Appeals Court Throws Monkey Wrench into FDA Regulatory Authority

For background see:
http://www.reuters.com/article/2012/12/04/us-offlabel-conviction-idUSBRE8B21DC20121204
http://www.healthreformwatch.com/2012/12/04/united-states-v-caronia-some-preliminary-thoughts-on-the-second-circuits-decision-invalidating-the-ban-on-off-label-promotion/
http://www.nejm.org/doi/full/10.1056/NEJMp1214926

Readers of HOOKED and this blog have seen this general scenario repeated more times than I can count:

1. A drug firm markets a drug aggressively for ineffective or unsafe uses.
2. A whistleblower within the company alerts the Feds.
3. The Feds begin investigating the company with an eye toward prosecution for legal violations.
4. As part of the investigation the Feds force the company to cough up internal documents. These documents provide folks like us with our only glimpse of what Pharma is really up to, as normally all that is buried deep as proprietary information.
5. In the end, the Feds reach a settlement with the company, which pays a fine of lots of bucks, which is often only a pittance compared to the revenues received from sales of the drug--so that the company then does it all over again with the next drug.

Now notice that for this process to work (Step #3), there has to be a legal violation that the Feds could find the company guilty of. The standard up till now has been off-label marketing--the company promoting the drug for uses that are not included in the official label. It is not that the off-label marketing aspect of the promotion of the drug is really what is most egregious, necessarily--it just turns out that that's often the handiest legal peg on which to hang the case. Bottom line--if the FDA lost its ability to prosecute companies for off-label marketing, the even-now-super wimpy degree of control that the FDA exercises over drug promotion gets wimpier still.

This is precisely what's threatened by the case of U.S. v. Caronia as decided by a 3-judge panel of the U.S. Second Court of Appeals for New York in December. Caronia was a drug detail rep who was working with a doc (one of those "key opionion leaders" aka shills) who was giving industry sponsored speeches recommending sodium oxybate (Xyrem, Orphan Medical/Jazz Pharmaceuticals) for off-label uses (it is only approved for catalepsy and narcolepsy in adults). The DOJ heard about this and conducted a sting, recorded both the rep and the doc, and then arrested them. The trial court convicted, and dismissed Caronia's defense that the conviction violated his first-amendment free speech rights.

The panel of the Appeals Court, by a 2-1 vote, overturned the conviction, ruling that  limiting Caronia's rights as a detail rep to recommend the drug for off-label uses, which are legal for docs to prescribe for, is an inappropriate limitation of his first amendment rights as he claimed, unless the Feds could show that the off-label promotion was itself false or misleading. The one dissenting judge mentioned the "well,duh" point that if reps had the first-amendment right to say whatever they wanted to docs, then that totally throws any powers of the FDA to regulate drug marketing out the window.

To unpack that concern just a bit, what's the rationale for the FDA's prerogative to regulate off-label marketing of drugs, even if docs can freely prescribe the drugs for those uses? If the company cannot market for off-label uses, then they have an incentive to apply for label changes to extend use of the drug when they discover possible new uses. They thus have an incentive to submit data to the FDA to prove safety and effectiveness when the drug is used in those ways. If companies can market off-label with impunity, their incentives change--they have an incentive to seek the narrowest possible label at first, spending the minimum on studies to prove safety and efficacy, and then they can market the drug for any old thing without having to prove that the drug is safe and effective over that much wider range of use. Hence--establishing marketing off-label as a free speech right basically eviscerates FDA regulatory powers.

The two-judge majority of the panel did not see it that way, and stated that if the goal of the FDA is to limit off-label prescribing, they could do so just as well by imposing ceilings or caps on off-label prescriptions without interfering with commercial speech. The dissenting judge, no fool, was not buying that. She pointed out that ceilings or caps could require incredible record-keeping burdens and also result in some patients being denied a useful drug while others were prescribed a dangerous drug. To which I might add: the whole reason for the FDA regs as they now stand is that they presumably can regulate drug manufacture and marketing, but the FDA has no remit (as they say across the pond) to regulate medical practice. Setting ceilings on off-label prescribing sounds to me like trying to regulate medical practice.

What the various authors linked to above seem to disagree about is how big a deal this decision is. The New England Journal prespective by Marcia Boumil appears to see the matter as relatively dire--this case is sure to be appealed up to the Supreme Court, where the conservative majority is very likely to extend the first-amendment rights of "commercial speech." By contrast, Kate Greenwood at Seton Hall Law School's health blog seems a bit less concerned. She notes that the government has up its sleeve a number of arguments to defend FDA powers, including for instance the interpretation that what was effectively appealed in this case was a set of erroneous instructions to the trial court jury, and not the principle of free speech vs. drug regulation, severely limiting the scope of any unfavorable ruling.

Also, it's my understanding that before the case goes up to the Supreme Court it may be appealed to the entire Second Appeals Court bench, beyond just the 3 judges who initially ruled. I have no idea about the political makeup of that bench as to whether that would likely change the outcome.

I don't, as a non-lawyer, know what to make of the eventual implicatons except for two things:

• From an ethical and common-sense point of view the two-judge panel decision sounds like idiocy.
• If the prerogative of the FDA to limit off-label marketing is seriously restricted (and it has already been chipped away to a large degree), then expect to have even more problem in the future ever discovering what the drug industry is really up to--let alone seeing anyone held accountable for marketing unsafe drugs.