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FDA Pain Patch Decision: Making a 'Sophie's Choice' with People's Lives

At the Food and Drug Administration (FDA) advisory hearing on Thursday, February 9, a panel of scientists and clinicians voted unanimously not to recommend approval of the Qutenza capsaicin patch for HIV neuropathy pain, based on data from 2 clinical trials. As the sole patient representative on the panel, it was an incredibly demoralizing experience.

FDA hearings are sometimes convened to bring in experts to vote on whether to recommend approval of a new drug or product when evidence is conflicting or controversial. The FDA almost always rubber-stamps the advisory panel’s recommendations for final approval, but is not required to do so.

I'm sure many AIDS activists have had similar experiences, but this was one of the most agonizing of my life. FDA hearings always include a patient representative who is allowed to discuss and vote on the issue at hand. The other panelists were scientists and clinicians, statisticians and researchers who were more sensitive than I've ever witnessed at an FDA hearing. We all left the poorly attended 6-hour hearing feeling drained and heartbroken for the thousands of people with HIV neuropathy who have no other approved treatments.

I went into this hearing hoping for a new treatment for this horrible condition, which I have not experienced myself, but have borne witness to with so many friends over the years.

But truth be told, the evidence in favor of the pain patch was just not strong enough based on data that were allowed to be considered by the FDA. In one trial, the effectiveness of the patch was not solidly demonstrated in the primary analysis and did not achieve expected primary outcomes. The FDA would not allow us to consider other post-hoc (after the fact) company data using other pain scales, even though one of them was apparently a more conservative scale showing a slight improvement compared to the initial scale used.

There were other statistical and trial design problems, including the fact that the company, NeurogesX, used an “active control,” meaning a lower-dose capsaicin patch, in order to blind the application site pain caused by capsaicin. Most trials use a placebo control, also known as a “dummy” drug, but in this case doing so could have tipped off patients about whether they were receiving the real or placebo patch. For ethical reasons, the studies also allowed opiates and other analgesics, which were used by a large proportion of the participants, who were all reporting foot pain. Both of these factors might have weakened the study outcomes.

NeurogesX also chose to apply for approval of a 30-minute patch application instead of 60 or 90 minutes. I believe they selected the 30-minute application due to less capsaicin exposure, which causes pain itself. But it just wasn't clear that this was the most effective exposure duration after all was said and done.

I think the company made the right decisions in these trials designs in the interest of the patients, but unfortunately, we all had to vote on whether the study showed "substantial" effectiveness based on the initial analysis. Some panelists would have voted yes if we had been allowed to consider the totality of the data, which really was only slightly better.

I think the “no” vote was the only way to go in order to hold to the standards of FDA rules. I honestly think the patch is a slight improvement over what little is now available. Panelists kept saying that patients could buy the patch off-label (it is approved for shingles nerve pain), not understanding that many of us do not have the money to pay for off-label medications not covered by insurance or public benefits.

I learned so much from this experience, the third FDA panel I have sat on. Needless to say, this has been a heavy load to bear given this horrible painful condition. Rigorous standards have to be upheld in any scientific process, and so many times they are not. I actually applaud the FDA and the panelists for agreeing on the importance of this, so that other companies cannot bend the rules in the future. However, this time strict standards weighed against HIV positive people with a painful condition.

Principles were torn in half yesterday, and I don't think I will ever rectify my vote. It was almost like making a 'Sophie’s choice' with people's lives.

Matt Sharp is an independent HIV education and advocacy consultant based in San Francisco.

2/14/12