Subgroup analysis of differences in ordinal scale at days 28–35.

Estimated proportional odds ratios comparing day 28–35 ordinal scale in HCQ/CQ versus control groups. Estimates are given for the pooled patient population and for subgroups. Blue circles represent model-standardized estimates; blue horizontal lines represent 95% credible intervals. Open grey circles represent plug-in estimates; grey horizontal lines represent 95% confidence intervals. Grey circle size represents the number of patients in the corresponding subgroup. Arrows indicate uncertainty intervals extending beyond plot limits. Study acronyms are explained in Fig 1. Two trials did not have study acronyms (only trial registration numbers). Abbreviations: 95% CrI, 95% credible intervals; HCQ/CQ, hydroxychloroquine or chloroquine; NA, not applicable; NIV, noninvasive ventilation (includes BiPAP/CPAP and/or high-flow oxygen); OR, odds ratio.</p

Trial characteristics: Treatment groups, participant assessment, and inclusion/exclusion criteria.

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Trial selection process.

aTwo of the trials did not have study acronyms (only trial registration numbers). Abbreviations: COVID MED, Comparison Of Therapeutics for Hospitalized Patients Infected With SARS-CoV-2 In a Pragmatic aDaptive randoMizED Clinical Trial During the COVID-19 Pandemic; HAHPS, Hydroxychloroquine vs. Azithromycin for Hospitalized Patients With Suspected or Confirmed COVID-19; OAHU-COVID19, A Randomized, Controlled Clinical Trial of the Safety and Efficacy of Hydroxychloroquine for the Treatment of COVID-19 in Hospitalized Patients; ORCHID, Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among In-patients With Symptomatic Disease; TEACH, Treating COVID-19 With Hydroxychloroquine; WU352, Washington University 352: Open-label, Randomized Controlled Trial of Hydroxychloroquine Alone or Hydroxychloroquine Plus Azithromycin or Chloroquine Alone or Chloroquine Plus Azithromycin in the Treatment of SARS CoV-2 Infection.</p

Search strategy in detail.

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Posterior predictive check of primary outcomes by study.

Shown are observed outcome data (first row) and draws for the posterior predictive distribution (subsequent rows) of the ordinal outcome scale at day 28–35, plotted against the expected linear predictor for each individual. Each column corresponds to one study in our analysis. Data points have been jittered for clarity. (PDF)</p

Changes to the prespecified statistical analysis plan.

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Data dictionary from data harmonization spreadsheet.

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Primary, secondary, and safety outcomes, overall and by trial.

Primary, secondary, and safety outcomes, overall and by trial.</p

Risk of bias assessment.

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Conditional covariate effects.

Conditional effects from the Bayesian proportional odds model. Shown are (1) the relative risk of mechanical ventilation or death at day 28–35; (2) the estimated probabilities of mechanical ventilation or death at day 28–35 under control and HCQ/CQ; and (3) the log proportional odds ratio comparing HCQ/CQ and control. Each of these effects are shown for reference individuals with the following covariate values: age 60, BMI 25, no baseline comorbidities, baseline ordinal score of 5, and sex coefficient set between male and female values. Curves for continuous covariates are accompanied by 50% and 95% credible bands; intervals for discrete covariates are accompanied by 66% and 95% credible intervals. BMI indicates body mass index; HCQ/CQ, hydroxychloroquine or chloroquine. (PDF)</p