If a drug’s label is not the final word on what is true – or untrue – about a product, then who decides what can and cannot be said during a sales detail?
[To listen to the full oral arguments given at the 2nd US Circuit Court of Appeals on December 2, 2010, which presaged the court's decision discussed below, click here.]
For as long as most of us can recall, without consulting the internet, the FDA has served as industry’s head arbiter of truth with respect to what can and cannot be said about a prescription drug’s safety and efficacy, at least in the US.
For pharmaceutical manufacturers selling products in the world’s largest drug market, if it’s not on the FDA-sanctioned drug label, it’s patently false or misleading, ipso facto. The 2nd US Circuit Court of Appeals, in its decision on US v. Caronia, calls FDA’s authority to regulate “truthful” commercial speech into question under the First Amendment.
While the Food, Drug and Cosmetic Act (FDCA) does not expressly prohibit off-label promotion, “government has treated [off-label] promotional speech as more than merely evidence of a drug’s intended use – it has construed the FDCA to prohibit [off-label] promotional speech as misbranding itself,” wrote US Circuit Judge Denny Chin, a President Obama appointee to the appeals court, in the majority opinion.
Beyond discussing off-label drug uses with colleagues, physicians can prescribe any medication for any medical condition they choose, regardless of what the drug’s label says. Academics, patients, and essentially anyone who isn’t a salaried employee of a pharmaceutical company, are also free to discuss off-label uses, to publish about them, and in the case of patients, to inject or ingest products off-label. In US v. Caronia, the appeals court found it unjust – under the First Amendment – that pharma marketers be left out of the conversation, so long as the information they’re sharing is true, and not false or misleading.
“One of the things this decision does is to switch the burden of proof,” says Alan Bennett, partner at the law firm Ropes & Gray, and a former attorney in FDA’s Office of the General Counsel. “It’s very easy to say something is off-label. This decision certainly maintains, as it should, that FDA has the authority to go after false or misleading speech. But I think it switches the burden of proof, so that FDA has to show that something is false or misleading rather than simply off-label.”
In the case of Alfred Caronia, a sales rep working for Orphan Medical (now Jazz Pharmaceuticals) and promoting Xyrem – a drug with gamma-hydroxybutryate (GHB) as its active ingredient, which is federally classified as the “date rape drug” – Caronia was caught on tape having discussions with physicians about a litany of off-label uses, including the suggestion that Xyrem might be used to treat fibromyalgia, periodic leg movement, restless leg and other muscle disorders, chronic pain, Parkinson’s disease and potentially multiple sclerosis. Xyrem’s label at the time contained only two indications: for patients with narcolepsy who experience cataplexy, and narcolepsy patients with excessive daytime sleepiness.
Whether or not Caronia’s off-label statements were “true” at the time of the speech, in 2005, or if they are true today for that matter, was not considered and did not have any bearing on the appellate court’s decision. The statements were assumed to be true, or true enough, and thus protected under the commercial speech doctrine and the First Amendment. Caronia was prosecuted under the strict language of the FDCA, which prohibits “introducing a misbranded drug into interstate commerce.”
The decision does not prevent government regulators from prosecuting other types of misbranding, such as the failure to present fair and balanced information in advertisements, for example, but if the decision stands – and Bennett says it’s too early to tell how this decision will shake out – it puts an end to the “blanket rule that says: off-label speech is a violation and by itself creates misbranding.”
For the sake of argument, let’s assume that the decision does stand, and drug labels lose their status as preeminent deciders of what in fact is true in relation to a prescribed medicine. How might regulators – and pharmaceutical companies – agree on what constitutes the truth?
“My guess is, the safest way for the FDA to assess truth would be to begin using the Federal Trade Commission (FTC) standard,” says John Kamp, executive director of the Coalition for Healthcare Communication, and a First Amendment advocate. “It’s safe, because it has been litigated under the First Amendment for 40 years.”
The FTC’s jurisdiction extends to over-the-counter (OTC) products, and the test it applies to assess whether speech is misleading is “quite a strict one,” says Lee Peeler, president and CEO of the National Advertising Review Council, and the FTC’s former deputy director of the Bureau of Consumer Protection. “If you conduct a test and find that [commercial speech] is misleading to 20 percent or more of the [targeted] consumers, then that has been held to be actionable under the FTC Act.”
Further, under the FTC Act, “speech is, per se, misleading if you don’t have competent, reliable scientific evidence supporting the claims that you’re making,” says Peeler. “You can’t go out and say things in advertisements – for laundry detergent, diapers, OTC drugs, whatever – unless you have good strong viable data showing that the claim as the consumer perceives it, is true.”
It’s not hard to imagine that regulators and pharmaceutical manufacturers, when it comes to marketing drugs to physicians, might disagree on what constitutes legitimate, or at least reliable, scientific data. Peeler says FTC “has a multi-pronged test that it uses to evaluate” the veracity of scientific data. “One of the key pieces of the test is that the data be of a quality and type that experts in the field would consider to be reliable,” says Peeler. “In a number of recent cases in the food and dietary supplement area, FTC has required two well-controlled clinical studies for any claims about the effectiveness of a product on the structure and function of the human body.”
Asked what does or should constitute – or better yet define – truthful versus misleading or false speech in the context of off-label discussions, PhRMA’s EVP and general counsel Mit Spears issued the following statement: “Federal jurisprudence provides a rich body of precedent, drawn from cases arising under the Lanham Act, FTC Act and a host of other statutory and regulatory regimes, that balances the rights of companies to engage in commercial speech with the consumer’s right to receive accurate and truthful information. As always, PhRMA stands ready to work with FDA to make sure that both patients and health care professionals receive timely and accurate information about medicines, which will improve health outcomes and protect patients.”
FDA and industry will need to come to an understanding on what exactly is needed to substantiate a product claim, if US v. Caronia holds up and product labeling isn’t the be-all and end-all conduit for truthfulness. The decision “should lead, I hope, to a thoughtful reassessment about the way the regulatory system [for pharmaceuticals] works,” says Bennett. “I do think there’s some information out there that’s outside of the technical four corners of the label that would be useful for physicians to have, and companies have the means to disseminate that information, as long as it’s truthful and not misleading.”
Indeed, under the “existing rules of the FDA, using comparative effectiveness research (CER) in marketing materials is most often illegal for companies,” says Kamp, due to the fact that CER is compiled after a drug and its label hit the market. “But it is not illegal for anyone else to use economic studies against companies.”
Bennett offers the example of treatment guidelines, which are “developed independently of companies, sometimes by government…and to say that everybody else can talk about that information, and that it’s good information, but that the company itself can’t talk about it, that doesn’t seem like a great system.”
In off-label conversations, though, it’s usually the pharmaceutical rep that has more skin in the game, financially speaking. Based on recent Supreme Court decisions, including Sorrell v. IMS Health – which is referenced and relied upon heavily in the US v. Caronia majority opinion – the contemporary system of American jurisprudence seems willing to overlook the financial motives which often lead to speech, and any questions of inherent bias therein, so long as the content of the speech in question meets muster. In the age of big data, it will be interesting to see how regulators and industry collaborate to produce an acceptable truth for everyone else.