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Regulatory Focus™ > News Articles > FDA Disputes Article Highlighting Lackluster Oversight of Postmarketing Studies

FDA Disputes Article Highlighting Lackluster Oversight of Postmarketing Studies

Posted 22 September 2017 | By Michael Mezher 

FDA Disputes Article Highlighting Lackluster Oversight of Postmarketing Studies

A paper appearing in the New England Journal of Medicine on Thursday argues that the US Food and Drug Administration (FDA) is not doing enough to ensure drugmakers complete postmarketing studies required by the agency at the time their drugs are approved.

In 2007, FDA gained the authority to establish postmarketing requirements for new drugs and biologics under the Food and Drug Administration Amendments Act (FDAAA). The act also gave FDA the authority to warn or fine companies for failing to follow postmarketing requirements.

Prior to that, the agency could only ask companies to agree to postmarketing commitments in writing, though those commitments were not required under statute or regulation.

The authors of the paper point to FDA's most recent report on postmarketing requirements and commitments from 2015, which includes data going back to requirements and commitments imposed in 2009 and 2010.

Looking at the data for requirements originating in those two years, the authors contend that "after 5 to 6 years, 20% of postapproval studies had not been started, 25% were delayed or ongoing, and 54% had been completed."

But a response from FDA officials published alongside the paper says the authors' analysis paints an inaccurate picture of the postmarket study landscape as it lumps postmarket requirements in with postmarket commitments and doesn't take into account justifiable delays. By their count, the FDA officials say 88% of postmarketing requirements in general, and 89% of FDAAA postmarketing requirements were progressing on schedule as of 2015.

"An accurate analysis of the effect of the FDAAA would evaluate the timeliness of FDAAA postmarketing requirements separately from that of other postmarketing requirements and commitments," the FDA officials write.

And the officials say that the status of the studies in the agency's annual reports are based on their original timetable at the time of approval and do not reflect revised timeframes as a result of justifiable delays.

FDA also disputes the claim that 20% of those studies had not been started, as the authors bunched together pending, terminated and released studies to come up with the figure. Those studies, FDA says could have been initiated and later ended.

"Over time, advances in science, changes in standards of care, and new clinical information can affect study feasibility, design requirements, and even the need for or the appropriateness of a study," the FDA officials write.

Nonetheless, the authors contend that FDA could further improve oversight of postmarketing requirements by exercising its power to fine companies for violating the terms of their postmarketing requirements, noting they were unaware of any instance of the agency issuing such fines in the ten years since the FDAAA was enacted.


FDA spokesperson Tralisa Colby told Focus that while FDA has not fined a firm for failing to follow a postmarketing requirement, the agency has warned firms over the issue in the past.

"FDA actively monitors and takes appropriate action when an applicant (drug firm) is noncompliant with a requirement to conduct a postmarket safety study or clinical trials under section 505(o)(3) of the Food, Drug and Cosmetic Act, and fails to demonstrate good cause for its noncompliance … it is FDA's practice to give firms an opportunity to take voluntary and prompt corrective action before the agency initiates an enforcement action, including issuing civil monetary penalties," Colby said.

A search of FDA warning letters since 2012 returned one warning letter over postmarketing requirements sent to Merck Sharp and Dohme for failing to meet milestone dates for a postmarketing study for its diabetes drugs Januvia (sitagliptin) and Janumet (sitagliptin + metformin HCI).

The authors of the NEJM piece also call on FDA to provide its rationale for releasing companies from specific postmarketing requirements to increase transparency and say the agency should tighten postmarketing study deadlines based on estimates from similar past studies.

But despite these issues, the authors say that FDA has improved its oversight of postapproval studies in the years since FDAAA was passed.

"FDA's approach to postapproval studies has improved over the past decade: it has cleared much of the pre-FDAAA backlog of open studies, established deadlines for study milestones, and created a public database for tracking open studies," the authors write.

NEJM, FDA Response


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