It's not the Kremlin, but since the FDA rarely (if ever) explains its own internal decision making process when it grants or denies marketing approval for a new drug, medical device, or diagnostic, agency watchers can only speculate about what signals the agency is sending to stakeholders, Congress, and the media when it changes its mind in very high profile cases.
There's a lot to speculate about this week.
The FDA reversed itself on two products that had drawn quite a bit of attention from Congress, think thanks, and the blogosphere.
First, the FDA did an about face and approved a new device, MelaFind, that can help dermatologists identify cancerous melanoma lesions - a rare but very deadly type of skin cancer. If melanoma is caught early, it is very easy and inexpensive to treat. If it isn't, it's one of the most deadly cancers.
As the Wall Street Journal noted yesterday, the FDA rejected MelaFind as recently as last year - after which Mela Sciences, the sponsor, filed a citizen's petition directly to the FDA's Commissioner, Margaret Hamburg. MelaFind was discussed at a House hearing on the FDA and medical device approvals earlier this summer.
If the FDA fails to approve MelaFind, it would be the equivalent of rejecting the first cell phone on the grounds that callers might mishear important messages.
(Matthew Yglesias, at Think Progress, takes a somewhat more skeptical view. My response would be that every technological advance is basically like MelaFind - including drugs and devices that the FDA routinely approves. "Tinkering" at the margins is how technology gets better, faster, and cheaper.)
The table below, courtesy of the Wall Street Journal, gives you some sense of how prevalent melanoma is. The survival rate for metastatic melanoma is much lower than it is for more common prostate and breast cancers. If it's caught early, survival rates are basically 100%. If the melanoma spreads, survival rates drop to about 15%.
The beauty of products like MelaFind is that they will improve over time with use (particularly with feedback from physicians) - so setting a prohibitively high standard for FDA approval doesn't make much sense.
For more background on MelaFind saga, see this article from CNN.
Obesity is another "unmet" need in the health care field, with few good medical options (apart from bariatric surgery) for obese patients who find it difficult to lose weight through simple exercise and dieting.
Contrave had received an "approvable" letter from the FDA - but only if they completed an additional enormously expensive and time consuming study. Bruce Booth, at Forbes, wrote that:
Ignoring the advice of their own Advisory Committee last December, which voted for approval, they have now rejected what seems on the surface to be a robust proposal by Orexigen to do one of the largest Phase 3 clinical trials ever to bring Contrave to market. In an attempt to address the cardiovascular risk questions posed by the FDA's Complete Response earlier this year, Orexigen proposed a very rational REMS approach to safe use of the drug and doing a monster 12-15,000 patient study. That's a huge trial. But apparently not big enough. Using the FDA's statistical powering methods implied that the trial size they wanted would need to include 50,000-100,000 patients. That's an absolutely untenable, multi-year, many billions of dollars study.
How is Orexigen, a small cap biotech, supposed to fund that? It's not. The FDA doesn't want Contrave to see the light of day. [Emphasis in original]
Some combination of the Orexigen's appeal to FDA leadership, Congressional hearings, and patient advocacy groups appears to have tipped the agency towards a better approch: a 10,000 person trial with requirements more in line with those used for diabetes drugs (which are still very stringent). The new agreement doesn't bind the agency to approve the drug if it meets it's new endpoints, but it's still a better outcome than the previously proposed requirements. If all goes well, Contrave could be approved in 2014.
What to make of these decisions?
Both are promising signs that the agency's top leadership - people like Commissioner Margaret Hamburg and CDER Director Janet Woodcock "get it", and recognize that setting too high approval standards slows patients access to innovative new medical devices and drugs.
Obesity and melanoma are both clearly product areas that represent "unmet" medical needs, and so loosening of approval standards makes eminent sense, and will help encourage investment in those fields.
What is disappointing is that we don't know how many other products are never developed because investors won't take the enormous financial and regulatory risks associated with FDA approval.
At the very least, Mela Find and Contrave suggests that the FDA's review processes can be arbitrary, and that less onerous and clearer approval standards are needed that are calibrated to the real needs of patients - and how innovation really works.
Also disapointing is the fact that even after the FDA was given new powers (called REMS) in the last PDUFA reauthorization to monitor products' use after they are marketed, it doesn't seem to have made the agency any more likely to allow products to go to market rather than ask for reams more pre-market data.
For now, it looks like we have the worst of both worlds: massive premarket data and testing requirements combined with sometimes onerous requirements for postmarket studies.
The agency's shift on Contrave and MelaFind are welcome - but must represent more than one-off compromises forced by the glare of the media and Congress.