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Off-label prescribing has entered standard treatments and is at the cutting edge of medical innovation, but it carries liability risks of which to be aware.

“Off-label prescribing” sounds suspect from the start. After all, it means using a drug differently than specifically defined by the manufacturer and approved by the FDA.

But it is not really outlier conduct at all. In fact, it is an accepted part of medical practice.

FDA approval actually only limits drug companies, physician marketers, and clinical researchers; it does not tell clinical physicians how they may use approved drugs. The Federal Food, Drug, and Cosmetic Act states that FDA approval does not “limit or interfere with the authority of a health care practitioner to prescribe” approved drugs “for any condition or disease.”  The Physician’s Desk Reference also notes that “Once a product has been approved for marketing, a physician may prescribe it for uses or in treatment regimens or patient populations that are not included in approved labeling.”

Fiduciary Duty to the Patient

Balancing that, though, is the prescribing physician’s fiduciary duty to their patient. Imprudently using a drug outside its approved use can, therefore, be the basis of a medical malpractice action or a complaint to a state medical board, and the plaintiff or complainant would start with the advantage of being able to cite the limits of the FDA-approved use.

The physician would then have to show that their own “unauthorized” use actually met the standard of care.

They would start with the fact that, as one court stated, “the pace of medical discovery runs ahead of the FDA’s regulatory machinery,” making what is “off-label” potentially “state of the art. For example, minoxidil was once off-label for baldness but was still widely used and then became approved for baldness but remains off-label for other types of hair loss for now.

They would then have to show that the individual off-label use was duly considered and appropriately carried out.

How to Protect Yourself

So, mindful that you may someday be facing an expert who blew up the package insert to the size of a living room rug and is pointing out that your use is not on it, or an ex-patient who has conveniently forgotten that they once begged you to try “anything!” but is now insisting that you made them a guinea pig, how can you protect yourself while still offering innovative options to your patients?

Start with the overall standard of all medical care, which is to be reasonable under the circumstances, and set yourself the same algorithm of analysis that jurors or a medical board would use.

The threshold question is whether good results are really expected. If they are not, stop. A well-intentioned crapshoot is still actionable malpractice or misconduct, and no patient consent can change that.

If good results are expected, then the next question is whether they also come with risks. If they do not, then that’s great, but if there is serious risk potential, then you need to look at whether there is still significant use in your specialty and for patients comparable to yours and to consider whether the benefits really do outweigh the risks.

You then need to determine whether there is support in the literature. Be wary, though, because drug companies have used journal editors, advisory boards, consultant meetings, and CME events to promote off-label use of their products and have actually “ghost authored” studies. There is also the practical reality of researchers using statistical analyses that make for good outcomes because positive results are more likely to be published. You are not likely going to be in a position to vet an article, but at least remain circumspect regarding company-sponsored studies and results that just look too good. Contacting other physicians who have used the drug the same way and getting their personal assessments is also a good idea.

If you are still unsure as to whether the off-label prescribing that you are contemplating has sufficient support, you can also submit the matter to your local (within your hospital or region) institutional review board (IRB) for evaluation. An IRB’s formal approval would be virtually dispositive if your choice to prescribe off-label was later called into question.

Next, consider whether to run the issue by your malpractice carrier. If an off-label use is so common as to now be routine in your field (again, think of minoxidil being widely used for baldness for many years), this will not be necessary; but if it is newer or you are actually an innovator, then you should get this input. The company can disclaim coverage if it finds you have exceeded the scope of what it agreed to insure you for, and therefore, it has a real economic incentive to call what you did “experimental.” So make sure that you are covered before you start.

You then want to inform the patient and get their consent. Even though you are not legally required to tell a patient that the use of the drug that you are prescribing is off-label because FDA regulatory status is not classified as a material risk or benefit, you should still do it as an ethical matter. It is also basic self-protection because getting agreement to any treatment encompasses telling the patient what they would reasonably want to know, and so you want to be able to show a jury or a medical board that you did address the nonstandard use of the drug with the patient.

The worst thing that a plaintiff or a complainant can later say about you to a jury or to a board investigator is “The doctor never even told me that this wasn’t approved for what they used it for in me!”

Of course, document what you said and any questions that you answered and that the patient agreed. And do it in human speech and with actual details of what both you and the patient said. Generic boilerplate such as “Risks and benefits were discussed and patient indicated assent” might as well not be there at all.

Then make consenting a process. You and the patient are jointly entering territory that is not fully charted, so there should be continued discussions of the risks and benefits as these begin to accrue or fail to do so. The consent process should be well documented to demonstrate the ongoing collaborative nature of the choice to use the drug in this fashion.

Your side of that process will then also be to stay alert for news about the off-label use that you are engaging in. Check the topic periodically to keep yourself abreast of new developments that may change how you are dealing with your patient. Keeping in touch with other physicians whom you know are using the drug in the same way is also a good idea. Document that you took these steps because they will be very important in any subsequent defense.

Of course, if there are guidelines on off-label use, follow them. These will be proffered as the standard of care for what is inherently a nonstandard situation.

Treatment or Research?

Finally, do not cross the line into research.

Using a drug in a nonstandard fashion for an individual patient for the benefit of that patient is treatment, whereas setting out to test efficacy that can then be applied to a population is research. You can, after receiving permission from the patient and protecting their confidentiality, publish your experience with off-label use of a drug as a case study without being deemed a researcher, but if you are considering publication of information on a group of patients, then the line between what is treatment and what is research can blur. A very nonstandard use can also be deemed “experimental” by virtue of its unusualness. Once such a step is reached, the full panoply of federal regulations on clinical trials will kick in, beginning with the requirement to obtain approval from the local IRB—which itself operates under both the US Department of Health and Human Services and the FDA—and extending to all required patient protection requirements. If you are not sure about how your actual plans may be considered, contact your IRB for an assessment.

However, even if you are sure that you are within the scope of solely individualized treatment, keep what is in patient charts only about that patient, with literature searches and any notes from other physicians in a separate file. The supportive research that you did will still be used in your defense in a malpractice case or board review, but the treatment file will not look like a research template.

In summary, off-label prescribing has entered standard treatments and is also at the cutting edge of medical innovation, but it does carry liability risks that the physician should be aware of and proactive about.