Completion and outcomes of postmarketing requirements and commitments issued by the US Food and Drug Administration for new drugs, 2016-24: cross sectional evaluation of postmarketing studies.

OBJECTIVES

To evaluate the use of postmarketing requirements under the FDA Amendments Act (FDAAA) and postmarketing commitments issued by the US Food and Drug Administration (FDA), for new drugs approved from 2016 to 2024, and to determine rates of study completion and changes in drug labelling resulting from these studies.

DESIGN

Cross sectional evaluation of postmarketing studies.

SETTING

All new drugs and their associated indications approved by the FDA's Center for Drug Evaluation and Research, 1 January 2016 to 31 December 2024.

POPULATION: 420 drugs approved by the FDA for 567 indications, associated with 913 FDAAA postmarketing requirements and 434 postmarketing commitments.

MAIN OUTCOME MEASURES: Drug characteristics associated with issuance of FDAAA postmarketing requirements and issuance of postmarketing commitments, rates of study completion and on-time completion, and proportion of studies leading to changes in drug labelling.

RESULTS

More than two thirds of drugs (n=287, 68.3%) had at least one FDAAA postmarketing requirement and 42.9% (n=180) had at least one postmarketing commitment. Indications with an orphan designation were more likely to have an FDAAA postmarketing requirement (63.3% v 48.6%; absolute difference 14.7%, 95% confidence interval (CI) 6.7% to 22.8%), as were indications approved with an expedited programme (59.6% v 48.1%; absolute difference 11.5%, 2.7% to 20.3%). Similarly, postmarketing commitments were more likely to be issued for indications with an orphan designation (47.0% v 33.6%; absolute difference 13.4%, 5.4% to 21.4%) and those using expedited approval programmes (47.9% v 23.8%; absolute difference 24.1%, 16.2% to 32.1%). Among studies due by the end of 2024, 73.4% (95% CI 69.2% to 77.3%; n=345) of FDAAA postmarketing requirements and 81.5% (76.3% to 86.1%; n=212) of postmarketing commitments were completed, although only 33.4% (29.1% to 37.9%) (n=157) and 36.2% (30.3% to 42.3%) (n=94), respectively, were completed on time. Of the 311 fulfilled FDAAA postmarketing requirement studies, 63.3% (n=197) resulted in at least one labelling change, most often in the section on use in specific populations and clinical pharmacology. Fewer postmarketing commitment studies (n=94, 49.7%) resulted in changes in drug labelling, with most changes found in the clinical pharmacology and clinical studies sections.

CONCLUSIONS

FDAAA postmarketing requirements and postmarketing commitments are important regulatory tools for generating postapproval evidence, particularly for drugs approved with orphan designation or under expedited programmes. Although a large proportion of studies resulted in changes in drug labelling, delays in completion were common, highlighting the need to ensure effective oversight and timely study completion and reporting.