Hydroxychloroquine and chloroquine have been at the center of debate in recent weeks over which drugs should be used to treat COVID-19. Neither product has strong evidence to support use for this purpose, and small studies have either had significant flaws or failed to demonstrate effect.
Nonetheless, President Donald Trump can’t seem to stop pushing them, arguing that patients have nothing to lose. But we should inject caution here. As public officials and scientists rush to innovate, no one should overlook the critical role of strong regulatory protections in supporting our ability to actually figure out which drugs work against COVID-19. Weakening commitment to science and evidence during this crisis truly would be “a cure worse” than the disease.
There are no Food and Drug Administration-approved drugs to treat COVID-19, and no product has strong data to support its use against this disease. Nonetheless, on March 28, the FDA issued an emergency use authorization for certain hydroxychloroquine sulfate and chloroquine phosphate products donated to the strategic national stockpile by various pharmaceutical companies. The EUA was granted exclusively to the Biomedical Advanced Research and Development Authority, allowing it to distribute these drugs for the unapproved use of treating hospitalized COVID-19 patients unable to participate in clinical trials.
Policy in this area should be driven by scientific expertise, not false hope.
An EUA is not the same as the FDA’s traditional marketing approval. To be approved under normal rules, drugs must be shown safe and effective for their intended use. An EUA, in contrast, is a temporary authorization granted in the face of a public health emergency, based only on a determination that a product “may” be effective and that its likely benefits outweigh its likely risks.
An EUA is not the only way that COVID-19 patients may access hydroxychloroquine and chloroquine. A physician is generally free to prescribe approved drugs for “off-label” use. Because several hydroxychloroquine and chloroquine products have been FDA-approved for malaria, lupus and rheumatoid arthritis, they’re eligible for off-label use against COVID-19.
Following the president’s comments that these drugs could be a potential “game changer,” attention and prescriptions sky-rocketed, despite caution from experts. Although there have been efforts to help protect supply for those patients needing the drug for their proven indications, some of these patients have been told they may have to go without.
It is too soon to say whether chloroquine products work for COVID-19. Severe side effects have caused some hospitals to stop using them altogether. There is a great need for rigorously conducted clinical trials.
There are other drugs with some potential to combat COVID-19, but that have not yet been approved for any use and therefore may not be prescribed off-label. These drugs are under investigation in clinical trials. For seriously ill patients, the FDA has a pathway known as “expanded access” by which patients may be dosed with unapproved drugs for treatment use, if they are unable to enroll in a clinical trial. This eligibility restriction is critical because it ensures that patients cannot secure access by opting out of the trials designed to produce the evidence needed to confidently assess a product’s safety and efficacy.
Drug maker Gilead has emphasized this approach with its investigational antiviral drug remdesivir.
Pragmatism is needed to collect data in real time, as patients are also in desperate need of treatment. That’s precisely the approach taken by the World Health Organization in its large trial of four potential treatments for COVID-19 with over 70 countries participating. The trial is designed to minimize the burden on physicians and patients, while allowing random assignment and collection of systematic, anonymous data.
We have to stop guessing about what’s going to work. Patients today and tomorrow need a commitment from politicians, policymakers, companies and physicians to prioritize science and rigorous study. Off-label use and expanded access may be reasonable options for patients when there is no clinical trial available, but if there is, we have to prioritize enrollment.
The FDA has demonstrated its willingness to help speed trials and facilitate the collection of data. But its regulatory standards must not be short-circuited and its flexibility must be used judiciously. Policy in this area should be driven by scientific expertise, not false hope, hunches or short-sighted political demands.
Christopher Robertson is a law professor at the University of Arizona; Alison Bateman-House is a research assistant professor at New York University Langone Medical Center; Holly Fernandez Lynch is an assistant professor of medical ethics at the University of Pennsylvania; and Keith Joiner is a professor of medicine, economics and health promotions science at the University of Arizona. Distributed by The Associated Press.
