B. Shea

ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions

Non-randomised studies of the effects of interventions are critical to many areas of healthcare evaluation, but their results may be biased. It is therefore important to understand and appraise their strengths and weaknesses. We developed ROBINS-I (“Risk Of Bias In Non-randomised Studies - of Interventions”), a new tool for evaluating risk of bias in estimates of the comparative effectiveness (harm or benefit) of interventions from studies that did not use randomisation to allocate units (individuals or clusters of individuals) to comparison groups. The tool will be particularly useful to those undertaking systematic reviews that include non-randomised studies.

A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.

Abstract: The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1–3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

Fluoride for the Treatment of Postmenopausal Osteoporotic Fractures: A Meta-Analysis

Abstract: We conducted an efectiveness meta-analysis to determine the efficacy of fluoride therapy on bone loss, vertebral and nonvertebral fractures and side effects in postmenopausal women. A literature search was conducted on MEDLINE, Current Contents and the Cochrane Controlled Trial Registry. Two independent reviewers selected randomized controlled trials which met predetermined inclusion criteria. They independently extracted data using predetermined forms and assessed the methodologic quality of the trials using a validated scale. For dichotomous outcomes, the relative risk (RR) was calculated, and for continuous outcomes, the weighted mean difference (WMD) of percentage change from baseline was calculated. Where heterogeneity existed (determined by a chi-square test) a random effects model was used. Eleven studies (1429 subjects) met the inclusion criteria. The increase in lumbar spine bone mineral density (BMD) was found to be higher in the treatment group than in the control group with a WMD 8.1% (95% CI: 7.15, 9.09) after 2 years of treatment and 16.1% (95% CI: 14.65, 17.5) after 4 years. The RR for new vertebral fractures was not significant at 2 years [0.87 (95% CI: 0.51, 1.46)] or at 4 years [0.9 (95% CI: 0.71, 1.14)]. The RR for new nonvertebral fractures was not significant at 2 years [1.2 (95% CI: 0.68, 2.10)] but was increased at 4 years in the treated group [1.85 (95% CI: 1.36, 2.50)], especially if used at high doses and in a non-slow-release form. The RR for gastrointestinal side effects was not significant at 2 years [2.18 (95% CI: 0.86, 1.21)] but was increased at 4 years in the treated group [2.18 (95% CI: 1.69, 4.57)], especially if fluoride was used at high doses and in a non-slow-release form. The number of withdrawals and dropouts was not different between treated and control groups at 2 and 4 years. Thus, although fluoride has an ability to increase bone mineral density at the lumbar spine, it does not result in a reduction in vertebral fractures. Increasing the dose of fluoride increases the risk of nonvertebral fractures and gastrointestinal side effects without any effect on the vertebral fracture rate.

Protocol for the development of a CONSORT-equity guideline to improve reporting of health equity in randomized trials

BackgroundHealth equity concerns the absence of avoidable and unfair differences in health. Randomized controlled trials (RCTs) can provide evidence about the impact of an intervention on health equity for specific disadvantaged populations or in general populations; this is important for equity-focused decision-making. Previous work has identified a lack of adequate reporting guidelines for assessing health equity in RCTs. The objective of this study is to develop guidelines to improve the reporting of health equity considerations in RCTs, as an extension of the Consolidated Standards of Reporting Trials (CONSORT).Methods/designA six-phase study using integrated knowledge translation governed by a study executive and advisory board will assemble empirical evidence to inform the CONSORT-equity extension. To create the guideline, the following steps are proposed: (1) develop a conceptual framework for identifying “equity-relevant trials,” (2) assess empirical evidence regarding reporting of equity-relevant trials, (3) consult with global methods and content experts on how to improve reporting of health equity in RCTs, (4) collect broad feedback and prioritize items needed to improve reporting of health equity in RCTs, (5) establish consensus on the CONSORT-equity extension: the guideline for equity-relevant trials, and (6) broadly disseminate and implement the CONSORT-equity extension.DiscussionThis work will be relevant to a broad range of RCTs addressing questions of effectiveness for strategies to improve practice and policy in the areas of social determinants of health, clinical care, health systems, public health, and international development, where health and/or access to health care is a primary outcome. The outcomes include a reporting guideline (CONSORT-equity extension) for equity-relevant RCTs and a knowledge translation strategy to broadly encourage its uptake and use by journal editors, authors, and funding agencies.

Reporting of sex and gender in randomized controlled trials in Canada: a cross-sectional methods study

BackgroundAccurate reporting on sex and gender in health research is integral to ensuring that health interventions are safe and effective. In Canada and internationally, governments, research organizations, journal editors, and health agencies have called for more inclusive research, provision of sex-disaggregated data, and the integration of sex and gender analysis throughout the research process. Sex and gender analysis is generally defined as an approach for considering how and why different subpopulations (e.g., of diverse genders, ages, and social locations) may experience health conditions and interventions in different or similar ways.The objective of this study was to assess the extent and nature of reporting about sex and/or gender, including whether sex and gender analysis (SGA) was carried out in a sample of Canadian randomized controlled trials (RCTs) with human participants.MethodsWe searched MEDLINE from 01 January 2013 to 23 July 2014 using a validated filter for identification of RCTs, combined with terms related to Canada. Two reviewers screened the search results to identify the first 100 RCTs that were either identified in the trial publication as funded by a Canadian organization or which had a first or last author based in Canada. Data were independently extracted by two people from 10% of the RCTs during an initial training period; once agreement was reached on this sample, the remainder of the data extraction was completed by one person and verified by a second.ResultsThe search yielded 1433 records. We screened 256 records to identify 100 RCTs which met our eligibility criteria. The median sample size of the RCTs was 107 participants (range 12–6085). While 98% of studies described the demographic composition of their participants by sex, only 6% conducted a subgroup analysis across sex and 4% reported sex-disaggregated data. No article defined “sex” and/or “gender.” No publication carried out a comprehensive sex and gender analysis.ConclusionsFindings highlight poor uptake of sex and gender considerations in the Canadian RCT context and underscore the need for better articulated guidance on sex and gender analysis to improve reporting of evidence, inform policy development, and guide future research.

GRADE equity guidelines 4: considering health equity in GRADE guideline development: evidence to decision process

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.

When is a randomised controlled trial health equity relevant? Development and validation of a conceptual framework

Background Randomised controlled trials can provide evidence relevant to assessing the equity impact of an intervention, but such information is often poorly reported. We describe a conceptual framework to identify health equity-relevant randomised trials with the aim of improving the design and reporting of such trials. Methods An interdisciplinary and international research team engaged in an iterative consensus building process to develop and refine the conceptual framework via face-to-face meetings, teleconferences and email correspondence, including findings from a validation exercise whereby two independent reviewers used the emerging framework to classify a sample of randomised trials. Results A randomised trial can usefully be classified as ‘health equity relevant’ if it assesses the effects of an intervention on the health or its determinants of either individuals or a population who experience ill health due to disadvantage defined across one or more social determinants of health. Health equity-relevant randomised trials can either exclusively focus on a single population or collect data potentially useful for assessing differential effects of the intervention across multiple populations experiencing different levels or types of social disadvantage. Trials that are not classified as ‘health equity relevant’ may nevertheless provide information that is indirectly relevant to assessing equity impact, including information about individual level variation unrelated to social disadvantage and potentially useful in secondary modelling studies. Conclusion The conceptual framework may be used to design and report randomised trials. The framework could also be used for other study designs to contribute to the evidence base for improved health equity.