Off-label marketing and the First Amendment.

O December 3, 2012, a three­ judge panel of a U.S. appeals court took a controversial leap toward what some fear will be license by the courts to invalidate a host of state and federal regu­ lations, including some applica­ ble to health care. In recent years, the Supreme Court has broadened the reach of the First Amend­ ment, defining “protected speech” in such a way as to curtail or eliminate certain familiar govern­ mental restraints. (See table for an overview of cases related to commercial speech and the phar­ maceutical industry.) At issue in the December 3 opinion — which is doubtless headed for further appeal — were the Food and Drug Administration (FDA) regu­ lations applicable to marketing of prescription pharmaceuticals for off­label uses. Overturning the conviction of a sales representa­ tive who was found to have en­ gaged in off­label promotion of a prescription drug, a three­judge panel of the U.S. Court of Ap­ peals for the Second Circuit (New York) held in United States v. Caronia that “the government cannot prosecute pharmaceutical manufacturers and their represen­ tatives under the [Food, Drug, and Cosmetic Act] for speech promot­ ing the lawful, off­label use of an FDA­approved drug.”1 In 2011, in Sorrell v. IMS Health,2 the precursor to Caronia, the U.S. Supreme Court held that a phar­ maceutical marketing tool known as data mining — purchasing in­ formation about prescribers from pharmacies and others and sell­ ing it to pharmaceutical compa­ nies — may be protected by the First Amendment, and the Court invalidated a Vermont law that prohibited the practice. Just a year earlier, in a similar expan­ sion of First Amendment protec­ tions, the Court had overturned portions of the McCain–Feingold Act, which limited the spending of tax­exempt political organiza­ tions, holding that campaign con­ tributions may constitute com­ mercial speech that is entitled to the protection of the First Amend­ ment.3 Now, the Second Circuit has seized the first appellate op­ portunity since Sorrell to interpret that Supreme Court precedent in the context of FDA restrictions concerning off­label drug mar­ keting. Alfred Caronia, a pharma­ ceutical detailer, defended his off­label marketing with the argu­ ment that the FDA regulations prohibiting it infringed his First Amendment right of free speech and were therefore void. The FDA is vested with the re­ sponsibility of overseeing the safe­ ty of pharmaceutical production and the veracity of marketing. Its rigorous approval process requires that each new product be tested for safety and efficacy for each in­ tended use. Although FDA regu­ lations warn that it is considered “misbranding” for marketers to “recommend or suggest” that a drug is appropriate for an indica­ tion for which it has not specifi­ cally been approved, the FDA’s authority does not extend to the practice of medicine, and thus it cannot prohibit physicians from prescribing approved drugs for nonapproved uses. The Vermont law at issue in Sorrell permitted mining of physi­ cians’ prescribing data from pa­ tient information for some pur­ poses (e.g., research), but not for others (primarily marketing), in order to advance the state’s goal of limiting the promotion of ex­ pensive, brand­name products. The Supreme Court held that a law that constrains speech on the ba­ sis of its content and its speaker must be reviewed for First Amendment purposes, applying a standard of “heightened” con­ stitutional scrutiny. Although it acknowledged the importance of Vermont’s asserted interests in medical privacy and the reduction of health care costs, the Court nevertheless concluded that Ver­ mont’s data­mining prohibition unduly restricted free speech and was therefore unconstitutional. At the heart of Sorrell was the question of whether governments are permitted to enact regula­ tions, even those protecting the health of the public, that single out a particular industry (e.g., the pharmaceutical industry) and allow some messages (e.g., pro­ moting brand­name drugs for off­label uses) but not others. As noted in the dissent, traditional regulatory programs do, in fact, target particular industries, and when they are narrowly tailored to advance significant state ob­ jectives, they have generally been upheld. The key to passing con­ stitutional scrutiny is whether the law at issue discriminates on the basis of the content of the message. Disposing first of Vermont’s argument that data mining in­ volves conduct rather than speech, Sorrell held that the creation and Off-Label Marketing and the First Amendment