The state of off-label drug laws

Dermatology Times, Dermatology Times, October 2018 (Vol. 39, No. 10), Volume 39, Issue 10

Congress has proposed two bills that are designed to promote a "scientific exchange" between drug manufacturers and physcians. As a result, drug manufacturers may be able to share clinical data and non-FDA-approved uses of drugs with healthcare providers in the future.

Prescribing drugs off label can sometimes be the best option for patients. It’s an unavoidable part of medicine. Some of the most important discoveries have been accidental discoveries in which a patient has benefited from an off-label use of a drug.

Currently, federal law allows manufacturers to respond to unsolicited questions from physicians, share peer-reviewed articles and sponsor continuing medical education courses. Congress has proposed two bills that are designed to expand those rules.

Introduced in March 2017, the Medical Product Communications Act of 2017 (H.R. 1703) seeks to create a “scientific exchange” in which healthcare providers can receive scientific, non-promotional off-label information about drugs. The legislation would allow sharing of clinical data.

H.R. 1703 was followed by H.R. 2026, the Pharmaceutical Information Exchange Act, in April 2017. It would allow drug manufacturers to share information about unapproved uses to formulary or technology review committees that the manufacturers believe might be sufficient to support future FDA approval of unapproved use, including preclinical data.

“Both bills would require manufacturers to include disclaimers that the FDA had not approved the information,” write Michael Sinha, M.D., J.D., MPH, of Brigham and Women’s Hospital in Boston, and, Aaron S. Kesselheim, M.D., J.D., M.P.H., of the Center for Bioethics at Harvard Medical School in the May 8 issue of PLOS Medicine.

In both cases, manufacturers would have to make clear that these are off-label, not FDA-approved uses. However, similar disclaimers for nutritional supplements have proven ineffective, Drs. Singha said.


“Off-label promotion is an important health policy because of the substantial amount of harm such promotion has caused patients in the past. And, while off-label marketing is currently illegal―apart from some safe harbors―there are advocacy groups pushing to change rules and make it more widespread,” Dr. Sinha said in an interview with Dermatology Times.

The 2012 case, US v. Caronia, involved Alfred Caronia, a former sales rep for the pharmaceutical firm Orphan Medical who was convicted of conspiring to promote the drug Xyrem for indications other than cataplexy in narcolepsy, its approved condition. He was sentenced to one year of probation, 100 hours of community service and a $25 fine. He appealed and won.

“The ruling limits the degree to which the government can restrict off-label marketing. This creates a situation in which pharmaceutical manufacturers can freely promote their products for non-FDA-approved uses that might be dangerous for patients. Classic examples of such cases include widespread off-label promotion of anti-psychotics for elderly patients with dementia or antidepressants for children,” Dr. Sinha said.

The Caronia decision led to some changes in off-label promotion. The 21st Century Cures Act of 2016 allows manufacturers to provide “healthcare economic information” about off-label drug uses to formulary committees insurers rely on when considering whether to approve coverage for a specific drug.


Manufacturers would have to make clear that these are off-label, not FDA-approved uses. However, similar disclaimers for nutritional supplements have proven ineffective, Drs. Singha said.

“In addition to these federal efforts, states are marching forward with their own laws aimed at undermining restrictions on off-label promotion spurred by lobbying by various advocacy groups. These state laws could place additional pressure on Congress to pass national legislation addressing the topic,” he said.

In March 2017, Arizona became the first state to broaden off-label marketing with its Free Speech in Medicine Act, which explicitly allows manufacturers to communicate with physicians and other prescribers about off-label uses.

“State laws change rapidly,” Dr. Sinha says. For example, after the publication of the editorial, Tennessee became the second state to pass similar legislation, with the same stipulation that information given to clinicians be truthful. That law went into effect July 1.


The FDA itself continues to advocate additional safe harbors for off-label marketing, like in 2014 when the agency proposed two draft guidances that would have allowed manufacturers to distribute non-peer-reviewed clinical practice guidelines describing off-label uses. Peer-reviewed studies showing lower estimates of product risks than those deemed by the FDA would have also been sanctioned.

Knowing the distinctions between FDA indications and off-label uses are paramount for individual physicians because physicians neither have the time nor the expertise to evaluate the critical data as do highly trained FDA scientists, Drs. Sinha and Kesselheim wrote.

Patients could also be exposed to more high-cost drugs that lack efficacy and safety evidence, thus posing increased risk.
Marketing of off-label indications might also lead pharmaceutical firms to saturate the market with biased and/or incomplete information that could influence prescribing practices.

Drs. Sinha and Kesselheim write that over the past three decades, tens of billions of dollars in civil and criminal penalties have been paid by nearly all the major pharmaceutical manufacturers for engaging in illegal off-label promotion.


This research was supported by the Laura and John Arnold Foundation. ASK is also funded by the Engelberg Foundation and the Harvard Program in Therapeutic Science.


Sinha, MS, Kesselheim AS. “The Next Forum for Unraveling FDA Off-Label Marketing Rules: State and Federal Legislatures,” PLOS Medicine, May 8, 2018. DOI:org/10.1371/journal.pmed.1002564