The life and death of living systematic reviews: a methodological survey.

OBJECTIVES: The objectives of this study are to describe the characteristics of living systematic reviews (LSRs) and to understand their life cycles. STUDY DESIGN AND SETTING: We conducted a comprehensive search up to April 2021 then selected articles and abstracted data in duplicate and independently. We undertook descriptive analyses and calculated delay in version update and delay since the last published version. RESULTS: We included 76 eligible LSRs with a total of 279 eligible versions. The majority of LSRs was from the clinical field (70%), was COVID-19 related (63%), and had a funding source specified (62%). The median number of versions per LSR was 2 (interquartile range (IQR) 1-4; range 1-19). The median and IQR for the ratio of the actual period of update to the planned period of update was 1.12 (0.81; 1.71). Out of all reviews with a 'planned period of update' and at least one update (N = 19), eight LSRs (42%) had a period since last published version greater than 3 times the planned period of update. No LSR included a 'retirement notice' in their latest published version. CONCLUSION: While most LSR complied with the planned period of producing updates, a substantive proportion lagged since their last update.

Knowledge mobilization activities to support decision-making by youth, parents, and adults using a systematic and living map of evidence and recommendations on COVID-19: protocol for three randomized controlled trials and qualitative user-experience studies.

INTRODUCTION: The COVID-19 pandemic underlined that guidelines and recommendations must be made more accessible and more understandable to the general public to improve health outcomes. The objective of this study is to evaluate, quantify, and compare the public's understanding, usability, satisfaction, intention to implement, and preference for different ways of presenting COVID-19 health recommendations derived from the COVID-19 Living Map of Recommendations and Gateway to Contextualization (RecMap). METHODS AND ANALYSIS: This is a protocol for a multi-method study. Through an online survey, we will conduct pragmatic allocation-concealed, blinded superiority randomized controlled trials (RCTs) in three populations to test alternative formats of presenting health recommendations: adults, parents, and youth, with at least 240 participants in each population. Prior to initiating the RCT, our interventions will have been refined with relevant stakeholder input. The intervention arm will receive a plain language recommendation (PLR) format while the control arm will receive the corresponding original recommendation format as originally published by the guideline organizations (standard language version). Our primary outcome is understanding, and our secondary outcomes are accessibility and usability, satisfaction, intended behavior, and preference for the recommendation formats. Each population's results will be analyzed separately. However, we are planning a meta-analysis of the results across populations. At the end of each survey, participants will be invited to participate in an optional one-on-one, virtual semi-structured interview to explore their user experience. All interviews will be transcribed and analyzed using the principles of thematic analysis and a hybrid inductive and deductive approach. ETHICS AND DISSEMINATION: Through Clinical Trials Ontario, the Hamilton Integrated Research Ethics Board has reviewed and approved this protocol (Project ID: 3856). The University of Alberta has approved the parent portion of the trial (Project ID:00114894). Findings from this study will be disseminated through open-access publications in peer-reviewed journals and using social media. TRIAL REGISTRATION: Clinicaltrials.gov NCT05358990 . Registered on May 3, 2022.

Immune-Based Therapy for Hospitalized Patients With COVID-19 and Risk of Secondary Infections: A Systematic Review and Meta-analysis.

Background: Immune-based therapies are standard-of-care treatment for coronavirus disease 2019 (COVID-19) patients requiring hospitalization. However, safety concerns related to the potential risk of secondary infections may limit their use. Methods: We searched OVID Medline, Ovid EMBASE, SCOPUS, Cochrane Library, clinicaltrials.gov, and PROSPERO in October 2020 and updated the search in November 2021. We included randomized controlled trials (RCTs). Pairs of reviewers screened abstracts and full studies and extracted data in an independent manner. We used RevMan to conduct a meta-analysis using random-effects models to calculate the pooled risk ratio (RR) and 95% CI for the incidence of infection. Statistical heterogeneity was determined using the I 2 statistic. We assessed risk of bias for all studies and rated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation methodology. We conducted a meta-regression using the R package to meta-explore whether age, sex, and invasive mechanical ventilation modified risk of infection with immune-based therapies. The protocol is registered with PROSPERO (CRD42021229406). Results: This was a meta-analysis of 37 RCTs including 32 621 participants (mean age, 60 years; 64% male). The use of immune-based therapy for COVID-19 conferred mild protection for the occurrence of secondary infections (711/15 721, 4.5%, vs 616/16 900, 3.6%; RR, 0.82; 95% CI, 0.71-0.95; P = .008; I 2 = 28%). A subgroup analysis did not identify any subgroup effect by type of immune-based therapies (P = .85). A meta-regression revealed no impact of age, sex, or mechanical ventilation on the effect of immune-based therapies on risk of infection. Conclusions: We identified moderate-certainty evidence that the use of immune-based therapies in COVID-19 requiring hospitalization does not increase the risk of secondary infections.

The Global Evidence Commission's Report provided a wake-up call for the evidence community.

The Global Evidence Commission report was published in early January 2022. As potential users of the report from France, Lebanon, and South Africa, we have reflected on the value of the report and the next steps for the community. We commend the report for its consideration of a wide range of audiences, and clear recommendations for each. We value its ability to draw lessons from the COVID-19 pandemic, and wider health and non-health fields. The report is an important wake up call for the evidence community and a call to action for us all. Whilst the report is not without its limitations, it is a useful starting point to improve the use of evidence, both in routine times and in future global crises. We all have a role to play in taking forward its recommendations to shape the future of the global evidence movement.

Using Explicit Thresholds were valuable for judging Benefits and Harms in partially contextualized GRADE Guidelines.

OBJECTIVES: Guideline panels must assess the magnitude of health benefits and harms to develop sensible recommendations. However, they rarely use explicit thresholds. In this paper we report on the piloting and the use thresholds for benefits and harms. STUDY DESIGN AND SETTING: We piloted the use of thresholds in a Chilean COVID-19 living guideline. For each of the critical outcomes, we asked panelists to suggest values of the thresholds for large, moderate, small, or trivial or no effect. We collected this information through a survey and an on-line discussion. RESULTS: Twelve panelists decided on thresholds for three critical outcomes (mortality, need for mechanical ventilation and serious adverse events). For all outcomes, an absolute risk reduction was considered larger with more than 50 events, moderate with less than 50 events, small with less than 25 events, and trivial with less than 10 events. Having these a priori thresholds in place significantly impacted on the development of recommendations. CONCLUSION: Explicit thresholds were a valuable addition to the judgment of the certainty in the evidence, to decide the direction and strength of the recommendation and to evaluate the need for update. We believe this is a line of research worth perusing.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients.

BACKGROUND: COVID-19-related critical illness is associated with an increased risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. METHODS: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. RESULTS: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. CONCLUSIONS: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19-related critical illness.

Which actionable statements qualify as good practice statements In Covid-19 guidelines? A systematic appraisal.

OBJECTIVES: To evaluate the development and quality of actionable statements that qualify as good practice statements (GPS) reported in COVID-19 guidelines. DESIGN AND SETTING: Systematic review . We searched MEDLINE, MedSci, China National Knowledge Infrastructure (CNKI), databases of Grading of Recommendations Assessment, Development and Evaluation (GRADE) Guidelines, NICE, WHO and Guidelines International Network (GIN) from March 2020 to September 2021. We included original or adapted recommendations addressing any COVID-19 topic. MAIN OUTCOME MEASURES: We used GRADE Working Group criteria for assessing the appropriateness of issuing a GPS: (1) clear and actionable; (2) rationale necessitating the message for healthcare practice; (3) practicality of systematically searching for evidence; (4) likely net positive consequences from implementing the GPS and (5) clear link to the indirect evidence. We assessed guideline quality using the Appraisal of Guidelines for Research and Evaluation II tool. RESULTS: 253 guidelines from 44 professional societies issued 3726 actionable statements. We classified 2375 (64%) as GPS; of which 27 (1%) were labelled as GPS by guideline developers. 5 (19%) were labelled as GPS by their authors but did not meet GPS criteria. Of the 2375 GPS, 85% were clear and actionable; 59% provided a rationale necessitating the message for healthcare practice, 24% reported the net positive consequences from implementing the GPS. Systematic collection of evidence was deemed impractical for 13% of the GPS, and 39% explained the chain of indirect evidence supporting GPS development. 173/2375 (7.3%) statements explicitly satisfied all five criteria. The guidelines' overall quality was poor regardless of the appropriateness of GPS development and labelling. CONCLUSIONS: Statements that qualify as GPS are common in COVID-19 guidelines but are characterised by unclear designation and development processes, and methodological weaknesses.

Good or best practice statements: proposal for the operationalisation and implementation of GRADE guidance.

An evidence-based approach is considered the gold standard for health decision-making. Sometimes, a guideline panel might judge the certainty that the desirable effects of an intervention clearly outweigh its undesirable effects as high, but the body of supportive evidence is indirect. In such cases, the application of the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach for grading the strength of recommendations is inappropriate. Instead, the GRADE Working Group has recommended developing ungraded best or good practice statement (GPS) and developed guidance under which circumsances they would be appropriate.Through an evaluation of COVID-1- related recommendations on the eCOVID Recommendation Map (COVID-19.recmap.org), we found that recommendations qualifying a GPS were widespread. However, guideline developers failed to label them as GPS or transparently report justifications for their development. We identified ways to improve and facilitate the operationalisation and implementation of the GRADE guidance for GPS.Herein, we propose a structured process for the development of GPSs that includes applying a sequential order for the GRADE guidance for developing GPS. This operationalisation considers relevant evidence-to-decision criteria when assessing the net consequences of implementing the statement, and reporting information supporting judgments for each criterion. We also propose a standardised table to facilitate the identification of GPS and reporting of their development. This operationalised guidance, if endorsed by guideline developers, may palliate some of the shortcomings identified. Our proposal may also inform future updates of the GRADE guidance for GPS.

American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE). OBJECTIVE: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE. METHODS: ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest. The panel included 3 patient representatives. The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. RESULTS: The panel agreed on 2 recommendations. The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE. CONCLUSIONS: These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation. They will be updated using a living recommendation approach as new evidence becomes available.

Use of Chest Imaging in the Diagnosis and Management of COVID-19: A WHO Rapid Advice Guide.

The World Health Organization (WHO) undertook the development of a rapid guide on the use of chest imaging in the diagnosis and management of coronavirus disease 2019 (COVID-19). The rapid guide was developed over 2 months by using standard WHO processes, except for the use of "rapid reviews" and online meetings of the panel. The evidence review was supplemented by a survey of stakeholders regarding their views on the acceptability, feasibility, impact on equity, and resource use of the relevant chest imaging modalities (chest radiography, chest CT, and lung US). The guideline development group had broad expertise and country representation. The rapid guide includes three diagnosis recommendations and four management recommendations. The recommendations cover patients with confirmed or who are suspected of having COVID-19 with different levels of disease severity, throughout the care pathway from outpatient facility or hospital entry to home discharge. All recommendations are conditional and are based on low certainty evidence (n = 2), very low certainty evidence (n = 2), or expert opinion (n = 3). The remarks accompanying the recommendations suggest which patients are likely to benefit from chest imaging and what factors should be considered when choosing the specific imaging modality. The guidance offers considerations about implementation, monitoring, and evaluation, and also identifies research needs. Published under a CC BY 4.0 license. Online supplemental material is available for this article.