A descriptive analysis of postmarketing requirement studies and clinical trials

Purpose: Under the Food and Drug Administration Amendments Act of 2007 (FDAAA), the FDA has the authority to require applicants to conduct postmarketing studies or clinical trials. These postmarketing requirements (PMRs) provide additional data on the safety of the drug product. The purpose of the study was to conduct a descriptive analysis of FDAAA PMRs and the resulting regulatory actions.Methods: This study evaluated FDAAA PMRs established between 2013 and 2019. We used the Medical Dictionary for Regulatory Activities (MedDRA) to map preferred terms (PTs) for serious risks associated with the PMRs. Relevant documents available in the FDA's document archiving, reporting, and regulatory tracking system (DARRTS), including but not limited to internal letters and reviews, documents submitted by applicants, and publicly available data sources were assessed for data collection of study elements.Results: Of the 1079 new FDAAA PMRs established between January 01, 2013, and December 31, 2019, 82% (n = 884) were associated with new drug applications (NDAs) and 18% (n = 195) with biologic license applications (BLAs). Most PMRs were established at the time of drug approval (73%, n = 789) compared to post-approval (27%, n = 290). The majority of PMRs had an open status (59%, n = 639) and 41% (n = 440) were closed. The median time from the PMR establishment date to submission of the results to the FDA was 690 days (interquartile range [IQR]: 748 days) for 167 completed clinical trials and 483 days (IQR: 603 days) for 241 completed studies. Approximately 53% (180/339) of fulfilled FDAAA PMRs resulted in labeling changes.Conclusions: FDAAA PMRs are useful in informing postmarket safety of drugs. Most FDAAA PMRs were established at the time of drug approval, reflecting safety signals identified during the review of the marketing application, and over half of fulfilled FDAAA PMRs resulted in regulatory action.