From SARS and MERS to COVID-19: a review of the quality and responsiveness of clinical management guidelines in outbreak settings

Objective To assess the responsiveness and quality of clinical management guidelines (CMGs) in SARS, MERS and COVID-19 and determine whether this has improved over time. Design Rapid literature review, quality assessment and focus group consultation. Data Sources – Google and Google Scholar were systematically searched from inception to 6th June 2020.This was supplemented with hand searches of national and international public health agency and infectious disease society websites as well as directly approaching clinical networks in regions where few CMGs had been identified via the primary search. Eligibility Criteria CMGs for the treatment of COVID-19/SARS/MERS providing recommendations on supportive care and/or specific treatment. Methods Data extraction was performed using a standardised form. The Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool was used to evaluate the quality of the CMGs. Six COVID-19 treatments were selected to assess the responsiveness of a subset of guidelines and their updates to 20th November 2020. We ran two sessions of focus groups with patient advocates to elicit their views on guideline development. Results We included 37 COVID-19, six SARS, and four MERS CMGs. Evidence appraisals in CMGs generally focused on novel drugs rather than basic supportive care; where evidence for the latter was provided it was generally of a low quality. Most CMGs had major methodological flaws (only two MERS-CoV and four COVID-19 CMGs were recommended for use by both reviewers without modification) and there was no evidence of improvement in quality over time. CMGs scored lowest in the following AGREE-II domains: scope and purpose, editorial independence, stakeholder engagement, and rigour of development. Of the COVID-19 CMGs, only eight included specific guidance for the management of elderly patients and only ten for high-risk groups; a further eight did not specify the target patient group at all. Early in the pandemic, multiple guidelines recommended unproven treatments and whilst in general findings of major clinical trials were eventually adopted, this was not universally the case. Eight guidelines recommended that use of unproven agents should be considered on a case-by-case basis. Patient representatives expressed concern about the lack of engagement with them in CMG development and that these documents are not accessible to non-experts. Conclusion The quality of most CMGs produced in coronaviridae outbreaks is poor and we have found no evidence of improvement over time, highlighting that current development frameworks must be improved. There is an need to strengthen the evidence base surrounding basic supportive care and develop methods to engage patients in CMG development from the beginning in outbreak settings. Systematic review registration PROSPERO CRD42020167361 ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Wellcome Trust. The results presented have been obtained with the financial support of the EU FP7 project PREPARE (602525). SL is an MRC Clinical Research Training Fellow (MR/T001151/1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The quality assessment and review aspect of this work did not require ethical approval. The University of Oxford ethics committee opined that the involvement of a patient group constituted patient and public involvement (PPI) and thus did not require ethical review. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Raw data has been deposited on Figshare. * CMG : Clinical Management guidelines SARS-CoV-1 : Severe Acute Respiratory Syndrome Coronavirus-1 MERS-CoV : Middle East Respiratory Syndrome Coronavirus COVID-19 : Coronavirus Disease-19 SARS-CoV-2 : Severe Acute Respiratory Syndrome Coronavirus-2 PREPARE : Platform for European Preparedness Against (Re-)emerging Epidemics PROSPERO : International Prospective Register of Systematic Reviews AGREE-II : Appraisal of Guidelines for Research and Evaluation II HCID : High Consequence Infectious Disease ISARIC : International Severe Acute Respiratory and emerging Infection Consortium IQR : Interquartile Range NIV : Non-invasive ventilation IV : Intravenous RECOVERY : Randomised Evaluation of COVID-19 Therapy CDC : Centers for Disease Control and Prevention IDSA : Infectious Diseases Society of America WHO : World Health Organisation REMAP-CAP : Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia RCT : Randomised Control Trial ACTT-1 : Adaptive COVID-19 Treatment Trial ARDS : Acute Respiratory Distress Syndrome