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America's Frontline Doctors aren't the only physicians pushing hydroxychloroquine (HCQ); another expert frequently toeing that line is Harvey Risch, MD, PhD, an epidemiologist at Yale University in New Haven, Connecticut.

Risch authored a on July 23 calling on doctors to immediately start treating patients with HCQ.

Risch points readers to his review -- he is the only author -- published in late May that cites five studies in support of HCQ, particularly when used early in the course of COVID-19.

None are randomized controlled trials. One is the heavily publicized and now , and colleagues in March that sparked initial hopes for HCQ. Two have no corresponding data or publications.

Risch asserts his own re-analysis of the French study suggests a stronger benefit for HCQ plus azithromycin when started earlier in the illness compared with standard of care. But researchers have called the original data involving only 42 patients "uninterpretable."

A published in May involved 973 patients all of whom got HCQ; there was no randomization or control.

For his third study, Risch links to a , a doctor who cares for a large Orthodox Jewish population in Monsey, New York. Zelenko has made headlines for managing to catch the ear of FDA Commissioner Stephen Hahn, MD, to request help with access to HCQ for an outpatient trial.

Risch cites data from Zelenko on 405 outpatients who were treated with HCQ, azithromycin, and zinc, of whom six were hospitalized and two died. There was no control group, and the Google document doesn't provide more detail on the data.

The fourth citation is a controlled, but not randomized, study from Brazil with a total of 636 patients; 412 were treated with HCQ and azithromycin, with 224 who declined treatment serving as controls. Fewer of those on the drugs had to be hospitalized, but with no randomization, the treatment's role is uncertain.

Finally, Risch cites a small ongoing study in a long-term care facility on Long Island in New York that gave HCQ plus doxycycline to about 200 high-risk COVID patients, again with no control group. Only nine died, suggesting a treatment benefit, but Risch gave no source for the data nor other details.

Risch published a follow-up to that paper -- , on July 20, and again as sole author -- that outlined an additional seven studies that he said support HCQ early in disease. None appear to be large randomized controlled trials, though some have comparator groups. Some lack any citation at all. One study is additional data from Zelenko, on another 400 patients, but again unpublished and without full data.

In the Newsweek editorial and in the later journal submission, both of which were published following three highly publicized randomized trials that reported no benefit from HCQ, Risch did not address or even acknowledge them.

posted on Yale's website, Sten Vermund, MD, PhD, dean of the Yale School of Public Health, distanced himself from Risch's papers.

"My role as Dean is not to suppress the work of the faculty, but rather, to support the academic freedom of our faculty, whether it is in the mainstream of thinking or is contrarian," Vermund wrote.

"Yale-affiliated physicians used HCQ early in the response to COVID-19, but it is only used rarely at present due to evidence that it is ineffective and potentially risky."

Just this week, about two dozen of Risch's Yale colleagues , acknowledging his renown in cancer epidemiology but criticizing his "ardent advocacy" for HCQ. The letter notes that Risch is "not an expert in infectious disease epidemiology and he has not been swayed by the body of scientific evidence from rigorously conducted clinical trials which refute the plausibility of his belief and arguments."

"If HCQ was shown to be effective, even among subgroups of patients with COVID-19 in ongoing high quality trials, we would join our colleagues in promoting access to it for all who need it," the Yale experts wrote. "However, the evidence thus far has been unambiguous in refuting the premise that HCQ is a potentially effective early therapy for COVID-19."

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