Using Medications Off Label:
What Are Your Legal Concerns?

Off-label prescribing is something most of us probably do on a regular basis. Without off-label use of medications, our patients’ well-being would be compromised. However, off-label prescribing isn’t without limits. In this column, I’ll give you some legal background into physicians’ rights to prescribe medications off label, and I’ll outline the legal limitations of this type of prescribing to give you a better understanding of this much-used prescribing method. Many of Us Frequently Prescribe Medications Off Label One study noted that all surveyed dermatologists use medications off label.1 Another study found that one-third of “all prescriptions in cancer treatment were off label.”2 The rate of off-label prescribing is so high that most hospital patients receive at least one drug off label. 3 This makes sense because off-label uses are important in enhancing health because innovations advance the standard of care much more rapidly than the FDA approves new uses for existing drugs. FDA approval is slow and expensive, complicating the use of medications that have been shown to be safe at least in some contexts. Patients with terminal diseases may rationally demand non-approved treatments. Off-label prescribing commonly occurs for rare diseases (for example, lichen planus) — too rare to justify applying to the FDA for an indication, a situation common in dermatology. Use of drugs in an off-label manner to treat children is widespread, because clinical trials are more difficult to perform than in adults and markets are smaller. This situation complicates care because children are not just small adults. Recent federal legislation extending a drug patent’s life in exchange for performing pediatric clinical trials has improved this situation somewhat. (For more details about this, see this months “News & Trends” section under the heading of “FDA News and Approvals.”) Landmark Cases Supporting Off-Label Prescribing As you know, once a medication is approved, a physician may begin prescribing it for “off-label” uses. This was the intention of the Federal Food Drug and Cosmetic Act of 1938 and the Drug amendments of 1962, in which Congress stated that the FDA was not to interfere with the practice of medicine. Congress has repeatedly stated that physicians may prescribe medications for a condition based on their medical judgment rather than the package insert but this is subject to possible medical malpractice claims. The FDA also recognizes the value and propriety of off-label use.4 United States courts have also supported the practice of physicians prescribing medications off label. A doctor’s right to use ethylene diamine-tetra-acetic acid (EDTA) — which was approved 50 years ago by the FDA for treatment of lead, mercury, aluminum and cadmium toxicity — for an unapproved use in an unapproved dosage as long as it was not contraindicated was sanctioned in U.S. vs. Ever 643 F2d 1043 (Fifth Cir. 1981). In Thompson vs. Western States Medical Center, the Supreme Court, noting that off-label prescription was licit, found that the First Amendment barred Congress from precluding advertising about “drug compounding” when other restrictions, such as a warning about the lack of FDA testing, provided adequate alternatives to protect the public.5 Another court has explained that off-label use of FDA-approved drugs by physicians is an established aspect of the modern practice of medicine.6 The firm legal underpinnings of “off-label” prescribing were reiterated in Chaney vs. Heckler, a case reviewing the FDA’s decision to take no action — either investigatory or regulatory — against the unapproved use of approved drugs in state capital punishment systems. In this case, the court stated: The better explanation for the practice-of-medicine exemption is that Congress did not want to interfere with physicians’ treatment of their patients. New uses for drugs are often discovered after FDA approves the package inserts that explain a drug’s approved uses. Congress would have created havoc in the practice of medicine had it required physicians to follow the expensive and time-consuming procedure of obtaining FDA approval before putting drugs to new uses. Thus Congress exempted the practice of medicine from the Act so as not to limit a physician’s ability to treat his patients.7 Our Rights Are Not Unlimited The rights of physicians to prescribe medications are not unlimited. A physician violates the law when he sells illicit drugs to addicts.8 Moreover, if a physician uses a drug outside the scope of the practice of medicine, then he or she is also violating the law.9 Furthermore, if a physician uses a medication for experimental purposes, the legal protections involved with “off-label” prescribing do not attach. Experimental use of medications or devices engenders FDA involvement and regulation. This is the case when actual clinical research is being done and data are being compiled for the FDA approval process. If, however, a medication is being used for purposes of treatment in a novel fashion, the strictures of clinical research do not attach, and the medication can be used legally. No specific liability attaches to off-label use of medications, nor does the law provide any cause of action for not following a medication’s package insert. While state law varies, generally, medical malpractice lawsuits fall into one of three categories: 1. failure to provide informed consent 2. negligence/malpractice 3. fraud. Negligence requires a breach of the prevailing professional standard of care for that healthcare provider. The prevailing professional standard of care for a given healthcare provider is that level of care, skill and treatment which, in light of all relevant surrounding circumstances, is recognized as acceptable and appropriate by reasonably prudent similar healthcare providers. Standards of Care for Generalists vs. Specialists Different standards of care exist for generalists and specialists. To be held to the standard of a generalist the following scenario would apply: If the healthcare provider whose negligence is claimed to have created the cause of action is not certified by the appropriate American board as a specialist, is not trained and experienced in a medical specialty, or does not hold himself or herself out as a specialist, he is held to the standard of a generalist. The standard of a generalist is based on the standard of care of a similar physician. First of all, the physician must be licensed by the appropriate regulatory agency of his or her state. Second, the person must be trained and experienced in the same discipline or school of practice; and last, the physician must be practicing in the same or similar medical community. For the standard of a specialist to apply, the healthcare provider must be certified by the appropriate American board as a specialist, he or she must be trained and experienced in a medical specialty, or hold himself or herself out as a specialist. The standard of care used in assessing the activity of a specialist is based on the practice of similar physicians who are trained and experienced in the same specialty and who are certified by the appropriate American board in that specialty. Off-Label Prescribing and the Standard of Care The off-label use of medication has practical effects in medical practice even if it is the standard of care. It can cause a plaintiff’s case of action to withstand outright dismissal, so-called summary judgment.5 Off-label use is expected and is not evidence of malpractice because the practice of medicine doctrine that underlies FDA legislation stands firmly for the proposition that regulatory efforts are directed primarily at marketing by manufacturers, not device use by physicians.6 However, for example, if off-label prescribing of isotretinoin is the standard of care of moderate acne and full-informed consent of the patient is received, legal liability, in all likelihood will not attach. The package insert along with expert testimony and medical scholarship furnishes evidence as to the standard of care. Obviously, the physician must prescribe medications both on and off label in an ethical fashion and engage in the process of informed consent with patients. The Controversy over Marketing Off-Label Uses Much of the controversy regarding labeling involves marketing by pharmaceutical companies. In order to provide valid scientific research about unapproved drug uses available to doctors and to provide a legal mechanism to limit unapproved off-label marketing, Congress passed the Food and Drug Administration Modernization Act of 1997 (FDAMA). FDAMA states that, a company selling a medication approved by the FDA can disseminate “off-label” written data consisting of unabridged scientific or medical peer-reviewed journal articles or reference publications with a note about the following: — that the use of the drug mentioned in the article is unapproved — mention of who’s paying to disseminate the information — the names of authors or consultants and any relation they have to the manufacturer. In addition, the off-label written data can’t include false or misleading materials, and the manufacturer must further notify the FDA every 6 months of distributions and their recipients. How Off-Label Use Relates to Insurance Coverage The issue of labeling of medication has arisen in the context of pharmaceutical coverage for expensive medication. For example, insurance companies have denied insurance coverage for etanercept (Enbrel) for psoriasis because it’s only indicated for psoriatic and rheumatoid arthritis and not psoriasis itself. The drug’s cost of more than $10,000 for a course of treatment underlies such denials of treatment. Many insurance companies review medications on a case-by-case basis using experts and text references. However, nothing in the law compels an insurance company to cover a medication; coverage is based on the contract between patients and their insurance companies. As the Practice Stands Today Off-label prescribing is an accepted part of medicine. It’s recognized as an integral aspect of the practice of physicians by the FDA and the courts, and there’s no cause of action for using medications off-label. Medical malpractice claims turn on the standard of care rather than on a medications package insert — although off-label use of medications can buttress a claim of malpractice. All medications should be prescribed after a dialogue between the physician and patient results in informed consent. Lastly, medication labels are important issues in matters of the marketing of medications and sometimes in coverage of medications by insurance companies.