Food and Drug Administration

New York Times reporter Gardiner Harris has a front page article in today’s paper on the head of the Food and Drug Administration’s Office of Oncology Drug Products, Richard Pazdur.  As the article notes, Pazdur has come under severe criticism in recent years for obstructing the approval of numerous innovative cancer drugs.  Some of this criticism is unfair, and Harris is clearly attempting to defend Pazdur and the FDA, while proving the critics wrong. After all, Pazdur has implemented reforms that permit the FDA to occasionally consider New Drug Applications for cancer drugs that are supported by fewer clinical trials, with fewer patients in those trials, and that measure progress toward a “surrogate end-point” such as tumor suppression instead of increased length of patient survival.

But that’s not the whole story.  Steven Walker, a co-founder of the patient advocacy group Abigail Alliance, is rightly quoted saying “Patients are right to be angry and frustrated with Richard Pazdur. … He is a dinosaur.”

Indeed, in his zeal to defend Pazdur, Harris gets a few important facts wrong.  For example, he writes that “Federal law requires that the agency demand two ‘well controlled’ trials before approving a drug; in cancer, the Food and Drug Administration is often satisfied with just one.”  Wow, you might think, this Pazdur guy must really be special if he’s willing to disregard federal law in order to speed new drugs to market.  Except that federal law hasn’t required two Phase III trials in all cases since passage of the FDA Modernization Act (FDAMA) in 1997, which specifically permits FDA to approve a drug on the basis of a single Phase III trial if the Secretary of HHS (of which FDA is a part) determines the information sufficient to prove the drug is effective.  Similarly, FDAMA specifically grants FDA permission to “fast track” the approval of important new drugs by considering surrogate end-points rather than increased length of survival.  Pazdur’s contribution was not to come up with these great ideas, but merely to implement them at the request of Congress and President Clinton.

Pazdur looks even less good when you consider some of the products he’s accused of derailing, such as the prostate cancer drug Provenge, which I wrote about two years ago. Provenge works like a vaccine to help a patient’s immune system fight off prostate cancer, a disease with few other available treatments.  The independent panel of scientific experts that advises the agency on new oncology drug approvals unanimously agreed that Provenge was safe, and voted 13 to 4 that it was effective enough for approval, but the agency demanded additional testing before it would approve the drug.  In one trial, 34 percent of patients receiving the drug were alive three years after treatment, compared to just 11 percent of patients receiving the placebo. But the median survival time for those taking Provenge was just 4½ months longer than for the placebo group. Still, Taxotere, the only currently approved alternative for advanced prostate cancer, extends survival for just half that time, while killing some 300 patients outright every year.  FDA’s main contention was that the clinical trial showing these benefits in Provenge was actually designed to find a different end-point.  So, under Pazdur’s leadership, the FDA oncology drugs unit refused to approve Provenge despite pretty reliable evidence of its safety and efficacy.  That story doesn’t make it into Gardiner Harris’s article, however, since it might weaken his case for Pazdur’s sainthood.

Harris does, however, trot out a patient advocate and an industry analyst to make the case that, even safe drugs with uncertain benefits shouldn’t be approved.  “We want drugs that prolong survival, not drugs that just improve a test result,” said Frances Visco of the National Breast Cancer Coalition.  Naturally, we don’t want snake-oil salesmen touting non-existent benefits of sham treatments.  But, why can’t we require full disclosure of the ambiguity, and let patients and their doctors choose?  In far too many cases, waiting for absolute proof of some huge benefit serves only to keep promising new drugs off the market.  It also means that dying patients are refused the only option that might prevent or delay their death.

Harris notes, as a humanizing aside, that Pazdur doesn’t eat meat “because he believes a vegetarian diet will help protect him from cancer, although the supporting evidence is as thin as vegetable broth.”  That’s wonderful; a balanced vegetarian diet certainly can’t hurt, and there is some evidence suggesting that it may well help improve Pazdur’s health.  But, if this dietary choice were subject to the same evidentiary standards that Pazdur places on new drugs, he wouldn’t have that choice.  What seems not to have occurred to Pazdur, Harris, and Pazdur’s other supporters is that, if a drug with uncertain effectiveness is approved, those who “want drugs that prolong survival, not drugs that just improve a test result,” don’t have to use it.  They can hold out for a product with more certain benefits.  But, when a drug with uncertain benefits is not approved, it means that everyone is denied the choice.