Table 3.

Allocation, blinding, and statistical methods

SPIRIT	ORCHID
Allocation
Sequence generation	Patient-level randomization
	1:1 ratio of hydroxychloroquine to placebo
	Randomized in permuted blocks of varying size, stratified by treatment site
Allocation concealment enrollment and randomization	The randomized sequence is stored on a secure server and not available to site study personnel; patients are enrolled via central web-based randomization, accessible 24 h/d.
Blinding	Blinded, placebo-controlled
Statistical methods	Intention-to-treat comparison between groups using a proportional odds model with the COVID ordinal outcome score 14 d after randomization (assessed on Study Day 15) as the dependent variable, randomized group assignment as the primary independent variable, and the following covariates: age, sex, baseline COVID ordinal outcome score, baseline SOFA score, and duration of acute respiratory infection symptoms before randomization.
Interim analyses	Bayesian sequential design with interim analyses at least every 102 patients and suggested stopping rules for efficacy and futility. Statistician will present unblinded outcomes with Bayesian posterior probabilities to data and safety monitoring board at each interim analysis.

Definition of abbreviations: COVID = coronavirus disease; ORCHID = Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease; SOFA = Sequential Organ Failure Assessment; SPIRIT = Standardized Protocol Items: Recommendations for Interventional Trials.