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

Abstract

Abstract Background Postmarketing commitments are clinical studies that pharmaceutical companies agree to conduct at the time of FDA approval, but which are not required by statute or regulation. As FDA increasingly adopts a lifecycle evaluation process, greater emphasis will be placed on postmarket evidence as a component of therapeutic evaluation. Therefore, the objectives of this study were to determine how often postmarketing commitments agreed upon by pharmaceutical companies at first FDA approval lead to new clinical trials and to establish the characteristics and rates of completion and dissemination of postmarketing commitments. Methods For new drugs and biologics approved in 2009–2012, we used public FDA documents, ClinicalTrials.gov, and Scopus, to determine postmarketing commitments and their characteristics known at the time of FDA approval; number 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. Results Among 110 novel drugs and biologics approved by the FDA between 2009 and 2012, 61 (55.5%) had at least one postmarketing commitment at the time of first approval. Of 331 total postmarketing commitments, 33 (10.0%) were for new clinical trials; 27 of these were 506B studies subject to public reporting requirements, of which 12 (44.4%) did not have a recent (i.e., up-to-date) or closed (i.e., fulfilled or released) status provided publicly by the FDA. Although two postmarketing commitments were insufficiently described in FDA records to perform searches on ClinicalTrials.gov, nearly all (28, 90.3%) of the 31 remaining postmarketing commitments for new clinical trials were registered on ClinicalTrials.gov. Among the registered trials, 23 (23 of 28, 82.1%) were classified as completed or terminated, of which 22 (95.7%) had reported results. When considering all 29 completed or terminated clinical trials, registered or unregistered on ClinicalTrials.gov, only half (14, 48.3%) were published in peer-reviewed journals. Conclusions While only 15% of postmarketing commitments agreed to by pharmaceutical companies at the time of FDA approval were for new clinical trials, these trials were nearly always registered with reported results on ClinicalTrials.gov. However, only half were published, and despite FDA public reporting requirements, recent status information was often unavailable for 506B studies.

Keywords

• Postmarketing commitments
• Postmarketing requirements
• FDA
• Lifecycle evaluation
• Pharmaceutical regulation