ABSTRACT
Response to the COVID-19 pandemic included a wide range of Public Health and Social Measures (PHSM). PHSM refer to a broad array of nonpharmaceutical interventions implemented by individuals, communities and governments to reduce the risk and scale of transmission of epidemic- and pandemic-prone infectious diseases. In order to inform decisions by the public, health workforce and policy-makers, there is a need to synthesize the large volume of published work on COVID-19. This study protocol describes the methodology for an overview of reviews focusing on the effectiveness and/or unintended health and socio-economic consequences of PHSM implemented during the COVID-19 pandemic. Findings can shape policy and research related to PHSM moving forward.
Subject(s)
COVID-19ABSTRACT
Purpose: To assess the trustworthiness and impact of preprint trial reports during the COVID-19 pandemic. Data sources: WHO COVID-19 database and the L-OVE COVID-19 platform by the Epistemonikos Foundation (up to August 3rd, 2021) Design: We compare the characteristics of COVID-19 trials with and without preprints, estimate time to publication of COVID-19 preprint reports, describe discrepancies in key methods and results between preprint and published trial reports, report the number of retracted preprints and publications, and assess whether including versus excluding preprint reports affects meta-analytic estimates and the certainty of evidence. For the effects of eight therapies on mortality and mechanical ventilation, we performed meta-analyses including preprints and excluding preprints at 1 month, 3 months, and 6 months after the first trial addressing the therapy became available either as a preprint or publication (120 meta-analyses in total). Results: We included 356 trials, 101 of which are only available as preprints, 181 as journal publications, and 74 as preprints first and subsequently published in journals. Half of all preprints remain unpublished at six months and a third at one year. There were few important differences in key methods and results between trial preprints and their subsequent published reports. We identified four retracted trials, three of which were published in peer-reviewed journals. With two exceptions (2/60; 3.3%), point estimates were consistent between meta-analyses including versus excluding preprints as to whether they indicated benefit, no appreciable effect, or harm. There were nine comparisons (9/60; 15%) for which the rating of the certainty of evidence differed when preprints were included versus excluded, for four of these comparisons the certainty of evidence including preprints was higher and for five of these comparisons the certainty of evidence including preprints was lower. Limitations: The generalizability of our results is limited to COVID-19. Preprints that are subsequently published in journals may be the most rigorous and may not represent all trial preprints. Conclusion: We found no compelling evidence that preprints provide less trustworthy results than published papers. We show that preprints remain the only source of findings of many trials for several months, for a length of time that is unacceptable in a health emergency. We show that including preprints may affect the results of meta-analyses and the certainty of evidence. We encourage evidence users to consider data from preprints in contexts in which decisions are being made rapidly and evidence is being produced faster than can be peer-reviewed.
Subject(s)
COVID-19ABSTRACT
ObjectiveCOVID-19 Living OVerview of Evidence (COVID-19 L{middle dot}OVE) is a public repository and classification platform for COVID-19 articles. The repository contains over 430,000 articles as of 20 September 2021 and intends to provide a one-stop shop for COVID-19 evidence. Considering that systematic reviews conduct high-quality searches, this study assesses the comprehensiveness and currency of the repository against the total number of studies in a representative sample of COVID-19 systematic reviews. MethodsOur sample was generated from all the studies included in the systematic reviews of COVID-19 published during April 2021. We estimated the comprehensiveness of COVID-19 L{middle dot}OVE repository by determining how many of the individual studies in the sample were included in the COVID-19 L{middle dot}OVE repository. We estimated the currency as the percentage of studies that were available in the COVID-19 L{middle dot}OVE repository at the time the systematic reviews conducted their own search. ResultsWe identified 83 eligible systematic reviews that included 2132 studies. COVID-19 L{middle dot}OVE had an overall comprehensiveness of 99.67% (2125/2132). The overall currency of the repository, that is, the proportion of articles that would have been obtained if the search of the reviews was conducted in COVID-19 L{middle dot}OVE instead of searching the original sources, was 96.48% (2057/2132). Both the comprehensiveness and the currency were 100% for randomised trials (82/82). ConclusionThe COVID-19 L{middle dot}OVE repository is highly comprehensive and current. Using this repository instead of traditional manual searches in multiple databases can save a great amount of work to people conducting systematic reviews and would improve the comprehensiveness and timeliness of evidence syntheses. This tool is particularly important for supporting living evidence synthesis processes
Subject(s)
COVID-19ABSTRACT
Objective This living systematic review aims to provide a timely, rigorous and continuously updated summary of the evidence available on the role of remdesivir in the treatment of patients with COVID-19 Methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. Eligible studies were randomised trials evaluating the effect of remdesivir versus placebo or no treatment. We conducted searches in the LOVE (Living OVerview of Evidence) platform for COVID-19, a system that maps PICO questions to a repository maintained through regular searches in electronic databases, preprint servers, trial registries and other resources relevant to COVID-19. All the searches covered the period until 25 August 2020. No date or language restrictions were applied. Two reviewers independently evaluated potentially eligible studies according to predefined selection criteria, and extracted data on study characteristics, methods, outcomes, and risk of bias, using a predesigned, standardised form. We performed meta-analyses using random-effect models and assessed overall certainty in evidence using the GRADE approach. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it every time the conclusions change or whenever there are substantial updates. Results Our search strategy yielded 574 references. Finally, we included 3 randomised trials evaluating remdesivir in addition to standard care versus standard care alone. The evidence is very uncertain about the effect of remdesivir on mortality (RR 0.7, 95% CI 0.46 to 1.05; very low certainty evidence) and the need for invasive mechanical ventilation (RR 0.69, 95% CI 0.39 to 1.24; very low certainty evidence). On the other hand, remdesivir likely results in a large reduction in the incidence of adverse effects in patients with COVID-19 (RR 1.29, 95% CI 0.58 to 2.84; moderate certainty evidence). Conclusions The evidence is insufficient for the outcomes critical for making decisions about the role of remdesivir in the treatment of patients with COVID-19, so it is not possible to balance the potential benefits, if any, with the adverse effects and costs. PROSPERO Registration number CRD42020183384 Keywords COVID-19, Coronavirus disease, Severe Acute Respiratory Syndrome Coronavirus 2, Coronavirus Infections, Systematic Review, Remdesivir, Antivirals
Subject(s)
COVID-19ABSTRACT
Objective To assess the efficacy and safety of lopinavir/ritonavir for the treatment of patients with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods We adapted an already published common protocol for multiple parallel systematic reviews to the specificities of this question. We will include randomised trials evaluating the effect of lopinavir/ritonavir - as monotherapy or in combination with other drugs - versus placebo or no treatment in patients with COVID-19. Randomised trials evaluating lopinavir/ritonavir in infections caused by other coronaviruses, such as MERS-CoV and SARS-CoV, and non-randomised studies in COVID-19 will be searched in case no direct evidence from randomised trials is found, or if the direct evidence provides low- or very low-certainty for critical outcomes. Two reviewers will independently screen each study for eligibility, extract data, and assess the risk of bias. We will perform random-effects meta-analyses and use GRADE to assess the certainty of the evidence for each outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.