Healthy Skepticism Library item: 13102

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Publication type: news

Is Faster Better? Senators Question Surrogate Endpoints, Fast Track Status
FDALegislativeWatch 2008 Mar 11
http://www.fdalegislativewatch.com/2008/03/is-faster-bette.html#more

Full text:

Ranking Member of the Senate Finance Committee Chuck Grassley, R-Iowa, announced March 4 that he is calling for a Government Accountability Office investigation into how the FDA follows up on the safety and efficacy of drugs approved based on surrogate endpoints.

Similarly, Sen. Sherrod Brown, D-Ohio, has announced that he and Senate Health, Education, Labor and Pensions Committee Chairman Ted Kennedy, D-Mass., will be looking into whether the FDA’s “Fast Track” designation program should be changed or eliminated based on conclusions of a Congressional Research Service report released in February.

Does “Fast Track” Status Mislead?

Though CRS sought to uncover whether products that receive Fast Track designation are more likely to have their NDA/BLA approved by FDA than products without the designation, the report states that “the answer is we don’t know, because, while FDA provides statistics on the products it designated as Fast Track, it does not make public information on the NDA/BLAs it receives unless and until the product is approved/licensed.”

Brown, who requested the information from CRS, was unsatisfied with the findings: “My biggest concern is that misconceptions about the significance of fast track could be tilting investment decisions toward the wrong drugs, at the expense of patients and investors alike,” he said. “I am working with Sen. Kennedy to explore this issue further.”

It is unclear whether the Senators will propose legislation to change or eliminate the provision.

CRS reports that since the program was set into law in 1997 with the FDA Modernization Act, FDA has granted Fast Track designation to 74.5 percent of the 569 drug requests, and 63.6 percent of the 195 biologics requests. Of products with Fast Track designation, the agency eventually approved 10.6 percent of the drugs and licensed 17.7 percent of the biologics.

Sen. Grassley’s GAO investigation request was inspired by the agency’s use of surrogate endpoints to approve drugs such as GlaxoSmithKline’s Avandia (rosiglitazone) and Merck/Schering Plough’s Vytorin (ezetimibe/simvastatin), the safety and efficacy of which were called into question with the release of postmarket data.

Follow-up For Surrogate Endpoint Approvals

“The way things have turned out with drugs like Vytorin and Avandia raise enough questions that a review is warranted,” Grassley said in a statement. “It’s not clear if the FDA’s own policies are being enforced internally, where the agency is supposed to require companies to perform follow-up studies.”

The senator has asked that the GAO investigate the number of drugs approved based on surrogate endpoints, what those endpoints were, and the dates of approval. He also wants the GAO to assess FDA’s past requests of postmarket studies, and the need to expand the agency’s ability to require them in the future.

Grassley’s request for a review comes, however, as the agency is set to enter a new era in terms of its ability to oversee postmarketing studies. Under new authority provided through the FDA Amendments Act, FDA can now essentially unilaterally request a postmarketing study, and fine a company if it fails to complete it.

Even after Vytorin showed no significant benefit in preventing formation of arterial plaque, and a meta-analysis showed an increased risk for myocardial ischemia for Avandia, FDA has been steadfast in its commitment to surrogate endpoints used to approve the products.

The Democratic Congress has produced several unpleasant regulatory developments for the pharmaceutical industry – from jacking up user fees to pay for safety oversight to cancelling the user fee program for TV ads – but these most recent inquires could be even more troubling for drug companies.

The Fast Track and surrogate endpoint probes do not so much question how the agency is organized and how it interacts with industry, but how it handles data – its core scientific function. In many respects, these questions build off of Grassley’s scrutiny of safety debates within the agency, especially how the review of Sanofi-Aventis’ antibiotic Ketek (telithromycin) was managed.