The covid-19 pandemic and related “infodemic” have highlighted the importance of quickly available and trustworthy guidance to inform policy and practice worldwide. The flood of new research, clinical trials, and other information makes it nearly impossible for any country or healthcare system to keep up-to-date and make timely decisions.

Source: The BMJ Blog

Reprinted for educational purposes and social benefit, not for profit. 

New treatments for covid-19 exemplify the challenge: hydroxychloroquine and convalescent plasma were presented and perceived as game-changers with limited evidence and a lack of careful scrutiny regarding their benefit and harms to patients. We are at risk that a similar scenario repeats itself for new therapeutic and diagnostic strategies.

One of the perennial challenges of clinical practice guidelines is that their development and updating is slow, often with months or years between a guideline update. The covid-19 pandemic has demanded a different approach, and guideline developers are rising to the challenge, bringing the concept of living evidence and guidance to the fore with dynamic updating of recommendations once new practice-changing evidence is publicly available. Pioneers of living evidence and guidance have innovated processes and apply digital technologybased on best current methods and standards for both systematic reviews and guidelines. [1] The Cochrane collaboration and scientific journals like Annals of Internal Medicine  and BMJ publish living systematic reviews for covid-19. Examples of national living covid-19 guidelines have emerged. They are authored, updated weekly, and published online in user-friendly formats making use of the MAGICapp; an online platform designed for living guidelines, re-use and adaptation to other contexts.

The living WHO guideline on drugs for covid-19, first tackling systemic corticosteroids and also published in the BMJ today, demonstrate some additional innovations in what we call the evidence ecosystem. [2-4] Here, actors need to trust each other and work closely together to rapidly transform new evidence into trustworthy and living guidance for policy and practice, while reducing duplication of efforts. In this specific collaboration the WHO works with the non-profit Magic Evidence Ecosystem Foundation (MAGIC), including the BMJ Rapid Recommendations. MAGIC provides methodological support to develop and disseminate living guidance for covid-19 drug treatments. Another contribution is the use of MAGICapp, available through the BMJ Rapid Recommendations. It will be used by WHO in the subsequent updates of the living guideline. WHO is piloting this platform, among others, for additional uses in other guidance and contexts.

This living guideline shows how global guidance can be rapidly produced and disseminated without sacrificing methods and standards for trustworthy guidelines. It is also the first living guideline publication in a scientific journal with a format to accommodate for additions of any new drug of relevance to covid-19. Updates of the linked living systematic review and network meta-analysis of covid-19 treatments will inform updates of this living guidance, as well as the early BMJ Rapid Recommendation on remdesivir. [5]

For any evidence ecosystem to work, central governance, orchestration, and support are needed to coordinate the work of multiple parties. [2] Here WHO liaised with the trialists who agreed to share their new evidence on corticosteroids. WHO also orchestrated a prospective meta-analysis of these trial results performed by trusted collaborators, complementing evidence from the living network meta-analysis published in the BMJ. [5-6] It allowed the standing guideline panel of WHO-appointed experts to create recommendations two days after receiving the new evidence. The panel concluded that the new trial evidence confirmed a mortality reduction in both the severe and critically ill patients with covid-19, as previously suggested by a subgroup analysis of the landmark RECOVERY trial. [7] The joined efforts in rapidly synthesizing more trial evidence allowed for the experts to arrive at trustworthy global WHO guidance.

A burning question was whether WHO could launch the guidance with practice-changing recommendations on corticosteroids before the trials were peer-reviewed and made available in the public domain. Staying with normal practice, WHO guidance published the guidance in parallel with the new trials and prospective meta-analysis published in JAMA. [6] Although this last step was done at record speed, we believe the next update of the living WHO guideline can demonstrate greater speed and efficiency, by working even more closely with trialists and journals.

What remains now is for countries to make optimal use of this guidance for efficient implementation. This should be made easier by the guidelines being available for re-use, translation and adaptation in different local contexts. With corticosteroids being an available, low-cost and well-known drug used for decades, issues related to resources, applicability, feasibility and equity are typically of minor concerns. A bigger concern is the traditional approach of each country and healthcare system continuing to develop their own guidance of variable quality and timeliness, rather than making use of trustworthy guidance from trusted sources such as the WHO, here in a living format.

Drug treatments are one key part of a range of drug and non-drug interventions to manage or prevent covid-19. Our focus has been drug treatments in part because high quality evidence is anticipated from trials. This approach could work in other areas. We welcome and encourage post-publication peer review of the living guideline and readers can leave feedback as a rapid response. There is really no time to lose if we aim to tackle the covid-19 pandemic and related infodemic with trustworthy evidence and guidance, of critical importance to policy and practice.

Per Olav Vandvik is co-founder and CEO of the non-profit MAGIC Evidence Ecosystem Foundation (MAGIC). Twitter: @PerVandvik

Navjoyt Ladher is head of education at The BMJ. Twitter: @navjoytladher

Janet Diaz is lead for the clinical team, emergency response at WHO. Twitter: @diazjv

Helen Macdonald is research editor at The BMJ. Twitter: @drhelmac

John Grove is Director of Quality Assurance, Norms & Standards at WHO, HQ, Science Division. Twitter: @GroveJohn

Thomas Agoritsas is co-founder and deputy CEO of MAGIC. Twitter: @ThomasAgoritsas

Declarations of interest: All authors were involved in the project through their respective organisations

References:

  1. Akl EA, Meerpohl JJ, Elliott J, Kahale LA, Schunemann HJ, Living systematic review network. Living systematic reviews: 4. Living guideline recommendations
  2. World Health Organization. Corticosteroids for COVID-19. Living guidance 2 September 2020  https://www.who.int/publications/i/item/WHO-2019-nCoV-Corticosteroids-2020.1
  3. Lamontagne F, Agoritsas T, Macdonald H, et al. A living WHO guideline on drugs for covid-19. BMJ 2020; 370:m337
  4. Vandvik PO, Brandt L. Future of evidence ecosystem series. Evidence ecosystems and learning health systems: why bother?   J Clin Epidemiol 2020: 123; 166-170
  5. Siemieniuk RAC, Bartoszko JJ, Ge L, et al. Drug treatments for covid-19: living systematic review and network meta-analysis. BMJ 2020; 370:m2980
  6. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis. JAMA 2020 doi:10.1001/jama.2020.17023
  7. Horby P, Lim WS, Emberson JR, et al. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with covid-19- preliminary report. N Engl J Med 2020; doi:10.1056

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