Ex-Intel chief Andy Grove’s idea to reform clinical trials didn’t get much of a reception around here, although (in the end) I was more receptive to the idea than many people were (the comments to the posts here followed similar lines).
So it’s quite interesting to see former FDA commissioner Andy Eschenbach making what sounds like a very similar pitch in the Wall Street Journal. It’s near the end of an op-ed about reforming the FDA, and it goes like this:
Breakthrough technologies deserve a breakthrough in the wa the FDA evaluates them. Take regenerative medicine. If a company can grow cells that repair the retina in a lab, patients shouldn’t have to wait years while the FDA asks the company to complete laborious clinical trials proving efficacy. Instead, after proof of concept and safety testing, the product could be approved for marketing with every eligible patient entered in a registry so the company and the FDA can establish efficacy through post-market studies.
There are several ways to look at that idea. One is to translate it into less editorial language and propose that “Patients (and their insurance companies) should be able to pay to try therapies before they’re proven to have worked, as long as that proof is forthcoming”. That’s not prima facie a crazy idea, but it’s subject to the same sorts of objections as Grove’s earlier proposal. The post-marketing data will likely be of lower quality than a properly run clinical trial, and it will be harder to use it to establish efficacy. On the other hand, useful therapies would get into the hands of patients faster than happens now, and the expense of drug development would (presumably) go down. But useless therapies would also get into the hands of patients faster than happens now, too, and that’s something that we’re not currently equipped to deal with.
Any such scheme is going to have to deal with the legal aspect. People don’t currently feel as if they’re enrolled in a clinical trial when a new drug is offered for sale (although perhaps they should), and it’s going to take some doing to make clear that an investigative therapy is just that. Will patients sue, or try to sue, if it doesn’t work? If it goes further than that and causes actual harm? I’m thinking of Lilly’s gamma-secretase inhibitor that actually seemed to make Alzheimer’s worse – how do we handle things like that?
What about the insurers? Will they be happy to have the costs of a Phase III trial offloaded onto them? Not likely. There’s also the question of what therapies will get to hop onto this conveyor belt: how much proof-of-concept will be needed? Will that be for the insurers to decide, what investigational drugs they’re willing to pay for, so that data can be obtained?
And about that data – it would be of great importance to establish, up front, just what sort of endpoint is being sought. Clear criteria would need to be established (both positive and negative) so that a regulatory decision could be reached in a reasonable time frame. Otherwise, I fear that there are any number of entrepreneurial types who would gladly stretch things out, as long as someone else is paying, in the hopes of finally seeing something useful. No one will – or should – pay for extending fishing expeditions.
Even after all these objections, I can still see some merit in the whole idea. But the question is, after you take all the objections into account (and there are surely more), how much merit is left over? It’s not as clear-cut a case as Eschenbach (or Grove) would have a person believe. . .
Some early reactions to Eschenbach’s proposal are here and here. There are, I should note, a few other aspects to his op-ed that will be subject of another post.
Update: John LaMattina has similar views.