Matthew Ventresca

Guidelines 2.0: systematic development of a comprehensive checklist for a successful guideline enterprise

Background: Although several tools to evaluate the credibility of health care guidelines exist, guidance on practical steps for developing guidelines is lacking. We systematically compiled a comprehensive checklist of items linked to relevant resources and tools that guideline developers could consider, without the expectation that every guideline would address each item. Methods: We searched data sources, including manuals of international guideline developers, literature on guidelines for guidelines (with a focus on methodology reports from international and national agencies, and professional societies) and recent articles providing systematic guidance. We reviewed these sources in duplicate, extracted items for the checklist using a sensitive approach and developed overarching topics relevant to guidelines. In an iterative process, we reviewed items for duplication and omissions and involved experts in guideline development for revisions and suggestions for items to be added. Results: We developed a checklist with 18 topics and 146 items and a webpage to facilitate its use by guideline developers. The topics and included items cover all stages of the guideline enterprise, from the planning and formulation of guidelines, to their implementation and evaluation. The final checklist includes links to training materials as well as resources with suggested methodology for applying the items. Interpretation: The checklist will serve as a resource for guideline developers. Consideration of items on the checklist will support the development, implementation and evaluation of guidelines. We will use crowdsourcing to revise the checklist and keep it up to date.

A review of patient-reported outcomes for children and adolescents with obesity

IntroductionObesity is a chronic condition that can impact the physical, emotional, mental and social elements that encompass a child’s life. The objectives of this study were to identify which generic and obesity-specific patient-reported outcome (PRO) instruments are used in obesity literature, as well as review their conceptual approach, health and health-related content, ethical content and psychometric properties.MethodPubMed, CINAHL, EMBASE and PsycINFO were searched from the inception of each database to May 2012 to identify all studies using multi-dimensional PRO instruments with children who are overweight or obese. The most common generic and all obesity-specific instruments were analyzed according to the study objectives.ResultsFrom 4,226 articles identified by our search, 70 articles used 6 generic and 4 obesity-specific PRO instruments. While the most commonly used PRO instrument was the generic PedsQL 4.0 (used in 53 studies), many health domains were found in the obesity-specific instruments that are not measured by the PedsQL 4.0. Summary of the development and psychometric properties of the generic and obesity PROs identified that no one instrument meets all the guideline criteria for instrument development and validation, e.g., only one instrument included qualitative input from children with obesity in the content development phase.DiscussionThis comprehensive review provides information to aid in selecting multi-dimensional PRO instruments in children with obesity according to various aspects of content as well as psychometric properties. The conceptual analysis shows that the reviewed PRO instruments contain inconsistencies in their conceptual approaches. Also, certain relevant health domains to children and youth with obesity were not included in the most commonly used generic instrument. The obesity-specific instruments require further validation before they can be used in intervention studies.

Bleeding risk in atrial fibrillation patients taking vitamin K antagonists: systematic review and meta-analysis.

Vitamin K antagonists (VKAs) prevent stroke in atrial fibrillation (AF) at the cost of bleeding risk. To determine major bleeding rates in AF patients, we conducted a systematic review that identified 51 eligible studies including more than 342,699 patients. The pooled estimate of the rate of major bleeding was 2.51 (99% confidence interval: 2.03–3.11) bleeds per 100 patient‐years. The results represent the best estimates of bleeding risk that most patients contemplating VKA use may expect.

Use of heparins in patients with cancer: individual participant data meta-analysis of randomised trials study protocol.

Introduction Parenteral anticoagulants may improve outcomes in patients with cancer by reducing risk of venous thromboembolic disease and through a direct antitumour effect. Study-level systematic reviews indicate a reduction in venous thromboembolism and provide moderate confidence that a small survival benefit exists. It remains unclear if any patient subgroups experience potential benefits. Methods and analysis First, we will perform a comprehensive systematic search of MEDLINE, EMBASE and The Cochrane Library, hand search scientific conference abstracts and check clinical trials registries for randomised control trials of participants with solid cancers who are administered parenteral anticoagulants. We anticipate identifying at least 15 trials, exceeding 9000 participants. Second, we will perform an individual participant data meta-analysis to explore the magnitude of survival benefit and address whether subgroups of patients are more likely to benefit from parenteral anticoagulants. All analyses will follow the intention-to-treat principle. For our primary outcome, mortality, we will use multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We will adjust analysis for important prognostic characteristics. To investigate whether intervention effects vary by predefined subgroups of patients, we will test interaction terms in the statistical model. Furthermore, we will develop a risk-prediction model for venous thromboembolism, with a focus on control patients of randomised trials. Ethics and dissemination Aside from maintaining participant anonymity, there are no major ethical concerns. This will be the first individual participant data meta-analysis addressing heparin use among patients with cancer and will directly influence recommendations in clinical practice guidelines. Major cancer guideline development organisations will use eventual results to inform their guideline recommendations. Several knowledge users will disseminate results through presentations at clinical rounds as well as national and international conferences. We will prepare an evidence brief and facilitate dialogue to engage policymakers and stakeholders in acting on findings. Trial registration number PROSPERO CRD42013003526.

Improving GRADE evidence tables part 2: a systematic survey of explanatory notes shows more guidance is needed

OBJECTIVES The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) working group has developed GRADE evidence profiles (EP) and summary of findings (SoF) tables to present evidence summaries in systematic reviews, clinical guidelines, and health technology assessments. Explanatory notes are used to explain choices and judgments in these summaries, for example, on rating of the quality of evidence. STUDY DESIGN AND SETTING A systematic survey of the explanations in SoF tables in 132 randomly selected Cochrane Intervention reviews and in EPs of 10 guidelines. We analyzed the content of 1,291 explanations using a predefined list of criteria. RESULTS Most explanations were used to describe or communicate results and to explain downgrading of the quality of evidence, in particular for risk of bias and imprecision. Addressing the source of baseline risk (observational data or control group risk) was often missing. For judgments about downgrading the quality of evidence, the percentage of informative explanations ranged between 41% (imprecision) and 79% (indirectness). CONCLUSION We found that by and large explanations were informative but detected several areas for improvement (e.g., source of baseline risk and judgments on imprecision). Guidance about explanatory footnotes and comments will be provided in the last article in this series.

Systematic Review of Observational Studies Assessing Bleeding Risk in Patients with Atrial Fibrillation Not Using Anticoagulants

Background Patients with atrial fibrillation considering use of anticoagulants must balance stroke reduction against bleeding risk. Knowledge of bleeding risk without the use of anticoagulants may help inform this decision. Purpose To determine the rate of major bleeding reported in observational studies of atrial fibrillation patients not receiving Vitamin K antagonists (VKA). Data Sources We searched MEDLINE, EMBASE and CINAHL to October 2011 and examined reference lists of eligible studies and related reviews. Study Selection All longitudinal cohort studies that included over 100 adult patients with atrial fibrillation not receiving VKA. Data Extraction Teams of two reviewers independently and in duplicate adjudicated eligibility, assessed risk of bias and abstracted study characteristics and outcomes. Data Synthesis Twenty-one eligible studies included 96,448 patients. Major bleeding rates varied widely, from 0 to 4.69 events per 100 patient-years. The pooled estimate in 13 studies with 78839 patients was 1.59 with a 99% confidence interval of 1.10 to 2.3 and median 1.42 (interquartile range 0.62–2.70). Pooled estimates for fatal bleeding and non-fatal bleeding from 4 studies that reported these outcomes were, respectively, 0.40 (0.34 to 0.46) and 1.18 (0.30 to 4.56) per 100 patient-years. In 9 randomized controlled trials (RCTs) the median rate of major bleeding in patients not receiving either anticoagulant or antiplatelet therapy was 0.6 (interquartile 0.2 to 0.90), and in 12 RCTs the median rate of major bleeding in patients receiving a single antiplatelet agent was 0.75 (interquartile 0.4 to 1.4). Conclusion Results suggest that patients with atrial fibrillation not receiving VKA enrolled in observational studies represent a population on average at higher risk of bleeding.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 3: a systematic review shows limitations in most tools designed to assess quality and develop recommendations

OBJECTIVES The objective of this study was to identify and describe critical appraisal tools designed for assessing the quality of evidence (QoE) and/or strength of recommendations (SoRs) related to health care-related tests and diagnostic strategies (HCTDSs). STUDY DESIGN AND SETTING We conducted a systematic review to identify tools applied in guidelines, methodological articles, and systematic reviews to assess HCTDS. RESULTS We screened 5,534 titles and abstracts, 1,004 full-text articles, and abstracted data from 330 references. We identified 29 tools and 14 modifications of existing tools for assessing QoE and SoR. Twenty-three out of 29 tools acknowledge the importance of assessing the QoE and SoR separately, but in 8, the SoR is based solely on QoE. When making decisions about the use of tests, patient values and preferences and impact on resource utilization were considered in 6 and 8 tools, respectively. There is also confusion about the terminology that describes the various factors that influence the QoE and SoR. CONCLUSION Although at least one approach includes all relevant criteria for assessing QoE and determining SoR, more detailed guidance about how to operationalize these assessments and make related judgments will be beneficial. There is a need for a better description of the framework for using evidence to make decisions and develop recommendations about HCTDS.

Decision making about healthcare-related tests and diagnostic test strategies. Paper 4: International guidelines show variability in their approaches

OBJECTIVES The objective of the study was to describe and compare current practices in developing guidelines about the use of healthcare-related tests and diagnostic strategies (HCTDS). STUDY DESIGN AND SETTING We sampled 37 public health and clinical practice guidelines about HCTDS from various sources without language restrictions. RESULTS Detailed descriptions of the systems used to assess the quality of evidence and develop recommendations were challenging to find within guidelines. We observed much variability among and within organizations with respect to how they develop recommendations about HCTDS. Twenty-four percent of the guidelines did not consider health benefits and harms but based decisions solely on test accuracy. We did not identify guidelines that described the main potential care pathways involving tests for a healthcare problem. In addition, we did not identify guidelines that systematically assessed, described, and referenced the evidence that linked test accuracy and patient-important outcomes. CONCLUSION There is considerable variability among the processes used and factors considered in developing recommendations about the use of tests. This variability may be the cause for the disagreement we observed in recommendations about testing for the same condition.

041 MAKING RECOMMENDATIONS ABOUT DIAGNOSTIC TESTS AND STRATEGIES: WHAT DO EXPERTS SAY?

Background Current practices in developing guidelines about the use of diagnostic tests and strategies (DTS) are out of step with the conceptual discussion among experts. Objectives Identify the essential factors to consider when making recommendations about DTS. Methods We conducted semi-structured in-depth interviews with experts in assessing evidence and producing guidelines about DTS. Results We interviewed 23 international experts. Although diagnostic test accuracy (DTA) was the factor most commonly considered by organisations when developing recommendations, experts agreed that DTA is never sufficient and may be misleading. Experts identified the following additional essential factors in making decisions about DTS: resource implications, complications, inconclusive results, additional benefits of the test, diagnostic/therapeutic impact, safety, feasibility, ethical, legal, and organisational considerations, patients’ and societies’ values and preferences and the link between the test results and patient important outcomes. Because direct evidence on DTS’s effects on patient outcomes and resource implications is frequently unavailable, most experts agreed that decision analysis and mathematical modelling will be useful, but their opinion varied about the extent of details needed. Discussion Formal decision modelling can be a useful framework for organising the clinical, cost, and preference data relevant to the use of diagnostic tests. Although it requires resources, it is useful for integrating these factors into decision making, identifying evidence gaps, and high priority research areas. Implications Developing guidelines about the use of DTS requires considering factors beyond solely DTA but implementing this demand is challenging. Further development and testing of a framework that can guide this process is needed.