Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort.
Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."
Vernaz et al., 12/31/2020, retrospective, propensity score matching, Switzerland, Europe, peer-reviewed, 15 authors.
risk of death, 15.3% lower, RR 0.85, p = 0.71, treatment 12 of 93 (12.9%), control 16 of 105 (15.2%), HCQ vs. SOC, PSM.
hospitalization time, 49.0% higher, relative time 1.49, p = 0.002, treatment 93, control 105, HCQ vs. SOC, PSM.
This study is excluded in the after exclusion results of meta analysis: substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, substantial unadjusted confounding by indication likely.
Effect extraction follows pre-specified rules
prioritizing more serious outcomes. For an individual study the most serious
outcome may have a smaller number of events and lower statistical signficance,
however this provides the strongest evidence for the most serious outcomes
when combining the results of many trials.