Big pharma wins a battle on off-label prescribing

There’s a phenomenon known as off-label prescribing. Basically, to prescribe something off-label is to prescribe it for an indication that is not FDA-approved but that is supported by considerable evidence. For example, it could involve using an FDA-approved drug for an indication that is not within its approval, for an unapproved age range (such as children), or at an unapproved dose or in an unapproved form. Although the FDA has the power to approve drugs for specific indications, it doesn’t actually have the power to regulate the practice of medicine, which means that physicians can use drugs off-label for indications when they think it will benefit the patient and it is completely legal. off-label prescribing is very common and often beneficial. However, there is always the potential for harm as indications for the use of a drug expands beyond its original FDA-approved indication.

The one thing that the FDA has been able to do to regulate the off-label use of drugs is through the Office of Prescription Drug Promotion (OPDP, formerly the Division for Drug Marketing, Advertisement and Communication (DDMAC). In essence, the FDA can regulate drug promotion, and traditionally the FDA has forbidden drug companies from promoting off-label uses of their drugs. Basically, drug companies have been unable to advertise their drugs or promote them to doctors for use off-label, and the FDA has gone after drug companies that have tried to promote off-label uses of their products, particularly through encouraging doctors to use them that way.

Possibly until now:

In a case that could have broad ramifications for the pharmaceutical industry, a federal appeals court on Monday threw out the conviction of a sales representative who sold a drug for uses not approved by the Food and Drug Administration. The judges said that the ban on so-called off-label marketing violated the representative’s freedom of speech.

The 2-to-1 decision by a three-judge panel of the Court of Appeals for the Second Circuit in Manhattan addresses a long-running and costly issue for the industry, which has paid billions of dollars in penalties to the federal government in recent years after being accused of marketing blockbuster drugs for off-label uses.

In July, for example, the British drug maker GlaxoSmithKline agreed to pay $3 billion in fines, in part for promoting antidepressants and other drugs for unapproved uses; a month later, Johnson & Johnson announced that its pharmaceutical unit had reached a $181 million consumer fraud settlement with 36 states and the District of Columbia over its marketing of Risperdal, an antipsychotic drug.

The case, United States v. Caronia, involved the conviction of a man named Alfred Caronia, who was a sales rep for Orphan Medical. He was selling Xyrem, a drug approved for narcolepsy and was convicted of promoting it as a treatment for conditions such as insomnia, fibromyalgia. Caronia appealed his conviction by arguing that his First Amendment right to free speech was illegally restricted when he was prevented from promoting legal uses for a drug. The ruling only applies to the the Second Circuit (New York, Connecticut, and Vermont), but it’s very possible that the case could find its way to the U.S. Supreme Court.

It’s actually a very interesting legal and philosophical question to ask whether it violates the First Amendment to restrict companies from promoting legal uses of their products. At least, it is as an intellectual exercise. As public policy, it’s a disaster, as the lone dissenting judge points out:

“The government clearly prosecuted Caronia for his words — for his speech,” the majority wrote, concluding later “the government cannot prosecute pharmaceutical manufacturers and their representatives under the F.D.C.A. for speech promoting the lawful, off-label use of an F.D.A.-approved drug.”

The lone dissenting judge, Judge Debra Ann Livingston, vigorously disagreed, arguing that by throwing out Mr. Caronia’s conviction “the majority calls into question the very foundations of our century-old system of drug regulation.” She argued that if drug companies “were allowed to promote F.D.A.-approved drugs for nonapproved uses, they would have little incentive to seek F.D.A. approval for those uses.”

Indeed. I’ve actually pointed out a similar principle with respect to allowing wider access to drugs for cancer patients. If drug companies were permitted to sell, for instance, drugs that had only passed phase I trials, there would be no incentive to do the phase II and III trials to prove efficacy and win FDA approval. In any case, it’s not surprising that pharmaceutical companies are “pleased” with the ruling. Actually, they’re more than pleased with it; they’re practically salivating over the opportunity to market their drugs for indications that go beyond what the FDA has approved. It’s not clear whether this ruling will end up being generalized, but it is clear that it is likely to go to the Supreme Court, as Pharmalot explains. If the Supreme Court sides with the ruling, then it’s possible that drug companies will have more freedom for direct-to-consumer advertising. One thing’s for sure, if this ruling stands you can be very sure that the FDA will be even more constrained than it already is, because it will then have to prove that the statements being used to promote the drug for off-label use are actually false or misleading.

In fact, the problem with this ruling is that it would make it very difficult to know when advertising for off-label uses crosses the line. As long as it’s not illegal for a doctor to prescribe drugs for off-label uses, then it’s much harder to show that promoting off-label prescribing is “false or misleading.” The only way to fix the problem would be to revise the Food and Drug Act to eliminate the loophole, and that itself could have unintended consequences.

There’s also another group besides big pharma that could like this ruling, and like it a lot. Can you guess who it is? Let’s wander on over to the Alliance for Natural Health website, a major trade group for supplement manufacturers, and see the headline Free Speech Court Ruling Could Have Far-reaching Consequences, in which the ANH-USA proclaims:

Big Pharma seems to be the winner. But this could open the door for natural health companies to cite truthful science about supplements.

As we have noted before, the FDA thinks that “misbranding” can mean making a completely true statement about a product but without FDA permission. The FDA is definitely not a fan of free speech.

A cherry producer who cites peer-reviewed scientific research from prestigious universities on the health benefits of cherries would, in FDA-speak, have engaged in “false” and actionable “misbranding” which suddenly turns the cherries into what FDA calls “drugs.” It’s because of this “misbranding” threat that supplement producers are not allowed to discuss scientific research on the efficacy of their products.

And concludes:

The Pharmaceutical Research and Manufacturers of America (PhRMA), a trade group representing the drug companies, was of course pleased with the decision. A spokesperson says saying PhRMA “believes that truthful and non-misleading communication between biopharmaceutical companies and healthcare professionals is good for patients, because it facilitates the exchange of up-to-date and scientifically accurate information about new treatments.”

Now remove the word “biopharmaceutical” in the above quote and put “supplement” in its place. The sword that is our freedom of speech cuts both ways!

I can actually see supplement manufacturers also salivating over this ruling. One of the biggest marketing ploys favored by supplement manufacturers. Basically, they cherry pick the literature and find scientific studies, no matter how dubious, to support their use of supplements, and if they can’t find anything they tend to make them up. There is a little fly in the proverbial ointment here, though: The DSHEA of 1994. Supplements don’t have to have FDA approval. On the other hand, even the minimal to nonexistent regulation of dietary supplements that does exist chafes at the supplement manufacturers. That regulation consists of rules saying that they can’t make specific health claims for their supplements, claims that fall under the rubric of drug claims, and can only restrict their claims to relatively vague “structure-function” claims.

How supplement manufacturers would fare if they tried to make the same free speech argument that big pharma has made in a court of law is not known. However, it is very striking just how similar the arguments made by pharma over this case are to free speech argument arguments that supplement manufacturers have been making as they railed against the DSHEA. Or maybe it’s that pharma has learned from supplement manufacturers. At their core, the two industries are much more similar than the “natural” supplement industry would ever care to admit.