key: cord-1028326-w96ncfla
authors: Gautret, Philippe; Raoult, Didier
title: Nullane salus extra ecclesiam
date: 2020-08-01
journal: New Microbes New Infect
DOI: 10.1016/j.nmni.2020.100714
sha: be7abfbbb7c9294566f32a76e69c36de253e6d2a
doc_id: 1028326
cord_uid: w96ncfla

Abstract Randomized clinical trials are not relevant for infectious disease outbreaks due to a new pathogen, for which public health decisions have to be made urgently. An approach based on group comparisons, in silico, may provide valuable results in a reasonably short period of time for a negligible amount of money.

Randomized clinical trials are not relevant for infectious disease outbreaks due to a new pathogen, for which public health decisions have to be made urgently. An approach based on group comparisons, in silico, may provide valuable results in a reasonably short period of time for a negligible amount of money. and usually directed toward high-risk groups in order to increase the likelihood of capturing enough numbers of endpoints. 1 RCTs are typically interventions aiming at assessing the effectiveness of a new preventive or curative treatment, as opposed to observational studies conducted in patients under standard care treatment. Interestingly, based on careful review of meta-analyses of RCT and cohort or case-control studies assessing the same intervention, the "average results" from the latter, did not systematically overestimate the magnitude of the associations between exposure and outcome as compared to RCT. 2 In addition, RCTs are not relevant for urgent health matters such as infectious disease outbreaks due to a new or re-emerging pathogen, for which public health decisions have to be made urgently. 1 In such situation, decisions have to be taken on the basis of limited and often imperfect available data. In the current context of the COVID-19 pandemic, measures that have good rationale, but for which little data are available (eg, travel restrictions, lockdowns, and compassionate use of drugs), should also be considered as options and should be assessed and amended in a continuous manner. 3 Such almost-empirical but pragmatic approach is likely to be considered highly blasphemous by those believing that there is no salvation outside the RCT church, whatever the context. Expressing a view against the main stream, i. patients under such treatments have been recently published. [6] [7] [8] In the meanwhile, RCT results have been also released. 4, 5, 9, 10 We propose assembling that which is scattered. By bringing together the sparse published data on the subject, it may become possible to carefully compare, a selection of outcomes in patients treated with chloroquine derivatives with matched patients receiving another treatment or standard care. Such approach based on group comparisons, in silico, may provide valuable results in a reasonably short period of time for a negligible amount of money. Our group conducted such an analysis using aggregated data from published studies matched with our own observational data showing that patients treated with a combination of hydroxychloroquine and azithromycin (HCQ-AZ) were three times less likely to die than matched patients treated either with lopinavir-ritonavir or standard care.

Compared with patients included in a remdesivir study, we also showed a significant difference in the clinical outcome (proportion of cured patients with negative viral load) in favor of HCQ-AZ. 11 Full access to original dataset of COVUD-19 studies should be warranted to public, allowing comparison of raw data rather than aggregated data and avoiding retraction of doubtful studies whose authors declined to share raw data for an external audit. 12 

Evidence for Health Decision Making -Beyond Randomized, Controlled Trials

Randomized, controlled trials, observational studies, and the hierarchy of research designs

Making decisions to mitigate COVID-19 with limited knowledge

Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial

Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial

Clinical and microbiological effect of a combination of hydroxychloroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study

Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in

Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data

A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)

Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial

Adjusting series of patients for trial comparisons for COVID-19 treatments

High-profile coronavirus retractions raise concerns about data oversight