Is Grassley barking up the wrong tree at FDA?

Dr. Mark Thornton, former medical officer at the FDA’s Office of Oncology Products, takes Senator Charles Grassley (R-IA) to task on the Wall Street Journal’s op-ed page. (See Grassley’s War on Cancer Patients.) Thornton is upset that Grassley is challenging the FDA’s acceptance of surrogate endpoints and accelerated approval timelines. As Thornton writes:

This kind of measurement [surrogate endpoints] – as opposed to an assessment of a drug’s impact on a patient’s overall survival – has dramatically increased the pace of cancer clinical trials. It also has won near-universal acceptance within the cancer community. The FDA does require follow-on studies to assure that a surrogate finding shows clinical benefit. But if all cancer clinical trials were required to show a survival benefit from the get-go, progress in cancer-drug development would slow to an absolute crawl.

Enter Mr. Grassley. It seems not a week goes by without him making a public accusation of evil doings within the drug industry or the FDA. Yes, Mr. Grassley did some good after the Vioxx episode, by focusing on the woeful manner in which postmarketing drug safety is managed and regulated by the FDA. But he and his staff should have kept their eyes on the ball. In the case of Avastin, the senator implied in his GAO request that something sinister occurred during the FDA’s premarket deliberations, and that surrogate endpoints were the new bogeyman. Nothing could be further from the truth…

The damage done by Mr. Grassley’s decision to make an issue of this decision cannot be understated. Having served at the FDA during the Congressional hearings over the Imclone/Martha Stewart insider trading scandal, I can attest to how an action like this GAO inquiry will resonate within the halls of FDA. An extremely cautious and protective bureaucracy will respond to such intimidation by being even more protective…

Mr. Grassley’s legacy could be thousands of additional cancer deaths.

Pretty harsh stuff, but I generally agree with Thornton. Surrogate endpoints aren’t bad, and neither are accelerated approval timelines. However Grassley isn’t totally off base. In particular, not all surrogate endpoints are actually meaningful. Sometimes they’re elevated in importance at the end of a study to salvage a drug when a primary endpoint fails. Combine a situation like that with accelerated approval and a failure to conduct post-marketing studies in a timely fashion and it’s a recipe for trouble.

It’s clear Thornton is speaking from experience when he talks about the bureaucracy becoming “even more protective.” This is really something to avoid and Grassley probably doesn’t realize the harm he’s doing here by putting a chill on the examiners.

It would be more useful if Grassley and others put pressure on FDA to accept (or even encourage!) the use of new assessment technologies, endpoints and personalized medicine in clinical development. Companies often take the path of least resistance and use old-fashioned, ill-suited tests like the Hamilton Anxiety Scale in drug development just because they’ve been used before and the FDA is accustomed to seeing them.  If Senators want to shake FDA out of its conservatism they need to draw attention to some of the hidebound practices, not inadvertently encourage their perpetuation as Grassley seems to be doing.

May 29, 2008

3 thoughts on “Is Grassley barking up the wrong tree at FDA?”

  1. Roy, Thanks as usual for your thorough analysis. I have to admit I was lulled into a false sense of security on Thornton’s identity here. The blurb at the end of the Journal article reads “Dr. Thornton is a former medical officer in the Office of Oncology Products at the Food and Drug Administration. He volunteers as president of the Sarcoma Foundation of America.”

    That sure doesn’t make it sound like he’s SVP of Product Development at GenVec, which he is.

    I should have investigated that but I’m also disappointed in the Wall Street Journal.

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