Explore the vast range of titles available.

The final rule for reporting clinical trial results has now been issued by the Department of Health and Human Services. It aims to increase accountability in the clinical research enterprise, making key information available to researchers, funders, and the public. Title VIII of the Food and Drug Administration (FDA) Amendments Act of 2007 (FDAAA) expanded the legal mandate for sponsors and others responsible for certain clinical trials of FDA-regulated drug, biologic, and device products to register their studies and report summary results information to ClinicalTrials.gov, 1 which is managed by the National Library of Medicine at the National Institutes of Health (NIH). The statute expanded registration requirements and provided a legally defined timeline with specific requirements for the systematic reporting of summary trial results. Although statutory components took effect before 2010, the FDAAA directed the Department of Health and Human Services . . .

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.

ClinicalTrials.gov, a repository of information about clinical studies and their results, together with specialised search tools, provides a unique window into the clinical research enterprise, which includes all initiated, ongoing, and completed or terminated clinical studies. Researchers are increasingly using information from the database to assess research reporting practices, or to characterise the clinical research enterprise. Conducting valid analyses requires an understanding of both the capabilities and limitations of the database (that is, intrinsic factors) as well as reporting policies and other factors external to the database that influence the types of studies in ClinicalTrials.gov in a specified time. This article discusses 10 key issues that researchers need to consider when using the database to conduct research.

A decade after ClinicalTrials.gov launched a database for reporting results of clinical trials, the database includes results of approximately 36,000 trials. The authors discuss laws, regulations, and policies relevant to results reporting, trends over time in the frequency of reporting, and adherence to requirements for the completeness and quality of the results reported.

This article reviews the history and current status of clinical trial registrations and results data posted on the National Library of Medicine's Web site ClinicalTrials.gov. The ClinicalTrials.gov trial registry was launched more than a decade ago. Since that time, it has been evolving in response to various policy initiatives. The registry now contains information on more than 100,000 clinical studies and has emerged as a key element of many public health policy initiatives aimed at improving the clinical research enterprise. In 2008, a database for reporting summary results was added to the registry. In this article, we present an update on relevant policies, summarize the structure and contents of the results database, and show how ClinicalTrials.gov data can be used to gain insight into the . . .

  Abbreviations: CONSORT, Consolidated Standards of Reporting Trials; CRE, clinical research enterprise; CRF, case report form; DICOM, Digital Imaging and Communications in Medicine; FDG, fluorodeoxyglucose; GSK, GlaxoSmithKline; IOM, Institute of Medicine; IPD, individual participant data; NLM, National Library of Medicine; PET, positron emission tomography; RIAT, Restoring Invisible and Abandoned Trials; SSRI, selective serotonin reuptake inhibitor; TRS, trial reporting system Provenance: Commissioned; externally peer reviewed Summary Points * The role of individual participant data (IPD) sharing can best be understood as part of an overall three-level trial reporting system (TRS) framework. * Different \"types\" of IPD, which reflect varying degrees of information granularity, have different potential benefits and harms. * Study 329 of Paxil (paroxetine) in children with depression is used as a case study to highlight the potential value of different components of the TRS. [...]proposals would only require the sharing of a subset of IPD and documents for those aggregate data reported in the publication and not the full dataset, precluding secondary analyses intended to go beyond validation and reproducibility of the original publication.

Medical progress is possible only because altruistic volunteers put themselves at risk in clinical trials. The results of those trials are then used to inform medical decisions. The traditional system of relying on investigators, sponsors, and journal editors to decide whether, when, and how to report trial results was based on trust. There was no way to know what trials had been conducted, what data were collected, how they were analyzed, and whether the reported data were complete and accurate. Policies mandating the registration of trials and the reporting of summary results were instituted to provide greater transparency. In turn, . . .

Prior studies suggest that clinical trials are often hampered by problems in design, conduct, and reporting that limit their uptake in clinical practice. We have described ‘informativeness’ as the ability of a trial to guide clinical, policy, or research decisions. Little is known about the proportion of initiated trials that inform clinical practice. We created a cohort of randomized interventional clinical trials in three disease areas (ischemic heart disease, diabetes mellitus, and lung cancer) that were initiated between January 1, 2009 and December 31, 2010 using ClinicalTrials.gov . We restricted inclusion to trials aimed at answering a clinical question related to the treatment or prevention of disease. Our primary outcome was the proportion of clinical trials fulfilling four conditions of informativeness: importance of the clinical question, trial design, feasibility, and reporting of results. Our study included 125 clinical trials. The proportion meeting four conditions for informativeness was 26.4% (95% CI 18.9–35.0). Sixty-seven percent of participants were enrolled in informative trials. The proportion of informative trials did not differ significantly between our three disease areas. Our results suggest that the majority of randomized interventional trials designed to guide clinical practice possess features that may compromise their ability to do so. This highlights opportunities to improve the scientific vetting of clinical research.

[...]industry-sponsored trials are more likely to be published when the results favor the industry's financial interests. [...]among other types of bias, positive trial results are more likely to be published than negative results, even when the sponsor does not have an obvious financial interest in the intervention under study.1 In this issue, Morrow et al2 explore how the implicit and explicit incentives related to the pharmaceutical industry influence the publication decision. There are many international trial registration policies, including the International Committee of Medical Journal Editors.7 However, Canada, from where the findings of Morrow et al2 come, encourages but does not require the registration or results reporting from all clinical trials.8 Importantly, Canada encourages the use of either ClinicalTrials.gov or the International Standard Randomized Controlled Trial Number Registry; we applaud the decision to use an existing registry rather than creating a separate national trial reporting infrastructure. [...]the participation of humans in these trials conveys a responsibility for providing public knowledge. [...]participation by university faculty in trials that prohibit trial reporting or that do not provide access to the trial data should not be tolerated.

The following “lessons learned” from clinical trial registration might inform current efforts to improve the reporting of database studies.1 Potential goal: identify and mitigate publication bias 1.1 An unambiguous list of studies is required A study registration system can address publication bias by providing a list of initiated studies that can then be used to determine the studies that have reported results and the studies that have not. Without external validation into the start time of a database study, it is possible for an investigator to conduct several potential analyses before choosing the most promising one for registration.1.2 Well-defined and broadly enforced policies are essential to achieve a comprehensive listing of studies Trial registration gained traction in 2005 when the International Committee of Medical Journal Editors (ICMJE) announced that journals would decline to consider any manuscript describing an unregistered trial, and was further reinforced when a number of articles were rejected for failing to comply [6]. A subsequent law, The Food and Drug Administration Amendments Act of 2007 (FDAAA), created a legal requirement that applied to many trials, added additional specific data elements, and created fines and other penalties for noncompliance [7]. The enforcement of registration requirements for database studies would require systems that provide transparency into when data are accessed so that start dates can be verified.1.3 International collaboration on a registration system is essential for the prevention of informational “chaos” The full power of trial registration to provide an unambiguous listing of initiated clinical trials has been hampered by the proliferation of World Health Organization-approved registries that are accepted by the ICMJE.