With the urgent need for treatments and vaccines for the new coronavirus, there is intensive pressure to make those products available before there is enough evidence to show they work, said Mark McClellan, director of the Duke-Margolis Center for Health Policy.
Mark McClellan, director of the Duke-Margolis Center for Health Policy
The malaria drug hydroxychloroquine is a prime example, where there is limited evidence it may be effective in COVID-19 — the disease caused by the novel coronavirus — but there is a growing demand for the medicine, said McClellan, a former commissioner of the U.S. Food and Drug Administration during the George W. Bush administration.
Much of the interest in hydroxychloroquine and a related drug, chloroquine, was sparked by President Donald Trump, who has promoted the medicines to treat and prevent COVID-19, despite a lack of evidence they are safe and effective in the disease.
Because the drugs are approved in the U.S. to treat malaria, lupus and rheumatoid arthritis, U.S. doctors can prescribe them off-label for other uses, including COVID-19 — a disease that lacks any approved treatments.
Off-label prescribing is a long-time common practice.
NIAID Director Anthony Fauci, coronavirus response coordinator Deborah Birx and President Donald Trump
Trump made no secret about wanting the FDA to make hydroxychloroquine and chloroquine available for COVID-19 and on March 28, the agency issued an emergency use authorization for the pills, but only for supplies of the products donated to the U.S. Strategic National Stockpile for use in hospitalized patients with the disease.
But the two medicines have been linked to a number of serious side effects, including fatal cardiac arrhythmias and suicide.
Demand impedes studies
The demand for the two drugs has not only created a shortage of the medicines, it has made studies in COVID-19 more complicated, McClellan said during an April 6 online forum hosted by the Alliance for Health Policy.
Even in desperate times, like the current COVID-19 crisis, it is important to recognize that drugs that may seem promising early on — in test tubes, animal studies or small clinical trials — often end up not working in broad populations of people, Margaret Hamburg, a former FDA commissioner during the Obama administration, said during a separate April 6 online forum co-hosted by the Commonwealth Fund and the Alliance for Health Policy.
"Some people say, 'Well, in a crisis, anything must be better than nothing,' but that also isn't the case because drugs have toxicities, vaccines can have safety issues," said Hamburg, who now serves as the foreign secretary at the National Academy of Medicine. "You could make someone worse off and you could also prevent them from getting other treatments that might have benefited them."
Margaret Hamburg, foreign secretary at the National Academy of Medicine
While pursuing more innovative ways to conduct clinical studies and more rapidly obtain data, "we still have to always have true scientific rigor, because we're not doing anybody any favors if we don't know whether the products actually work," Hamburg said.
Rushing unproven products to patients not only risks harming them but also makes it more difficult to ultimately figure out what products are safe and effective, said Holly Fernandez Lynch, assistant professor of medical ethics at the University of Pennsylvania.
If everyone starts using an experimental treatment or an approved medicine off-label, "there's nothing to compare outcomes against," Fernandez Lynch told S&P Global Market Intelligence.
With a disease like COVID-19, "it's hard to know if someone spontaneously gets better or gets better because of the intervention," she said.
By saying it is appropriate to broadly market unproven interventions for COVID-19, "we may be undermining the importance, in general, of doing the hard work to study potential therapies and vaccines to understand what works and what doesn't, even outside the COVID-19 context," Patti Zettler, assistant professor of law at The Ohio State University, said in an interview.
Damaging the public trust
Public trust in researchers and the biomedical enterprise could be damaged if an investigational drug or biologic that is prematurely rushed into clinical trials causes serious harm to study participants, said Leigh Turner, associate professor at the University of Minnesota Center for Bioethics.
Alison Bateman-House, assistant professor of medical ethics at NYU Langone Health
It could become difficult for researchers to recruit study participants to clinical studies testing experimental products if other drugs, on the basis of flimsy evidence, are falsely touted as therapies or cures, Turner told S&P Global Market Intelligence.
Substantial public investments could also be lost if products with little data are procured and distributed but later fail to show they work in COVID-19, he said.
If regulators fail to ensure the first products approved for a new disease like COVID-19 are truly effective, once they are in use, there may be less incentive to bring additional drugs or vaccines to market, Alison Bateman-House, assistant professor of medical ethics at NYU Langone Health, said in an interview.
For vaccines, approving anything less than a robust safety and efficacy data portfolio risks "fanning the flames" of the anti-vaccine proponents and "increasing reluctance to vaccinate, which could have implications for far more diseases than just COVID-19," Bateman-House said.