President Trump has been promoting chloroquine, an anti-malarial drug, as “a game changer” in combating the coronavirus, perhaps in combination with the antibiotic Azithromycin. “As the expression goes, ‘What do we have to lose?’ ” Trump asked during Saturday’s media briefing. The answer is: a lot. Experience teaches that promoting untested drugs in this way is irresponsible patient care, sloppy science and dangerous public policy.
It is tempting to ask, as Trump suggests, whether the rigors of scientific inquiry are too demanding in the midst of a pandemic, a luxury of proof the country can’t afford. But laboratory studies and anecdotal treatment of individuals are notoriously unreliable at judging what truly saves lives. Indeed, just last week in the New England Journal of Medicine, we learned that one suggested combination that worked against SARS — lopinavir-ritonavir — does not help treat, much less cure coronavirus.
For patients infected with the coronavirus, particularly those whose condition is worsening, it is a natural human reaction to try something, anything. Unfortunately, this impulse is misguided. Indeed, these “what do we have to lose?” treatments can be very dangerous to individuals and the public health showing that we do have something to lose. Cancer, the oldest malady, offers useful guidance on covid-19, the youngest disease on Earth.
When it comes to cancer drugs, time and again, we have seen that drugs that might help, that should help, actually hurt. For instance, a drug called bevacizumab, better known as Avastin, was once highly promising for breast cancer. The Food and Drug Administration approved it without evidence that it saved lives. It was then rigorously tested in at least three randomized controlled trials — and was shown to make dying cancer patients worse. Those tested suffered increased rates of dangerously high blood pressure, heart failure and nerve damage — and gained no prolonged survival, much less a cure. This prompted the FDA to revoke its use in breast cancer. Plenty of other cancer drugs, such as olaratumab, a drug to combat sarcoma, have been withdrawn from the market as the initial promise from laboratory data, animal studies and a preliminary experiment vanished when a careful trial found the drug worsened the last few months of desperate patients’ lives — producing nausea, vomiting, diarrhea and sores in the mouth, but no increase in longevity.
When it comes to covid-19, physicians, out of desperation, are giving several drugs to patients all at once. Some people recover, and some do not, but the consequence of this kitchen-sink approach is that we don’t know which, if any, of these drugs help or hurt. As immunologist Anthony S. Fauci explained, “at the end of the day, if you’ve given a lot of stuff to people. . . . You don’t know what works. . . . It may have satisfied your humanitarian instincts of giving something to someone when there’s no proven therapy, but you’ve in some respects done a disservice.”
Indeed, unpredictable harms may be unleashed when you combine drugs in people. Already, some nations have reported a rise in patients presenting with chloroquine poisoning. Shortages of chloroquine and another drug promoted by Trump, hydroxychloroquine, threaten the ability of people with lupus and rheumatoid arthritis to obtain these medications.
There is also the problem of fairness in accessing these treatments. Many are not available in the United States or are extremely expensive. Tocilizumab, an immunosuppressant that is being tested for effectiveness against covid-19, costs several thousand dollars per dose. Without FDA approval, only the rich may obtain these drugs, or those receiving care in resource-rich hospitals. Others may use their wealth and connections to obtain promising drugs from foreign countries. Favipiravir, a drug used to treat new strains of influenza, is not available in the United States but only in Japan. The rich have found ways to get the limited supply.
Finally, there is a huge opportunity cost to the “What do I have to lose?” approach. Compassionate use of medications interferes with conducting research. Every person taking chloroquine or some other drug secretly, quietly and outside of a trial is someone’s whose information is being lost and not contributing to our collective knowledge of whether it works. We saw this, too, in cancer medicine. During the 1990s, more than 40,000 women underwent bone marrow transplantation for breast cancer — then, like chloroquine, a highly promising intervention touted as giving hope to desperately ill women. As a result, the vast majority of breast cancer patients, more than 75 percent, received the bone marrow transplantation outside of a research study and delayed completion of necessary trials. Eventually, after many years delay because of the transplants performed outside of research, that treatment was found to inflict serious and even fatal toxicities, without prolonging life.
When it comes to fearsome, fatal conditions, it is human nature to try something because it should help, because it might help, because it must help, or because it couldn’t hurt. But often it does harm people and our quest for a real cure. The best thing we can do in any plague is to make sure what we think works actually does, and if not, to use those resources towards finding a treatment that does work.