17 Jun ClinicalTrials.gov and [email protected] Report Complementary Information

MedicalResearch.com Interview with:

Dr. Steven Woloshin

Steven Woloshin, MD
Professor of The Dartmouth Institute
Professor of Medicine
Professor of Community and Family Medicine
New Hamphsire

MedicalResearch.com: What is the background for this study?

Dr. Woloshin: Drug companies are required by law to post results of trials used to support drug applications to the FDA on the clinicaltrials.gov website – but it is not clear whether posted results are complete and accurate. Recent studies attempting to validate posted results by comparing them to corresponding peer reviewed medical journal publications suggest that discrepancies are relatively common. But it is which source is more likely to be correct. We tried to validate posted results against an arguably better gold standard, the drug approval packages from the FDA (ie, the medical and statistical reviews posted on the [email protected] website). FDA reviews have an advantage over peer reviewed publications: unlike medical journal editors and peer reviewers, FDA has access to the individual participant data from the trials. This means FDA can see all the trials and all the outcomes (avoiding sleective publication) and it means FDA can independently reanalyze according to what they believe to be the best statistical practices (data can be analyzed in many ways – and different decisions, for example, how to account for missing data, can yield very different results).

MedicalResearch.com: What are the main findings?

Dr. Woloshin: Primary outcome definitions and results were
largely concordant between ClinicalTrials.gov and Drugs@FDA.
Half the secondary outcomes, as well as serious events and
deaths, could not be validated because Drugs@FDA includes
only “key outcomes” for regulatory decision making and frequently
includes only adverse event results aggregated across
multiple trials.

MedicalResearch.com: What should readers take away from your report?

Response: An important message from this work is that clinicaltrials.gov and fda reviews serve different purposes. Clinicaltrials.gov is meant to provide a complete reporting of all summary data as planned in the study protocols. FDA reviews provide FDA’s take – independent, expert assessement of the evidence as analyzed for the purposes of regulatory decision making. These sources are complementary. Clinicaltrials gives “all the data”, FDA gives context for interpreting the evidence.

As we said, even if all the numbers reported in ClinicalTrials.gov were completely accurate,questions would remain about the trial design, conduct, or analysis, which may affect conclusions about the trial results assessed in Drugs@FDA.

For example, reviewers may have raised questions about the appropriateness of an active comparator used (or its dose) or about unvalidated outcome measures.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:
Schwartz LM, Woloshin S, Zheng E, Tse T, Zarin DA. ClinicalTrials.gov and Drugs@FDA: A Comparison of Results Reporting for New Drug Approval Trials. Ann Intern Med. [Epub ahead of print 14 June 2016] doi:10.7326/M15-2658

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on June 17, 2016 by Marie Benz MD FAAD