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Two Studies Question FDA’s Fast-Track Review Process

Nevertheless, the program seems to work as intended

Accelerated and expedited FDA reviews of drug-marketing applications have been awarded primarily to "me too" products and usually have not involved trials using active comparators or clinical outcome measures, according to two evaluations of these programs conducted by academic researchers and published in BMJ.

A group led by Aaron Kesselheim, MD, JD, MPH, of Harvard's T.H. Chan School of Public Health, examined records of FDA fast-track reviews going back to 1987, according to a report by MedPage Today. Not only has the number of such reviews grown steadily over that time (by about 3% per year), but this trend was driven mainly by applications involving drugs that were not first in class and/or sought expanded indications for already approved products (supplemental new drug applications [sNDAs]).

Separately, Kesselheim and Harvard colleague Bo Wang, PharmD, analyzed data on drugs with approved sNDAs conducted from 2005 to 2014 and found that the types of evidence underlying the approvals had varied widely. Most used nonclinical endpoints, and many were for nonorphan indications involving products originally approved as orphan drugs.

"Though expedited programs should be strictly limited to drugs providing noticeable clinical advances, this trend is being driven by drugs that are not first in class and thus potentially less innovative," Kesselheim and colleagues concluded. In the second paper, Kesselheim and Wang referred to "decreasing evidentiary standards" for expanded indication approvals that "underscore the need" for post-approval monitoring and confirmatory studies.

Neither analysis examined individual approvals to assess their specific effects on patient care. In fact, for the analysis of expedited and accelerated reviews, Kesselheim and colleagues did not address any aspects of the drugs involved except whether they were designated as first-in-class agents.

The analysis of sNDAs drew on drug labels, because the full FDA medical reviews were not available for 80% of the NDAs they identified. These were the "earliest FDA drug label[s] in the Drugs@FDA database that mentioned the newly approved use," and so would not include information from post-marketing studies that the FDA may have requested or required as a condition of approval.

The fact that the agency accepts a variety of endpoints and study types in approving drugs has been a well-recognized part of its approval process since the inception of the various expedited review programs. The use of surrogate markers, for example, is valid as long as they are “reasonably likely to predict” clinical outcomes and the actual effect on clinical outcomes is proven in post-marketing studies, analysis of which was not part of the current studies.

Thus, while the findings by Kesselheim and colleagues raise questions about the programs, they can also be seen as consistent with the programs working as intended. The reports lacked any direct evidence that ineffective drugs have been approved or that patient safety was ever compromised.

Source: MedPage Today; September 24, 2015.

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