Article type
Abstract
Background: Evolution in SARS-CoV-2 variants, paired with new clinical trials, has necessitated updated evidence and guidance regarding COVID-19 pharmacotherapies. The World Health Organization (WHO) has responded, leveraging living network meta-analyses (NMAs) to provide iteratively updated practice guidance.
Objectives: To summarize successes and challenges associated with WHO’s living COVID-19 practice guidance
Methods: The living guideline receives methodological support from the MAGIC Evidence Ecosystem Foundation and is informed by living NMAs of randomized trials addressing the effectiveness of COVID-19 pharmacotherapies for patients with nonsevere and severe or critical COVID-19. The guideline adheres to trustworthiness standards.
WHO convened an unconflicted Guideline Development Group (GDG) panel including clinicians, methodologists, content experts, and patient partners. WHO severity definitions facilitated risk-stratified recommendations. Recommendations for nonsevere illness were stratified based on risk of hospitalization as determined by individual patient factors. When moving from evidence to recommendations, the GDG considered a combination of evidence regarding benefits and harms, values and preferences, practical issues, resources, feasibility, and equity. Given lack of empirical data regarding patient values, a key innovation was formal polling of panel members regarding their views of effects that patients feel are important.
Results: Fourteen versions of the living guideline incorporating recommendations for 15 therapeutics have been cross-published across MAGICapp, the WHO website, and The BMJ. For severe or critical illness, corticosteroids, interleukin-6 receptor blockers, and baricitinib are strongly recommended; for severe illness only, remdesivir is conditionally recommended. For nonsevere illness, the GDG strongly recommended nirmatrelvir-ritonavir in patients at high risk of hospitalization and conditionally recommended use in those at moderate risk; the GDG conditionally recommended remdesivir and molnupiravir for patients at high risk. Across iterations, updated evidence led to updated recommendations for nirmatrelvir-ritonavir, remdesivir, molnupiravir, casirivimab-imdevimab, sotrovimab, VV116, ivermectin, and bariticinib and to updated baseline risks for all-cause death and hospital admission.
Ongoing challenges include the absence of accurate prognostic models to estimate risk of hospitalization for patients with nonsevere illness and a paucity of evidence regarding patient preferences.
Conclusions: The WHO living COVID-19 guideline has successfully leveraged living evidence to produce up-to-date trustworthy guidance. Ongoing challenges include limited evidence to inform prognosis and patient preferences.
Objectives: To summarize successes and challenges associated with WHO’s living COVID-19 practice guidance
Methods: The living guideline receives methodological support from the MAGIC Evidence Ecosystem Foundation and is informed by living NMAs of randomized trials addressing the effectiveness of COVID-19 pharmacotherapies for patients with nonsevere and severe or critical COVID-19. The guideline adheres to trustworthiness standards.
WHO convened an unconflicted Guideline Development Group (GDG) panel including clinicians, methodologists, content experts, and patient partners. WHO severity definitions facilitated risk-stratified recommendations. Recommendations for nonsevere illness were stratified based on risk of hospitalization as determined by individual patient factors. When moving from evidence to recommendations, the GDG considered a combination of evidence regarding benefits and harms, values and preferences, practical issues, resources, feasibility, and equity. Given lack of empirical data regarding patient values, a key innovation was formal polling of panel members regarding their views of effects that patients feel are important.
Results: Fourteen versions of the living guideline incorporating recommendations for 15 therapeutics have been cross-published across MAGICapp, the WHO website, and The BMJ. For severe or critical illness, corticosteroids, interleukin-6 receptor blockers, and baricitinib are strongly recommended; for severe illness only, remdesivir is conditionally recommended. For nonsevere illness, the GDG strongly recommended nirmatrelvir-ritonavir in patients at high risk of hospitalization and conditionally recommended use in those at moderate risk; the GDG conditionally recommended remdesivir and molnupiravir for patients at high risk. Across iterations, updated evidence led to updated recommendations for nirmatrelvir-ritonavir, remdesivir, molnupiravir, casirivimab-imdevimab, sotrovimab, VV116, ivermectin, and bariticinib and to updated baseline risks for all-cause death and hospital admission.
Ongoing challenges include the absence of accurate prognostic models to estimate risk of hospitalization for patients with nonsevere illness and a paucity of evidence regarding patient preferences.
Conclusions: The WHO living COVID-19 guideline has successfully leveraged living evidence to produce up-to-date trustworthy guidance. Ongoing challenges include limited evidence to inform prognosis and patient preferences.