About a year ago, we discussed precedent establishing that off-label use can be, and often is, the medical standard of care. Conversely, that means that it could be considered medical malpractice not to prescribe certain off-label therapies. All of a sudden, that issue has popped up again, with two cases in the last week, both dealing with the off-label use of drugs in the abortion context.
Abortion-performing physicians have since developed a medication-abortion protocol using mifepristone that, although varying significantly from the FDA protocol, has become the de facto standard of care in Texas. This protocol, or one substantially identical, accounts for the vast majority of medication abortions performed nationwide since 2007. The new protocol [is] endorsed by the American College of Obstetricians and Gynecologists.
The practice of developing new protocols using different dosages or using medications for different uses than for which they were approved by the FDA is not unique to mifepristone. It is common in medicine, when supported by adequate study, to use and prescribe medication in this “off-label” use. . . . [I]n addition to being used as a part of medical-abortion protocols, [mifepristone] is also used in obstetrics to ripen the cervix prior to the induction of labor and to stop postpartum hemorrhage.
How does this figure in Abbott? The Texas legislature, as it no doubt ordinarily would have the power to do (see id. at *10 (recognizing “the [state] government’s broad discretion to regulate medical practice”)), undertook to regulate physician off-label use – uniquely in the abortion context. While states can regulate off-label use as part of their overall power to set standards of medical practice, they generally have not done so – except to require insurance companies to pay for certain off-label treatments (discussion of which is beyond the scope of this post). Other than in the abortion context, we know of only a couple of states that actually undertook to regulate an off-label use – Utah did so with respect to the diet drug combination fen-phen. See Utah R.156-37-604(2) (requiring a specific form of informed consent). Note: there may be other instances, particularly in the form of regulations (such as Tennessee’s former “Elvis Law”) but we’re not familiar with them; this one we knew about from previous involvement in fen-phen litigation.
The targeting of off-label use limited to the abortion context prompted constitutional litigation under the “undue burden” standard set in Gonzales v. Carhart, 550 U.S. 124, (2007), specifically that there must be “reasonably alternative procedures.” Abbott, 2013 WL 5781583, at *10. Thus, as a first step, the court had to find the off-label use in question was safe and effective. It did. “[W]hen performed in accordance with the off-label protocol, medication abortion is a safe and effective procedure.” Id. at *9. Abbott is thus a rare case in which a formal judicial determination exists that an off-label use is “safe and effective” – which is the standard that the FDA itself applies.
In contrast, the FDA-approved on-label procedure, was found to be “more imposing and unpleasant,” “requires more of the physician’s time,” “more expensive,” and narrower in scope. Id. But while the FDA-approved use was “clearly more burdensome” compared to the off-label use prohibited by the Texas statute, that burden was not “undue,” which under the constitutional standard, was required to invalidate the law. Id. at *10. Only in situations where “medication abortion is the only safe and medically sound option” did the burden become “undue” and the statutory prohibition of that particular off-label use was unconstitutional as applied. Id. at *10-11.
Far more interesting, and more emphatic, with respect to the virtues of off-label use is Cline v. Oklahoma Coalition for Reproductive Justice, ___ P.3d ___, 2013 WL 5799863 (Okla. Oct. 29, 2013). Note: this is by the Oklahoma Supreme Court. When we last visited that court, it had just federalized Oklahoma tort law, by generally recognizing FDCA (and other federal statute/regulation)-based negligence per se. We were very concerned that the Howard v. Zimmer, Inc., 299 P.3d 463 (Okla. 2013), could be used to expand traditional tort causes of action under Oklahoma law in all sorts of novel and bizarre ways.
Well, we still have that general concern, but if Cline is any indication, off-label use is not going to be one of those areas. In Cline – answering questions of state law certified to it by the United States Supreme Court – the Oklahoma Supreme Court had nothing but good things to say about off-label use.
Cline was somewhat different than Abbott in its facts. The Oklahoma statute was ultimately more restrictive than the Texas statute, in that it “effectively bans all medication abortions,” 2013 WL 5799863, at *7, whether on or off-label. See also id. at *8 (prohibition includes “a protocol approved by the [FDA]”). The statute’s impact on FDA-approved use thus is different (and may well be preempted, although that is not what Cline addresses), but its impact on off-label use, while wider in scope, is of the same nature as was the Texas statute in Abbott.
The Oklahoma Supreme Court’s reaction, however, was much more protective of the position of off-label use under Oklahoma law generally. Indeed, the court used a phrase we haven’t heard before – “evidence-based regimen” – as a synonym for off-label use. While we’ve always preferred “off-label use” to other terms such as “unapproved use” or “unlabeled use,” we certainly wouldn’t object if the Oklahoma terminology were to catch on:
The practice of providing approved medications using regimens different from that described in the medication’s final printed label is known as an “off-label use,” or an “evidence-based regimen.” The FDA has stated that evidence-based regimens are common, permissible, and can be required by good medical practice.
Cline, 2013 WL 5799863, at *3 (footnote omitted). This omitted footnote is also relevant to our interests. The court quoted Planned Parenthood v. Dewine, 696 F.3d 490 (6th Cir. 2012), about off-label use: “[I]t is standard medical practice in the United States for physicians to prescribe FDA-approved drugs in dosages and for medical indications that were not specifically approved − or even contemplated − by the FDA, particularly where the alternative use is supported by adequate study.” Cline, 2013 WL 5799863, at *3 n.10 (quoting Dewine, 696 F.3d at 496). Under Oklahoma law generally, there’s nothing wrong with physicians engaging in off-label use.
Later on in the opinion, after extensive discussion of off-label use specifically in the abortion context, the court in Cline returns to the status of off-label use generally, holding that, “FDA-approved labeling is not intended to limit or interfere with the practice of medicine nor to preclude physicians from using their best judgment in the interest of the patient.” Id. at *5. The court adopts a position long taken by the FDA itself:
The FD & C Act does not, however, limit the manner in which a physician may use an approved drug. 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. Such “unapproved” or, more precisely, “unlabeled” uses may be appropriate and rational in certain circumstances, and may, in fact, reflect approaches to drug therapy that have been extensively reported in medical literature. The term “unapproved uses” is, to some extent, misleading. It includes a variety of situations ranging from unstudied to thoroughly investigated drug uses. Valid new uses for drugs already on the market are often first discovered through serendipitous observations and therapeutic innovations, subsequently confirmed by well-planned and executed clinical investigation.
Cline, 2013 WL 5799863, at *5 (quoting and following FDA Drug Bulletin 12:4-5 (1982), and 59 Fed.Reg. 59,820, 59,821 (FDA Nov. 18, 1994)).
In the opinion of the Oklahoma Supreme Court, off-label use is necessitated by ongoing scientific developments in the medical field, which necessarily outpace what manufacturers can be expected to present to the FDA at any given time:
[H]uman progress is not static: medical research and advances do not stop upon a particular drug’s approval by the FDA. Researchers continue to perform clinical trials, doctors continue to gain experience, and widespread use of a particular treatment allows the medical community to collect data about side effects, alternative doses, and potential new uses for treatments.
[P]hysicians . . . have concluded that the protocol in the mifepristone FDA-approved label likely no longer meets the standard of care. Both the American College of Obstetricians and Gynecologists and the World Health Organization have endorsed these alternate regimens as safer and more effective than the now-outdate regimen provided for in mifepristone’s FDA-approved label. Good medical practice and the best interests of the patient require that physicians use legally available drugs, biologics and devices according to their best knowledge and judgment.
Id. (quotation marks and footnotes omitted).
Cline also points out that in every area other than abortion “the Oklahoma Legislature has recognized the importance of allowing physicians to prescribe medications based on science and their medical judgment rather than dogmatic adherence to FDA labeling.” Id. (citing statutes governing physician professional conduct and prohibiting insurance companies from refusing to cover off-label use in oncological treatment). Likewise, in terms of treatment regimens covered by Medicare in Oklahoma:
Nowhere . . . is the [Medicare] board constrained by uses authorized in the FDA-approved labels for prescription drugs in making its determinations. Instead, the statute uses the term “medically necessary” in deference to the knowledge and experience of physicians exercised in the practice of medicine.
Id. at *7 (citations to Medicare statutes omitted).
In concluding, the Cline opinion has more to say about the “long-respected medical discretion of physicians” in the therapeutic treatment of their patients in the context of off-label use:
The role of the physician is to heal the sick and the injured, and physicians are required to undergo rigorous training to develop the required knowledge and experience to perform that role well. Physicians must inform their patient of the risks involved in any treatment, and together with the patient, must determine the best course of treatment. Part of the Hippocratic Oath requires Physicians to “follow that system of regimen which, according to my ability and judgment, I consider for the benefit of my patients, and abstain from whatever is deleterious and mischievous.”
2013 WL 5799863, at *7-8 (footnote omitted).
Whatever one thinks about abortion, or about reproductive freedom generally, from our defense perspective in product liability litigation, the extensive discussion off-label use generally by the Oklahoma Supreme Court in Cline is music to our ears, particularly as a brake, at least in the off-label context, on the potential ramifications of FDCA-based negligence per se in that court’s earlier Howard decision.