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Objectives: Guidelines and essential medicine lists (EMLs) bear similarities and differences in the process that lead to decisions. Access to essential medicines is central to achieve universal health coverage. The World Health Organization (WHO) EML has guided prioritization of essential medicines globally for nearly 50 years, and national EMLs (NEMLs) exist in over 130 countries. Guideline and EML decisions, at WHO or national levels, are not always coordinated and aligned. We sought to explore challenges, and potential solutions, for decision-making to support trustworthy medicine selection for EMLs from a Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group perspective. We primarily focus on the WHO EML; however, our findings may be applicable to NEML decisions as well., Study Design and Setting: We identified key challenges in connecting the EML to health guidelines by involving a broad group of stakeholders and assessing case studies including real applications to the WHO EML, South Africa NEML, and a multiple sclerosis guideline connected to a WHO EML application for multiple sclerosis treatments. To address challenges, we utilized the results of a survey and feedback from the stakeholders, and iteratively met as a project group. We drafted a conceptual framework of challenges and potential solutions. We presented a summary of the results for feedback to all attendees of the GRADE Working Group meetings in November 2022 (approximately 120 people) and in May 2023 (approximately 100 people) before finalizing the framework., Results: We prioritized issues and insights/solutions that addressed the connections between the EML and health guidelines. Our suggested solutions include early planning alignment of guideline groups and EMLs, considering shared participation to strengthen linkage, further clarity on price/cost considerations, and using explicit shared criteria to make guideline and EML decisions. We also provide recommendations to strengthen the connection between WHO EML and NEMLs including through contextualization methods., Conclusion: This GRADE concept article, jointly developed by key stakeholders from the guidelines and EMLs field, identified key conceptual issues and potential solutions to support the continued advancement of trustworthy EMLs. Adopting structured decision criteria that can be linked to guideline recommendations bears the potential to advance health equity and gaps in availability of essential medicines within and between countries., Competing Interests: Declaration of competing interest Tamara Kredo is a member of the South African National Essential Medicines List Committee and Standard Treatment Guidelines; Co-lead of South African GRADE Network; Cochrane Board member; Member of the National Advisory Group on Immunisation. Trudy Leong is a member of the SA GRADE Network. Michael McCaul is a Member of the South African Primary Health Care and Adult Hospital Level Expert Review Committee; Founding member of the SA GRADE Network. The remaining authors are all members of the GRADE Working Group, however, have no other interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objectives: The World Health Organization Model List of Essential Medicines has led to at least 137 national lists. Essential medicines should be grounded in evidence-based guideline recommendations and explicit decision criteria. Essential medicines should be available, accessible, affordable, and the supporting evidence should be accompanied by a rating of the certainty one can place in it. Our objectives were to identify criteria and considerations that should be addressed in moving from a guideline recommendation regarding a medicine to the decision of whether to add, maintain, or remove a medicine from an essential medicines list. We also seek to explore opportunities to improve organizational processes to support evidence-based health decision-making more broadly., Methods: We conducted a qualitative study with semistructured interviews of key informant stakeholders in the development and use of guidelines and essential medicine lists (EMLs). We used an interpretive descriptive analysis approach and thematic analysis of interview transcripts in NVIVO v12., Results: We interviewed 16 key informants working at national and global levels across all WHO regions. We identified five themes: three descriptive/explanatory themes 1) EMLs and guidelines, the same, but different; 2) EMLs can drive price reductions and improve affordability and access; 3) Time lag and disconnect between guidelines and EMLs; and two prescriptive themes 4) An "evidence pipeline" could improve coordination between guidelines and EMLs; 5) Facilitating the link between the WHO Model List of Essential Medicines (WHO EML) and national EMLs could increase alignment., Conclusion: We found significant overlap and opportunities for alignment between guideline and essential medicine decision processes. This finding presents opportunities for guideline and EML developers to enhance strategies for collaboration. Future research should assess and evaluate these strategies in practice to support the shared goal of guidelines and EMLs: improvements in health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To describe divergence between actionable statements issued by coronavirus disease 2019 (COVID-19) guideline developers cataloged on the "COVID-19 Recommendations and Gateway to Contextualization" platform., Study Design and Setting: We defined divergence as at least two comparable actionable statements with different explicit judgments of strength, direction, or subgroup consideration of the population or intervention. We applied a content analysis to compare guideline development methods for a sample of diverging statements and to evaluate factors associated with divergence., Results: Of the 138 guidelines evaluated, 85 (62%) contained at least one statement that diverged from another guideline. We identified 223 diverging statements in these 85 guidelines. We grouped statements into 66 clusters. Each cluster addressed the same population, intervention, and comparator group or just similar interventions. Clinical practice statements were more likely to diverge in an explicit judgment of strength or direction compared to public health statements. Statements were more likely to diverge in strength than direction. The date of publication, used evidence, interpretation of evidence, and contextualization considerations were associated with divergence., Conclusion: More than half of the assessed guidelines issued at least one diverging statement. This study helps in understanding the types of differences between guidelines issuing comparable statements and factors associated with their divergence., (Copyright © 2022. Published by Elsevier Inc.)

Objective: 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 it using randomly selected recommendations from published guidelines addressing COVID-19 from different organizations, evaluated its results, and refined it before retesting. The urgency and availability of evidence for development of these recommendations varied. We consulted with experts in research methodology and guideline developers to improve the final framework., Results: The resulting taxonomy and framework distinguishes five types of actional statements: formal recommendations; research recommendations; good practice statements; implementation considerations, tools and tips; and informal recommendations. These statements should respond to a priori established criteria and require a clear structure and recognizable presentation in a guideline. Most importantly, this framework identifies informal recommendations that differ from formal recommendations by how they consider evidence and in their development process., Conclusion: The identification, standardization and explicit labelling of actionable statements according to the framework may support guideline developers to create actionable statements with clear intent, avoid informal recommendations and improve their understanding and implementation by users., (Copyright © 2021. Published by Elsevier Inc.)

Background: Data extraction from reports about experimental or observational studies is a crucial methodological step informing evidence syntheses, such as systematic reviews (SRs) and overviews of SRs. Reporting discrepancies were defined as pairs of statements that could not both be true. Authors of SRs and overviews of SRs can encounter reporting discrepancies among multiple sources when extracting data-a manuscript and a conference abstract, and a manuscript and a clinical trial registry. However, these discrepancies can also be found within a single manuscript published in a scientific journal., Objectives: Hereby, we describe examples of internal reporting discrepancies that can be found in a single source, with the aim of raising awareness among authors of SRs and overviews of SRs about such potential methodological issues., Conclusions: Authors of SRs and overviews of SRs should check whether the same information is reported in multiple places within a study and compare that information. Independent data extraction by two reviewers increases the chance of finding discrepancies, if they exist. We provide advice on how to deal with different types of discordances and how to report such discordances when conducting SRs and overviews of SRs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To explore disagreements in multiple systematic reviews (SRs) assessing the benefit-to-harm ratio of thrombolytic therapy in patients with intermediate-risk pulmonary embolism (PE)., Study Design and Setting: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Database of Abstracts and Reviews of Effectiveness were searched up to April 14, 2016. We included SRs and guidelines that evaluated thrombolytic therapy, compared with anticoagulation alone, in intermediate-risk PE. We calculated pooled risk ratio (RR) and absolute risk difference (RD), with interquartile range (IQR), for all-cause mortality, recurrent PE, and major bleeding., Results: We marked the Pulmonary Embolism Thrombolysis trial, the largest trial, as a research milestone. Since its release in 2014, 12 SRs (2-15 included trials) and two major guidelines were published. Studies were concordant in reporting that thrombolysis reduced all-cause mortality (median RD -1.55%, IQR -1.60% to -1.40%; median RR 0.55, IQR 0.48-0.61). Discordant results were found for major bleeding (median RD 4.70%, IQR 0.90%-5.70%), with SRs reporting results in opposite directions. Relevant magnitude of effects and precision for benefits and harms were never prespecified., Conclusion: Fourteen evidence syntheses were published within 25 months. Conclusions suggested mortality reduction associated with thrombolytics. Therapy harm was more dispersed and alternatively considered. Interpretation of the benefit-to-harm ratio was elusive, and modest incremental advantages might or not be important, facilitating the origin of disputes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The aim of this paper is to provide detailed guidance on how to incorporate health equity within the GRADE (Grading Recommendations Assessment and Development Evidence) evidence to decision process., Study Design and Setting: We developed this guidance based on the GRADE evidence to decision framework, iteratively reviewing and modifying draft documents, in person discussion of project group members and input from other GRADE members., Results: Considering the impact on health equity may be required, both in general guidelines and guidelines that focus on disadvantaged populations. We suggest two approaches to incorporate equity considerations: (1) assessing the potential impact of interventions on equity and (2) incorporating equity considerations when judging or weighing each of the evidence to decision criteria. We provide guidance and include illustrative examples., Conclusion: Guideline panels should consider the impact of recommendations on health equity with attention to remote and underserviced settings and disadvantaged populations. Guideline panels may wish to incorporate equity judgments across the evidence to decision framework. This is the fourth and final paper in a series about considering equity in the GRADE guideline development process. This series is coming from the GRADE equity subgroup., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To clarify the impact of multiple (covering the same population, intervention, control, and outcomes) systematic reviews (SRs) on interventions for myocardial infarction (MI)., Study Design and Setting: Clinical Evidence (BMJ Group) sections and related search strategies regarding MI were used to identify multiple SRs published between 1997 and 2007. Multiple SRs were classified as discordant if they featured conflicting results or interpretation of them., Results: Thirty-six SRs (23.5% of 153 on the treatment or prevention of MI) were classified as multiple and grouped in 16 clusters [ie, at least two SRs with the same PICO (population, condition/disease, intervention, control) and at least one common outcome] exploring angioplasty, angiotensin-converting enzyme inhibitors, anticoagulants, antiplatelets, β-blockers, and stents. Complete agreement on statistically significant differences between interventions was found in 7 of 10 clusters with a shared composite outcome. Agreement was reduced when single outcomes were considered. Despite substantial variation and limited agreement in reporting of major outcomes, SRs agreed in their conclusions on the superiority of either the intervention or control in 14 of 16 clusters. Sources of minor discrepancies were found in terms of study and outcome selection, subgroup analyses, and interpretation of findings., Conclusion: Multiple SRs agreed in their qualitative conclusions but not on reporting and on analyses of hard outcomes. Discordance on significance of treatment effects was due to a combination of variation in design with inclusion of different studies and lack of precision for single hard outcomes compared with a composite outcome. Such inconsistencies among SRs could potentially slow the translation of SRs' results to clinical and public health decision making and suggest the need for a broader methodological and clinical agreement on their design., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To evaluate a new format of a summary, which presents research from synthesized evidence to patients and the public., Study Design and Setting: We conducted a randomized controlled trial in 143 members of the public from five countries (Canada, Norway, Spain, Argentina, and Italy). Participants received either a new summary format (a plain language summary [PLS]) or the current format used in Cochrane systematic reviews. The new PLS presents information about the condition and intervention, a narrative summary of results, and a table of results with absolute numbers for effects of the intervention and quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation., Results: With the new PLS, more participants understood the benefits and harms and quality of evidence (53% vs. 18%, P < 0.001); more answered each of the five questions correctly (P ≤ 0.001 for four questions); and they answered more questions correctly, median 3 (interquartile range [IQR]: 1-4) vs. 1 (IQR: 0-1), P < 0.001). Better understanding was independent of education level. More participants found information in the new PLS reliable, easy to find, easy to understand, and presented in a way that helped make decisions. Overall, participants preferred the new PLS., Conclusion: This new PLS format for patients and the public is a promising tool to translate evidence from synthesized research., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the strength of causal inferences reported in randomized and nonrandomized evaluations of quality improvement (QI) interventions in relation to the study design and the direction of results for the primary outcomes., Study Design and Setting: We searched 11 journals for QI intervention studies that aimed to change clinician behavior. Statements that addressed the causal inference between intervention and outcomes were extracted and were rated by 34 researchers for the strength of causality., Results: We found 38 randomized controlled trials (RCTs) and 35 non-RCTs, and extracted 68 quotes from the abstracts and 139 from the main text. A significant interaction was found between study design and direction of results for the abstract quotes (P=0.022). The ratings for non-RCTs were higher when the results were mixed, but for RCTs, they were higher if the results were positive or no effect, although none of the differences were statistically significant at alpha=0.05 after adjusting for multiple comparisons. For the main text quotes, the causality rating was higher by 0.43 for RCTs than for non-RCTs after adjusting for the direction of results (P<0.001)., Conclusion: Authors might have overstated the strength of causal inference in the abstracts of non-RCTs, but appeared to report causality appropriately in the main text.