key: cord-0738316-3lbkh5c8
authors: Huffman, Alan
title: The Ethics of Using Off-Label Medications to Treat COVID-19
date: 2022-06-30
journal: Annals of Emergency Medicine
DOI: 10.1016/j.annemergmed.2022.04.007
sha: b217dad3b2cb80965780babbc4633d0936667f29
doc_id: 738316
cord_uid: 3lbkh5c8

nan

has noted that treating the disease with the off-label antiparasitic drug ivermectin has developed a "weird cult following." 1 There is so much support for using the drug that the state health department issued an alert advising people not to take ivermectin when not prescribed and that it should not be used for treating COVID-19. 2 This alert followed a jump in the number of calls to a poison control center over ingestion of the drug, often purchased from animal supply stores. "This is medical treatment. You wouldn't get your chemotherapy at a feed store," Dobbs said in a media interview. 3 Similar stories have been reported in other states, including Oklahoma, Utah, and Alabama. [4] [5] [6] As Dobbs and other health officials have noted, there is likewise no evidence that another off-label drug, hydroxychloroquine, is effective in treating patients with COVID-19. Instead, Dobbs recommended COVID-19 treatment medications that have been authorized by the Food and Drug Administration (FDA), including nirmatrelvir/ritonavir (Paxlovid, Pfizer) and molnupiravir, with the usual caveats regarding possible drug interactions. 7 The fact that a state health care official would need to stress these points illustrates the currently fraught environment of the pandemic, in which some patients pressure providers to prescribe offlabel medications even though authorized treatments are available. From an ethical and legal standpoint, the issue seems like a no-brainer for providers: treatments that have been approved on the basis of randomized evidence, even on an emergency basis, are the best. Early in the pandemic, when there were no known effective options, some experimentation in the face of numerous dying patients may have been warranted, even worthy, but that is no longer true.

Nonetheless, some doctors still use off-label COVID-19 treatments. Some have been sued or fired, but then again, some physicians have been sued for not prescribing them. In one case, John Witcher, MD, an emergency physician and outspoken opponent of vaccine mandates in Yazoo City, Mississippi, claimed on social media that he was fired from the city's Baptist Memorial Hospital after taking 3 patients off FDAapproved remdesivir and replacing it with ivermectin. 8 In another case, a Washington state physician had his license suspended for prescribing ivermectin for COVID-19 treatment, and in Arkansas, 4 jail inmates filed a suit after being dosed with ivermectin without their knowledge. 9,10 On the other hand, there have also been numerous lawsuits-some of them successful-filed by patients or their guardians to force providers to use ivermectin for COVID-19 treatment.

As an observer noted in an article published by the American Bar Association (ABA), the schism over unapproved treatments puts providers in a position of "damned if you do, damned if you don't." 11 However, is that truly the case?

The ABA referred questions about provider legal issues to Robyn Shapiro, JD, BA, with the Health Sciences Law Group, although both stressed that she does not speak for the ABA. Shapiro, a lawyer and bioethicist, said the issue of off-label drug treatment is "interesting from both ethics and legal perspectives." Nonetheless, she said, "It doesn't seem to be a close question." It is not uncommon for drugs to be prescribed off-label, typically when there is no effective alternative, especially with children or when a patient has not responded well to recommended therapies. In the case of COVID-19, however, authorized treatments are available and off-label medications are not effective and could have side effects, she said.

"If you're going to prescribe an offlabel drug in a context where approved drugs are available, are you promoting your patient's best interests?" Shapiro asked. The proper response is to defer to medical standard of care, she said, and added, "The only other legal issue is: Do doctors have a mandate to offer or provide off-label drugs? The answer is: They don't. They may get patient or political pressure to do so, but it is not required."

Shapiro cautioned that when a patient asks for a less effective, unauthorized treatment, a provider should adhere to approved procedures while addressing the patient's wishes respectfully, without offending them. A provider may also choose not to treat a patient.

"Say there is a parent who doesn't want their kid vaccinated, but the pediatrician wants them vaccinated, and they're in the waiting room. Do you keep that patient on?" she asked. "If a physician feels a patient's demands run counter to his or her best judgment about how to treat that patient, that's what they say: 'I'm not able to help you out in doing that.'" Arthur Caplan, PhD, director of the Division of Medical Ethics at New York University's Grossman School of Medicine, said that providers should hold the line on using any unapproved, ineffective medications. Caplan has said that using ivermectin against COVID-19 is "utter nonsense" today and that it would be irresponsible for a doctor to prescribe or tout it for that purpose. Should a physician be pushed to do so, he said in an interview, "The correct response is: 'I'm not doing that.'" He added, "If you're doing this, my view is you should have your license examined and possibly revoked. You're basically practicing outside accepted standard of care."

However, Caplan noted that legislation has passed or is under consideration in several state legislatures that would give patients the right to demand off-label medications for COVID-19 treatment. He said that it is understandable that providers may consider the legal ramifications of refusing to use unapproved treatments. "You might be thinking you should listen more carefully" to such patients, he said. "But state legislators are very, very rarely doctors or nurses. This is not the place where medical standards of care are set. Professionally, you still look to standard of care, to your peers and the guidelines. You can still be sued, but you can't practice medicine from a state capitol without a license. If there were to be such a lawsuit, I would hope that the medical specialty involved, such as emergency medicine, would quickly come to the defense of the doctor. When it comes to lawsuits, where the real liability exists is when someone claims harm due to off-label use."

As providers navigate this ethical and legal terrain, Caplan said, "It's important to keep up with the literature, with what's approved and unapproved, which can change. But the bottom line is: Patients don't dictate medical care. Doctors do, and they should act on their experience, their education, and their peer recommendations." Vin Gupta, MD, MPA, MSc, who is on the faculty of the University of Washington's Institute for Health Metrics and Evaluation, offered similar guidance. Gupta said that as an ICU doctor, "I'd have zero concerns on being sued, since science and health policy clearly states these meds are not to be used for COVID-19." He said that the true ethical and legal risk is for prescribers of off-label medications.

Although ivermectin has received the most recent media attention, similar issues are in play for other unapproved medications, such as hydroxychloroquine. In a recent essay, Jonathan Zenilman, MD, 12 an infectious disease and public health physician at Johns Hopkins in Baltimore, wrote that prescribing hydroxychloroquine for COVID-19 would constitute medical malpractice. "If I, as a physician, stated that a drug is unequivocally effective against COVID-19, ignored the side effects, and stated that there was 'nothing to lose' by taking it, I would be in conflict with the Hippocratic oath dictum, primum non nocere (first do no harm), and working contrary to the medical standard of care which is expected of me," Zenilman 12 wrote. "If I did not carefully balance the risk and benefits, I would be potentially liable for medical malpractice."

Nonetheless, in Texas, a Houston medical doctor was exonerated in 2020 by the Texas Medical Board of Medicine after he was accused of malpractice stemming from his use of hydroxychloroquine to treat patients with COVID-19. The board stated, "the standard of care was met." 13 A Harvard Law School blog noted that an Ohio judge had ruled that a hospital must administer ivermectin to a patient with COVID-19 in its ICU despite the decision by the medical staff, in agreement with the FDA and the Centers for Disease Control and Prevention, that ivermectin is not an appropriate treatment. 14 The author noted that health care providers have a fiduciary duty to act in their patient's best interests and that to directly override the judgment of treating physicians to administer a medication prescribed by a doctor who is not part of the treatment team where the patient has been admitted is "new and frightening ground which raises a host of legal questions." 15 The following questions arise: Do medical professionals directly caring for a patient have a right to refuse to administer a treatment that they think is unwarranted and possibly harmful? Would they be protected from doing so by Ohio's new law that allows health care providers to refuse treatment that violates their conscience? Moreover, what about the doctor willing to prescribe ivermectin-is he likely to get in trouble from the state licensure board? (Probably not, in Caplan's view.)

In its article about lawsuits related to COVID-19 treatment with ivermectin, the ABA argued that no law empowers courts to medicate from the bench by forcing hospitals to administer an off-label drug. Although some courts have ruled otherwise, the article observed, "the better view is that courts should respect the standard of care for COVID-19 treatment developed by hospitals and healthcare providers, and they should recognize that there is no right to try ivermectin for this use." The article concluded, "For the time being, off-label ivermectin treatment is not part of the COVID-19 standard of care, and courts likely cannot force hospitals to change that." Section editors: Truman J. Milling, Jr, MD, and Jeremy Faust, MD, MS Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The author was paid by ACEP to research and write this article.

The views expressed in News and Perspective are those of the authors, and do not reflect the views and opinions of the American College of Emergency Physicians or the editorial board of Annals of Emergency Medicine.

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