Off-label prescription of a drug is generally legal, but promotion of off-label uses by a drug manufacturer is illegal. In an article in this week's PLoS Medicine, two physician researchers describe the techniques that drug companies use to covertly promote off-label use, even when such promotion is illegal.

Adriane Fugh-Berman (Georgetown University Medical Center, Washington DC) and Douglas Melnick (a preventive medicine physician working in North Hollywood, California) argue that while off-label drug use is "sometimes unavoidable" and sometimes "demonstrably beneficial," it has also been linked with serious side effects. Off-label drug use, they say, "should be undertaken with care and caution due to the uncontrolled experiment to which a patient is being subjected".

Nevertheless, drug companies have a stake in promoting such off-label use, say the authors, since increased off-label use means "larger revenues from larger user populations, especially for products with narrow indications".

Based on Dr Melnick's previous experience working in the pharmaceutical industry in medical affairs (supporting drug marketing) and both authors' current contacts within the industry, they outline some of the ways that drug companies can promote such off-label use.

One example is known as the "decoy indication".

In development, say the authors, drugs may be promising for several uses, and companies must choose one or two conditions on which to focus research. Ease of approval is the most important factor in this decision. If extensive off-label use is anticipated, a company may seek approval for just a narrow indication in order to speed a drug to market. In other words, a drug may be approved for this very narrow "decoy indication" while an extensive off-label campaign is not disclosed to drug regulators.

Another technique is to use drug representatives, even though in the US drug reps are not supposed to detail doctors on off-label uses. The authors quote an article in Medical Marketing and Media in which a pharmaceutical industry attorney says: "Before engaging in off-label promotion, companies should ascertain the risk profile, safety, efficacy, and potential commercial benefits of the use--without committing that last bit to print". In other words, say Fugh-Berman and Melnick, illegal promotion may be cost-effective if potential profits trump potential fines.

Pharmaceutical marketing, they say, has "distorted the discourse on off-label uses and encouraged the unmonitored, potentially dangerous use of drugs by patients for whom risks and benefits are unknown."

"Companies that engage in off-label promotion should be heavily fined and their future marketing practices subject to increased scrutiny by regulatory agencies."

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Citation: Fugh-Berman A, Melnick D (2008) Off-label promotion, on-target sales. PLoS Med 5(10): e210. doi:10.1371/journal.pmed.0050210

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CONTACT:

Adriane Fugh-Berman

Georgetown University

Physiology and Biophysics

Box 571460

Washington, DC 20057-1460

United States of America

+1 202-467-0816

+1 202-687-7407 (fax)

ajf29@georgetown.edu