Use of hydroxychloroquine in multidrug protocols for SARS-CoV-2
IntroductionWe read with interest an editorial by Millar1 concerning the role of hydroxychloroquine in the treatment of COVID-19 patients. Community standard of care multidrug therapies for COVID-19 were based on signals of benefit and acceptable safety.2-9 At the onset of the pandemic, there was insufficient time for large prospective randomized controlled trials (RCT) to validate community standard of care protocols. In such studies, randomization should handle the validity threats of selection bias and both known and unknown confounders, however successful randomization requires a large number of patients with outcome events (e.g. hospitalizations, deaths), to ensure that the patients experiencing these events are also randomized.10 As an example, the number n of events needed to randomize a dichotomous equiprobable confounder variable (i.e. similar to male/female) within x = 10% margin (with 95% confidence) can be obtained by bounding the ratio σ/µ of standard deviation to mean with 2(σ/µ) = 2(1/n)1/2 ≤