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United States v. Caronia


The FDA approves drugs only for particular uses, but once a drug is approved as safe, doctors can use their medical judgment to prescribe them for whatever therapeutic purpose they wish. (Network newsmagazines sometimes try to pretend that this is a scandal, running fifteen-minute stories on the issue without once mentioning that it's entirely legal rather than the equivalent of a campus drug ring selling Ecstacy.)

Pharmaceutical companies sometimes run into trouble as a result; the FDA only allows them to advertise the drug for approved uses (accusing them of "misbranding" otherwise), and sales representatives earning commissions have the incentive to go outside of those regulatory bounds. Prosecutors strike hard when that happens, and the threat of debarment can extract billions of dollars from pharmaceutical companies whether or not they are culpable. The public policy problem is especially vexing when medical science is ahead of the regulatory decisionmaking. A pharmaceutical company is, according to the government, breaking the law if it truthfully states "Medical journal M published a study showing that drug D is effective in treating problem X," or even just distributes a copy of the published study. Forbidding the dissemination of truthful information has obvious First Amendment implications, but no pharmaceutical company dares litigate the issue: even aside from the possible consequences of bureaucratic retaliation by speaking out against regulators' power, the same threat of debilitating debarment makes it economically irrational to risk the randomness of the civil justice system, even if the drug company thinks it has a 95% chance of prevailing. This costs lives, as medicine moves faster than the over-cautious regulators do.

Until now. Alfred Caronia, a pharmaceutical sales representative, promoted the narcolepsy drug Xyrem to doctors for unapproved uses and subpopulations, such as "extended daytime sleepiness"—a use later approved by the FDA. His, employer, Jazz Pharmaceuticals, quickly settled for a $20 million fine, but Caronia faced criminal prosecution. He fought the law, was convicted, and appealed.

On appeal, argued in 2010, the Second Circuit reversed yesterday on First Amendment grounds in a 2-1 decision. Beck has thorough analysis that we won't repeat. Also: Gottlieb @ AEI; Bashman link roundup; and I'm sure MI's Medical Progress Today will have something to say.

Gottlieb writes that the decision "should prompt FDA to come up with a more balanced approach that allows findings from scientific studies to be disseminated even if these results aren't in the FDA-approved label and haven't met the agency's high bar." "Should," perhaps, but I'm skeptical about "will." The DOJ and FDA will fight Caronia through at least two more levels of appeal, and the economics of pharmaceutical companies refusing to fight the question means that the FDA and federal prosecutors have no incentive not to continue to overreach: they'll just bring their cases in one of the 47 states not bound by the Second Circuit.


Doctors have prescribed drugs for "off label" uses for decades. This would be the use of a drug for a non-FDA approved disease or condition. Sometimes, the drug may be approved in another country for a certain use, but not in the US. Or there may be a long tradition of treatment which has never had official FDA recognition.

So long as a doctor follows a legitimate "school of thought," claims of substandard care a unlikely to succeed, even in the absence of FDA approval. A "school of thought" is defined as a group of physicians who practice in a certain way (in this case, using a drug in an "off label" manner), who meet to discuss treatment options, and carry on credible research which is published in peer reviewed journals of international circulation which are generally available, and disseminate that information at meetings and in other formats.

Whether it is appropriate for drug reps to participate in this kind of activity can be argued either way.

In the last twenty years, an opposite problem has emerged. It involves famous professors in medical schools starting their own drug companies, then carrying out studies which have a veneer of reliability, then publishing the results in the most famous and prominent medical journals. Since the "peer review" boards on these journals are all inbred, it is easy for phoney-baloney studies to get published. In the mean time, the professors cash in big time selling drugs of questionable efficacy.

Or drug companies will hire a famous professor to "oversee" the study of the drug, done at pharmaceutical expense. Of course the study will show the drug to be much superior than some less expensive drug.

Recently, there has been a movement by the FDA to remove all drugs from the market which do not have "official" status. Examples are seen in colchicine which is an ancient treatment for gout. It could be purchased for a few cents a pill. But the FDA removed it, replacing it with an expensive gout preparation of colchicine costing a small fortune. Maybe you have seen it advertised on TV. That pill has official "recognition" by the FDA.

Another example is quinine which has been used for centuries for leg cramps. It is off the market.

The drug companies have argued for years they can't make money selling the "old" drugs which have been used forever and are cheap. So they are being removed and replaced with expensive preparations which are essentially the same thing, but cost a lot more.

I posted the comment shown supra on the Medscape blog entry concerning this case. This response by a neurologist was posted in regard to my comment. (RLS is Restless Leg Syndrome. Plasmodium falciparum is malaria.):

Comment: "Another example is quinine which has been used for centuries for leg cramps. It is off the market."

Quinine is a unique example. It is not off the market (Qualaquin, AR Scientific 324 mg capsules).

The FDA took up the cause to squash off label use of quinine when expensive dopamine agonist drugs became indicated for RLS. I saw a FDA report back in 2006 or 2007 that showed over the previous 15 or 20 years there were POSSIBLY 70 or so deaths associated with quinine use. Then between 2005 and 2008 there were 34 adverse events including 5 deaths. Their logic was that the drug was "too dangerous" to be used for anything but the labeled indication of symptomatically treating Plasmodium falciparum infections. Never mind the 20,000 deaths per year that are attributed to NSAIDS. As far as I'm concerned, any drug that kills less than a hundred people over decades of use is a safe drug compared to many other medications that are commonly used.

I stand corrected on this but my understanding is that we can still prescribe quinine for off label use. However, the FDA criminalizes this and prevents domestic sales by the prosecutorial threat that will occur if a pharmacist dispenses quinine for any medical use aside for treatment of malaria. Bottom line is that you can continue to prescribe it but patients can't get it dispensed at licensed pharmacies for anything other than malaria.

In my experience, the dopamine agonists can be quite helpful for RLS and PLMD's, albeit with side effects for many. But patients with ol' fashioned nocturnal leg cramps don't get the relief from dopamine agonists that they did from quinine. In many cases the dopamine agonist provide no benefit for nocturnal leg cramps.

So the end result of the FDA's efforts is that domestic internet purchases from foreign vendors for quinine have increased.

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Rafael Mangual
Project Manager,
Legal Policy

Manhattan Institute


Published by the Manhattan Institute

The Manhattan Insitute's Center for Legal Policy.