COVID-19: Why SOLIDARITY and DisCoVeRy trials may fail to bring informative and timely results

ObjectiveThe SOLIDARITY and DisCoVeRy trials were launched to facilitate the rapid worldwide comparison of the efficacy and safety of treatments against COVID-19. This study aimed to review the trial designs of SOLIDARITY and DisCoVeRy and their feasibility to generate high-quality evidence. MethodA systematic search of the European Clinical trial registry, the U.S. National Library of Medicine ClinicalTrials.gov, and the World Health Organizations (WHO) International Clinical Trials Registry Platform (ICTRP) was conducted on May 10th, 2020 to identify the study details of the SOLIDARITY and DisCoVeRy trials. A supplementary search of PubMed, WHOs website, French authorities websites, and Google search engine was conducted. A critical review was performed on the findings. ResultsThe DisCoVeRy trial design was detailed consistently in both the European and the US clinical rial registries. SOLIDARITY was registered on ICTRP, with country-specific information reported on country-level registry platforms. The DisCoVeRy trials design appears to be ideal from the methodological perspective. Both trials appear difficult to implement, impractical, and disconnected from the pandemic reality. This is consistent with the apparent failure of the trials to deliver conclusions before the end of the pandemic. ConclusionBoth trials constitute an interesting initiative yet may lack the resources to support a high-quality implementation. The authors call for a pandemic task force, with various experts on the front-line of COVID-19, to inform policy-makers to make effective decisions that may not be based on traditional, methodological state-of-the-art evidence, but rather pragmatic and revisable decisions reflecting emerging evidence for the benefit of patients and society.

Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials

PurposeThis study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. MethodA rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. ResultsA total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. ConclusionBased on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties.

A Protocol Introduction of Rapid Advice Guideline for Intravenous Azithromycin in Pediatrics / 中国药房

OBJECTIVE: To standardize and guide the formulation process of guideline and guarantee the evidence-based formulation of Rapid Advice Guideline for Intravenous Azithromycin in Pediatrics scientifically. METHODS: The protocol of the guideline was introduced, such as guideline-making institution and registration, establishment of project group, scope of application, declaration of interest and funding support, identification of the clinical issues and outcome indexes, evidence retrieval and processing, invastigation of patients preferences and values, economics analysis, development of recommendation, external review and approval, guideline release, dissemination and update, etc. RESULTS: The construction of guidance committee, expert group and secretarial group, the registration (registration number: IPGRP-2016CN013) of the guideline had been achieved according to this protocol; clinical issues (such as indications, usage and dosage, ADR and treatment, drug use in special population) and effectiveness, safety outcome indexes had been formed. The recommendations have been issued by the end of 2017; the full text and interpretation of the guideline will be published in 2018; the guideline will be updated in 2022. CONCLUSIONS: This protocol provides the methodological and programmatic guide and provides reference for evidence-based formulation of the guideline scientifically so as to promote clinical rational drug use.