Drug treatments for covid-19: living systematic review and network meta-analysis

Objective To compare the effects of treatments for coronavirus disease 2019 

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 10 August 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.

Results 35 trials with 16 588 patients met inclusion criteria; 12 (24.3%) trials and 6853 (41.3%) patients are new from the previous iteration. Twenty-seven randomised controlled trials were included in the analysis performed on 29 July 2020. Compared with standard care, glucocorticoids probably reduce death (risk difference 31 fewer per 1000 patients, 95% credible interval 55 fewer to 5 fewer, moderate certainty), mechanical ventilation (28 fewer per 1000 patients, 45 fewer to 9 fewer, moderate certainty), and duration of hospitalisation (mean difference −1.0 day, −1.4 to −0.6 days moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, and length of hospital stay is uncertain, but it probably reduces duration of symptoms (−2.6 days −4.3 to −0.6 days, moderate certainty) and probably does not substantially increase adverse effects leading to drug discontinuation (3 more per 1000, 7 fewer to 43 more, moderate certainty). Hydroxychloroquine may not reduce risk of death (13 more per 1000, 15 fewer to 43 more, low certainty) or mechanical ventilation (19 more per 1000, 4 fewer to 45 more, moderate certainty). The certainty in effects for all other interventions was low or very low certainty.

Conclusion Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas hydroxychloroquine may not reduce either. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important limitations.

Systematic reviews aim to provide an accurate summary of available evidence for specific health questions. In practice, an increase in methodological expectations and an increasing deluge of primary studies challenges the ability of many review teams to produce timely, high quality systematic reviews and to keep them up to date

One estimate is that 7% of systematic reviews are inaccurate the day they are published and after two years 23% of reviews that are not updated will present incorrect conclusions. 

Living systematic review (LSR) is an emerging approach to the updating of systematic reviews in which the review is updated frequently, typically at least each month, and usually published as online-only systematic reviews. New processes and technologies can help to keep review findings constantly up to date, even in fast moving research areas. 

Conclusion Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas hydroxychloroquine may not reduce either. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important limitations.

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