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U.S. v. Caronia: Second Circuit Holds that the First Amendment Protects Speech Promoting Off-Label Drug Use

Health Law Update Larry P. Cote

In a 2-1 decision, the Second Circuit Court of Appeals recently vacated the criminal conviction of a pharmaceutical sales representative who marketed a narcolepsy drug for "off-label" uses, or uses of the drug that had not been approved by the Food and Drug Administration ("FDA"). The court held that the conviction violated the sales representative's First Amendment right to free speech.

The FDA and Off-Label Drug Promotion

As you all know, a drug must be approved by the FDA for a particular use before it can be distributed into interstate commerce. Once approved, a physician is generally permitted to prescribe the drug for any use the physician deems appropriate in his or her medical judgment. The use of a drug for a purpose not approved by the FDA is referred to as "off-label use." Off-label use of a drug is not illegal. In fact, as the Caronia court noted, off-label use of a drug can have great potential public value and, in some instances, may even constitute "a medically-recognized standard of care." 

Despite the potential benefits of off-label use, the FDA has taken the position that drug manufacturers and their representatives may not promote off-label uses of a drug. According to the FDA, such promotion constitutes criminal "misbranding" in violation of the Food, Drug, and Cosmetic Act ("FDCA"). Specifically, the FDA contends that the promotion of off-label use is "misbranding" because the labeling of a drug never has adequate directions for the drug's off-label use.

Alfred Caronia and the Promotion of Xyrem

Alfred Caronia, a pharmaceutical sales representative, promoted the drug Xyrem for drug manufacturer Orphan Medical, Inc. (now known as Jazz Pharmaceutical). Xyrem is a powerful central nervous system depressant approved by the FDA to treat narcolepsy patients who experience cataplexy or excessive daytime sleepiness.[1] The FDA requires that the drug be accompanied by a "black box" warning, which indicates that the drug's safety has not been established in patients under 16 years of age.

In 2005 the federal government began investigating Orphan for off-label promotion of Xyrem. The investigation uncovered evidence that Caronia and Dr. Gleason, a physician hired by Orphan to promote Xyrem, were promoting the drug for unapproved uses. Specifically, the government obtained audio recording of Caronia telling a physician (who was working as a "government cooperator," posing as a Xyrem customer) that Xyrem could be used to treat Fibromyalgia, chronic fatigue, or chronic pain. Caronia also stated that Xyrem could be used with patients under the age of sixteen.

Caronia was ultimately indicted for violations of the FDCA. After a jury trial he was found guilty of conspiracy to introduce a misbranded drug into interstate commerce.

The Appeal

Caronia appealed, contending that his conviction violated his right of free speech under the First Amendment. He prevailed.

The court first rejected the government's argument that Caronia was not prosecuted for his speech and that instead his speech was used only as evidence of the intended use of the drug. The court explained that it was clear from the government's arguments at trial that Caronia was, in fact, prosecuted for his speech, and his speech did not merely play an evidentiary role in determining whether the drug was misbranded.

Next, the court turned to whether the criminalization of pharmaceutical manufacturers' speech promoting off-label use violates the First Amendment. Because the restriction on speech at issue here was content-based (no promotion of off-label uses, but promotion of FDA-approved uses is allowed) and speaker-based (pharmaceutical manufacturers only), the court subjected the restriction to a higher level of scrutiny. The court also noted that heightened scrutiny is appropriate because the statute imposes criminal penalties.

In its analysis of whether the First Amendment protected Caronia's speech, the court explained that Caronia's speech was not misleading, and it related to a lawful activity - the off-label use of a drug. The court next noted that although the government had a substantial interest in preserving the integrity of the drug approval process and reducing patient exposure to unsafe drugs, this prohibition on speech does not directly advance the government's goals. In fact, allowing off-label use, but prohibiting the dissemination of information related to that use, could inhibit informed and intelligent treatment decisions to the public's detriment. Finally, the court noted that the government's construction of the FDCA, which imposed a complete and criminal ban on off-label promotion by pharmaceutical manufacturers, is more extensive than necessary to achieve the government's goals. For example, instead of prohibiting this speech, the government could develop its warning systems or even prohibit particular off-label uses altogether. With this, the court held Caronia's conviction violated the First Amendment.


So what does this mean for pharmaceutical manufacturers? Can you finally share truthful and non-misleading information about off-label uses of drugs you manufacture? For most of you, the answer is not quite yet. This decision is only binding in the Second Circuit, which covers Connecticut, New York and Vermont.

In addition, the court did not address whether such speech can be relied on as evidence of the crime of introducing a misbranded drug. As discussed, the court concluded that the government did not use the speech as evidence but instead used it as the sole basis for Caronia's guilt. This means that evidence of speech promoting off-label use may still be used in criminal misbranding prosecutions.

Although the immediate impact of the decision is somewhat limited, this decision could change the direction of the government's enforcement agenda. For now, it is possible that the government may decide to focus its efforts on prosecuting those who engage in false or misleading marketing, instead of focusing on those who share truthful information about off-label use.

For more information, please contact Larry Cote at (202) 372-9524 / [email protected], Leah McNeely at (608) 283-2412 / [email protected] or your Quarles & Brady attorney.

[1] Cataplexy is a condition associated with weak or paralyzed muscles. Excessive daytime sleepiness is a neurological disorder caused by the brain's inability to regulate sleep-wake cycles.