Objectives: To establish whether items included in instruments published in the last decade assessing risk of bias of randomized controlled trials (RCTs) are indeed addressing risk of bias.Study Design and Setting: We searched Medline, Embase, Web of Science, and Scopus from 2010 to October 2021 for instruments assessing risk of bias of RCTs. By extracting items and summarizing their essential content, we generated an item list. Items that two re-viewers agreed clearly did not address risk of bias were excluded. We included the remaining items in a survey in which 13 experts judged the issue each item is addressing: risk of bias, applicability, random error, reporting quality, or none of the above.Results: Seventeen eligible instruments included 127 unique items. After excluding 61 items deemed as clearly not addressing risk of bias, the item classification survey included 66 items, of which the majority of respondents deemed 20 items (30.3%) as addressing risk of bias; the majority deemed 11 (16.7%) as not addressing risk of bias; and there proved substantial disagreement for 35 (53.0%) items. Conclusion: Existing risk of bias instruments frequently include items that do not address risk of bias. For many items, experts disagree on whether or not they are addressing risk of bias.(c) 2022 Elsevier Inc. All rights reserved.

OBJECTIVE To compare the effects of treatments for coronavirus disease 2019 (covid-19). DESIGN Living systematic review and network meta-analysis. DATA SOURCES US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 20 July 2020. STUDY SELECTION Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. METHODS After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. RESULTS 23 randomised controlled trials were included in the analysis performed on 26 June 2020. The certainty of the evidence for most comparisons was very low because of risk of bias (lack of blinding) and serious imprecision. Glucocorticoids were the only intervention with evidence for a reduction in death compared with standard care (risk difference 37 fewer per 1000 patients, 95% credible interval 63 fewer to 11 fewer, moderate certainty) and mechanical ventilation (31 fewer per 1000 patients, 47 fewer to 9 fewer, moderate certainty). These estimates are based on direct evidence; network estimates for glucocorticoids compared with standard care were less precise because of network heterogeneity. Three drugs might reduce symptom duration compared with standard care: hydroxychloroquine (mean difference -4.5 days, low certainty), remdesivir (-2.6 days, moderate certainty), and lopinavir-ritonavir (-1.2 days, low certainty). Hydroxychloroquine might increase the risk of adverse events compared with the other interventions, and remdesivir probably does not substantially increase the risk of adverse effects leading to drug discontinuation. No other interventions included enough patients to meaningfully interpret adverse effects leading to drug discontinuation. CONCLUSION Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important study limitations.