For much of the past year, the FDA accelerated approval program has come under withering scrutiny. Last June, Pfizer withdrew a drug used to treat acute myeloid leukemia, or AML, after a study found a lack of clinical benefit and an unexpected number of deaths. But the study didn’t get under way until four years after approval was granted in 2000 (back story).

More recently, the FDA decided the breast-cancer indication for Roche’s Avastin should be withdrawn after studies found patients on the med and chemotherpay didn’t survive longer than those given chemo alone. And Avastin patients suffered more serious side effects. The decision amounted to an about-face, having endorsed the indication in 2008 under accelerated approval (look here).

And so the FDA’s Oncologic Drugs Advisory Committee met yesterday to debate the program and, while no vote was held, the panel urged the FDA to require drugmakers to submit at least one controlled trial for approval for their cancer meds. Why? More than half of the drugs passing through accelerated approval do so by relying on a single-arm trial, MedPage Today notes.

You may recall the FDA requires two randomized, controlled trials to demonstrate safety and effectiveness before approval, but oncology drugs can sometimes get a pass. However, the FDA panel was concerned that drugmakers are failing to conduct required post-marketing studies to verify surrogate endpoints on a timely basis, undermining the veracity of the accelerated approval program.

“There is almost no situation when (a single-arm trial) would be adequate in human beings,” said panel member Silvana Martino, director of the Breast Cancer Program at the Angeles Clinic and Research Institute in Santa Monica, Ca., according to MedPage. She called the FDA “ignorant” for relying on single-arm trials and complained “we are willing to accept drugs with the absolute minimal evidence that they do anything.”

A telling remark, however, was made by Richard Pazdur, who heads the FDA’s Office of Oncology Drug Products, who essentially acknowledged that the bar is too low. “We frequently get sponsors who say ‘What’s the lowest number of patients and response rates you’ll take?’ ” Last summer, he told us the FDA will be asking drugmakers to provide required confirmatory studies, not just accelerated approval studies, and completion dates, as well. And any delays would have to be explained (see his comments here).

But Gary Lyman of the Duke Comprhensive Cancer Center, another FDA panel member yesterday insisted that randomized, controlled trials should be the “default position” for all trials. Of course, that would likely mean delays. “If we start to require randomized studies for approval, it’s going to also take longer to get the drugs to patients,” Wyndham Wilson of the Lymphoma Therapeutics Section at the National Cancer Institute noted, according to MedPage.

And therein lies the conundrum. The program emerged after criticism that the FDA did not move fast enough to approve new drugs, especially as national awareness of AIDS appeared. But at the same time terminally ill patients clamored for salves, safety concerns have arisen because new meds are released before traditional clinical testing requirements would normally allow. What do you think?

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