Not All Evidence Is Created Equal

Health care providers frequently prescribe drugs and medical devices for uses different from those approved by the Food and Drug Administration. Such “off-label” treatment could involve giving patients a different dose of a drug, prescribing it for a different age group than has been approved, or using the drug for an entirely different condition. Off-label use is legal and an important part of the toolkit for physicians as they encounter clinical situations that may not mimic those in clinical trials. For example, the decision is sometimes made out of necessity when limited treatment options exist. But off-label use is not without risk, and FDA has asked for public comment on when and if companies should be able to promote products for off-label uses.

In FDA-speak, the “label” is not the information listed on a drug bottle or package, but is the entirety of the document written for practitioners that includes information about the uses, warnings, and ingredients of an approved drug or medical device. The label also lists results from clinical trials and lab tests showing that the drug is safe and effective when used as intended, and clearly defines what treatments FDA has approved for the drug. That approval process is rigorous, involving careful consideration of how the clinical studies were designed, the statistical methods used to evaluate them, and the trade-offs between likely benefits and risks of a product.

But when drugs are used off-label, patients don’t have the protection of FDA review. The evidence supporting a drug’s off-label use can come from a number of sources, such as early stage clinical trials or other research and analyses. Promising findings may be reported in medical journals, but the evidence behind them does not need to be as comprehensive as what is required for FDA approval. For a variety of reasons, results may highlight the positive while minimizing or ignoring negative findings.   

In comments to FDA, Pew considered the role of companies in promoting products for unapproved uses (distinct from their ability to provide scientific information to doctors and others upon request), and suggested that FDA consider the following factors:

1. The quality and rigor of published literature, even peer-reviewed literature, is variable. Selective publication of studies, or of outcomes within studies, can create misleading impressions of a product’s safety and effectiveness.
2. FDA reviewers are unique in that they have access to all data supporting a company’s claims about a product, the study protocol, and the scientific expertise to determine whether the claims are corroborated by the clinical evidence. Peer review alone does not fulfill this role.
3. FDA’s authority to require companies to substantiate claims about a product will be undermined if they may offer or promote products for sale for off-label use without first providing evidence.
4. FDA plays a critical role in ensuring that health care providers and the public know whether drugs work and the potential harms associated with each of the uses for which products are being promoted.

Off-label prescriptions are an important element of health care, but FDA’s approval process is still the gold standard in terms of patient protection.