As an epidemiologist, I believe that America has been profoundly ill-served by the contribution of its public health authorities to the debate on the efficacy of treating vulnerable COVID-19 patients with hydroxychloroquine (HCQ). It is a debate with a direct link to whether America’s schools should reopen next month. Even those who reject the World Health Organization’s misleading comparison of COVID-19 with the horrendous 1918 Spanish flu pandemic and its presumption that humans lack any immunity against SARS-CoV-2 would welcome improvements in our ability to treat patients with COVID-19, in order to reduce the risk in reopening schools.
Distinguished Yale epidemiologist Harvey Risch has written extensively on the meticulous research demonstrating the efficacy of the early administration of HCQ in combination with the antibiotic azithromycin and zinc. Conclusions from this research are based on criteria developed by British epidemiologist Sir Bradford Hill and Sir Richard Doll, two of the first scientists to discover the causal link between tobacco smoking and lung cancer, criteria that laid the foundations of modern epidemiology and that are used to this day to determine whether an observed association can be ascribed to causation.
Far from exploring this potential breakthrough in the treatment of COVID-19, the National Institutes of Health and the Food and Drug Administration (FDA) were both dismissive, condemning early outpatient treatment with the HCQ triple therapy as ineffective and dangerous. Instead, these agencies state that the only permissible way to determine its efficacy and safety is with randomized clinical trials (RCTs). Virologist Steven Hatfill has described a circle of self-reinforcing media commentary based on flawed, fraudulent, and withdrawn studies and the FDA’s mistaken decision to withdraw its HCQ Emergency Use Authorization, costing thousands of American lives.
Demanding proof when time is short and when there is highly suggestive observational evidence has been condemned by Drs. George Fareed, Michael Jacobs, and Donald Pompan in an open letter to Dr. Fauci. They point out that the FDA has approved many drugs without RCTs—penicillin was so efficacious in treating pneumonia that there was no need for RCTs. Moreover, RCTs are not designed to test the efficacy of a therapy in high-risk outpatient settings before a patient is notified of the results of a test for COVID-19. It cannot be ethical for public health bodies to demand impossible standards of proof for potential lifesaving therapies.
To require an RCT for the HCQ triple therapy is indeed unethical; evidence supporting its use comes from large patient series, controlled trials, and even a natural experiment in the Brazilian state of Pará. In assessing ongoing patient outcomes, keep in mind that observations might be affected should the SARS-CoV-2 virus lose virulence. Spanish authorities report that fatality rates have fallen, even among elderly patients, which would be consistent with reduced SARS-CoV-2 virulence. This, too, should be considered by public authorities in assessing the risks associated with reopening schools.
Yet rather than engage in proper debate, Dr. Fauci has resorted to name-calling. “The pushback has been furious,” Risch writes. Dr. Fauci “has implied that I am incompetent, notwithstanding my hundreds of highly regarded, methodologically relevant publications in peer-reviewed scientific literature.” Dr. Fauci’s position calls to mind that of English statistician Ronald A. Fisher, who in the 1950s vehemently argued against Hill and Doll and their finding that smoking causes lung cancer, on very similar grounds to those used by Dr. Fauci to dispute the efficacy of HCQ—that observational data cannot prove causality. This is an extraordinary position for America’s leading health official to adopt; by the same logic, Dr. Fauci would deny the evidence that tobacco smoking kills.
Dr. Fauci has also waded into the debate on reopening schools, arguing that they should remain closed where the virus is circulating. While the effect of reopening schools on community transmission is uncertain, we know that keeping them closed harms children, especially those in poorer communities. This should not be a matter of politics, left or right. In Britain, chief medical officers have issued a statement on the benefits of school to children and the “exceptionally small risk” of children dying from COVID-19. In my country, Finland, Prime Minister Sanna Marin, a left-of-center Social Democrat, decided in May that Finnish children should return to school, despite opposition from the teachers’ union.
It would be a needless calamity for America’s schools not to reopen at the start of the new school year—and a calamity not to protect the vulnerable with the most efficacious therapies we have. Clinical evidence strongly supports the use of the HCQ triple therapy at an early stage for the elderly and those with comorbidities. I earnestly hope that Dr. Fauci reconsiders his opposition to HCQ and restores his hitherto considerable reputation.