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CRITical Thinking is a blog written by staff, directors, and friends of the Collaboration for Research Integrity and Transparency (CRIT), a joint program of Yale Law School, Yale School of Public Health, and Yale School of Medicine. CRIT's mission is to promote health by improving the integrity and transparency of biomedical and clinical research.

This blog is published by and reflects the personal views of the individual authors, in their individual capacities. It does not purport to represent Yale University's institutional views, if any. No representation is made about the accuracy of the information, which solely constitutes the authors’ personal views on issues discussed. The information contained in this blog is provided only as general information and personal opinions, and blog topics may be updated after being initially posted.


FDA Regulatory Review: It’s still faster

April 6, 2017

The speed with which the Food and Drug Administration (FDA) reviews new drug, biologic and medical device applications remains a contentious subject of criticism. And with attention focused on the impending reauthorization of the Prescription Drug User Fee Act (PDUFA), it’s worth revisiting the commonly heard rhetoric that FDA regulatory review is too slow.

PDUFA, first enacted in 1992, authorized the Food and Drug Administration (FDA) to collect user fees from sponsors of each new drug application as an additional source of funding to support the agency’s review infrastructure. This funding was used to hire and support staff, and improve its technological systems, but was contingent upon the FDA’s meeting numerous regulatory performance goals, many of which are focused on timely regulatory review and are recalibrated in each 5-year authorization cycle. Since PDUFA’s enactment in 1992, this bolstered infrastructure has provided the foundation for eliminating an application review backlog, streamlining new application submissions, improving communication between FDA and sponsors, and setting narrowing FDA target timelines for review, all of which have contributed to shortening review times overall as measured by the Government Accountability Office.

Even so, agency review time continues to be a target for both those who criticize the FDA for undue delay in approving novel and potentially life-saving therapeutics, and those who express concern that faster reviews or approvals near review deadlines may be linked to higher rates of post-marketing adverse safety events. In 2012, we published the results of our study in the New England Journal of Medicine characterizing review times for novel therapeutics approved between 2001-2010 by the FDA and two peer regulatory agencies, the European Medicines Agency (EMA) and Health Canada. On average, novel therapeutics were reviewed 2-3 months more quickly by the FDA than the two comparator regulatory agencies, and were more likely to be first approved for use in the United States.

The current authorization of PDUFA is set to expire in September 2017. Although formal discussions for reauthorization with industry and stakeholders have concluded, provisions of the bill have not yet been finalized. Goalposts may yet move in the dynamic political landscape in which decisions about health care infrastructure are now rendered – exemplified by President Trump’s FY2018 budget blueprint, which deals an unprecedented $15.1 billion cut, 17.9% of the budget, to the Department of Health and Human Services, the parent agency of the FDA, and proposes the use of significant user fee increases to offset lost FDA Congressional appropriations.

Yesterday, we published a follow-up study in the New England Journal of Medicine that can inform these continued PDUFA reauthorization discussions, especially with respect to review time as a performance goal. We extended our evaluation of the FDA and EMA to the period between 2011-2015 and found that total review times continue to be 2-3 months faster at the FDA than the EMA, representing stable or perhaps even faster reviews than in the past. In particular, review times for drugs treating orphan diseases and cancer/hematologic diseases were significantly faster at the FDA than the EMA.

These findings rebut the rhetoric that FDA review lags in comparison to its peer agencies, and challenge the urgency of using PDUFA VI as a means to further shorten review times. However, these findings can neither support nor counter claims as to whether the FDA reviews and approves drugs with the “right” speed.

Further changes in review time targets may be attainable, but may require trade-offs in certainty about the safety or efficacy of novel therapeutics. The confirmation hearing testimony of FDA commissioner nominee Scott Gottlieb, who has voiced concerns about the current speed of the FDA approval process, reinforces the salience of this issue. As the direction of FDA leadership in the current administration becomes more defined, discussions about the relative merits and drawbacks of faster reviews and approvals will certainly continue.

Audrey D. Zhang is a second year medical student at the NYU School of Medicine.

Nicholas S. Downing is a resident in internal medicine at the Brigham and Women’s Hospital.

Joseph S. Ross is an Associate Professor of Medicine (General Medicine) and Public Health (Health Policy and Management) at Yale University.