In the past 5 years, prospective registration of clinical trials has become standard practice. Public reporting of summary results, independent of the interests of the trial sponsor, represents the next step in this international experiment in systematic disclosure of clinical trial information. It has been 2 years since the launch of the ClinicalTrials.gov results database, and people can now access summary trial data that were not previously available publicly. Researchers, policymakers, and others can now examine features and trends of the clinical research enterprise that were previously difficult to study. For example, methodologists may evaluate the appropriateness of designing trials with many primary outcome measures. Policymakers may consider how current patterns in the use of data monitoring committees might affect the quality and safety of the resulting research. Others may use the data to monitor trends in the clinical research enterprise and raise questions about the portfolio of trials relative to public health needs. The ultimate usefulness of the registry and results database will become apparent as more trial information and results are posted and as persons with different interests and needs incorporate these data into their analyses. ClinicalTrials.gov is continually adding features and linkages to facilitate the use of the data by different audiences, and other groups repackage these data for more specific audiences. For example, BreastCancerTrials.org (www.breastcancertrials.org
) augments registry data to serve the breast-cancer community. The Clinical Trials Transformation Initiative is leading an effort to develop a publicly accessible research-quality data set in order to facilitate examination of the clinical research enterprise.28
When one is using the data in ClinicalTrials.gov, however, certain limitations should be kept in mind. First, there are undoubtedly trials that are not registered in ClinicalTrials.gov or any other publicly accessible registry. Coverage in ClinicalTrials.gov is likely to be most complete for trials of drugs or devices that are sponsored by U.S.-based or multinational organizations (e.g., major pharmaceutical companies). Second, some records are missing information (e.g., optional data elements) or contain imprecise entries. We are not able to impose requirements beyond those of the prevailing federal law; trials registered since the passage of the FDAAA have to meet more requirements than do older trials, but investigators who use all ClinicalTrials.gov data will encounter many records with missing fields. In addition, given the demands of individual record review, some problematic entries will find their way onto the public site. Third, new registry and registration policies are being implemented in specific regions and countries around the world. The World Health Organization has established a search portal that includes data from ClinicalTrials.gov and 11 other registries, totaling more than 123,500 records as of November 23, 2010. However, overlapping scope and inadequate coordination internationally have contributed to the difficulty in determining the precise number of unique trials being conducted.
Disclosure requirements for clinical trials continue to evolve. In the United States, the FDAAA calls for the expansion of the basic results database through rulemaking “to provide more complete results information” and mandates the consideration of issues such as requiring results reporting for trials of drugs and devices that have not been approved by the FDA, the inclusion of narrative summaries, and the submission of full study protocols. In general, a guiding principle is that expansion of the registry and results database should only improve on, not reduce, the functionality and usefulness of ClinicalTrials.gov. Information about the status of the rulemaking process, including notification of the opportunity to provide comments, can be found at http://prsinfo.clinicaltrials.gov/fdaaa.html
. Internationally, the European Medicines Agency is planning to make summary protocol and results information publicly available for clinical trials of approved and unapproved drugs conducted in the European Union. Efforts are under way to ensure the compatibility of the European Medicines Agency database with ClinicalTrials.gov, thus potentially minimizing reporting burdens for those conducting multinational trials and supporting seamless access to results from many parts of the world.29
Despite the change in cultural expectations regarding trial disclosure and the fact that many trial sponsors and investigators are successfully meeting the requirement to submit summary results, our experience to date indicates that others are still struggling. In addition, the poor quality of some submitted entries is troubling. As Beecher observed in 1966, a “truly responsible
investigator [emphasis in the original]” is essential if the rules governing clinical research are to have the intended effect.30
Similarly, the usefulness of ClinicalTrials.gov ultimately depends on whether responsible investigators and sponsors make diligent efforts to submit complete, timely, accurate, and informative data about their studies.