The First Amendment to the U.S. Constitution states in totality, “Congress shall make no law respecting an establishment of religion, or prohibiting the free exercise thereof; or abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.” This freedom of speech, so often cited, is not absolute. For example, you cannot legally yell, “Fire!” in a crowded movie theater, intentionally publish untruthful facts about another person, or untruthfully advertise commercial products.
Recently, commercial speech has been the center of much debate in medical-legal circles.
Historical Review
The Food and Drug Administration (FDA) received its congressional power to regulate medicines and medical devices through the Federal Food, Drug, and Cosmetic Act (FFDCA) of 1938.1 Through this act, the FDA controls the commercialization of new medical products through a rigorous multistage approval process. The process not only allows entry of products into the stream of commerce but also determines the labeling of those products. Product labeling articulates the specifically approved uses supported by previously performed medical research, along with side effects and other precautions to be considered. Unapproved indications or off-label uses communicated in the product labeling will identify the product as being mislabeled or misbranded and subject the manufacturer to FDA scrutiny and penalties. Although the approval process may yield additional product benefits, only FDA-approved indications are permitted on the label.
The FDA recognized that significant costs and lengthy approval times precluded many manufacturers from pursuing additional useful indications for their medical products. As such, the FDA introduced the FDA Modernization Act (FDAMA) of 1997, which allowed manufacturers to disseminate literature and have discussions regarding off-label uses of its medical products. Unfortunately, any communications regarding off-label uses had to occur following the filing or imminent filing of a supplemental new drug application (sNDA).
Until recently, discussions of off-label uses between pharmaceutical representatives and medical professionals outside the scope of the FDAMA were considered criminal offenses. Dissemination of off-label medical product usages were limited to discussions at non-pharmaceutical-sponsored continuing medical education events, independent drug compendia resources, peer-reviewed journal articles, and other non-pharmaceutical manufacturer internet resources.
Recent Developments
All this changed in 2017 when the Arizona legislature passed HB 2382, the Free Speech in Medicine Act. The law forbids punishment by any Arizona state agency of a pharmaceutical manufacturer, its representatives, or medical health professional for the “truthful promotion of an off-label use of a drug, biological product, or device.” Proponents of the bill touted the free speech protections of the First Amendment that should allow such open conversations and the ability to freely pass along any beneficial alternate uses of the medical products as foundational support for its adoption.2
Opponents of the law feared drug makers would use the off-label pathway as an easier route to widespread drug adoption without the rigorous oversight of the traditional multistage FDA approval process. Challengers to the law also opined that the pharmaceutical industry would be disincentivized to share adverse medical information regarding off-label uses, culminating in another Fen-Phen disaster.
In any event, the Arizona law received the attention of many other state legislatures that ultimately moved to pass their own versions of the Free Speech in Medicine Act. Missouri, Mississippi, Tennessee, and Colorado have recently proposed similar versions of the Arizona law, but only Tennessee’s version had become law at press time.
The federal courts have similarly ruled favorably for the pharmaceutical industry when it has been prosecuted under the off-label restrictions of the FFDCA. In United States v. Caronia, an appeals court overturned the lower district court’s conviction of a pharmaceutical representative who had discussed off-label usages of a previously FDA-approved narcolepsy drug, Xyrem. The court held, “The government cannot prosecute pharmaceutical manufacturers and their representatives under the FFDCA for speech promoting the lawful, off-label use of an FDA-approved drug.”3 The U.S. Court of Appeals for the Second Circuit further clarified that any false or misleading promotions would not be entitled to similar First Amendment protections.
In contrast to the defensive posture of the defendant in the Caronia case, Amarin Pharmaceuticals went on the offensive against the FDA in Amarin Pharma, Inc. v. United States FDA, after the FDA failed to approve one of its cholesterol medications for extended indications. The FDA insisted it would consider the drug misbranded should Amarin elect to share any of its favorable research data with physicians.4 In Amarin, the district court dealt another blow to the FDA by reaffirming its earlier findings in Caronia—that is, that First Amendment commercial speech protections apply to truthful and non-misleading speech.
So the next time your favorite drug rep comes calling, feel free to discuss off-label uses of their medical products. You may be quite surprised to learn some of your colleagues have found some novel and helpful uses for common medications and/or medical devices in your emergency department.
Note: No information within this report should be construed as medical or legal advice. Independent medical and/or legal advice should be sought based on each individual’s particular circumstances.
Dr. Totz is facility medical director at First Choice Emergency Room at Adeptus Health in Texas.
References
- Ventola CL. Off-label drug information: regulation, distribution, evaluation, and related controversies. P T. 2009;34(8):428-440.
- Adams RK, Crudele L. The eroding off-label drug use promotion prohibition. J Health Life Sci Law. 2019;12(2):1-20.
- Sullivan T. US v. Caronia, one year later: FDA’s position on off-label promotion remains the same, but changes are looming. May 6, 2018. Policy & Medicine website. Accessed April 10, 2019.
- Amarin Pharma, Inc. v. FDA. Harvard Law Rev. 2016;29(7):2021-2028.
Pages: 1 2 | Multi-Page
No Responses to “U.S. Constitution vs. FDA: Off-Label Discussions No Longer Faux Pas?”