Healthcare Recommendations: Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) Approach

The objective of this study was to assess the comparative efficacy and safety of different antifungal agents used for the treatment of oropharyngeal candidiasis (OPC) in adult patients with HIV. A systematic search was performed on the four major databases (Medline, Embase, CENTRAL and Scopus) to identify randomized controlled trials (RCTs) that evaluated the efficacy of antifungal agents in HIV patients with OPC. A network meta-analysis was performed from the data extracted from the selected studies. The agents were ranked according using surface under the cumulative ranking (SUCRA). The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to determine the quality of evidence. A total of 15 trials were included in the quantitative analysis involving the data from a total of 2883 participants. Fluconazole was ranked as the most effective antifungal agent to achieve clinical cure (SUCRA = 0.87) in OPC followed by posaconazole and itraconazole. Posaconazole was ranked the most efficacious agent in achieving mycological cure (SUCRA = 0.81), followed by fluconazole. While nystatin was ranked the safest, the effect estimates of none of the other systemic antifungal agents were significantly higher than fluconazole. Based on the available evidence, fluconazole can be considered as the most effective drug in the treatment of OPC among HIV-infected adults and has a favorable safety profile, followed by posaconazole.

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Introduction to network meta-analysis for evidence synthesis

Medwave ◽

10.5867/medwave.2021.06.8315 ◽

2021 ◽

Vol 21 (06) ◽

pp. e8315-e8315

Author(s):

Catalina Gracia González-Xuriguera ◽

Laura Vergara-Merino ◽

Luis Garegnani ◽

Luis Ortiz-Muñoz ◽

Nicolás Meza

Keyword(s):

Graphical Representation ◽

Clinical Epidemiology ◽

Evidence Synthesis ◽

Meta Analysis ◽

Distinctive Features ◽

Assessment Development ◽

Analysis Of Results ◽

Multiple Treatments ◽

Therapeutic Alternatives ◽

Grade Approach

This article belongs to a collaborative methodological series of narrative reviews about biostatistics and clinical epidemiology. The goal is to present basics concepts concerning the systematics reviews of multiple treatments comparisons with network meta-analysis. For clinical ques-tions with several therapeutic alternatives to be compared, the central question is how to classify or rank their effectiveness (benefit and harm) to choose the best option. The network meta-analysis aims to answer questions related to the effectiveness and safety of comparing multiple treatments by the simultaneous analysis of results raised from direct and indirect comparisons. The network geometry is the general graphical representation of the network meta-analysis and allows to understand and assess the strength of comparisons. The network meta-analysis should check several assumptions to be valid, especially the transitivity assumption, which allows assuming that there are no systematic differences among the included comparisons, except their compared interventions. Thus, it is possible to know the relative therapeutic effectiveness of each pair of interventions included in the network meta-analysis and their ranking in terms of categorization. It has been proposed to use a modified Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach considering the distinctive features of network meta-analysis to assess the certainty of the evidence for each comparison and the ranking of interventions.

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How to report E-values for meta-analyses: Recommended improvements and additions to the new GRADE approach

10.31219/osf.io/xb25k ◽

2021 ◽

Author(s):

Maya B Mathur ◽

Tyler VanderWeele

Keyword(s):

Working Group ◽

Assessment Development ◽

Confounding Bias ◽

Evidence Strength ◽

Specific Proposal ◽

Meta Analyses ◽

Assessing Sensitivity ◽

Grade Approach

In a recent concept paper (Verbeek et al., 2021), the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group provides a preliminary proposal to improve its existing guidelines for assessing sensitivity to uncontrolled confounding in meta-analyses of nonrandomized studies. The new proposal centers on reporting the E-value for the meta-analytic mean and on comparing this E-value to a measured “reference confounder” to determine whether residual uncontrolled confounding in the meta-analyzed studies could or could not plausibly explain away the meta-analytic mean. Although we agree that E-value analogs for meta-analyses could be an informative addition to future GRADE guidelines, we suggest improvements to the Verbeek et al. (2021)’s specific proposal regarding: (1) their interpretation of comparisons between the E-value and the strengths of associations of a reference confounder; (2) their characterization of evidence strength in meta-analyses in terms of only the meta-analytic mean; and (3) the possibility of confounding bias that is heterogeneous across studies.

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Introduction to the GRADE Approach for Guideline Development: Considerations for Physical Therapist Practice

Physical Therapy ◽

10.2522/ptj.20130627 ◽

2014 ◽

Vol 94 (11) ◽

pp. 1652-1659 ◽

Cited By ~ 16

Author(s):

Tricia M. Austin ◽

Randy R. Richter ◽

Chris A. Sebelski

Keyword(s):

Health Care ◽

International Organizations ◽

Physical Therapists ◽

Physical Therapist ◽

Guideline Development ◽

Care Delivery ◽

Assessment Development ◽

Diagnosis And Prognosis ◽

Use Of Resources ◽

Grade Approach

BackgroundPractice guidelines (guidelines) have an increasing role in health care delivery and are being published more frequently. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) is an approach for guideline development. The GRADE approach has been adopted by multiple national and international organizations producing guidelines related to physical therapist care.ObjectiveThe purpose of this article is to introduce physical therapists to the GRADE approach for guideline development.ResultsGRADE provides a consistent approach for guideline development and transparency in the communication of how the guidelines were developed and how the recommendations were reached, leading to informed choices by patients, clinicians, and policy makers in health care. GRADE leads to a clear distinction between the strength of the evidence and the recommendation. Both the direction (for or against) and the strength (weak or strong) of the recommendation are considered. For determining the strength of the recommendation, GRADE takes into account the quality of evidence, the balance of benefit and harm, uncertainty about or variability in patients' values and preferences, and uncertainty about whether the intervention is a wise use of resources.LimitationsThe GRADE approach has been used primarily with interventions and clinical questions and less often with questions related to diagnosis and prognosis.ConclusionsThe frequency of publication of guidelines is increasing. To make informed choices in the health care system, physical therapists should understand how guidelines are developed. The GRADE approach has been adopted by national and international organizations that produce guidelines relevant to physical therapist practice. Understanding the GRADE approach will enable physical therapists to make informed clinical choices.

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Perspectives for systems biology in the management of tuberculosis

European Respiratory Review ◽

10.1183/16000617.0377-2020 ◽

2021 ◽

Vol 30 (160) ◽

pp. 200377

Author(s):

Irina Kontsevaya ◽

Christoph Lange ◽

Patricia Comella-del-Barrio ◽

Cristian Coarfa ◽

Andrew R. DiNardo ◽

...

Keyword(s):

Systems Biology ◽

Response To Therapy ◽

Drug Resistant ◽

Assessment Development ◽

Resistant Tuberculosis ◽

Tuberculosis Prevention ◽

Novel Biomarkers ◽

Prospective Cohorts ◽

Grade Approach

Standardised management of tuberculosis may soon be replaced by individualised, precision medicine-guided therapies informed with knowledge provided by the field of systems biology. Systems biology is a rapidly expanding field of computational and mathematical analysis and modelling of complex biological systems that can provide insights into mechanisms underlying tuberculosis, identify novel biomarkers, and help to optimise prevention, diagnosis and treatment of disease. These advances are critically important in the context of the evolving epidemic of drug-resistant tuberculosis. Here, we review the available evidence on the role of systems biology approaches – human and mycobacterial genomics and transcriptomics, proteomics, lipidomics/metabolomics, immunophenotyping, systems pharmacology and gut microbiomes – in the management of tuberculosis including prediction of risk for disease progression, severity of mycobacterial virulence and drug resistance, adverse events, comorbidities, response to therapy and treatment outcomes. Application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach demonstrated that at present most of the studies provide “very low” certainty of evidence for answering clinically relevant questions. Further studies in large prospective cohorts of patients, including randomised clinical trials, are necessary to assess the applicability of the findings in tuberculosis prevention and more efficient clinical management of patients.

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The GRADE approach, Part 2: Evidence to decision frameworks—outlining decision-making in health

Medwave ◽

10.5867/medwave.2021.04.8182 ◽

2021 ◽

Vol 21 (04) ◽

pp. e8182-e8182

Author(s):

Carlos Quilodrán ◽

Matías Kirmayr ◽

Bárbara Valente ◽

Javier Pérez-Bracchiglione ◽

Luis Garegnani ◽

...

Keyword(s):

Decision Making ◽

Resource Use ◽

Evaluation Methodology ◽

Adoption Process ◽

Trade Off ◽

Assessment Development ◽

Extensive Information ◽

Structured System ◽

Grade Methodology ◽

Grade Approach

The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology provides a framework for assessing the certainty of the evidence and making recommendations. The Evidence to Decision Framework (EtD) is a transparent and structured system for formulating health recommendations. Once the problem is identified and the certainty of the evidence is assessed, EtD provides several criteria for formulating a recommendation. These criteria include the trade-off between benefits and harms, patients’ values and preferences, acceptability, feasibility, resource use, and impact on equity. The resulting recommendations may differ in strength (strong or weak) and direction (for or against). The process is transparent, allowing other users to adjust the framework of recommendations by modifying the criteria to fit the desired context through an adaptation-adoption process. Given the extensive information available on EtD and the GRADE methodology in general, this narrative review seeks to explain the main concepts involved in decision-making in health by using simplified and friendly descriptions, accompanied by practical examples, thus facilitating its understanding by inexperienced readers.

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Evidence-based Medicine (Dr. Gordon Guyatt)

The Meducator ◽

10.15173/m.v1i36.2336 ◽

2019 ◽

Vol 1 (36) ◽

pp. 26-28

Author(s):

The Meducator ◽

Daniel Rayner ◽

Hargun Kaur

Keyword(s):

Evidence Based Medicine ◽

Large Scale ◽

Research Evidence ◽

Evidence Based ◽

Assessment Development ◽

Department Of Health ◽

Study Methodology ◽

Based Medicine ◽

Grade Approach ◽

Development And Evolution

Dr. Gordon Guyatt is a Distinguished Professor in the Department of Health Research Methods, Evidence, and Impact at McMaster University, and is one of the founders of “evidence-based medicine.” He has played a significant role in over 30 major clinical studies, including large-scale observational and randomized trials and has extensive expertise in study methodology. As the co-founder and co-chair of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group, he has been intimately involved in the development and evolution of the GRADE approach for evaluating research evidence.

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Association between Stress at Work and Temporomandibular Disorders: A Systematic Review

BioMed Research International ◽

10.1155/2021/2055513 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Ricardo Luiz de Barreto Aranha ◽

Renata de Castro Martins ◽

Diego Rodrigues de Aguilar ◽

Johana Alejandra Moreno-Drada ◽

Woosung Sohn ◽

...

Keyword(s):

Occupational Stress ◽

Temporomandibular Disorders ◽

Positive Association ◽

Signs And Symptoms ◽

Epidemiologic Studies ◽

Inclusion Criteria ◽

Assessment Development ◽

Stress At Work ◽

Publication Period ◽

Grade Approach

Temporomandibular disorders (TMD) have been traditionally associated with psychosocial factors; however, occupational stress as a factor related to TMD has not been adequately assessed in the literature. The aim was to investigate the association between stress at work and TMD on adult paid workers. An electronic search included PubMed, Scopus, Web of Science, Embase, and LILACS databases. Manual searches in the included articles’ reference and gray literature were performed. There were no restrictions regarding language or publication period. The inclusion criteria comprised observational studies with paid workers of any category, of both sexes, above 18 years old, assessing occupational stress/stress or distress and TMD as diagnosis or isolated signs and symptoms. Methodological quality was evaluated using Joanna Briggs tools. We narratively assessed the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We collected 12 studies. 50% reported a positive association between stress and TMD diagnostic across various job categories. On the other hand, TMJ sounds (a TMD sign) and work stress were associated only in a musicians’ population. However, the shortage of eligible articles and the methodological limitations provided a very low certainty of the evidence; only 4 of the studies used validated tools for both stress and TMD (2 reporting positive association). The association between stress and TMD is inconclusive by the available data. In the future, we expect more robust epidemiologic studies addressing these relevant aspects.

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The GRADE approach, Part 1: how to assess the certainty of the evidence

Medwave ◽

10.5867/medwave.2021.02.8109 ◽

2021 ◽

Vol 21 (02) ◽

pp. e8109-e8109

Author(s):

Matías Kirmayr ◽

Carlos Quilodrán ◽

Bárbara Valente ◽

Cristóbal Loezar ◽

Luis Garegnani ◽

...

Keyword(s):

Dose Response ◽

Risk Of Bias ◽

Classification Systems ◽

Second Step ◽

Large Magnitude ◽

Assessment Development ◽

Evaluation Approach ◽

Response Gradient ◽

Residual Confounding ◽

Grade Approach

The certainty of the evidence for interventions is the certainty or confidence that the true effect is within a particular range or relative to a threshold. In the new pyramid of evidence, systematic reviews represent the magnifying glass through which this certainty is evaluated. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach arises in response to the existence of multiple evidence classification systems, and it offers a transparent and structured process to develop and present summaries of evidence considering its certainty and, in a second step, the strength of the recommendations that they inform. The GRADE process begins with an explicit question that includes all important and critical outcomes explicitly. The main domains used to assess the certainty of the evidence are risk of bias, inconsistency, indirectness of evidence, imprecision, and publication bias. The factors that can increase the certainty of the evidence are dose-response gradient, large magnitude of an effect, and effect of plausible residual confounding. Finally, the Summary of Findings tables summarize the process in a simplified way and with controlled language. This narrative review’s purpose is to address the GRADE approach’s theoretical and practical underlying concepts in a simplified way and with practical examples.

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Anti-Androgen Drugs in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review

Current Medicinal Chemistry ◽

10.2174/0929867326666191209142209 ◽

2020 ◽

Vol 27 (40) ◽

pp. 6825-6836

Author(s):

Homa Nomani ◽

Amir Hooshang Mohammadpour ◽

Seyed Mohammad Hassan Moallem ◽

Mahdi Jannati YazdanAbad ◽

George E. Barreto ◽

...

Keyword(s):

Clinical Trials ◽

Obsessive Compulsive Disorder ◽

Randomized Trials ◽

Obsessive Compulsive ◽

Compulsive Disorder ◽

Assessment Development ◽

Clinical Trials Registry ◽

Positive Results ◽

Grade Approach ◽

Group Grade

Objective: This study aimed to systematically investigate whether anti-androgens could significantly reduce Obsessive-Compulsive Disorder (OCD) symptoms compared to placebo or usual care in OCD patients. Methods: PubMed, EMBASE, CENTRAL and International Clinical Trials Registry Platform (ICTRP) databases were searched up to October 2018 using relevant keywords. All randomized and if not available non-randomized studies conducted on a population including OCD patients who were administered with anti-androgen, which reported changes in their symptoms, were included. The studies on compulsive hypersexuality were excluded. Required data were extracted from full-text of the included articles by two independent authors. One randomized and four non-randomized trials were found. Results: The only randomized trial showed that flutamide, an anti-androgen agent, was effective in reducing compulsion scores in male OCD patients with comorbid Tourette syndrome, compared to placebo. Three out of four non-randomized trials showed that different anti-androgens including finasteride, cyproterone acetate and triptorelin were effective in reducing OCD symptoms. The only study, which failed to show the efficacy of an anti-androgen agent, administered OCD patients with flutamide. Despite the positive results, available studies provide the evidence with low quality based on the Grades of Recommendation, Assessment, Development and Evaluation Working Group (GRADE) approach. Conclusions : Available studies are not sufficient for a precise answer to our study question. There is still a need for further large randomized blinded clinical trials to evaluate the effectiveness of antiandrogens in OCD patients. It is recommended that gender, comorbidities and subscales of Yale- Brown Obsessive-Compulsive Score (Y-BOCS) should be considered in designing the studies and interpreting their results.

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