Sharing and reporting the results of clinical trials.

Theprinciple of data sharingdates to the dawnof scientificdiscovery—it ishowresearchers fromdifferentdisciplines and countries form collaborations, learn from others, identify new scientific opportunities, and work to turnnewlydiscovered information intosharedknowledgeandpracticaladvances.Whenresearch involveshumanvolunteerswhoagree toparticipate in clinical trials to test new drugs, devices, or other interventions, this principleofdata sharingproperly assumes the roleof an ethical mandate. These participants are often informed that such research might not benefit them directly, butmayaffect the livesofothers. If theclinical researchcommunity fails tosharewhat is learned,allowing data to remainunpublishedor unreported, researchers are reneging on the promise to clinical trial participants, are wasting time and resources, and are jeopardizing public trust. Acrosspublic andprivate sectors, theUnitedStates has increasingly focused on data sharing, including throughdirectives fromtheWhiteHouse toensure that valuable scientific data generated with federal funding arepublicly available anduseable.1 As the largest public funder of biomedical research in the world, the National Institutes of Health (NIH) has a special responsibility to share data while safeguarding the interests of researchers and research participants. Today, the US Department of Health and Human Services (HHS) proposed a rule2 to implement the requirements of the Food and Drug Administration Amendments Act of 2007 (FDAAA), to require public sharing of summary data from certain clinical trials of FDA-regulateddrugs anddevices.3 Such summarydata would need to includedemographic andother baseline characteristics of participants, dataonprimary and secondary outcomes, and information about adverse events. Although the FDAAA,with such a requirement, has been in place for several years, the proposed regulationwill, when finalized, clarify the requirements and extend them in ways permitted by law. HHS is seeking public comment2 to informthe final contentof the regulations. The scientific community has a disappointing track record for dissemination of clinical trial results. Numerous factors may contribute to these poor publication rates, including some that are beyond the control of researchers. Despite the best efforts of investigators, the results of some trials may never reach the threshold deemed necessary to merit the attention of journal editors and readers. Even published results may focus only on the findings of most interest to the investigators. Other means to share such data are necessary because both real and potential harm can result from failure to fully disclose the results of clinical trials. However, difficulty with achieving publication in scientific journals for negative results cannot be blamed entirely. A recent analysis of 400 clinical studies revealed that 30% had not shared results through publication or through results reporting in ClinicalTrials.gov within 4 years of completion.4 This is a serious issue and the proposed rule underscores the intent of NIH to take strong action to promote timely dissemination of clinical trial results. Withoutaccesstocomplete informationaboutaparticular scientific question, including negative or inconclusivedata,duplicativestudiesmaybe initiatedthatunnecessarily put patients at risk or expose them to interventions that are known to be ineffective for specific uses. If multiple related studies are conducted but only positive results are reported, publication bias can distort the evidence base. Incomplete knowledge can then be incorporated into clinical guidelines and patientcare.However,oneof thegreatestharmsfromnondisclosure of resultsmay be the erosion of the trust accorded to researchers by trial participants and, when public funds are used, by taxpayers. The efforts to make information derived from clinical trials public has been under way for nearly 2 decades. In 2000, following passage of the FDA Modernization Act of 1997, NIH established ClinicalTrials.gov, a public database operated by NIH’s National Library of Medicine. In 2007, the FDAAA expanded the subset of clinical trials required to register within 21 days of enrolling the first participant.3 Registration involves submitting important information about the condition under study, the interventions tested, recruitment criteria, and location of trial sites into ClinicalTrials.gov. This information allows patients and clinicians to find currently enrolling trials focused on conditions of specific interest; more than 57 000 unique visitors access the site every day. The FDAAA also mandates, with some exceptions, that basic summary results from registered trials of approved products be submitted to the database generally within 1 year of the trial’s completion of collection of primary outcome data. More than 14 000 results records have already been posted, but reporting of results has not yet become routine across the clinical research enterprise. Thesubsetofclinical trials subject totheFDAAAproposed regulation includes certain controlled interventional studies of drugs, biological products, and devices that are regulatedby theFDA; excludedarephase 1 studies of drugs andbiological products and small feasibilitystudiesofdevices.Data fromcoveredclinical trials must be submitted irrespective of who funds or conducts the trial. Although the FDAAA currently requires results onlyof trials of approvedproducts, it allowsHHS tobroadenthescopetounapprovedproducts.Giventhe importance of data from trials of drugs or devices that never result inFDAclearance, licensure,orapproval,HHS VIEWPOINT