Orthopedic Medical Legal Advisor

The question of off-label drug promotion vs free speech

The FDA prohibits promotional statements by pharmaceutical companies and their sales staff concerning drug or device uses that are not specifically approved by the federal agency. When the FDA grants approval for a specific application of a drug or device, any use outside the scope of the approval is deemed off-label. However, off-label use of a drug or device is a matter of physician and patient discretion and judgment. Indeed, the FDA has clarified that its regulatory scheme is not an attempt to practice medicine.

Accordingly, despite the negative connotation of the term, off-label use is relatively common among physicians and, in many instances, has benefitted patients and industry alike by identifying additional, useful indications for a drug or device. Once a useful and commercially attractive use of a drug is thus identified, the manufacturer can apply for expanded approval and labeling, and market the drug for those additional uses. However, pharmaceutical manufacturers are prohibited from promoting their drugs to health care professionals for off-label uses. Doing so results in the marketing of an unapproved and misbranded drug product, both of which are criminal offenses. Off-label statements by manufacturers and their sales staff, i.e., those statements that go beyond what is stated on the drug container, are prohibited in all forms. Exceptions exist to allow dissemination of certain off-label scientific information, but the promotion and advertisement of off-label use is prohibited in any form.

The first amendment states, “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.”

Because prohibitions on free speech run afoul of the first amendment, a number of legal cases have addressed the limits of the FDA power to restrict companies and their representatives from speaking to doctors about off-label use. The basic argument is that if off-label use of a drug is legal, then talking about off-label use should be protected under the first amendment. We examine two legal cases to understand the legal perspectives relating to free speech vs. off-label restrictions.

United States v. Caronia

Alfred Caronia, a sales representative for Orphan Medical Inc., a company acquired by Jazz Pharmaceuticals in 2005, was convicted in 2008 for conspiracy to misbrand the drug Xyrem, as a result of arranging for off-label statements by a promotional speaker. Orphan made a drug called Xyrem, a powerful central nervous system depressant, with serious adverse events and addictive potential such that the FDA required a black box warning to accompany the drug.

 

B. Sonny Bal

 

Lawrence H. Brenner

Caronia’s compensation depended on sales volume. He organized speaker programs to promote Xyrem, hiring physicians to talk about the drug. Under Orphan’s procedures, when Caronia was asked about off-label use of Xyrem, he was not permitted to answer. Instead, sales consultants were required to fill out medical information request forms and send them to Orphan for answers. Suspecting that Caronia was promoting off-label use of Xyrem for indications and patient subpopulations beyond those approved by the FDA, the government hired physician collaborators who posed as prospective Xyrem customers.

In audiotaped evidence, the government showed proof that Caronia conspired to misbrand Xyrem. In 2010, Caronia was convicted at jury trial and sentenced to 1 year probation, 100 hours of community service and a $25 fine. He appealed this conviction to the U.S. Court of Appeals, 2nd Circuit. The ruling in that court would invoke a decision of the U.S. Supreme Court, in a case titled Sorrell v. IMS Health Inc.

Sorrell v. IMS Health Inc.

Sorrell v. IMS Health Inc. was a 2011 legal case in which the Supreme Court held that a Vermont statute that restricted the sale, disclosure and use of records pertaining to the prescribing practices of individual doctors violated the first amendment. A few years before, the Vermont legislature had passed the Prescription Confidentiality Law that required, among other things, that records containing a physician’s prescribing practices could not be sold or used for marketing purposes without the physicians’ consent. The Prescription Confidentiality Act had been urged by lobbying efforts of the Vermont Medical Society. The medical society found that the marketing practices of large pharmaceutical companies relied, in large part, on data related to individual physicians’ prescribing habits and that this information was being sold to companies by state pharmacies without the physicians’ consent.

In the litigation that followed, the pharmaceutical companies and data mining services complained that the Vermont statute violated their first amendment free speech rights, and they sought declaratory and injunctive relief against Vermont officials. The U.S. District Court in Vermont denied relief, but the U.S. Court of Appeals for the 2nd Circuit reversed, holding that the Vermont law did in fact violate the first amendment by restricting the speech of pharmaceutical companies without adequate justification. The Supreme Court took up the case to resolve this conflict among federal court rulings and clarify the issue.

In the Sorrell ruling, Justice Anthony Kennedy delivered the majority opinion, joined by Chief Justice Roberts, justices Scalia, Thomas, Alito and Sotomayor. The court affirmed the judgment of the court of appeals, holding that the Vermont law violated the first amendment. Noting that the law placed content- and speaker-based restrictions on speech by specifically targeting marketing efforts by pharmaceutical companies, the court applied a heightened scrutiny standard and struck down the Vermont statute. The court observed that Vermont had not demonstrated a substantial government interest in imposing its restriction, and that the statute was not targeted at commercial regulation. Vermont’s argument that the law was necessary to protect medical privacy and achieve improved public healthcare was insufficient, in the court’s view. The dissent (justices Breyer, Ginsburg and Kagan) saw the Vermont law as acceptable economic regulation, with a small, incidental harm to first amendment interests.

Sorrell and off-label use

The Sorrell decision did not directly address off-label promotion of a drug or device, but it opened the door for further first amendment challenges. The language of Sorrell is particularly important for the medical profession, where professional interests, specialized knowledge and consumer protection are legitimate, and sometimes competing concerns. The court explained that:

“Those who seek to censor or burden free expression often assert that disfavored speech has adverse effects. But the fear that people would make bad decisions if given truthful information cannot justify content based burdens on speech. The first amendment directs us to be especially skeptical of regulations that seek to keep people in the dark for what the government perceives to be their own good. These precepts apply with full force when the audience, in this case prescribing physicians, consists of sophisticated and experienced consumers.”

“…There are divergent views regarding detailing and the prescription of brand-name drugs. Under the constitution, resolution of that debate must result from free and uninhibited speech. As one Vermont physician put it: ‘We have a saying in medicine, information is power. And the more you know, or anyone knows, the better decisions can be made.’ There are similar sayings in law, including that ‘information is not in itself harmful, that people will perceive their own best interests if only they are well enough informed, and that the best means to that end is to open the channels of communication rather than to close them.’ The choice between the dangers of suppressing information and the dangers of its misuse if it is freely available is one that the first amendment makes for us.”

These statements appear to set the stage for a Supreme Court challenge to the prohibition of off-label promotion. In fact, dissenting Justice Breyer acknowledged as much when he cited the FDA’s promotional regulations and stated, “If the court means to create constitutional barriers to regulatory rules that might affect the content of a commercial message, it has embarked upon an unprecedented task — a task that threatens significant judicial interference with widely accepted regulatory activity.”

Caronia appeal and dissent

In the 2nd Circuit, Caronia challenged the ruling of the trial court below that his first amendment rights were not violated. He argued that the FDA’s misbranding position was too restrictive and unconstitutional since it was not narrowly tailored to protect his constitutional rights. Generally, reasonable restrictions on constitutional rights are permissible if the government tailors them narrowly enough to protect some compelling government or societal interest. Caronia argued that the first amendment does not permit the government to prohibit and criminalize a pharmaceutical manufacturer’s truthful and non-misleading promotion of an FDA-approved drug to physicians for off-label use, where such use is not itself illegal, and others are permitted to engage in such speech. In a 2-1 decision, the panel vacated the conviction of Caronia and remanded the case to the district court.

The timing of litigation was such that Caronia’s appeal came just before the Supreme Court ruling in Sorrell, and accordingly, parties in the Caronia case submitted supplemental arguments derived from the Sorrell decision. For example, the Medical Information Working Group, a coalition of medical and device manufacturers, filed an amicus curiae brief in support of Caronia, arguing that the Sorrell opinion should apply to Caronia’s speech, thereby protecting it under the first amendment. Indeed, the U.S. Court of Appeals for the 2nd Circuit itself acknowledged that it had the benefit of the Sorrell opinion, something that was not available to the district court.

Dissenting Circuit Judge Debra Livingston would have upheld the district court’s conviction of Caronia, and she distinguished Sorrell from Caronia. According to Livingston, Sorrell targeted speech directly, in that as soon as a pharmacy in Vermont released a list of prescribing doctors to a pharmaceutical or data mining company, it ran afoul of the Vermont statute. Judge Livingston remarked that consistent with the first amendment, otherwise permissible conduct may become impermissible if undertaken with a prohibited motive, and speech may be used as evidence of such a motive.

Caronia had argued that he merely discussed a perfectly lawful practice, i.e., the use of a lawful drug, Xyrem, for off-label purposes. Justice Livingston disagreed and said that simply because a patient or doctor can legally use Xyrem for an off-label purpose is not enough to make out a sales rep’s first amendment claim. Citing the Warner Bros. film, Arsenic and Old Lace, she said that there is no law forbidding the consumption of arsenic. But this would not endow the film characters Abby and Martha Brewster with a first amendment right to offer arsenic-laced wine to lonely old bachelors with the intent that they drink it.

In other words, in the view of the dissenting judge, there was more to Caronia than a mere violation of a sales rep’s free speech constitutional rights; there was intent to misbrand a drug and introduce it into interstate commerce, which is criminal conduct. If drug manufacturers have a first amendment right to distribute drugs for any use to physicians, or even directly to patients, then the entire FDA regulatory scheme may well be unconstitutional. By vacating Caronia’s conviction, Judge Livingston said that “the majority calls into question the very foundations of our century-old system of drug regulation.”

Whether Caronia will reach the Supreme Court is yet to be seen, but the case is interesting in that it could bring profound changes in how drugs are promoted in the United States. What do you think of these rulings?

If the burden of off-label use and patient disclosure is subsumed in the doctor-patient relationship and the doctrine of informed consent, should pharmaceutical companies, device manufacturers and their sales staff not enjoy the first amendment freedom to promote their products without restraint?

Does aggressive promotion and marketing of a drug or medical device lead to such misinformation, confusion and unsafe conduct that the government should restrict the first amendment constitutional rights of targeted parties, such as the drug and medical device industry and their sales staff?

On a broader note, what is the price of freedom and liberty? Does our constitution assure our safety? Or does it assure only our liberty and freedom?

For more information:
B. Sonny Bal, MD, JD, MBA, and Lawrence H. Brenner, JD, are partners in the law firm of BalBrenner/Orthopedic Law Center and are the exclusive providers of loss prevention, risk management and quality improvement services for the Orthopedic Physician’s Insurance Company. Brenner can be reached at lbrenner@balbrenner.com.

The FDA prohibits promotional statements by pharmaceutical companies and their sales staff concerning drug or device uses that are not specifically approved by the federal agency. When the FDA grants approval for a specific application of a drug or device, any use outside the scope of the approval is deemed off-label. However, off-label use of a drug or device is a matter of physician and patient discretion and judgment. Indeed, the FDA has clarified that its regulatory scheme is not an attempt to practice medicine.

Accordingly, despite the negative connotation of the term, off-label use is relatively common among physicians and, in many instances, has benefitted patients and industry alike by identifying additional, useful indications for a drug or device. Once a useful and commercially attractive use of a drug is thus identified, the manufacturer can apply for expanded approval and labeling, and market the drug for those additional uses. However, pharmaceutical manufacturers are prohibited from promoting their drugs to health care professionals for off-label uses. Doing so results in the marketing of an unapproved and misbranded drug product, both of which are criminal offenses. Off-label statements by manufacturers and their sales staff, i.e., those statements that go beyond what is stated on the drug container, are prohibited in all forms. Exceptions exist to allow dissemination of certain off-label scientific information, but the promotion and advertisement of off-label use is prohibited in any form.

The first amendment states, “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.”

Because prohibitions on free speech run afoul of the first amendment, a number of legal cases have addressed the limits of the FDA power to restrict companies and their representatives from speaking to doctors about off-label use. The basic argument is that if off-label use of a drug is legal, then talking about off-label use should be protected under the first amendment. We examine two legal cases to understand the legal perspectives relating to free speech vs. off-label restrictions.

United States v. Caronia

Alfred Caronia, a sales representative for Orphan Medical Inc., a company acquired by Jazz Pharmaceuticals in 2005, was convicted in 2008 for conspiracy to misbrand the drug Xyrem, as a result of arranging for off-label statements by a promotional speaker. Orphan made a drug called Xyrem, a powerful central nervous system depressant, with serious adverse events and addictive potential such that the FDA required a black box warning to accompany the drug.

 

B. Sonny Bal

 

Lawrence H. Brenner

Caronia’s compensation depended on sales volume. He organized speaker programs to promote Xyrem, hiring physicians to talk about the drug. Under Orphan’s procedures, when Caronia was asked about off-label use of Xyrem, he was not permitted to answer. Instead, sales consultants were required to fill out medical information request forms and send them to Orphan for answers. Suspecting that Caronia was promoting off-label use of Xyrem for indications and patient subpopulations beyond those approved by the FDA, the government hired physician collaborators who posed as prospective Xyrem customers.

In audiotaped evidence, the government showed proof that Caronia conspired to misbrand Xyrem. In 2010, Caronia was convicted at jury trial and sentenced to 1 year probation, 100 hours of community service and a $25 fine. He appealed this conviction to the U.S. Court of Appeals, 2nd Circuit. The ruling in that court would invoke a decision of the U.S. Supreme Court, in a case titled Sorrell v. IMS Health Inc.

Sorrell v. IMS Health Inc.

Sorrell v. IMS Health Inc. was a 2011 legal case in which the Supreme Court held that a Vermont statute that restricted the sale, disclosure and use of records pertaining to the prescribing practices of individual doctors violated the first amendment. A few years before, the Vermont legislature had passed the Prescription Confidentiality Law that required, among other things, that records containing a physician’s prescribing practices could not be sold or used for marketing purposes without the physicians’ consent. The Prescription Confidentiality Act had been urged by lobbying efforts of the Vermont Medical Society. The medical society found that the marketing practices of large pharmaceutical companies relied, in large part, on data related to individual physicians’ prescribing habits and that this information was being sold to companies by state pharmacies without the physicians’ consent.

PAGE BREAK

In the litigation that followed, the pharmaceutical companies and data mining services complained that the Vermont statute violated their first amendment free speech rights, and they sought declaratory and injunctive relief against Vermont officials. The U.S. District Court in Vermont denied relief, but the U.S. Court of Appeals for the 2nd Circuit reversed, holding that the Vermont law did in fact violate the first amendment by restricting the speech of pharmaceutical companies without adequate justification. The Supreme Court took up the case to resolve this conflict among federal court rulings and clarify the issue.

In the Sorrell ruling, Justice Anthony Kennedy delivered the majority opinion, joined by Chief Justice Roberts, justices Scalia, Thomas, Alito and Sotomayor. The court affirmed the judgment of the court of appeals, holding that the Vermont law violated the first amendment. Noting that the law placed content- and speaker-based restrictions on speech by specifically targeting marketing efforts by pharmaceutical companies, the court applied a heightened scrutiny standard and struck down the Vermont statute. The court observed that Vermont had not demonstrated a substantial government interest in imposing its restriction, and that the statute was not targeted at commercial regulation. Vermont’s argument that the law was necessary to protect medical privacy and achieve improved public healthcare was insufficient, in the court’s view. The dissent (justices Breyer, Ginsburg and Kagan) saw the Vermont law as acceptable economic regulation, with a small, incidental harm to first amendment interests.

Sorrell and off-label use

The Sorrell decision did not directly address off-label promotion of a drug or device, but it opened the door for further first amendment challenges. The language of Sorrell is particularly important for the medical profession, where professional interests, specialized knowledge and consumer protection are legitimate, and sometimes competing concerns. The court explained that:

“Those who seek to censor or burden free expression often assert that disfavored speech has adverse effects. But the fear that people would make bad decisions if given truthful information cannot justify content based burdens on speech. The first amendment directs us to be especially skeptical of regulations that seek to keep people in the dark for what the government perceives to be their own good. These precepts apply with full force when the audience, in this case prescribing physicians, consists of sophisticated and experienced consumers.”

“…There are divergent views regarding detailing and the prescription of brand-name drugs. Under the constitution, resolution of that debate must result from free and uninhibited speech. As one Vermont physician put it: ‘We have a saying in medicine, information is power. And the more you know, or anyone knows, the better decisions can be made.’ There are similar sayings in law, including that ‘information is not in itself harmful, that people will perceive their own best interests if only they are well enough informed, and that the best means to that end is to open the channels of communication rather than to close them.’ The choice between the dangers of suppressing information and the dangers of its misuse if it is freely available is one that the first amendment makes for us.”

These statements appear to set the stage for a Supreme Court challenge to the prohibition of off-label promotion. In fact, dissenting Justice Breyer acknowledged as much when he cited the FDA’s promotional regulations and stated, “If the court means to create constitutional barriers to regulatory rules that might affect the content of a commercial message, it has embarked upon an unprecedented task — a task that threatens significant judicial interference with widely accepted regulatory activity.”

Caronia appeal and dissent

In the 2nd Circuit, Caronia challenged the ruling of the trial court below that his first amendment rights were not violated. He argued that the FDA’s misbranding position was too restrictive and unconstitutional since it was not narrowly tailored to protect his constitutional rights. Generally, reasonable restrictions on constitutional rights are permissible if the government tailors them narrowly enough to protect some compelling government or societal interest. Caronia argued that the first amendment does not permit the government to prohibit and criminalize a pharmaceutical manufacturer’s truthful and non-misleading promotion of an FDA-approved drug to physicians for off-label use, where such use is not itself illegal, and others are permitted to engage in such speech. In a 2-1 decision, the panel vacated the conviction of Caronia and remanded the case to the district court.

PAGE BREAK

The timing of litigation was such that Caronia’s appeal came just before the Supreme Court ruling in Sorrell, and accordingly, parties in the Caronia case submitted supplemental arguments derived from the Sorrell decision. For example, the Medical Information Working Group, a coalition of medical and device manufacturers, filed an amicus curiae brief in support of Caronia, arguing that the Sorrell opinion should apply to Caronia’s speech, thereby protecting it under the first amendment. Indeed, the U.S. Court of Appeals for the 2nd Circuit itself acknowledged that it had the benefit of the Sorrell opinion, something that was not available to the district court.

Dissenting Circuit Judge Debra Livingston would have upheld the district court’s conviction of Caronia, and she distinguished Sorrell from Caronia. According to Livingston, Sorrell targeted speech directly, in that as soon as a pharmacy in Vermont released a list of prescribing doctors to a pharmaceutical or data mining company, it ran afoul of the Vermont statute. Judge Livingston remarked that consistent with the first amendment, otherwise permissible conduct may become impermissible if undertaken with a prohibited motive, and speech may be used as evidence of such a motive.

Caronia had argued that he merely discussed a perfectly lawful practice, i.e., the use of a lawful drug, Xyrem, for off-label purposes. Justice Livingston disagreed and said that simply because a patient or doctor can legally use Xyrem for an off-label purpose is not enough to make out a sales rep’s first amendment claim. Citing the Warner Bros. film, Arsenic and Old Lace, she said that there is no law forbidding the consumption of arsenic. But this would not endow the film characters Abby and Martha Brewster with a first amendment right to offer arsenic-laced wine to lonely old bachelors with the intent that they drink it.

In other words, in the view of the dissenting judge, there was more to Caronia than a mere violation of a sales rep’s free speech constitutional rights; there was intent to misbrand a drug and introduce it into interstate commerce, which is criminal conduct. If drug manufacturers have a first amendment right to distribute drugs for any use to physicians, or even directly to patients, then the entire FDA regulatory scheme may well be unconstitutional. By vacating Caronia’s conviction, Judge Livingston said that “the majority calls into question the very foundations of our century-old system of drug regulation.”

Whether Caronia will reach the Supreme Court is yet to be seen, but the case is interesting in that it could bring profound changes in how drugs are promoted in the United States. What do you think of these rulings?

If the burden of off-label use and patient disclosure is subsumed in the doctor-patient relationship and the doctrine of informed consent, should pharmaceutical companies, device manufacturers and their sales staff not enjoy the first amendment freedom to promote their products without restraint?

Does aggressive promotion and marketing of a drug or medical device lead to such misinformation, confusion and unsafe conduct that the government should restrict the first amendment constitutional rights of targeted parties, such as the drug and medical device industry and their sales staff?

On a broader note, what is the price of freedom and liberty? Does our constitution assure our safety? Or does it assure only our liberty and freedom?

For more information:
B. Sonny Bal, MD, JD, MBA, and Lawrence H. Brenner, JD, are partners in the law firm of BalBrenner/Orthopedic Law Center and are the exclusive providers of loss prevention, risk management and quality improvement services for the Orthopedic Physician’s Insurance Company. Brenner can be reached at lbrenner@balbrenner.com.