Santesso, Nancy A.

When one initially targets the null effect and the point estimate falls close to the null, two challenges exist in rating certainty of evidence. First, when the point estimate is near the null and the data, therefore, suggests little or no effect, rating certainty in a benefit or harm is misleading. Second, since in general the narrower the confidence interval (CI) the more precise the estimate, if the CI is narrow, rating down for imprecision due simply to crossing the null is inappropriate. This paper addresses these issues and provides a solution: to revise the target of certainty rating from a non-zero effect to a little or no effect. This solution requires estimating a range in which the minimal important difference (MID) for benefit and an MID for harm might lie, and thus establishing a range that represents little or no effect. If GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) users are confident that the point estimate represents an effect less than the smallest plausible MID, they will revise their target and rate certainty to a little or no effect. If the entire CI falls within the range of little or no effect, they will not rate down for imprecision. Otherwise (if the CI includes an important effect), they will rate down. Using the solution provided in this paper GRADE users can make an optimal choice of the target of certainty rating.

Abstract In an effort to enhance the trustworthiness of its clinical practice guidelines, the Endocrine Society has recently adopted new policies and more rigorous methodologies for its guideline program. In this Clinical Practice Guideline Communication, we describe these recent enhancements—many of which reflect greater adherence to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to guideline development—in addition to the rationale for such changes. Improvements to the Society’s guideline development practices include, but are not limited to, enhanced inclusion of nonendocrinologist experts, including patient representatives, on guideline development panels; implementation of a more rigorous conflict/duality of interest policy; a requirement that all formal recommendations must be demonstrably underpinned by systematic evidence review; the explicit use of GRADE Evidence-to-Decision frameworks; greater use and explanation of standardized guideline language; and a more intentional approach to guideline updating. Lastly, we describe some of the experiential differences our guideline readers are most likely to notice.

Abstract Background Adult patients with diabetes or newly recognized hyperglycemia account for over 30% of noncritically ill hospitalized patients. These patients are at increased risk for adverse clinical outcomes in the absence of defined approaches to glycemic management. Objective To review and update the 2012 Management of Hyperglycemia in Hospitalized Patients in Non-Critical Care Settings: An Endocrine Society Clinical Practice Guideline and to address emerging areas specific to the target population of noncritically ill hospitalized patients with diabetes or newly recognized or stress-induced hyperglycemia. Methods A multidisciplinary panel of clinician experts, together with a patient representative and experts in systematic reviews and guideline development, identified and prioritized 10 clinical questions related to inpatient management of patients with diabetes and/or hyperglycemia. The systematic reviews queried electronic databases for studies relevant to the selected questions. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make recommendations. Results The panel agreed on 10 frequently encountered areas specific to glycemic management in the hospital for which 15 recommendations were made. The guideline includes conditional recommendations for hospital use of emerging diabetes technologies including continuous glucose monitoring and insulin pump therapy; insulin regimens for prandial insulin dosing, glucocorticoid, and enteral nutrition–associated hyperglycemia; and use of noninsulin therapies. Recommendations were also made for issues relating to preoperative glycemic measures, appropriate use of correctional insulin, and diabetes self-management education in the hospital. A conditional recommendation was made against preoperative use of caloric beverages in patients with diabetes. Conclusion The recommendations are based on the consideration of important outcomes, practicality, feasibility, and patient values and preferences. These recommendations can be used to inform system improvement and clinical practice for this frequently encountered inpatient population.

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.