Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis.

OBJECTIVES: To characterize postmarketing requirements for new drugs and biologics approved by the US Food and Drug Administration (FDA), and to examine rates and timeliness of registration, results reporting, and publication of required prospective cohort studies, registries, and clinical trials.
DESIGN: Cross sectional analysis.
SETTING: Postmarketing requirements for all new drugs and biologics approved by the FDA between 1 January 2009 and 31 December 2012, with follow-up up to 15 November 2017. MAIN OUTCOME MEASURES: Postmarketing requirements and their characteristics known at the time of FDA approval, including FDA authority, study design, and study characteristics. Rates and timeliness of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials.
RESULTS: Between 2009 and 12, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval, for a total of 437 postmarketing requirements. Postmarket study descriptions were short (median word count 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). 220 (50.3%) postmarketing requirements were for new animal or other studies (including pharmacokinetic studies); 134 (30.7%) were for prospective cohort studies, registries, and clinical trials; and 83 (19.0%) were for secondary analyses or follow-up studies. Of 110 clinical trials, 38 (34.5%), 44 (40.0%), 62 (56.4%), 66 (60.0%), and 98 (89.1%) did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled, respectively. Of 134 required prospective cohort studies, registries, and clinical trials, 102 (76.1%) were registered on ClinicalTrials.gov; of 50 registered and completed studies, 36 (72.0%) had reported results on ClinicalTrials.gov. Among 65 completed studies, 47 (72.3%) had either reported results or were published a median of 47 months (interquartile range 32-67) after FDA approval. 32 (68.1%) of these 47 studies did not report results publicly by the time of their original FDA report submission deadline.
CONCLUSIONS: Postmarketing requirements for new drugs and biologics were often briefly described and did not contain enough information to characterize study designs. Approximately three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, and nearly three quarters of completed studies reported results or were published, suggesting that at least a quarter of these required studies are not being publicly disseminated. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Wallach JD, Egilman AC, Dhruva SS, et al

Study question What are the characteristics of the US Food and Drug Administration’s (FDA) postmarketing requirements, and what are the rates of registration and results reporting on ClinicalTrials.gov and publication in peer reviewed journals of required prospective cohort studies, registries, and clinical trials?

Methods Postmarketing requirements known at the time of FDA approval (including FDA authority, study design, and study characteristics) for all new drugs and biologics approved in 2009-12 were characterised by use of publicly available FDA documents. ClinicalTrials.gov, PubMed, and Scopus were searched for registration records, reported results, and publications in peer reviewed journals for all required prospective cohort studies, registries, and clinical trials.

Study answer and limitations Between 2009 and 2012, the FDA approved 97 new drugs and biologics for 106 indications with at least one postmarketing requirement at the time of first approval (437 postmarketing requirements in total). Many postmarketing requirements were briefly described (median word count of 44 (interquartile range 29-71)) and often lacked information to determine an up to date progress (131 (30%)). Of 134 postmarketing requirements for prospective cohort studies, registries, and clinical trials, 102 (76%) were registered on ClinicalTrials.gov; 47 (72.3%) of 65 completed studies had either reported results on ClinicalTrials.gov or were published a median of 47 (32-67) months after FDA approval. Similar registration and reporting rates were observed in clinical trials only. Publicly available data sources used in the study contained limited information, which made categorizing and determining ClinicalTrials.gov registrations and publications difficult.

What this study adds Postmarket requirements for drugs and biologics are often briefly described in public documents, without enough information to determine the required study characteristics. Although three quarters of postmarketing requirements for prospective cohort studies, registries, and clinical trials were registered on ClinicalTrials.gov, at least one quarter of required studies for which results reporting or publication would be expected have not been publicly disseminated.

Funding, competing interests, data sharing Funded by the Laura and John Arnold Foundation. Full competing interests details included on bmj.com. Data requests can be made to the corresponding author.

Cite this as: BMJ 2018;361:k2031

Results reporting and publication of postmarketing requirements of new drugs and biologics approved by the US Food and Drug Administration (FDA) between 2009 and 2012. Data are number or number (%) of required studies

Category	Publication or results reporting*
	Eligible for publication	Published	Results reported or published
Prospective cohort studies, registries, and clinical trials	65	37 (56.9)	47 (72.3)
Authority
FDAAA	37	22 (59.5)	28 (75.7)
PREA	22	11 (50.0)	15 (68.2)
Accelerated approval	6	4 (66.7)	4 (66.7)

FDAAA=Food and Drug Administration Amendments Act; PREA=Pediatric Research Equality Act.

Indicates publication in the peer reviewed literature or results reporting on ClinicalTrials.gov.