Summary In response to limitations in the understanding and use of published evidence, evidence-based medicine (EBM) began as a movement in the early 1990s. EBM's initial focus was on educating ...clinicians in the understanding and use of published literature to optimise clinical care, including the science of systematic reviews. EBM progressed to recognise limitations of evidence alone, and has increasingly stressed the need to combine critical appraisal of the evidence with patient's values and preferences through shared decision making. In another progress, EBM incorporated and further developed the science of producing trustworthy clinical practice guidelines pioneered by investigators in the 1980s. EBM's enduring contributions to clinical medicine include placing the practice of medicine on a solid scientific basis, the development of more sophisticated hierarchies of evidence, the recognition of the crucial role of patient values and preferences in clinical decision making, and the development of the methodology for generating trustworthy recommendations.
Network meta-analysis (NMA), combining direct and indirect comparisons, is increasingly being used to examine the comparative effectiveness of medical interventions. Minimal guidance exists on how to ...rate the quality of evidence supporting treatment effect estimates obtained from NMA. We present a four-step approach to rate the quality of evidence in each of the direct, indirect, and NMA estimates based on methods developed by the GRADE working group. Using an example of a published NMA, we show that the quality of evidence supporting NMA estimates varies from high to very low across comparisons, and that quality ratings given to a whole network are uninformative and likely to mislead.
Correspondence to: A D Oxman oxman@online.no Summary points Clinicians, guideline developers, and policymakers sometimes neglect important criteria, give undue weight to criteria, and do not use the ...best available evidence to inform their judgments Explicit and transparent systems for decision making can help to ensure that all important criteria are considered and that decisions are informed by the best available research evidence The purpose of Evidence to Decision (EtD) frameworks is to help people use evidence in a structured and transparent way to inform decisions in the context of clinical recommendations, coverage decisions, and health system or public health recommendations and decisions EtD frameworks have a common structure that includes formulation of the question, an assessment of the evidence, and drawing conclusions, though there are some differences between frameworks for each type of decision EtD frameworks inform users about the judgments that were made and the evidence supporting those judgments by making the basis for decisions transparent to target audiences EtD frameworks also facilitate dissemination of recommendations and enable decision makers in other jurisdictions to adopt recommendations or decisions, or adapt them to their context Introduction Healthcare decision making is complex. Decision-making processes and the factors (criteria) that decision makers should consider vary for different types of decisions, including clinical recommendations, coverage decisions, and health system or public health recommendations or decisions.1 2 3 4 However, some criteria are relevant for all of these decisions, including the anticipated effects of the options being considered, the certainty of the evidence for those effects (also referred to as quality of evidence or confidence in effect estimates), and the costs and feasibility of the options. Rigorously developed guidelines synthesise the available relevant research, facilitating the translation of evidence into recommendations for clinical practice.9 However, the quality of guidelines is often suboptimal.10 11 If guidelines are not developed systematically and transparently, clinicians are not able to decide whether to rely on them or to explore disagreements when faced with conflicting recommendations.12 The GRADE (Grading of Recommendations Assessment, Development and Evaluation) Working Group has previously developed and refined a system to assess the certainty of evidence of effects and strength of recommendations.13 14 15 More than 100 organisations globally, including the World Health Organization, the Cochrane Collaboration, and the National Institute for Health and Care Excellence (NICE) now use or have adopted the principles of the GRADE system. Cure by 120 weeks, adverse drug reactions (clinical and biological serious adverse events), mortality, time to culture conversion, culture conversion at 24 weeks, acquired resistance to fluoroquinolone and injectable drugs Setting: Global, MDR-TB clinics Perspective: Population perspective (health system) Subgroups: Patients with extensively drug-resistant (XDR) or pre-XDR tuberculosis or those with resistance or contraindication to fluoroquinolones or injectables Background: The emergence of drug resistance is a major threat to global tuberculosis care and control.
This article describes conceptual advances of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group guidance to evaluate the certainty of evidence (confidence ...in evidence, quality of evidence) from network meta-analysis (NMA). Application of the original GRADE guidance, published in 2014, in a number of NMAs has resulted in advances that strengthen its conceptual basis and make the process more efficient. This guidance will be useful for systematic review authors who aim to assess the certainty of all pairwise comparisons from an NMA and who are familiar with the basic concepts of NMA and the traditional GRADE approach for pairwise meta-analysis. Two principles of the original GRADE NMA guidance are that we need to rate the certainty of the evidence for each pairwise comparison within a network separately and that in doing so we need to consider both the direct and indirect evidence. We present, discuss, and illustrate four conceptual advances: (1) consideration of imprecision is not necessary when rating the direct and indirect estimates to inform the rating of NMA estimates, (2) there is no need to rate the indirect evidence when the certainty of the direct evidence is high and the contribution of the direct evidence to the network estimate is at least as great as that of the indirect evidence, (3) we should not trust a statistical test of global incoherence of the network to assess incoherence at the pairwise comparison level, and (4) in the presence of incoherence between direct and indirect evidence, the certainty of the evidence of each estimate can help decide which estimate to believe.
•The application of the Grading of Recommendations Assessments, Development, and Evaluation approach to a number of network meta-analyses in the 3 years since the original guidance publication has led to advances that have strengthened the conceptual basis.•We present, discuss, and illustrate four conceptual advances. These are based on two principles: we need to rate the certainty of the evidence of each pairwise comparison within a network separately and that we need to consider both the direct and indirect evidence contributing to each network estimate.•Although maximizing the efficiency of the process is desirable, as illustrated in the conceptual advances, use of these strategies requires careful judgment.
Correspondence to: P Alonso-Coello palonso@santpau.cat Summary points Clinicians do not have the time or resources to consider the underlying evidence for the myriad decisions they must make each day ...and, as a consequence, rely on recommendations from clinical practice guidelines Guideline panels should consider all the relevant factors (criteria) that influence a decision or recommendation in a structured, explicit, and transparent way and provide clinicians with clear and actionable recommendations The GRADE working group has developed Evidence to Decision (EtD) frameworks for different types of decisions and recommendations. In this article we will describe EtD frameworks for clinical practice recommendations The general structure of the EtD framework for clinical recommendations is similar to EtD frameworks for other types of recommendations and decisions, and includes formulation of the question, an assessment of the different criteria, and conclusions Clinical recommendations require considering criteria differently, depending on whether an individual patient or a population perspective is taken. To ensure trustworthiness, clinical practice guidelines are made by groups of people (guideline panels) with relevant skills, perspectives, and knowledge; they are informed by the best available evidence; and they are systematically developed.1 2 3 4 In the first article in this series, we described GRADE Evidence to Decision (EtD) frameworks and their rationale for different types of decisions.5 In this second article, we describe the use of EtD frameworks for clinical recommendations and how they can help clinicians and patients who use those recommendations. Death, stroke, major bleeding, myocardial infarction, treatment burden Setting: High resource setting Perspective: Health system Subgroups: Patients who are well controlled with warfarin Background: Warfarin reduces the risk for ischaemic stroke in patients with atrial fibrillation but increases the risk for haemorrhage and requires frequent blood tests and clinic visits to monitor the international normalised ratio (INR) and adjust the dose.
Systematic reviewer authors intending to include all randomized participants in their meta-analyses need to make assumptions about the outcomes of participants with missing data.
The objective of ...this paper is to provide systematic reviewer authors with a relatively simple guidance for addressing dichotomous data for participants excluded from analyses of randomized trials.
This guide is based on a review of the Cochrane handbook and published methodological research. The guide deals with participants excluded from the analysis who were considered 'non-adherent to the protocol' but for whom data are available, and participants with missing data.
Systematic reviewer authors should include data from 'non-adherent' participants excluded from the primary study authors' analysis but for whom data are available. For missing, unavailable participant data, authors may conduct a complete case analysis (excluding those with missing data) as the primary analysis. Alternatively, they may conduct a primary analysis that makes plausible assumptions about the outcomes of participants with missing data. When the primary analysis suggests important benefit, sensitivity meta-analyses using relatively extreme assumptions that may vary in plausibility can inform the extent to which risk of bias impacts the confidence in the results of the primary analysis. The more plausible assumptions draw on the outcome event rates within the trial or in all trials included in the meta-analysis. The proposed guide does not take into account the uncertainty associated with assumed events.
This guide proposes methods for handling participants excluded from analyses of randomized trials. These methods can help in establishing the extent to which risk of bias impacts meta-analysis results.
Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding ...benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses.
We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects.
In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio RR 0.72, 95% confidence interval CI 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio HR 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia.
Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
Gefapixant for Chronic Cough-Reply Kum, Elena; Guyatt, Gordon H; Satia, Imran
JAMA : the journal of the American Medical Association,
02/2024, Volume:
331, Issue:
6
Journal Article
Guidelines are inconsistent in how they rate the quality of evidence and the strength of recommendations. This article explores the advantages of the GRADE system, which is increasingly being adopted ...by organisations worldwide
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