Timeliness of Postmarket Studies for New Pharmaceuticals Approved Between 2009 and 2012: a Cross-Sectional Analysis
Over the past decade, the US FDA’s framework for evaluating new drugs has shifted from a predominantly premarket to an increasingly “lifecycle” evaluation process, where benefits and risks are evaluated before and after market approval.1 In order to resolve remaining uncertainties at the time of premarket approval, such as whether a drug conditionally approved on a surrogate marker improves patient outcomes, many drugs receive postmarketing requirements (PMRs)—FDA-imposed studies that manufacturers must conduct after approval. To avoid delays translating these findings into practice, manufacturers need to complete PMRs on time and FDA should provide reasonable time frames for completion. However, concerns have been raised about manufacturers’ lack of adherence to and FDA’s lack of enforcement of PMR deadlines.2 Furthermore, nearly one quarter of PMR results are either not reported on ClinicalTrials.gov or published in the peer-reviewed literature.3, 4Therefore, our...
The authors thank Dr. Sanket Dhruva, who assisted with data collection for this project. Dr. Dhruva is an Assistant Professor within the Department of Medicine at the University of California, San Fransisco School of Medicine. During the time of this study, Dr. Dhruva was supported by the Robert Wood Johnson Foundation’s Clinical Scholars Program and the Department of Veterans Affairs; he has no additional conflicts of interest to disclose.
All authors had full access to all the data in the study and take responsibility for the accuracy and integrity of the data and analysis. All authors were responsible for the conception and design of this work, participated in the analysis and interpretation of the data, and critically revised the manuscript for important intellectual content. Dr. Wallach conducted the statistical analysis and drafted the manuscript. Dr. Wallach and Mr. Egilman were responsible for the acquisition of data. Drs. Ross, Woloshin, and Schwartz provided supervision. The corresponding author affirms that he has listed everyone who contributed significantly to the work.
This project was conduct as part of the Collaboration for Research Integrity and Transparency (CRIT) at Yale, funded by the Laura and John Arnold Foundation, which supports Mr. Egilman and Drs. Wallach and Ross. The Laura and John Arnold Foundation and other funders played no role in the design of the study; the collection, analysis, and interpretation of the data; and decision to approve publication of the finished manuscript.
Compliance with Ethical Standards
Conflict of Interest
In the past 36 months, Dr. Wallach received research support through the Meta Research Innovation Center at Stanford (METRICS) from the Laura and John Arnold Foundation. Dr. Ross has received research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing; from Medtronic, Inc. and the Food and Drug Administration (FDA) to develop methods for postmarket surveillance of medical devices (U01FD004585); 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; from the Centers of Medicare and Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting (HHSM-500-2013-13018I); from the Agency for Healthcare Research and Quality (R01HS022882); from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164); and from the Laura and John Arnold Foundation to establish the Good Pharma Scorecard at Bioethics International; in addition, Dr. Ross receives an honoraria as compensation for his role as an Associate Editor of JAMA Internal Medicine. Drs. Schwartz and Woloshin were cofounders of Informulary, Inc., a company that provided data on the benefits, harms, and uncertainties of prescription drugs. The company has ceased operations. Drs. Schwartz and Woloshin report personal fees from Ross Feller Case, LLP, for serving as medical experts in testosterone litigation. All remaining authors declare that they do not have a conflict of interest.
Reproducible Research Statement
Study protocol: Not available. Statistical Code and Data set: Available from Dr. Wallach (e-mail, Joshua.firstname.lastname@example.org)
- 4.Wallach JD, Egilman AC, Dhruva SS, McCarthy ME, Miller JE, Woloshin S, et al. Postmarket studies required by the US Food and Drug Administration for new drugs and biologics approved between 2009 and 2012: cross sectional analysis. BMJ. 2018;361:k2031.Google Scholar
- 5.U.S. Food and Drug Administration. Report on the performance of drug and biologics firms in conducting postmarketing requirements and commitments; availability. Fed Regist 2016;81:75411–75419.Google Scholar
- 6.Department of Health and Human Services Office of Inspector General. July 2016. FDA is Issuing More Postmarketing Requirements, but Challenges with Oversight Persist. https://oig.hhs.gov/oei/reports/oei-01-14-00390.pdf. Accessed 19 Oct 2018.