Predictive factors of clinical assays on hydroxychloroquine for COVID-19 mortality during the first year of the pandemic: A meta-synthesis

Abstract

Background: The COVID-19 pandemic led to a violent debate about the efficacy of a repurposed drug hydroxychloroquine (HCQ) and a new broad-spectrum antiviral (remdesivir) and about randomized controlled trials (RCTs) and observational studies. To understand conflicting results in the literature, we performed a meta-synthesis to determine whether intrinsic qualitative criteria within studies may predict apparent efficacy or ineffectiveness of HCQ and remdesivir. Methodology: Predictive criteria were identified through critical review of studies assessing HCQ and remdesivir for COVID-19 mortality from March to November 2020. Multiple correspondence analysis, comparative meta-analysis, and predictive value were used to explore and identify criteria associated with study outcomes. Results: Among the 61 included studies, potential conflict of interest, detailed therapeutic protocol, toxic treatment (overdose or use in contraindicated patients), known centers and doctors, and private data computing company were the most predictive criteria of the direction of effect of the studies. All 18 observational studies evaluating HCQ and reporting detailed therapeutic protocol without conflict of interest were Pro. Potential conflict of interest was a perfect predictor for remdesivir efficacy. RCTs were associated with HCQ inefficacy and potential conflict of interest. The most predictive criteria were validated and allowed perfect classification of 10 additional studies.Conclusion: In therapeutic trials on COVID-19, the major biases predicting the conclusions are not methodology nor data analysis, but conflict of interest and absence of medical expertise. The thorough search for declared or undeclared and direct or indirect conflict of interest, and medical expertise should be included in the quality criteria for the evaluation of future therapeutic studies in COVID-19 and beyond. A new checklist evaluating not only methodology but also conflict of interest and medical expertise is proposed.

Early Treatment with Hydroxychloroquine and Azithromycin: A ‘Real-World’ Monocentric Retrospective Cohort Study of 30,423 COVID-19 Patients

“…Accordingly, we particularly explicated impartiality (conflicts of interest), transparency (recruiting centre and doctors), and medical expertise (the authors are experts in the field who directly care for patients, and standard of care and treatment protocols are clearly detailed) in the supplementary data of the present work (28).…”

“…Data from patients cared for in our institute from March 2, 2020, to December 31, 2021, were recorded in the hospital information system. This retrospective study was conducted following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (34) and new criteria identified through a critical review of the literature assessing HCQ for COVID-19 mortality (28).…”

“…However, our impartiality, transparency and methodology were questioned. This challenged us to obtain and make public unbiased raw data to provide our impartial methodological criteria (28), and report results in the most transparent way possible. Indeed, transparency and verifiability of the raw data and their analysis were identified as important issues during the pandemic (29,30,31).…”

Outcomes of 2111 COVID-19 Hospitalized Patients Treated with Hydroxychloroquine/Azithromycin and Other Regimens in Marseille, France, 2020: A Monocentric Retrospective Analysis

“…In meta-analyses, the choice of the selected studies influences dramatically the results that may be biased. 50 We continue to believe that monocentric studies are highly valuable due to the homogeneity of standard care (the “in our hands” phenomenon). Moreover, the concentration in any given institute leads to a progression in the quality of care, which is linked to medical experience, the importance of which should not be neglected.…”

The pharmaceutical industry is dangerous to health. Further proof with COVID-19

“…[ 135 ] The conflicts of interest that caused the disapproval of HCQ and allowed the authorization of remdesivir, concern physicians, medical event organizers, publishers, and therapeutic trials. [ 135 , 114 ] In France, Gilead Sciences is estimated to have spent $65 million over the past 7 years to establish its influence with practitioners and institutions. [ 119 ] Despite the fact that remdesivir has no statistically significant clinical benefits,[ 157 ] and that it is highly toxic to the kidneys and lungs (p. 125–134),[ 95 ] a 1 billion euro contract was signed between the Gilead laboratory and the European Union.…”