National Survey Suggests that Off-Label Status is Material to Informed Consent

By Christopher Robertson

As many readers of this blog know, the FDA requires that, prior to entering the market, companies prove safety and efficacy for each intended use of their products, but physicians are then free to prescribe the products for any other uses.  (Companies are not allowed to promote off-label uses however.)

A recent national survey by Consumer Reports includes two interesting findings:

  1. About two-thirds (63%) of Americans “would not take a doctor prescribed medication that has been approved by the FDA, but not for their specific condition.”
  2. Almost all Americans (94%) “say they have never been told by a physician that a medication they were taking was not approved by the FDA for their condition.”

Patients are right to be skeptical of off-label uses, though they may not appreciate just how common they are.  In fact, most off-label use is unsupported by scientific evidence as to safety and efficacy.  A new report by the FDA illustrates several off-label uses that were subjected to rigorous clinical trials and turned out to be ineffective or dangerous.   For example, Aliskiren is approved for treatment of hypertension and was used off-label for prevention of congestive heart failure (CHF) complications.  A large trial showed that, although it did not significantly improve CHF mortality, it did significantly increase rates of kidney failure for CHF patients.  We do not know how many other off-label uses would fail if similarly tested.  

Thus, it is probably prudent for patients to use off-label status as a red flag to ask their physicians more searching questions about whether the product is right for them (and whether the physician may have a financial relationship with the company).  In principle, a physician’s careful and unbiased review of the scientific evidence could be a decent substitute for FDA-approval, if a robust and rigorous body of evidence does exist for the usage in question.

However, patients cannot use such a red flag if they are unaware that the doctor is recommending a product not FDA-approved for the patient’s indication.  Off-label use is quite common.  In a 2006 review, about 21% of prescriptions filled were for off-label uses.  Another study found that 79% of patients discharged from pediatric hospitals were taking at least one product-off label.  A 2016 JAMA paper found that 30% of antidepressant prescriptions were off-label.  Since the new survey shows that 94% of Americans don’t recall ever being told that they were being given a drug off-label, even though the practice is common, I speculate that many patients are taking drugs off-label without knowing it.

Legally, some have suggested that off-label status must be disclosed by physicians to secure informed consent. My co-authors and I have argued that any fact that would cause a substantial number of patients to change their decision should be considered “material” information that a physician must disclose.  Surveys like this one can answer that empirical question, though we suggest a more case-specific approach.

Until recently, I was not aware of any court holding that off-label use must be disclosed.  Times may be changing.  Based on a few anecdotal cases I found, I am now beginning a systematic review of that caselaw, so please send along any instances — whether styled as informed consent claims or medical negligence.

Before endorsing a broad duty to disclose, further research should explore whether patients over-react to such disclosures, or whether physicians can put them in appropriate context to increase the quality of decision-making overall.  There are also larger system-effects at stake, as well:  if physicians make such disclosures and patients become more scrutinizing, this may cause companies to more often invest in the clinical trials that will determine safety and efficacy.  When companies succeed, they will thereby secure a new labelled indication, moving more uses on-label.

This entry was posted in Christopher Robertson, FDA, Health Law Policy, Liability, Pharmaceuticals, Public Health and tagged , , , by crobertson. Bookmark the permalink.

About crobertson

Christopher Robertson is a professor at the James E. Rogers College of Law, University of Arizona, and affiliated faculty with the Petrie Flom Center for Health Care Policy, Bioethics and Biotechnology at Harvard. Robertson also leads the Regulatory Science program, a partnership with the Arizona Health Sciences Center and the Critical Path Institute. Professor Robertson's research focuses on how the law can improve decisions by individuals and institutions -- attending to informational limits, conflicting interests, and cognitive biases, especially in the domain of healthcare. Blending legal, philosophical, and empirical methods, Robertson's work has been published in the New England Journal of Medicine, New York University Law Review, Cornell Law Review, Emory Law Journal, and the Journal of Empirical Legal Studies. He has received research support from the Robert Wood Johnson Foundation, and runs the Law and Behavior Research Lab at the University of Arizona. Robertson graduated magna cum laude from Harvard Law School, where he also served as a Petrie Flom fellow and lecturer. He earned a doctorate in Philosophy at Washington University in St. Louis, where he also taught bioethics. For 2013-2014, he was a visiting professor at Harvard Law School, and will visit at NYU School of Law in 2016-2017. Robertson's legal practice has focused on complex litigation involving medical and scientific disputes.

One thought on “National Survey Suggests that Off-Label Status is Material to Informed Consent

  1. Off-label use of Miralax and other PEG 3350 laxatives for children is rampant and potentially dangerous. FDA acknowledges neuropsychiatric, kidney, and metabolic acidosis adverse events. Parents must be made aware that this prescribing is off-label – testing on children shows efficacy in producing bowel movements, not effects on nervous system, kidneys, blood – or gut microbiome. See our FDA Citizen Petition, granted with a study to Children’s Hospital of Philadelphia and correspondence with FDA on our website,

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