Clinical trial data as a public good.

KNOWLEDGE OF THE BENEFITS AND RISKS OF PRESCRIPtion drugs is based mainly on published reports of clinical trials, yet the medical literature may present an incomplete and potentially biased sample of clinical trials. Trials with positive results generally are published more frequently than studies that conclude that a new drug poses greater risks or is no more effective than standard therapy or a placebo. Furthermore, some articles may distort trial findings by omitting important data or by modifying prespecified outcome measures. Lack of access to detailed information about clinical trials can undermine the integrity of medical knowledge. To increase transparency, the International Committee of Medical Journal Editors decided in 2004 that their journals would not publish results of a clinical trial unless the trial was registered prior to patient enrollment. The committee stated that registries should include data specified by the World Health Organization, although these data elements do not provide a complete picture of the clinical trials. Since 2007, US law has required researchers to register phase 2 and higher trials of drugs and biologicals on the ClinicalTrials.gov website if there is a trial site in the United States or if the trial is part of a US Food and Drug Administration (FDA) investigational new drug application. Researchers are typically required to post key results within a year of completing data collection, but studies of off-label drug uses (ie, uses other than those described in an FDA-approved drug label) are allowed 3 years to post trial results. However, actual trial registration falls short of requirements. A review of 323 articles found that nearly 28% of the trials were unregistered. Among articles with adequately registered trials, 31% had discrepancies between outcomes reported in the registration and in the published report. Moreover, no authority checks whether registration information is accurate. Even more important, current law does not require registration of sufficient information to ensure accuracy, completeness, or reasonable interpretation of the findings. The Standardized Clinical Study Report Current policy does not consider a practical, inexpensive solution: mandatory disclosure of the standardized Clinical Study Report (CSR) for all clinical trials involving FDAapproved drugs. The FDA follows the International Conference on Harmonization Standards for Registration of Pharmaceuticals for Human Use, which requires submission of a CSR (with specified content and format) when reporting clinical trials to governmental authorities. The CSR summarizes the trial, clinical end points, methods, key data, and data analysis. The CSR includes “statistical description, presentations . . . tables and figures . . . with appendices containing the protocol, sample case report forms, investigator related information, information related to the test drugs/investigational products including active control/ comparators, technical statistical documentation, related publications, patient data listings, and technical statistical details such as derivations, computations, analyses, and computer output etc.” A CSR includes the most pertinent information about a clinical trial in an easily analyzed format. Drug manufacturers already produce these reports to meet international and national regulatory requirements. Making CSRs publicly available would not be expensive, yet disclosure would promote research integrity, medical knowledge, and public health. Furthermore, CSRs are more likely to be reliable than other summaries. Drug manufacturers submit CSRs to public authorities when they seek marketing approval and cannot alter or delete data without potentially jeopardizing their relationships with regulatory agencies and risking criminal prosecution. A review of the clinical trials that evaluated the efficacy of gabapentin for off-label use demonstrated the importance of disclosing CSRs. In litigation involving illegal marketing, internal corporate documents for 20 clinical trials (including 18 CSRs) for off-label use of gabapentin were discovered. However, the results for only 9 of these studies were fully published and only 1 published report presented both primary outcome measures and P values consistent with the