A day at the FDA

Posted by ChrisPMcCoy on Thursday, July 15, 2010 at 1:34 am

Is rosiglitazone (Avandia) safe?

That was the question discussed for two days at a FDA hearing outside Washington, DC. I attended the second day of the hearing to represent patients and the NPA during the open public testimony. I focused my comments; on the perspective of patient trust, as well as the impact of conflicts of interest on the discussion.

Let me set the scene. The meeting was held in a hotel ballroom. A giant U-shaped table for the 33 members of the two combined FDA advisory committees filled half of the room. Behind the table along the wall, sat staffers from the FDA, representatives from GSK, the uniformed members of the Public Health Service, and dozens of others. There was a large screen in the corner projecting the slides, as well as screens in front of all of the committee members showing the same material. The other half of the room, separated by a rope (“Committee members only beyond this point”), was set aside for the public and the media. There was a small section in the front for the invited speakers (such as Dr. Nissen, who started this discussion with his article in 2007), as well as those who had registered to speak during the open session (like me).  There were also two rows of chairs for the media, but media overflowed into the general seating area. Laptops, Blackberries, iPhones, and the like were being used by nearly everyone in the rows of chairs. Outside of the ballroom, the hallway was crowded with camera crews from the national media, each of whom had marked out their spot with tape on the floor. There were two large HD TVs with a closed-circuit feed from the hearing room – both surrounded by chairs and more media.

At the heart of the matter for discussion by the advisory broad was this issue: Do we have enough evidence based on the meta-analysis of adverse events in small randomized trials combined with observational studies to remove rosiglitazone from the market? Or do we need to conduct an additional, large, thorough randomized study to refute the concerns?

After a day and a half of listening to presentations from the clinical researchers, FDA reviewers, experts in trial design, the drug manufacturers and of course the public, the panel had nine questions to answer and report back to the FDA. The panel voted 18-6 (with 9 saying incomplete data) that rosiglitazone had “significant safety concerns” for cardiovascular events compared to other diabetic medications. When compared to just pioglitazone, the vote was 21-3-7. At the end of the day, a majority of the panel recommended either removing rosiglitazone from the market or restricting access.

But these are just recommendations from an advisory panel. The FDA commissioner will make a decision about rosiglitazone in the near future. Whatever the final decision, I am now confident that the FDA made that decision based on a thorough discussion, with what is best for our patients as primary concern, not only with rosiglitazone, but also setting a precedent about how drugs should be assessed for safety.

Reflecting on the day, I came away re-assured that the FDA has a rigorous way to debate challenging questions. In this era of sound-bite politics and talking heads with plenty of experience talking and little experience actually leading … it was refreshing to watch experts weigh the conflicting and incomplete evidence, all while trying to make the best decision for patients and the public health. It is unfortunate that discussion in the political sphere has come to the point of devaluing and denigrating “experts” and “elites”. There are definitely times, and this is one, where we want to technocrats to be engaged in the process. It was also refreshing to hear, as they discussed their rationale, that everyone recognized that individuals, acting in good faith and with patients’ best interests at heart, could look at the same data and come to different conclusions. There isn’t a clearly “wrong” answer to this question.

I was pleased in the way that the entire discussion was in the open to the public, as were the votes. I should recognize how trust is powerfully enhanced by this culture of openness. (A side point about democracy: In a representative democracy, when individuals are voting to represent themselves and their own interests, that vote should be secret – like on election day. However, when votes are being made on behalf of others, those votes must be public so that we know how our government is making decisions on our behalf.)

As I watched the committee take its voice (which was punctuated by humorous comments about the non-intuitive voting system: “I met to vote for [A], but I think I voted for Pat Buchanan”), I thought about how I would vote if I were on the committee. Having read much of the published literature on rosiglitazone since 2007, I’m well aware of the risks, as well as the methodological problems of all of the studies. But as a provider, I could not start a new patient on rosiglitazone – maybe it doesn’t increase risk of heart attacks, but do I want to take that chance with a patient’s life, especially when we have other options for treating diabetes? On the other hand, during the public forum, a patient testified about his ten-year experience on rosiglitazone (MI-free) and how he credits it for keeping him healthy. Would I want to completely remove it from the market, understanding that a very real (and very unintended) consequence could be that patients would simply stop taking diabetes medication altogether rather than switching to something safer? I believe we need to remove unsafe medications from the market – to not do so would rapidly erode trust in medicine. But there is also a slow erosion of trust if we leave questions unanswered about safety. And how do we empower patients to make decisions about their medical care? Should we simply leave it up to patients to research the risks and benefits (by asking their physician, or through the Internet, or going to medical school)? Should the FDA make some of those decisions, as they have been empowered to do so by laws written by the people’s representatives in Congress?

Regardless of the FDA’s final decision on rosiglitazone, this is a complex issue that we will need to explain to our patients. But after watching the FDA in action today, I trust that this process will be open and public so that we all understand the factors that were weighed in making that challenging decision.

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