This may sound a little odd coming from someone in the drug industry, but I have a lot of sympathy for the FDA. I'm not saying that I always agree with them, or that I think that they're doing exactly what we need them to do all the time. But I would hate to be the person that would have to decide how they should do things differently. And I think that no matter what, the agency is going to have a lot of people with reasons to complain.
These thoughts are prompted by this article in JAMA on whether or not drug safety is being compromised by the growing number of "Priority Review" drug approvals. There are three examples set out in detail: Caprelsa (vandetanib) for thyroid cancer, Gilenya (fingolimod) for multiple sclerosis, and the anticoagulant Pradaxa (dabigatran). In each of these accelerated cases, safety has turned out to be more of a concern than some people expected, and the authors of this paper are asking if the benefits have been worth the risks.
Pharmalot has a good summary of the paper, along with a reply from the FDA. Their position is that various forms of accelerated approval have been around for quite a few years now, and that the agency is committed to post-approval monitoring in these cases. What they don't say - but it is, I think, true - is that there is no way to have accelerated approvals without occasional compromises in drug safety. Can't be done. You have to try to balance these things on a drug-by-drug basis: how much the new medication might benefit people without other good options, versus how many people it might hurt instead. And those are very hard calls, which are made with less data than you would have under non-accelerated conditions. If these three examples are indeed problematic drugs that made it through the system, no one should be surprised at all. Given the number of accelerated reviews over the years, there have to be some like this. In fact, this goes to show you that the accelerated review process is not, in fact, a sham. If everything that passed through it turned out to be just as clean as things that went through the normal approval process, that would be convincing evidence that the whole thing was just window dressing.
If that's true - and as I said, I certainly believe it is - then the question is "Should there be such a thing as accelerated approval at all?" If you decide that the answer to that is "Yes", then the follow-up is "Is the risk-reward slider set to the right place, or are we letting a few too many things through?" This is the point the authors are making, I'd say, that the answer to that question is "Yes", and we need to move the settings back a bit. But here comes an even trickier question: if you do that, how far back do you go before the whole accelerated approval process is not worth the effort any more? (If you try to make it so that nothing problematic makes it through at all, you've certainly crossed into that territory, to my way of thinking). So if three recent examples like these represent an unacceptable number (and it may be), what is acceptable? Two? One? Those numbers, but over a longer period of time?
And if so, how are you going to do that without tugging on the other end of the process, helping patients who are waiting for new medications? No, these are very, very hard questions, and no matter how you answer them, someone will be angry with you. I have, as I say, a lot of sympathy for the FDA.