FDA’s Regulatory Approval Regime Questioned

Published May 31, 2016

Problems with GlaxoSmithKline’s Avandia drug have raised questions about the regulatory processes of the U.S. Food & Drug Administration (FDA), the bureaucracy that regulates all drugs and foods in the nation. While some are complaining that the FDA released the drug too soon, others point out the requirement that the agency’s give blanket approval or disapproval is too inflexible.

The FDA approved Avandia for diabetics, and it was later found to increase the risk of heart attacks.

Needlessly Restricting Access

Jack Calfee, an economist at the American Enterprise Institute in Washington, DC who has been following developments with the FDA for decades, says those attacking the FDA for releasing Avandia too soon are missing the point.

“Avandia is not nearly as dangerous as its opponents have made it out to be. They are finding that it does cause heart attacks in certain situations, but the FDA’s decision probably got it right:  Avandia, on the whole, is more dangerous than its chief competitors, but for some patients it is better than anything else,” Calfee said. “It is probably better to leave it out on the marketplace but with a warning for potential consumers.”

Calfee maintains the FDA is restricting medicines people desperately need, instead of focusing on warning people of potential problems with the medicines.

“With the FDA’s history, there was a bit of shift in the 1980s with the HIV drugs—they created the ‘accelerated approval process,’ but really they have not gone very far in that direction,” Calfee said. “There has been a big shift toward tough drug approval standards instead of relying on warning labels. The danger is actually the opposite of what the opponents of Avandia are saying: In making it harder for new drugs to come to market, you are making it harder for a new drug that could do some real good for patients to appear, and the FDA is now also sometimes putting restrictions on how a new drug is even used.”

Exceptions for Lifesaving Drugs

Rita Redberg, MD, of the University of California-San Francisco, says the FDA’s full testing regimen should be carried out for all drugs, but the agency should make an exception for lifesaving drugs, to speed the approval process.

“It is a good idea to consider lifesaving drugs differently than most of the drugs that get approval. Drugs on the market that the FDA approves quickly are often for treating diabetes and beta blockers, and for all those we want to be sure that any one of those drugs has assured benefits that would outweigh the risks,” Redberg said. “But I think it is not that fast a process if the drug is lifesaving.”

Redberg notes Avandia would not fall into the category of a lifesaving drug.

“In general, evidence of clinical benefits before approval—just to make sure there is enough high-quality data with a clinical end-point—is needed,” Redberg said. “We need to knock down barriers for lifesaving drugs where there is not another choice of therapy. But for most of the drugs, in the interest of public health, adequate data to ensure effectiveness and avoid risk needs to occur.”

Controversy Over Approval Times

For non-lifesaving drugs, Redberg wants the FDA to continue to err on the side of caution, continuing to withhold approval until there’s no doubt of their effectiveness and lack of serious side effects.

“I think it is better to have the evidence of high quality data and good certainty up-front. It is potentially dangerous to put people on a drug that is dangerous for them, that may not be of any real service to them, because they are desperate,” Dr. Redberg contends. “We all feel terrible, but hospice care has shown better quality of life results than trying therapies that may be toxic.

“I think the current leadership at the FDA is interested in making changes,” she added.

‘These Problems Are Not New’

Calfee disagrees, saying the process has been largely the same for the last 15 years. One reason for the FDA’s stagnation, he says, is the political and media environment, which blames the agency for approving drugs that have problems but not for holding up approval of drugs that could save lives.

“I do not think the FDA is doing a whole lot better or worse than 10 to 15 years ago. They have to deal with the New England Journal of Medicine or newspaper editorials attacking them for approving new drugs,” Calfee said. “There has been this pathway for accelerated approval, but now they do not use it very often, and they have been criticized for using it. They pulled back Avastin, the cancer drug, they have Avandia now—do not expect to see them getting praise for accelerated approval.”

Calfee says the FDA’s approach lags behind the rest of the world.

“The FDA has been around since 1906, and it’s had authority over new drugs since the 1930s, but it wasn’t until 1962 that revisions were made to the FDA law requiring manufacturers to demonstrate that their drugs are effective,” Calfee said. “At that point the FDA was reborn—and there is no doubt that getting new drugs approved since the 1962 amendments has been very lengthy.  Today they lag far behind European countries—these problems are not new.”

Thomas Cheplick ([email protected]) writes from Cambridge, Massachusetts.