Time to end the tyranny: the agency needs to be removed from the drug evaluation equation.

• Author: Emord, Jonathan W.
• Position: FDA - Food and Drug Administration - Editorial

THERE have been many instances in which drug industry executives have been complicit with Food and Drug Administration political appointees in causing unsafe drugs to enter the market over the objections of FDA medical reviewers. The political angst now expressed concerning just one of the drugs, GlaxoSmithKline's Avandia, is dreadfully late--coming a decade after FDA medical reviewer Robert I. Misbin first sounded the alarm on the link between that type 2 diabetes drug and heart problems. Had Misbin been credited instead of discredited, the drug never would have entered the market if it did, would have been accompanied by extreme warnings.

The story of the approval of Avandia over the objection of agency medical reviewers (and FDA defense of the drug for more than a decade) reveals precisely why the agency cannot be counted upon to protect the American public. In an April 21 1999, internal memo, Misbin explained to his superiors his concerns "about deleterious long-term effects on the heart" from the drug. His criticisms were rejected. On May 25, 1999, FDA approved the drug for marketing without referencing the heart risks. Dr. Misbin later stated that one of his superiors said something to him that he never forgot: "We have to maintain good relations with the drug companies because they are our customers." In February 2006, another FDA medical reviewer, Rosemary Johann-Liang, strenuously urged that the FDA require GlaxoSmithKline to put a black box warning on the drug, alerting people to its effect of increasing the risk of heart attack. Dr. Johann-Liang's supervisor told her that FDA management was "upset with [her] recommendation" and "decided to act like [her] review never happened."

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Rep. Diane E. Watson (D.-Calif.) used the drug for her diabetes. She developed a heart murmur that she attributed to Avandia in a congressional hearing. On the advice of her physician, she stopped taking the drug. Seven years after the drug entered the market, caving to pressure brought on in no small measure by the efforts of FDA Office of Drug Safety Associate Director David Graham, the FDA ordered a black box warning on Avandia labeling, but kept the drug on the market. In July 2007, an FDA advisory panel voted 20-3 that Avandia increases cardiac ischemic risk in type 2 diabetics, but voted in favor of keeping the drug on the market. In other words, the economic interests of the drug industry won out over sound medical judgment.

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