GRADE approach to rate the certainty from a network meta-analysis: addressing incoherence.

This article presents official guidance from the Grading of Recommendations Assessments, Development, and Evaluation (GRADE) working group on how to address incoherence when assessing the certainty in the evidence from network meta-analysis. Incoherence represents important differences between direct and indirect estimates that contribute to a network estimate. Bias due to limitations in study design or publication bias, indirectness, and intransitivity may be responsible for incoherence.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: diagnosis of venous thromboembolism.

Background: Modern diagnostic strategies for venous thromboembolism (VTE) incorporate pretest probability (PTP; prevalence) assessment. The ability of diagnostic tests to correctly identify or exclude VTE is influenced by VTE prevalence and test accuracy characteristics.

Objective: These evidence-based guidelines are intended to support patients, clinicians, and health care professionals in VTE diagnosis.

American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients.

Background: Venous thromboembolism (VTE) is the third most common vascular disease. Medical inpatients, long-term care residents, persons with minor injuries, and long-distance travelers are at increased risk.

Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about preventing VTE in these groups.

A risk of bias instrument for non-randomized studies of exposures: A users' guide to its application in the context of GRADE.

The objective of this paper is to explain how to apply, interpret, and present the results of a new instrument to assess the risk of bias (RoB) in non-randomized studies (NRS) dealing with effects of environmental exposures on health outcomes. This instrument is modeled on the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) instrument. The RoB instrument for NRS of exposures assesses RoB along a standardized comparison to a randomized target experiment, instead of the study-design directed RoB approach.

A systematic survey shows that reporting and handling of missing outcome data in networks of interventions is poor.

Background: To provide empirical evidence about prevalence, reporting and handling of missing outcome data in systematic reviews with network meta-analysis and acknowledgement of their impact on the conclusions.

Methods: We conducted a systematic survey including all published systematic reviews of randomized controlled trials comparing at least three interventions from January 1, 2009 until March 31, 2017.

Results: We retrieved 387 systematic reviews with network meta-analysis.

Evidence to Decision framework provides a structured "roadmap" for making GRADE guidelines recommendations.

Objectives: It is unclear how guidelines panelists discuss and consider factors (criteria) that are formally and not formally included in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. To describe the use of decision criteria, we explored how panelists adhered to GRADE criteria and sought to identify any emerging non-GRADE criteria when the panelists used the Evidence to Decision (EtD) framework as part of GRADE application.

Study Design And Setting: We used conventional and summative qualitative analyses to identify themes emerging from face-to-face, panel meeting discussions.

GRADE approach to rate the certainty from a network meta-analysis: avoiding spurious judgments of imprecision in sparse networks.

When direct and indirect estimates of treatment effects are coherent, network meta-analysis (NMA) estimates should have increased precision (narrower confidence or credible intervals compared with relying on direct estimates alone), a benefit of NMA. We have, however, observed cases of sparse networks in which combining direct and indirect estimates results in marked widening of the confidence intervals. In many cases, the assumption of common between-study heterogeneity across the network seems to be responsible for this counterintuitive result.

Certainty ranges facilitated explicit and transparent judgments regarding evidence credibility.

Objectives: The Grading of Recommendations Assessment, Development and Evaluation approach to rating certainty of evidence includes five domains of reasons for rating down certainty. Only one of these, precision, is easily amenable-through the confidence interval-to quantitation. The other four (risk of bias, inconsistency, indirectness, and publication bias) are not.

Evaluation of the risk of bias in non-randomized studies of interventions (ROBINS-I) and the 'target experiment' concept in studies of exposures: Rationale and preliminary instrument development.

Assessing the risk of bias (RoB) of individual studies is a critical part in determining the certainty of a body of evidence from non-randomized studies (NRS) that evaluate potential health effects due to environmental exposures. The recently released RoB in NRS of Interventions (ROBINS-I) instrument has undergone careful development for health interventions. Using the fundamental design of ROBINS-I, which includes evaluating RoB against an ideal target trial, we explored developing a version of the instrument to evaluate RoB in exposure studies.

Using systematic reviews in guideline development: the GRADE approach.

Systematic reviews are essential to produce trustworthy guidelines. 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 currently used by over 100 organisations, including the World Health Organization and the Cochrane Collaboration. GRADE provides operational definitions and instructions to rate the certainty of the evidence for each outcome in a review as high, moderate, low, or very low for the effects of interventions, prognostic estimates, values and preferences, test accuracy and resource utilization.

Development of rapid guidelines: 1. Systematic survey of current practices and methods.

Background: Guidelines in the healthcare field generally should contain evidence-based recommendations to inform healthcare decisions. Guidelines often require 2 years or more to develop, but certain circumstances necessitate the development of rapid guidelines (RGs) in a short period of time. Upholding methodological rigor while meeting the reduced development timeframe presents a challenge for developing RGs.

Development of rapid guidelines: 2. A qualitative study with WHO guideline developers.

Background: Situations such as public health emergencies and outbreaks necessitate the development and publication of high-quality recommendations within a condensed timeframe. For example, WHO has produced examples of and guidance for the development of rapid guidelines (RGs). However, more information is needed to understand the experiences and perceptions of guideline developers.

Development of rapid guidelines: 3. GIN-McMaster Guideline Development Checklist extension for rapid recommendations.

Background: Practice guidelines require a substantial investment of resources and time, often taking between 1 and 3 years from conceptualisation to publication. However, urgent situations require the development of recommendations in a shorter timeframe. In this third and final article in the series exploring challenges and solutions in developing rapid guidelines (RGs), we propose guiding principles for the development of RGs.

A systematic review of how patients value COPD outcomes.

Our objective was to summarise systematically all research evidence related to how patients value outcomes in chronic obstructive pulmonary disease (COPD).We conducted a systematic review (systematic review registration number CRD42015015206) by searching PubMed, Embase, PsycInfo and CINAHL, and included reports that assessed the relative importance of outcomes from COPD patients' perspective. Two authors independently determined the eligibility of studies, abstracted the eligible studies and assessed risk of bias.

The GRADE Evidence to Decision (EtD) framework for health system and public health decisions.

Objective: To describe a framework for people making and using evidence-informed health system and public health recommendations and decisions.

Background: We developed the GRADE Evidence to Decision (EtD) framework for health system and public health decisions as part of the DECIDE project, in which we simultaneously developed frameworks for these and other types of healthcare decisions, including clinical recommendations, coverage decisions and decisions about diagnostic tests.

Developing The Framework: Building on GRADE EtD tables, we used an iterative approach, including brainstorming, consultation of the literature and with stakeholders, and an international survey of policy-makers.

GRADE guidelines: 20. Assessing the certainty of evidence in the importance of outcomes or values and preferences-inconsistency, imprecision, and other domains.

Objective: To provide Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidance for assessing inconsistency, imprecision, and other domains for the certainty of evidence about the relative importance of outcomes.

Study Design And Setting: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance, and consulted GRADE members and other stakeholders for feedback.

Results: We describe the rationale for considering the remaining GRADE domains when rating the certainty in a body of evidence for the relative importance of outcomes.

Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis.

Background: Supplemental oxygen is often administered liberally to acutely ill adults, but the credibility of the evidence for this practice is unclear. We systematically reviewed the efficacy and safety of liberal versus conservative oxygen therapy in acutely ill adults.

Methods: In the Improving Oxygen Therapy in Acute-illness (IOTA) systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, HealthSTAR, LILACS, PapersFirst, and the WHO International Clinical Trials Registry from inception to Oct 25, 2017, for randomised controlled trials comparing liberal and conservative oxygen therapy in acutely ill adults (aged ≥18 years).

[GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health].

Objective: To describe the Grading of Recommendations Assessment, Development and Evaluation (GRADE) interactive Evidence to Decision (EtD) frameworks for tests and test strategies for clinical, public health or coverage decisions.

Study Design And Setting: As part of the GRADE Working Group's DECIDE project we conducted workshops, user testing with systematic review authors, guideline developers and other decision makers, and piloted versions of the EtD framework.

Results: EtD frameworks for tests share the structure, explicitness, and transparency of other EtD frameworks.

Association of Metformin with Breast Cancer Incidence and Mortality in Patients with Type II Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis.

Preclinical data suggest that metformin may reduce breast cancer incidence and improve cancer prognosis. However, the current evidence in observational studies is inconclusive. A systematic review and meta-analysis was conducted to assess the effect of metformin on the incidence of breast cancer and all-cause mortality in patients with type II diabetes (T2D).

Do clinicians want recommendations? A multicenter study comparing evidence summaries with and without GRADE recommendations.

Objectives: Evidence-based clinical practice guidelines provide recommendations to assist clinicians in decision-making and to reduce the gap between best current research evidence and clinical practice. However, some argue that providing preappraised evidence summaries alone, rather than recommendations, is more appropriate. The objective of the study is to evaluate clinicians' preferences, and understanding of the evidence and intended course of action in response to evidence summaries with and without recommendations.

GRADE Guidelines: 19. Assessing the certainty of evidence in the importance of outcomes or values and preferences-Risk of bias and indirectness.

Objectives: The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group defines patient values and preferences as the relative importance patients place on the main health outcomes. We provide GRADE guidance for assessing the risk of bias and indirectness domains for certainty of evidence about the relative importance of outcomes.

Study Design And Setting: We applied the GRADE domains to rate the certainty of evidence in the importance of outcomes to several systematic reviews, iteratively reviewed draft guidance and consulted GRADE members and other stakeholders for feedback.