Pharmaceuticals Regulation

Off Label Drug Use

Approximately one in five prescriptions for drugs in the US are for off label use.  In some cases, this may be inapprorpiate as there is typically limited clinical evidence supporting off label use.  In other cases, off label use is approrpiate.  Clinical trials rarely enroll children or pregnant women and thus medictions are often not indicaated for these populations; however, children and pregnant women get sick too, so it is entirely appropriate to have off-label prescribing for these populations, although doing so does carry additional risks.

Can drug companies promoto their drugs for off-label use?  Promote: no.  Communicate: sometimes.  Health Affairs has a nice policy brief that clarifies the off-label prescribing issue:

Under FDA rules, any promotional materials distributed by a company should be truthful, balanced, nonmisleading, and supported by substantial evidence. In addition, it has been illegal for drug manufacturers to directly promote or advertise a drug for any indication that the FDA has not approved. However, companies are not categorically prohibited from disseminating information about off-label uses, and the FDA’s approach to regulating and enforcing the distinction between communication and promotion has evolved over the past several decades in response to both legislative changes and legal challenges.

Manufacturers can communicate about off-label uses of their drugs in a number of ways. Companies are permitted to respond to unsolicited requests from health care professionals about unapproved uses and might also support independent continuing medical education activities at which off-label uses are discussed. Since the passage of the Food and Drug Administration Modernization Act (FDAMA) of 1997, companies are also permitted to distribute peer-reviewed journals and reference books that discuss off-label uses, although this practice is subject to certain limitations. In 2014 the FDA expanded this authority to include non-peer-reviewed clinical practice guidelines.

Under Section 114 of the FDAMA, companies were also given the power to share health care economic information about approved uses of their drugs with formulary committees, managed care organizations, and other entities that make reimbursement and coverage decisions. However, it is unclear how often drug companies have used this pathway, which some attribute to a lack of clarity on how the FDA interprets that section of the law, as well as to the availability of alternative channels for health economic communication (principally, the Academy of Managed Care Pharmacy’s Format for Formulary Submissions, which provides comprehensive drug information to managed care organizations).

Companies may not always follow these rules.  When they do not, they are liable for significant fines.

In 2012, for example, GlaxoSmithKline (GSK) was fined $3 billion by the federal government, in part for off-label promotion of several of its drugs

Why don’t pharmaceutical firms just do the clinical trials necessary to demonstrate that the drugs are safe and effective for other indication?  The answer is the cost.  The trials can cost millions of dollars and take many years to complete.

Regardless of the current off-label statutes, the law and regulations will almost certainly evolve over time.


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