By: Tamara Yunusova, Staff Editor

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On December 3, 2012, the U.S. Second Circuit Court of Appeals became the first court in the nation to authorize off-label drug promotion under the First Amendment.  The heavily-disputed ruling, which is headed for further appeal, will have far-reaching implications for pharmaceutical companies and drug regulation policy. In a 2-1 decision, the Court of Appeals revoked the conviction of a sales representative who sold drugs for conditions not approved by the Food and Drug Administration (FDA).

Alfred Caronia, a sales representative of Orphan Medical (later acquired by Jazz Pharmaceuticals), was promoting the prescription drug Xyrem (sodium oxybate).  Listed as a Schedule III drug under the Controlled Substances Act, Xyrem is a central nervous system depressant which won FDA approval in 2002 to treat cataplexy and narcolepsy.²  Caronia personally promoted Xyrem for insomnia, fibromyalgia, Parkinson’s disease, chronic pain, general muscle disorders and other off-label uses to prescribers.⁶  As a target of federal investigation in 2005, he was secretly recorded discussing the unapproved uses of the drug with a prescriber.¹  He was convicted in 2008 for introducing a misbranded drug into interstate commerce, a violation of the Food, Drug, and Cosmetic Act.¹

Contending that proscribing the provision of truthful and non-misleading information to prescribers for off-label use infringed upon his right to free speech, Mr. Caronia appealed to the higher courts.  The violation of a constitutionally protected right was echoed by the Second Circuit’s ruling which stated that “the government cannot prosecute pharmaceutical manufacturers and their representatives under the Food, Drug, and Cosmetic Act for speech promoting the lawful off-label use of an FDA approved drug.”⁵

“In the fields of medicine and public health, where information can save lives, it only furthers the public interest to ensure that decisions about the use of prescription drugs, including off-label usage, are intelligent and well-informed,” wrote Circuit Judge Denny Chin.⁴

While pharmaceutical representatives are barred from promoting drugs off-label, physicians are free to prescribe drugs for off-label conditions.  In that light, prohibiting sales representatives to promote drugs off label demands further scrutiny.  Barring sales representatives from imparting truthful information about off-label uses when such uses are not illegal to begin with, essentially, prosecutes sales representatives for their speech, a violation of their First-Amendment rights.

About off-label prescribing rights, the Second Circuit ruling stated “prohibiting off-label promotion by a pharmaceutical manufacturer while simultaneously allowing off-label use ‘paternalistically’ interferes with the ability of physicians and patients to receive potentially relevant treatment information; such barriers to information about off-label use could inhibit, to the public’s detriment, informed and intelligent treatment decisions.”⁶

Whereas granting off-labeling rights leads to informed and intelligent decisions, opponents argue that legalizing off-label drug promotion will undermine the FDA’s role in drug regulation.  “The majority calls into question the very foundations of our century-old system of drug regulation,” states dissenting Judge Debra Ann Livingston. “If drug companies were allowed to promote F.D.A. – approved drugs for unapproved uses, they would have little incentive to seek FDA approval for those uses.”⁵

The Caronia case is not the first of its kind to trigger the First Amendment reflex.  In Sorrell vs. IMS Health, the U.S. Supreme Court repealed a Vermont law that forbade pharmaceutical companies to purchase prescribing information for marketing purposes, a practice known as data mining.¹  Ruling that data mining is protected under the first amendment, the Supreme Court voided the Vermont law that sought to prohibit this action.

With a verdict that staggers between a misdemeanor and a constitutional right, the Alfred vs. Caronia case poses some serious legal questions about where the boundaries of the First Amendment lie.  Previously, off-labeling cases were settled as soon as it was proven that the drug was misbranded or promoted for unapproved purposes.  Now, however, with the authorization of off-label promotion, litigation must go further to prove that the efforts to promote the drug were untruthful and misleading.

“It’s very significant because it’s going to make F.D.A., in its promotion cases focus on the kinds of speech that are more likely to harm consumers, such as false or misleading marketing versus something that is not approved” said Gerald Masoudi, former chief counsel of the FDA. ⁵

In addition to its accompanying changes in litigation, the Caronia case promises dynamic changes in traditional business policy.  Prior to U.S. vs. Caronia, to avert the misbranding charge, pharmaceutical companies would invest millions of dollars annually on training programs.³  For instance, in July 2012, GlaxoSmithKline agreed to pay $3 million in fines for off-label promotion of antidepressants.⁶   Aside from the great investments devoted to compliance programs, companies would spend hefty sums to settle allegations of off-label promotion.  For its marketing of Risperidone (Risperdal) in August 2012, Johnson & Johnson pharmaceutical unit reached a $181 million consumer fraud settlement with 36 states and the District of Columbia.⁶  Under the formidable Park doctrine, the government could prosecute individual executives for off-label speech made by members in the company irrespective of the executive’s direct involvement or knowledge about the conduct.³  With the legalization of off-label promotion, pharmaceutical companies will no longer face such penalties.

The Caronia case raises prominent questions about drug promotion, regulation, and policy. If approved, off-label promotion will broaden the knowledge of both patients and physicians of various drug therapies, a hallmark of intelligent decisions.

SOURCES:

1. Boumil, M. (2013). Off-label marketing and the first amendment. The New England Journal of Medicine. 368 (2), 103-105 Retrieved February 6, 2013, from                        http://www.nejm.org/doi/full/10.1056/NEJMp1214926
2. Food and Drug Administration. (n.d.). Highlights of prescribing information. Retrieved February 7, 2013, from http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021196s013lbl.pdf
3. Sack, J. (2012). Does misdemeanor misbranding survive Caronia? Forbes.                                                                     Retrieved February 6, 2013, from http://www.forbes.com/sites/insider/2012/12/11/does-misdemeanor-misbranding-survive-caronia/
4. Stempel, J. (2012). U.S. court voids drug rep’s conviction, cites free speech. Reuters. Retrieved February 6, 2013 from http://www.reuters.com/article/2012/12/04/us-offlabel-conviction-idUSBRE8B21DC20121204
5. Thomas, K. (2012) Ruling is victory for drug companies in promoting medicine for other uses. The New York Times. Retrieved February 6, 2013 from http://www.nytimes.com/2012/12/04/business/ruling-backs-drug-industry-on-off-label-marketing.html?_r=0
6. Vivian, J. (2013). Off-label promotion is free speech. U.S.Pharmacist. Retrieved February 6, 2013 from  http://www.uspharmacist.com/content/d/pharmacy_law/c/38733/

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