Holger J Schünemann

McMaster University | McMaster

Objective To provide updated guidance on when GRADE users should consider rating down more than one level for imprecision using a minimally contextualized approach. Study design and setting Based on the first GRADE guidance addressing imprecision rating in 2011, a project group within the GRADE Working Group conducted iterative discussions and pre...

Introduction GRADE guidance to rate the certainty domain of imprecision is presently not fully operationalized for rating down by two levels and when different or uncertainty in baseline risks are considered. In addition, there are scenarios in which lowering the certainty of evidence by three levels for imprecision is more appropriate than lowerin...

Background: Living practice guidelines are increasingly being used to ensure that recommendations are responsive to rapidly emerging evidence. Objective: To develop a framework that characterizes the processes of development of living practice guidelines in health care. Design: First, 3 background reviews were conducted: a scoping review of me...

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 in patients with...

In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more rigorous methodologies for its guideline program. In this Clinical Practice Guideline Communication, we describe these recent enhancements—many of which reflect greater adherence to the Grading of Recomme...

Objectives: Analytical frameworks are graphical representation of the key questions answered by a systematic review and can support the development of guideline recommendations. Our objectives were to a) conduct a systematic review to identify, describe and compare all analytical frameworks published as part of a systematic and guideline developme...

Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., "real-world data"). Objective: To compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogu...

Introduction The COVID-19 pandemic underlined that guidelines and recommendations must be made more accessible and more understandable to the general public, including adults, parents, and youth, to improve health outcomes. The objective of this study is to the public’s (youth, parents, and adult populations) understanding, usability, satisfaction,...

Background: COVID-19 related acute 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 in patients with COV...

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 Evaluatio...

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 Recommendation...

Background “Biological plausibility” is a concept frequently referred to in environmental and public health when researchers are evaluating how confident they are in the results and inferences of a study or evidence review. Biological plausibility is not, however, a domain of one of the most widely-used approaches for assessing the certainty of evi...

Clinicians, patients, policy makers, funders, programme managers, regulators, and science communities invest considerable amounts of time and energy in influencing or making decisions at various levels, using systematic reviews, health technology assessments, guideline recommendations, coverage decisions, selection of essential medicines and diagno...

Objective There is little empirical evidence of the impact of pooling randomized controlled trials (RCTs) and cohort studies (CSs) on the certainty-of-evidence. To evaluate the hypothetical-scenario of pooling bodies-of-evidence from RCTs with matched bodies-of-evidence from CSs on the certainty-of-evidence. Study design and setting We extracted G...

Objective Our objective was to develop an extension of the widely used GIN-McMaster Guideline Development Checklist and Tool for the integration of quality assurance and improvement (QAI) schemes with guideline development. Study Design and Setting We used a mixed-methods approach incorporating evidence from a systematic review, an expert workshop...

Objective GRADE practice guideline developers often perform systematic reviews of potential economic evaluations to inform recommendation decision-making. We aimed to identify indirectness characteristics of economic evaluations, related to GRADE evidence-to-decision (EtD) theoretical frameworks, that influence selection of these articles. Study D...

Background The prevalence of cow's milk allergy (CMA) is approximately 2–4.5% in infants and less than 0.5% in adults. Most children outgrow cow's milk allergy in early childhood, particularly that to the baked milk products. Immunotherapy with unheated cow's milk has been used as a treatment option for those who have not yet outgrown CMA, but the...

Objective To develop a digital communication tool to improve the implementation of up-to-date COVID-19 recommendations. Specifically, to improve patient, caregiver and public understanding of healthcare recommendations on prevention, diagnoses and treatment. Study Design and Setting Multi-stakeholder engagement design. In conjunction with the COVI...

Systematic reviews are essential to produce trustworthy guidelines. To assess the body of evidence included in a systematic review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group has developed an approach that is used by over 100 organizations, including the World Health Organization and Cochrane. GRADE...

Hospitals continue to face challenges in reducing incorrect antibiotic use due to social and cultural factors at the level of the health system, the care facility, the provider, and the patient. The objective of this paper is to highlight the social and cultural drivers of antimicrobial use and resistance and targeted interventions for secondary an...

Background: Adaptation of existing guidelines can be an efficient way to develop contextualized recommendations. Transparent reporting of the adaptation approach can support the transparency and usability of the adapted guidelines. Objective: To develop an extension of the RIGHT (Reporting Items for practice Guidelines in HealThcare) statement for...

Objective To systematically compare the effect of direct oral anticoagulants and low molecular weight heparin for thromboprophylaxis on the benefits and harms to patients undergoing non-cardiac surgery. Design Systematic review and network meta-analysis of randomised controlled trials. Data sOurces Medline, Embase, and the Cochrane Central Register...

Introduction The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magn...

Objective 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....

Objective We conceptualize patient values and preferences as the relative importance of health outcomes (RIO) which are often obtained through utility elicitation research. A transparent and structured approach to present synthesized RIO evidence and the certainty of this evidence is needed. This study aims to adapt the summary of findings (SoF) ta...

Background: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementation of international guidelines in Latin American settings requires additional considerations. Objective: To provide evidence-based guidelines about VTE prevention for Latin American patients, clinicians, and decision makers. Methods: We used th...

Objectives Examining the availability of essential medicines is a necessary step to monitor country-level progress towards universal health coverage. We compared the 2017 essential medicine lists (EML) of 137 countries to the WHO Model List to assess differences by drug class and country setting. Methods We extracted all medicines prioritised at c...

Objective To identify and describe the use of the GRADE dose-response-gradient domain to upgrade the certainty-of-evidence (CoE) in nutrition systematic-reviews (SRs). Study design and setting We searched for SRs of observational studies of nutrition topics that used GRADE and upgraded the CoE of at least one outcome for a dose-response-gradient,...

Background : While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases o...

Introduction: The development process for clinical guidelines is influenced by factors that are relevant to the validity of a guideline but often are not captured sufficiently in the final guideline documents. PANELVIEW is an English-language tool that can be used to explore the guideline development process from the perspective of guideline group...

Background Grading of Recommendations Assessment, Development and Evaluation (GRADE)Evidence-to-Decision (EtDs) frameworks are increasingly applied by health guideline developers to improve the use of evidence and transparency of health recommendations. Typically, EtDs include 12 criteria but these are flexible and EtDs have been adapted to differe...

Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging bec...

Background: COVID-19 related acute 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 thromboprophylax...

Objective The objective of this paper is to propose an approach to visual unification of adapted guidelines and transformation of classifications of certainty of evidence (CoE) and strength of recommendations (SoR) into the approach suggested by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. Study desi...

This is the 24th in the ongoing series of articles describing the GRADE approach for assessing the certainty of a body of evidence in systematic reviews and health technology assessments and how to move from evidence to recommendations in guidelines. Guideline developers and authors of systematic reviews and other evidence syntheses use randomized...

Prognostic models combine several prognostic factors to provide an estimate of the likelihood (or risk) of future events in individual patients, conditional on their prognostic factor values. A fundamental part of evaluating prognostic models is undertaking studies to determine whether their predictive performance, such as calibration and discrimin...

Background: Health guideline development requires sequential prioritization of the guideline topic, questions, and health outcomes. In this paper we report on new approaches for prioritizing questions and outcomes in guidelines. Methods: Ten guideline panels on venous thromboembolism rated potential guideline questions on a 9-point scale according...

Background There are uncertainties about mitigating strategies for swimming-related activities in the context of the COVID-19 pandemic. There is an opportunity to learn from the experience of previous re-openings to better plan the future one. Our objectives are to systematically review the evidence on (1) the association between engaging in swimmi...

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 thromboprophy...

Suboptimal diet is recognized as a leading modifiable risk factor for non-communicable diseases. Non-randomized studies (NRSs) with patient relevant outcomes provide many insights into diet–disease relationships. Dietary guidelines are based predominantly on findings from systematic reviews of NRSs—mostly prospective observational studies, despite...

Long-term treatment with 6-thioguanine (6-TG) for pediatric acute lymphoblastic leukemia (ALL) is associated with high rates of hepatic sinusoidal obstruction syndrome (SOS). Nevertheless, current treatment continues to use short-term applications of 6-TG with only sparse information on toxicity. 6-TG is metabolized by thiopurine methyltransferase...

Objectives: Clear communication of health care recommendations to patients and the public is essential. Current work has focused on creating patient versions of guidelines without much attention to single recommendations. In this study, we built on previously conducted research to test a template and explore the public's perceptions of, and attitu...

Objectives: To propose a taxonomy and framework that identifies and presents actionable statements in guidelines. Study design and setting: We took an iterative approach reviewing case studies of guidelines produced by the World Health Organization and the American Society of Hematology to develop an initial conceptual framework. We then tested...

Objective: The goal of this study was to develop an approach that can be used where baseline risk estimates that are directly applicable to prioritized patient-important outcomes are not available from published studies. Study design: The McMaster University GRADE Centre and the ASH guideline panel for the prevention of VTE in surgical patients dev...

Objective This article describes GRADE guidance for assessing imprecision when rating the certainty of the evidence from network meta-analysis. Study design and setting A project group within the GRADE working group conducted iterative discussions, computer simulations, and presentations at GRADE working group meetings to produce and obtain approv...

Objective To develop guidance on the use of COVID-19 vaccines in patients with autoimmune rheumatic diseases (ARD). Methods The Canadian Rheumatology Association (CRA) formed a multidisciplinary panel including rheumatologists, researchers, methodologists, vaccine experts and patients. The panel used the GRADE approach. Outcomes were prioritized a...

Objective: Little is known about how developers and panel members report cost and cost effectiveness considerations in GRADE guideline Evidence-to-Decision (EtD) frameworks. A systematic survey was conducted to explore approaches and factors contributing to variability in economic information reporting. Study Design and Setting: Guideline organizat...

Objective Stakeholders involved in developing recommendations need to have a common understanding of health outcomes and the perspective of affected individuals. In this paper we report on the development and application of health outcome descriptors (HODs) to inform decision-making by panels developing guideline recommendations. Study Design and...

Background: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline...

Objective: To provide practical principles and examples to help GRADE users make optimal choices regarding their ratings of certainty of evidence using a minimally or partially contextualized approach. Study design and setting: Based on the GRADE clarification of certainty of evidence in 2017, a project group within the GRADE Working Group condu...

Background : While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases o...

Background : While the PRISMA flow diagram is widely used for reporting standard systematic reviews (SRs), it was not designed for capturing the results of continual searches for studies in living systematic reviews (LSRs). The objectives of this study are (1) to assess how published LSRs report on the flow of studies through the different phases o...

Objectives: Despite an extensive risk of exposure to COVID-19, the residents of Giglio Island, Italy, did not develop any symptom of SARS-CoV-2. The present study aims to characterize the nature of exposure and to describe the local population dynamics underlying its apparent resistance to COVID-19. Methods: Descriptive study of an islander part...

One essential requirement of trustworthy guidelines is that they should be based on systematic reviews of the best available evidence. The GRADE Working Group has provided guidance for evaluating the certainty of evidence based on several domains. However, for many clinical questions, published evidence may be limited, too indirect or simply not ex...

Objective Having up-to-date health policy recommendations accessible in one location is in high demand by guideline users. We developed an easy to navigate interactive approach to organize recommendations and applied it to tuberculosis (TB) guidelines of the World Health Organization (WHO). Study Design We used a mixed-methods study design to deve...

Background In 2017, the European Commission’s Joint Research Centre (JRC) started developing a methodological framework for a guideline-based quality assurance (QA) scheme to improve cancer quality of care. During the first phase of the work, inconsistency emerged about the use of terminology for the definition, the conceptual underpinnings and the...

Background Although quality indicators are frequently derived from guidelines, there is a substantial gap in collaboration between the corresponding parties. To optimise workflow, guideline recommendations and quality assurance should be aligned methodologically and practically. Learning from the European Commission Initiative on Breast Cancer (ECI...

Background Predicting the risk of recurrence and response to chemotherapy in women with early breast cancer is crucial to optimise adjuvant treatment. Despite the common practice of using multigene tests to predict recurrence, existing recommendations are inconsistent. Our aim was to formulate healthcare recommendations for the question “Should mul...

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 a...

Objectives The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach is accepted methodology to assess the certainty of the evidence included in systematic reviews and clinical practice guidelines. The GRADE approach is endorsed globally, in Australia, the National Health and Medical Research Council advocated for the...

Objective : To identify and describe the use of the GRADE approach for rating the certainty of evidence in nutrition systematic reviews (SRs). Study design and setting : We systematically searched for SRs using GRADE and were published between 2015 and 2019 in the 10 “nutrition” journals with the highest impact factor according to the JCR 2018. R...

Objective This paper explores the need for conceptual advances and practical guidance in the application of the GRADE approach within public health contexts. Study Design and Setting We convened an expert workshop and conducted a scoping review to identify challenges experienced by GRADE users in public health contexts. We developed this concept p...