Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysisBMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k2031 (Published 24 May 2018) Cite this as: BMJ 2018;361:k2031
- Joshua D Wallach, postdoctoral research fellow1 2,
- Alexander C Egilman, research associate1 2,
- Sanket S Dhruva, postdoctoral research fellow3 4,
- Margaret E McCarthy, executive director2,
- Jennifer E Miller, assistant professor5,
- Steven Woloshin, professor of medicine6,
- Lisa M Schwartz, professor of medicine6,
- Joseph S Ross, associate professor of medicine and public health1 3 7 8
- 1Center for Outcomes Research and Evaluation (CORE), Yale-New Haven Hospital, New Haven CT 06510, USA
- 2Collaboration for Research Integrity and Transparency (CRIT), Yale Law School, New Haven CT, USA
- 3National Clinician Scholars Program, Department of Internal Medicine, Yale School of Medicine, New Haven CT, USA
- 4Veterans Affairs Connecticut Healthcare System, New Haven CT, USA
- 5Division of Medical Ethics, Department of Population Health, NYU School of Medicine and Bioethics International, New York NY, USA
- 6Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine at Dartmouth, Lebanon NH, USA
- 7Section of General Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven CT, USA
- 8Department of Health Policy and Management, Yale School of Public Health, New Haven CT, USA
- Correspondence to: J D Wallach @JoshuaDWallach on Twitter) (or
- Accepted 16 April 2018
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.
Contributors: JDW, ACE, and JSR conceived and designed this study. JDW, ACE, and SSD acquired the data. JDW conducted the statistical analysis and drafted the manuscript. All authors participated in the interpretation of the data and critically revised the manuscript for important intellectual content. JDW and JSR had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. JSR provided supervision. JDW and JSR are guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
Funding: This project was conducted as part of the Collaboration for Research Integrity and Transparency (CRIT) at Yale, funded by the Laura and John Arnold Foundation, which supports JDW, ACE, MEM, and JSR. SSD is supported by the Robert Wood Johnson Foundation Clinical Scholars Program and the Department of Veterans Affairs. JEM receives funding from the Laura and John Arnold Foundation. These funders played no role in the design of the study, analysis or interpretation of findings, or drafting the manuscript and did not review or approval the manuscript before submission. The authors assume full responsibility for the accuracy and completeness of the ideas presented.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support from the Laura and John Arnold Foundation for the submitted work; in the past 36 months, JDW received research support through the Meta Research Innovation Center at Stanford (METRICS) from the Laura and John Arnold Foundation; JSR received research support through Yale from Johnson and Johnson to develop methods of clinical trial data sharing, from Medtronic and the US Food and Drug Administration (FDA) to develop methods for postmarket surveillance of medical devices (U01FD004585), from the Centers of Medicare and Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting, from the FDA to establish a Center for Excellence in Regulatory Science and Innovation (CERSI) at Yale University and the Mayo Clinic (U01FD005938), from the Blue Cross Blue Shield Association to better understand medical technology evaluation, and from the Agency for Healthcare Research and Quality (R01HS022882); SSD receives support as a scholar in the Yale University/Mayo Clinic FDA CERSI; LMS and SW were cofounders of Informulary, a company that proved data and the benefits, harms, and uncertainties of prescription drugs, and has since ceased operations; LMS and SW report personal fees from Ross Feller Case outside the submitted work; JEM receives funding from the Laura and John Arnold Foundation.
Ethical approval: As a cohort study using publicly available data, this study does not require research ethics approval or patient consent.
Data sharing: Requests for the dataset can be made to the corresponding author at email@example.com. The dataset will be made available via a publicly accessible repository after publication.
The lead authors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant registered) have been explained.
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