Off-label but not off-limits

By Ben Tesdahl, JD, LL.M, Megan La Suer, JD, MHA, and Rob Portman, JD, MPP, June 1, 2021

Every month, DermWorld covers legal issues in “Legally Speaking.” This month’s authors are health care attorneys with Powers Pyles Sutter & Verville in Washington, D.C. Portman is also general counsel for the AAD and AADA.

Dermatologists routinely use medications and treatments “off-label,” or outside of their approved label use, for a wide range of conditions. Third party payers, however, often use the lack of official Food and Drug Administration (FDA) approval for a treatment, device, or medication as a justification for refusing to cover the cost of said treatment, device, or medication.

Recently, the American Academy of Dermatology Association (AADA) Advisory Board developed a resolution addressing the AADA’s policy on off-label use of drugs. Specifically, the resolution 1) recognizes the “autonomous clinical decision-making authority of a physician” and the physician’s ability to “use an FDA-approved drug product or medical device for an off-label indication when such use is based upon scientific evidence and/or sound medical opinion,” and 2) opposes restrictions of “insurance coverage for ‘off-label’ prescribing of medications, when the prescription of a drug or use of a device is widely held within a professional community to represent safe and effective therapy.”

In light of the AADA’s resolution, the following provides a refresher on the environment for marketing and promoting certain off-label uses, and the implications for dermatologists involved in studies or presentations analyzing off-label uses.

What is off-label prescribing and is it regulated by the FDA?

The FDA regulates the safety and effectiveness of drugs and devices, and approves these products for specific uses, purposes, and indications. Once the FDA determines that there is sufficient evidence to demonstrate a drug’s safety, efficacy, and quality of manufacturing practices, that drug or device may be approved for marketing. As part of the approval process, certain information must be included on the drug’s label, including a statement of the medical conditions for which the drug has been demonstrated to be efficacious, dosage information, and route of administration. Off-label drug use generally involves prescribing currently available and marketed medications, but for a disease or a symptom that has never received FDA approval. Omission from the approved label does not mean that the FDA disapproves of an off-label use; it simply indicates that the agency has not reviewed that particular use.

While the FDA has authority to regulate the safety and effectiveness of drugs and devices, the agency does not directly regulate the practice of medicine. Under the so-called “Practice of Medicine” exception to the FDA’s authority, physicians are permitted to prescribe approved drugs and devices for other off-label uses. Dermatologists prescribe or administer off-label uses of drugs and devices in their practices every day. In fact, off-label prescribing is fairly common among all physicians — accounting for 21% of all prescriptions written. However, physicians may not use or advertise the use of unapproved drugs or devices except in very limited circumstances and must also be careful to avoid “promoting” the off-label use of otherwise approved drugs and devices. In some cases, dermatologists may unwittingly make claims on their practice websites or in promotional materials about the purpose or effectiveness of unregulated and unapproved health care products, like topical creams, enzymes, or other substances, that may qualify them as drugs or devices and thereby attract the attention of the FDA. The consequences of prescribing unapproved drugs or devices or violating the FDA’s rules for off-label uses can be severe. Dermatologists must, therefore, understand the FDA’s position and be aware of the other risks associated with unapproved or off-label uses of drugs or devices.

Are there are any legal and ethical implications that I should consider when prescribing a drug for off-label uses?

Physicians may decide to prescribe drugs for off-label use for a multitude of reasons. This decision may be based on new cutting-edge research, it may be cheaper than specialty drugs, or the physician may simply be trying a different treatment approach when more conventional treatments have failed. Prescribing medications for off-label use does not come without risk. When drugs are prescribed for off-label use, they do not have the benefit of an FDA-reviewed analysis of safety and effectiveness data. Thus, dermatologists should ensure that any off-label procedures or treatments they prescribe or administer are consistent with the prevailing standard of care and, where appropriate, should obtain informed consent for the use of drugs or devices off-label.

It is important for patients to know and be aware of the risk for adverse reactions for any prescribed medication or treatment. Under the doctrine of informed consent, a physician is required to present the patient with material information about proposed treatments, any alternatives, and the risk and associated benefits of the treatment or alternatives.

Dermatologists should consider preparing a comprehensive informed consent form to ensure the patient is fully and accurately informed when a drug or device is prescribed for off-label use. Not only does the form help to maintain communication between the physician and patient; it may serve as supporting documentation in the event the patient experiences a negative effect. However, where off-label treatments are routine, clearly constitute the standard of care, and raise no significant risk, there may be no need to mention them in the informed consent.

Are off-label drugs typically covered by insurance?

One of the biggest problems for physicians when it comes to off-label use can be getting insurance to reimburse for the drug when a patient uses it off-label. Whether insurance will cover the medication depends on the drug itself and what condition the drug is prescribed to treat. Most payers, including Medicare, require that an off-label use be listed in one of the recognized compendia before they will cover that use. Many payers deny the cost of drugs used off-label on the ground that such uses are “experimental” or “investigational.” Denial of payment or reimbursement for off-label use can interrupt or effectively deny access to necessary and appropriate treatment for individuals being treated for life-threatening illnesses, or when no other treatment has been successful.

Medicare covers safe and effective drugs and biologics approved for marketing by the FDA when the drugs are “reasonable and necessary for the diagnosis or treatment of illness or injury for which they are administered according to accepted standards of medical practice.” Medicare Administrative Contractors (MACs) will determine the reasonableness and medical necessity of drugs and biologics based on the “advice of medical consultants and with reference to accepted standards of medical practice and the medical circumstances of the individual case.” Medicare may cover off-label if the MAC concludes that the use is “medically accepted, taking into consideration the major drug compendia, authoritative medical literature and/or accepted standards of medical practice.” Commercial payers tend to publish their own clinical guidelines and policies for off-label or unapproved drug treatments, but most follow or closely align to the requirements for Medicare outlined by CMS.

Patients can seek prior authorization for coverage of drugs prescribed or used off-label, but the process is often complicated and time consuming. This process typically includes contacting the drug plan, submitting evidence in support of the prescribed use, seeking support of the doctor or other prescriber, and often appealing through multiple layers of review.

Are there specific rules about marketing or lecturing on off-label uses of drugs and devices?

Congress has passed legislation and the FDA has issued regulations that outline the circumstances under which manufacturers may disseminate information on the safety, effectiveness, or benefit of an off-label use to physicians, other health care practitioners, pharmacy benefit managers, health insurance issuers, group health plans, or a federal or state agency. Under these rules, a drug manufacturer can provide peer-reviewed articles on off-label uses to physicians and others covered if the manufacturer meets certain requirements, even if the physician has not requested them. In addition, the manufacturer can respond to a physician’s unsolicited request for information by supplying peer-reviewed articles or textbooks.

The FDA’s ability to crack down on a manufacturer’s communications about a drug’s off-label use has also been debated in federal court in the context of potential free speech violations. In 2012, a federal appeals court confirmed that a manufacturer’s, or its representative’s, truthful, non-misleading speech about off-label uses is protected from FDA regulation by the First Amendment. Three years later, a federal judge in New York City issued a preliminary injunction, prohibiting the FDA from pursuing an enforcement against off-label promotion.

Specifically, the court stated that “[w]here the speech at issue consists of truthful and non-misleading speech promoting the off-label use of an FDA-approved drug, such speech…cannot be the act upon which an action for misbranding is based.” The judge also provided some practical advice for manufacturers by noting that “[a] manufacturer that leaves its sales force at liberty to converse unscripted with doctors about off-label use of an approved drug invites a misbranding action if false or misleading (e.g., one-sided or incomplete) representations result.”

Although the two court cases discuss the FDA’s ability to regulate manufacturer promotion of off-label drug use, there are still indirect implications for health care professionals. A physician who is paid by a manufacturer to write an article on an off-label use would be subject to the same rules as the company with respect to the dissemination of that article. Physicians’ communications with manufacturer representatives should be limited to scientific evidence in support of the off-label uses of otherwise approved drugs and devices.

Additionally, any data provided by manufacturer representatives should be truthful and not misleading; information that fails to meet these basic standards would not be protected from FDA enforcement under the First Amendment. Moreover, the practice of medicine exception only applies within the context of a patient-doctor relationship; advertising the off-label use of a drug or device on a physician’s website or in promotional materials is barred to the same extent that the manufacturer is barred, regardless of any financial relationship between the physician and manufacturer.

The FDA has issued guidance on manufacturer support of continuing medical education (CME) events that relate to the manufacturer’s products or their competing products. Under the guidance, industry-supported events must be “truly independent and nonpromotional” and the manufacturer must have no influence on the program content of planning. Thus, physicians who speak at CME events about off-label uses of drugs or devices would be protected by the First Amendment, but that protection does not extend to non-speech actions to assist manufacturers in encouraging physicians to use a drug or device for unapproved indications.

This article is provided for informational and educational purposes and is not intended to provide legal advice and should not be relied upon as such. Readers should consult with their personal attorneys for legal advice regarding the subject matter of this article.

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