Holger J Schünemann

McMaster University | McMaster

Trustworthy evidence syntheses using systematic review methodology are essential to make trustworthy decisions. To assess the certainty of a 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 110 organizations, i...

Importance: To ensure that youths can make informed decisions about their health, it is important that health recommendations be presented for understanding by youths. Objective: To compare understanding, accessibility, usability, satisfaction, intention to implement, and preference of youths provided with a digital plain language recommendation...

Background: This is the 23rd in a series of articles describing the GRADE approach to grading the certainty of evidence and strength of recommendations for systematic reviews, health technology assessments, and clinical guideline development. Objectives: We outline how resource utilization and cost-effectiveness analyses (CEAs) are integrated in...

Objective: To assess the effectiveness of plain language compared with standard language versions of COVID-19 recommendations specific to child health. Study design and setting: Pragmatic, allocation-concealed, blinded, superiority randomized controlled trial (RCT) with nested qualitative component. Trial was conducted online, internationally. P...

Diese Ausgabe des Versorgungs-Reports widmet sich schwerpunktmäßig der Bedeutung von medizinischen Leitlinien in der Gesundheitsversorgung. Leitlinien geben den Behandelnden diagnostische und therapeutische Empfehlungen an die Hand. Sie werden nach systematischen und evidenzbasierten Kriterien entwickelt und zielen darauf ab, die Versorgungsqualitä...

There are concerns about bias arising from the interests that stakeholder representatives may bring into the process of health research. In this article we distinguish between the non-conflicting interests of stakeholder groups and the conflicting interests of their representatives. Non-conflicting interests of a stakeholder group (also referred to...

Purpose: To evaluate the reporting of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rating the certainty of evidence in systematic reviews (SRs) published in the urological literature. Materials and methods: Based on a predefined protocol we identified all SRs published in 5 major urological journals f...

Background: Hereditary and acquired thrombophilia are risk factors for venous thromboembolism (VTE). Whether testing helps in guiding management decisions is controversial. Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision-making about thrombophilia testing. Methods: ASH formed...

Objectives: This GRADE concept article offers systematic reviewers, guideline authors and other users of evidence assistance in addressing randomized trial situations in which interventions or comparators differ from those in the target people, interventions, comparators, outcomes (PICO). To clarify what GRADE considers under indirectness of inter...

One of the aims of the GRADE Working Group has been to develop a single system that would reduce confusion arising from a legion of multiple conflicting systems for grading evidence and recommendations and serve as unifying lingua franca. Although GRADE has been widely endorsed, the way it is being used is not infrequently inconsistent with GRADE g...

LINKED CONTENT This article is linked to Piovani et al papers. To view these articles, visit https://doi.org/10.1111/apt.17360 and https://doi.org/10.1111/apt.17461.

This paper is part of a series of methodological guidance from the Cochrane Rapid Reviews Methods Group. Rapid reviews (RRs) use modified systematic review methods to accelerate the review process while maintaining systematic, transparent and reproducible methods. This paper addresses considerations for rating the certainty of evidence (COE) in RRs...

Biomarkers for the diagnosis, treatment and follow-up of patients with rhinitis and/or asthma are urgently needed. Although some biologic biomarkers exist in specialist care for asthma, they cannot be largely used in primary care. There are no validated biomarkers in rhinitis or allergen immunotherapy (AIT) that can be used in clinical practice. Th...

Nonrandomized studies (NRS) on allergen immunotherapy (AIT) particularly lend themselves to evaluate outcomes that are insufficiently addressed in randomized controlled studies (RCTs). However, NRS are prone to several sources of bias, which limit their validity. We aimed at comparing AIT effects between RCTs and NRS and evaluate the reasons for di...

Objective: Clinical practice guidelines are often created through collaboration among organizations. Use of inconsistent terminology may cause poor communication and delays. This study aimed to develop a glossary of terms related to collaboration in guideline development. Study design and setting: A literature review of collaborative guidelines...

Background: Implementation of international guidelines in Latin American settings requires additional considerations (i.e., values and preferences, resources, accessibility, feasibility, and impact on health equity). Objective: To provide evidence-based guidelines about diagnosis of VTE and management in children and during pregnancy. Methods:...

Objective: To highlight how using the GRADE approach to understand the certainty in the evidence about the impact of climate change in health outcomes increases transparency. Also, how GRADE can enhance communication and decisions about adaptation and mitigation strategies. Study design: We developed a narrative review based on an assessment of...

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 dif...

Objectives: To evaluate alternative formats of summary of findings (SoF) tables for single comparison with multiple outcomes. Study design and setting: We conducted a three-arm randomized controlled non-inferiority trial (RCT) in the following systematic review (SR) users: researchers, clinical practice guideline developers, healthcare providers...

Background: Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks are well-known tools that enable guideline panels to structure the process of developing recommendations and making decisions in healthcare and public health. To date, they have not regularly been used for health policy-maki...

Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms....

Best practices for the dissemination of global health guidelines has not undergone rigorous research. We used a new approach to digitizing World Health Organization (WHO) global tuberculosis guideline recommendations (eTB RecMap) and compared its usability to the conventional method of accessing TB recommendations using the WHO website. We conducte...

Objectives Randomized controlled trials (RCTs) are the preferred source of evidence for the relative effect of healthcare interventions summarized in knowledge syntheses. Non-randomized studies of interventions (NRSI) may provide replacement, sequential, or complementary evidence to RCTs. The Grading of Recommendations, Assessment, Development and...

Background As systematically developed statements regarding possible courses of action, health system guidance (HSG) can assist with making decisions about addressing problems or achieving goals in health systems. However, there are conceptual and methodological challenges in HSG implementation due to the complexity of health-system policy-making,...

Background Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's mi...

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...