Regulatory Focus™ > News Articles > 2019 > 8 > New Research Questions FDA’s Reliance on and Inability to Enforce Postmarketing Requirements

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Posted 13 August 2019 | By Zachary Brennan 

New Research Questions FDA’s Reliance on and Inability to Enforce Postmarketing Requirements

3185 As the US Food and Drug Administration (FDA) has increasingly relied on postmarketing requirements (PMRs) to support its approval decisions, a new study published in the Milbank Quarterly discusses how FDA’s lack of ability to enforce PMRs reveals an agency “on guard against a set of larger political threats to its mandate.”

The study’s publication follows a recent report from FDA showing that most of the required PMRs and voluntary postmarketing commitments (PMCs) are progressing on schedule.

But as Matthew Herder, director of the Health Law Institute at Dalhousie University, explains in his paper, “FDA has difficulty enforcing the timely completion of PMRs, but acting upon PMR data once in hand is more vexed.”

An unidentified FDA official told Herder during his interviews with 23 past and present FDA leaders: “[E]ven if you get the study, and you often do, sometimes they don't confirm the efficacy of the product. […] What is FDA supposed to do with that? There's now a huge and vocal constituency for the product. Whether or not the study showed it worked, there are people out there who think it worked, and lots of people with a financial stake in it. It becomes a political nightmare to try to take a product off the market that's already developed that constituency by being approved for a period of time. […] [I]n some ways [it's] a bigger problem than whether you get the data. It's whether you can do anything with it when you have it.”

Overall, Herder told Focus that in his conversations with FDA officials, “What I found most surprising was how acutely aware most FDA officials were of the enforcement challenges involved with PMRs, yet -- at the same time -- fiercely defensive of continuing to rely on them.”

He discusses in the paper how FDA lacks the legal authority to withdraw an approval that carries a PMR due to a sponsor's failure to fulfill the PMR, and how companies “likely abide by the terms of a PMR not because they fear FDA enforcement, but rather because the approved indication carrying the PMR is one of several indications in a sequence that they plan to submit to the agency.” 

Defining what a PMR entails at the time of a new treatment’s approval can also be challenging.

“They tend to be short descriptions of the question(s) that the FDA would like to have answered through one or more postmarket studies, but they often fail to specify what type of study design should be employed to answer the question(s) of interest. Of 110 clinical trials that were encompassed in a cross‐sectional analysis of all PMRs issued by the FDA during 2009‐2012, many, if not most, ‘did not report enough information to establish use of randomization, comparator type, allocation, outcome, and number of patients to be enrolled,’” the study finds.

FDA officials also may be reticent to hold up an approval because the details of a PMR are not yet settled. 

And as FDA continues its push toward further using real-world evidence, one current FDA official told Herder: “You just let patients take them, and somehow all of these massive insurance databases will cough up an answer at the end of a year or two about how well the products work and how safe they are. We're not really anywhere near that degree of sophistication in our ability to analyze those big datasets, but there's a huge amount of pressure to push off lots of data collection there without a lot of methodology to do it.”

Herder added in an email to Focus: “I think the inability to effectively enforce PMRs presents tremendous risks for public health, especially for the proportion of drugs with a PMR that were approved on the basis of limited evidence.” 



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Tags: FDA, PMC, PMR, research

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