Postmarketing commitments for novel drugs and biologics approved by the US Food and Drug Administration: a cross-sectional analysis

Abstract

BackgroundPostmarketing commitments are clinical studies that drug sponsors agree to conduct at the time of FDA approval, but which are not required by statute or regulation. The objective of this study was to determine the characteristics, completion, and dissemination of postmarketing commitments agreed upon by sponsors at first FDA approval.\n\nMethodsWe performed a cross-sectional analysis of postmarketing commitments for new drugs and biologics approved 2009-2012. Using public FDA documents, ClinicalTrials.gov, and Scopus, we determined postmarketing commitments and their characteristics known at the time of FDA approval; number of postmarketing commitments subject to reporting requirements, for which FDA is required to make study status information available to the public (\"506B studies\"), and their statuses; and rates of registration and results reporting on ClinicalTrials.gov and publication in peer-reviewed journals for all clinical trials, with follow-up through July 2018.\n\nResultsAmong 110 novel drugs and biologics approved by the FDA between 2009-2012, 61 (55.5%) had at least one postmarketing commitment at the time of first approval. Of 331 total postmarketing commitments, 271 (81.9%) were non-human subjects research, predominantly chemistry, manufacturing, and controls studies; 49 (14.8%) were clinical trials (33 new and 16 ongoing trials for which follow-up results would be reported). Study descriptions for the new clinical trials often lacked information to establish study design features. Of the 89 (26.9%) 506B studies subject to public reporting requirements, of which 42 were clinical trials, 59 (66.3%) did not have an up-to-date status provided by FDA. Nearly all new clinical trials (28 of 31, 90.3%) were registered on ClinicalTrials.gov; of the 23 registered trials that were completed or terminated, 22 (95.7%) had reported results. Only half (14 of 29, 48.3%) of completed or terminated clinical trials, registered or unregistered, were published in peer-reviewed journals. Conclusions: The majority of postmarketing commitments agreed to by sponsors at the time of FDA approval for novel drugs and biologics approved between 2009-2012 were chemistry, manufacturing, and controls studies. While only 15% were clinical trials, these trials were nearly always registered with reported results on ClinicalTrials.gov. However, despite FDA public reporting requirements, up-to-date study status information was often unavailable for 506B studies.