Here's a new editorial on clinical trials and drug development by Tomas Philipson and Andy von Eschenbach (former head of the FDA). It continues his earlier theme of scaling back Phase III trials (which I commented on here).
These Phase 3 clinical trials served us well in the past. Today, in an era of precision or personalized-drug development, when medicines increasingly work for very specific patient groups, the system may be causing more harm than good for several reasons.
First, because of their restrictive design and the way the FDA interprets their results, Phase 3 trials often fail to recognize the unique benefits that medicines can offer to smaller groups of patients than those required in trials.
Second, information technologies have created improvements in our ability to monitor and improve product performance and safety after medicines are approved for sale. Post-market surveillance can and should reduce dependence on pre-market drug screening in Phase 3 trials.
Third, reducing reliance on Phase 3 trials is unlikely to introduce an offsetting harm induced by more dangerous drugs, since evidence supporting safety is produced in earlier phases. Manufacturers also have powerful incentives to maintain drug safety, since they take enormous financial hits -- well beyond the loss of sales -- when drugs are withdrawn after approval.
I'm still of two minds about this proposal. The idea of moving to less preclinical study and more post-marketing surveillance is not a ridiculous one, but our current system (and the expectations it generates) do make a good fit with it. The nasty details I noticed being glossed over earlier are still with us: how will health insurance companies deal with this change? How do we keep unscrupulous gaming of the system, with companies rushing things to market and spinning out the postmarketing studies as thinly and cheaply as possible? What would keep the real bottom-of-the-barrel types from pumping out high-priced placebos for demanding diseases like Alzheimer's, which compounds would fly through safety studies and reap big profits until they (slowly) were proved ineffective? What would be the legal aspect of all this - that is, when would a patient have the right to sue if something goes badly wrong, and when would they have to just realize that they're taking an investigational drug and that they're part of a research study?
These are real problems, but you wouldn't imagine that they even exist when you read these editorial pieces. I'm a fairly libertarian guy, but these are the sorts of things that occur to me within the first few minutes of thinking about such proposals, which means that there must be many other wrinkles I haven't thought of yet. I agree that increasing the research productivity of the drug industry would be an excellent thing, but I'm really not sure that this is the way to do it.