This analysis from experts on the ethics of pandemic drug and vaccine research raises significant concerns about promoting the use of unproven off-label uses drugs as part of COVID-19 response efforts.
While acknowledging there is limited evidence for its effectiveness, and that he is neither a research scientist or a physician, President Trump has tweeted and stated multiple times at recent COVID-19 press briefings his support for the use of hydroxychloriquine, a common malaria drug, as a preventative against Coronavirus. As he stated at the April 4, 2020 press briefing, “There is a possibility – a possibility – and I say it: what do you have to lose? I’ll say it again: what do you have to lose? Take it. I really think they should take it. But it’s their choice and it’s their doctor’s choice, or the doctors in the hospital. But hydroxychloroquine. Try it, if you like.”
In a recent blog post on the Health Affairs health policy journal web site, Drs. Holly Fernandez Lynch, Alison Bateman House, and Arthur L. Caplan answer the “What do you have to lose?” question with: quite a lot.
According to the authors, who are all experts in the ethics, regulation, research and use of experimental treatments during emergencies, such statements are “stunningly dangerous,” especially as these pronouncements give a false impression that, with access to these drugs, we may be able to quickly get things back to “normal” and ease up on the only intervention known to slow down the virus’ spread: sheltering in place.
In addition to creating conflict with efforts to “flatten the curve,” the authors discuss how doing what the President recommends will not only make the drug more scarce for use by those who use the drug for approved treatments (it is currently approved for use in cases of malaria, lupus, and rheumatoid arthritis), it also will make it more difficult to accurately determine:
- whether or not the treatment might work,
- safe and appropriate dosage levels, especially given the fact that these drugs can have severe side effects, and
- whether the benefits overall outweigh the drug’s risks of use for these purposes.
It is especially important that prescribers not cave to customer demand when the side effects are so well known but the benefits are so unclear. According to the authors:
Because FDA doesn’t regulate the practice of medicine, physicians can prescribe these drugs “off-label” for whatever they deem clinically appropriate, including COVID-19. With off-label use, there’s no requirement that trial participation be prioritized (for that drug or any other) – or that any patient data, even regarding safety, be tracked. Moreover, physicians who might otherwise have been cautious about off-label prescribing for COVID-19 on the basis of little to no data may be buoyed by the emergency grant of malpractice immunity for, among other things, the prescription or administration of “covered countermeasures” used to treat or prevent COVID-19. This comes on top of the common misperception during public health crises that doing anything is better than doing nothing and that using approved drugs off-label will be, at worst ineffective, but not unsafe. In these circumstances, unless all stakeholders take concerted steps to encourage the rigorous study of off-label uses, we’ll end up without critical data about their safety and efficacy.
As the authors state, citing a JAMA Commentary that similarly cautions against prescribing these drugs for COVID-19, “the reason to prioritize well-designed trials is that the resultant data are essential to figuring out how best to treat COVID-19 patients. But individual patients, fearful and desperate, may not be focused on the longer-term, greater good. Others must be.”