Evidence Based Medicine for Covid-19 Treatments after screening more than 30.000 publications @ BMJ — British Medical Journal
Drug treatments for covid-19: living systematic review and network meta-analysis
BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m2980 (Published 30 July 2020) Cite this as: BMJ 2020;370:m2980
BMJ, Last Updated, April 6th 2021
Key Messages:
After screening 31 848 titles and abstracts and 611 full texts, 206 unique randomised trials from 189 publications were identified that evaluated drug treatments as of 1 March 2021:
- Corticosteroids are likely to reduce mortality.
- Colchicine may reduce mortality.
- There is no convincing evidence yet that any of the other treatments have a benefit in this outcome when compared with standard care or each other.
- The main limitations of the evidence across comparisons are risk of bias and imprecision.
Abstract
Objective
To compare the effects of treatments for coronavirus disease 2019 (covid-19).
Design
Living systematic review and network meta-analysis.
Data sources
WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 1 March 2021 and six additional Chinese databases up to 20 February 2021. Studies identified as of 12 February 2021 were included in the analysis.
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 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
196 trials enrolling 76 767 patients were included;
111 (56.6%) trials and 35 098 (45.72%) patients are new from the previous iteration;
113 (57.7%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses.
- Compared with standard care, corticosteroids probably reduce death (risk difference 20 fewer per 1000 patients, 95% credible interval 36 fewer to 3 fewer, moderate certainty),
- mechanical ventilation (25 fewer per 1000, 44 fewer to 1 fewer, moderate certainty), and increase the number of days free from mechanical ventilation (2.6 more, 0.3 more to 5.0 more, moderate certainty).
- Interleukin-6 inhibitors probably reduce mechanical ventilation (30 fewer per 1000, 46 fewer to 10 fewer, moderate certainty) and may reduce length of hospital stay (4.3 days fewer, 8.1 fewer to 0.5 fewer, low certainty), but whether or not they reduce mortality is uncertain (15 fewer per 1000, 30 fewer to 6 more, low certainty).
- Janus kinase inhibitors may reduce mortality (50 fewer per 1000, 84 fewer to no difference, low certainty),
- mechanical ventilation (46 fewer per 1000, 74 fewer to 5 fewer, low certainty), and duration of mechanical ventilation (3.8 days fewer, 7.5 fewer to 0.1 fewer, moderate certainty).
- The impact of remdesivir on mortality and most other outcomes is uncertain.
- The effects of ivermectin were rated as very low certainty for all critical outcomes, including mortality.
- In patients with non-severe disease, colchicine may reduce mortality (78 fewer per 1000, 110 fewer to 9 fewer, low certainty) and
- mechanical ventilation (57 fewer per 1000, 90 fewer to 3 more, low certainty). Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low.
Conclusion
- Corticosteroids and interleukin-6 inhibitors probably confer important benefits in patients with severe covid-19.
- Janus kinase inhibitors appear to have promising benefits, but certainty is low.
- Azithromycin, hydroxychloroquine, lopinavir-ritonavir, and interferon-beta do not appear to have any important benefits.
- Whether or not remdesivir, ivermectin, and other drugs confer any patient-important benefit remains uncertain.
Systematic review registration
This review was not registered. The protocol is publicly available in the supplementary material.
Readers’ note
This article is a living systematic review that will be updated to reflect emerging evidence.
Updates may occur for up to two years from the date of original publication. This is the fourth version of the original article published on 30 July 2020 (BMJ 2020;370:m2980),
and previous versions can be found as data supplements.
When citing this paper please consider adding the version number and date of access for clarity.
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For the full disclaimer wording see BMJ’s terms and conditions: http://www.bmj.com/company/legal-information/Current evidence for covid-19 treatmentsVisual summary of living systematic review and network meta-analysis©
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InteractiveThis graphic gives a visual overview of the evidence for covid-19 treatments that is published to date, and will be updated regularly as more trials are published.
The information presented comes from a network meta-analysis that combines all the evidence and allows us to obtain estimates for all potential comparisons, even those that have not been included in trials.
We assessed how trustworthy the evidence is using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and present the most trustworthy estimates of effect.
Corticosteroids are likely to reduce mortality.
Colchicine may reduce mortality.
There is no convincing evidence yet that any of the other treatments have a benefit in this outcome when compared with standard care or each other.
The main limitations of the evidence across comparisons are risk of bias and imprecision.
About the authors
Reed AC Siemieniuk, methodologist, internist1 *,
Jessica J Bartoszko, methodologist1 *,
Long Ge, methodologist2 *,
Dena Zeraatkar, methodologist1 *,
Ariel Izcovich, methodologist, internist3,
Elena Kum, methodologist1,
Hector Pardo-Hernandez, methodologist45,
Anila Qasim, research associate1,
Juan Pablo Díaz Martinez, statistician1,
Bram Rochwerg, methodologist, critical care physician16,
Francois Lamontagne, methodologist, critical care physician7,
Mi Ah Han, methodologist8,
Qin Liu, professor910,
Arnav Agarwal, methodologist, internist111,
Thomas Agoritsas, methodologist, internist112,
Derek K Chu, methodologist, immunologist16,
Rachel Couban, librarian13,
Ellen Cusano, physician,
Andrea Darzi, methodologist1,
Tahira Devji, methodologist1,
Bo Fang, methodologist910,
Carmen Fang, registered nurse15,
Signe Agnes Flottorp, senior researcher1617,
Farid Foroutan, methodologist118,
Maryam Ghadimi, PhD student1,
Diane Heels-Ansdell, statistician1,
Kimia Honarmand, methodologist, critical care physician19,
Liangying Hou, medical doctor candidate2,
Xiaorong Hou, librarian20,
Quazi Ibrahim, statistician1,
Assem Khamis, data analyst33,
Bonnie Lam, student1,
Mark Loeb, methodologist, infectious disease physician16,
Maura Marcucci, methodologist, internist16,
Shelley L McLeod, methodologist, assistant professor2122,
Sharhzad Motaghi, methodologist1,
Srinivas Murthy, clinical associate professor, pediatric critical care, infectious diseases physician23,
Reem A Mustafa, associate professor, nephrologist124,
John D Neary, methodologist, internist6,
Gabriel Rada, methodologist2526,
Irbaz Bin Riaz, methodologist, internist27,
Behnam Sadeghirad, assistant professor113,
Nigar Sekercioglu, assistant professor1,
Lulu Sheng, methodologist910,
Ashwini Sreekanta, methodologist1,
Charlotte Switzer, methodologist1,
Britta Tendal, methodologist28,
Lehana Thabane, professor1,
George Tomlinson, senior biostatistician29,
Tari Turner, senior research fellow28,
Per O Vandvik, methodologist, internist15,
Robin WM Vernooij, methodologist3031,
Andrés Viteri-García, methodologist2532,
Ying Wang, methodologist, pharmacist1,
Liang Yao, methodologist1,
Zhikang Ye, methodologist, pharmacist1,
Gordon H Guyatt, methodologist, internist16,
Romina Brignardello-Petersen, methodologist1
Correspondence to:
R Siemieniuk reed.siemieniuk@medportal.ca
Accepted 23 July 2020
Final version accepted 19 March 2021
Edited for Brazil by:
Joaquim Cardoso, MSc
Senior Advisor for Health Care Strategy to BCG
Boston Consulting Group
MSc in BA from London Business School (LBS) — MIT Sloan Program
Post Graduation in Production Engineering
Bsc in Mechanical Engineering
