Collection of seven retrospective database analyses in the USA, showing higher mortality with treatment (not statistically significant).
Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication.
Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason.
Authors do not mention the possibility of any of these likely confounding factors.
Stewart et al., 3/17/2021, retrospective, USA, North America, peer-reviewed, 37 authors.
risk of death, 18.0% higher, RR 1.18, p = 0.27, treatment 90 of 429 (21.0%), control 141 of 737 (19.1%), adjusted per study, VA, HCQ+AZ.
risk of death, 1.0% lower, RR 0.99, p = 0.95, treatment 66 of 578 (11.4%), control 188 of 1,243 (15.1%), adjusted per study, TriNetX, HCQ+AZ.
risk of death, 129.9% higher, RR 2.30, p < 0.001, treatment 32 of 108 (29.6%), control 33 of 256 (12.9%), Synapse, HCQ+AZ.
risk of death, 9.0% higher, RR 1.09, p = 0.65, treatment 212 of 1,157 (18.3%), control 203 of 1,101 (18.4%), adjusted per study, Health Catalyst, HCQ+AZ.
risk of death, 90.0% higher, RR 1.90, p = 0.09, treatment 46 of 208 (22.1%), control 47 of 1,334 (3.5%), adjusted per study, Dascena, HCQ+AZ.
risk of death, 16.0% higher, RR 1.16, p = 0.26, treatment 428 of 1,711 (25.0%), control 123 of 688 (17.9%), adjusted per study, COTA/HMH, HCQ+AZ.
risk of mechanical ventilation, 29.0% higher, RR 1.29, p = 0.09, treatment 48 of 305 (15.7%), control 95 of 1,302 (7.3%), adjusted per study, Aetion, HCQ.
This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication likely, substantial time varying confounding likely due to declining usage over the early period when overall treatment protocols improved dramatically, includes PCR+ patients that may be asymptomatic for COVID-19 but in hospital for other reasons.
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.