Important information about completed and ongoing clinical trials is missing from the ClinicalTrials.gov, a web-based registry of clinical trials conducted worldwide, according to a research article by Joseph Ross (Mount Sinai School of Medicine and the James J. Peters VA Medical Center, New York, USA) and colleagues. The work, published in the open access journal PLoS Medicine, also shows that for many of the completed clinical trials registered at ClinicalTrials.gov results are not available in the medical literature.
Clinicaltrials.gov was established in 2000 following the US 1997 FDA Modernization Act and was created to provide public access to information on clinical trials; it provides a registry of both federally and privately funded trials. Ross and colleagues sampled a large cross-section of trials (7,515 of over 77,000 trials held on ClinicalTrials.gov) registered after 31 December 1999 and completed by 8 June 2007. All trials reported the essential information required by ClinicalTrials.gov, but optional data – including information such as the primary outcome of the trial and start and end dates – were less complete, report the authors. A random 10% subsample of the trials (677 in total) revealed that less than half were eventually published in the medical literature, and for only a third of these was the publication linked back to the ClinicalTrials.gov registry record.
Selective publication of trials (a preference towards publishing results of studies with a "positive" outcome) can distort the evidence available for clinical decision making. Policy statements – such as the World Medical Association’s Declaration of Helsinki – declare that researchers have a duty to publish the results of all research on human subjects, including both negative and inconclusive studies as well as positive studies.
The authors argue that "without greater attention to reporting of all data elements, the potential for ClinicalTrials.gov to address selective publication of clinical trials will be limited." Accurate and up-to-date trial information helps researchers, clinicians and patients to access all of the data available and prevents trial results from being hidden, say the authors. They argue that open access to trial data would encourage publication of all results, both positive and negative, from completed trials.
Funding: Joseph Ross is funded by the National Institute of Aging and by the Paul B. Beeson Career Development Award Program from the American Federation of Aging Research, and has received support from the Department of Veteran Affairs Health Services Research and Development Service and the Hartford Foundation during the early stages of the work. The funders had no role in study design, data collection and analysis, or preparation of the manuscript.
Competing interests: Joseph Ross, Gregory Mulvey and Harlan Krumholz were consultants at the request of plaintiffs in litigation against Merck and Co., related to rofecoxib. Steven Nissen has received support for clinical trials through the Cleveland Clinic Coordinating Center for Clinical Research from Pfizer, Astra Zeneca, Daiichi-Sankyo, Takeda, Roche, Novartis, Sanofi-Aventis, and Eli Lilly. Steven Nissen also consults for Novartis, Anylam, Sanofi-Aventis, Astra Zeneca, Forbes Meditech, Ganedon, Genzyme, Hollis-Eden, Eli Lilly, Pfizer, Karo Bio, Novo Nordisk, Roche, Daiichi-Sankyo, Takeda, Resverlogix, and Glaxo-Smith-Kline, but requires them to donate all honoraria or consulting fees directly to charity so that he receives neither income nor a tax deduction. Harlan Krumholz has research contracts with the American College of Cardiology and the Colorado Foundation for Medical Care, has served on the advisory boards of Amgen and UnitedHealthcare, has been a subject expert for VHA, and is academic editor-in-Chief of Circulation: Cardiovascular Quality and Outcomes, and Journal Watch Cardiology of the Massachusetts Medical Society.
(Source: Public Library of Science: PLoS Medicine: September 2009)