Peer-reviewed articles about off-label use of approved drugs are ALLOWED by FDA to be distributed from companies to physicians. FDA relinquished control of dissemination of scientific/clinical data regarding off-label use long time ago.

If you search recent legal cases about off-label use in the U.S., you may find that the pharmaceutical companies gained quite a few court battles using the First Amendment protection on commercial speech.

Previously FDA and DOJ were able to prosecute companies who were caught promoting off-label use of their drugs illegally to physicians. In 2011, the Supreme Court’s decision in Sorrell v. IMS Health laid down the legal foundation for pharmaceutical companies to wrestle with the FDA over the control of the promotion of off-label use. In Sorrell, the issue was the constitutionality of a Vermont statute which restricted drug companies to purchase patient data for subsequent use in their product marketing campaigns, in particular, a Vermont law prohibiting the sale and use of such data. The Court held that such prohibition is unconstitutional because the statute imposed both content- and speaker-based burdens on a protected speech and a heightened level for First Amendment scrutiny was warranted. By applying the Central Hudson’s commercial speech inquiry, the Court found that the Vermont law did not advance the stated goals of achieving the state’s policy objectives to protect medical privacy. In the opinion, both the majority and the dissent acknowledged that the heightened level of scrutiny applied to commercial speech has implications for the FDA’s prohibition of off-babel marketing practice by the pharmaceutical industry. The key take-away message from the Sorrell decision is that the heightened First Amendment scrutiny may provide the legal challenge against FDA’s control over off-label promotion under circumstances where a pharmaceutical company is proposing truthful and non-misleading information about its drug.

Following the framework laid out in Sorrell, the U.S. Court of Appeals for the Second Circuit determined that the prosecution of truthful speech though the misbranding provisions in the Food, Drug, and Cosmetic Act (“FD&C Act”) is unconstitutional and a violation of the First Amendment. In United States v. Caronia, the defendant Caronia was a pharmaceutical sales representative for Orphan Medical, Inc., which manufactures the drug Xyrem. She was charged with and convicted of misdemeanor conspiracy related to the off-label promotion of Xyrem. The thrust of the Caronia decision was that the speech by Caronia served as evidence of intent to misbrand according to the State, and the misbranding provisions of the FD&C Act represented both content- and speaker-based restrictions. Therefore, the court employed the lesser Central Hudson test and determined that the State’s interest were not directly advanced, nor were they narrowly drawn, to achieve the State’s objectives because the speech was truthful and non-misleading. In addition, the court held that the FDA regulations were not narrowly drawn because other options would appropriately achieve the State’s interest.

In 2013, the United States Court of Appeals for the Ninth Circuit affirmed the conviction of W. Scott Harkonen, who had been tried by a jury for charges of wire fraud and misbranding under FD&C Act for issuing a fraudulent press release regarding the results of a clinical trial. He was convicted of wire fraud. But the same jury acquitted Harkonen of distribution of a misbranded drug with intent to defraud or mislead. Harkonen was a medical doctor and the CEO of InterMune. InterMune was the manufacturer of Actimmune, a drug approved for treating severe osteoporosis but not for treating idiopathic pulmonary fibrosis (IPF). In 2002 InterMune conducted a clinical trial in patients targeting IPF, the results of which had missed the study’s primary endpoint and all ten of the secondary endpoints. Nonetheless Harkonen directed InterMune to issue a press release which touted the results of the IPF trial with the headline of “InterMune announces Phase III data demonstrating survival benefit of Actimmune in IPF,” and stated that Actimmune had demonstrated “a significant survival benefit” in certain patient populations. On appeal against the wire fraud conviction, Harkonen claimed that the press releases and communication about Actimmune’s efficacy for treating IPF were arguably protected under the First Amendment. In its opinion, the Ninth Circuit stated that “[t]he First Amendment does not protect fraudulent speech . . . so the core constitutional issue in Harkonen's case is whether the facts the jury found establish that the Press Release was fraudulent.” The court then concluded that the jury's findings that “the Press Release was misleading, that Harkonen knew it was misleading, and that Harkonen had the specific intent to defraud,” were supported by “sufficient evidence,” and therefore affirmed Harkonen's conviction. In particular, the court rejected Harkonen's argument that he was “engaging in a genuine scientific debate” and that “genuine debates of any sort are, by definition, [are] not fraudulent.”

The implications of the Circuit Court Decisions:

1) On the one hand, because the Caronia decision was essentially a death knell of FDA’s contention that it regulations prohibiting any off-label promotion by the pharmaceutical companies are essential to maintaining the integrity of its rigorous drug approval process, it provides a powerful defense for both pharmaceutical companies and their employees in cases built on misbranding charges if their speech and communication promoting off-label use are truthful and non-misleading.

2) On the other hand, the Harkonen decision highlights that the First Amendment protection of the promotional speech for off-label use is qualified in that speech has to be truthful and non-misleading, at least in the context of a wire fraud charge. As the Ninth Circuit stated in Harkonen, “the First Amendment does not protect fraudulent speech.” What remains to be seen is that whether the First Amendment protects a fraudulent speech in a misbranding charge under the FD&C Act. Although I doubt that it would be the case, the Harkonen court did not have a chance to review that question because the jury acquitted Harkonen of the misbranding charge.

3) While the Caronia decision left the enforcement of the FD&C Act’s misbranding provisions on shaky ground, the Harkonen decision buttressed the FDA’s ability to keep regulating misleading off-label promotion and pursuing the corresponding violations without fearing the First Amendment defense argument. The FDA still maintains its tight grip on false or misleading promotion of off-label use of approved drugs. But the fact that the jury in Harkonen did not convict Harkonen of misbranding or the illegal off-label promotion charge, put serious doubt on FDA’s future enforcement of prohibiting off-label promotion conducts by the pharmaceutical companies and its representatives.