key: cord-0842561-se7hu3bx
authors: Risch, Harvey A
title: Response to: “Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis”
date: 2020-07-20
journal: Am J Epidemiol
DOI: 10.1093/aje/kwaa152
sha: cef8b71ea5c6ba1d1b61418dd4e48e30836558fa
doc_id: 842561
cord_uid: se7hu3bx

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Conflicts of Interest: Dr. Risch acknowledges past advisory consulting work with two of the more than 50 manufacturers of hydroxychloroquine, azithromycin and doxycycline. This past work was not related to any of these three medications and was completed more than two years ago. He has no ongoing, planned or projected relationships with any of these companies, nor any other potential conflicts-of-interest to disclose.

Dr. Korman's thesis is that no available treatments are effective in preventing hospitalization for the overwhelming majority of COVID-19 patients, and that potential hazards are associated with use of hydroxychloroquine (HCQ) + azithromycin (AZ) (1) . The studies that I reviewed (2) contradict this. Dr. Korman superficially describes the same studies that I discussed at length, except with negative adjectives and numerous terms in "quotation" marks to imply, without evidence, their lack of validity. He calls all these studies "anecdotal," to distinguish from the "magic" of randomized controlled trials (3), when government medical and scientific regulatory agencies of western countries around the world routinely use epidemiologic evidence to establish facts of causation, benefit and harm (4) . This disingenuous argument has been discussed at length elsewhere (5) . Dr. Korman's only novel point is that macrolide antibiotics such as AZ can lead to development of antibiotic resistance. Such instances can occur but are uncommon, and this issue has seemingly not been of substantial concern in the hundreds of millions of uses of AZ world-over during the past 30 years.

Drs. Peiffer-Smadja and Costagliola (6) discuss the data in some of the studies that I reviewed.

They first question the small non-randomized trial by Gautret et al. (7) . I also have concerns about subject baseline differences between the treated and untreated subjects in that study and I have discussed those data at length in my response (9) to Dr. Fleury (10) . Third, they label a carefully performed, sequential-patient non-randomized controlled clinical trial an "unpublished, poorly designed studies whose quality is even lower than the papers discussed above." I disagree with this characterization as it is unsupported by the evidence. Fourth, Drs. Peiffer-Smadja and Costagliola assert that the Boulware prevention trial (11) demonstrates lack of treatment efficacy. That prevention trial is not relevant to treatment of high-risk outpatients, because virtually all its subjects were low-risk; it would be difficult for any active treatment to do much better than the one hospitalization observed among the 58 test-positive placebo patients. In fact, a preventive medication that allows subjects to develop antibodies while protecting them from

severe disease and hospitalization is a better goal than blocking infection altogether. Fifth, Drs.

Peiffer-Smadja and Costagliola take issue with the use of case series of treated patients. In the mass-mortality circumstances we face, a cohort of 400 treated high-risk outpatients with one or two deaths can only be considered informative about the fact of treatment efficacy.

Finally, in pandemic times when months and years of delay cannot be tolerated before large randomized controlled trials are completed, it is possible to quibble with apparent imperfections in almost any study. That misses the forest for the trees. Since my paper (2) (12, 13) , and a meta-analysis of studies to-date completely demonstrates this benefit (14) . 

Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients

Early outpatient treatment of symptomatic, high-risk Covid-19 patients that should be ramped-up immediately as key to the pandemic crisis

The magic of randomization versus the myth of real-world evidence

Evidence for health decision making-beyond randomized, controlled trials

The Media Sabotage of Hydroxychloroquine Use for COVID-19: Doctors Worldwide Protest the Disaster. Media and Big Pharma are in lockstep to suppress a cheap, life-saving Covid-19 therapy in order to reap pandemic-sized profits

Re: Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France

Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients That Should be Ramped-Up Immediately as Key to the Pandemic Crisis

Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients That Should be Ramped-Up Immediately as Key to the Pandemic Crisis

A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19

Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19

Risk factors for mortality in patients with COVID-19 in New York City

Hydroxychloroquine and azithromycin as a treatment of COVID-19: Results of an open-label non-randomized clinical trial: Response to David Spencer

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Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine

Doxycycline and hydroxychloroquine as treatment for high-risk COVID-19 patients: Experience from case series of 54 patients in long-term care facilities

Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis

Local physician has 100% survival rate with early administration of hydroxychloroquine