Do Drugs Approved Via Expedited Pathways Offer Greater Benefits? Study and Doctors Debate

Posted 09 August 2017 By Michael Mezher

placeholder+image

A recent study in Health Affairs suggests that drugs given an expedited review by the US Food and Drug Administration (FDA) offer greater health gains than drugs that receiving a conventional review. But experts caution that the study might only show incremental benefits.

The study, conducted by Peter Neumann, director of the Center for the Evaluation of Value and Risk in Health and three of his colleagues at Tufts Medical Center, compared the change in quality-adjusted life-years (QALYs) for new drugs approved from 1999-2012, focusing on three of FDA's expedited review pathways—priority review, accelerated approval and fast track designation.

While the authors observed greater health gains for drugs approved through those programs, they caution that QALY data was not available for all the drugs approved in those years and that drugs with shorter reviews are more likely to be withdrawn or given boxed warnings down the line.

Background

FDA currently offers multiple programs to expedite the review and development of promising drugs, including its priority review, accelerated approval, fast track, and breakthrough therapy programs.

Each of these programs provides specific benefits to drugmakers, such as a shorter review timeline, increased communication and guidance or the ability to rely on surrogate endpoints to predict clinical benefit.

Interest in these programs has increased over time, and in recent years most new drugs approved by the agency have qualified for at least one of the programs (60% in 2015 and 73% in 2016).

Incremental Benefits

To compare health gains across the various products, the authors measured the incremental changes in QALYs reported in previously published literature.

The authors also restricted the study to include measures of QALYs from studies that looked at on-label uses, selected the most effective comparator in cases where the drug of interest was compared to multiple treatments and excluded studies funded by industry.

In total, the study looked at 135 drug-indication pairs, 68 of which were granted a priority review, 31 had fast track designation and 17 received accelerated approval. Of those, 30 were in more than one program, and 59 underwent a conventional review.

The authors found that drug-indication pairs given a conventional review had a median increase in QALYs of 0.003, while pairs that were in a single expedited program had a median gain of 0.126 QALYs.

Pairs that were in more than one expedited program were associated with greater gains, with indications that qualified for two expedited programs seeing a median gain of 0.182 QALYs and indications that qualified for all three having a median gain of 0.389 QALYs.

Questions

Joseph Ross, an associate professor at the Yale School of Medicine, told Focus he was reassured to see that drugs approved through an expedited pathway were associated with larger QALY gains.

But Ross said he was concerned that many of the drug-indication pairs the study looked at had very small QALY gains compared to previous treatments.

"I was surprised that so many drugs approved by the FDA, including some that were approved through expedited regulatory review pathways, were associated with incremental QALY benefits of [less than 0.1] … this suggests that the drugs are associated with no benefit, or even harm (if the QALY is negative)," he said.

According to the study, 39 (29%) drug-indication pairs had zero or negative gain in QALYs, 15 of which were in one or more expedited program, and around a third of the drugs that had a conventional review had QALY gains between zero and 0.1.

Ross also pointed out that coming up with QALYs often relies on multiple assumptions that are only as good as the available data for the drugs.

"If QALY calculations are based on trials which use surrogate markers of disease as endpoints, even more assumptions are being made until evidence is generated that proves the drugs have the same clinical benefit when tested using patient-important outcomes," he said.

In May, a paper by Ross and fellow Yale professor Harlan Krumholz found that in many cases, drugs approved based on limited evidence are not adequately studied after entering the market.

The authors of the study note this as well, saying, "FDA has had limited success in ensuring the mandated postapproval trials to validate the findings from surrogate endpoints are performed in a timely manner."

Health Affairs

Share this article:

Categories: Biologics and biotechnology, Drugs, Submission and registration, News, US, FDA

Tags: Priority Review, Accelerated Approval, Fast Track, Breakthrough Therapy

Regulatory Exchange: Latest Updates From the Community