When a pharmaceutical representative leaves clinical training and enters the field, she very quickly learns two things: First, doctors don't always respond the way they did in role-play scripts. And second, doctors don't always prescribe medications for their government-approved indications.

The prevalence of off-label prescribing can make navigation within the physician community fraught with regulatory risks. The government has shown that it can dish out expensive punishment to companies short-sighted enough to flirt with off-label promotion.

What is off-label use?

Under Section 906 of the Food, Drug and Cosmetic Act, the FDA does not restrict the authority of doctors to prescribe a drug for an unapproved use. In fact, the FDA recognizes that off-label prescribing may represent the standard of practice among the medical community. However, the FDA restricts pharmaceutical manufacturers from proactively disseminating information on off-label use of a therapeutic, whether the dissemination is verbal (as in a face-to-face sales call by a representative) or written (as in visual aids or clinical reprints that mention off-label use of a therapeutic).

Safety and ethics

The medical community's debate on off-label use of therapeutics often focuses on the pediatric population and the use of a drug in children or adolescents when studies supporting the use of that drug have only been conducted in adults. Past FDA presentations on off-label use of therapeutics in children have looked at both safety and ethical issues. The pediatric population may metabolize drugs differently, and the long-term pharmacologic effects of drugs on development are often unknown. Furthermore, the pediatric population is vulnerable, and decisions about a child's treatment or participation in a clinical trial are often made by a parent or adult guardian.

The ethical issues behind off-label use can cut both ways. In some situations, failing to use a drug prior to its approval may be considered unethical. For example, oncologists have a longstanding practice of off-label prescribing. Despite the wealth of oncology research and advances in treatment, most cancer therapies come with a heavy price, both financially and in terms of treatment side effects. Even with this high price, few oncologists could use the word "cure" when describing the outcomes of cancer patients. In this environment, off-label use often makes sense for cancer patients and is sometimes ethical, because the patient may not be able to wait for the completion of clinical trials.

Economics

The government has many valid reasons for its policy on promotion of off-label uses. For example, since clinical trials leading to a new indication are extremely expensive, allowing a manufacturer to market its products for non-approved uses would give the manufacturer less incentive to invest in clinical trials to support a new use.

There is certainly an economic advantage for manufacturers that see off-label use of their products, because off-label sales of a product are counted toward its total sales. Investors and analysts further tempt the industry by openly discussing how much of a product's sales may come from off-label use and translating these numbers into statements on how well a company may perform and, in turn, whether investors should buy the company's stock.

Given the clashing perspectives of business and medical science when it comes to off-label prescribing, we should not be surprised that regulation and investigation of the pharmaceutical industry have reached such sensational levels.