S. Sen. Grassley: Secures independent review of FDA approvals based on narrow health benefits

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S. Sen. Grassley: Secures independent review of FDA approvals based on narrow health benefits

3/4/2008

WASHINGTON — Senator Chuck Grassley has asked for an independent assessment of how the Food and Drug Administration follows up on the effects of medicines that it approves based on narrowly defined benefits.

“The way things have turned out with drugs like Vytorin and Avandia raise enough questions that a review is warranted,” Grassley said. “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. These policies are designed for patient safety.”

Grassley’s questions stem from a practice of the Food and Drug Administration to use goals called surrogate endpoints to study whether a particular drug achieves a certain benefit, such as lowering blood sugar in diabetics. Grassley said it’s critically important that the agency adhere to its complementary policies that require drug-safety reviewers to follow up on drugs that are approved based on surrogate endpoints.

“The public relies on the FDA to keep it safe from dangerous drugs and not just stick to narrow judgments that may not incorporate overall health,” Grassley said. The diabetes drug Avandia was approved because it lowered blood sugar but later found to increase the risk of heart attack, even though lower blood sugar is tied to lower heart attack risk.

The Government Accountability Office, which is the investigative arm of Congress, has agreed to conduct the review that Grassley requested in the letter posted below.

February 28, 2008

The Honorable David M. Walker
Comptroller General
U.S. Government Accountability Office
441 G St, NW
Washington, D.C. 20548

Dear Comptroller Walker:

The Food and Drug Administration (FDA) has approved several drugs that appear to have little to no effect in protecting lives and increasing health. For instance, FDA recently approved Genentech's cancer drug, Avastin, to treat breast cancer.[1] Genentech's studies showed that Avastin halted tumor growth, but that breast cancer patients did not live significantly longer than those that did not receive the drug. Surprisingly, FDA's own advisory panel argued against the approval over concerns that Avastin's benefits do not outweigh its toxic side effects.

Further, a study last year found that Avandia, which controls glucose levels, was associated with an increased risk of heart attack. And last month, Schering-Plough and Merck announced that Vytorin, which controls cholesterol levels, provided no benefit to cardiovascular outcomes.

In all three cases, these drugs were approved by FDA because they had an effect on surrogate endpoints (tumor growth for Avastin; glucose levels for Avandia; and cholesterol levels for Vytorin). However, none of these drugs were studied sufficiently to see if they added any benefit to the health and/or lifespan of the patient. Typically, such results can be found through phase IV trials.

Therefore, I request that the Government Accountability Office conduct an inquiry into the FDA's approval of drugs based on surrogate endpoints, including an examination of FDA's process to ensure that drugs approved on surrogate endpoints are both safe and effective. In particular, GAO's inquiry should include an analysis of the following:

C The number of drugs that were approved based on surrogate endpoints;
C The surrogate endpoints that FDA uses to approve drugs;
C For each of these drugs identified, the date each was approved and whether FDA required the companies to complete phase IV trials;

C For each of these phase IV trials, the date they were started and the date they were completed and/or are expected to be completed;
C Describe the tools that FDA has to compel companies to complete phase IV trials;
C Describe any actions that FDA has taken against companies for failing to complete phase IV trials or failing to complete trials in a timely manner; and
C Describe any additional powers that FDA may need to compel companies to complete phase IV trials, in the event the tools that FDA has presently are insufficient.

Thank you for your attention to this important matter.

Sincerely,
Charles E. Grassley
United States Senator
Ranking Member of the Committee on Finance