May 2, 2012, Vol 307, No. 17, pp 1775-1877
Characteristics of Clinical Trials Registered in ClinicalTrials.gov, 2007-2010
Robert M. Califf, Deborah A. Zarin, Judith M. Kramer, Rachel E. Sherman, Laura H. Aberle, Asba Tasneem
Context 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.
Objective To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database.
Methods 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.
Main Outcome Measures 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).
Results 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.
Conclusion 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.
The Evolution of Trial Registries and Their Use to Assess the Clinical Trial Enterprise
Kay Dickersin, Drummond Rennie
The original purpose of registries of clinical trials was to reveal the existence of all trials, published or not, to investigators and systematic reviewers. Trials left unpublished because results were unfavorable to their sponsors, or simply because investigators never submitted them to journals for publication, could then be discovered, the trial investigators contacted, and the available trial evidence involving medical interventions could then be assessed. This would help eliminate publication bias, shown originally in the 1980s,1 demonstrated by Simes2 to affect the treatment of patients, and later revealed to be widespread by the expanding efforts of the Cochrane Collaboration. A seemingly arcane statistical point became a pressing clinical problem.
Although the 1997 US Food and Drug Administration Modernization Act (FDAMA)3 established a US-based trial registry, ClinicalTrials.gov, the mandated content was narrowly defined by law, and trial investigators, whether funded by commercial sponsors, government agencies, or academic institutions, …