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HCQ study #174 of 360   Meta Analysis
10/8 Late treatment study
Soto-Becerra et al., medRxiv, doi:10.1101/2020.10.06.20208066 (Preprint)
Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
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Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care.
This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication.
In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group.
For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More than the total excess mortality happened on the first day. This is consistent with treated patients being in more serious condition, and with many of the control group patients being in hospital for something unrelated to COVID-19.
Authors use a machine learning based propensity scoring system that appears over-parameterized and likely to result in significant overfitting and inaccurate results. Essentially they test for all interactions between two and three covariates. The nature and large number of covariates means many random correlations may be found. COVID-19 severity is not used.
This study also does not compare treatments with a control group not receiving the treatment - authors put patients receiving treatments after 48 hours in the control group.
Authors state that outcomes within 24 hours were excluded, however KM curves show significant mortality at day 1 (only for the treatment groups).
Several protocol violations and missing data have also been reported in this study: [1, 2].
See also: [3].
Ivermectin dosage details: [4]
Soto-Becerra et al., 10/8/2020, retrospective, database analysis, Peru, South America, preprint, median age 59.4, 4 authors.
risk of death, 18.1% lower, RR 0.82, p < 0.001, treatment 346 of 692 (50.0%), control 1,606 of 2,630 (61.1%), day 54 (last day available) weighted KM.
risk of death, 84.0% higher, RR 1.84, p = 0.02, treatment 165 of 692 (23.8%), control 401 of 2,630 (15.2%), adjusted per study, day 30.
This study is excluded in the after exclusion results of meta analysis: substantial unadjusted confounding by indication likely, 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.
All 360 studies   Meta Analysis
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