PHARMA: The FDA, the new safety board and the Cox-2 debacle–an opportunity seemingly being lost

None of this is quite as timely as it would have been 24 hours ago, but it’s worth giving my take on the new developments at FDA, and with the Cox-2s.

Logo3cThe news is that a new board within the FDA will oversee drug safety, and publicize more about its inner workings reviewing drug safety on the Internet. That’s all very well, although it’s not the announcement of an entirely new Federal agency to review post approval marketing and safety that some people might want. And of course it’s a role that will be subject to the FDA overall. The FDA will be led by an insider, Lester Crawford, who has been there all the while that the sky has been falling. THCB contributor Blunter is not alone in describing his appointment as a cop-out.

But it does appear that the FDA ostrich is lifting its head out of the sand. In today’s testimony on the Cox-2s, internal whistleblower David Graham revealed that he was given permission by Crawford to discuss unpublished studies and to give his full opinion. That marks a big change since his last testimony and it suggests that the FDA higher-ups realize that politically they can’t get away with their stonewalling.

It’s also good news that there are now promises to release more information earlier in the process. Part of the issue with the Cox-2s, particularly with Celebrex, is that the FDA (eventually) found out information about trials that it didn’t release to the public. The most pressing example of this is discussed by John Abramson in the excellent Overdosed America. Pfizer had basically hidden results of a 12 month Celebrex study from the FDA and only initially put forward the 6 month interim data. But while FDA got the new results eventually, it required a Freedom of Information Act request so that the public could discover what the FDA knew.

Now that the Cox-2 cat is out of the bag, there’s more and more bad news:

"A new study has linked pain killers Vioxx, Celebrex and Bextra to increased cardiovascular risk, reinforcing findings of other trials that have already sparked concern over the safety of a popular category of drugs."

It’s not just the FDA and big pharma that comes out of this looking bad. The NEJM which published the original results doesn’t seem to be falling all over itself to eat crow. Abramson called them yesterday a "mouthpiece for the industry". The short comment from Jeff Drazen in the NEJM basically in a most understated way suggests that if just possibly Merck and Pfizer had conducted studies to investigate problems with the Cox-2s rather than new trials to get other indications, we might just have figured out the severity of those problems a little sooner. But nowhere is there a real admission from the NEJM that it either misrepresented the VIGOR results in its peer review process, or allowed itself to get conned by big pharma. In terms of further FDA reform, the slightly more aggressive piece also in NEJM by Psaty and Furberg notes that:

For an approved drug, the FDA currently engages in protracted negotiations with manufacturers rather than mandating manufacturers (1) to change a product label, (2) to conduct patient or physician education, (3) to limit advertising to patients or physicians, (4) to modify approved indications, (5) to restrict use to selected patients, (6) to complete post-marketing studies agreed on at the time of approval, (7) to conduct additional post-marketing studies or trials, and (8) to suspend marketing or immediately withdraw a drug. The FDA has recently claimed to lack adequate authority in these areas. We believe that to protect the health of the public, Congress needs to provide the FDA with the necessary authority and also to create an independent Center for Drug Safety with new authority and funding. Civil penalties should be commensurate with the scale of drug sales. Provisional approval and regular repeated review would provide opportunities to reevaluate risk and benefit. In addition, ongoing congressional oversight of the FDA would afford an important forum for the public discussion of drug safety.

But of course we’re probably not going that far anytime soon with the news out yesterday that the drug safety office will be staying within the FDA, which makes it unlikely to be quite as "independent" as all that.

And we’re never going to get to the rational debate about making more drugs available to more patients with everyone concerned having a real understanding of the potential risks and benefits involved. Which is a big pity because that’s what a grown up responsible FDA and medical system should be doing. I’m not convinced that Vioxx should, in a perfect world, be taken off the market. All drugs have some side effects and while Vioxx and Celebrex clearly shouldn’t be given out like candy, there may be patients where they work well with few side-effects and where they are a big improvement over NSAIDs. Theoretically the clinical trial data should be able to identify those patients, and patients on those products could be monitored for cardio-vascular risk, and taken off them if bad things start to happen.

But because the FDA didn’t do its job in the first place, and because the NEJM looked the other way, and because big pharma’s marketing machine ran roughshod over the minimal checks and balances in the system, we’re now in a mess which will likely see more good drugs not getting to market and the development of an overly-conservative approach to patient safety.

Perhaps integrating the use of drugs fully into the medical care delivery process might be a good place to start, rather than having the use of a prescription as a way for a doctor to get a patient out of their office. But that would require a whole new mind-set.

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