therefore, despite the advancements observed, there are still several areas that can be improved in psychopharmacology clinical trials.

Clinical trial allocation in multinational pharmaceutical companies - a qualitative study on influential factors.

PubMed

Dombernowsky, Tilde; Haedersdal, Merete; Lassen, Ulrik; Thomsen, Simon F

2017-06-01

Clinical trial allocation in multinational pharmaceutical companies includes country selection and site selection. With emphasis on site selection, the overall aim of this study was to examine which factors pharmaceutical companies value most when allocating clinical trials. The specific aims were (1) to identify key decision makers during country and site selection, respectively, (2) to evaluate by which parameters subsidiaries are primarily assessed by headquarters with regard to conducting clinical trials, and (3) to evaluate which site-related qualities companies value most when selecting trial sites. Eleven semistructured interviews were conducted among employees engaged in trial allocation at 11 pharmaceutical companies. The interviews were analyzed by deductive content analysis, which included coding of data to a categorization matrix containing categories of site-related qualities. The results suggest that headquarters and regional departments are key decision makers during country selection, whereas subsidiaries decide on site selection. Study participants argued that headquarters primarily value timely patient recruitment and quality of data when assessing subsidiaries. The site-related qualities most commonly emphasized during interviews were study population availability, timely patient recruitment, resources at the site, and site personnel's interest and commitment. Costs of running the trials were described as less important. Site personnel experience in conducting trials was described as valuable but not imperative. In conclusion, multinational pharmaceutical companies consider recruitment-related factors as crucial when allocating clinical trials. Quality of data and site personnel's interest and commitment are also essential, whereas costs seem less important. While valued, site personnel experience in conducting clinical trials is not imperative.

Randomized controlled trials in mild cognitive impairment

PubMed Central

Thomas, Ronald G.; Aisen, Paul S.; Mohs, Richard C.; Carrillo, Maria C.; Albert, Marilyn S.

2017-01-01

Objective: To examine the variability in performance among placebo groups in randomized controlled trials for mild cognitive impairment (MCI). Methods: Placebo group data were obtained from 2 National Institute on Aging (NIA) MCI randomized controlled trials, the Alzheimer's Disease Cooperative Study (ADCS) MCI trial and the Alzheimer's Disease Neuroimaging Initiative (ADNI), which is a simulated clinical trial, in addition to industry-sponsored clinical trials involving rivastigmine, galantamine, rofecoxib, and donepezil. The data were collated for common measurement instruments. The performance of the placebo participants from these studies was tracked on the Alzheimer's Disease Assessment Scale–cognitive subscale, Mini-Mental State Examination, and Clinical Dementia Rating–sum of boxes, and for progression on these measures to prespecified clinical study endpoints. APOE status, where available, was also analyzed for its effects. Results: The progression to clinical endpoints varied a great deal among the trials. The expected performances were seen for the participants in the 2 NIA trials, ADCS and ADNI, with generally worsening of performance over time; however, the industry-sponsored trials largely showed stable or improved performance in their placebo participants. APOE4 carrier status influenced results in an expected fashion on the study outcomes, including rates of progression and cognitive subscales. Conclusions: In spite of apparently similar criteria for MCI being adopted by the 7 studies, the implementation of the criteria varied a great deal. Several explanations including instruments used to characterize participants and variability among study populations contributed to the findings. PMID:28381516

[Design requirements for clinical trials on re-evaluation of safety and efficacy of post-marketed Chinese herbs].

PubMed

Xie, Yanming; Wei, Xu

2011-10-01

Re-evaluation of post-marketed based on pharmacoepidemiology is to study and collect clinical medicine safety in large population under practical applications for a long time. It is necessary to conduct re-evaluation of clinical effectiveness because of particularity of traditional Chinese medicine (TCM). Right before carrying out clinical trials on re-evaluation of post-marketed TCM, we should determine the objective of the study and progress it in the assessment mode of combination of disease and syndrome. Specical population, involving children and seniors who were excluded in pre-marketed clinical trial, were brought into drug monitoring. Sample size needs to comply with statistical requirement. We commonly use cohort study, case-control study, nested case-control, pragmatic randomized controlled trials.

Use of ClinicalTrials.gov to estimate condition-specific nocebo effects and other factors affecting outcomes of analgesic trials.

PubMed

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

2013-04-01

ClinicalTrials.gov is a registry and results database of federally and privately supported clinical trials conducted worldwide. We sought to answer: what are the characteristics of pain trials; how frequently are these trials stopped and why; what is the magnitude of attrition due to lack of efficacy or adverse events; and whether the withdrawal rates depend on pain syndrome. To facilitate this and subsequent studies, we have developed a system called Sherlock that automatically downloads data from ClinicalTrials.gov into a relational database. We included pain interventional trials. To evaluate attrition, we restricted consideration to prospective randomized, parallel, double-blind, placebo-controlled trials. Of the 82,867 trials, 6% reported results and 5.6% terminated before the planned number of subjects was accrued. Of these early terminations, 38% were due to enrollment difficulties. In the placebo arms, 3.8% of participants withdrew due to lack of efficacy and 4.9% due to adverse events, with proportions differing among pain conditions. Compared with migraine trials, in fibromyalgia trials 5.1% more participants withdrew due to lack of efficacy (95% confidence interval [CI], 2.5-7.8%), and 6.4% more withdrew due to adverse events (95% CI, 4.3-8.6%). Nonsteroidal anti-inflammatory drugs were the treatment class with the lowest adverse events withdrawals. Recruitment challenges account for the largest proportion of noncompleted trials. Attrition rates differ across pain conditions. Migraine studies had the lowest withdrawal rate. Tools like Sherlock facilitate conducting research in the ClinicalTrials.gov registry. ClinicalTrials.gov registry enables researchers to get a snapshot of a specific field and observe changes over time in trial design, including numbers of subjects accrued, and it can inform clinical trial design. We learned that recruitment challenges account for the largest proportion of noncompleted trials, attrition rates differed across pain conditions, and migraine studies had the lowest withdrawal rate. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

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.

Review of ongoing clinical trials in non-small-cell lung cancer: a status report for 2012 from the ClinicalTrials.gov Web site.

PubMed

Subramanian, Janakiraman; Regenbogen, Thomas; Nagaraj, Gayathri; Lane, Alex; Devarakonda, Siddhartha; Zhou, Gongfu; Govindan, Ramaswamy

2013-07-01

Clinical research in non-small-cell lung cancer (NSCLC) is a rapidly evolving field. In an effort to identify the current trends in lung cancer clinical research, we reviewed ongoing clinical trials in NSCLC listed in the ClinicalTrials.gov registry in 2012, and we also compared this data to a similar survey conducted by us in 2009. The Web site's advanced search function was used to search for the term "non-small cell lung cancer." The search was further refined by using the following options from the search page drop-down menu, "open studies" and "interventional." Studies with non-NSCLC tumor histologies and pediatric studies were excluded. Of the 477 trials included in the analysis, 105 (22.0%) were phase I, 223 phase II (46.8%), and 63 phase III trials (13.2%). When compared with data from 2009, university-sponsored trials decreased in number (45.4%-34.2%; p < 0.001) whereas industry-sponsored trials remained almost the same. There was a significant increase in trials conducted exclusively outside of the United States (35.9%-48.8%; p = 0.001). The number of studies with locations in China (61, 12.8%) was second only to that in the United States (244, 51.2%). Studies reporting biomarker analysis increased significantly from 37.5% to 49.1% in 2012 (p < 0.001). Biomarker-based patient selection also increased significantly from 7.9% to 25.8% (p < 0.001). Targeted therapies were evaluated in 70.6% of phase I/II and II trials, and the most common class of targeted agent studied was epidermal growth factor receptor tyrosine kinase inhibitors (38.0%). Prespecified accrual times were observed to increase when compared with data reported in 2009, especially among industry-sponsored studies. Our survey identified major changes in lung cancer clinical research since 2009. Almost half of all studies registered at the ClinicalTrials.gov Web site are being conducted outside the United States, and several novel molecularly targeted agents are being evaluated in the treatment of patients with NSCLC. More importantly, we identified a threefold increase in the number of studies that perform biomarker testing to determine patient selection over the last 3 years.

A call for more transparency of registered clinical trials on endometriosis

PubMed Central

Guo, Sun-Wei; Hummelshoj, Lone; Olive, David L.; Bulun, Serdar E.; D'Hooghe, Thomas M.; Evers, Johannes L.H.

2009-01-01

In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis. PMID:19264712

International Pediatric MS Study Group Clinical Trials Summit: meeting report.

PubMed

Chitnis, Tanuja; Tardieu, Marc; Amato, Maria Pia; Banwell, Brenda; Bar-Or, Amit; Ghezzi, Angelo; Kornberg, Andrew; Krupp, Lauren B; Pohl, Daniela; Rostasy, Kevin; Tenembaum, Silvia; Waubant, Emmanuelle; Wassmer, Evangeline

2013-03-19

Pediatric studies for new biological agents are mandated by recent legislation, necessitating careful thought to evaluation of emerging multiple sclerosis (MS) therapies in children with MS. Challenges include a small patient population, the lack of prior randomized clinical trials, and ethical concerns. The goal of this meeting was to assess areas of consensus regarding clinical trial design and outcome measures among academic experts involved in pediatric MS care and research. The Steering Committee of the International Pediatric MS Study Group identified key focus areas for discussion. A total of 69 meeting attendees were assembled, including 35 academic experts. Regulatory and pharmaceutical representatives also attended, and provided input, which informed academic expert consensus decisions. The academic experts agreed that clinical trials were necessary in pediatric MS to obtain pharmacokinetic, safety and efficacy data, and regulatory approval allowing for greater medication access. The academic experts agreed that relapse was an appropriate primary outcome measure for phase III pediatric trials. An international standardized cognitive battery was identified. The pros and cons of various trial designs were discussed. Guidelines surrounding MRI studies, pharmacokinetics, pharmacodynamics, and registries were developed. The academic experts agreed that given the limited subject pool, a stepwise approach to the launch of clinical trials for the most promising medications is necessary in order to ensure study completion. Alternative approaches could result in unethical exposure of patients to trial conditions without gaining knowledge. Consensus points for conduct of clinical trials in the rare disease pediatric MS were identified amongst a panel of academic experts, informed by regulatory and industry stakeholders.

Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy.

PubMed

Peay, Holly L; Tibben, Aad; Fisher, Tyler; Brenna, Ethan; Biesecker, Barbara B

2014-02-01

The social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders. We describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial. This qualitative study was based on interviews with clinical investigators and parents of sons with Duchenne and Becker muscular dystrophy (DBMD) who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis. Participants were 12 parents of affected boys receiving active drug and 9 clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents' expectations; several worried about their own involvement in increasing parents' expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents' expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for the possibility of trial termination. This was a retrospective study of one clinical trial. We were unable to recruit participants whose children received placebo. The interviews occurred during a time of significant uncertainty and distress for many of the participants. This pilot study reflects complex outcomes of strong community engagement. The findings highlight a need for renewed education about, and support for, clinical trial termination and loss of drug access. The primary positive outcome was demonstration of strong relationships among committed parents and study teams. These relationships were highly valued by both parties and may suggest an ideal intervention opportunity for efforts to improve psychological well-being. A negative outcome attributed, in part, to community engagement was inappropriately high trial expectations. More optimistically, high expectations were attributed, in part, to the importance of hope and powerful feelings associated with active efforts to affect the disease course.

Expectations and experiences of investigators and parents involved in a clinical trial for Duchenne/Becker muscular dystrophy

PubMed Central

Peay, Holly L; Tibben, Aad; Fisher, Tyler; Brenna, Ethan; Biesecker, Barbara B

2014-01-01

Background The social context of rare disease research is changing, with increased community engagement around drug development and clinical trials. This engagement may benefit patients and families, but may also lead to heightened trial expectations and therapeutic misconception. Clinical investigators are also susceptible to harboring high expectations. Little is known about parental motivations and expectations for clinical trials for rare pediatric disorders. Purpose We describe the experience of parents and clinical investigators involved in a phase II clinical trial for Duchenne and Becker muscular dystrophy: their expectations, hopes, motivations, and reactions to the termination of the trial. Methods This qualitative study was based on interviews with clinical investigators and parents of sons with DBMD who participated in the phase IIa or IIb ataluren clinical trial in the United States. Interviews were transcribed and coded for thematic analysis. Results Participants were twelve parents of affected boys receiving active drug and nine clinical investigators. High trial expectations of direct benefit were reported by parents and many clinicians. Investigators described monitoring and managing parents’ expectations; several worried about their own involvement in increasing parents’ expectations. Most parents were able to differentiate their expectations from their optimistic hopes for a cure. Parents’ expectations arose from other parents, advocacy organizations, and the sponsor. All parents reported some degree of clinical benefit to their children. Secondary benefits were hopefulness and powerful feelings associated with active efforts to affect the disease course. Parents and clinical investigators reported strong, close relationships that were mutually important. Parents and clinicians felt valued by the sponsor for the majority of the trial. When the trial abruptly stopped, they described loss of engagement, distress, and feeling unprepared for the possibility of trial termination. Limitations This was a retrospective study of one clinical trial. We were unable to recruit participants whose children received placebo. The interviews occurred during a time of significant uncertainty and distress for many of the participants. Conclusions This pilot study reflects complex outcomes of strong community engagement. The findings highlight a need for renewed education about, and support for, clinical trial termination and loss of drug access. The primary positive outcome was demonstration of strong relationships among committed parents and study teams. These relationships were highly valued by both parties, and may suggest an ideal intervention opportunity for efforts to improve psychological wellbeing. A negative outcome attributed, in part, to community engagement was inappropriately high trial expectations. More optimistically, high expectations were attributed, in part, to the importance of hope and powerful feelings associated with active efforts to affect the disease course. PMID:24311736

[Priorities of clinical drug trials in Brazil and neglected diseases of poverty].

PubMed

Santana, Rafael Santos; Leite, Silvana Nair

2016-11-01

To identify clinical drug trials performed in Brazil between 2012 and 2015, with emphasis on those focusing on neglected diseases of poverty. Two clinical trial registries, ReBEC (Brazilian registry) and ClinicalTrials.gov were surveyed. The following aspects were investigated: distribution of clinical trials in relation to the burden of disease in Brazil, distribution of trials regarding their focus on diseases of poverty vs. diseases not linked to poverty, phase of trials, performing institution, and type of funding (private, public, or mixed). The search revealed 866 eligible trials, 88 registered in ReBEC and 778 in ClinicalTrials.gov. Of these, 73 (8.5%) were phase I trials, 610 (70.5%) were phase II and III trials, and 183 (21%) were phase IV trials. There were 38 trials (4%) focusing on neglected diseases of poverty. Regarding the burden of disease, 734 (84.8%) trials focused on noncommunicable diseases, which in fact represent the largest burden of disease in Brazil. Most trials were carried out by pharmaceutical companies (55.3%), with predominance of private funding (57.1%); however, if only the diseases of poverty are considered, 63.1% were financed by public resources. The clinical drug trials carried out in Brazil in the study period are in agreement with the proportional burden of disease for the country. However, the neglected diseases of poverty were not prioritized. More effective action is necessary to redirect clinical research on drug development to meet national needs.

Women's Health and Complementary Approaches

MedlinePlus

... Information Center Ongoing Medical Studies Find Active Medical Research Studies on Cranberry (ClinicalTrials.gov) Find Active Medical Research Studies on Menopause (ClinicalTrials.gov) Safety Information Dream Body ...

Management of Acute Hypertensive Response in Intracerebral Hemorrhage Patients After ATACH-2 Trial.

PubMed

Majidi, Shahram; Suarez, Jose I; Qureshi, Adnan I

2017-10-01

Acute hypertensive response is elevation of systolic blood pressure (SBP) in the first 24 h after symptom onset which is highly prevalent in patients with intracerebral hemorrhage (ICH). Observational studies suggested association between acute hypertensive response and hematoma expansion, peri-hematoma edema and death and disability, and possible reduction in these adverse outcomes with treatment of acute hypertensive response. Recent clinical trials have focused on determining the clinical efficacy of early intensive SBP reduction in ICH patients. The Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-2) trial was the latest phase 3 randomized controlled multicenter clinical trial aimed to study the efficacy of early intensive reduction of SBP in ICH patients. In this review article, we summarize the results of recent clinical trials, treatment principles based on the latest guidelines, and the anticipated interpretation and incorporation of ATACH-2 trial results in clinical practice.

Understanding clinical development of chimeric antigen receptor T cell therapies.

PubMed

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2017-06-01

In the past decade, many clinical trials with gene- and cell-based therapies (GCTs) have been performed. Increased interest in the development of these drug products by various stakeholders has become apparent. Despite this growth in clinical studies, the number of therapies receiving marketing authorization approval (MAA) is lagging behind. To enhance the success rate of GCT development, it is essential to better understand the clinical development of these products. Chimeric antigen receptor (CAR) T cells are a GCT product subtype with promising efficacy in cancer treatment which are tested in many clinical trials, but have not yet received MAA. We generated an overview of the characteristics of CAR T-cell clinical development in the United States, Canada and Europe. Subsequently, the characteristics of clinical trials with CAR T-cell products that proceeded to a subsequent clinical trial, used as a proxy for success, were compared with those that did not proceed. From the U.S. and European Union clinical trial databases, 106 CAR T-cell trials were selected, from which 49 were linked to a subsequent trial and 57 were not. The majority of the trials had an academic sponsor from which most did not proceed, whereas most commercially sponsored trials were followed by another clinical trial. Furthermore, trials with a subsequent trial more frequently recruited large patient cohorts and were more often multicenter compared with trials that were not followed up. These characteristics can be used by investigators to better design clinical trials with CAR T cells. We encourage sponsors to plan clinical development ahead for a higher efficiency of product development and thereby achieving a higher success rate of development towards MAA. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

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 low quality and may not reflect what is in the protocol, thus limiting the detection of modifications between planned and published outcomes. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Embedding clinical interventions into observational studies.

PubMed

Newman, Anne B; Avilés-Santa, M Larissa; Anderson, Garnet; Heiss, Gerardo; Howard, Wm James; Krucoff, Mitchell; Kuller, Lewis H; Lewis, Cora E; Robinson, Jennifer G; Taylor, Herman; Treviño, Roberto P; Weintraub, William

2016-01-01

Novel approaches to observational studies and clinical trials could improve the cost-effectiveness and speed of translation of research. Hybrid designs that combine elements of clinical trials with observational registries or cohort studies should be considered as part of a long-term strategy to transform clinical trials and epidemiology, adapting to the opportunities of big data and the challenges of constrained budgets. Important considerations include study aims, timing, breadth and depth of the existing infrastructure that can be leveraged, participant burden, likely participation rate and available sample size in the cohort, required sample size for the trial, and investigator expertise. Community engagement and stakeholder (including study participants) support are essential for these efforts to succeed. Copyright © 2015. Published by Elsevier Inc.

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

PubMed Central

Stauder, Reinhard; van Munster, Barbara C.

2014-01-01

Introduction. Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. Methods. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Conclusion. Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. PMID:25170014

Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry.

PubMed

Hamaker, Marije E; Stauder, Reinhard; van Munster, Barbara C

2014-10-01

Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. ©AlphaMed Press.

Factors Contributing to Exacerbating Vulnerabilities in Global Clinical Trials

PubMed Central

da Silva, Ricardo E.; Amato, Angélica A.; Guilhem, Dirce B.; de Carvalho, Marta R.; Lima, Elisangela da C.; Novaes, Maria Rita C. G.

2018-01-01

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because vulnerability is not applicable to all risk situations. PMID:29403381

Factors Contributing to Exacerbating Vulnerabilities in Global Clinical Trials.

PubMed

da Silva, Ricardo E; Amato, Angélica A; Guilhem, Dirce B; de Carvalho, Marta R; Lima, Elisangela da C; Novaes, Maria Rita C G

2017-01-01

Background: Although policies and guidelines make use of the concept of vulnerability, few define it. The European Union's directive for clinical trials does not include explanations for or the reasoning behind the designation of certain groups as vulnerable. Emerging economies from lower middle-income countries have, in recent years, had the largest average annual growth rate, as well as increase, in number of clinical trials registered in the US government's database. Nevertheless, careful supervision of research activities has to be ensured. Objective: To describe and analyze the features of the clinical trials involving vulnerable populations in various countries classified by development status and geographic region. Methods: Retrospective study that involved analysis of data obtained from the International Clinical Trials Registry Platform (ICTRP) database between 01/2014 and 12/2014 from countries with (i) highest trial densities during 2005 to 2012, (ii) highest average growth rate in clinical trials, and (iii) greatest trial capabilities. Results: Statistical analysis of this study showed that patients incapable of giving consent personally are 11.4 times more likely to be vulnerable patients than patients who are capable, and that patients in upper-middle-income countries are 1.7 times more likely to be vulnerable patients than patients from high-income countries when participating in global clinical trials. Malaysia (21%), Egypt (20%), Turkey (19%), Israel (18%), and Brazil (17%) had the highest percentages of vulnerable populations involving children. Conclusions: Although the inability to provide consent personally was a factor associated with vulnerability, arbitrary criteria may have been considered when classifying the populations of clinical trials as vulnerable. The EU Clinical Trials Register should provide guidance regarding exactly what aspects or factors should be taken into account to frame given populations as vulnerable, because vulnerability is not applicable to all risk situations.

[Knowledge and willingness to participate in research: a descriptive study of volunteers in a clinical trial].

PubMed

Lobato, Lucas; Gazzinelli, Maria Flávia; Gazzinelli, Andréa; Soares, Amanda Nathale

2014-06-01

The aim of this study was to evaluate volunteers' knowledge of the information on the free informed consent form and their willingness to participate in a clinical trial. This was a quantitative, descriptive, cross-sectional study conducted in November 2011 with subjects from a clinical trial in Americaninhas, northeast Minas Gerais State, Brazil. A convenience sample included 143 adults of both sexes, 18 to 45 years of age. A structured questionnaire was applied one week after signing the free informed consent form. Most participants signed the free informed consent without sufficient knowledge of the research information and were influenced in their decision to participate in the trial. The authors conclude that signing the free informed consent form fails to express all participants' autonomy in clinical trials.

"I will miss the study, God bless you all": participation in a nutritional chemoprevention trial.

PubMed

Moreno-Black, Geraldine; Shor-Posner, Gail; Miguez, Maria-Jose; Burbano, Ximena; O'Mellan, Sandra; Yovanoff, P

2004-01-01

Randomized controlled clinical trials are often considered to be the "gold standard" for health research. Consequently, understanding the reasons people participate in these trials, especially minority groups who are often under-represented in clinical trials, or populations who have chronic illnesses or abuse drugs, is salient for successful recruitment, retention, and project design. This paper describes the results of a study that was designed to examine some of the ways in which participants in a randomized double blind clinical trial perceived their participation in the clinical trial, and the reasons they gave for continuing in the study. All of the participants were individuals who were using drugs and were infected with the HIV-1 virus, and had participated in a chemoprevention trial. The data from an exit interview were analyzed thematically in order to reveal units of meaning concerning participation and continuation in the clinical trial. The analysis revealed 3 higher-level concepts, or themes, that guided participation: increased health awareness, personal enhancement, and sociability. The data clearly indicated that involvement and retention in the trial were directly related to the ways in which the participants interpreted the study, perceived the benefits they derived from participating, and imbued their participation with value so that it was important and relevant to their own perceptions of health, as well as personal and social well being.

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.

Vitamins in Pancreatic Cancer: A Review of Underlying Mechanisms and Future Applications12

PubMed Central

Davis-Yadley, Ashley H; Malafa, Mokenge P

2015-01-01

Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. PMID:26567201

Vitamins in pancreatic cancer: a review of underlying mechanisms and future applications.

PubMed

Davis-Yadley, Ashley H; Malafa, Mokenge P

2015-11-01

Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. © 2015 American Society for Nutrition.

Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis.

PubMed

Wallach, Joshua D; Egilman, Alexander C; Dhruva, Sanket S; McCarthy, Margaret E; Miller, Jennifer E; Woloshin, Steven; Schwartz, Lisa M; Ross, Joseph S

2018-05-24

To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials. Cross sectional analysis. Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials. Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline. Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A Randomized Prospective Trial Comparing Paravertebral Block and General Anesthesia for Operative Treatment of Breast Cancer

DTIC Science & Technology

2001-10-01

block the anesthetic of choice for operative treatment of breast cancer. To test this hypothesis we proposed a prospective randomized clinical trial ...coordinators. Months 4-6. Status: Complete The study’s existing part-time Clinical Trial Coordinator, Mr. John Arbo, was enlisted full-time in June...of full-time Clinical Trial Coordinator for Mount Sinai. ■ Poster presentation by Mount Sinai staff of study goals and methods at a Department of

Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study

PubMed Central

Tompkins, Charlotte N. E.; McDonald, Rebecca; Strang, John

2018-01-01

Abstract Aim To explore potential study participants’ views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Design Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Settings Drug and alcohol services and a peer support recovery service (London, UK). Participants Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33–66 years). Measurements Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio‐recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Findings Participants’ willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers’ explanations. Conclusions Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. PMID:29356208

The clinical and financial impact of a pediatric surgical neuro-oncology clinical trial.

PubMed

Thompson, Eric M; Gururangan, Sridharan; Grant, Gerald; Mitchell, Duane; Sampson, John H

2017-03-01

Pediatric surgical trials are rare and the impact of such trials on the institutions in which they are conducted is unknown. The purpose of this study was to analyze the clinical and financial impact of The Re-MATCH trial, a Phase I clinical trial requiring the biopsy or resection of recurrent medulloblastoma or PNET for enrollment. Inpatient financial and clinical volume information was collected during the 3 years of trial enrollment and the years preceding and following it. The primary endpoints were the difference in direct contribution margin (DCM), or net gain, of study and non-study patients and the difference in surgical volume during the study and non-study periods. The trial enrolled 18 patients; 15 had surgery at the sponsor institution and three had surgery at their home institution, then transferred tumor material to the sponsor institution. There were no differences between the two groups for potentially confounding variables such as neurosurgical procedure work relative value units (P = 0.13) or insurance provider (P = 0.26). There was no difference between the inpatient DCM per case for the institution for non-study patients (mean ± SD, $9039 ± $28,549) and study patients ($14,332 ± $20,231) (P = 0.4819). During the non-study period, there were a mean of 2.78 ± 1.65 pediatric brain tumor resections per month compared to 3.34 ± 1.66 cases per month during the study period, a 17% increase. When the 15 study patients were excluded, there were 2.97 ± 1.64 cases per month, a 7% increase. However, this increase in total case volume including study and non-study patients was not significant (P = 0.121). Phase I investigator-initiated surgically-based clinical trials may increase institutional surgical volume without imposing a financial burden. Finances are unlikely to be a barrier for researchers negotiating for resources to conduct such trials.

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

PubMed

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

2017-10-01

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

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

Trust is the cornerstone of clinical trial recruitment and retention. Efforts to decrease barriers and increase clinical trial participation among diverse populations have yielded modest results. There is an urgent need to better understand the complex interactions between trust and clinical trial participation. The process of trust-building has been a focus of intense research in the business community. Yet, little has been published about trust in oncology clinical trials or the process of building trust in clinical trials. Both clinical trials and business share common dimensions. Business strategies for building trust may be transferable to the clinical trial setting. This study was conducted to understand and utilize contemporary thinking about building trust to develop an Integrated Model of Trust that incorporates both clinical and business perspectives. A key word-directed literature search of the PubMed, Medline, Cochrane, and Google Search databases for entries dated between 1 January 1985 and 1 September 2015 was conducted to obtain information from which to develop an Integrated Model of Trust. Successful trial participation requires both participants and clinical trial team members to build distinctly different types of interpersonal trust to effect recruitment and retention. They are built under conditions of significant emotional stress and time constraints among people who do not know each other and have never worked together before. Swift Trust and Traditional Trust are sequentially built during the clinical trial process. Swift trust operates during the recruitment and very early active treatment phases of the clinical trial process. Traditional trust is built over time and operates during the active treatment and surveillance stages of clinical trials. The Psychological Contract frames the participants' and clinical trial team members' interpersonal trust relationship. The "terms" of interpersonal trust are negotiated through the psychological 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.

[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 responsibilities in clinical practice.

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

PubMed

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

2013-09-01

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

A Qualitative Study of Motivations for Minority Recruitment in Cancer Clinical Trials Across Five NCI-Designated Cancer Centers.

PubMed

Simoni, Zachary R; Martin, Michelle; Wenzel, Jennifer A; Cook, Elise D; Konety, Badrinath; Vickers, Selwyn M; Chen, Moon S; Foaud, Mona N; Durant, Raegan W

2016-11-08

Minority enrollment in cancer clinical trials is traditionally low. In light of this fact, numerous studies have investigated barriers to recruitment and retention within minority populations. However, very little research has investigated the importance of clinicians' and researchers' motivations for minority recruitment in cancer clinical trials. Therefore, we sought to examine motivations for minority recruitment across four professional stakeholder groups (principal investigators, clinicians, research staff, and Cancer Center leaders) at five National Cancer Institute (NCI)-designated Comprehensive Cancer Centers. This study is based on the data from 91 qualitative interviews conducted across the five NCI-designated Comprehensive Cancer Centers to investigate stakeholders' motivations for minority recruitment in cancer clinical trials. Emergent themes include (a) minority recruitment increases generalizability of cancer clinical trials, (b) minority recruitment is motivated by social justice, (c) some institutions promote minority recruitment through the use of supplemental financial support, (d) federal funding requirements for minority inclusion in clinical research motivate investigators to focus on minority recruitment, and (e) some stakeholders favor a more race-neutral approach to participant recruitment rather than an emphasis on targeted minority recruitment. The perspectives of clinical and research stakeholders potentially inform the assessment of existing strategies and the development of new strategies to increase motivation for minority recruitment in cancer clinical trials.

Talking About Trials: Overcoming Bottlenecks in Clinical Communication

Cancer.gov

Participation in clinical trials by adult patients is dismally low. No one knows how many patients are offered the opportunity to enroll in trials. NCI researchers are studying how patients hear about trials, whether they discuss enrollment with their providers, and the roles they play in deciding to participate in a trial.

Publication proportions for registered breast cancer trials: before and following the introduction of the ClinicalTrials.gov results database.

PubMed

Asiimwe, Innocent Gerald; Rumona, Dickson

2016-01-01

To limit selective and incomplete publication of the results of clinical trials, registries including ClinicalTrials.gov were introduced. The ClinicalTrials.gov registry added a results database in 2008 to enable researchers to post the results of their trials as stipulated by the Food and Drug Administration Amendment Act of 2007. This study aimed to determine the direction and magnitude of any change in publication proportions of registered breast cancer trials that occurred since the inception of the ClinicalTrials.gov results database. A cross-sectional study design was employed using ClinicalTrials.gov, a publicly available registry/results database as the primary data source. Registry contents under the subcategories 'Breast Neoplasms' and 'Breast Neoplasms, Male' were downloaded on 1 August 2015. A literature search for included trials was afterwards conducted using MEDLINE and DISCOVER databases to determine publication status of the registered breast cancer trials. Nearly half (168/340) of the listed trials had been published, with a median time to publication of 24 months (Q1 = 14 months, Q3 = 42 months). Only 86 trials were published within 24 months of completion. There was no significant increase in publication proportions of trials that were completed before the introduction of the results database compared to those completed after (OR = 1.00, 95 % CI = .61 to 1.63; adjusted OR = 0.84, 95 % CI = .51 to 1.39). Characteristics associated with publication included trial type (observational versus interventional adjusted OR = .28, 95 % CI = .10 to .74) and completion/termination status (terminated versus completed adjusted OR = .22, 95 % CI = .09 to .51). Less than a half of breast cancer trials registered in ClinicalTrials.gov are published in peer-reviewed journals.

Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization

PubMed Central

Luo, Jake; Chen, Weiheng; Wu, Min; Weng, Chunhua

2018-01-01

Background Prior studies of clinical trial planning indicate that it is crucial to search and screen recruitment sites before starting to enroll participants. However, currently there is no systematic method developed to support clinical investigators to search candidate recruitment sites according to their interested clinical trial factors. Objective In this study, we aim at developing a new approach to integrating the location data of over one million heterogeneous recruitment sites that are stored in clinical trial documents. The integrated recruitment location data can be searched and visualized using a map-based information retrieval method. The method enables systematic search and analysis of recruitment sites across a large amount of clinical trials. Methods The location data of more than 1.4 million recruitment sites of over 183,000 clinical trials was normalized and integrated using a geocoding method. The integrated data can be used to support geographic information retrieval of recruitment sites. Additionally, the information of over 6000 clinical trial target disease conditions and close to 4000 interventions was also integrated into the system and linked to the recruitment locations. Such data integration enabled the construction of a novel map-based query system. The system will allow clinical investigators to search and visualize candidate recruitment sites for clinical trials based on target conditions and interventions. Results The evaluation results showed that the coverage of the geographic location mapping for the 1.4 million recruitment sites was 99.8%. The evaluation of 200 randomly retrieved recruitment sites showed that the correctness of geographic information mapping was 96.5%. The recruitment intensities of the top 30 countries were also retrieved and analyzed. The data analysis results indicated that the recruitment intensity varied significantly across different countries and geographic areas. Conclusion This study contributed a new data processing framework to extract and integrate the location data of heterogeneous recruitment sites from clinical trial documents. The developed system can support effective retrieval and analysis of potential recruitment sites using target clinical trial factors. PMID:29132636

Systematic data ingratiation of clinical trial recruitment locations for geographic-based query and visualization.

PubMed

Luo, Jake; Chen, Weiheng; Wu, Min; Weng, Chunhua

2017-12-01

Prior studies of clinical trial planning indicate that it is crucial to search and screen recruitment sites before starting to enroll participants. However, currently there is no systematic method developed to support clinical investigators to search candidate recruitment sites according to their interested clinical trial factors. In this study, we aim at developing a new approach to integrating the location data of over one million heterogeneous recruitment sites that are stored in clinical trial documents. The integrated recruitment location data can be searched and visualized using a map-based information retrieval method. The method enables systematic search and analysis of recruitment sites across a large amount of clinical trials. The location data of more than 1.4 million recruitment sites of over 183,000 clinical trials was normalized and integrated using a geocoding method. The integrated data can be used to support geographic information retrieval of recruitment sites. Additionally, the information of over 6000 clinical trial target disease conditions and close to 4000 interventions was also integrated into the system and linked to the recruitment locations. Such data integration enabled the construction of a novel map-based query system. The system will allow clinical investigators to search and visualize candidate recruitment sites for clinical trials based on target conditions and interventions. The evaluation results showed that the coverage of the geographic location mapping for the 1.4 million recruitment sites was 99.8%. The evaluation of 200 randomly retrieved recruitment sites showed that the correctness of geographic information mapping was 96.5%. The recruitment intensities of the top 30 countries were also retrieved and analyzed. The data analysis results indicated that the recruitment intensity varied significantly across different countries and geographic areas. This study contributed a new data processing framework to extract and integrate the location data of heterogeneous recruitment sites from clinical trial documents. The developed system can support effective retrieval and analysis of potential recruitment sites using target clinical trial factors. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

PubMed Central

Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

2016-01-01

Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

Mitochondrial Replacement Therapy: Halachic Considerations for Enrolling in an Experimental Clinical Trial

PubMed Central

Tendler, Rabbi Moshe D.; Loike, John D.

2015-01-01

The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal. PMID:26241230

Generalizability of Clinical Trial Results for Adolescent Major Depressive Disorder.

PubMed

Blanco, Carlos; Hoertel, Nicolas; Franco, Silvia; Olfson, Mark; He, Jian-Ping; López, Saioa; González-Pinto, Ana; Limosin, Frédéric; Merikangas, Kathleen R

2017-12-01

Although there have been a number of clinical trials evaluating treatments for adolescents with major depressive disorder (MDD), the generalizability of those trials to samples of depressed adolescents who present for routine clinical care is unknown. Examining the generalizability of clinical trials of pharmacological and psychotherapy interventions for adolescent depression can help administrators and frontline practitioners determine the relevance of these studies for their patients and may also guide eligibility criteria for future clinical trials in this clinical population. Data on nationally representative adolescents were derived from the National Comorbidity Survey: Adolescent Supplement. To assess the generalizability of adolescent clinical trials for MDD, we applied a standard set of eligibility criteria representative of clinical trials to all adolescents in the National Comorbidity Survey: Adolescent Supplement with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of MDD ( N = 592). From the overall MDD sample, 61.9% would have been excluded from a typical pharmacological trial, whereas 42.2% would have been excluded from a psychotherapy trial. Among those who sought treatment ( n = 412), the corresponding exclusion rates were 72.7% for a pharmacological trial and 52.2% for a psychotherapy trial. The criterion leading to the largest number of exclusions was "significant risk of suicide" in both pharmacological and psychotherapy trials. Pharmacological and, to a lesser extent, psychotherapy clinical trials likely exclude most adolescents with MDD. Careful consideration should be given to balancing eligibility criteria and internal validity with applicability in routine clinical care while ensuring patient safety. Copyright © 2017 by the American Academy of Pediatrics.

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Key cost drivers of pharmaceutical clinical trials in the United States.

PubMed

Sertkaya, Aylin; Wong, Hui-Hsing; Jessup, Amber; Beleche, Trinidad

2016-04-01

The increasing cost of clinical research has significant implications for public health, as it affects drug companies' willingness to undertake clinical trials, which in turn limits patient access to novel treatments. Thus, gaining a better understanding of the key cost drivers of clinical research in the United States is important. The study which is based on a report prepared by Eastern Research Group, Inc., for the US Department of Health and Human Services, examined different factors, such as therapeutic area, patient recruitment, administrative staff, and clinical procedure expenditures, and their contribution to pharmaceutical clinical trial costs in the United States by clinical trial phase. The study used aggregate data from three proprietary databases on clinical trial costs provided by Medidata Solutions. We evaluated per-study costs across therapeutic areas by aggregating detailed (per patient and per site) cost information. We also compared average expenditures on cost drivers with the use of weighted mean and standard deviation statistics. Therapeutic area was an important determinant of clinical trial costs by phase. The average cost of a Phase 1 study conducted at a US site ranged from US$1.4 million (pain and anesthesia) to US$6.6 million (immunomodulation), including estimated site overhead and monitoring costs of the sponsoring organization. A Phase 2 study cost from US$7.0 million (cardiovascular) to US$19.6 million (hematology), whereas a Phase 3 study cost ranged from US$11.5 million (dermatology) to US$52.9 (pain and anesthesia) on average. Across all study phases and excluding estimated site overhead costs and costs for sponsors to monitor the study, the top three cost drivers of clinical trial expenditures were clinical procedure costs (15%-22% of total), administrative staff costs (11%-29% of total), and site monitoring costs (9%-14% of total). The data were from 2004 through 2012 and were not adjusted for inflation. Additionally, the databases used represented a convenience, that is, non-probability, sample and did not allow for statistically valid estimates of cost drivers. Finally, the data were from trials funded by the global pharmaceutical and biotechnology industry only. Hence, our study findings are limited to that segment. Therapeutic area being studied as well as number and types of clinical procedures involved were the key drivers of direct costs in Phase 1 through Phase 3 studies. Research shows that strategies exist for reducing the price tag of some of these major direct cost components. Therefore, to increase clinical trial efficiency and reduce costs, gaining a better understanding of the key direct cost drivers is an important step. © The Author(s) 2016.

Linking quality indicators to clinical trials: an automated approach

PubMed Central

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

2017-01-01

Abstract Objective Quality improvement of health care requires robust measurable indicators to track performance. However identifying which indicators are supported by strong clinical evidence, typically from clinical trials, is often laborious. This study tests a novel method for automatically linking indicators to clinical trial registrations. Design A set of 522 quality of care indicators for 22 common conditions drawn from the CareTrack study were automatically mapped to outcome measures reported in 13 971 trials from ClinicalTrials.gov. Intervention Text mining methods extracted phrases mentioning indicators and outcome phrases, and these were compared using the Levenshtein edit distance ratio to measure similarity. Main Outcome Measure Number of care indicators that mapped to outcome measures in clinical trials. Results While only 13% of the 522 CareTrack indicators were thought to have Level I or II evidence behind them, 353 (68%) could be directly linked to randomized controlled trials. Within these 522, 50 of 70 (71%) Level I and II evidence-based indicators, and 268 of 370 (72%) Level V (consensus-based) indicators could be linked to evidence. Of the indicators known to have evidence behind them, only 5.7% (4 of 70) were mentioned in the trial reports but were missed by our method. Conclusions We automatically linked indicators to clinical trial registrations with high precision. Whilst the majority of quality indicators studied could be directly linked to research evidence, a small portion could not and these require closer scrutiny. It is feasible to support the process of indicator development using automated methods to identify research evidence. PMID:28651340

Study of obligations defined in agreements between parties involved in clinical trials of medicinal products in Bulgaria.

PubMed

N Getov, Ilko; Gocheva-Hristova, Tanya; Lebanova, Hristina V; Grigorov, Evgeni E

2012-08-01

To analyse and assess the legislative and contractual obligations of the parties involved in the conduct of clinical trials, with identification of the needs for comprehensive contractual regulation of their rights and responsibilities. This survey has been carried out by means of review, analysis of comprehensiveness, comparative legislative analysis and assessment of compliance with the legislation of sample of investigator and site agreements governing the process of conducting clinical trials. The survey comprises analyses of contractual relations between the sponsor of the study and the investigator, and between the sponsor of the study and the trial site, respectively, relevant to clinical trials which are actually conducted in Bulgaria at the time of and following the survey. Comparative method based on pre-defined structured indices was employed to outline the major variances in the volume of responsibilities and obligations of the said parties to the clinical trial, as regulated by the investigator and site agreements. The analysis of comprehensiveness showed evident omissions in the regulation of relations and interactions between the parties to the agreements. The detailed contractual regulation providing for the statutory obligations and responsibilities of the parties involved in the conduct of clinical trials is a good guarantee for proper understanding of the obligations of each party and for compliance with their relevant responsibilities in view of protecting the rights of the participants in the clinical trials - patients or healthy volunteers.

Patient perspectives on physician conflict of interest in industry-sponsored clinical trials for multiple sclerosis therapeutics.

PubMed

Solomon, Andrew J; Klein, Eran P; Corboy, John R; Bernat, James L

2015-10-01

Pharmaceutical industry financial support of physicians, physician practices, and academic departments involved in multicenter industry-sponsored clinical trials of novel therapeutic agents is a relatively new and infrequently acknowledged source of potential physician conflict of interest. Detailed disclosure of these relationships to study participants is not uniformly a part of informed consent and documentation practices. To understand attitudes of patients with multiple sclerosis concerning disclosure of potential physician-industry conflicts of interest created by clinical trials and how such disclosures may influence study participation An anonymous online instrument was developed. 597 people with multiple sclerosis participated in the study. The study found that detailed disclosure of conflicts of interest is important to potential participants in industry-sponsored clinical trials for multiple sclerosis therapies and that the presence of these conflicts of interest may influence patients' decisions to participate in these studies. Findings from this study support a call for uniform guidelines regarding disclosure of physician-industry relationships to prospective research participants for industry-sponsored clinical trials. © The Author(s), 2015.

In Silico Simulation of a Clinical Trial Concerning Tumour Response to Radiotherapy

NASA Astrophysics Data System (ADS)

Dionysiou, Dimitra D.; Stamatakos, Georgios S.; Athanaileas, Theodoras E.; Merrychtas, Andreas; Kaklamani, Dimitra; Varvarigou, Theodora; Uzunoglu, Nikolaos

2008-11-01

The aim of this paper is to demonstrate how multilevel tumour growth and response to therapeutic treatment models can be used in order to simulate clinical trials, with the long-term intention of both better designing clinical studies and understanding their outcome based on basic biological science. For this purpose, an already developed computer simulation model of glioblastoma multiforme response to radiotherapy has been used and a clinical study concerning glioblastoma multiforme response to radiotherapy has been simulated. In order to facilitate the simulation of such virtual trials, a toolkit enabling the user-friendly execution of the simulations on grid infrastructures has been designed and developed. The results of the conducted virtual trial are in agreement with the outcome of the real clinical study.

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

Clinical Trials: Information and Options for People with Mood Disorders

MedlinePlus

... experts as well as nonscientists) that oversees the design of a clinical study and periodically reviews clinical research to ensure there ... Nothing is without risks, including illness itself. A study may not benefit you personally at the time of the clinical trial. You may have to ...

Depression severity in electroconvulsive therapy (ECT) versus pharmacotherapy trials.

PubMed

Kellner, Charles H; Kaicher, David C; Banerjee, Hiya; Knapp, Rebecca G; Shapiro, Rachael J; Briggs, Mimi C; Pasculli, Rosa M; Popeo, Dennis M; Ahle, Gabriella M; Liebman, Lauren S

2015-03-01

We sought to compare the level of severity of depressive symptoms on entry into electroconvulsive therapy (ECT) clinical trials versus pharmacotherapy clinical trials. English-language MEDLINE/PubMed publication databases were searched for ECT literature (search terms: ECT, electroconvulsive therapy, depression, and Hamilton) for clinical trials in which depressed patients had baseline Hamilton Rating Scale for Depression (HRSD) scores. For comparison, we used a convenience sample of 7 large pharmacotherapy trials in major depression (N = 3677). The search included articles from 1960 to 2011. We included 100 studies that met the following criteria: ECT trial for depression, patients adequately characterized by diagnosis at baseline, and patients rated at baseline by 15-item HRSD (HRSD15), HRSD17, HRSD21, HRSD24, or HRSD28, with mean (SD) and sample size (n) reported. For the comparator pharmacotherapy trials, we chose to use a subset of the studies (excluding one study of minor depression) in the widely publicized meta-analysis of Fournier et al, as well as the STAR*D study and one additional study by Shelton et al. This provided 7 studies of major depression using HRSD17 (total N = 3677). Data extracted included number of subjects and baseline and final HRSD scores, with mean (SD) values. Of 100 ECT studies, 56 studies (N = 2243) used the HRSD17 version. The mean baseline HRSD17 score in the ECT trials was 27.6, the mean in the pharmacotherapy trials was 21.94, a statistically, and clinically, significant difference. In a subanalysis of the 16 ECT studies that used the HRSD24 version, the mean baseline score was 32.2. This selective literature review confirms that patients who entered ECT clinical trials were more severely ill than those who entered the selected comparator pharmacotherapy trials. Such data highlight the critical role of ECT in the treatment of severe and treatment-resistant mood disorders.

Role of Clinical Trial Participation in Cancer Research: Barriers, Evidence, and Strategies

PubMed Central

Unger, Joseph M.; Cook, Elise; Tai, Eric; Bleyer, Archie

2017-01-01

OVERVIEW Fewer than 1 in 20 adult cancer patients enroll in cancer clinical trials. But although barriers to trial participation have been the subject of frequent study, the rate of trial participation has not changed substantially over time. Barriers to trial participation are structural, clinical, and attitudinal, and differ according to demographic and socioeconomic factors. In this paper, we characterize the nature of cancer clinical trial barriers, and we consider global and local strategies for reducing barriers. We also consider the specific case of adolescents with cancer, and show that the low rate of trial enrollment in this age group strongly correlates with limited improvements in cancer population outcomes compared to other age groups. Our analysis suggests that a clinical trial system that enrolls patients at higher rates produces treatment advances at a faster rate and corresponding improvements in cancer population outcomes. Viewed in this light, the issue of clinical trial enrollment is foundational, lying at the heart of the cancer clinical trial endeavor. Fewer barriers to trial participation would allow trials to be completed more quickly and would improve the generalizability of trial results. Moreover, increased accrual to trials is important to patients, since trials provide patients the opportunity to receive the newest treatments. In an era of increasing emphasis on a treatment decision-making process that incorporates the patient perspective, the opportunity for patients to choose trial participation for their care is vital. PMID:27249699

75 FR 73104 - Clinical Development Programs for Sedation Products; Request for Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

... sedation claims? Would dose-escalation comparative trial designs be useful in studying sedation products? 5... understanding the physiology of sedation and clinical trial design issues related to the development of sedation... to procedural and intensive care unit (ICU) sedation, as well as associated clinical trial design...

Clinical Trials Using Anti-CD19/CD28/CD3zeta CAR Gammaretroviral Vector-transduced Autologous T Lymphocytes KTE-C19

Cancer.gov

NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying anti-cd19/cd28/cd3zeta car gammaretroviral vector-transduced autologous t lymphocytes kte-c19.

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

PubMed

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

2017-07-05

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

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

Factors predicting publication of spinal cord injury trials registered on www.ClinicalTrials. gov.

PubMed

DePasse, J Mason; Park, Sara; Eltorai, Adam E M; Daniels, Alan H

2018-02-06

Treatment options for spinal cord injuries are currently limited, but multiple clinical trials are underway for a variety of interventions, drugs, and devices. The Food and Drug Administration website www.ClinicalTrials.gov catalogues these trials and includes information on the status of the trial, date of initiation and completion, source of funding, and region. This investigation assesses the factors associated with publication and the publication rate of spinal cord injury trials. Retrospective analysis of publically available data on www.ClinicalTrials.gov. The www.ClinicalTrials.gov was queried for all trials on patients with spinal cord injury, and these trials were assessed for status, type of intervention, source of funding, and region. Multiple literature searches were performed on all completed trials to determine publication status. There were 626 studies identified concerning the treatment of patients with spinal cord injury, of which 250 (39.9%) were completed. Of these, only 119 (47.6%) were published. There was no significant difference in the rate of publication between regions (p> 0.16) or by study type (p> 0.29). However, trials that were funded by the NIH were more likely to be published than trials funded by industry (p= 0.01). The current publication rate of spinal cord injury trials is only 47.6%, though this rate is similar to the publication rate for trials in other fields. NIH-funded trials are significantly more likely to become published than industry-funded trials, which could indicate that some trials remain unpublished due to undesirable results. However, it is also likely that many trials on spinal cord injury yield negative results, as treatments are often ineffective.

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project.

PubMed

Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-01-01

Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development.

Improving recruitment to pharmacological trials for illicit opioid use: findings from a qualitative focus group study.

PubMed

Neale, Joanne; Tompkins, Charlotte N E; McDonald, Rebecca; Strang, John

2018-06-01

To explore potential study participants' views on willingness to join clinical trials of pharmacological interventions for illicit opioid use to inform and improve future recruitment strategies. Qualitative focus group study [six groups: oral methadone (two groups); buprenorphine tablets (two groups); injectable opioid agonist treatment (one group); and former opioid agonist treatment (one group)]. Drug and alcohol services and a peer support recovery service (London, UK). Forty people with experience of opioid agonist treatment for heroin dependence (26 males, 14 females; aged 33-66 years). Data collection was facilitated by a topic guide that explored willingness to enrol in clinical pharmacological trials. Groups were audio-recorded and transcribed. Transcribed data were analysed inductively via Iterative Categorization. Participants' willingness to join pharmacological trials of medications for opioid dependence was affected by factors relating to study burden, study drug, study design, study population and study relationships. Participants worried that the trial drug might be worse than, or interfere with, their current treatment. They also misunderstood aspects of trial design despite the researchers' explanations. Recruitment of participants for clinical trials of pharmacological interventions for illicit opioid use could be improved if researchers became better at explaining clinical trials to potential participants, dispelling misconceptions about trials and increasing trust in the research process and research establishment. A checklist of issues to consider when designing pharmacological trials for illicit opioid use is proposed. © 2018 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

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

PubMed

Marin Dos Santos, Douglas H; Atallah, Álvaro N

2015-01-01

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

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

PubMed Central

Atallah, Álvaro N.

2015-01-01

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

Using ClinicalTrials.gov to supplement information in ophthalmology conference abstracts about trial outcomes: a comparison study.

PubMed

Scherer, Roberta W; Huynh, Lynn; Ervin, Ann-Margret; Dickersin, Kay

2015-01-01

Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching "new" outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned.

Clinical trials in palliative care: a systematic review of their methodological characteristics and of the quality of their reporting.

PubMed

Bouça-Machado, Raquel; Rosário, Madalena; Alarcão, Joana; Correia-Guedes, Leonor; Abreu, Daisy; Ferreira, Joaquim J

2017-01-25

Over the past decades there has been a significant increase in the number of published clinical trials in palliative care. However, empirical evidence suggests that there are methodological problems in the design and conduct of studies, which raises questions about the validity and generalisability of the results and of the strength of the available evidence. We sought to evaluate the methodological characteristics and assess the quality of reporting of clinical trials in palliative care. We performed a systematic review of published clinical trials assessing therapeutic interventions in palliative care. Trials were identified using MEDLINE (from its inception to February 2015). We assessed methodological characteristics and describe the quality of reporting using the Cochrane Risk of Bias tool. We retrieved 107 studies. The most common medical field studied was oncology, and 43.9% of trials evaluated pharmacological interventions. Symptom control and physical dimensions (e.g. intervention on pain, breathlessness, nausea) were the palliative care-specific issues most studied. We found under-reporting of key information in particular on random sequence generation, allocation concealment, and blinding. While the number of clinical trials in palliative care has increased over time, methodological quality remains suboptimal. This compromises the quality of studies. Therefore, a greater effort is needed to enable the appropriate performance of future studies and increase the robustness of evidence-based medicine in this important field.

Current globalization of drug interventional clinical trials: characteristics and associated factors, 2011-2013.

PubMed

Jeong, Sohyun; Sohn, Minji; Kim, Jae Hyun; Ko, Minoh; Seo, Hee-Won; Song, Yun-Kyoung; Choi, Boyoon; Han, Nayoung; Na, Han-Sung; Lee, Jong Gu; Kim, In-Wha; Oh, Jung Mi; Lee, Euni

2017-06-21

Clinical trial globalization is a major trend for industry-sponsored clinical trials. There has been a shift in clinical trial sites towards emerging regions of Eastern Europe, Latin America, Asia, the Middle East, and Africa. Our study objectives were to evaluate the current characteristics of clinical trials and to find out the associated multiple factors which could explain clinical trial globalization and its implications for clinical trial globalization in 2011-2013. The data elements of "phase," "recruitment status," "type of sponsor," "age groups," and "design of trial" from 30 countries were extracted from the ClinicalTrials.gov website. Ten continental representative countries including the USA were selected and the design elements were compared to those of the USA. Factors associated with trial site distribution were chosen for a multilinear regression analysis. The USA, Germany, France, Canada, and United Kingdom were the "top five" countries which frequently held clinical trials. The design elements from nine continental representative countries were quite different from those of the USA; phase 1 trials were more prevalent in India (OR 1.517, p < 0.001) while phase 3 trials were much more prevalent in all nine representative countries than in the USA. A larger number of "child" age group trials was performed in Poland (OR 1.852, p < 0.001), Israel (OR 1.546, p = 0.005), and South Africa (OR 1.963, p < 0.001) than in the USA. Multivariate analysis showed that health care expenditure per capita, Economic Freedom Index, Human Capital Index, and Intellectual Property Rights Index could explain the variance of regional distribution of clinical trials by 63.6%. The globalization of clinical trials in the emerging regions of Asia, South Africa, and Eastern Europe developed in parallel with the factors of economic drive, population for recruitment, and regulatory constraints.

Trends in Research with U.S. Military Service Member Participants: A Population-Specific ClinicalTrials.gov Review.

PubMed

Cook, Wendy A; Doorenbos, Ardith Z; Bridges, Elizabeth J

2016-08-15

ClinicalTrials.gov reviews have evaluated research trends for specific conditions and age groups but not for specific populations of research participants. No ClinicalTrials.gov reviews have evaluated research with military service member participants. Study objectives were (a) to use ClinicalTrials.gov to identify trends in biomedical research from 2005 to 2014 in which U.S. military service members actively participated as research participants and (b) to describe a search strategy for adaptation in future ClinicalTrials.gov reviews of specific participant populations. A systematic review of ClinicalTrials.gov was performed to identify studies that included U.S. service members as participants, either exclusively or with other groups of participants. U.S. service members were identified as participants in 512 studies. Service members participated together with other groups in 392 studies, while 120 studies included only service members. The top five conditions of interest were post-traumatic stress disorder, traumatic brain injury, amputations, burns, and ocular injuries/disorders. The number of studies started each year peaked in 2011 and declined from 2012 to 2014. Twenty-five percent of studies exclusive to service members aimed to enroll 500 or more participants. Research exclusive to Guard and Reserve service members during this period was limited. U.S. military service members participate in biomedical research. To address the health needs of U.S. service members, it is important to ensure there is not a prolonged decline in research among this population. The search strategy may be adapted to ClinicalTrials.gov reviews of specific participant populations for which straightforward searches are not possible.

Quality of registration for clinical trials published in emergency medicine journals.

PubMed

Jones, Christopher W; Platts-Mills, Timothy F

2012-10-01

In 2005, the International Committee of Medical Journal Editors established clinical trial registration as a requirement for articles submitted to member journals, with the goal of improving the transparency of clinical research. The objective of this study is to characterize the registration of clinical trials published in emergency medicine journals. Randomized trials involving human subjects and published between June 1, 2008, and May 31, 2011 in the 5 emergency medicine journals with the highest impact factors were included. We assessed the clarity of registered primary outcomes, timing of registration relative to patient enrollment, and consistency between registered and published outcomes. Of the 123 trials included, registry entries were identified for 57 (46%). Of the 57 registered studies, 45 (79%) were registered after the initiation of subject enrollment, 9 (16%) had registered outcomes that were unclear, and 26 (46%) had discrepancies between registered and published outcomes. Only 5 studies were registered before patient enrollment with a clear primary outcome that was consistent with the published primary outcome. Annals of Emergency Medicine was the only journal in which the majority of trials were registered. Current compliance with clinical trial registration guidelines is poor among trials published in emergency medicine journals. Copyright © 2012. Published by Mosby, Inc.

A mixed methods study to assess the feasibility of a randomised controlled trial of invasive urodynamic testing versus clinical assessment and non-invasive tests prior to surgery for stress urinary incontinence in women: the INVESTIGATE-I study.

PubMed

Hilton, Paul; Armstrong, Natalie; Brennand, Catherine; Howel, Denise; Shen, Jing; Bryant, Andrew; Tincello, Douglas G; Lucas, Malcolm G; Buckley, Brian S; Chapple, Christopher R; Homer, Tara; Vale, Luke; McColl, Elaine

2015-09-08

The position of invasive urodynamic testing (IUT) in diagnostic pathways for urinary incontinence is unclear, and systematic reviews have called for further trials evaluating clinical utility. The objective of this study was to inform the decision whether to proceed to a definitive randomised trial of IUT compared to clinical assessment with non-invasive tests, prior to surgery in women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI). A mixed methods study comprising a pragmatic multicentre randomised pilot trial, a qualitative face-to face interview study with patients eligible for the trial, an exploratory economic evaluation including value of information study, a survey of clinicians' views about IUT, and qualitative telephone interviews with purposively sampled survey respondents. Only the first and second of these elements are reported here. Trial participants were randomised to either clinical assessment with non-invasive tests (control arm) or clinical assessment with non-invasive tests plus IUT (intervention arm). The main outcome measures of these feasibility studies were confirmation that units can identify and recruit eligible women, acceptability of investigation strategies and data collection tools, and acquisition of outcome data to determine the sample size for a definitive trial. The primary outcome proposed for a definitive trial was ICIQ-FLUTS (total score) 6 months after surgery or the start of nonsurgical treatment. Of 284 eligible women, 222 (78%) were recruited, 165/219 (75%) returned questionnaires at baseline, and 125/200 returned them (63%) at follow-up. Most women underwent surgery; management plans were changed in 19 (19%) participants following IUT. Participants interviewed were positive about the trial and the associated documentation. All elements of a definitive trial were rehearsed. Such a trial would require between 232 and 922 participants, depending on the target difference in the primary outcome. We identified possible modifications to our protocol for application in a definitive trial including clarity over inclusion/exclusions, screening processes, reduction in secondary outcomes, and modification to patient questionnaire booklets and bladder diaries. A definitive trial of IUT versus clinical assessment prior to surgery for SUI or stress predominant MUI is feasible and remains relevant. Current Controlled Trials: ISRCTN 71327395, registered 7 June 2010.

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

PubMed Central

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

2018-01-01

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

Measuring health-related quality of life in drug clinical trials: is it given due importance?

PubMed

Miguel, Ramón San; López-González, Ana María; Sanchez-Iriso, Eduardo; Mar, Javier; Cabasés, Juan M

2008-04-01

Efficacy estimations of drug clinical trials have been based on clinical measurements and survival rates. However, advances in psychometric techniques have allowed to incorporate a new dimension based on quality of life. Questionnaires aimed at measuring patients' health status outlook, now enable us to quantify the loss of quality of life caused by disease and the improvement that can be achieved by pharmacological treatments. The Aim of this study is to make a quantitative evaluation of the use of health related quality of life (HRQL) measures in drug clinical trials. A systematic review was performed, in duplicate, of the five journals with highest contribution to the ACP Journal Club, i.e. New England Journal of Medicine, JAMA, The Lancet, Annals of Internal Medicine and the British Medical Journal. HRQL measures were evaluated in published articles referring to drug clinical trials. We identified 193 articles that reported the results of clinical trials, of which 28 included QOL measures as secondary end points and two as primary end points: in total, these comprised 16% of the articles analysed. Discussion Without considering the relevance of HRQL measures as a tool in the allocation of resources, it should be included as a health outcome dimension in drug clinical trials. The absence of this evaluation in studies about chronic diseases that affects patients' daily life activities would not be justified. HRQL measures are not used on a regular basis in drug clinical trials that are reported in the relevant literature. Systematic incorporation of QOL measures into clinical trials would make it possible to measure the benefit obtained from drug treatments taking into account the patients' perceptions. Moreover, it would encourage the development of prospective cost-effectiveness studies with patient recorded data in the context of clinical trials. Our findings have a direct impact on practice. Being conscious of the low use of HRQL in clinical trials, it could contribute to increase the demand for these measures by health care professionals. The manuscript is also a useful tool to identify where basic concepts about HRQL measures can be found.

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

PubMed

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

2017-01-01

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

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.

Optimal dose selection accounting for patient subpopulations in a randomized Phase II trial to maximize the success probability of a subsequent Phase III trial.

PubMed

Takahashi, Fumihiro; Morita, Satoshi

2018-02-08

Phase II clinical trials are conducted to determine the optimal dose of the study drug for use in Phase III clinical trials while also balancing efficacy and safety. In conducting these trials, it may be important to consider subpopulations of patients grouped by background factors such as drug metabolism and kidney and liver function. Determining the optimal dose, as well as maximizing the effectiveness of the study drug by analyzing patient subpopulations, requires a complex decision-making process. In extreme cases, drug development has to be terminated due to inadequate efficacy or severe toxicity. Such a decision may be based on a particular subpopulation. We propose a Bayesian utility approach (BUART) to randomized Phase II clinical trials which uses a first-order bivariate normal dynamic linear model for efficacy and safety in order to determine the optimal dose and study population in a subsequent Phase III clinical trial. We carried out a simulation study under a wide range of clinical scenarios to evaluate the performance of the proposed method in comparison with a conventional method separately analyzing efficacy and safety in each patient population. The proposed method showed more favorable operating characteristics in determining the optimal population and dose.

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

PubMed

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

2011-09-01

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

[The Coordinating Centers for Clinical Trials (KKS) and the KKS Network: competence for clinical research].

PubMed

Ohmann, Christian; Bruns, Insa; Wolff, Stephanie

2010-01-01

The Network of the Coordination Centers for Clinical Trials (CTCs; Koordinierungszentren für Klinische Studien(KKS)) comprises 17 institutions working as scientific service provider for universities, study groups, the pharmaceutical and medical devices industry as well as additional clients associated with clinical research. The CTCs have established planning and conduct of clinical trials according to Good Clinical Practice (GCP) guidelines,with a wide range of study support in academia. One focus according to indications is cancer. Expertise in hematological/oncological research can be requested nationwide and cross-institutional. The KKS network currently cooperates with medical societies and other, even European networks in 20 countries and has been established as a strong platform for oncological trials. Copyright © 2010 S. Karger AG, Basel.

A Review of Clinical Trials in Spinal Cord Injury including Biomarkers.

PubMed

Badhiwala, Jetan H; Wilson, Jefferson R; Kwon, Brian K; Casha, Steve; Fehlings, Michael G

2018-06-11

Acute traumatic spinal cord injury (SCI) entered the arena of prospective randomized clinical trials almost 40 years ago, with the undertaking of the National Acute Spinal Cord Study (NASCIS) I trial. Since then, a number of clinical trials have been conducted in the field, spurred by the devastating physical, social, and economic consequences of acute SCI for patients, families, and society at large. Many of these have been controversial and attracted criticism. The current review provides a critical summary of select past and current clinical trials in SCI, focusing in particular on the findings of prospective randomized controlled trials (RCTs), the challenges and barriers encountered, and the valuable lessons learned that can be applied to future trials.

Clinical trial registration in physical therapy journals: a cross-sectional study.

PubMed

Babu, Abraham Samuel; Veluswamy, Sundar Kumar; Rao, Pratiksha Tilak; Maiya, Arun G

2014-01-01

Clinical trial registration has become an important part of editorial policies of various biomedical journals, including a few physical therapy journals. However, the extent to which editorial boards enforce the need for trial registration varies across journals. The purpose of this study was to identify editorial policies and reporting of trial registration details in MEDLINE-indexed English-language physical therapy journals. This study was carried out using a cross-sectional design. Editorial policies on trial registration of MEDLINE-indexed member journals of the International Society of Physiotherapy Journal Editors (ISPJE) (Journal of Geriatric Physical Therapy, Journal of Hand Therapy, Journal of Neurologic Physical Therapy, Journal of Orthopaedic and Sports Physical Therapy, Journal of Physiotherapy [formerly Australian Journal of Physiotherapy], Journal of Science and Medicine in Sport, Manual Therapy, Physical Therapy, Physical Therapy in Sport, Physiotherapy, Physiotherapy Research International, Physiotherapy Theory and Practice, and Revista Brasileira de Fisioterapia) were reviewed in April 2013. Full texts of reports of clinical trials published in these journals between January 1, 2008, and December 31, 2012, were independently assessed for information on trial registration. Among the 13 journals, 8 recommended trial registration, and 6 emphasized prospective trial registration. As of April 2013, 4,618 articles were published between January 2008 and December 2012, of which 9% (417) were clinical trials and 29% (121/417) of these reported trial registration details. A positive trend in reporting of trial registration was observed from 2008 to 2012. The study was limited to MEDLINE-indexed ISPJE member journals. Editorial policies on trial registration of physical therapy journals and a rising trend toward reporting of trial registration details indicate a positive momentum toward trial registration. Physical therapy journal editors need to show greater commitment to prospective trial registration to make it a rule rather than an option.

The impact of cardiovascular disease prevalence on women's enrollment in landmark randomized cardiovascular trials: a systematic review.

PubMed

Tsang, Wendy; Alter, David A; Wijeysundera, Harindra C; Zhang, Tony; Ko, Dennis T

2012-01-01

Many studies have demonstrated that women are substantially underrepresented in cardiovascular trials, but few have considered that women develop cardiovascular disease at older ages than men. The extent to which observed gender enrollment inequalities persist after accounting for age-gender differences in disease prevalence is unknown. The purpose of the study was to compare observed rates of women participating in cardiovascular clinical trials with expected rates of female participation based on age- and gender-specific population disease prevalence. Publications between 1997 and 2009 in the three leading medical journals were included to calculate observed women's enrollment rates. Population-based data in Canada were used to determine the expected enrollment rates of women. Multicenter, randomized cardiovascular clinical trials that enrolled both men and women were analyzed. Two reviewers independently extracted data on women's enrollment and important clinical trial characteristics. The female enrollment rate was 30% in the included 325 trials, which ranged from 27% in trials of coronary artery disease, 27% in heart failure, 31% in arrhythmia, to 45% in primary prevention. Increased female enrollment correlated strongly with increasing age at recruitment in cardiovascular clinical trials (P < 0.001). After accounting for age- and gender-specific differences in disease prevalence, gaps in female enrollment were much lower than the expected enrollment rates estimated by 5% in coronary artery disease, 13% in heart failure, 9% in arrhythmia, and 3% in primary prevention. Only cardiovascular trials were evaluated in our study. Female underrepresentation in cardiovascular clinical trials is smaller than conventionally believed after accounting for age- and gender-specific population disease prevalence. Our findings suggest that greater representation of women in cardiovascular clinical trials can be achieved through the recruitment of older populations.

Characteristics and trends of clinical trials funded by the National Institutes of Health between 2005 and 2015.

PubMed

Gresham, Gillian K; Ehrhardt, Stephan; Meinert, Jill L; Appel, Lawrence J; Meinert, Curtis L

2018-02-01

Background The National Institutes of Health is one of the largest biomedical research agencies in the world. Clinical trials are an important component of National Institutes of Health research efforts. Given the recent updates in National Institutes of Health trial reporting requirements, more information regarding the current state of National Institutes of Health-funded clinical trials is warranted. The objective of this analysis was to describe characteristics and trends of clinical trials funded by the National Institutes of Health over time and by Institutes and Centers of the National Institutes of Health. Methods Interventional studies funded by the National Institutes of Health and registered in ClinicalTrials.gov between 2005 and 2015 were included in the analysis. Trials were identified from the 27 March 2016 Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov database. A descriptive analysis of trials by year and National Institutes of Health Institute/Center was performed. Results There were 12,987 National Institutes of Health-funded clinical trials registered between 2005 and 2015. There were 1,580, 1,116, and 930 trials registered in 2005, 2010, and 2015, respectively. The majority were early-development trials (phases 0, 1, or 2; 53%), randomized (61%), and single-center (63%). Trial demographics have remained unchanged over time. Median trial sample size was 64 (interquartile range 29-192) with 10% of trials enrolling ≥500 participants. Most trials were completed within 5 years of enrollment start (69%). Trial characteristics varied considerably across National Institutes of Health Institutes and Centers. Results were reported under the assumptions that most National Institutes of Health-funded trials are registered in ClinicalTrials.gov and that trials are being registered completely and accurately. Conclusion In conclusion, there has been a decline in the number of trials being funded over time, explained in part by a relatively constant budget, increases in trial costs, or other factors that cannot be quantified. National Institutes of Health-funded trials are relatively small and tend to be single-centered. There are substantial differences in the number and types of trials done by Institutes and Centers within the National Institutes of Health.

Challenges and lessons learned in conducting comparative-effectiveness trials.

PubMed

Herrick, Linda M; Locke, G Richard; Zinsmeister, Alan R; Talley, Nicholas J

2012-05-01

The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication.

Challenges and Lessons Learned in Conducting Comparative-Effectiveness Trials

PubMed Central

Herrick, Linda M.; Locke, G. Richard; Zinsmeister, Alan R.; Talley, Nicholas J.

2014-01-01

The current health-care environment is demanding evidence-based medicine that relies on clinical trials as the basis for decisions. Clinician investigators are more often finding that they are personally responsible for coordinating large, multisite trials. We present strategies for successful implementation and management of multisite clinical trials and knowledge gained through an international, multisite randomized clinical trial. Topics include team composition, regulatory requirements, study organization and governance, communication strategies, recruitment and retention efforts, budget, technology transfer, and publication. PMID:22552235

Moving toward the reduction of publication/reporting biases in clinical trials using a new international standard.

PubMed

Doi, Yuriko

2016-01-01

Evidence-based medicine (EBM) is fundamental to ensuring high-quality medical care. It requires systematic reviews and meta-analyses to synthesize diverse information available from individual clinical studies. However, the literature reviewed may represent an incomplete and selective set of research findings, which could lead to publication/reporting biases and distort the true picture of research as a whole. Prospective registry of all clinical trials in the world is mandatory to reduce the biases, which have been disclosed on the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (WHO) since 2007. The Japan Primary Registries Network (JPRN) is included in the ICTRP. ClinicalTrials.gov, the U.S. clinical trial registry, reports the standardized data of registered trials and offers access to submitted outcomes online. However, the JPRN does not systematically include the outcomes. On April 14, 2015, the WHO published a new statement online on the public disclosure of clinical trial results, which requires researchers to define the timeframes of reporting main findings and key outcomes, to call for results-reporting older, but still unpublished trials, and to outline steps to improve linkages between clinical trial registry entries and their published results. The WHO's new position will facilitate global efforts to reduce publication/reporting biases in clinical trials. Japan will have to actively participate in these efforts as well.

Willingness to Participate in Clinical Trials Among African Americans and Whites Previously Exposed To Clinical Research

PubMed Central

Durant, Raegan W.; Legedza, Anna T.; Marcantonio, Edward R.; Freeman, Marcie B.; Landon, Bruce E.

2011-01-01

The objective of this study was to identify racial differences in willingness to participate in a population with previous exposure to clinical research. A survey instrument was administered to community-dwelling whites and African Americans who were voluntarily receiving a lay research and health education newsletter from a local Boston geriatric clinical research institution. The survey instrument assessed willingness to participate in 3 hypothetical clinical trials (diet trial for obesity, medication trial for hypertension [HTN], chemotherapy trial for cancer). Surveys were received from 473 whites and 279 African Americans (53% response rate) with mean age 74 (SD ± 9). In multivariate models, race was not significantly related to willingness to participate in the multivariate models for any of the 3 trials. Previous trial participation was related to a higher odds of willingness to participate in the diet trial only (OR 1.8, 95% CI 1.2,2.6). Lower levels of trust in one’s primary care physician were associated with a lower odds of willingness to participate in clinical trials for the diet and HTN trials (OR 0.5, 95% CI 0.3,0.8 and OR 0.6, 95% CI 0.3,0.9, respectively). These findings suggest that, within populations previously exposed to clinical research, African Americans are no less willing to participate in clinical trials compared to whites. PMID:21526582

Clinical studies in restorative dentistry: New directions and new demands.

PubMed

Opdam, N J M; Collares, K; Hickel, R; Bayne, S C; Loomans, B A; Cenci, M S; Lynch, C D; Correa, M B; Demarco, F; Schwendicke, F; Wilson, N H F

2018-01-01

Clinical research of restorative materials is confounded by problems of study designs, length of trials, type of information collected, and costs for trials, despite increasing numbers and considerable development of trials during the past 50 years. This opinion paper aims to discuss advantages and disadvantages of different study designs and outcomes for evaluating survival of dental restorations and to make recommendations for future study designs. Advantages and disadvantages of randomized trials, prospective and retrospective longitudinal studies, practice-based, pragmatic and cohort studies are addressed and discussed. The recommendations of the paper are that clinical trials should have rational control groups, include confounders such as patient risk factors in the data and analysis and should use outcome parameters relevant for profession and patients. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

The utility of observational studies in clinical decision making: lessons learned from statin trials.

PubMed

Foody, JoAnne M; Mendys, Phillip M; Liu, Larry Z; Simpson, Ross J

2010-05-01

Contemporary clinical decision making is well supported by a wide variety of information sources, including clinical practice guidelines, position papers, and insights from randomized controlled trials (RCTs). Much of our fundamental understanding of cardiovascular risk factors is based on multiple observations from major epidemiologic studies, such as The Seven Country Studies and the US-based Framingham Heart Study. These studies provided the framework for the development of clinical practice guidelines, including the National Cholesterol Education Program Adult Treatment Panel series. The objective of this article is to highlight the value of observational studies as a complement to clinical trial data for clinical decision making in real-world practice. Although RCTs are still the benchmark for assessing clinical efficacy and safety of a specific therapeutic approach, they may be of limited utility to practitioners who must then adapt the lessons learned from the trial into the patient care environment. The use of well-structured observational studies can improve our understanding of the translation of clinical trials into clinical practice, as demonstrated here with the example of statins. Although such studies have their own limitations, improved techniques for design and analysis have reduced the impact of bias and confounders. The introduction of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines has provided more uniformity for such studies. When used together with RCTs, observational studies can enhance our understanding of effectiveness and utility in real-world clinical practice. In the examples of statin observational studies, the results suggest that relative effectiveness of different statins and potential impact of switching statins should be carefully considered in treating individual patients by practicing physicians.

The interaction between equipoise and logistics in clinical trials: A case study.

PubMed

Warshaw, Meredith G; Carey, Vincent J; McFarland, Elizabeth J; Dawson, Liza; Abrams, Elaine; Melvin, Ann; Fairlie, Lee; Spiegel, Hans; Jay, Jonathan; Agwu, Allison L

2017-06-01

Equipoise is usually discussed as an ethical issue in clinical trials. However, it also has practical implications. Clinical equipoise is usually construed to mean uncertainty or disagreement among the expert clinician community. However, an individual physician's sense of equipoise may vary by location, based on the local standard of care or availability of specific treatment options, and these differences can affect providers' willingness to enroll participants into clinical trials. There are also logistical barriers to enrollment in international trials due to prolonged timelines for approvals by government agencies and ethical review boards. A multinational clinical trial of bridging strategies for treatment of non-adherent HIV-infected youth, experienced differing perceptions of equipoise due to disparities in availability of treatment options by country. Unfortunately, the countries with most demand for the trial were those where the approval process was most delayed, and the study was closed early due to slow accrual. When planning multicenter clinical trials, it is important to take into account heterogeneity among research sites and try to anticipate differences in equipoise and logistical factors between sites, in order to plan to address these issues at the design stage.

Strengthening the reliability and credibility of observational epidemiology studies by creating an Observational Studies Register.

PubMed

Swaen, Gerard M H; Carmichael, Neil; Doe, John

2011-05-01

To evaluate the need for the creation of a system in which observational epidemiology studies are registered; an Observational Studies Register (OSR). The current scientific process for observational epidemiology studies is described. Next, a parallel is made with the clinical trials area, where the creation of clinical trial registers has greatly restored and improved their credibility and reliability. Next, the advantages and disadvantages of an OSR are compared. The advantages of an OSR outweigh its disadvantages. The creation of an OSR, similar to the existing Clinical Trials Registers, will improve the assessment of publication bias and will provide an opportunity to compare the original study protocol with the results reported in the publication. Reliability, credibility, and transparency of observational epidemiology studies are strengthened by the creation of an OSR. We propose a structured, collaborative, and coordinated approach for observational epidemiology studies that can provide solutions for existing weaknesses and will strengthen credibility and reliability, similar to the approach currently used in clinical trials, where Clinical Trials Registers have played a key role in strengthening their scientific value. Copyright © 2011 Elsevier Inc. All rights reserved.

Hope for a cure and altruism are the main motives behind participation in phase 3 clinical cancer trials.

PubMed

Godskesen, T; Hansson, M G; Nygren, P; Nordin, K; Kihlbom, U

2015-01-01

It is necessary to carry out randomised clinical cancer trials (RCTs) in order to evaluate new, potentially useful treatments for future cancer patients. Participation in clinical trials plays an important role in determining whether a new treatment is the best therapy or not. Therefore, it is important to understand on what basis patients decide to participate in clinical trials and to investigate the implications of this understanding for optimising the information process related to study participation. The aims of this study were to (1) describe motives associated with participation in RCTs, (2) assess if patients comprehend the information related to trial enrolment, and (3) describe patient experiences of trial participation. Questionnaires were sent to 96 cancer patients participating in one of nine ongoing clinical phase 3 trials at the Department of Oncology, Uppsala University Hospital in Sweden. Eighty-eight patients completed the questionnaire (response rate 92%); 95% of these were patients in adjuvant therapy and 5% participated in clinical trials on palliative care. Two main reasons for participation were identified: personal hope for a cure and altruism. Patients show adequate understanding of the information provided to them in the consent process and participation entails high patient satisfaction. © 2014 John Wiley & Sons Ltd.

Hunner's Ulcers

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

Bladder Retraining

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

Reinventing clinical trials: a review of innovative biomarker trial designs in cancer therapies.

PubMed

Lin, Ja-An; He, Pei

2015-06-01

Recently, new clinical trial designs involving biomarkers have been studied and proposed in cancer clinical research, in the hope of incorporating the rapid growing basic research into clinical practices. Journal articles related to various biomarkers and their role in cancer clinical trial, articles and books about statistical issues in trial design, and regulatory website, documents, and guidance for submission of targeted cancer therapies. The drug development process involves four phases. The confirmatory Phase III is essential in regulatory approval of a special treatment. Regulatory agency has restrictions on confirmatory trials 'using adaptive designs'. No rule of thumb to pick the most appropriate design for biomarker-related trials. Statistical issues to solve in new designs. Regulatory acceptance of the 'newly proposed trial designs'. Biomarker-related trial designs that can resolve the statistical issues and satisfy the regulatory requirement. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Recent Clinical Trials in Osteoporosis: A Firm Foundation or Falling Short?

PubMed Central

Lakey, Wanda C.; Batch, Bryan C.; Chiswell, Karen; Tasneem, Asba; Green, Jennifer B.

2016-01-01

The global burden of osteoporotic fractures is associated with significant morbidity, mortality, and healthcare costs. We examined the ClinicalTrials.gov database to determine whether recently registered clinical trials addressed prevention and treatment in those at high risk for fracture. A dataset of 96,346 trials registered in ClinicalTrials.gov was downloaded on September 27, 2010. At the time of the dataset download, 40,970 interventional trials had been registered since October 1, 2007. The osteoporosis subset comprised 239 interventional trials (0.6%). Those trials evaluating orthopedic procedures were excluded. The primary purpose was treatment in 67.0%, prevention in 20.1%, supportive care in 5.8%, diagnostic in 2.2%, basic science in 3.1%, health services research in 0.9%, and screening in 0.9%. The majority of studies (61.1%) included drug-related interventions. Most trials (56.9%) enrolled only women, 38.9% of trials were open to both men and women, and 4.2% enrolled only men. Roughly one fifth (19.7%) of trials excluded research participants older than 65 years, and 33.5% of trials excluded those older than 75 years. The funding sources were industry in 51.0%, the National Institutes of Health in 6.3%, and other in 42.7%. We found that most osteoporosis-related trials registered from October 2007 through September 2010 examined the efficacy and safety of drug treatment, and fewer trials examined prevention and non-drug interventions. Trials of interventions that are not required to be registered in ClinicalTrials.gov may be underrepresented. Few trials are specifically studying osteoporosis in men and older adults. Recently registered osteoporosis trials may not sufficiently address fracture prevention. PMID:27191848

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

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

PubMed Central

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

2014-01-01

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

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines

PubMed Central

2012-01-01

Background A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. Results We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. Conclusions There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Trial registration Current Controlled Trials ISRCTN62323832 PMID:22676626

Description of interventions is under-reported in physical therapy clinical trials.

PubMed

Hariohm, K; Jeyanthi, S; Kumar, J Saravan; Prakash, V

Amongst several barriers to the application of quality clinical evidence and clinical guidelines into routine daily practice, poor description of interventions reported in clinical trials has received less attention. Although some studies have investigated the completeness of descriptions of non-pharmacological interventions in randomized trials, studies that exclusively analyzed physical therapy interventions reported in published trials are scarce. To evaluate the quality of descriptions of interventions in both experimental and control groups in randomized controlled trials published in four core physical therapy journals. We included all randomized controlled trials published from the Physical Therapy Journal, Journal of Physiotherapy, Clinical Rehabilitation, and Archives of Physical Medicine and Rehabilitation between June 2012 and December 2013. Each randomized controlled trial (RCT) was analyzed and coded for description of interventions using the checklist developed by Schroter et al. Out of 100 RCTs selected, only 35 RCTs (35%) fully described the interventions in both the intervention and control groups. Control group interventions were poorly described in the remaining RCTs (65%). Interventions, especially in the control group, are poorly described in the clinical trials published in leading physical therapy journals. A complete description of the intervention in a published report is crucial for physical therapists to be able to use the intervention in clinical practice. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

A screening tool to enhance clinical trial participation at a community center involved in a radiation oncology disparities program.

PubMed

Proctor, Julian W; Martz, Elaine; Schenken, Larry L; Rainville, Rebecca; Marlowe, Ursula

2011-05-01

To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute-funded disparities program but lacking on-site clinical trials personnel. The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials.

A Screening Tool to Enhance Clinical Trial Participation at a Community Center Involved in a Radiation Oncology Disparities Program

PubMed Central

Proctor, Julian W.; Martz, Elaine; Schenken, Larry L.; Rainville, Rebecca; Marlowe, Ursula

2011-01-01

Purpose: To investigate the effectiveness of a screening tool to enhance clinical trial participation at a community radiation oncology center involved in a National Cancer Institute–funded disparities program but lacking on-site clinical trials personnel. Patients and Methods: The screening form was pasted to the front of the charts and filled out for all new patients over the 9-month period of the study, during which time five external beam radiation therapy (EBRT) trials and a patient perception study were open for accrual. Patient consent was obtained by assorted personnel at several different sites. Patients potentially eligible for a trial were identified and approached by one of the clinic staff. Patients who were under- or uninsured, age > 80 years, members of an racial/ethnic minority, or recipients of medical assistance were identified as at risk for health care disparities and were offered patient navigator services. Results: Of 196 patients consulted during the study, 144 were treated with EBRT. Of the 24 patients eligible for EBRT trials, 23 were approached (one had an incomplete screening form), and 15 accepted. Of 77 patients eligible for a patient perception trial, 72 were approached (five had incomplete forms), and 45 accepted. The eligibility and acceptance rates for EBRT trials were similar for disparities and nondisparities patients. Screening was completed for 96 patients (67%). Conclusion: When completed, the screening tool ensured clinical trial accrual. The major factor limiting overall accrual was a shortage of available trials. PMID:21886496

Effects of a Brief Multimedia Psychoeducational Intervention on the Attitudes and Interest of Patients With Cancer Regarding Clinical Trial Participation: A Multicenter Randomized Controlled Trial

PubMed Central

Jacobsen, Paul B.; Wells, Kristen J.; Meade, Cathy D.; Quinn, Gwendolyn P.; Lee, Ji-Hyun; Fulp, William J.; Gray, Jhanelle E.; Baz, Rachid C.; Springett, Gregory M.; Levine, Richard M.; Markham, Merry-Jennifer; Schreiber, Fred J.; Cartwright, Thomas H.; Burke, James M.; Siegel, Robert D.; Malafa, Mokenge P.; Sullivan, Daniel

2012-01-01

Purpose The negative attitudes of patients with cancer regarding clinical trials are an important contributor to low participation rates. This study evaluated whether a brief psychoeducational intervention was effective in improving patients' attitudes as well as their knowledge, self-efficacy for decision making, receptivity to receiving more information, and general willingness to participate in clinical trials. Patients and Methods A total of 472 adults with cancer who had not been asked previously to participate in a clinical trial were randomly assigned to receive printed educational information about clinical trials or a psychoeducational intervention that provided similar information and also addressed misperceptions and concerns about clinical trials. The primary (attitudes) and secondary outcomes (knowledge, self-efficacy, receptivity, and willingness) were assessed via patient self-report before random assignment and 7 to 28 days later. Results Patients who received the psychoeducational intervention showed more positive attitudes toward clinical trials (P = .016) and greater willingness to participate (P = .011) at follow-up than patients who received printed educational information. Evidence of an indirect effect of intervention assignment on willingness to participate (estimated at 0.168; 95% CI, 0.088 to 0.248) suggested that the benefits of psychoeducation on willingness to participate were explained by the positive impact of psychoeducation on attitudes toward clinical trials. Conclusion A brief psychoeducational intervention can improve the attitudes of patients with cancer toward clinical trials and thereby increase their willingness to participate in clinical trials. Findings support conducting additional research to evaluate effects of this intervention on quality of decision making and rates of participation among patients asked to enroll onto therapeutic clinical trials. PMID:22614993

The ClinicalTrials.gov results database--update and key issues.

PubMed

Zarin, Deborah A; Tse, Tony; Williams, Rebecca J; Califf, Robert M; Ide, Nicholas C

2011-03-03

The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data.

Design of control-group conditions in clinical trials of behavioral interventions.

PubMed

Lindquist, Ruth; Wyman, Jean F; Talley, Kristine M C; Findorff, Mary J; Gross, Cynthia R

2007-01-01

To review considerations in the design of placebo (attention) control conditions for community-based clinical trials of health behavior change interventions and to provide practical strategies for the design of control conditions. A well-designed control condition is an essential component of a clinical trial to foster the unambiguous interpretation of study findings. Pitfalls in the design of control conditions in clinical trials of behavioral interventions are identified and strategies to address them are offered. Types of control conditions that have been used in fall prevention trials are described, along with their strengths and weaknesses. The control condition used in the recent fall evaluation and prevention program (FEPP) was designed to overcome limitations of previous trial designs; it is provided to illustrate how to apply specific design principles. Pitfalls in the design of behavioral intervention studies may be avoided with the application of sound design principles. The FEPP active control condition can be used as a model in the design of future studies.

Offering African Americans Opportunities to Participate in Clinical Trials Research: How Social Workers Can Help

ERIC Educational Resources Information Center

Mason, Susan E.

2005-01-01

Historically, African Americans have resisted participation in clinical trials and other research projects because of distrust of the mostly white research establishment. Although there are legitimate reasons for refusing to join clinical trials, most notably the abuses of the Tuskegee Syphilis Study, African Americans may be passing up…

78 FR 39736 - Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-02

..., choosing a study population, using a control group and blinding, dose selection, treatment plans...] Draft Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of Cellular... document entitled ``Guidance for Industry: Considerations for the Design of Early-Phase Clinical Trials of...

Prediction of black box warning by mining patterns of Convergent Focus Shift in clinical trial study populations using linked public data.

PubMed

Ma, Handong; Weng, Chunhua

2016-04-01

To link public data resources for predicting post-marketing drug safety label changes by analyzing the Convergent Focus Shift patterns among drug testing trials. We identified 256 top-selling prescription drugs between 2003 and 2013 and divided them into 83 BBW drugs (drugs with at least one black box warning label) and 173 ROBUST drugs (drugs without any black box warning label) based on their FDA black box warning (BBW) records. We retrieved 7499 clinical trials that each had at least one of these drugs for intervention from the ClinicalTrials.gov. We stratified all the trials by pre-marketing or post-marketing status, study phase, and study start date. For each trial, we retrieved drug and disease concepts from clinical trial summaries to model its study population using medParser and SNOMED-CT. Convergent Focus Shift (CFS) pattern was calculated and used to assess the temporal changes in study populations from pre-marketing to post-marketing trials for each drug. Then we selected 68 candidate drugs, 18 with BBW warning and 50 without, that each had at least nine pre-marketing trials and nine post-marketing trials for predictive modeling. A random forest predictive model was developed to predict BBW acquisition incidents based on CFS patterns among these drugs. Pre- and post-marketing trials of BBW and ROBUST drugs were compared to look for their differences in CFS patterns. Among the 18 BBW drugs, we consistently observed that the post-marketing trials focused more on recruiting patients with medical conditions previously unconsidered in the pre-marketing trials. In contrast, among the 50 ROBUST drugs, the post-marketing trials involved a variety of medications for testing their associations with target intervention(s). We found it feasible to predict BBW acquisitions using different CFS patterns between the two groups of drugs. Our random forest predictor achieved an AUC of 0.77. We also demonstrated the feasibility of the predictor for identifying long-term BBW acquisition events without compromising prediction accuracy. This study contributes a method for post-marketing pharmacovigilance using Convergent Focus Shift (CFS) patterns in clinical trial study populations mined from linked public data resources. These signals are otherwise unavailable from individual data resources. We demonstrated the added value of linked public data and the feasibility of integrating ClinicalTrials.gov summaries and drug safety labels for post-marketing surveillance. Future research is needed to ensure better accessibility and linkage of heterogeneous drug safety data for efficient pharmacovigilance. Copyright © 2016 Elsevier Inc. All rights reserved.

Vitamin K for upper gastrointestinal bleeding in people with acute or chronic liver diseases.

PubMed

Martí-Carvajal, Arturo J; Solà, Ivan

2015-06-09

Upper gastrointestinal bleeding is one of the most frequent causes of morbidity and mortality in the course of liver cirrhosis. Several treatments are used for upper gastrointestinal bleeding in people with liver diseases. One of them is vitamin K administration, but it is not known whether it benefits or harms people with acute or chronic liver disease and upper gastrointestinal bleeding. This is an update of this Cochrane review. To assess the beneficial and harmful effects of vitamin K for people with acute or chronic liver disease and upper gastrointestinal bleeding. We searched The Cochrane Hepato-Biliary Controlled Trials Register (February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2 of 12, 2015), MEDLINE (Ovid SP) (1946 to February 2015), EMBASE (Ovid SP) (1974 to February 2015), Science Citation Index EXPANDED (1900 to February 2015), and LILACS (1982 to 25 February 2015). We sought additional randomised trials from two registries of clinical trials: the World Health Organization Clinical Trials Search Portal and the metaRegister of Controlled Trials. We looked through the reference lists of the retrieved publications and review articles. Randomised clinical trials irrespective of blinding, language, or publication status for assessment of benefits and harms. We considered observational studies for assessment of harms only. \\We aimed to summarise data from randomised clinical trials using Standard Cochrane methodology and assess them according to the GRADE approach. We found no randomised trials on vitamin K for upper gastrointestinal bleeding in people with liver diseases assessing benefits and harms of the intervention. We identified no quasi-randomised studies, historically controlled studies, or observational studies assessing harms. This updated review found no randomised clinical trials of vitamin K for upper gastrointestinal bleeding in people with liver diseases. The benefits and harms of vitamin K need to be tested in randomised clinical trials. Until randomised clinical trials are conducted to assess the trade-off between benefits and harms, we cannot recommend or refute the use of vitamin K for upper gastrointestinal bleeding in people with liver diseases.

Remote preconditioning and major clinical complications following adult cardiovascular surgery: systematic review and meta-analysis.

PubMed

Healy, D A; Khan, W A; Wong, C S; Moloney, M Clarke; Grace, P A; Coffey, J C; Dunne, C; Walsh, S R; Sadat, U; Gaunt, M E; Chen, S; Tehrani, S; Hausenloy, D J; Yellon, D M; Kramer, R S; Zimmerman, R F; Lomivorotov, V V; Shmyrev, V A; Ponomarev, D N; Rahman, I A; Mascaro, J G; Bonser, R S; Jeon, Y; Hong, D M; Wagner, R; Thielmann, M; Heusch, G; Zacharowski, K; Meybohm, P; Bein, B; Tang, T Y

2014-09-01

A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Methodological aspects of clinical trials in tinnitus: A proposal for an international standard

PubMed Central

Landgrebe, Michael; Azevedo, Andréia; Baguley, David; Bauer, Carol; Cacace, Anthony; Coelho, Claudia; Dornhoffer, John; Figueiredo, Ricardo; Flor, Herta; Hajak, Goeran; van de Heyning, Paul; Hiller, Wolfgang; Khedr, Eman; Kleinjung, Tobias; Koller, Michael; Lainez, Jose Miguel; Londero, Alain; Martin, William H.; Mennemeier, Mark; Piccirillo, Jay; De Ridder, Dirk; Rupprecht, Rainer; Searchfield, Grant; Vanneste, Sven; Zeman, Florian; Langguth, Berthold

2013-01-01

Chronic tinnitus is a common condition with a high burden of disease. While many different treatments are used in clinical practice, the evidence for the efficacy of these treatments is low and the variance of treatment response between individuals is high. This is most likely due to the great heterogeneity of tinnitus with respect to clinical features as well as underlying pathophysiological mechanisms. There is a clear need to find effective treatment options in tinnitus, however, clinical trials differ substantially with respect to methodological quality and design. Consequently, the conclusions that can be derived from these studies are limited and jeopardize comparison between studies. Here, we discuss our view of the most important aspects of trial design in clinical studies in tinnitus and make suggestions for an international methodological standard in tinnitus trials. We hope that the proposed methodological standard will stimulate scientific discussion and will help to improve the quality of trials in tinnitus. PMID:22789414

A Systems Approach to Designing Effective Clinical Trials Using Simulations

PubMed Central

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

2013-01-01

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

Development of an online clinical trial recruitment portal for the NIHR mental health BRC.

PubMed

Markham, Sarah

2016-01-01

In order to test whether or not new treatments for mental health disorders help patients get better according to clinician/patient selected criteria, it is often necessary to test them on patients under safe, carefully monitored conditions called clinical trials. It is necessary to find enough patients to take part in a clinical trial so that the results of the trial are reliable. The NIHR Mental Health BRC (here after abbreviated to BRC) is a centre for research in London which seeks to find out better ways to treat patients with mental health difficulties. The BRC has experienced problems trying to find sufficient numbers of patients to participate in its clinical trials as it appears that insufficient patients were being told by their doctor about opportunities to participate in clinical research. In order to help the BRC find enough patients to volunteer to take part in its clinical trials, the author (a patient representative) of this article and a clinical researcher in the nearby Institute of Psychiatry, Psychology and Neuroscience (IoPPN) decided to work together to try to find the best way to let patients know more about what clinical trials are, what it is like to take part in them and which clinical trials are seeking patients to take part. The author and researcher used a report by the Association of Medical Research Charities (AMRC) on patient difficulties in finding clinical trials to take part in, and the recommendations it made, to guide them in building a website to give such patients the information on clinical trials they wanted (including clinical trials run by the BRC). The author and researcher also asked patients, carers, staff at the IoPPN and BRC what they thought of the website and how to make it better. They used the ideas, suggestions and criticisms to improve the website. The author and researcher also asked mental health charities and research organisations if they would advertise the final version of this website on their own websites; many said yes, they would. The manager of the BRC on reviewing the website, agreed that a final version of the website with the NIHR Mental Health BRC logo would be paid for and will form part of a new main website for the BRC in early 2016. ᅟ. Public & patient recruitment to clinical trials is viewed as one of the main barriers to the implementation of clinical trials. This difficulty is often attributed to the working culture of the NHS, rapid turnover of staff and patients and poor-gatekeeping in referring patients to suitable clinical trials. In response to the recruitment difficulties experienced by the Psychosis Studies Clinical Academic Group at the NIHR Mental Health Biomedical Research Centre, Denmark Hill, London, a member of the Office of Psychosis Studies at King's College London and a member (the author) of the King's Clinical Trials Unit, King's College London developed an initiative to create an online clinical trial recruitment portal/information hub for the NIHR Mental Health BRC. The primary purpose of this initiative being to promote patient and public awareness of and interest in participating in clinical trials.

Implementation and value of using a split-plot reader design in a study of digital breast tomosynthesis in a breast cancer assessment clinic

NASA Astrophysics Data System (ADS)

Mall, Suneeta; Brennan, Patrick C.; Mello-Thoms, Claudia

2015-03-01

The rapid evolution in medical imaging has led to an increased number of recurrent trials, primarily to ensure that the efficacy of new imaging techniques is known. The cost associated with time and resources in conducting such trials is usually high. The recruitment of participants, in a medium to large reader study, is often very challenging as the demanding number of cases discourages involvement with the trial. We aim to evaluate the efficacy of Digital Breast Tomosynthesis (DBT) in a recall assessment clinic in Australia in a prospective multi-reader-multi-case (MRMC) trial. Conducting such a study with the more commonly used fully crossed MRMC study design would require more cases and more cases read per reader, which was not viable in our setting. With an aim to perform a cost effective yet statistically efficient clinical trial, we evaluated alternative study designs, particularly the alternative split-plot MRMC study design and compared and contrasted it with more commonly used fully crossed MRMC study design. Our results suggest that `split-plot', an alternative MRMC study design, could be very beneficial for medium to large clinical trials and the cost associated with conducting such trials can be greatly reduced without adversely effecting the variance of the study. We have also noted an inverse dependency between number of required readers and cases to achieve a target variance. This suggests that split-plot could also be very beneficial for studies that focus on cases that are hard to procure or readers that are hard to recruit. We believe that our results may be relevant to other researchers seeking to design a medium to large clinical trials.

Herbal remedy clinical trials in the media: a comparison with the coverage of conventional pharmaceuticals

PubMed Central

Bubela, Tania; Boon, Heather; Caulfield, Timothy

2008-01-01

Background This study systematically compares newspaper coverage of clinical trials for herbal remedies, a popular type of complementary and alternative medicine, with clinical trials for pharmaceuticals using a comparative content analysis. This is a timely inquiry given the recognized importance of the popular press as a source of health information, the complex and significant role of complementary and alternative medicine in individual health-care decisions, and the trend toward evidence-based research for some complementary and alternative medical therapies. We searched PubMed for clinical trials, Lexis/Nexis for newspaper articles in the UK, US, Australia/New Zealand, and Factiva for Canadian newspaper articles from 1995 to 2005. We used a coding frame to analyze and compare 48 pharmaceutical and 57 herbal remedy clinical trials as well as 201 pharmaceutical and 352 herbal remedy newspaper articles. Results Herbal remedy clinical trials had similar Jadad scores to pharmaceutical trials but were significantly smaller and of shorter duration. The trials were mostly studies from Western countries and published in high-ranking journals. The majority of pharmaceutical (64%) and herbal remedy (53%) clinical trials had private sector funding involvement. A minority declared further author conflicts of interest. Newspaper coverage of herbal remedy clinical trials was more negative than for pharmaceutical trials; a result only partly explained by the greater proportion of herbal remedy clinical trials reporting negative results (P = 0.0201; χ2 = 7.8129; degrees of freedom = 2). Errors of omission were common in newspaper coverage, with little reporting of dose, sample size, location, and duration of the trial, methods, trial funding, and conflicts of interest. There was an under-reporting of risks, especially for herbal remedies. Conclusion Our finding of negative coverage of herbal remedy trials is contrary to the positive trends in most published research based primarily on anecdotal accounts. Our results highlight how media coverage is not providing the public with the information necessary to make informed decisions about medical treatments. Most concerning is the lack of disclosure of trial funding and conflicts of interest that could influence the outcome or reporting of trial results. This lack of reporting may impact the medical research community, which has the most to lose by way of public trust and respect. PMID:19036123

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

PubMed

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

2008-04-05

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

Beyond journal publications - a new format for the publication of clinical trials.

PubMed

Wieseler, Beate

2017-02-01

Journal publications are the major route to communicate methods and results of clinical trials. However, the shortcomings of this format are well known, including insufficient quality of the information provided as well as publication and outcome reporting bias. Attempts to improve the situation via peer review, reporting guidelines or study registration did not solve the problem. Currently, new ways of data presentation in electronic databases, increased access to previously confidential documents, and the potential use of anonymized individual patient data from clinical trials beyond the individual trial, have led to discussions about new publication formats for clinical trials. The current paper describes the components required for full information on a clinical trial and discusses a new format to provide this information. Copyright © 2016. Published by Elsevier GmbH.

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

PubMed

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

2018-04-01

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

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.

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

Men and IC

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

IC Associated Conditions

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

General IC Symptoms

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

Children and IC

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group.

PubMed

Vergouwen, Mervyn D I; Vermeulen, Marinus; van Gijn, Jan; Rinkel, Gabriel J E; Wijdicks, Eelco F; Muizelaar, J Paul; Mendelow, A David; Juvela, Seppo; Yonas, Howard; Terbrugge, Karel G; Macdonald, R Loch; Diringer, Michael N; Broderick, Joseph P; Dreier, Jens P; Roos, Yvo B W E M

2010-10-01

In clinical trials and observational studies there is considerable inconsistency in the use of definitions to describe delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage. A major cause for this inconsistency is the combining of radiographic evidence of vasospasm with clinical features of cerebral ischemia, although multiple factors may contribute to DCI. The second issue is the variability and overlap of terms used to describe each phenomenon. This makes comparisons among studies difficult. An international ad hoc panel of experts involved in subarachnoid hemorrhage research developed and proposed a definition of DCI to be used as an outcome measure in clinical trials and observational studies. We used a consensus-building approach. It is proposed that in observational studies and clinical trials aiming to investigate strategies to prevent DCI, the 2 main outcome measures should be: (1) cerebral infarction identified on CT or MRI or proven at autopsy, after exclusion of procedure-related infarctions; and (2) functional outcome. Secondary outcome measure should be clinical deterioration caused by DCI, after exclusion of other potential causes of clinical deterioration. Vasospasm on angiography or transcranial Doppler can also be used as an outcome measure to investigate proof of concept but should be interpreted in conjunction with DCI or functional outcome. The proposed measures reflect the most relevant morphological and clinical features of DCI without regard to pathogenesis to be used as an outcome measure in clinical trials and observational studies.

Global issues in drug development for Alzheimer's disease.

PubMed

Doody, Rachelle S; Cole, Patricia E; Miller, David S; Siemers, Eric; Black, Ronald; Feldman, Howard; Schindler, Rachel; Graham, Stephen; Heath, Theresa; Khachaturian, Ara S; Evans, Rebecca; Carrillo, Maria C

2011-03-01

The number of clinical trials for Alzheimer's disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer's Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer's disease. Copyright © 2011 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Knowledge and skills of cancer clinical trials nurses in Australia.

PubMed

Scott, Kathleen; White, Kate; Johnson, Catherine; Roydhouse, Jessica K

2012-05-01

  This paper is a report of the development and testing of a questionnaire measuring knowledge and skills of cancer clinical trials nurse in Australia.   The role of cancer clinical trials nurse, widely acknowledged as an integral member of the clinical research team, has evolved in recent years. Elements of the clinical trials nurse role in cancer have previously been described. To evaluate specific cancer clinical trials nurse educational and training needs, the development of a valid and reliable tool is required.   In 2009, a study was conducted in three stages. Stage I: questionnaire development and pilot testing; stage II: focus group; stage III: national survey. Internal consistency reliability testing and multi-trait analysis of item convergent/divergent validity were employed. Regression analysis was used to identify predictors of clinical trials nurse knowledge and skills.   The national survey was a 48-item questionnaire, measuring six clinical trial knowledge and seven skills sub-scales. Of 61 respondents, 90% were women, with mean age 43 years, 19 years as a Registered Nurse and 5 years as a cancer clinical trials nurse. Self-reported knowledge and skills were satisfactory to good. Internal consistency reliability was high (Cronbach's alpha: knowledge = 0·98; skills = 0·90). Criteria for item convergent/divergent validity were met. Number of years as cancer clinical trials nurse was positively related to self-reported knowledge and skills.   Preliminary data suggest that the national survey is reliable and valid. Data have contributed to better understanding the knowledge and skills of cancer clinical trials nurse in Australia and development of a postgraduate course in clinical trials. © 2011 Blackwell Publishing Ltd.

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.

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.

[Clinical Tests Testing New Therapies for Stargardt Disease].

PubMed

Kousal, B; Ďuďáková, Ľ; Hlavatá, L; Lišková, P

2016-02-01

To provide information on currently ongoing clinical trials for Stargardt disease. We have searched the clinical trial register (www.clinicaltrials.gov) for the keyword "Stargardt" and list active ongoing studies. There are currently eight registered clinical trials enrolling patients with Stargardt disease; all in phase I or II aiming at four mechanisms of action: inhibition of the production of vitamin A toxic dimers, gene therapy restoring wild type transcription of the ABCA4 gene, neuroprotection preventing retinal cells from oxidative damage, and replacement of the damaged retinal pigment epithelium using stem cell therapy. The basic prerequisite for enrolment in the vast majority of clinical trials is confirmation of the clinical diagnosis by mutational analysis. The wide variety of therapies that are registered as clinical trials for Stargardt disease significantly raises the possibility that effective treatments will be available in the near future for this currently incurable condition and that molecular genetic testing should be increasingly considered. Stargardt disease, clinical trial, ABCA4, mutation.

The experience of adolescents participating in a randomised clinical trial in the field of mental health: a qualitative study.

PubMed

Midgley, Nick; Isaacs, Danny; Weitkamp, Katharina; Target, Mary

2016-07-28

This descriptive study aimed to investigate adolescents' motivations for participating in a randomised controlled trial (RCT), to explore the understanding that the young people had regarding a number of aspects of the trial design, to examine whether or not they found participation in the trial to be acceptable and what affected this, and to identify whether and how the young people felt that their participation in the RCT impacted on their experience of therapy and on therapeutic change. Seventy-six adolescents who were taking part in a large-scale RCT to evaluate the clinical and cost effectiveness of psychological therapies for depression were interviewed at two time-points after completing therapy. The semi-structured interviews, which included a focus on the young people's experience of the research study, were analysed using framework analysis. The vast majority of adolescents found it acceptable to participate in the clinical trial, and many agreed to participate for reasons of 'conditional altruism'. However consent was often given without great understanding of the key elements of the trial, including the difference between treatment arms and the randomisation process. Although the adolescents were largely positive about their experiences from taking part, the study raises questions about whether clinical outcomes may be influenced by participation in the research elements of the trial. Although adolescents are under-represented in clinical trials, those who do participate are generally positive about the experience; however, careful thought needs to be given to key elements of the trial design and the potential impact of the research participation on clinical outcomes. ISRCTN registry, ISRCTN83033550 . Registered on 15 October 2009.

Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals.

PubMed

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-12-01

The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration-approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article.

Patient characteristics driving clinical utility in psychiatric pharmacogenetics: a reanalysis from the AB-GEN multicentric trial.

PubMed

Menchón, J M; Espadaler, J; Tuson, M; Saiz-Ruiz, J; Bobes, J; Vieta, E; Álvarez, E; Pérez, V

2018-05-04

Clinical utility of commercial multi-gene pharmacogenetic tests in depression is starting to be studied with some promising results on efficacy and tolerability. Among the next steps is the definition of the patient profile that is most likely to benefit from testing. Here we present a reanalysis of data from the AB-GEN randomized clinical trial showing that clinical utility of pharmacogenetic testing can be markedly influenced by patient characteristics such as age, baseline severity and duration of current depressive episode.Trial registration ClinicalTrials.gov NCT02529462.

Physicians' perspective on the clinical meaningfulness of inflammatory bowel disease trial results: an International Organization for the Study of Inflammatory Bowel Disease (IOIBD) survey.

PubMed

Olivera, P; Sandborn, W J; Panés, J; Baumann, C; D'Haens, G; Vermeire, S; Danese, S; Peyrin-Biroulet, L

2018-03-01

Several novel compounds are being developed for inflammatory bowel diseases (IBD). In addition, biosimilar drugs are being approved. An increasing number of head-to-head, superiority and non-inferiority trials in patients with IBD are expected in the future. The clinical relevance of the magnitude of the effect size is often debated. To better understand physicians' perspectives on the clinical meaningfulness of IBD trial results. We conducted an online survey among all IOIBD (International Organization for the Study of Inflammatory Bowel Diseases) members, asking their opinion on the clinical relevance of the results of IBD trials. Forty-six IOIBD members responded to the survey (52.3%). In biologic-naïve ulcerative colitis (UC) and Crohn's disease (CD) patients, most of the participants considered a 15% difference with placebo for clinical remission and endoscopic remission to be clinically relevant. In head-to-head trials, most of participants considerer a 10% difference between groups for clinical remission and endoscopic remission to be clinically relevant. Half of respondents considered 10% to be an adequate margin in non-inferiority trials. In bioequivalence studies, most of the participants considered adequate a ± 5% difference between a biosimilar and the originator for pharmacokinetic parameters, efficacy, safety and immunogenicity. Regarding safety, the difference between two drugs considered clinically relevant varied from 1% to 5%, depending on the type of adverse event. This is the first survey exploring how physicians perceive IBD trial results, providing an estimation of the magnitude of the difference between treatment arms that may directly influence clinical practice. © 2018 John Wiley & Sons Ltd.

Age and rate of cognitive decline in Alzheimer disease: implications for clinical trials.

PubMed

Bernick, Charles; Cummings, Jeffrey; Raman, Rema; Sun, Xiaoying; Aisen, Paul

2012-07-01

Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. To determine the influence of age on AD course in a clinical trial setting. Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. Alzheimer disease research centers from across the United States. Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Intention-to-treat analysis and accounting for missing data in orthopaedic randomized clinical trials.

PubMed

Herman, Amir; Botser, Itamar Busheri; Tenenbaum, Shay; Chechick, Ahron

2009-09-01

The intention-to-treat principle implies that all patients who are randomized in a clinical trial should be analyzed according to their original allocation. This means that patients crossing over to another treatment group and patients lost to follow-up should be included in the analysis as a part of their original group. This principle is important for preserving the randomization scheme, which is the basis for correct inference in any randomized trial. In this study, we examined the use of the intention-to-treat principle in recently published orthopaedic clinical trials. We surveyed eight leading orthopaedic journals for randomized clinical trials published between January 2005 and August 2008. We determined whether the intention-to-treat principle was implemented and, if so, how it was used in each trial. Specifically, we ascertained which methods were used to account for missing data. Our search yielded 274 randomized clinical trials, and the intention-to-treat principle was used in ninety-six (35%) of them. There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; this practice was most notable in studies of surgical interventions. The most popular method of adjusting for missing data was the "last observation carried forward" technique. In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission might introduce bias to orthopaedic randomized clinical trials and their analysis.

A New Ethical Challenge for Institutional Review Boards (IRBs)/Ethics Committees (ECs) in the Assessment of Pediatric Clinical Trials.

PubMed

Rose, Klaus; Kummer, Hans

2015-05-28

Both the US and EU have introduced pediatric pharmaceutical legislation to facilitate clinical trials in children and development of better medicines for children. The first concerns were published in 2014 that the European Medicines Agency (EMA)'s Pediatric Committee (PDCO) may be over-enthusiastic and has compelled questionable pediatric clinical trials from pharmaceutical companies. Numerous clinical trials are mandated in rare conditions for which not enough patients exist for even one trial. Furthermore, where these trials are mandated in adolescent patients, the legal age limit of the 18th birthday is confused with a medical age limit and can result in separate clinical trials in adolescent patients that neither make medical nor scientific sense nor will ever recruit enough patients for a meaningful outcome. To confirm our concerns we searched the registry clinicaltrials.gov and found examples for PDCO-triggered unethical trials. We conclude that such trials should not be accepted by institutional review boards (IRBs)/ethics committees (ECs) and that clinical trials resulting from negotiations with EMA's PDCO need extra careful scrutiny by IRBs/ECs in order to prevent unethical studies and damage to pediatric research and unnecessary risks to pediatric patients.

Gender indexing in publications of clinical trials: 1991-2008.

PubMed

Drye, Lea T; Meinert, Jill L; Meinert, Curtis L

2010-12-01

In 1993 Congress passed the NIH Revitalization Act, which instructed the Director of the NIH to ensure that phase III clinical trials are 'designed and carried out in a manner sufficient to provide for a valid analysis of whether the variables being studied in the trial affect females or members of minority groups, as the case may be, differently than other subjects in the trial.' The purpose of this article is to track the PubMed indexing of gender in clinical trial publications since 1991 with a view toward assessing the impact of the legislation on the number of gender specific trials. We searched PubMed for full-length publications from years 1991 to 2008 of research on humans indexed as publication type 'clinical trial', 'randomized clinical trial' and multicenter randomized trial ('multicenter study' AND 'randomized clinical trial'), and counted the number of trials indexed as male-only, female-only, male and female, and gender unknown in PubMed. The majority of trial publications were indexed in PubMed as including both genders. The proportion of publications indexed as including both genders has increased while the number of publications not indexed with respect to gender and the number of publications indexed as male-only have decreased. In 2005, approximately 13% of NIH expenditures were for female specific or related research compared to 6% for male specific or related research. The proportion of clinical trial publications that were indexed in PubMed as including females began to increase before the legislation so it is difficult to conclude that changes in the number of female-only or male-only trials are due to the legislation. PubMed listings do not include gender enrollment, so female and male enrollment totals could not be compared. The NIH policy should be rewritten to be made gender neutral to bring it in line with the principle of justice as embodied in the Belmont Report.

Clinical trial resources on the internet must be designed to reach underrepresented minorities.

PubMed

Wilson, John J; Mick, Rosemarie; Wei, S Jack; Rustgi, Anil K; Markowitz, Sanford D; Hampshire, Maggie; Metz, James M

2006-01-01

Internet-based clinical trial information services are being developed to increase recruitment to studies. However, there are limited data that evaluate their ability to reach elderly and underrepresented minority populations. This study was designed to evaluate the ability of an established clinical trials registry to reach these populations based on expected Internet use. This study compares general Internet users to participants who enrolled in an Internet based colorectal cancer clinical trials registry established by OncoLink (www.oncolink.org) and the National Colorectal Cancer Research Alliance. Observed rates of demographic groupings were compared to those established for general Internet users. Two thousand, four hundred and thirty-seven participants from the continental United States used the Internet to register for the database. New England, the Mid-Atlantic region, and the Southeast had the highest relative frequency of participation in the database, whereas the Upper Midwest, California, and the South had the lowest rates. Compared to general Internet users, there was an overrepresentation of women (73% vs. 50%) and participants over 55 years old (27% vs. 14%). However, there was an underrepresentation of minorities (10.3% vs. 22%), particularly African Americans (3.1% vs. 8%) and Hispanics (2.8% vs. 9%). The Internet is a growing medium for registry into clinical trials databases. However, even taking into account the selection bias of Internet accessibility, there are still widely disparate demographics between general Internet users and those registering for clinical trials, particularly the underrepresentation of minorities. Internet-based educational and recruitment services for clinical trials must be designed to reach these underrepresented minorities to avoid selection biases in future clinical trials.

Interstitial Cystitis and Diet

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

IC Treatment: Surgical Procedures

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

IC: Frequently Asked Questions

MedlinePlus

... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ... Epidemiology (RICE) Study Boston Area Community Health (BACH) Survey ICA Pilot Research Program Funding Opportunities Clinical Trial ...

ClinicalTrials.gov, stem cells and 'pay-to-participate' clinical studies.

PubMed

Turner, Leigh

2017-09-01

Numerous US businesses that engage in direct-to-consumer advertising of stem cell interventions that are not US FDA-approved also recruit clients by listing 'pay-to-participate' studies listed on ClinicalTrials.gov . Individuals considering enrolling in such studies and NIH officials responsible for overseeing the database need to be aware that some businesses are using the registry to promote unapproved stem cell interventions that study subjects are charged to receive. Inclusion of such studies in ClinicalTrials.gov reveals that the database needs better screening tools. In particular, screening should evaluate whether studies submitted to the registry have been reviewed and permitted to proceed by the FDA in the case of clinical studies requiring FDA clearance in addition to institutional review board approval.

Computerized patient identification for the EMBRACA clinical trial using real-time data from the PRAEGNANT network for metastatic breast cancer patients.

PubMed

Hein, Alexander; Gass, Paul; Walter, Christina Barbara; Taran, Florin-Andrei; Hartkopf, Andreas; Overkamp, Friedrich; Kolberg, Hans-Christian; Hadji, Peyman; Tesch, Hans; Ettl, Johannes; Wuerstlein, Rachel; Lounsbury, Debra; Lux, Michael P; Lüftner, Diana; Wallwiener, Markus; Müller, Volkmar; Belleville, Erik; Janni, Wolfgang; Fehm, Tanja N; Wallwiener, Diethelm; Ganslandt, Thomas; Ruebner, Matthias; Beckmann, Matthias W; Schneeweiss, Andreas; Fasching, Peter A; Brucker, Sara Y

2016-07-01

As breast cancer is a diverse disease, clinical trials are becoming increasingly diversified and are consequently being conducted in very small subgroups of patients, making study recruitment increasingly difficult. The aim of this study was to assess the use of data from a remote data entry system that serves a large national registry for metastatic breast cancer. The PRAEGNANT network is a real-time registry with an integrated biomaterials bank that was designed as a scientific study and as a means of identifying patients who are eligible for clinical trials, based on clinical and molecular information. Here, we report on the automated use of the clinical data documented to identify patients for a clinical trial (EMBRACA) for patients with metastatic breast cancer. The patients' charts were assessed by two independent physicians involved in the clinical trial and also by a computer program that tested patients for eligibility using a structured query language script. In all, 326 patients from two study sites in the PRAEGNANT network were included in the analysis. Using expert assessment, 120 of the 326 patients (37 %) appeared to be eligible for inclusion in the EMBRACA study; with the computer algorithm assessment, a total of 129 appeared to be eligible. The sensitivity of the computer algorithm was 0.87 and its specificity was 0.88. Using computer-based identification of patients for clinical trials appears feasible. With the instrument's high specificity, its application in a large cohort of patients appears to be feasible, and the workload for reassessing the patients is limited.

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Hai, Mary T Thanh; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-02-27

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. © 2018 American Heart Association, Inc.

Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

PubMed Central

Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

2014-01-01

Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects present for a specific study phase may have been masked by combining protocols into phase groupings. Presence of informative censoring, such as withdrawal of some protocols from development if they began showing signs of lost interest among investigators, complicates interpretation of Kaplan-Meier estimates. Because this study constitutes a retrospective examination over an extended period of time, it does not allow for the precise identification of relative factors impacting timing. Conclusions Delays not only increase the time and cost to complete clinical trials, but they also diminish their usefulness by failing to answer research questions in time. We believe that research analyzing the time spent traversing defined intervals across the clinical trial protocol development and implementation continuum can stimulate business process analyses and reengineering efforts that could lead to reductions in the time from clinical trial concept to results, thereby accelerating progress in clinical research. PMID:24980279

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.

A Pilot Study of a Culturally Targeted Video Intervention to Increase Participation of African American Patients in Cancer Clinical Trials

PubMed Central

Libin, Alexander V.; Wang, Hong; Swain, Sandra M.

2012-01-01

Purpose. Barriers to clinical trial participation among African American cancer patients are well characterized in the literature. Attitudinal barriers encompassing fear, distrust, and concerns about ethical misconduct are also well documented. To increase trial accrual, these attitudes must be adequately addressed, yet there remains a lack of targeted interventions toward this end. We developed a 15-minute culturally targeted video designed to impact six specific attitudes of African American cancer patients toward therapeutic trials. We conducted a pilot study to test in the first such intervention to increase intention to enroll. Patients and Methods. The primary study outcome was self-reported likelihood to participate in a therapeutic trial. Using a mixed methods approach, we developed the Attitudes and Intention to Enroll in Therapeutic Clinical Trials (AIET) instrument, a 30-item questionnaire measuring six attitudinal barriers to African American trial participation. We enrolled 108 eligible active treatment patients at a large urban cancer institute. McNemar's test for matched pairs was used to assess changes in attitudes and likelihood to enroll in a clinical trial at baseline and immediately after the video. Pre- and post-video AIET summative scores were analyzed by paired t-test for each attitudinal barrier. Results. Patients' likelihood of enrolling in a clinical trial significantly increased post-video with 36% of the sample showing positive changes in intention [McNemar's χ2 = 33.39, p < .001]. Paired t-tests showed significant changes in all six attitudinal barriers measured via AIET summative scores from pre- to post-video. Conclusion. These data suggest utility of our video for increasing African American participation in clinical trials. PMID:22639112

'The trial is owned by the team, not by an individual': a qualitative study exploring the role of teamwork in recruitment to randomised controlled trials in surgical oncology.

PubMed

Strong, Sean; Paramasivan, Sangeetha; Mills, Nicola; Wilson, Caroline; Donovan, Jenny L; Blazeby, Jane M

2016-04-26

Challenges exist in recruitment to trials involving interventions delivered by different clinical specialties. Collaboration is required between clinical specialty and research teams. The aim of this study was to explore how teamwork influences recruitment to a multicentre randomised controlled trial (RCT) involving interventions delivered by different clinical specialties. Semi-structured interviews were conducted in three centres with a purposeful sample of members of the surgical, oncology and research teams recruiting to a feasibility RCT comparing definitive chemoradiotherapy with chemoradiotherapy and surgery for oesophageal squamous cell carcinoma. Interviews explored factors known to influence healthcare team effectiveness and were audio-recorded and thematically analysed. Sampling, data collection and analysis were undertaken iteratively and concurrently. Twenty-one interviews were conducted. Factors that influenced how team working impacted upon trial recruitment were centred on: (1) the multidisciplinary team (MDT) meeting, (2) leadership of the trial, and (3) the recruitment process. The weekly MDT meeting was reported as central to successful recruitment and formed the focus for creating a 'study team', bringing together clinical and research teams. Shared study leadership positively influenced healthcare professionals' willingness to participate. Interviewees perceived their clinical colleagues to have strong treatment preferences which led to scepticism regarding whether the treatments were being described to patients in a balanced manner. This study has highlighted a number of aspects of team functioning that are important for recruitment to RCTs that span different clinical specialties. Understanding these issues will aid the production of guidance on team-relevant issues that should be considered in trial management and the development of interventions that will facilitate teamwork and improve recruitment to these challenging RCTs. International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN89052791 .

Trial sponsorship and self-reported conflicts of interest in breast cancer radiation therapy: An analysis of prospective clinical trials.

PubMed

Leite, Elton T T; Moraes, Fabio Y; Marta, Gustavo N; Taunk, Neil K; Vieira, Marina T L; Hanna, Samir A; Silva, João Luis F; Carvalho, Heloisa A

2017-06-01

We aim to assess any association between study and self-reported conflict of interest (COI) or trial sponsorship in breast cancer radiation clinical trials. We searched PubMed for all clinical trials (CTs) published between 09/2004 and 09/2014 related to breast cancer. We included only radiotherapy CTs with primary clinical endpoints. We classified eligible trials according to the funding source, presence or absence of conflict of interest, study conclusion and impact factor (IF). 1,603 CTs were retrieved. 72 randomized clinical trials were included for analysis. For-profit (PO), not for profit organization (nPO), none and not reported sponsorship rates were 9/72 (12.5%), 35/72 (48.6%), 1/72 (1.4%), 27/72 (37.5%), respectively. Present, absent or not reported COI were found in 6/72 (8.3%), 43/72 (59.7%) and 23/72 (32%) of the CTs, respectively. Conclusion was positive, neutral and negative in 57/72 (79.1%), 9/72 (12.5%) and 6/72 (8.4%) of the trials, respectively. Positive conclusion was reported in 33/44 (75%) funded trials (PO and nPO) and 5/6 (83.3%) CTs with reported COI. On univariate analysis no association with funding source (P=0.178), COI (P=0.678) or trial region (P=0.567) and trial positive conclusion was found. Sponsored trials (HR 4.50, 95CI-0.1.23-16.53;P=0.0023) and positive trials (HR 4.78, 95CI- 1.16-19.63;P=0.030) were more likely to be published in higher impact factor journals in the multivariate analysis. nPO funding was reported in almost 50% of the evaluated CTs. No significant association between study conclusion and funding source, COI or trial region was identified. Sponsored trials and positive trials were more likely to be published in higher impact factor journals. Copyright © 2017 Elsevier Ltd. All rights reserved.

The use of systematic reviews in clinical trials and narrative reviews in dermatology: is the best evidence being used?

PubMed

Conde-Taboada, A; Aranegui, B; García-Doval, I; Dávila-Seijo, P; González-Castro, U

2014-04-01

Systematic reviews -the most comprehensive type of literature review-should be taken into account before a clinical trial or a narrative review on a topic is undertaken. The objective of this study was to describe the use of systematic reviews in clinical trials and narrative reviews in dermatology. This was a descriptive cross-sectional study. We selected randomized clinical trials and narrative reviews from the dermatological clinical research journals identified as most important (according to impact factor) and from Actas Dermosifiliográficas, and studied the bibliographies to ascertain whether the authors made reference to existing systematic reviews and Cochrane reviews. Of the 72 clinical trials for which a systematic review was available, 24 (33.3%) cited at least 1 review; reference was made to relevant Cochrane reviews in 15.6% of cases and to non-Cochrane reviews in 32%. In the case of the 24 narrative reviews for which a review was available, 10 (41.7%) cited at least 1 review; Cochrane reviews were cited in 20% and non-Cochrane reviews in 35.3%.In the case of Actas Dermosifiliográficas, very few clinical trials were found and the findings for narrative review articles were similar to those observed for the other journals. Systematic reviews are not often taken into account by the authors of clinical trials and narrative reviews and this may lead to redundant studies and publications. Authors appear to use Cochrane reviews even less than non-Cochrane reviews and are therefore ignoring one of the main sources of available evidence. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

Design and analysis issues for economic analysis alongside clinical trials.

PubMed

Marshall, Deborah A; Hux, Margaret

2009-07-01

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

Equitable treatment for HIV/AIDS clinical trial participants: a focus group study of patients, clinician researchers, and administrators in Western Kenya.

PubMed

Shaffer, D N; Yebei, V N; Ballidawa, J B; Sidle, J E; Greene, J Y; Meslin, E M; Kimaiyo, S J N; Tierney, W M

2006-01-01

To describe the concerns and priorities of key stakeholders in a developing country regarding ethical obligations held by researchers and perceptions of equity or "what is fair" for study participants in an HIV/AIDS clinical drug trial. Qualitative study with focus groups. Teaching and referral hospital and rural health centre in Western Kenya. Potential HIV/AIDS clinical trial participants, clinician researchers, and administrators. Eighty nine individuals participated in a total of 11 focus groups over a four month period. The desire for continued drug therapy, most often life long, following an HIV/AIDS clinical trial was the most common priority expressed in all focus groups. Patients with and without HIV/AIDS also thought subsidizing of drug therapies and education were critical forms of compensation for clinical trial participation. Financial incentives were considered important primarily for purchasing drug therapy as well as obtaining food. Patients noted a concern for the potential mismanagement of any money offered. Clinician researchers and administrators felt strongly that researchers have a moral obligation to participants following a trial to provide continued drug therapy, adverse event monitoring, and primary care. Finally, clinician researchers and administrators stressed the need for thorough informed consent to avoid coercion of study participants. Kenyan patients, clinician researchers, and administrators believe that it would be unfair to stop antiretroviral therapy following an HIV/AIDS clinical trial and that researchers have a long term obligation to participants.

Recommendations for Self-Report Outcome Measures in Vulvodynia Clinical Trials.

PubMed

Pukall, Caroline F; Bergeron, Sophie; Brown, Candace; Bachmann, Gloria; Wesselmann, Ursula

2017-08-01

Vulvodynia (idiopathic chronic vulvar pain) is a prevalent condition associated with significant and negative impacts in many areas of function. Despite the increased research interest in vulvodynia in recent years, recommendations for outcome measures for use in clinical trials are missing. The purpose of this paper, therefore, was to provide recommendations for outcome measures for vulvodynia clinical trials so that consistent measures are used across trials to facilitate between-study comparisons and the conduct of large multicenter trials, and to improve measurement of the multiple dimensions of vulvodynia. Given that provoked vestibulodynia (PVD)-characterized by provoked pain localized to the vaginal opening-is the most common subtype of vulvodynia and the current main focus of clinical trials, this paper focused on recommended outcome measures in PVD clinical trials. The framework used to guide the selection of outcome measures was based on the one proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). The IMMPACT framework provided a well-suited guideline for outcome measure recommendations in PVD clinical trials. However, given the provoked presentation of PVD and the significant impact it has on sexuality, modifications to some of the IMMPACT recommendations were made and specific additional measures were suggested. Measures that are specific to vulvovaginal pain are ideal for adoption in PVD clinical trials, and many such measures currently exist that allow the relevant IMMPACT domains to be captured.

Asian Americans and Cancer Clinical Trials: A Mixed-Methods Approach to Understanding Awareness and Experience

PubMed Central

Paterniti, Debora A.; Chen, Moon S.; Chiechi, Christine; Beckett, Laurel A.; Horan, Nora; Turrell, Corinne; Smith, Ligaya; Morain, Claudia; Montell, Lisa; Gonzalez, Jose Luis; Davis, Sharon; Lara, Primo N.

2006-01-01

Cancer clinical trials have been based on low accrual rates. Barriers to recruitment of minority populations affect the generalizability and impact of trial findings for those populations. The authors undertook a mixed-methods approach to understanding levels of awareness and experiences with cancer clinical trials. A survey was administered to new cancer patients and their caretakers (family, close friends, or other social support) at outpatient oncology clinics. Field observations of the trial accrual process also were conducted by employing the grounded theory approach in qualitative methods. Comparison of survey results for Asian-American respondents and non-Asian respondents indicated that Asians were less likely to have heard the term “clinical trial” and were more likely to define a clinical trial as “an experiment” or “a test procedure in a clinic” than non-Asians. Asians were more likely to have employer-based insurance and to report understanding issues related to cost reimbursement. Asians were less likely to have been involved in or to know someone in a trial and reported less willingness than white respondents to consider trial participation. Qualitative observations suggested that Asians who presented for a potential trial were interested in the availability of a novel cancer therapy but were not eligible for available trials. Multiple strategies will be necessary to enhance awareness of and experience with accrual to cancer clinical trials for Asians, including richer understanding and increased involvement of Asians in cancer clinical trials and greater attention to the location and diversity of the Asian population in structuring study centers and evaluating trial results. PMID:16247795

Improving decision making about clinical trial participation - a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial.

PubMed

Juraskova, I; Butow, P; Bonner, C; Bell, M L; Smith, A B; Seccombe, M; Boyle, F; Reaby, L; Cuzick, J; Forbes, J F

2014-07-08

Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS-DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation.

Considerations of sex and gender differences in preclinical and clinical trials.

PubMed

Raz, Limor; Miller, Virginia M

2012-01-01

Women continue to be underrepresented in clinical trials, particularly in Phases I and II of experimental drug studies in spite of legislative guidelines in the USA, Canada, the European Union, Australia, and Japan requiring the inclusion of women in clinical trials. As such, women remain a vulnerable population subject to the adverse effects of pharmacological therapies. Thus, women experience higher rates of adverse drug reactions than do men and for women of reproductive age or who may be pregnant, therapeutic options may be limited. This chapter provides a brief history of inclusion of sex and gender as variables in clinical trials, summarizes governmental legislation for consideration of sex and gender in clinical trials and provides specific examples of drugs which have been withdrawn from the market because of side effects in women. Additional information related to sex and gender in preclinical testing, trial design, challenges to recruitment of women for clinical trials and statistical methods for analysis of data also is considered.

Generalisation and extension of a web-based data collection system for clinical studies using Java and CORBA.

PubMed

Eich, H P; Ohmann, C

1999-01-01

Inadequate informatical support of multi-centre clinical trials lead to pure quality. In order to support a multi-centre clinical trial a data collection via WWW and Internet based on Java has been developed. In this study a generalization and extension of this prototype has been performed. The prototype has been applied to another clinical trial and a knowledge server based on C+t has been integrated via CORBA. The investigation and implementation of security aspects of web-based data collection is now under evaluation.

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

Design of a Bayesian adaptive phase 2 proof-of-concept trial for BAN2401, a putative disease-modifying monoclonal antibody for the treatment of Alzheimer's disease.

PubMed

Satlin, Andrew; Wang, Jinping; Logovinsky, Veronika; Berry, Scott; Swanson, Chad; Dhadda, Shobha; Berry, Donald A

2016-01-01

Recent failures in phase 3 clinical trials in Alzheimer's disease (AD) suggest that novel approaches to drug development are urgently needed. Phase 3 risk can be mitigated by ensuring that clinical efficacy is established before initiating confirmatory trials, but traditional phase 2 trials in AD can be lengthy and costly. We designed a Bayesian adaptive phase 2, proof-of-concept trial with a clinical endpoint to evaluate BAN2401, a monoclonal antibody targeting amyloid protofibrils. The study design used dose response and longitudinal modeling. Simulations were used to refine study design features to achieve optimal operating characteristics. The study design includes five active treatment arms plus placebo, a clinical outcome, 12-month primary endpoint, and a maximum sample size of 800. The average overall probability of success is ≥80% when at least one dose shows a treatment effect that would be considered clinically meaningful. Using frequent interim analyses, the randomization ratios are adapted based on the clinical endpoint, and the trial can be stopped for success or futility before full enrollment. Bayesian statistics can enhance the efficiency of analyzing the study data. The adaptive randomization generates more data on doses that appear to be more efficacious, which can improve dose selection for phase 3. The interim analyses permit stopping as soon as a predefined signal is detected, which can accelerate decision making. Both features can reduce the size and duration of the trial. This study design can mitigate some of the risks associated with advancing to phase 3 in the absence of data demonstrating clinical efficacy. Limitations to the approach are discussed.

Standardizing clinical trials workflow representation in UML for international site comparison.

PubMed

de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia M O; Rodrigues, Maria J; Shah, Jatin; Loures, Marco R; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo

2010-11-09

With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows.

Standardizing Clinical Trials Workflow Representation in UML for International Site Comparison

PubMed Central

de Carvalho, Elias Cesar Araujo; Jayanti, Madhav Kishore; Batilana, Adelia Portero; Kozan, Andreia M. O.; Rodrigues, Maria J.; Shah, Jatin; Loures, Marco R.; Patil, Sunita; Payne, Philip; Pietrobon, Ricardo

2010-01-01

Background With the globalization of clinical trials, a growing emphasis has been placed on the standardization of the workflow in order to ensure the reproducibility and reliability of the overall trial. Despite the importance of workflow evaluation, to our knowledge no previous studies have attempted to adapt existing modeling languages to standardize the representation of clinical trials. Unified Modeling Language (UML) is a computational language that can be used to model operational workflow, and a UML profile can be developed to standardize UML models within a given domain. This paper's objective is to develop a UML profile to extend the UML Activity Diagram schema into the clinical trials domain, defining a standard representation for clinical trial workflow diagrams in UML. Methods Two Brazilian clinical trial sites in rheumatology and oncology were examined to model their workflow and collect time-motion data. UML modeling was conducted in Eclipse, and a UML profile was developed to incorporate information used in discrete event simulation software. Results Ethnographic observation revealed bottlenecks in workflow: these included tasks requiring full commitment of CRCs, transferring notes from paper to computers, deviations from standard operating procedures, and conflicts between different IT systems. Time-motion analysis revealed that nurses' activities took up the most time in the workflow and contained a high frequency of shorter duration activities. Administrative assistants performed more activities near the beginning and end of the workflow. Overall, clinical trial tasks had a greater frequency than clinic routines or other general activities. Conclusions This paper describes a method for modeling clinical trial workflow in UML and standardizing these workflow diagrams through a UML profile. In the increasingly global environment of clinical trials, the standardization of workflow modeling is a necessary precursor to conducting a comparative analysis of international clinical trials workflows. PMID:21085484

Clinical trials involving cats: what factors affect owner participation?

PubMed

Gruen, Margaret E; Jiamachello, Katrina N; Thomson, Andrea; Lascelles, B Duncan X

2014-09-01

Clinical trials are frequently hindered by difficulties in recruiting eligible participants, increasing the timeline and limiting generalizability of results. In veterinary medicine, where proxy enrollment is required, no studies have detailed what factors influence owner participation in clinical trials involving cats. We aimed to investigate these factors through a survey of owners at first opinion practices. The survey was designed using feedback from a pilot study and input from clinical researchers. Owners were asked demographic questions and whether they would, would not, or were unsure about participating in a clinical trial with their cat. They then ranked the importance and influence of various factors on participation using a five-point Likert-type scale, and incentives from most to least encouraging. A total of 413 surveys were distributed to cat owners at four hospitals, two feline-only and two multi-species; 88.6% were completed. Data for importance and influence factors as well as incentive rankings were analyzed overall, and by hospital type, location and whether owners would consider participating. The most influential factors were trust in the organization, benefit to the cat and veterinarian recommendation. Importance and influence factors varied by willingness to participate. Ranked incentives were not significantly different across groups, with 'Free Services' ranked highest. This study provides a first look at what factors influence participation in clinical trials with cats. Given the importance placed in the recommendation of veterinarians, continued work is needed to determine veterinarian-related factors affecting clinical trial participation. The results provide guidance towards improved clinical trial design, promotion and education. © ISFM and AAFP 2014.

Effects of an Art-Based Curriculum on Clinical Trials Attitudes and Breast Cancer Prevention Knowledge

ERIC Educational Resources Information Center

Herman, Patricia M.; Larkey, Linda K.

2006-01-01

Although Latinos now comprise the largest minority in the U.S. population, they continue to be seriously underrepresented in clinical trials. A nonrandomized controlled study of an innovative community-developed clinical trial and breast cancer education program targeting Latinas tested whether use of an art-based curriculum could increase…

Clinical trials of a personal electrocardiograph

NASA Astrophysics Data System (ADS)

Boyakhchyan, A.; Lezhnina, I.; Overchuk, K.; Perchatkin, V.; Lvova, A.; Alexander, U.

2018-05-01

The article describes the results of a clinical trial at the Cardiology Research Institute in Tomsk. Clinical trials were conducted to identify different important information for diagnosis. These tests were also conducted to remotely monitor the treatment of patients who had already been discharged from the hospital.The study involved 15 patients, the most interesting cases are described in this article.

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.

Current Experience in Testing Mitochondrial Nutrients in Disorders Featuring Oxidative Stress and Mitochondrial Dysfunction: Rational Design of Chemoprevention Trials

PubMed Central

Pagano, Giovanni; Aiello Talamanca, Annarita; Castello, Giuseppe; Cordero, Mario D.; d’Ischia, Marco; Gadaleta, Maria Nicola; Pallardó, Federico V.; Petrović, Sandra; Tiano, Luca; Zatterale, Adriana

2014-01-01

An extensive number of pathologies are associated with mitochondrial dysfunction (MDF) and oxidative stress (OS). Thus, mitochondrial cofactors termed “mitochondrial nutrients” (MN), such as α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and l-carnitine (CARN) (or its derivatives) have been tested in a number of clinical trials, and this review is focused on the use of MN-based clinical trials. The papers reporting on MN-based clinical trials were retrieved in MedLine up to July 2014, and evaluated for the following endpoints: (a) treated diseases; (b) dosages, number of enrolled patients and duration of treatment; (c) trial success for each MN or MN combinations as reported by authors. The reports satisfying the above endpoints included total numbers of trials and frequencies of randomized, controlled studies, i.e., 81 trials testing ALA, 107 reports testing CoQ10, and 74 reports testing CARN, while only 7 reports were retrieved testing double MN associations, while no report was found testing a triple MN combination. A total of 28 reports tested MN associations with “classical” antioxidants, such as antioxidant nutrients or drugs. Combinations of MN showed better outcomes than individual MN, suggesting forthcoming clinical studies. The criteria in study design and monitoring MN-based clinical trials are discussed. PMID:25380523

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

PubMed Central

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

2011-01-01

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

Understanding Study Participants Views on Co-Creation of Data and Use of EHR in Clinical Studies.

PubMed

Scott Duncan, Therese; Hägglund, Maria

2018-01-01

In order to increase clinical trial participation, the reasons for participating need to be observed. Since there is rather inadequate information concerning how individuals such as patients, decides to participate in clinical trials semi-structured interviews have been done. Examining the use of EHR in clinical trials and co-creation of data, the result showed that it is important for the researches to have access to the patients' EHR and for the patients to contribute with their own ideas of research. Important aspects of further participation in clinical trials were that it should be fun and informative. The patients agreed on that the effort of participating could decrease with the use of electronically collection and self-reporting of data, e.g. through a patient portal.

1-year clinical outcomes of diabetic patients treated with everolimus-eluting bioresorbable vascular scaffolds: a pooled analysis of the ABSORB and the SPIRIT trials.

PubMed

Muramatsu, Takashi; Onuma, Yoshinobu; van Geuns, Robert-Jan; Chevalier, Bernard; Patel, Tejas M; Seth, Ashok; Diletti, Roberto; García-García, Hector M; Dorange, Cécile C; Veldhof, Susan; Cheong, Wai-Fung; Ozaki, Yukio; Whitbourn, Robert; Bartorelli, Antonio; Stone, Gregg W; Abizaid, Alexandre; Serruys, Patrick W

2014-05-01

The aim of this study was to evaluate 1-year clinical outcomes of diabetic patients treated with the Absorb bioresorbable vascular scaffold (BVS). Clinical outcomes of diabetic patients after BVS implantation have been unreported. This study included 101 patients in the ABSORB Cohort B trial and the first consecutive 450 patients with 1 year of follow-up in the ABSORB EXTEND trial. A total of 136 diabetic patients were compared with 415 nondiabetic patients. In addition, 882 diabetic patients treated with everolimus-eluting metal stents (EES) in pooled data from the SPIRIT trials (SPIRIT FIRST [Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT II [A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System], SPIRIT III [Clinical Trial of the XIENCE V Everolimus Eluting Coronary Stent System (EECSS)], SPIRIT IV Clinical Trial [Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System]) were used for the comparison by applying propensity score matching. The primary endpoint was a device-oriented composite endpoint (DoCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization at 1-year follow-up. The cumulative incidence of DoCE did not differ between diabetic and nondiabetic patients treated with the BVS (3.7% vs. 5.1%, p = 0.64). Diabetic patients treated with the BVS had a similar incidence of the DoCE compared with diabetic patients treated with EES in the matched study group (3.9% for the BVS vs. 6.4% for EES, p = 0.38). There were no differences in the incidence of definite or probable scaffold/stent thrombosis (0.7% for both diabetic and nondiabetic patients with the BVS; 1.0% for diabetic patients with the BVS vs. 1.7% for diabetic patients with EES in the matched study group). In the present analyses, diabetic patients treated with the BVS showed similar rates of DoCEs compared with nondiabetic patients treated with the BVS and diabetic patients treated with EES at 1-year follow-up. (ABSORB Clinical Investigation, Cohort B; NCT00856856; ABSORB EXTEND Clinical Investigation; NCT01023789; Clinical Trial of the Abbott Vascular XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT FIRST]; NCT00180453; A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT II]; NCT00180310; Clinical Trial of the XIENCE V Everolimus Eluting Coronary Stent System [EECSS] [SPIRIT III]; NCT00180479; Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System [SPIRIT IV Clinical Trial]; NCT00307047). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Health effects of intermittent fasting: hormesis or harm? A systematic review.

PubMed

Horne, Benjamin D; Muhlestein, Joseph B; Anderson, Jeffrey L

2015-08-01

Intermittent fasting, alternate-day fasting, and other forms of periodic caloric desistance are gaining popularity in the lay press and among animal research scientists. Whether clinical evidence exists for or is strong enough to support the use of such dietary regimens as health interventions is unclear. This review sought to identify rigorous, clinically relevant research studies that provide high-quality evidence that therapeutic fasting regimens are clinically beneficial to humans. A systematic review of the published literature through January 2015 was performed by using sensitive search strategies to identify randomized controlled clinical trials that evaluated the effects of fasting on either clinically relevant surrogate outcomes (e.g., weight, cholesterol) or actual clinical event endpoints [e.g., diabetes, coronary artery disease (CAD)] and any other studies that evaluated the effects of fasting on clinical event outcomes. Three randomized controlled clinical trials of fasting in humans were identified, and the results were published in 5 articles, all of which evaluated the effects of fasting on surrogate outcomes. Improvements in weight and other risk-related outcomes were found in the 3 trials. Two observational clinical outcomes studies in humans were found in which fasting was associated with a lower prevalence of CAD or diabetes diagnosis. No randomized controlled trials of fasting for clinical outcomes were identified. Clinical research studies of fasting with robust designs and high levels of clinical evidence are sparse in the literature. Whereas the few randomized controlled trials and observational clinical outcomes studies support the existence of a health benefit from fasting, substantial further research in humans is needed before the use of fasting as a health intervention can be recommended. © 2015 American Society for Nutrition.

International Conference on Harmonisation; Guidance on M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals; availability. Notice.

PubMed

2010-01-21

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "M3(R2) Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals.'' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance, which is a revision of an existing guidance, discusses the types of nonclinical studies, their scope and duration, and their relation to the conduct of human clinical trials and marketing authorization for pharmaceuticals. The guidance is intended to facilitate the timely conduct of clinical trials and reduce the unnecessary use of animals and other drug development resources.

Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy

PubMed Central

Bartus, Raymond T; Weinberg, Marc S; Samulski, R. Jude

2014-01-01

Over the past decade, nine gene therapy clinical trials for Parkinson's disease (PD) have been initiated and completed. Starting with considerable optimism at the initiation of each trial, none of the programs has yet borne sufficiently robust clinical efficacy or found a clear path toward regulatory approval. Despite the immediately disappointing nature of the efficacy outcomes in these trials, the clinical data garnered from the individual studies nonetheless represent tangible and significant progress for the gene therapy field. Collectively, the clinical trials demonstrate that we have overcome the major safety hurdles previously suppressing central nervous system (CNS) gene therapy, for none produced any evidence of untoward risk or harm after administration of various vector-delivery systems. More importantly, these studies also demonstrated controlled, highly persistent generation of biologically active proteins targeted to structures deep in the human brain. Therefore, a renewed, focused emphasis must be placed on advancing clinical efficacy by improving clinical trial design, patient selection and outcome measures, developing more predictive animal models to support clinical testing, carefully performing retrospective analyses, and most importantly moving forward—beyond our past limits. PMID:24356252

Impact of Prior Cancer on Eligibility for Lung Cancer Clinical Trials

PubMed Central

Laccetti, Andrew L.; Xuan, Lei; Halm, Ethan A.; Pruitt, Sandi L.

2014-01-01

Background In oncology clinical trials, the assumption that a prior cancer diagnosis could interfere with study conduct or outcomes results in frequent exclusion of such patients. We determined the prevalence and characteristics of this practice in lung cancer clinical trials and estimated impact on trial accrual. Methods We reviewed lung cancer clinical trials sponsored or endorsed by the Eastern Oncology Cooperative Group for exclusion criteria related to a prior cancer diagnosis. We estimated prevalence of prior primary cancer diagnoses among lung cancer patients using Surveillance Epidemiology and End Results (SEER)-Medicare linked data. We assessed the association between trial characteristics and prior cancer exclusion using chi-square analysis. All statistical tests were two-sided. Results Fifty-one clinical trials (target enrollment 13072 patients) were included. Forty-one (80%) excluded patients with a prior cancer diagnosis as follows: any prior (14%), within five years (43%), within two or three years (7%), or active cancer (16%). In SEER-Medicare data (n = 210509), 56% of prior cancers were diagnosed within five years before the lung cancer diagnosis. Across trials, the estimated number and proportion of patients excluded because of prior cancer ranged from 0–207 and 0%-18%. Prior cancer was excluded in 94% of trials with survival primary endpoints and 73% of trials with nonsurvival primary endpoints (P = .06). Conclusions A substantial proportion of patients are reflexively excluded from lung cancer clinical trials because of prior cancer. This inclusion criterion is applied widely across studies, including more than two-thirds of trials with nonsurvival endpoints. More research is needed to understand the basis and ramifications of this exclusion policy. PMID:25253615

Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial.

PubMed

Koeneman, M M; Kruse, A J; Kooreman, L F S; Zur Hausen, A; Hopman, A H N; Sep, S J S; Van Gorp, T; Slangen, B F M; van Beekhuizen, H J; van de Sande, A J M; Gerestein, C G; Nijman, H W; Kruitwagen, R F P M

2017-02-07

The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia (CIN). The lagging inclusions were mainly due to a strong patient preference for either of the two treatment modalities. This prompted us to initiate a new study on the same subject, with a non-randomized, open-label design: the 'TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC)-3' study. Original TOPIC-trial: Medical Ethics Committee approval number METC13231; ClinicalTrials.gov Identifier: NCT02329171, 22 December 2014. TOPIC-3 study: Medical Ethics Committee approval number METC162025; ClinicalTrials.gov Identifier: NCT02917746, 16 September 2016.

Electronic Cigarettes for Smoking Cessation.

PubMed

Orellana-Barrios, Menfil A; Payne, Drew; Medrano-Juarez, Rita M; Yang, Shengping; Nugent, Kenneth

2016-10-01

The use of electronic cigarettes (e-cigarettes) is increasing, but their use as a smoking-cessation aid is controversial. The reporting of e-cigarette studies on cessation is variable and inconsistent. To date, only 1 randomized clinical trial has included an arm with other cessation methods (nicotine patches). The cessation rates for available clinical trials are difficult to compare given differing follow-up periods and broad ranges (4% at 12 months with non-nicotine e-cigarettes to 68% at 4 weeks with concomitant nicotine e-cigarettes and other cessation methods). The average combined abstinence rate for included prospective studies was 29.1% (combination of 6-18 months׳ rates). There are few comparable clinical trials and prospective studies related to e-cigarettes use for smoking cessation, despite an increasing number of citations. Larger randomized clinical trials are essential to determine whether e-cigarettes are effective smoking-cessation devices. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools

PubMed Central

2012-01-01

Background Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW) store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. Methods The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Results Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. Conclusions This software is intended to provide an initial list of eligible patients to a clinical study coordinators, which provides a starting point for further eligibility screening by the coordinator. Because this software has a high “rule in” ability, meaning that it is able to remove patients who are not eligible for the study, the use of an automated tool built to leverage an existing enterprise DW can be beneficial to determining eligibility and facilitating clinical trial recruitment through pre-screening. While the results of this study are promising, further refinement and study of this and related approaches to automated eligibility screening, including comparison to other approaches and stakeholder perceptions, are needed and future studies are planned to address these needs. PMID:22646313

Computational challenges and human factors influencing the design and use of clinical research participant eligibility pre-screening tools.

PubMed

Pressler, Taylor R; Yen, Po-Yin; Ding, Jing; Liu, Jianhua; Embi, Peter J; Payne, Philip R O

2012-05-30

Clinical trials are the primary mechanism for advancing clinical care and evidenced-based practice, yet challenges with the recruitment of participants for such trials are widely recognized as a major barrier to these types of studies. Data warehouses (DW) store large amounts of heterogenous clinical data that can be used to enhance recruitment practices, but multiple challenges exist when using a data warehouse for such activities, due to the manner of collection, management, integration, analysis, and dissemination of the data. A critical step in leveraging the DW for recruitment purposes is being able to match trial eligibility criteria to discrete and semi-structured data types in the data warehouse, though trial eligibility criteria tend to be written without concern for their computability. We present the multi-modal evaluation of a web-based tool that can be used for pre-screening patients for clinical trial eligibility and assess the ability of this tool to be practically used for clinical research pre-screening and recruitment. The study used a validation study, usability testing, and a heuristic evaluation to evaluate and characterize the operational characteristics of the software as well as human factors affecting its use. Clinical trials from the Division of Cardiology and the Department of Family Medicine were used for this multi-modal evaluation, which included a validation study, usability study, and a heuristic evaluation. From the results of the validation study, the software demonstrated a positive predictive value (PPV) of 54.12% and 0.7%, respectively, and a negative predictive value (NPV) of 73.3% and 87.5%, respectively, for two types of clinical trials. Heuristic principles concerning error prevention and documentation were characterized as the major usability issues during the heuristic evaluation. This software is intended to provide an initial list of eligible patients to a clinical study coordinators, which provides a starting point for further eligibility screening by the coordinator. Because this software has a high "rule in" ability, meaning that it is able to remove patients who are not eligible for the study, the use of an automated tool built to leverage an existing enterprise DW can be beneficial to determining eligibility and facilitating clinical trial recruitment through pre-screening. While the results of this study are promising, further refinement and study of this and related approaches to automated eligibility screening, including comparison to other approaches and stakeholder perceptions, are needed and future studies are planned to address these needs.

SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2015-12-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

SPIRIT 2013 Statement: Defining Standard Protocol Items for Clinical Trials

PubMed Central

Chan, An-Wen; Tetzlaff, Jennifer M.; Altman, Douglas G.; Laupacis, Andreas; Gøtzsche, Peter C.; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A.; Doré, Caroline J.; Parulekar, Wendy R.; Summerskill, William S.M.; Groves, Trish; Schulz, Kenneth F.; Sox, Harold C.; Rockhold, Frank W.; Rennie, Drummond; Moher, David

2016-01-01

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders. PMID:23295957

SPIRIT 2013 statement: defining standard protocol items for clinical trials.

PubMed

Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krleža-Jerić, Karmela; Hróbjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Doré, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

2013-02-05

The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol.The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

Recommendations for pharmacological clinical trials in children with functional constipation: The Rome foundation pediatric subcommittee on clinical trials.

PubMed

Koppen, I J N; Saps, M; Lavigne, J V; Nurko, S; Taminiau, J A J M; Di Lorenzo, C; Benninga, M A

2018-04-01

Evidence for the efficacy of commonly used drugs in the treatment of childhood functional constipation (FC) is scarce, studies are often of low quality and study designs are heterogeneous. Thus, recommendations for the design of clinical trials in childhood FC are needed. Members of the Rome Foundation and a member of the Pediatric Committee of the European Medicines Agency formed a committee to create recommendations for the design of clinical trials in children with FC. This committee recommends conducting randomized, double-blind, placebo-controlled, parallel-group clinical trials to assess the efficacy of new drugs for the treatment of childhood FC. Pediatric study participants should be included based on fulfilling the Rome IV criteria for FC. A treatment free run-in period for baseline assessment is recommended. The trial duration should be at least 8 weeks. Treatment success is defined as no longer meeting the Rome IV criteria for FC. Stool consistency should be reported based on the Bristol Stool Scale. Endpoints of drug efficacy need to be tailored to the developmental age of the patient population. © 2018 John Wiley & Sons Ltd.

Using ClinicalTrials.gov to Supplement Information in Ophthalmology Conference Abstracts about Trial Outcomes: A Comparison Study

PubMed Central

Scherer, Roberta W.; Huynh, Lynn; Ervin, Ann-Margret; Dickersin, Kay

2015-01-01

Background Including results from unpublished randomized controlled trials (RCTs) in a systematic review may ameliorate the effect of publication bias in systematic review results. Unpublished RCTs are sometimes described in abstracts presented at conferences, included in trials registers, or both. Trial results may not be available in a trials register and abstracts describing RCT results often lack study design information. Complementary information from a trials register record may be sufficient to allow reliable inclusion of an unpublished RCT only available as an abstract in a systematic review. Methods We identified 496 abstracts describing RCTs presented at the 2007 to 2009 Association for Research in Vision and Ophthalmology (ARVO) meetings; 154 RCTs were registered in ClinicalTrials.gov. Two persons extracted verbatim primary and non-primary outcomes reported in the abstract and ClinicalTrials.gov record. We compared each abstract outcome with all ClinicalTrials.gov outcomes and coded matches as complete, partial, or no match. Results We identified 800 outcomes in 152 abstracts (95 primary [51 abstracts] and 705 [141 abstracts] non-primary outcomes). No outcomes were reported in 2 abstracts. Of 95 primary outcomes, 17 (18%) agreed completely, 53 (56%) partially, and 25 (26%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among 705 non-primary outcomes, 56 (8%) agreed completely, 205 (29%) agreed partially, and 444 (63%) had no match with a ClinicalTrials.gov primary or non-primary outcome. Among the 258 outcomes partially agreeing, we found additional information on the time when the outcome was measured more often in ClinicalTrials.gov than in the abstract (141/258 (55%) versus 55/258 (21%)). We found no association between the presence of non-matching “new” outcomes and year of registration, time to registry update, industry sponsorship, or multi-center status. Conclusion Conference abstracts may be a valuable source of information about results for outcomes of unpublished RCTs that have been registered in ClinicalTrials.gov. Complementary additional descriptive information may be present for outcomes reported in both sources. However, ARVO abstract authors also present outcomes not reported in ClinicalTrials.gov and these may represent analyses not originally planned. PMID:26107924

The life cycles of six multi-center adaptive clinical trials focused on neurological emergencies developed for the Advancing Regulatory Science initiative of the National Institutes of Health and US Food and Drug Administration: Case studies from the Adaptive Designs Accelerating Promising Treatments Into Trials Project

PubMed Central

Guetterman, Timothy C; Fetters, Michael D; Mawocha, Samkeliso; Legocki, Laurie J; Barsan, William G; Lewis, Roger J; Berry, Donald A; Meurer, William J

2017-01-01

Objectives: Clinical trials are complicated, expensive, time-consuming, and frequently do not lead to discoveries that improve the health of patients with disease. Adaptive clinical trials have emerged as a methodology to provide more flexibility in design elements to better answer scientific questions regarding whether new treatments are efficacious. Limited observational data exist that describe the complex process of designing adaptive clinical trials. To address these issues, the Adaptive Designs Accelerating Promising Treatments Into Trials project developed six, tailored, flexible, adaptive, phase-III clinical trials for neurological emergencies, and investigators prospectively monitored and observed the processes. The objective of this work is to describe the adaptive design development process, the final design, and the current status of the adaptive trial designs that were developed. Methods: To observe and reflect upon the trial development process, we employed a rich, mixed methods evaluation that combined quantitative data from visual analog scale to assess attitudes about adaptive trials, along with in-depth qualitative data about the development process gathered from observations. Results: The Adaptive Designs Accelerating Promising Treatments Into Trials team developed six adaptive clinical trial designs. Across the six designs, 53 attitude surveys were completed at baseline and after the trial planning process completed. Compared to baseline, the participants believed significantly more strongly that the adaptive designs would be accepted by National Institutes of Health review panels and non-researcher clinicians. In addition, after the trial planning process, the participants more strongly believed that the adaptive design would meet the scientific and medical goals of the studies. Conclusion: Introducing the adaptive design at early conceptualization proved critical to successful adoption and implementation of that trial. Involving key stakeholders from several scientific domains early in the process appears to be associated with improved attitudes towards adaptive designs over the life cycle of clinical trial development. PMID:29085638

The data management of a phase III efficacy trial of an 11-valent pneumococcal conjugate vaccine and related satellite studies conducted in the Philippines.

PubMed

Sanvictores, Diozele Hazel M; Lucero, Marilla G; Nohynek, Hanna; Tallo, Veronica L; Tanskanen, Antti; Nillos, Leilani T; Williams, Gail

2012-06-07

A large phase III placebo-controlled, randomized efficacy trial of an investigational 11-valent pneumococcal conjugate vaccine against pneumonia in children less than 2 years of age was conducted in the Philippines from July 2000 to December 2004. Clinical data from 12,194 children who were given either study vaccine or placebo was collected from birth up to two years of age for the occurrence of radiologically proven pneumonia as the primary endpoint, and for clinical pneumonia and invasive pneumococcal disease as the secondary endpoints. Several tertiary endpoints were also explored. Along the core trial, several satellite studies on herd immunity, cost-effectiveness of the study vaccine, acute otitis media, and wheezing were conducted. We describe here in detail how the relevant clinical records were managed and how quality control procedures were implemented to ensure that valid data were obtained respectively for the core trial and for the satellite studies. We discuss how the task was achieved, what the challenges were and what might have been done differently. There were several factors that made the task of data management doable and efficient. First, a pre-trial data management system was available. Secondly, local committed statisticians, programmers and support staff were available and partly familiar to clinical trials. Thirdly, the personnel had undergone training during trial and grew with the task they were supposed to do. Thus the knowledge needed to develop and operate clinical data system was fully transferred to local staff. Current Controlled Trials ISRCTN62323832.

The ClinicalTrials.gov Results Database — Update and Key Issues

PubMed Central

Zarin, Deborah A.; Tse, Tony; Williams, Rebecca J.; Califf, Robert M.; Ide, Nicholas C.

2011-01-01

BACKGROUND The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. METHODS We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. RESULTS As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. CONCLUSIONS ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data. PMID:21366476

Factors influencing participation of psychiatry inpatients in clinical trials.

PubMed

Mopuru, Nandeeshwar Reddy; Jose, Sam Padamadan; Viswanath, Biju; Kumar, C Naveen; Math, Suresh Bada; Thirthalli, Jagadisha

2018-02-01

Serious concerns have arisen in recent years regarding the unethical and illegal practices resorted to during clinical trials. Clinical trials in psychiatry are further complicated by issues such as 'validity of consent' and 'decision making capacity' of patients. This study was planned to explore the factors determining patient participation in clinical trials. A random sample of 123 consenting psychiatry inpatients were provided the information and consent-form of a hypothetical clinical drug trial. They were interviewed regarding their decision, the decision maker and factors that led to the decision. Family members tended to be the decision makers when patients were females, had low-income, were from rural background or had severe illnesses. Anticipated side effects and not wanting to interfere with existing treatment were the common reasons for refusal to participate while hope of betterment of the patient and benefit to humanity were cited for consent. The educated, urban, affluent class had more awareness regarding unethical trials and tended to be mistrustful of the medical community leading to higher rates of non-participation. Those who were adherent with ongoing treatment were also unwilling to participate. The lesser educated, low-income patients and rural domicile patients on the other hand had lesser awareness regarding clinical trials, trusted doctors and were more likely to participate. A good doctor-patient relationship, detailed explanations and clarification regarding the study and its conduct, and building awareness regarding clinical trials among vulnerable groups is necessary to ensure a valid consent involving no coercion, removal of prejudices, and ethical conduct of trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Stock market returns and clinical trial results of investigational compounds: an event study analysis of large biopharmaceutical companies.

PubMed

Hwang, Thomas J

2013-01-01

For biopharmaceutical companies, investments in research and development are risky, and the results from clinical trials are key inflection points in the process. Few studies have explored how and to what extent the public equity market values clinical trial results. Our study dataset matched announcements of clinical trial results for investigational compounds from January 2011 to May 2013 with daily stock market returns of large United States-listed pharmaceutical and biotechnology companies. Event study methodology was used to examine the relationship between clinical research events and changes in stock returns. We identified public announcements for clinical trials of 24 investigational compounds, including 16 (67%) positive and 8 (33%) negative events. The majority of announcements were for Phase 3 clinical trials (N = 13, 54%), and for oncologic (N = 7, 29%) and neurologic (N = 6, 24%) indications. The median cumulative abnormal returns on the day of the announcement were 0.8% (95% confidence interval [CI]: -2.3, 13.4%; P = 0.02) for positive events and -2.0% (95% CI: -9.1, 0.7%; P = 0.04) for negative events, with statistically significant differences from zero. In the day immediately following the announcement, firms with positive events were associated with stock price corrections, with median cumulative abnormal returns falling to 0.4% (95% CI: -3.8, 12.3%; P = 0.33). For firms with negative announcements, the median cumulative abnormal returns were -1.7% (95% CI: -9.5, 1.0%; P = 0.03), and remained significantly negative over the two day event window. The magnitude of abnormal returns did not differ statistically by indication, by trial phase, or between biotechnology and pharmaceutical firms. The release of clinical trial results is an economically significant event and has meaningful effects on market value for large biopharmaceutical companies. Stock return underperformance due to negative events is greater in magnitude and persists longer than abnormal returns due to positive events, suggesting asymmetric market reactions.

Economic benefits of sponsored clinical trials on pharmaceutical expenditures at a medical center in Taiwan.

PubMed

Shen, Li-Jiuan; Chou, Hua; Huang, Chih-Fen; Chou, Guann-Miaw; Chan, Wing Kai; Wu, Fe-Lin Lin

2011-07-01

Concerns exist regarding the additional cost of patient care when patients are enrolled in clinical trials at hospitals. To assess the avoidance of drug costs by conducting sponsored clinical trials, a retrospective analysis evaluating drug cost avoidance in all sponsored clinical trials was conducted in 2008 at the most prominent medical center in Taiwan. The National Health Insurance (NHI) reimbursement prices of either the investigated drugs or the standardized drug therapy for each specific disease were used to calculate the cost avoidance. Drug cost avoidance from sponsored clinical trials per year, per trial, per patient, in different therapeutic areas, and in different phases was analyzed. Three quarters of the cost avoidance in drug expenditures from 194 sponsored clinical trials were estimated. All cost values are in US Dollars. Around $11.2 million was avoided at the center in 2008. The average value of cost avoidance was $58,000/trial-year or $3,900/participant-year. The early-phase trials and phase III trials accounted for 25% and 56% of all trials, respectively, while they constituted 32% and 49% of the total costs avoided, respectively. The most frequently conducted and highest cost-avoiding trials were those for antineoplastic agents, especially targeted therapy which accounted for 85% of the total cost avoidance of anti-cancer trials. This study demonstrates the profoundly positive economic impact on the healthcare system in Taiwan by sponsored clinical trials. To understand the trend of economic benefits of the trials on pharmaceutical expenditure, it would be important to analyze the cost avoidance of trials regularly in an institution. Copyright © 2011 Elsevier Inc. All rights reserved.

Editorial--Avoiding Unethical Helicobacter pylori Clinical Trials: Susceptibility-Based Studies and Probiotics as Adjuvants.

PubMed

Graham, David Y

2015-10-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g., in a population with known clarithromycin resistance) is unethical. As susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance >0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies, and studies of adjuvants and probiotics. However, the journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors, we provide examples and suggestions regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. © 2015 John Wiley & Sons Ltd.

Birth Rates Among Hispanics and Non-Hispanics and their Representation in Contemporary Obstetric Clinical Trials.

PubMed

Kahr, Maike K; De La Torre, Rosa; Racusin, Diana A; Suter, Melissa A; Mastrobattista, Joan M; Ramin, Susan M; Clark, Steven L; Dildy, Gary A; Belfort, Michael A; Aagaard, Kjersti M

2016-10-01

Objective Our study aims were to establish whether subjects enrolled in current obstetric clinical trials proportionately reflects the contemporary representation of Hispanic ethnicities and their birth rates in the United States. Methods Using comprehensive source data over a defined interval (January 2011-September 2015) on birth rates by ethnicity from the Centers for Disease Control and Prevention (CDC), we evaluated the proportional rate by ethnicity, then analyzed the observed to expected relative ratio of enrolled subjects. Results Hispanic women comprise a significant contribution to births in the United States (23% of all births). Systematic analysis of 90 published obstetric clinical trials showed a correlation between inclusion of Hispanic gravidae and the corresponding state's birth rates (r = 0.501, p < 0.001). While the mean was strongly correlated, individual clinical trials may have relatively over-enrolled (n = 31, or 34%) or under-enrolled (n = 33, or 37%) relative to their regional population. In 48% of obstetric clinical trials the Hispanic proportion of the study population was not reported. Conclusion Hispanic gravidae represent a significant number of contemporary U.S. births, and are generally adequately represented as obstetric subjects in clinical trials. However, this is trial-dependent, with significant trial-specific under- and over-enrollment of Hispanic subjects relative to the regional birth population. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Raising Public Awareness of Clinical Trials: Development of Messages for a National Health Communication Campaign.

PubMed

Massett, Holly A; Dilts, David M; Bailey, Robert; Berktold, Jennifer; Ledsky, Rebecca; Atkinson, Nancy L; Mishkin, Grace; Denicoff, Andrea; Padberg, Rose Mary; Allen, Marin P; Silver, Karen; Carrington, Kelli; Johnson, Lenora E

2017-05-01

Clinical trials are essential for developing new and effective treatments and improving patient quality of life; however, many trials cannot answer their primary research questions because they fall short of their recruitment goals. This article reports the results of formative research conducted in two populations, the public and primary care physicians, to identify messages that may raise awareness and increase interest in clinical trials and be used in a national communication campaign. Results suggested that participants were primarily motivated to participate in clinical trials out of a self-interest to help themselves first. Messages illustrated that current treatments were tested via clinical trials, helped normalize trials as routine practices, and reduced concerns over trying something new first. Participants wanted messages that portray trials as state-of-the-art choices that offer some hope, show people like themselves, and are described in a clear, concise manner with actionable steps for them to take. The study revealed some differences in message salience, with healthy audiences exhibiting lower levels of interest. Our results suggest that targeted messages are needed, and that communication with primary health-care providers is an important and necessary component in raising patient awareness of the importance of clinical trials.

On the value of therapeutic interventions targeting the complement system in acute myocardial infarction.

PubMed

Emmens, Reindert W; Wouters, Diana; Zeerleder, Sacha; van Ham, S Marieke; Niessen, Hans W M; Krijnen, Paul A J

2017-04-01

The complement system plays an important role in the inflammatory response subsequent to acute myocardial infarction (AMI). The aim of this study is to create a systematic overview of studies that have investigated therapeutic administration of complement inhibitors in both AMI animal models and human clinical trials. To enable extrapolation of observations from included animal studies toward post-AMI clinical trials, ex vivo studies on isolated hearts and proof-of-principle studies on inhibitor administration before experimental AMI induction were excluded. Positive therapeutic effects in AMI animal models have been described for cobra venom factor, soluble complement receptor 1, C1-esterase inhibitor (C1-inh), FUT-175, C1s-inhibitor, anti-C5, ADC-1004, clusterin, and glycosaminoglycans. Two types of complement inhibitors have been tested in clinical trials, being C1-inh and anti-C5. Pexelizumab (anti-C5) did not result in reproducible beneficial effects for AMI patients. Beneficial effects were reported in AMI patients for C1-inhibitor, albeit in small patient groups. In general, despite the absence of consistent positive effects in clinical trials thus far, the complement system remains a potentially interesting target for therapy in AMI patients. Based on the study designs of previous animal studies and clinical trials, we discuss several issues which require attention in the design of future studies: adjustment of clinical trial design to precise mechanism of action of administered inhibitor, optimizing the duration of therapy, and optimization of time point(s) on which therapeutic effects will be evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

QIN. Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials

PubMed Central

Doot, Robert K.; Thompson, Tove; Greer, Benjamin E.; Allberg, Keith C.; Linden, Hannah M.; Mankoff, David A.; Kinahan, Paul E.

2012-01-01

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging is a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. PMID:22795929

Early experiences in establishing a regional quantitative imaging network for PET/CT clinical trials.

PubMed

Doot, Robert K; Thompson, Tove; Greer, Benjamin E; Allberg, Keith C; Linden, Hannah M; Mankoff, David A; Kinahan, Paul E

2012-11-01

The Seattle Cancer Care Alliance (SCCA) is a Pacific Northwest regional network that enables patients from community cancer centers to participate in multicenter oncology clinical trials where patients can receive some trial-related procedures at their local center. Results of positron emission tomography (PET) scans performed at community cancer centers are not currently used in SCCA Network trials since clinical trials customarily accept results from only trial-accredited PET imaging centers located at academic and large hospitals. Oncologists would prefer the option of using standard clinical PET scans from Network sites in multicenter clinical trials to increase accrual of patients for whom additional travel requirements for imaging are a barrier to recruitment. In an effort to increase accrual of rural and other underserved populations to Network trials, researchers and clinicians at the University of Washington, SCCA and its Network are assessing the feasibility of using PET scans from all Network sites in their oncology clinical trials. A feasibility study is required because the reproducibility of multicenter PET measurements ranges from approximately 3% to 40% at national academic centers. Early experiences from both national and local PET phantom imaging trials are discussed, and next steps are proposed for including patient PET scans from the emerging regional quantitative imaging network in clinical trials. There are feasible methods to determine and characterize PET quantitation errors and improve data quality by either prospective scanner calibration or retrospective post hoc corrections. These methods should be developed and implemented in multicenter clinical trials employing quantitative PET imaging of patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Gene Editing: Regulatory and Translation to Clinic.

PubMed

Ando, Dale; Meyer, Kathleen

2017-10-01

The clinical application and regulatory strategy of genome editing for ex vivo cell therapy is derived from the intersection of two fields of study: viral vector gene therapy trials; and clinical trials with ex vivo purification and engraftment of CD34 +  hematopoietic stem cells, T cells, and tumor cell vaccines. This article covers the regulatory and translational preclinical activities needed for a genome editing clinical trial modifying hematopoietic stem cells and the genesis of this current strategy based on previous clinical trials using genome-edited T cells. The SB-728 zinc finger nuclease platform is discussed because this is the most clinically advanced genome editing technology. Copyright © 2017 Elsevier Inc. All rights reserved.

COP - Pet Owners - Open Clinical Trials | Center for Cancer Research

Cancer.gov

Current Open Clinical Trials If you are interested in learning more about the eligibility requirements for any of open studies listed below, please contact the nearest participating University or Christina Mazcko. To search studies being conducted by other groups please visit Vet Cancer Trials. This will allow you to search by location and tumor type.

Utilization of Clinical Trials Registries in Obstetrics and Gynecology Systematic Reviews.

PubMed

Bibens, Michael E; Chong, A Benjamin; Vassar, Matt

2016-02-01

To evaluate the use of clinical trials registries in published obstetrics and gynecologic systematic reviews and meta-analyses. We performed a metaepidemiologic study of systematic reviews between January 1, 2007, and December 31, 2015, from six obstetric and gynecologic journals (Obstetrics & Gynecology, Obstetrical & Gynecological Survey, Human Reproduction Update, Gynecologic Oncology, British Journal of Obstetrics and Gynaecology, and American Journal of Obstetrics & Gynecology). All systematic reviews included after exclusions were independently reviewed to determine whether clinical trials registries had been included as part of the search process. Studies that reported using a trials registry were further examined to determine whether trial data were included in the analysis of these systematic reviews. Our initial search resulted in 292 articles, which was narrowed to 256 after exclusions. Of the 256 systematic reviews meeting our selection criteria, 47 (18.4%) used a clinical trials registry. Eleven of the 47 (23.4%) systematic reviews found unpublished data and two included unpublished data in their results. A majority of systematic reviews in clinical obstetrics and gynecology journals do not conduct searches of clinical trials registries or do not make use of data obtained from these searches. Failure to make use of such data may lead to an inaccurate summary of available evidence and may contribute to an overrepresentation of published, statistically significant outcomes.

Clinical development of gene- and cell-based therapies: overview of the European landscape

PubMed Central

de Wilde, Sofieke; Guchelaar, Henk-Jan; Zandvliet, Maarten Laurens; Meij, Pauline

2016-01-01

In the last decade, many clinical trials with gene- and cell-based therapies were performed and increasing interest in the development was established by (national) authorities, academic developers, and commercial companies. However, until now only eight products have received marketing authorization (MA) approval. In this study, a comprehensive overview of the clinical development of gene- and cell-based therapies in Europe is presented, with a strong focus on product-technical aspects. Public data regarding clinical trials with gene- and cell-based therapies, obtained from the European Union (EU) clinical trial database (EudraCT) between 2004 and 2014 were analyzed, including product-technical variables as potential determinants affecting development. 198 unique gene and cell therapy products were identified, which were studied in 278 clinical trials, mostly in phase 1/2 trials and with cell therapies as major group. Furthermore, most products were manufactured from autologous starting material mostly manufactured from stem cells. The majority of the trials were sponsored by academia, whereas phase 3 trials mostly by large companies. Academia dominated early-stage development by mainly using bone marrow derived products and stem cells. Conversely, commercial sponsors were more actively pursuing in vivo gene therapy medicinal product development, and cell therapies derived from differentiated tissue in later-stage development. PMID:27990447

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

PubMed Central

2013-01-01

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

Applying a Conceptual Framework to Maximize the Participation of Diverse Populations in Cancer Clinical Trials

PubMed Central

Napoles, Anna; Cook, Elise; Ginossar, Tamar; Knight, Kendrea D.; Ford, Marvella E.

2017-01-01

The underrepresentation of ethnically diverse populations in cancer clinical trials results in the inequitable distribution of the risks and benefits of this research. Using a case study approach, we apply a conceptual framework of factors associated with the participation of diverse population groups in cancer clinical trials developed by Dr. Jean Ford and colleagues to increase understanding of the specific strategies, and barriers and promoters addressed by these strategies, that resulted in marked success in accrual of racially and ethnically diverse populations in cancer clinical research. Results indicate that the studies presented were able to successfully engage minority participants due to the creation and implementation of multi-level, multifaceted strategies that included: culturally and linguistically appropriate outreach, education, and research studies that were accessible in local communities; infrastructure to support engagement of key stakeholders, clinicians, and organizations serving minority communities; testimonials by ethnically diverse cancer survivors; availability of medical interpretation services; and providing infrastructure that facilitated the engagement in clinical research of clinicians who care for minority patient populations. These strategic efforts were effective in addressing limited awareness of trials, lack of opportunities to participate, and acceptance of engagement in cancer clinical trials. Careful attention to the context and population characteristics in which cancer clinical trials are conducted will be necessary to address disparities in research participation and cancer outcomes. These studies illustrate that progress on minority accrual into clinical research requires intentional efforts to overcome barriers at all three stages of the accrual process: awareness, opportunity and acceptance of participation. PMID:28052822

Editorial - Avoiding unethical Helicobacter pylori clinical trials: Susceptibility-based studies and probiotics as adjuvants

PubMed Central

Graham, David Y.

2016-01-01

As a general rule, any clinical study where the result is already known or when the investigator(s) compares an assigned treatment against another assigned treatment known to be ineffective in the study population (e.g. in a population with known clarithromycin resistance) is unethical. Since susceptibility-based therapy will always be superior to empiric therapy in any population with a prevalence of antimicrobial resistance greater than 0%, any trial that randomizes susceptibility-based therapy with empiric therapy would be unethical. The journal Helicobacter welcomes susceptibility or culture-guided studies, studies of new therapies and of adjuvants and probiotics. However, the Journal will not accept for review any study we judge to be lacking clinical equipoise or which assign subjects to a treatment known to be ineffective, such as a susceptibility-based clinical trial with an empiric therapy comparator. To assist authors we provide examples and suggestion regarding trial design for comparative studies, for susceptibility-based studies, and for studies testing adjuvants or probiotics. PMID:26123529

Participants’ perceptions and understanding of a malaria clinical trial in Bangladesh

PubMed Central

2014-01-01

Background Existing evidence suggests that there is often limited understanding among participants in clinical trials about the informed consent process, resulting in their providing consent without really understanding the purpose of the study, specific procedures, and their rights. The objective of the study was to determine the subjects’ understanding of research, perceptions of voluntariness and motivations for participation in a malaria clinical trial. Methods In this study semi-structured interviews of adult clinical trial participants with uncomplicated falciparum malaria were conducted in Ramu Upazila Health Complex, in Bangladesh. Results Of 16 participants, the vast majority (81%) were illiterate. All subjects had a ‘therapeutic misconception’ i.e. the trial was perceived to be conducted primarily for the benefit of individual patients when in fact the main objective was to provide information to inform public health policy. From the patients’ perspective, getting well from their illness was their major concern. Poor actual understanding of trial specific procedures was reported despite participants’ satisfaction with treatment and nursing care. Conclusion There is frequently a degree of overlap between research and provision of clinical care in malaria research studies. Patients may be motivated to participate to research without a good understanding of the principal objectives of the study despite a lengthy consent process. The findings suggest that use of a standard consent form following the current ICH-GCP guidelines does not result in achieving fully informed consent and the process should be revised, simplified and adapted to individual trial settings. PMID:24893933

Participants' perceptions and understanding of a malaria clinical trial in Bangladesh.

PubMed

Das, Debashish; Cheah, Phaik Yeong; Akter, Fateha; Paul, Dulal; Islam, Akhterul; Sayeed, Abdullah A; Samad, Rasheda; Rahman, Ridwanur; Hossain, Amir; Dondorp, Arjen; Day, Nicholas P; White, Nicholas J; Hasan, Mahtabuddin; Ghose, Aniruddha; Ashley, Elizabeth A; Faiz, Abul

2014-06-04

Existing evidence suggests that there is often limited understanding among participants in clinical trials about the informed consent process, resulting in their providing consent without really understanding the purpose of the study, specific procedures, and their rights. The objective of the study was to determine the subjects' understanding of research, perceptions of voluntariness and motivations for participation in a malaria clinical trial. In this study semi-structured interviews of adult clinical trial participants with uncomplicated falciparum malaria were conducted in Ramu Upazila Health Complex, in Bangladesh. Of 16 participants, the vast majority (81%) were illiterate. All subjects had a 'therapeutic misconception' i.e. the trial was perceived to be conducted primarily for the benefit of individual patients when in fact the main objective was to provide information to inform public health policy. From the patients' perspective, getting well from their illness was their major concern. Poor actual understanding of trial specific procedures was reported despite participants' satisfaction with treatment and nursing care. There is frequently a degree of overlap between research and provision of clinical care in malaria research studies. Patients may be motivated to participate to research without a good understanding of the principal objectives of the study despite a lengthy consent process. The findings suggest that use of a standard consent form following the current ICH-GCP guidelines does not result in achieving fully informed consent and the process should be revised, simplified and adapted to individual trial settings.

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.

Circadian Genes and Risk for Prostate Cancer

DTIC Science & Technology

2011-09-01

placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

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.

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

PubMed

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

2017-08-01

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

Evaluating Adaptation of a Cancer Clinical Trial Decision Aid for Rural Cancer Patients: A Mixed-Methods Approach.

PubMed

Pathak, Swati; George, Nerissa; Monti, Denise; Robinson, Kathy; Politi, Mary C

2018-06-03

Rural-residing cancer patients often do not participate in clinical trials. Many patients misunderstand cancer clinical trials and their rights as participant. The purpose of this study is to modify a previously developed cancer clinical trials decision aid (DA), incorporating the unique needs of rural populations, and test its impact on knowledge and decision outcomes. The study was conducted in two phases. Phase I recruited 15 rural-residing cancer survivors in a qualitative usability study. Participants navigated the original DA and provided feedback regarding usability and implementation in rural settings. Phase II recruited 31 newly diagnosed rural-residing cancer patients. Patients completed a survey before and after using the revised DA, R-CHOICES. Primary outcomes included decisional conflict, decision self-efficacy, knowledge, communication self-efficacy, and attitudes towards and willingness to consider joining a trial. In phase I, the DA was viewed positively by rural-residing cancer survivors. Participants provided important feedback about factors rural-residing patients consider when thinking about trial participation. In phase II, after using R-CHOICES, participants had higher certainty about their choice (mean post-test = 3.10 vs. pre-test = 2.67; P = 0.025) and higher trial knowledge (mean percentage correct at post-test = 73.58 vs. pre-test = 57.77; P < 0.001). There was no significant change in decision self-efficacy, communication self-efficacy, and attitudes towards or willingness to join trials. The R-CHOICES improved rural-residing patients' knowledge of cancer clinical trials and reduced conflict about making a trial decision. More research is needed on ways to further support decisions about trial participation among this population.

Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials

PubMed Central

Federer, Callie; Yoo, Minjae

2016-01-01

Abstract Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov (https://clinicaltrials.gov/), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov. Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs. PMID:27631620

Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

PubMed

Federer, Callie; Yoo, Minjae; Tan, Aik Choon

2016-12-01

Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

Clinical Trials: A Crucial Key to Human Health Research

MedlinePlus

... Clinical Trials: A Crucial Key to Human Health Research Past Issues / Summer 2006 Table of Contents For ... Photo: PhotoDisc At the forefront of human health research today are clinical trials—studies that use human ...

Practical characteristics of adaptive design in phase 2 and 3 clinical trials.

PubMed

Sato, A; Shimura, M; Gosho, M

2018-04-01

Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive designs were used more in phase 2 trials. Approximately 82% (202 of 245 trials) resulted in early termination at the interim analysis. Among the 202 trials, 132 (54% of 245 trials) had fewer randomized patients than initially planned. This result supports the motive to use adaptive design to make study durations shorter and include a smaller number of subjects. We found that adaptive designs have been applied to clinical trials in various therapeutic areas and interventions. The applications were frequently reported in neoplasm or cardiovascular clinical trials. The adaptive dose/treatment group selection and sample-size adjustment are increasingly common, and these adaptations generally follow the Food and Drug Administration's (FDA's) recommendations. © 2017 John Wiley & Sons Ltd.

Cancer clinical trials in persons with HIV infection.

PubMed

Little, Richard F

2017-01-01

The era of modern HIV therapeutics is well underway. The cancer and infectious disease epidemiology of HIV disease has markedly altered as populations are availed to the benefits of antiretroviral therapy (ARV). The types of cancers occurring among those with HIV infection has broadened but the case burden in absolute numbers is very low relative to the background population. There are fewer incident cases of the AIDS-defining cancers (aggressive B-cell lymphomas, Kaposi's sarcoma, and cervical cancer). There is an increased risk for certain non-AIDS-defining cancers, but these occur somewhat sporadically relative to clinical trial enrollment. The changing epidemiology of cancer in HIV poses challenges as well as opportunities for participation of persons with HIV in cancer therapy clinical trials. There are excellent examples of cancer trials that inform cancer therapy for patients with HIV infection. Examples include those from HIV-specific trials and from trials mainly focused on the background population that included patients with HIV infection. Interpretation of clinical trials to guide therapy for those with HIV infection and cancer largely depends on data that does not include HIV-infected patients. The ability to extend clinical trial findings to populations not included in clinical trials remains problematic for a variety of populations, including those with HIV or AIDS. Careful prioritization of studies designed to bridge this gap is needed. However, there are published studies that serve as excellent examples bridging these gaps and the portfolio of cancer therapy trials underway will inform HIV and cancer better than at any time in the past.

Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics.

PubMed

Van Poucke, Sven; Thomeer, Michiel; Heath, John; Vukicevic, Milan

2016-07-06

Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers' scientific epistemology of "falsificationism." Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation.

Are Randomized Controlled Trials the (G)old Standard? From Clinical Intelligence to Prescriptive Analytics

PubMed Central

2016-01-01

Despite the accelerating pace of scientific discovery, the current clinical research enterprise does not sufficiently address pressing clinical questions. Given the constraints on clinical trials, for a majority of clinical questions, the only relevant data available to aid in decision making are based on observation and experience. Our purpose here is 3-fold. First, we describe the classic context of medical research guided by Poppers’ scientific epistemology of “falsificationism.” Second, we discuss challenges and shortcomings of randomized controlled trials and present the potential of observational studies based on big data. Third, we cover several obstacles related to the use of observational (retrospective) data in clinical studies. We conclude that randomized controlled trials are not at risk for extinction, but innovations in statistics, machine learning, and big data analytics may generate a completely new ecosystem for exploration and validation. PMID:27383622

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

PubMed Central

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

2015-01-01

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

Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury.

PubMed

Howard, Randy B; Sayeed, Iqbal; Stein, Donald G

2017-06-01

To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.

Influences on visit retention in clinical trials: Insights from qualitative research during the VOICE trial in Johannesburg, South Africa

PubMed Central

2014-01-01

Background Although significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular. Methods The research used qualitative methodologies, including in-depth interviews (IDI), serial ethnographic interviews (EI), and focus group discussions (FGD) among a random sub-sample of 102 female trial participants, 18 to 40 years of age. A socio-ecological framework that explored those factors that shaped trial participation and adherence to study products, guided the analysis. Key codes were developed to standardize subsequent coding and a node search was used to identify texts relating to obstacles to visit adherence. Our analysis includes coded transcripts from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women). Results Women’s kinship, social, and economic roles shaped their ability to participate in the clinical trial. Although participants expressed strong commitments to attend study visits, clinic visit schedules and lengthy waiting times interfered with their multiple obligations as care givers, wage earners, housekeepers, and students. Conclusions The research findings highlight the importance of the social context in shaping participation in HIV prevention trials, beyond focusing solely on individual characteristics. This points to the need to focus interventions to improve visit attendance by promoting a culture of active and engaged participation. PMID:25065834

Influences on visit retention in clinical trials: insights from qualitative research during the VOICE trial in Johannesburg, South Africa.

PubMed

Magazi, Busisiwe; Stadler, Jonathan; Delany-Moretlwe, Sinead; Montgomery, Elizabeth; Mathebula, Florence; Hartmann, Miriam; van der Straten, Ariane

2014-07-28

Although significant progress has been made in clinical trials of women-controlled methods of HIV prevention such as microbicides and Pre-exposure Prophylaxis (PrEP), low adherence to experimental study products remains a major obstacle to being able to establish their efficacy in preventing HIV infection. One factor that influences adherence is the ability of trial participants to attend regular clinic visits at which trial products are dispensed, adherence counseling is administered, and participant safety is monitored. We conducted a qualitative study of the social contextual factors that influenced adherence in the VOICE (MTN-003) trial in Johannesburg, South Africa, focusing on study participation in general, and study visits in particular. The research used qualitative methodologies, including in-depth interviews (IDI), serial ethnographic interviews (EI), and focus group discussions (FGD) among a random sub-sample of 102 female trial participants, 18 to 40 years of age. A socio-ecological framework that explored those factors that shaped trial participation and adherence to study products, guided the analysis. Key codes were developed to standardize subsequent coding and a node search was used to identify texts relating to obstacles to visit adherence. Our analysis includes coded transcripts from seven FGD (N = 40), 41 IDI, and 64 serial EI (N = 21 women). Women's kinship, social, and economic roles shaped their ability to participate in the clinical trial. Although participants expressed strong commitments to attend study visits, clinic visit schedules and lengthy waiting times interfered with their multiple obligations as care givers, wage earners, housekeepers, and students. The research findings highlight the importance of the social context in shaping participation in HIV prevention trials, beyond focusing solely on individual characteristics. This points to the need to focus interventions to improve visit attendance by promoting a culture of active and engaged participation.

From randomized controlled trials to observational studies.

PubMed

Silverman, Stuart L

2009-02-01

Randomized controlled trials are considered the gold standard in the hierarchy of research designs for evaluating the efficacy and safety of a treatment intervention. However, their results can have limited applicability to patients in clinical settings. Observational studies using large health care databases can complement findings from randomized controlled trials by assessing treatment effectiveness in patients encountered in day-to-day clinical practice. Results from these designs can expand upon outcomes of randomized controlled trials because of the use of larger and more diverse patient populations with common comorbidities and longer follow-up periods. Furthermore, well-designed observational studies can identify clinically important differences among therapeutic options and provide data on long-term drug effectiveness and safety.

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.

Phase II cancer clinical trials for biomarker-guided treatments.

PubMed

Jung, Sin-Ho

2018-01-01

The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

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.

A single center analysis of factors influencing study start-up timeline in clinical trials.

PubMed

Krafcik, Brianna M; Doros, Gheorghe; Malikova, Marina A

2017-11-01

Efficient start-up phase in clinical trials is crucial to execution. The goal was to determine factors contributing to delays. The start-up milestones were assessed for 38 studies and analyzed. Total start-up time was shorter for following studies: device trials, no outsourcing, fewer ancillary services used and in interventional versus observational designs. The use of a centralized Institutional Review Board (IRB) versus a local IRB reduced time to approval. Studies that never enrolled took longer on average to finalize their budget/contract, and obtain IRB than ones that did enroll. Different features of clinical trials can affect timeline of start-up process. An understanding of the impact of each feature allows for optimization.

Analysis of Participant Withdrawal in Huntington Disease Clinical Trials.

PubMed

Banno, Haruhiko; Andrzejewski, Kelly L; McDermott, Michael P; Murphy, Alyssa; Majumder, Madhurima; de Blieck, Elisabeth A; Auinger, Peggy; Cudkowicz, Merit E; Atassi, Nazem

2017-01-01

Excellent retention in Huntington disease (HD) clinical trials is essential for testing new therapies. The stage of disease, cognitive status, and availability of a care partner may influence retention in HD clinical trials. We sought to analyze reasons for early withdrawal in three HD clinical trials, and evaluated if either baseline characteristics or follow-up assessments were associated with time to withdrawal. Analyses of participant withdrawal were performed for three randomized, double-blind, placebo-controlled trials including the CARE-HD (coenzyme Q10 and remacemide in HD, n = 347), DOMINO (pilot study of minocycline in HD, n = 114), and 2CARE (coenzyme Q10 in HD, n = 609) trials. Reasons for withdrawal were obtained by review of textual data in the study databases. Participant demographic and clinical characteristics were analyzed as potential predictors of time to withdrawal using Cox-proportional hazards models. Estimated probabilities of withdrawal at 12 months were 2.9% for CARE-HD, 10.5% for DOMINO, and 5.9% for 2CARE. The top reasons for withdrawal (202 in total), expressed as mean percentage across the three trials, were loss to follow-up (23.2%), death (15.9%), and loss of interest/desire to participate (15.2%). Baseline and time-dependent variables associated with time to withdrawal were mainly motor, behavioral, and functional scores. Age, gender, ethnicity, and educational level were not associated with time to withdrawal in any of the three studies. The estimated withdrawal probability at 12 months ranged from 2.9% to 10.5% in the three HD trials considered here. A possible strategy to improve retention of participants in future HD clinical trials is to enroll individuals with higher baseline functional and behavioral status.

Timing and Completeness of Trial Results Posted at ClinicalTrials.gov and Published in Journals

PubMed Central

Riveros, Carolina; Dechartres, Agnes; Perrodeau, Elodie; Haneef, Romana; Boutron, Isabelle; Ravaud, Philippe

2013-01-01

Background The US Food and Drug Administration Amendments Act requires results from clinical trials of Food and Drug Administration–approved drugs to be posted at ClinicalTrials.gov within 1 y after trial completion. We compared the timing and completeness of results of drug trials posted at ClinicalTrials.gov and published in journals. Methods and Findings We searched ClinicalTrials.gov on March 27, 2012, for randomized controlled trials of drugs with posted results. For a random sample of these trials, we searched PubMed for corresponding publications. Data were extracted independently from ClinicalTrials.gov and from the published articles for trials with results both posted and published. We assessed the time to first public posting or publishing of results and compared the completeness of results posted at ClinicalTrials.gov versus published in journal articles. Completeness was defined as the reporting of all key elements, according to three experts, for the flow of participants, efficacy results, adverse events, and serious adverse events (e.g., for adverse events, reporting of the number of adverse events per arm, without restriction to statistically significant differences between arms for all randomized patients or for those who received at least one treatment dose). From the 600 trials with results posted at ClinicalTrials.gov, we randomly sampled 50% (n = 297) had no corresponding published article. For trials with both posted and published results (n = 202), the median time between primary completion date and first results publicly posted was 19 mo (first quartile = 14, third quartile = 30 mo), and the median time between primary completion date and journal publication was 21 mo (first quartile = 14, third quartile = 28 mo). Reporting was significantly more complete at ClinicalTrials.gov than in the published article for the flow of participants (64% versus 48% of trials, p<0.001), efficacy results (79% versus 69%, p = 0.02), adverse events (73% versus 45%, p<0.001), and serious adverse events (99% versus 63%, p<0.001). The main study limitation was that we considered only the publication describing the results for the primary outcomes. Conclusions Our results highlight the need to search ClinicalTrials.gov for both unpublished and published trials. Trial results, especially serious adverse events, are more completely reported at ClinicalTrials.gov than in the published article. Please see later in the article for the Editors' Summary PMID:24311990

Design of a cluster-randomized minority recruitment trial: RECRUIT.

PubMed

Tilley, Barbara C; Mainous, Arch G; Smith, Daniel W; McKee, M Diane; Amorrortu, Rossybelle P; Alvidrez, Jennifer; Diaz, Vanessa; Ford, Marvella E; Fernandez, Maria E; Hauser, Robert A; Singer, Carlos; Landa, Veronica; Trevino, Aron; DeSantis, Stacia M; Zhang, Yefei; Daniels, Elvan; Tabor, Derrick; Vernon, Sally W

2017-06-01

Racial/ethnic minority groups remain underrepresented in clinical trials. Many strategies to increase minority recruitment focus on minority communities and emphasize common diseases such as hypertension. Scant literature focuses on minority recruitment to trials of less common conditions, often conducted in specialty clinics and dependent on physician referrals. We identified trust/mistrust of specialist physician investigators and institutions conducting medical research and consequent participant reluctance to participate in clinical trials as key-shared barriers across racial/ethnic groups. We developed a trust-based continuous quality improvement intervention to build trust between specialist physician investigators and community minority-serving physicians and ultimately potential trial participants. To avoid the inherent biases of non-randomized studies, we evaluated the intervention in the national Randomized Recruitment Intervention Trial (RECRUIT). This report presents the design of RECRUIT. Specialty clinic follow-up continues through April 2017. We hypothesized that specialist physician investigators and coordinators trained in the trust-based continuous quality improvement intervention would enroll a greater proportion of minority participants in their specialty clinics than specialist physician investigators in control specialty clinics. Specialty clinic was the unit of randomization. Using continuous quality improvement, the specialist physician investigators and coordinators tailored recruitment approaches to their specialty clinic characteristics and populations. Primary analyses were adjusted for clustering by specialty clinic within parent trial and matching covariates. RECRUIT was implemented in four multi-site clinical trials (parent trials) supported by three National Institutes of Health institutes and included 50 associated specialty clinics from these parent trials. Using current data, we have 88% power or greater to detect a 0.15 or greater difference from the currently observed control proportion adjusting for clustering. We detected no differences in baseline matching criteria between intervention and control specialty clinics (all p values > 0.17). RECRUIT was the first multi-site randomized control trial to examine the effectiveness of a trust-based continuous quality improvement intervention to increase minority recruitment into clinical trials. RECRUIT's innovations included its focus on building trust between specialist investigators and minority-serving physicians, the use of continuous quality improvement to tailor the intervention to each specialty clinic's specific racial/ethnic populations and barriers to minority recruitment, and the use of specialty clinics from more than one parent multi-site trial to increase generalizability. The effectiveness of the RECRUIT intervention will be determined after the completion of trial data collection and planned analyses.

A New Ethical Challenge for Institutional Review Boards (IRBs)/Ethics Committees (ECs) in the Assessment of Pediatric Clinical Trials

PubMed Central

Rose, Klaus; Kummer, Hans

2015-01-01

Both the US and EU have introduced pediatric pharmaceutical legislation to facilitate clinical trials in children and development of better medicines for children. The first concerns were published in 2014 that the European Medicines Agency (EMA)’s Pediatric Committee (PDCO) may be over-enthusiastic and has compelled questionable pediatric clinical trials from pharmaceutical companies. Numerous clinical trials are mandated in rare conditions for which not enough patients exist for even one trial. Furthermore, where these trials are mandated in adolescent patients, the legal age limit of the 18th birthday is confused with a medical age limit and can result in separate clinical trials in adolescent patients that neither make medical nor scientific sense nor will ever recruit enough patients for a meaningful outcome. To confirm our concerns we searched the registry clinicaltrials.gov and found examples for PDCO-triggered unethical trials. We conclude that such trials should not be accepted by institutional review boards (IRBs)/ethics committees (ECs) and that clinical trials resulting from negotiations with EMA’s PDCO need extra careful scrutiny by IRBs/ECs in order to prevent unethical studies and damage to pediatric research and unnecessary risks to pediatric patients. PMID:27417359

B-cell depletion in SLE: clinical and trial experience with rituximab and ocrelizumab and implications for study design.

PubMed

Reddy, Venkat; Jayne, David; Close, David; Isenberg, David

2013-01-01

B cells are believed to be central to the disease process in systemic lupus erythematosus (SLE), making them a target for new therapeutic intervention. In recent years there have been many publications regarding the experience in SLE of B-cell depletion utilising rituximab, an anti-CD20 mAb that temporarily depletes B cells,reporting promising results in uncontrolled open studies and in routine clinical use. However, the two large randomised controlled trials in extra-renal lupus (EXPLORER study) and lupus nephritis (LUNAR study) failed to achieve their primary endpoints. Based on the clinical experience with rituximab this failure was somewhat unexpected and raised a number of questions and concerns, not only into the true level of benefit of B-cell depletion in a broad population but also how to test the true level of effectiveness of an investigational agent as we seek to improve the design of therapeutic trials in SLE. A better understanding of what went wrong in these trials is essential to elucidate the underlying reasons for the disparate observations noted in open studies and controlled trials. In this review, we focus on various factors that may affect the ability to accurately and confidently establish the level of treatment effect of the investigational agent, in this case rituximab, in the tw studies and explore hurdles faced in the randomised controlled trials investigating the efficacy of ocrelizumab, the humanised anti-CD20 mAb, in SLE. Further, based on the lessons learned from the clinical trials, we make suggestions that could be implemented in future clinical trial design to overcome the hurdles faced.

Feasibility, acceptability and findings from a pilot randomized controlled intervention study on the impact of a book designed to inform patients about cancer clinical trials.

PubMed

Carney, Patricia A; Tucker, Erin K; Newby, Timothy A; Beer, Tomasz M

2014-03-01

This study was conducted to assess the feasibility, acceptability, and changes in knowledge among cancer patients assigned to receive a 160-page book on experimental cancer therapies and clinical trials. We enrolled 20 patients with cancer who had never participated in a clinical trial and randomly assigned them to receive the book either during week 1 or week 4 of the study. We collected baseline patient demographic and cancer-related information as well as knowledge about cancer clinical trials at week 0. Follow-up surveys were administered at weeks 3 and 6 for both study groups. Comparisons were made within and between groups randomized to receive the book early (at week 1) to those who received it later (at week 4). One hundred percent of data were captured in both groups at baseline, which decreased to 77.8% by week 6. The vast majority of participants found the book moderately or very useful (89% in the Early Group at week 3 and 95.5% in the Late Group at week 6). Within group pairwise comparisons found significant difference between baseline and week 6 in content-specific knowledge scores among participants in the Late Group [79% versus 92.1%, p = 0.01). Global knowledge scores increased significantly for variables reflecting knowledge that promotes decisions to participate in clinical trials. Providing published reading material to patients with cancer is both feasible and acceptable. Offering information to patients about cancer clinical trials, using a book designed for patients with cancer may influence knowledge related to decision to participate in clinical trials.

Generalizing from clinical trial data: A case study. The risk of suicidality among pediatric antidepressant users

PubMed Central

Greenhouse, Joel B.; Kaizar, Eloise E.; Kelleher, Kelly; Seltman, Howard; Gardner, William

2010-01-01

Summary For the results of randomized controlled clinical trials (RCTs) and related meta-analyses to be useful in practice, they must be relevant to a definable group of patients in a particular clinical setting. To the extent this is so, we say that the trial is generalizable or externally valid. Although concern about the generalizability of the results of RCTs is often discussed, there are few examples of methods for assessing the generalizability of clinical trial data. In this paper, we describe and illustrate an approach for making what we call generalizability judgments and illustrate the approach in the context of a case study of the risk of suicidality among pediatric antidepressant users. PMID:18381709

Interim analysis: A rational approach of decision making in clinical trial.

PubMed

Kumar, Amal; Chakraborty, Bhaswat S

2016-01-01

Interim analysis of especially sizeable trials keeps the decision process free of conflict of interest while considering cost, resources, and meaningfulness of the project. Whenever necessary, such interim analysis can also call for potential termination or appropriate modification in sample size, study design, and even an early declaration of success. Given the extraordinary size and complexity today, this rational approach helps to analyze and predict the outcomes of a clinical trial that incorporate what is learned during the course of a study or a clinical development program. Such approach can also fill the gap by directing the resources toward relevant and optimized clinical trials between unmet medical needs and interventions being tested currently rather than fulfilling only business and profit goals.

Despite law, fewer than one in eight completed studies of drugs and biologics are reported on time on ClinicalTrials.gov.

PubMed

Law, Michael R; Kawasumi, Yuko; Morgan, Steven G

2011-12-01

Clinical trial registries are public databases created to prospectively document the methods and measures of prescription drug studies and retrospectively collect a summary of results. In 2007 the US government began requiring that researchers register certain studies and report the results on ClinicalTrials.gov, a public database of federally and privately supported trials conducted in the United States and abroad. We found that although the mandate briefly increased trial registrations, 39 percent of trials were still registered late after the mandate's deadline, and only 12 percent of completed studies reported results within a year, as required by the mandate. This result is important because there is evidence of selective reporting even among registered trials. Furthermore, we found that trials funded by industry were more than three times as likely to report results than were trials funded by the National Institutes of Health. Thus, additional enforcement may be required to ensure disclosure of all trial results, leading to a better understanding of drug safety and efficacy. Congress should also reconsider the three-year delay in reporting results for products that have been approved by the Food and Drug Administration and are in use by patients.

Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report.

PubMed

Ramsey, Scott D; Willke, Richard J; Glick, Henry; Reed, Shelby D; Augustovski, Federico; Jonsson, Bengt; Briggs, Andrew; Sullivan, Sean D

2015-03-01

Clinical trials evaluating medicines, medical devices, and procedures now commonly assess the economic value of these interventions. The growing number of prospective clinical/economic trials reflects both widespread interest in economic information for new technologies and the regulatory and reimbursement requirements of many countries that now consider evidence of economic value along with clinical efficacy. As decision makers increasingly demand evidence of economic value for health care interventions, conducting high-quality economic analyses alongside clinical studies is desirable because they broaden the scope of information available on a particular intervention, and can efficiently provide timely information with high internal and, when designed and analyzed properly, reasonable external validity. In 2005, ISPOR published the Good Research Practices for Cost-Effectiveness Analysis Alongside Clinical Trials: The ISPOR RCT-CEA Task Force report. ISPOR initiated an update of the report in 2014 to include the methodological developments over the last 9 years. This report provides updated recommendations reflecting advances in several areas related to trial design, selecting data elements, database design and management, analysis, and reporting of results. Task force members note that trials should be designed to evaluate effectiveness (rather than efficacy) when possible, should include clinical outcome measures, and should obtain health resource use and health state utilities directly from study subjects. Collection of economic data should be fully integrated into the study. An incremental analysis should be conducted with an intention-to-treat approach, complemented by relevant subgroup analyses. Uncertainty should be characterized. Articles should adhere to established standards for reporting results of cost-effectiveness analyses. Economic studies alongside trials are complementary to other evaluations (e.g., modeling studies) as information for decision makers who consider evidence of economic value along with clinical efficacy when making resource allocation decisions. Copyright © 2015 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Clinical Knowledge from Observational Studies: Everything You Wanted to Know but Were Afraid to Ask.

PubMed

Gershon, Andrea S; Jafarzadeh, S Reza; Wilson, Kevin C; Walkey, Allan J

2018-05-07

Well-done randomized trials provide accurate estimates of treatment effect by producing groups that are similar on all measures except for the intervention of interest. However, inferences of efficacy in tightly-controlled experimental settings may not translate into similar effectiveness in real-world settings. Observational studies generally enable inferences over a wider range of patient characteristics and evaluation of a broader range of outcomes over a longer period than randomized trials. However, clinicians are often reluctant to incorporate the findings of observational studies into clinical practice. Reason for uncertainty regarding observational studies include a lack of familiarity with observational research methods, occasional disagreements between results of observational studies and randomized trials, the perceived risk of spurious results from systematic bias, and prior teaching that randomized trials are the most reliable source of medical evidence. We propose that a better understanding of observational research will enhance clinicians' ability to distinguish reliable observational studies from those that are subjected to biases and, therefore, provide more confidence to apply observational research results into clinical practice when appropriate. Herein, we explain why observational studies may be perceived as less conclusive than randomized trials, address situations in which observational research and randomized trials produced different findings, and provide information on observational study design so that quality can be evaluated. We conclude that observational research is a valuable source of medical evidence and that clinical action is strongest when supported by both high quality observational studies and randomized trials.

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.

Cross-System Evaluation of Clinical Trial Search Engines

PubMed Central

Jiang, Silis Y.; Weng, Chunhua

2014-01-01

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

Cross-system evaluation of clinical trial search engines.

PubMed

Jiang, Silis Y; Weng, Chunhua

2014-01-01

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

Clinical studies in orthodontics--an overview of NIDR-sponsored clinical orthodontic studies in the US.

PubMed

Baumrind, S

1998-11-01

A number of clinical trials sponsored by the National Institutes of Health (NIH) use rigorous methods of data acquisition and analysis previously developed in fundamental biology and the physical sciences. The naive expectation that these trials would lead relatively rapidly to definitive answers concerning the therapeutic strategies and techniques under study is dispelled. This presentation focuses on delineating differences between the study of central tendencies and individual variation, more specifically on the strategy to study this variation: measure additional sources of variance within each patient at more timepoints and perhaps with greater precision. As rigorous orthodontic research is still in its infancy, the problem of defining the proper mix between prospective and retrospective trials is discussed. In view of the high costs of prospective clinical trials, many of the questions germane to orthodontics can be answered by well-conducted retrospective trials, assuming that properly randomized sampling procedures are employed. Definitive clinical trials are likely to require better theoretical constructs, better instrumentation, and better measures than now available. Reasons for concern are the restricted resources available and the fact that current mensurational approaches may not detect many of the individual differences. The task of constructing sharable databases and record bases stored in digital form and available either remotely from servers, or locally from CD-ROMs or optical disks, is crucial to the optimization of future investigations.

The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee

PubMed Central

Seymour, Lesley; Ivy, S. Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

2010-01-01

The optimal design of phase II studies continues to be the subject of vigorous debate, especially with regards to studies of newer molecularly targeted agents. The observations that many new therapeutics ‘fail’ in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials further emphasizes the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force(CTD-TF)of the NCI Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on Phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations regarding aspects of phase II trial design which are the subject of frequent debate such as endpoints(response vs. progression free survival), randomization(single arm designs vs. randomization), inclusion of biomarkers, biomarker based patient enrichment strategies, and statistical design(e.g. two stage designs vs. multiple-group adaptive designs). While these recommendations in general encourage the use of progression-free survival as the primary endpoint, the use of randomization, the inclusion of biomarkers and the incorporation of newer designs, we acknowledge that objective response as an endpoint, and single arm designs, remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on the characteristic specific to the situation. PMID:20215557

Improving outcomes in adults with epilepsy and intellectual disability (EpAID) using a nurse-led intervention: study protocol for a cluster randomised controlled trial.

PubMed

Ring, Howard; Gilbert, Nakita; Hook, Roxanne; Platt, Adam; Smith, Christopher; Irvine, Fiona; Donaldson, Cam; Jones, Elizabeth; Kelly, Joanna; Mander, Adrian; Murphy, Caroline; Pennington, Mark; Pullen, Angela; Redley, Marcus; Rowe, Simon; Wason, James

2016-06-24

In adults with intellectual disability (ID) and epilepsy there are suggestions that improvements in management may follow introduction of epilepsy nurse-led care. However, this has not been tested in a definitive clinical trial and results cannot be generalised from general population studies as epilepsy tends to be more severe and to involve additional clinical comorbidities in adults with ID. This trial investigates whether nurses with expertise in epilepsy and ID, working proactively to a clinically defined role, can improve clinical and quality of life outcomes in the management of epilepsy within this population, compared to treatment as usual. The trial also aims to establish whether any perceived benefits represent good value for money. The EpAID clinical trial is a two-arm cluster randomised controlled trial of nurse-led epilepsy management versus treatment as usual. This trial aims to obtain follow-up data from 320 participants with ID and drug-resistant epilepsy. Participants are randomly assigned either to a 'treatment as usual' control or a 'defined epilepsy nurse role' active arm, according to the cluster site at which they are treated. The active intervention utilises the recently developed Learning Disability Epilepsy Specialist Nurse Competency Framework for adults with ID. Participants undergo 4 weeks of baseline data collection, followed by a minimum of 20 weeks intervention (novel treatment or treatment as usual), followed by 4 weeks of follow-up data collection. The primary outcome is seizure severity, including associated injuries and the level of distress manifest by the patient in the preceding 4 weeks. Secondary outcomes include cost-utility analysis, carer strain, seizure frequency and side effects. Descriptive measures include demographic and clinical descriptors of participants and clinical services in which they receive their epilepsy management. Qualitative study of clinical interactions and semi-structured interviews with clinicians and participants' carers are also undertaken. The EpAID clinical trial is the first cluster randomised controlled trial to test possible benefits of a nurse-led intervention in adults with epilepsy and ID. This research will have important implications for ID and epilepsy services. The challenges of undertaking such a trial in this population, and the approaches to meeting these are discussed. International Standard Randomised Controlled Trial Number: ISRCTN96895428 version 1.1. Registered on 26 March 2013.

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.

Surrogate clinical endpoints to predict overall survival in non-small cell lung cancer trials-are we in a new era?

PubMed

Clarke, Jeffrey M; Wang, Xiaofei; Ready, Neal E

2015-12-01

Surrogate endpoints for clinical trials in oncology offer an alternative metric for measuring clinical benefit, allowing for shorter trial duration, smaller patient cohorts, and single arm design. The correlation of surrogate endpoints with overall survival (OS) in therapeutic studies is a central consideration to their validity. The Food and Drug Administration (FDA) recently published an analysis of fourteen clinical trials in advanced non-small cell lung cancer (NSCLC), and discovered a strong association between response rate and progression free survival. Furthermore, a correlation between response rate and OS is demonstrated when analyzing the experimental treatment arm separately, minimizing bias from patient crossover. We also highlight multiple, important considerations when using response as an endpoint in clinical trials involving NSCLC patients.

Acupuncture for Children with Autism Spectrum Disorders: A Systematic Review of Randomized Clinical Trials

ERIC Educational Resources Information Center

Lee, Myeong Soo; Choi, Tae-Young; Shin, Byung-Cheul; Ernst, Edzard

2012-01-01

This study aimed to assess the effectiveness of acupuncture as a treatment for autism spectrum disorders (ASD). We searched the literature using 15 databases. Eleven randomized clinical trials (RCTs) met our inclusion criteria. Most had significant methodological weaknesses. The studies' statistical and clinical heterogeneity prevented us from…

Improving decision making about clinical trial participation – a randomised controlled trial of a decision aid for women considering participation in the IBIS-II breast cancer prevention trial

PubMed Central

Juraskova, I; Butow, P; Bonner, C; Bell, M L; Smith, A B; Seccombe, M; Boyle, F; Reaby, L; Cuzick, J; Forbes, J F

2014-01-01

Background: Decision aids may improve informed consent in clinical trial recruitment, but have not been evaluated in this context. This study investigated whether decision aids (DAs) can reduce decisional difficulties among women considering participation in the International Breast Cancer Intervention Study-II (IBIS-II) trial. Methods: The IBIS-II trial investigated breast cancer prevention with anastrazole in two cohorts: women with increased risk (Prevention), and women treated for ductal carcinoma in situ (DCIS). Australia, New Zealand and United Kingdom participants were randomised to receive a DA (DA group) or standard trial consent materials (control group). Questionnaires were completed after deciding about participation in IBIS-II (post decision) and 3 months later (follow-up). Results: Data from 112 Prevention and 34 DCIS participants were analysed post decision (73 DA; 73 control); 95 Prevention and 24 DCIS participants were analysed at follow-up (58 DA; 61 control). There was no effect on the primary outcome of decisional conflict. The DCIS–DA group had higher knowledge post decision, and the Prevention-DA group had lower decisional regret at follow-up. Conclusions: This was the first study to evaluate a DA in the clinical trial setting. The results suggest DAs can potentially increase knowledge and reduce decisional regret about clinical trial participation. PMID:24892447

[Discussion on development of four diagnostic information scale for clinical re-evaluation of postmarketing herbs].

PubMed

He, Wei; Xie, Yanming; Wang, Yongyan

2011-12-01

Post-marketing re-evaluation of Chinese herbs can well reflect Chinese medicine characteristics, which is the most easily overlooked the clinical re-evaluation content. Since little attention has been paid to this, study on the clinical trial design method was lost. It is difficult to improving the effectiveness and safety of traditional Chinese medicine. Therefore, more attention should be paid on re-evaluation of the clinical trial design method point about tcm syndrome such as the type of research program design, the study of Chinese medical information collection scale and statistical analysis methods, so as to improve the clinical trial design method study about tcm syndrome of Chinese herbs postmarketing re-evalutation status.

A pilot survey of African-American physician perceptions about clinical trials.

PubMed

Lynch, G F; Gorelick, P B; Raman, R; Leurgans, S

2001-12-01

African Americans have been underrepresented in clinical trials. However, African-American physician attitudes about clinical trials may influence patient recruitment. We identified the perceptions of African-American physician members of the Cook County Physicians Association (CCPA) about clinical trials in the Chicago Metropolitan area using a self-administered questionnaire. An 18-item, 2-page survey that included information about physician demographics, practice type, and specialty, and perceptions regarding clinical research was sent to each of the 609 active or inactive members of the CCPA, a predominantly African-American physician organization. Each survey was accompanied by a letter of explanation and a self-addressed, return envelope. Data from the surveys were stored and analyzed in a database. A total of 166 members (27%) completed the survey. Fifty percent of the respondents were men and 50% were women. The mean age of the group was 45 years, and almost half had participated previously as a local investigator, or assisted on a clinical or laboratory study. Factors identified by the members as possibly being disadvantages to participation in a clinical trial, or factors influencing African-American recruitment included: (a) lack of patient awareness of clinical trials (93%); (b) patient mistrust of the medical community (92%); (c) additional administrative tasks in conjunction with a patient enrolled in a study (56%); (d) blind drug assignment (41.6%). African-American physicians perceive inherent disadvantages from participation in clinical trials and have pinpointed factors that may influence patient recruitment. These factors may be addressed by focused physician and community education.

How Have Cancer Clinical Trial Eligibility Criteria Evolved Over Time?

PubMed Central

Yaman, Anil; Chakrabarti, Shreya; Sen, Anando; Weng, Chunhua

2016-01-01

Knowledge reuse of cancer trial designs may benefit from a temporal understanding of the evolution of the target populations of cancer studies over time. Therefore, we conducted a retrospective analysis of the trends of cancer trial eligibility criteria between 1999 and 2014. The yearly distributions of eligibility concepts for chemicals and drugs, procedures, observations, and medical conditions extracted from free-text eligibility criteria of 32,000 clinical trials for 89 cancer types were analyzed. We identified the concepts that trend upwards or downwards in all or selected cancer types, and the concepts that show anomalous trends for some cancers. Later, concept trends were studied in a disease-specific manner and illustrated for breast cancer. Criteria trends observed in this study are also validated and interpreted using evidence from the existing medical literature. This study contributes a method for concept trend analysis and original knowledge of the trends in cancer clinical trial eligibility criteria. PMID:27570681

Developing a clinical trial unit to advance research in an academic institution.

PubMed

Croghan, Ivana T; Viker, Steven D; Limper, Andrew H; Evans, Tamara K; Cornell, Alissa R; Ebbert, Jon O; Gertz, Morie A

2015-11-01

Research, clinical care, and education are the three cornerstones of academic health centers in the United States. The research climate has always been riddled with ebbs and flows, depending on funding availability. During a time of reduced funding, the number and scope of research studies have been reduced, and in some instances, a field of study has been eliminated. Recent reductions in the research funding landscape have led institutions to explore new ways to continue supporting research. Mayo Clinic in Rochester, MN has developed a clinical trial unit within the Department of Medicine, which provides shared resources for many researchers and serves as a solution for training and mentoring new investigators and study teams. By building on existing infrastructure and providing supplemental resources to existing research, the Department of Medicine clinical trial unit has evolved into an effective mechanism for conducting research. This article discusses the creation of a central unit to provide research support in clinical trials and presents the advantages, disadvantages, and required building blocks for such a unit. Copyright © 2015 Mayo Clinic. Published by Elsevier Inc. All rights reserved.

Parallel multicentre randomised trial of a clinical trial question prompt list in patients considering participation in phase 3 cancer treatment trials.

PubMed

Tattersall, Martin H N; Jefford, Michael; Martin, Andrew; Olver, Ian; Thompson, John F; Brown, Richard F; Butow, Phyllis N

2017-03-01

To evaluate the effect of a clinical trial question prompt list in patients considering enrolment in cancer treatment trials. Tertiary cancer referral hospitals in three state capital cities in Australia. 88 patients with cancer attending three cancer centres in Australia, who were considering enrolment in phase 3 treatment trials, were invited to enrol in an unblinded randomised trial of provision of a clinical trial question prompt list (QPL) before consenting to enrol in the treatment trial. We developed and pilot tested a targeted QPL for patients with cancer considering clinical trial participation (the clinical trial QPL). Consenting patients were randomised to receive the clinical trial QPL or not before further discussion with their oncologist and/or trial nurse about the treatment trial. Questionnaires were completed at baseline and within 3 weeks of deciding on treatment trial participation. scores on the Quality of Informed Consent questionnaire (QuIC). 88 patients of 130 sought for the study were enrolled (43 males), and 45 received the clinical trial QPL. 49% of trials were chemotherapy interventions for patients with advanced disease, 35% and 16% were surgical adjuvant and radiation adjuvant trials respectively. 70 patients completed all relevant questionnaires. 28 of 43 patients in the control arm compared with 39 of 45 patients receiving the clinical trial QPL completed the QuIC (p=0.0124). There were no significant differences in the QuIC scores between the randomised groups (QuIC part A p=0.08 and QuIC part B p=0.92). There were no differences in patient satisfaction with decisions or in anxiety levels between the randomised groups. Use of a question prompt list did not significantly change the QuIC scores in this randomised trial. ANZCTR 12606000214538 prospectively registered 31/5/2006. Results, ACTRN12606000214538. 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/.

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

PubMed

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

2017-06-01

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

2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials.

PubMed

Hicks, Karen A; Mahaffey, Kenneth W; Mehran, Roxana; Nissen, Steven E; Wiviott, Stephen D; Dunn, Billy; Solomon, Scott D; Marler, John R; Teerlink, John R; Farb, Andrew; Morrow, David A; Targum, Shari L; Sila, Cathy A; Thanh Hai, Mary T; Jaff, Michael R; Joffe, Hylton V; Cutlip, Donald E; Desai, Akshay S; Lewis, Eldrin F; Gibson, C Michael; Landray, Martin J; Lincoff, A Michael; White, Christopher J; Brooks, Steven S; Rosenfield, Kenneth; Domanski, Michael J; Lansky, Alexandra J; McMurray, John J V; Tcheng, James E; Steinhubl, Steven R; Burton, Paul; Mauri, Laura; O'Connor, Christopher M; Pfeffer, Marc A; Hung, H M James; Stockbridge, Norman L; Chaitman, Bernard R; Temple, Robert J

2018-03-06

This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials. Copyright © 2018 American College of Cardiology Foundation and American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of published and unpublished phase I clinical cancer trials: an analysis of the CliniclTrials.gov database.

PubMed

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

2017-12-13

Introduction The role of phase I cancer trials is constantly evolving and they are increasingly being used in 'go/no' decisions in drug development. As a result, there is a growing need to ensure trials are published when completed. There are limited data on the publication rate and the factors associated with publication in phase I trials. Methods The ClinicalTrials.gov database was searched for completed adult phase I cancer trials with reported results. PubMed was searched for matching publications published prior to April 1, 2017. Logistic regression was used to identify factors associated with unpublished trials. Linear regression was used to explore factors associated with time lag from study database lock to publication for published trials. Results The study cohort included 319 trials. 95 (30%) trials had no matching publication. Thirty (9%) trials were not published in abstract form as well. On multivariable analysis, the most significant factor associated with unpublished trials was industry funding (odds ratio 3.3, 95% confidence interval 1.7-6.6, p=0.019). For published trials, time lag between database lock and publication was longer by 10.9 months (standard error 3.6, p<0.001) for industry funded trials compared with medical center funded trials. Conclusions Timely publishing of early cancer clinical trials results remains unsatisfactory. Industry funded phase I cancer trials were more likely to remain unpublished, and were associated with a longer time lag from database lock to publication. Policies that promote transparency and data sharing in clinical trial research might improve accountability among industry and investigators and improve timely results publication.

Current Pipelines for Neglected Diseases

PubMed Central

di Procolo, Paolo; Jommi, Claudio

2014-01-01

This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target (disease) choice, and the object of the trials. PMID:25187946

Current pipelines for neglected diseases.

PubMed

di Procolo, Paolo; Jommi, Claudio

2014-09-01

This paper scrutinises pipelines for Neglected Diseases (NDs), through freely accessible and at-least-weekly updated trials databases. It updates to 2012 data provided by recent publications, and integrates these analyses with information on location of trials coordinators and patients recruitment status. Additionally, it provides (i) disease-specific information to better understand the rational of investments in NDs, (ii) yearly data, to understand the investment trends. The search identified 650 clinical studies. Leishmaniasis, Arbovirus infection, and Dengue are the top three diseases by number of clinical studies. Disease diffusion risk seems to be the most important driver of the clinical trials target choice, whereas the role played by disease prevalence and unmet need is controversial. Number of trials is stable between 2005 and 2010, with an increase in the last two years. Patient recruitment was completed for most studies (57.6%), and Phases II and III account for 35% and 28% of trials, respectively. The primary purpose of clinical investigations is prevention (49.3%), especially for infectious diseases with mosquitoes and sand flies as the vector, and treatment (43.2%), which is the primary target for parasitic diseases Research centres and public organisations are the most important clinical studies sponsors (58.9%), followed by the pharmaceutical industry (24.1%), foundations and non-governmental organisations (9.3%). Many coordinator centres are located in less affluent countries (43.7%), whereas OECD countries and BRICS account for 34.7% and 17.5% of trials, respectively. Information was partially missing for some parameters. Notwithstanding, and despite its descriptive nature, this research has enhanced the evidence of the literature on pipelines for NDs. Future contributions may further investigate whether trials metrics are consistent with the characteristics of the interested countries and the explicative variables of trials location, target (disease) choice, and the object of the trials.

Translational medicine in the field of ablative fractional laser (AFXL)-assisted drug delivery: A critical review from basics to current clinical status.

PubMed

Haedersdal, Merete; Erlendsson, Andrés M; Paasch, Uwe; Anderson, R Rox

2016-05-01

Ablative fractional lasers enhance uptake of topical therapeutics and the concept of fractional laser-assisted drug delivery has now been taken into clinical practice. We systematically reviewed preclinical data and clinical evidence for fractional lasers to enhance drug uptake and improve clinical efficacy. We searched PubMed and Embase databases; 34 articles met the inclusion criteria. Studies were categorized into experimental preclinical studies and clinical trials, the latter graded according to level of evidence. All preclinical trials (n = 16) documented enhanced topical drug uptake into skin after ablative fractional laser treatment. Clinical evidence encompassed 18 studies, of which 9 were randomized controlled trials and 2 were controlled trials, examining neoplastic lesions, photodamaged skin, scars, onychomycosis, and topical anesthetics. The highest level of evidence was reached for actinic keratoses treated with methylaminolevulinate for photodynamic therapy (level IB, 5 randomized controlled trials), substantiating superior and long-lasting efficacy versus conventional photodynamic therapy. No adverse events were reported, but ablative fractional laser-assisted drug delivery implies risks of systemic drug absorption, especially when performed over large skin areas. Fractional laser-assisted drug delivery is beneficial in enhancing preclinical and clinical outcomes for certain skin conditions. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

A personal history of the MASTER Trial and its link to the clinical trials network of the Australian and New Zealand College of Anaesthetists.

PubMed

Rigg, J R A

2016-07-01

The aim of this paper is to link the history of the Multicentre Australian Study of Epidural Anaesthesia in high risk surgery, the MASTER Trial, the first National Health and Medical Research Council (NHMRC) funded multicentre randomised clinical trial in Australia led by anaesthetist researchers, and the decision of The Australian and New Zealand College of Anaesthetists (ANZCA) to establish a clinical trials network, in 2003, to the success of contemporary researchers in Australia and New Zealand in anaesthesia and perioperative medicine.

Trial Promoter: A Web-Based Tool for Boosting the Promotion of Clinical Research Through Social Media.

PubMed

Reuter, Katja; Ukpolo, Francis; Ward, Edward; Wilson, Melissa L; Angyan, Praveen

2016-06-29

Scarce information about clinical research, in particular clinical trials, is among the top reasons why potential participants do not take part in clinical studies. Without volunteers, on the other hand, clinical research and the development of novel approaches to preventing, diagnosing, and treating disease are impossible. Promising digital options such as social media have the potential to work alongside traditional methods to boost the promotion of clinical research. However, investigators and research institutions are challenged to leverage these innovations while saving time and resources. To develop and test the efficiency of a Web-based tool that automates the generation and distribution of user-friendly social media messages about clinical trials. Trial Promoter is developed in Ruby on Rails, HTML, cascading style sheet (CSS), and JavaScript. In order to test the tool and the correctness of the generated messages, clinical trials (n=46) were randomized into social media messages and distributed via the microblogging social media platform Twitter and the social network Facebook. The percent correct was calculated to determine the probability with which Trial Promoter generates accurate messages. During a 10-week testing phase, Trial Promoter automatically generated and published 525 user-friendly social media messages on Twitter and Facebook. On average, Trial Promoter correctly used the message templates and substituted the message parameters (text, URLs, and disease hashtags) 97.7% of the time (1563/1600). Trial Promoter may serve as a promising tool to render clinical trial promotion more efficient while requiring limited resources. It supports the distribution of any research or other types of content. The Trial Promoter code and installation instructions are freely available online.

Clinical trials in the Middle East and North Africa (MENA) Region: grandstanding or grandeur?

PubMed

Nair, Satish Chandrasekhar; Ibrahim, Halah; Celentano, David D

2013-11-01

Nearly 31% of the world's clinical trials are conducted outside the US and 25% of the new drug applications include data from international sites. The high population growth, demand for medication, increased prevalence of life-style related and rare genetic diseases in the MENA countries should be associated with a consequent scale-up of clinical trials in these countries. However, the region sponsors under 1% of global clinical trials. Determinants including the regulatory environment, patient protection, physician-preparedness, types of diseases, costs of trials and pace of subject recruitment, were analyzed to identify critical factors that influence barriers to the conduct clinical trials in MENA. Strategic planning by the CRO can help overcome challenges related to regulatory and oversight requirements. Barriers related to trial quality and subject protection can be mitigated by risk-based monitoring. Growing healthcare infrastructure and communication technologies provide clear advantages for subject recruitment. Low operating costs combined with the increase in pharmaceutical sales provide incentives for the future conduct of clinical trials. Although the opportunities and challenges cited are common to the MENA region, further studies are needed to assess other potential contributing variables for the conduct of clinical trials specific to each MENA country. Challenges in drug importation and site oversight can be overcome with systematic interventions. Social media network and community awareness programs can assist reductions in barriers in obtaining effective informed consents. Increasing pharmaceutical sales, population growth, high prevalence of genetic and life-style related diseases and reduced clinical trial development costs offer expanding opportunities for future clinical trials in MENA. Copyright © 2013 Elsevier Inc. All rights reserved.

Trial Promoter: A Web-Based Tool for Boosting the Promotion of Clinical Research Through Social Media

PubMed Central

Ukpolo, Francis; Ward, Edward; Wilson, Melissa L

2016-01-01

Background Scarce information about clinical research, in particular clinical trials, is among the top reasons why potential participants do not take part in clinical studies. Without volunteers, on the other hand, clinical research and the development of novel approaches to preventing, diagnosing, and treating disease are impossible. Promising digital options such as social media have the potential to work alongside traditional methods to boost the promotion of clinical research. However, investigators and research institutions are challenged to leverage these innovations while saving time and resources. Objective To develop and test the efficiency of a Web-based tool that automates the generation and distribution of user-friendly social media messages about clinical trials. Methods Trial Promoter is developed in Ruby on Rails, HTML, cascading style sheet (CSS), and JavaScript. In order to test the tool and the correctness of the generated messages, clinical trials (n=46) were randomized into social media messages and distributed via the microblogging social media platform Twitter and the social network Facebook. The percent correct was calculated to determine the probability with which Trial Promoter generates accurate messages. Results During a 10-week testing phase, Trial Promoter automatically generated and published 525 user-friendly social media messages on Twitter and Facebook. On average, Trial Promoter correctly used the message templates and substituted the message parameters (text, URLs, and disease hashtags) 97.7% of the time (1563/1600). Conclusions Trial Promoter may serve as a promising tool to render clinical trial promotion more efficient while requiring limited resources. It supports the distribution of any research or other types of content. The Trial Promoter code and installation instructions are freely available online. PMID:27357424

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 to assess adverse events in clinical trial protocols. In order to improve on the safety of participants and marketed drug, there is a need to develop national guidelines for clinical trials by the government, and to improve evaluation procedures and monitoring of ongoing trials by the ethics committee.

[Clinical trial data management and quality metrics system].

PubMed

Chen, Zhao-hua; Huang, Qin; Deng, Ya-zhong; Zhang, Yue; Xu, Yu; Yu, Hao; Liu, Zong-fan

2015-11-01

Data quality management system is essential to ensure accurate, complete, consistent, and reliable data collection in clinical research. This paper is devoted to various choices of data quality metrics. They are categorized by study status, e.g. study start up, conduct, and close-out. In each category, metrics for different purposes are listed according to ALCOA+ principles such us completeness, accuracy, timeliness, traceability, etc. Some general quality metrics frequently used are also introduced. This paper contains detail information as much as possible to each metric by providing definition, purpose, evaluation, referenced benchmark, and recommended targets in favor of real practice. It is important that sponsors and data management service providers establish a robust integrated clinical trial data quality management system to ensure sustainable high quality of clinical trial deliverables. It will also support enterprise level of data evaluation and bench marking the quality of data across projects, sponsors, data management service providers by using objective metrics from the real clinical trials. We hope this will be a significant input to accelerate the improvement of clinical trial data quality in the industry.

Unique Study Designs in Nephrology: N-of-1 Trials and Other Designs.

PubMed

Samuel, Joyce P; Bell, Cynthia S

2016-11-01

Alternatives to the traditional parallel-group trial design may be required to answer clinical questions in special populations, rare conditions, or with limited resources. N-of-1 trials are a unique trial design which can inform personalized evidence-based decisions for the patient when data from traditional clinical trials are lacking or not generalizable. A concise overview of factorial design, cluster randomization, adaptive designs, crossover studies, and n-of-1 trials will be provided along with pertinent examples in nephrology. The indication for analysis strategies such as equivalence and noninferiority trials will be discussed, as well as analytic pitfalls. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

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.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

The Use of Facebook Advertising to Recruit Healthy Elderly People for a Clinical Trial: Baseline Metrics

PubMed Central

2018-01-01

Background This report provides data on the use of social media advertising as a clinical trial recruitment strategy targeting healthy volunteers aged 60 years and older. The social media advertising campaign focused on enrollment for a Phase 1 clinical trial. Traditional means of recruiting—billboards, newspaper advertising, word of mouth, personal referrals, and direct mail—were not producing enough qualified participants. Objective To demonstrate the effectiveness of using targeted advertising on the social networking site Facebook to recruit people aged 60 years and older for volunteer clinical trial participation. Methods The trial sponsor used a proactive approach to recruit participants using advertising on social media. The sponsor placed and monitored an Institutional Review Board-approved advertising campaign on Facebook to recruit potential candidates for a Phase 1 clinical trial. The clinical trial required a 10-day residential (overnight) stay at a clinic in Michigan, with one follow-up visit. The sponsor of the clinical trial placed the advertising, which directed interested respondents to a trial-specific landing page controlled by the Contract Research Organization (CRO). The CRO provided all follow-up consenting, prescreening, screening, and enrollment procedures. The campaign was waged over an 8-week period to supplement recruiting by the CRO. Results A total of 621 people responded to a Facebook advertising campaign by completing an online form or telephoning the CRO, and the clinical trial was fully enrolled at 45 subjects following an 8-week Facebook advertising campaign. Conclusions An 8-week Facebook advertising campaign contributed to 868 inquiries made regarding a Phase 1 clinical trial seeking to enroll healthy elderly subjects. Over the initial 11 weeks of recruitment, 178 inquiries were received using traditional methods of outreach. Respondents to the Facebook advertising campaign described in this report engaged with the sponsored advertising at a higher rate than is typical for social media-based clinical trial recruitment strategies. The older adults’ engagement rate of 4.92% was more than twice as high as click-through rates of younger adults engaged with social media advertising in other clinical trial recruitment studies. Advertising placed on the social media platform Facebook is effective with the healthy volunteer population aged 60 years and older. This approach can quickly and cost-effectively reach qualified candidates for clinical trial recruitment as a supplement to traditional means of recruiting. Trial Registration ClinicalTrials.gov: NCT02840279; https://clinicaltrials.gov/ct2/show/NCT02840279 (Archived by WebCite at http://www.webcitation.org/6wamIWXAt) PMID:29367186

Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings.

PubMed

Mtove, George; Kimani, Joshua; Kisinza, William; Makenga, Geofrey; Mangesho, Peter; Duparc, Stephan; Nakalembe, Miriam; Phiri, Kamija S; Orrico, Russell; Rojo, Ricardo; Vandenbroucke, Pol

2018-03-22

Multinational clinical trials are logistically complex and require close coordination between various stakeholders. They must comply with global clinical standards and are accountable to multiple regulatory and ethical bodies. In resource-limited settings, it is challenging to understand how to apply global clinical standards to international, national, and local factors in clinical trials, making multiple-level stakeholder engagement an important element in the successful conduct of these clinical trials. During the planning and implementation of a large multinational clinical trial for intermittent preventive treatment of malaria in pregnancy in resource-limited areas of sub-Saharan Africa, we encountered numerous challenges, which required implementation of a range of engagement measures to ensure compliance with global clinical and regulatory standards. These challenges included coordination with ongoing global malaria efforts, heterogeneity in national regulatory structures, sub-optimal healthcare infrastructure, local practices and beliefs, and perspectives that view healthcare providers with undue trust or suspicion. In addition to engagement with international bodies, such as the World Health Organization, the Malaria in Pregnancy Consortium, the Steve Biko Centre for Bioethics, and the London School of Hygiene and Tropical Medicine, in order to address the challenges just described, Pfizer Inc. and Medicines for Malaria Venture (the "Sponsoring Entities" for these studies) and investigators liaised with national- and district-level stakeholders such as health ministers and regional/local community health workers. Community engagement measures undertaken by investigators included local meetings with community leaders to explain the research aims and answer questions and concerns voiced by the community. The investigators also engaged with family members of prospective trial participants in order to be sensitive to local practices and beliefs. Engagement with key stakeholders at international and national levels enabled the Sponsoring Entities to address challenges by aligning the study design with the requirements of health and regulatory agencies and to understand and address healthcare infrastructure needs prior to trial initiation. Local stakeholder engagement, including community members, study participants, and family enabled the investigators to address challenges by ensuring that study design and conduct were adapted to local considerations and ensuring accurate information about the study aims was shared with the public. ClinicalTrials.gov, ID: NCT01103063 . Registered on 7 April 2010.

Study protocol for the G-SPIRIT trial: a randomised, placebo-controlled, double-blinded phase III trial of granulocyte colony-stimulating factor-mediated neuroprotection for acute spinal cord injury

PubMed Central

Koda, Masao; Hanaoka, Hideki; Sato, Takatoshi; Fujii, Yasuhisa; Hanawa, Michiko; Takahashi, Sho; Furuya, Takeo; Ijima, Yasushi; Saito, Junya; Kitamura, Mitsuhiro; Ohtori, Seiji; Matsumoto, Yukei; Abe, Tetsuya; Watanabe, Kei; Hirano, Toru; Ohashi, Masayuki; Shoji, Hirokazu; Mizouchi, Tatsuki; Takahashi, Ikuko; Kawahara, Norio; Kawaguchi, Masahito; Orita, Yugo; Sasamoto, Takeshi; Yoshioka, Masahito; Fujii, Masafumi; Yonezawa, Katsutaka; Soma, Daisuke; Taneichi, Hiroshi; Takeuchi, Daisaku; Inami, Satoshi; Moridaira, Hiroshi; Ueda, Haruki; Asano, Futoshi; Shibao, Yosuke; Aita, Ikuo; Takeuchi, Yosuke; Mimura, Masaya; Shimbo, Jun; Someya, Yukio; Ikenoue, Sumio; Sameda, Hiroaki; Takase, Kan; Ikeda, Yoshikazu; Nakajima, Fumitake; Hashimoto, Mitsuhiro; Ozawa, Tomoyuki; Hasue, Fumio; Fujiyoshi, Takayuki; Kamiya, Koshiro; Watanabe, Masahiko; Katoh, Hiroyuki; Matsuyama, Yukihiro; Yamamoto, Yu; Togawa, Daisuke; Hasegawa, Tomohiko; Kobayashi, Sho; Yoshida, Go; Oe, Shin; Banno, Tomohiro; Arima, Hideyuki; Akeda, Koji; Kawamoto, Eiji; Imai, Hiroshi; Sakakibara, Toshihiko; Sudo, Akihiro; Ito, Yasuo; Kikuchi, Tsuyoshi; Osaki, Shuhei; Tanaka, Nobuhiro; Nakanishi, Kazuyoshi; Kamei, Naosuke; Kotaka, Shinji; Baba, Hideo; Okudaira, Tsuyoshi; Konishi, Hiroaki; Yamaguchi, Takayuki; Ito, Keigo; Katayama, Yoshito; Matsumoto, Taro; Matsumoto, Tomohiro; Idota, Masaru; Kanno, Haruo; Aizawa, Toshimi; Hashimoto, Ko; Eto, Toshimitsu; Sugaya, Takehiro; Matsuda, Michiharu; Fushimi, Kazunari; Nozawa, Satoshi; Iwai, Chizuo; Taguchi, Toshihiko; Kanchiku, Tsukasa; Suzuki, Hidenori; Nishida, Norihiro; Funaba, Masahiro; Yamazaki, Masashi

2018-01-01

Introduction Granulocyte colony-stimulating factor (G-CSF) is generally used for neutropaenia. Previous experimental studies revealed that G-CSF promoted neurological recovery after spinal cord injury (SCI). Next, we moved to early phase of clinical trials. In a phase I/IIa trial, no adverse events were observed. Next, we conducted a non-randomised, non-blinded, comparative trial, which suggested the efficacy of G-CSF for promoting neurological recovery. Based on those results, we are now performing a phase III trial. Methods and analysis The objective of this study is to evaluate the efficacy of G-CSF for acute SCI. The study design is a prospective, multicentre, randomised, double-blinded, placebo-controlled comparative study. The current trial includes cervical SCI (severity of American Spinal Injury Association (ASIA) Impairment Scale B/C) within 48 hours after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group is administered 400 µg/m2/day×5 days of G-CSF in normal saline via intravenous infusion for 5 consecutive days. The placebo group is similarly administered a placebo. Our primary endpoint is changes in ASIA motor scores from baseline to 3 months. Each group includes 44 patients (88 total patients). Ethics and dissemination The study will be conducted according to the principles of the World Medical Association Declaration of Helsinki and in accordance with the Japanese Medical Research Involving Human Subjects Act and other guidelines, regulations and Acts. Results of the clinical study will be submitted to the head of the respective clinical study site as a report after conclusion of the clinical study by the sponsor-investigator. Even if the results are not favourable despite conducting the clinical study properly, the data will be published as a paper. Trial registration number UMIN000018752. PMID:29730616

Geographic Proximity and Racial Disparities in Cancer Clinical Trial Participation

PubMed Central

Kanarek, Norma F.; Tsai, Hua-Ling; Metzger-Gaud, Sharon; Damron, Dorothy; Guseynova, Alla; Klamerus, Justin F.; Rudin, Charles M.

2011-01-01

This study assessed the effects of race and place of residence on clinical trial participation by patients seen at a designated NCI comprehensive cancer center. Clinical trial accrual to cancer case ratios were evaluated using a database of residents at the continental United States seen at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins from 2005 to 2007. Place of residence was categorized into 3 nonoverlapping geographic areas: Baltimore City, non–Baltimore City catchment area, and non–catchment area. Controlling for age, sex, county poverty level, and cancer site, significant race and place of residence differences were seen in therapeutic or nontherapeutic clinical trials participation. White non–Baltimore City catchment area residents, the designated reference group, achieved the highest participation rate. Although the test of interaction (control group compared with all others) was not significant, some race–geographic area group differences were detected. In therapeutic trials, most race–place of residence group levels were statistically lower and different from reference; in nontherapeutic trials, race-specific Baltimore City groups participated at levels similar to reference. Baltimore City residents had lower participation rates only in therapeutic trials, irrespective of race. County poverty level was not significant but was retained as a confounder. Place of residence and race were found to be significant predictors of participation in therapeutic and nontherapeutic clinical trials, although patterns differed somewhat between therapeutic and nontherapeutic trials. Clinical trial accruals are not uniform across age, sex, race, place of residence, cancer site, or trial type, underscoring that cancer centers must better understand their source patients to enhance clinical trial participation. PMID:21147901

An electronic regulatory document management system for a clinical trial network.

PubMed

Zhao, Wenle; Durkalski, Valerie; Pauls, Keith; Dillon, Catherine; Kim, Jaemyung; Kolk, Deneil; Silbergleit, Robert; Stevenson, Valerie; Palesch, Yuko

2010-01-01

A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Ethical considerations of neuro-oncology trial design in the era of precision medicine.

PubMed

Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

2017-08-01

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

Defining Research: The Effect of Linguistic Choices on the Intentions to Participate in Clinical Research.

PubMed

Strekalova, Yulia A

2017-06-01

Significant barriers to participant recruitment for clinical research (CR) are related to effective communication, and nurse coordinators are entrusted with being knowledge brokers between investigators and prospective participants. This prospective cohort study sought to identify linguistic choices that could inform and facilitate recruitment efforts. Healthy adults ( N = 204) were invited to join an online survey to assess the likelihood of participation in CR based on short and extended definitions of CR. Five short definitions included clinical trial, clinical study, health-related research study, community participatory study, and quality improvement study. The likelihood of participation in CR was the lowest for clinical trial and the highest for health-related research study. However, when only an extended definition was provided, those differences were not observed. A linguistic change from trial to study could lead to positive attitude toward CR and improvements in recruitment. However, ethical implications of linguistic choices should be considered.

Cost Drivers of a Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia Phase 3 Clinical Trial

PubMed Central

Stergiopoulos, Stella; Calvert, Sara B; Brown, Carrie A; Awatin, Josephine; Tenaerts, Pamela; Holland, Thomas L; DiMasi, Joseph A; Getz, Kenneth A

2018-01-01

Abstract Background Studies indicate that the prevalence of multidrug-resistant infections, including hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP), has been rising. There are many challenges associated with these disease conditions and the ability to develop new treatments. Additionally, HABP/VABP clinical trials are very costly to conduct given their complex protocol designs and the difficulty in recruiting and retaining patients. Methods With input from clinicians, representatives from industry, and the US Food and Drug Administration, we conducted a study to (1) evaluate the drivers of HABP/VABP phase 3 direct and indirect clinical trial costs; (2) to identify opportunities to lower these costs; and (3) to compare (1) and (2) to endocrine and oncology clinical trials. Benchmark data were gathered from proprietary and commercial databases and used to create a model that calculates the fully loaded (direct and indirect) cost of typical phase 3 HABP/VABP endocrine and oncology clinical trials. Results Results indicate that the cost per patient for a 200-site, 1000-patient phase 3 HABP/VABP study is $89600 per patient. The cost of screen failures and screen failure rates are the main cost drivers. Conclusions Results indicate that biopharmaceutical companies and regulatory agencies should consider strategies to improve screening and recruitment to decrease HABP/VABP clinical trial costs. PMID:29020279

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

[Clinical trials of laparoscopic gastric cancer surgery in South Korea: review and prospect].

PubMed

Zhu, Chunchao; Zhao, Gang; Cao, Hui

2018-02-25

Laparoscopic technology is gradually accepted in gastric cancer surgery, whose efficacy has been demonstrated by some clinical researches. Randomized controlled trials (RCT) are considered as the most important evidence to prove clinical outcomes of laparoscopic surgery for gastric cancer. Korean gastric surgeons have made great contributions to RCT in laparoscopic gastric cancer surgery. KLASS (Korean Laparoscopic Gastrointestinal Surgery Study Group) is one of the most important forerunner and global leader of clinical trials of gastric cancer treatment. KLASS series clinical trials are attracting global attention because of the significant value of surgical treatment for gastric cancer. The RCTs in Korea involve in many aspects of laparoscopic gastrectomy for gastric cancer, including laparoscopy application in early gastric cancer (KLASS-01, KLASS-03 and KLASS-07), advanced gastric cancer (KLASS-02 and KLASS-06), function-preserving gastrectomy (KLASS-04,KLASS-05) and sentinel node navigation surgery (SENORITA trial). In order to share some informations of these RCTs, we review and prospect some important clinical trials of laparoscopic gastric cancer surgery in Korea. With the experience of Korean gastric surgeons, we can make more progress in our own clinical trials of laparoscopic gastric cancer surgery.

Factors associated with willingness to participate in a vaccine clinical trial among elderly Hispanic patients.

PubMed

Rikin, Sharon; Shea, Steven; LaRussa, Philip; Stockwell, Melissa

2017-09-01

A population specific understanding of barriers and facilitators to participation in clinical trials could improve recruitment of elderly and minority populations. We investigated how prior exposure to clinical trials and incentives were associated with likelihood of participation in a vaccine clinical trial through a questionnaire administered to 200 elderly patients in an academic general internal medicine clinic. Wilcoxon signed rank sum test compared likelihood of participation with and without monetary incentives. Logistic regression evaluated characteristics associated with intent to participate in an influenza vaccine trial, adjusted for age, gender, language, and education history. When asked about likelihood of participation if there was monetary compensation, there was a 12.2% absolute increase in those reporting that they would not participate, with a significant difference in the distribution of likelihood before and after mentioning a monetary incentive (Wilcoxon signed rank test, p = 0.001). Those with previous knowledge of clinical trials (54.4%) were more likely to report they would participate vs. those without prior knowledge (OR 2.5, 95% CI [1.2, 5.2]). The study highlights the importance of pre-testing recruitment materials and incentives in key group populations prior to implementing clinical trials.

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.

Last resort or roll of the die? Exploring the role of metaphors in cancer clinical trials education among medically underserved populations.

PubMed

Krieger, Janice L

2014-01-01

Improving communication about cancer clinical trials may help increase patients' understanding of medical research and their interest in participating. It is unfortunate that there is little empirical research to provide guidance on how to adapt clinical trial messages to maximize cultural sensitivity. This study examines (a) how medically underserved women conceptualize clinical trials by examining the language they use to describe them and (b) how this audience interprets metaphorical language used to explain randomization in the context of Phase III cancer clinical trials. The author conducted in-depth interviews and focus groups with 41 rural, low-income older women who either had been diagnosed with cancer or were caregivers for a person with cancer. The most commonly used lay metaphors for clinical trials had strong negative connotations and included treatment by trial and error, patients are guinea pigs, and treatment of last resort. Participants also expressed strong, unfavorable responses to conventional metaphors that equate randomization with the roll of a die or use other gambling language. Low-literacy definition approaches were unexpectedly problematic, suggesting the potential effectiveness of culturally grounded metaphors for communicating about clinical trials. Ethical implications of these findings for cancer communication are discussed.

A lay patient navigation training curriculum targeting disparities in cancer clinical trials.

PubMed

Bryant, Debbie Chatman; Williamson, Deborah; Cartmell, Kathleen; Jefferson, Melanie

2011-12-01

African-Americans experience a disproportionate share of thoracic cancer burden compared to Whites. Low socioeconomic status (SES) and race are factors in low clinical trial enrollment, accounting for the disparities between African-Americans and Whites. Less than 3% of newly diagnosed cancer patients enroll in clinical trials, and of that number, only 10% represent ethnic minorities. The value of clinical trials research is not generalizable without sufficient representation by ethnic minorities. Patient navigation, an intervention designed to ensure timely and efficient access to healthcare, may improve clinical trial enrollment among African-Americans in lung and esophageal trials by influencing a patient's perception of clinical trials. The lack of navigation programs and training may negatively influence standardization of navigation techniques. The purpose of this project was to deliver and evaluate an evidence-based navigation-training curriculum for "lay" navigators. The primary outcomes measured were confidence in the role as navigator, understanding a navigator's role, and knowledge and perception of clinical trials. The results revealed overall confidence in the role as lay navigators increased from pre-to-post test. Lessons learned included the need for preparatory classes to build the navigator's confidence, and additional training components in death and dying. A larger study is warranted to confirm the findings.

Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

PubMed

Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

2016-04-01

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML. © 2015 UICC.

Clinical outcomes research in gynecologic oncology.

PubMed

Melamed, Alexander; Rauh-Hain, J Alejandro; Schorge, John O

2017-09-01

Clinical outcomes research seeks to understand the real-world manifestations of clinical care. In particular, outcomes research seeks to reveal the effects of pharmaceutical, procedural, and structural aspects of healthcare on patient outcomes, including mortality, disease control, toxicity, cost, and quality of life. Although outcomes research can utilize interventional study designs, insightful use of observational data is a defining feature of this field. Many questions in gynecologic oncology are not amenable to investigation in randomized clinical trials due to cost, feasibility, or ethical concerns. When a randomized trial is not practical or has not yet been conducted, well-designed observational studies have the potential to provide the best available evidence about the effects of clinical care. Such studies may use surveys, medical records, disease registries, and a variety of administrative data sources. Even when a randomized trial has been conducted, observational studies can be used to estimate the real-world effect of an intervention, which may differ from the results obtained in the controlled setting of a clinical trial. This article reviews the goals, methodologies, data sources, and limitations of clinical outcomes research, with a focus on gynecologic oncology. Copyright © 2017. Published by Elsevier Inc.

A survey of facilitators and barriers to recruitment to the MAGNETIC trial.

PubMed

Kaur, Geetinder; Smyth, Rosalind L; Powell, Colin V E; Williamson, Paula

2016-12-23

Recruitment to randomised controlled trials with children is challenging. It is imperative to understand the factors that boost or hinder recruitment of children to clinical trials. We conducted a survey of facilitators and barriers to recruitment to the MAGNETIC trial, using a previously developed web-based tool. MAGNETIC is a multicentre randomised trial of nebulised magnesium in acute severe asthma, recruiting 508 children from 30 UK sites. Recruiters were asked to grade a list of factors from -3 to +3 depending on whether the factor was perceived as a strong, intermediate or weak barrier (-3 to -1) or facilitator (+1 to + 3), and using (0) if it was thought to be not applicable. Free text responses were invited on strategies applied to counter the identified barriers. The commonly identified facilitators were motivation and experience of study teams, effective communication and coordination between teams at site and between sites and the Clinical Trials Unit, the presence of designated research nurses, good trial management, clinical trial publicity, simple inclusion criteria, effective communication with parents and presentation of trial information in a simple and clear manner. The commonly identified barriers were heavy clinical workload, shift patterns of work, Good Clinical Practice (GCP) training, inadequate number of trained staff, time and setting of consent seeking, non-availability of research staff out of hours and parents' concerns about their child taking an experimental medicine. Having a designated research nurse, arranging GCP training and trial-related training sessions for staff were the most commonly reported interventions. This study highlights important generic and trial-specific facilitators and barriers to recruitment to a paediatric trial in the acute setting and provides information on the recruitment strategies or interventions that were applied to overcome these barriers. This information can be very useful in informing the design and conduct of future clinical trials with children, particularly in the acute or emergency setting. ISRCTN, ISRCTN81456894 . Registered on 15 November 2007.

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods

PubMed Central

Wiljer, David; Cafazzo, Joseph A

2016-01-01

Background Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Objective Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. Methods We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Results Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η2=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η2=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η2=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r2=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). Conclusions mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients. PMID:27613084

Beyond the Randomized Controlled Trial: A Review of Alternatives in mHealth Clinical Trial Methods.

PubMed

Pham, Quynh; Wiljer, David; Cafazzo, Joseph A

2016-09-09

Randomized controlled trials (RCTs) have long been considered the primary research study design capable of eliciting causal relationships between health interventions and consequent outcomes. However, with a prolonged duration from recruitment to publication, high-cost trial implementation, and a rigid trial protocol, RCTs are perceived as an impractical evaluation methodology for most mHealth apps. Given the recent development of alternative evaluation methodologies and tools to automate mHealth research, we sought to determine the breadth of these methods and the extent that they were being used in clinical trials. We conducted a review of the ClinicalTrials.gov registry to identify and examine current clinical trials involving mHealth apps and retrieved relevant trials registered between November 2014 and November 2015. Of the 137 trials identified, 71 were found to meet inclusion criteria. The majority used a randomized controlled trial design (80%, 57/71). Study designs included 36 two-group pretest-posttest control group comparisons (51%, 36/71), 16 posttest-only control group comparisons (23%, 16/71), 7 one-group pretest-posttest designs (10%, 7/71), 2 one-shot case study designs (3%, 2/71), and 2 static-group comparisons (3%, 2/71). A total of 17 trials included a qualitative component to their methodology (24%, 17/71). Complete trial data collection required 20 months on average to complete (mean 21, SD 12). For trials with a total duration of 2 years or more (31%, 22/71), the average time from recruitment to complete data collection (mean 35 months, SD 10) was 2 years longer than the average time required to collect primary data (mean 11, SD 8). Trials had a moderate sample size of 112 participants. Two trials were conducted online (3%, 2/71) and 7 trials collected data continuously (10%, 7/68). Onsite study implementation was heavily favored (97%, 69/71). Trials with four data collection points had a longer study duration than trials with two data collection points: F4,56=3.2, P=.021, η(2)=0.18. Single-blinded trials had a longer data collection period compared to open trials: F2,58=3.8, P=.028, η(2)=0.12. Academic sponsorship was the most common form of trial funding (73%, 52/71). Trials with academic sponsorship had a longer study duration compared to industry sponsorship: F2,61=3.7, P=.030, η(2)=0.11. Combined, data collection frequency, study masking, sample size, and study sponsorship accounted for 32.6% of the variance in study duration: F4,55=6.6, P<.01, adjusted r(2)=.33. Only 7 trials had been completed at the time this retrospective review was conducted (10%, 7/71). mHealth evaluation methodology has not deviated from common methods, despite the need for more relevant and timely evaluations. There is a need for clinical evaluation to keep pace with the level of innovation of mHealth if it is to have meaningful impact in informing payers, providers, policy makers, and patients.

Clinical Trials Targeting Aging and Age-Related Multimorbidity

PubMed Central

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

2017-01-01

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

Methodology of Clinical Trials Aimed at Assessing Interventions for Cutaneous Leishmaniasis

PubMed Central

Olliaro, Piero; Vaillant, Michel; Arana, Byron; Grogl, Max; Modabber, Farrokh; Magill, Alan; Lapujade, Olivier; Buffet, Pierre; Alvar, Jorge

2013-01-01

The current evidence-base for recommendations on the treatment of cutaneous leishmaniasis (CL) is generally weak. Systematic reviews have pointed to a general lack of standardization of methods for the conduct and analysis of clinical trials of CL, compounded with poor overall quality of several trials. For CL, there is a specific need for methodologies which can be applied generally, while allowing the flexibility needed to cover the diverse forms of the disease. This paper intends to provide clinical investigators with guidance for the design, conduct, analysis and report of clinical trials of treatments for CL, including the definition of measurable, reproducible and clinically-meaningful outcomes. Having unified criteria will help strengthen evidence, optimize investments, and enhance the capacity for high-quality trials. The limited resources available for CL have to be concentrated in clinical studies of excellence that meet international quality standards. PMID:23556016

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.

Challenging Assumptions About Minority Participation in US Clinical Research

PubMed Central

Kalbaugh, Corey A.

2011-01-01

Although extensive research addresses minorities’ low participation in clinical research, most focuses almost exclusively on therapeutic trials. The existing literature might mask important issues concerning minorities’ participation in clinical trials, and minorities might actually be overrepresented in phase I safety studies that require the participation of healthy volunteers. It is critical to consider the entire spectrum of clinical research when discussing the participation of disenfranchised groups; the literature on minorities’ distrust, poor access, and other barriers to trial participation needs reexamination. Minority participation in clinical trials is an important topic in public health discussions because this representation touches on issues of equality and the elimination of disparities, which are core values of the field. PMID:22021285

Design and implementation of a controlled clinical trial to evaluate the effectiveness and efficiency of routine opt-out rapid human immunodeficiency virus screening in the emergency department.

PubMed

Haukoos, Jason S; Hopkins, Emily; Byyny, Richard L; Conroy, Amy A; Silverman, Morgan; Eisert, Sheri; Thrun, Mark; Wilson, Michael; Boyett, Brian; Heffelfinger, James D

2009-08-01

In 2006, the Centers for Disease Control and Prevention (CDC) released revised recommendations for performing human immunodeficiency virus (HIV) testing in health care settings, including implementing routine rapid HIV screening, the use of an integrated opt-out consent, and limited prevention counseling. Emergency departments (EDs) have been a primary focus of these efforts. These revised CDC recommendations were primarily based on feasibility studies and have not been evaluated through the application of rigorous research methods. This article describes the design and implementation of a large prospective controlled clinical trial to evaluate the CDC's recommendations in an ED setting. From April 15, 2007, through April 15, 2009, a prospective quasi-experimental equivalent time-samples clinical trial was performed to compare the clinical effectiveness and efficiency of routine (nontargeted) opt-out rapid HIV screening (intervention) to physician-directed diagnostic rapid HIV testing (control) in a high-volume urban ED. In addition, three nested observational studies were performed to evaluate the cost-effectiveness and patient and staff acceptance of the two rapid HIV testing methods. This article describes the rationale, methodologies, and study design features of this program evaluation clinical trial. It also provides details regarding the integration of the principal clinical trial and its nested observational studies. Such ED-based trials are rare, but serve to provide valid comparisons between testing approaches. Investigators should consider similar methodology when performing future ED-based health services research.

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.

Patient and family member perspectives on searching for cancer clinical trials: A qualitative interview study.

PubMed

Ridgeway, Jennifer L; Asiedu, Gladys B; Carroll, Katherine; Tenney, Meaghan; Jatoi, Aminah; Radecki Breitkopf, Carmen

2017-02-01

Clinical trials are vital in the context of ovarian cancer and may offer further treatment options during disease recurrence, yet enrollment remains low. Understanding patient and family member experiences with identifying trials can inform engagement and education efforts. Interviews were conducted with 33 patients who had experience with clinical trial conversations and 39 nominated family members. Thematic analysis examined experiences and generated findings for clinical practice. Trial conversations with providers at diagnosis were uncommon and often overwhelming. Most participants delayed engagement until later in the disease course. With hindsight, though, some wished they considered trials earlier. Difficulty identifying appropriate trials led some to defer searching to providers, but then they worried about missed opportunities. Most family members felt unqualified to search. Trial conversations during clinical encounters should start early and include specifying search responsibilities of providers, patients, and family. Patients and family members can be engaged in searches but need guidance. Trials should be discussed throughout the disease course, even if patients are not ready to participate or are not making a treatment decision. Education should focus on identifying trials that meet search criteria. Transparency regarding each individual's role in identifying trials is critical. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical efficacy of composite versus ceramic inlays and onlays: a systematic review.

PubMed

Fron Chabouis, Hélène; Smail Faugeron, Violaine; Attal, Jean-Pierre

2013-12-01

Large tooth substance losses are frequent in posterior teeth because of primary caries or aging restorations. Inlays and onlays are often the minimal invasive solution in such cases, but the efficacy of the composite and ceramic materials used is unknown. We performed a systematic review of randomized controlled trials comparing the efficacy of composite and ceramic inlays or onlays. MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched without any restriction on date or language, as were references of eligible studies and ClinicalTrials.gov. Eligible studies were randomized trials comparing the clinical efficacy of composite to ceramic inlays or onlays in adults with any clinical outcome for at least 6 months. From 172 records identified, we examined reports of 2 randomized controlled trials involving 138 inlays (no onlays evaluated) in 80 patients and exhibiting a high-risk of bias. Outcomes were clinical scores and major failures. The 3-year overall failure risk ratio was 2 [0.38-10.55] in favor of ceramic inlays although not statistically significant. The reported clinical scores (United States Public Health Services and Californian Dental Association) showed considerable heterogeneity between trials and could not be combined. We have very limited evidence that ceramics perform better than composite material for inlays in the short term. However, this result may not be valid in the long term, and other trials are needed. Trials should follow Fédération dentaire internationale recommendations and enhance their methodology. Trials comparing composite and ceramic onlays are needed. Copyright © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Selection of Patients in Ongoing Clinical Trials on Lung Cancer.

PubMed

Schulkes, Karlijn J G; Nguyen, Cindy; van den Bos, Frederiek; van Elden, Leontine J R; Hamaker, Marije E

2016-12-01

Lung cancer is predominantly a disease of the elderly: half of all newly diagnosed patients are over 70 years old. Older patients and those with comorbidities are underrepresented in clinical trials; scientific communities have addressed this issue since the end of the 20th century. We set out to determine the characteristics of the selection of patients in lung cancer trials that are currently recruiting. We searched The United States National Institutes of Health (NIH) clinical trial registry ( www.clinicaltrials.gov ) on April 23, 2015 for currently recruiting phase I, II, or III clinical trials in lung cancer. Trial characteristics and study objectives were extracted from the registry website. Of the 419 trails selected in this overview, 88 % explicitly or implicitly excluded elderly patients. Patients were excluded based on stringent organ selection in 76 % of the trials, based on performance status (57 %) and based on age (13 %). The median number of placed restrictions per trial was seven. In the 2 % of the trials that were exclusively designed for elderly patients only fit patients were included. In this overview of current lung cancer trials registered in the NIH clinical trial registry, we found that elderly patients and those with comorbidities are often excluded from participation in clinical trials. Therefore, it is difficult for physicians and their frail patients to properly evaluate the efficacy and safety of current treatment options. More research that includes the elderly and those with comorbidities is urgently needed.

Ten-year NEDO BVAD development program: moving forward to the clinical arena.

PubMed

Motomura, Tadashi; Okubo, Hisashi; Oda, Takeshi; Ogawa, Daisuke; Okahisa, Toshiya; Igo, Stephen; Shinohara, Toshiyuki; Yamamoto, Yoshiro; Noguchi, Chikaya; Ishizuka, Tsukasa; Okamoto, Eiji; Nosé, Yukihiko

2006-01-01

Since 1995, the Baylor Group has been developing a totally implantable NEDO BVAD system. This 10-year program was completed in March 2005, and preparation for clinical trials is underway. This article summarizes the entire 10-year NEDO program and describes the strategy for clinical trials. The project aimed to achieve: (1) dual centrifugal pumps with the ability of full biventricular support, (2) a compact system implantable into small adults, (3) a totally implantable system with transcutaneous energy transmission system (TETS), (4) a durable system with a lifetime of over 5 years, and (5) a system free of thrombus and with minimal hemolysis. The final goals are to complete preclinical system evaluations and commence the clinical trials in the near future. In vitro studies have demonstrated a pump capacity of over 8.5 l/min and an Index of Hemolysis of <0.004 g/100 l. The pump-bearing life expectancy was over 5 years. To date, eight pumps endured in vivo studies of over 3 months without complications, including thromboembolic events. The in vitro endurance studies of eight pumps are longer than 1 year. There were no mechanical malfunctions or pump failure. A stepwise clinical trial is being planned: Step1, a wearable BVAD/VAD will be clinically studied; Step 2, the BVAD/VAD will be implanted intracorporeally without TETS; and, Step 3, a totally implantable system will be clinically evaluated. The NEDO BVAD system has completed preclinical testing. Clinical trial preparation is underway.

Strategies and Challenges in Clinical Trials Targeting Human Aging

PubMed Central

Newman, John C.; Milman, Sofiya; Hashmi, Shahrukh K.; Austad, Steve N.; Kirkland, James L.; Halter, Jeffrey B.

2016-01-01

Interventions that target fundamental aging processes have the potential to transform human health and health care. A variety of candidate drugs have emerged from basic and translational research that may target aging processes. Some of these drugs are already in clinical use for other purposes, such as metformin and rapamycin. However, designing clinical trials to test interventions that target the aging process poses a unique set of challenges. This paper summarizes the outcomes of an international meeting co-ordinated by the NIH-funded Geroscience Network to further the goal of developing a translational pipeline to move candidate compounds through clinical trials and ultimately into use. We review the evidence that some drugs already in clinical use may target fundamental aging processes. We discuss the design principles of clinical trials to test such interventions in humans, including study populations, interventions, and outcomes. As examples, we offer several scenarios for potential clinical trials centered on the concepts of health span (delayed multimorbidity and functional decline) and resilience (response to or recovery from an acute health stress). Finally, we describe how this discussion helped inform the design of the proposed Targeting Aging with Metformin study. PMID:27535968

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 Elsevier Inc. All rights reserved.

Review of clinical trials evaluating safety and efficacy of milk thistle (Silybum marianum [L.] Gaertn.).

PubMed

Tamayo, Carmen; Diamond, Suzanne

2007-06-01

Milk thistle extracts have been used as traditional herbal remedies for almost 2000 years. The extracts are still widely used to protect the liver against toxins and to control chronic liver diseases. Recent experimental and clinical studies suggest that milk thistle extracts also have anticancer, antidiabetic, and cardioprotective effects. This article reviews clinical trials of milk thistle conducted in the past 5 years including pharmacokinetic and toxicity studies, herb-drug interactions, and other safety issues. Several trials have studied the effects of milk thistle for patients with liver diseases, cancer, hepatitis C, HIV, diabetes, and hypercholesterolemia. Promising results have been reported in the protective effect of milk thistle in certain types of cancer, and ongoing trials will provide more evidence about this effect. In addition, new established doses and improvement on the quality and standardization of this herb will provide the much-awaited evidence about the efficacy of milk thistle in the treatment of liver diseases. Milk thistle extracts are known to be safe and well tolerated, and toxic or adverse effects observed in the reviewed clinical trials seem to be minimal. The future of milk thistle research is promising, and high-quality randomized clinical trials on milk thistle versus placebo may be needed to further demonstrate the safety and efficacy of this herb.

Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

PubMed Central

Miller, Jennifer E; Wilenzick, Marc; Ritcey, Nolan; Ross, Joseph S; Mello, Michelle M

2017-01-01

Objectives To define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs. Design Cross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies. Data sources Data from over 45 sources, including Drugs@FDA.gov, ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers. Outcome measures Trial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level. Results The FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries. Conclusions Among large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress. PMID:29208616