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First Amendment Protection and Off-Label Promotion: What Drug Companies Can and Can’t Say

The First Amendment of the United States Constitution protects the freedom of speech.  Not all forms of speech, however, receive total protection, such as yelling “fire” in a crowded theater if doing so is likely to cause injury.  So-called “commercial speech” is a category of speech afforded partial, but not total, protection by the country’s courts.  Regarding the First Amendment debate, the FDA faces a conflict: to balance the need for neutral and candid research within the medical community concerning off-label uses against the self interest of drug makers, who stand to profit if their drugs may be sold for more medical conditions. To achieve the proper balance, the FDA distinguishes between promotional (unlawful) and non-promotional (lawful) off-label speech. By making this distinction, the FDA allows for considerable freedom of speech by drug makers to discuss off-label uses in a manner that does not endanger the public health or further their profit motives.

What the Drug Makers Cannot Say

Prohibitions on off-label speech may be found in both the New Drug Approval and Misbranding provisions of the Food, Drug and Cosmetics Act (FDCA). The New Drug Approval requirement mandates that a drug maker seek approval for every intended use of a drug. 21 U.S.C. § 355.

The Misbranding provision makes it unlawful to make and distribute misbranded drugs. 21 U.S.C. § 352. According to this provision, a misbranded drug is either a drug whose labeling is “false or misleading” or one whose labeling does not include adequate directions for all intended uses of the drug. Intended uses are determined by the objective intent of the drug maker and are oftentimes reflected in oral or written statements, promotional claims, advertising, and contextual circumstances.

What Drug Makers Can Say: FDA Guidelines

FDA regulations concerning lawful off-label speech are found in two places: the 1997 Guidelines and the 2009 Good Reprint Practices. The 1997 Guidelines apply to company-supported Continuing Medical Education classes, which may relate to the sponsor company’s products or a targeted off-label condition.  Because medical licensing boards require doctors to accumulate education credits from such classes periodically, company sponsored classes have a ready audience and often appear more attractive if the sponsorship results in lower fees.

The Guidelines permit independent, non-promotional activities supported by drug companies. The legality of an activity hinges on the degree of independence, measured by a host of factors. The control of content and selection of presenters can be the critical difference, but the focus of the program, restrictions on a company’s grant, and whether the program offers opportunities for discussion all may be difference makers in whether a company oversteps its bounds.

The 2009 Good Reprint Practices permit the dissemination of journal articles and other publications which evaluate off-label use. Passed as a response to growing First Amendment concerns, the Practices ensure the dissemination of helpful and independent scientific information, but put the decision of what articles to distribute to pharmaceutical companies, who have little incentive to purchase and share reprints that do not support the sale of drugs for off-label uses.

The guiding principle of the Practices appears to be that as long as medical writing is peer reviewed and not later altered, it should be safe to allow companies to distribute that writing. According to the Practices, journal articles must be: peer-reviewed, contain information resulting from well-controlled clinical investigations, be accompanied by any conflicting authority, and may not contain false or misleading information.

Additionally, reprints may be not marked, highlighted, summarized, or characterized in any way by the manufacturer. Nor may they be attached or distributed with promotional materials or serve as the topic of discussion between pharmaceutical representatives and doctors. The Practices also prohibit dissemination of letters to the editor, publication abstracts, and reference publications containing little or no substantive discussion of the relevant investigation, as they are unlikely to have undergone the peer review process on which the medical profession relies.