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Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial (Gautret et al., 2020)

Lover, medRxiv, doi:10.1101/2020.03.22.20040949

Apr 2020

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HCQ for COVID-19

1st treatment shown to reduce risk in March 2020

^*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.

Lower risk for mortality, hospitalization, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,000+ studies for 60+ treatments. c19hcq.org

Secondary analysis of Gautret et al. showing "modest to no impact of HCQ treatment, with more significant effects from [HCQ+AZ]".

7 meta analyses show significant improvements with hydroxychloroquine for mortality Landsteiner de Sampaio Amêndola, Risch, Risch (B), Stricker, hospitalization Landsteiner de Sampaio Amêndola, recovery Prodromos, combined death/hospitalization/cases Ladapo, and cases García-Albéniz.

Currently there are 39 HCQ for COVID-19 early treatment studies, showing 76% lower mortality [61‑85%], 67% lower ventilation [-710‑99%], 31% lower ICU admission [1‑53%], and 41% lower hospitalization [28‑51%].

1. García-Albéniz et al., Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19, European Journal of Epidemiology, doi:10.1007/s10654-022-00891-4.springer.com, doi.org.

2. Ladapo et al., Randomized Controlled Trials of Early Ambulatory Hydroxychloroquine in the Prevention of COVID-19 Infection, Hospitalization, and Death: Meta-Analysis, medRxiv, doi:10.1101/2020.09.30.20204693.medrxiv.org, doi.org.

3. Landsteiner de Sampaio Amêndola et al., COVID-19 Infection in Rheumatic Patients on Chronic Antimalarial Drugs: A Systematic Review and Meta-Analysis, Journal of Clinical Medicine, doi:10.3390/jcm11226865.mdpi.com, doi.org.

4. Prodromos et al., Hydroxychloroquine is effective, and consistently so used early, for Covid-19: A systematic review, New Microbes and New Infections, doi:10.1016/j.nmni.2020.100776.sciencedirect.com, doi.org.

5. Risch, H., Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis, American Journal of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093.oup.com, doi.org.

6. Risch (B), H., 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”, American Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152.oup.com, doi.org.

7. Stricker et al., Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Workers from India: A Meta-Analysis, Journal of Infection and Public Health, doi:10.1016/j.jiph.2021.08.001.sciencedirect.com, doi.org.

Important missing comments or errors? Let us know.

Lover et al., 10 Apr 2020, preprint, 1 author.

This Paper HCQ All

Quantifying treatment effects of hydroxychloroquine and azithromycin for COVID-19: a secondary analysis of an open label non-randomized clinical trial

Andrew A Lover

doi:10.1101/2020.03.22.20040949

The author stands by all analytical and statistical aspects of this preprint. However, subsequent to this analysis, further details of the original study have been released-with major uncertainties in study design, reporting, choice of endpoints, and most importantly, data integrity [1, 2] . Therefore, all results from the original study should be viewed with considerable skepticism.

References

Bik, Thoughts on the Gautret et al. paper about Hydroxychloroquine and Azithromycin treatment of COVID-19 infections

Coveney, Firthlogit: Stata module to calculate bias reduction in logistic regression

Gautret, Lagier, Parola, Van Thuan, Hoang et al., Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial, medRxiv

Ian R White, Horton, Carpenter, Pocock, Strategy for intention to treat analysis in randomised trials with missing outcome data, Bmj

Lorenc, Oliver, Adverse effects of public health interventions: a conceptual framework, J Epidemiol Community Health

Mcnutt, Wu, Xue, Hafner, Estimating the relative risk in cohort studies and clinical trials of common outcomes, American journal of epidemiology

Michael A Johansson, Reich, Meyers, Lipsitch, Preprints: An underutilized mechanism to accelerate outbreak science, PLoS medicine

Nakagawa, Innes, Cuthill, Effect size, confidence interval and statistical significance: a practical guide for biologists, Biological reviews

Pubpeer, Pubpeer: Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial

Rivers, Chretien, Riley, Pavlin, Woodward et al., Using "outbreak science" to strengthen the use of models during epidemics, Nature Communications

Royston, Parmar, Flexible parametric proportional-hazards and proportional-odds models for censored survival data, with application to prognostic modelling and estimation of treatment effects, Statistics in medicine

Sandeep, Gupta, Intention-to-treat concept: a review, Perspectives in clinical research

Tjur, Coefficients of determination in logistic regression models-a new proposal: The coefficient of discrimination, The American Statistician

Late treatment
is less effective

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