Journal of Clinical Epidemiology最新文献

Objective: In evidence synthesis, inconsistency is typically assessed visually and with the I² and the Q statistics. However, these measures have important limitations (i) if there are few primary studies of small sample sizes, or (ii) if there are multiple studies with precise estimates. In addition, with the increasing use of decision thresholds (DT), for example in GRADE Evidence to Decision frameworks, inconsistency judgments can be anchored around DTs. In this article, we developed quantitative measures to assess inconsistency based on DTs.

Study design and setting: We developed two measures to quantify inconsistency based on DTs - the Decision Inconsistency (DI) and the Across-Studies Inconsistency (ASI) indices. The DI and the ASI are based on the distribution of the posterior samples studies' effect sizes across interpretation categories defined by DTs. We developed these indices for the Bayesian context, followed by a frequentist extension.

Results: The DI informs on the overall inconsistency of effect sizes across interpretation categories, while the ASI quantifies how different studies are compared to each other (in relation to interpretation categories) based on absolute effects. A DI≥50% and an ASI≥25% are suggestive of important unexplained inconsistency. We provide an R package (metainc) and a web tool (https://metainc.med.up.pt/) to support the computation of the DI and ASI, including in the context of sensitivity analyses assessing the impact of potential uncertainty in inconsistency.

Conclusion: The DI and the ASI can contribute to quantitatively assess inconsistency, particularly as DTs are gaining recognition in evidence synthesis and health decision-making.

Objective: The aim of this study was to examine the distribution of country, region, language, and gender diversity in the authorship of Cochrane reviews and compare it to non-Cochrane systematic reviews.

Study design and setting: We retrieved all published articles from the Cochrane Library (until November 6, 2023) using a web crawling technique that extracted pre-specified data fields, including publication date, review category, and author affiliations. For comparison, non-Cochrane systematic reviews were identified through PubMed using E-utility calls. We determined the country, region of affiliations and gender of the first, corresponding, and last authors for Cochrane reviews; the same fields were determined for first authors only for non-Cochrane reviews due to data availability. Trends in geographical and gender diversity over time were evaluated using logistic regression. Fisher's exact test was used for comparisons. Diversity trends between Cochrane and non-Cochrane reviews were explored through visual presentation, Pearson's product-moment correlation, and the Granger Causality Test.

Results: This comprehensive analysis included 22,681 Cochrane reviews and 224,484 non-Cochrane reviews. Cochrane reviews showed increasing diversity in several areas: representation of first authors from non-English speaking countries rose substantially (from 16.7% in 1996 to 42.8% in 2023), and female first authorship more than tripled (from 15.0% in 1996 to 55.6% in 2023). Representation from LMICs in Cochrane reviews has declined recently (from a peak of 23.2% in 2012 to 18.4% in 2023). Among Cochrane Review Groups, diversity varied notably, with Sexually Transmitted Infections achieving the highest representation from LMICs (68.1% of first authors). In 2023, non-Cochrane reviews showed higher representation from non-English speaking countries (56.9%) and LMICs (50.8%) compared to Cochrane reviews. The patterns of gender diversity between Cochrane and non-Cochrane reviews showed strong correlations for female first authorship (r=0.829, P<0.001), suggesting parallel evolution over time.

Conclusion: Both Cochrane and non-Cochrane reviews demonstrate important progress in author diversity, particularly in gender representation and inclusion of authors from non-English speaking countries. While non-Cochrane reviews show stronger representation from LMICs, both review sources reflect the evolving landscape of global evidence synthesis.

Background and objectives: Routinely collected data (RCD) from healthcare claims and encounters are increasingly used for outcomes in randomized trials; however, methods for estimating the validity and relative precision of RCD-derived outcomes compared to those from conventional outcome ascertainment are limited. We developed an approach to measuring validity and relative precision of RCD and quantifying uncertainty.

Methods: We reanalyzed data from the Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE) cluster-randomized, controlled trial. Eighty-six primary care practices in 10 United States healthcare systems were randomized to either a multifactorial intervention delivered by nurse falls care managers, or enhanced usual care, with 5,451 persons age ≥ 70 at increased fall injury risk enrolled in the study. We estimated the hazard ratio (HR) and confidence interval (CI) for STRIDE's primary outcome (time to first serious fall injury) using original study data and RCD. The ratio of the RCD HR to original HR ("ratio of HRs") measured validity. The confidence limit ratio (CLR; upper divided by lower confidence limits of CI) measured precision, with the ratio of the CLR with RCD to the CLR from the original study data ("ratio of CLRs") measuring relative precision. We estimated uncertainty around ratio of HRs and ratio of CLRs using bootstrapped 95% CIs and performed sensitivity analyses to assess the effects of adaptations needed to use RCD.

Results: Among the original sample of 5,451 study participants, 5,036 (92%) linked to RCD. The intervention to control HR was 0.91 (95% CI: 0.78-1.07) in RCD, compared to 0.92 (95% CI: 0.80-1.06) in the original data. Using all RCD through STRIDE's administrative end date, the ratio of HRs was 1.00 (95% CI: 0.89-1.11) and ratio of CLRs was 1.03 (95% CI: 0.96-1.06). The CI around ratio of HRs was about three-fold wider for RCD than for the original STRIDE data in individuals who linked to RCD. Relative precision of RCD improved with increased length of follow-up.

Conclusion: Relying solely on RCD to ascertain the primary outcome in STRIDE would have resulted in similar point estimates and confidence limits for the treatment effect as in the original data. However, there was meaningful uncertainty around the estimate of validity. Efforts to validate RCD-derived outcomes for use as clinical trial endpoints should include measurement of uncertainty around validity estimates.

Objective: This study extends methods to estimate average causal effect of aneurysm repair surgery on (i) overall survival and (ii) aneurysm-related mortality, accounting for competing risks using data from the Effective Treatments for Thoracic Aortic Aneurysms (ETTAA) cohort.

Study design and setting: ETTAA, a prospective cohort study, recruited 886 patients between 2014 and 2018. Patients were linked to UK national hospital and mortality databases by NHS digital and followed-up for later surgeries and deaths. We compared a strategy of open or endovascular surgery (whichever appropriate) within 12 months of enrolment to ETTAA with no surgery within 12 months using the trial emulation framework, and cloning-censoring-weighting analysis. Key confounders at baseline were controlled for using inverse probability weighting methods.

Results: In complete case analysis, estimated 7-year survival probability if everyone received surgery within a 12-month grace period was 57.4% (95% CI: 47.3%, 67.4%) versus 49.9% (44.0%, 55.0%) if no one received surgery. This benefit was primarily attributable to reduction in aneurysm-related deaths (difference -8.7%, 95% CI: -14.0%, -3.9%), with no significant effect on deaths from other causes. Findings were consistent under sensitivity analyses, including multiple imputation of missing confounders. Our cloning-censoring-weighting approach addressed selection-for-treatment, allowed for surgery to be received within a grace period and used appropriate methods to separate aneurysm-related mortality from competing risks.

Conclusion: The study demonstrates the utility of trial emulation and counterfactual methods in estimation of causal effects on competing risks using observational data. Findings suggest a benefit for aneurysm-related survival up to 7 years after enrolment.

Objective: To understand the level of equity considerations within Cochrane systematic reviews (CSR) on glaucoma and their primary studies.

Methods: A review of equity-considerations in systematic reviews on glaucoma published in The Cochrane Library from inception (2003) to January 31, 2024, and a sample of recently published primary studies included in those reviews (n=122). Extraction was performed by two independent reviewers using a pre-piloted extraction form based on a validated, contemporary, structured equity framework. If consensus could not be reached, a third reviewer was involved.

Results: A total of 40 CSRs on glaucoma were identified, all of which exclusively included randomized control trials (RCTs) or quasi-RCTs. Twenty-nine (72.5%) reviews acknowledged populations experiencing inequities in glaucoma care; none were able to perform subgroup analysis due to data unavailability in primary studies. Six (15.0%) reviews considered equity-relevant factors when discussing applicability or limitations of study findings to specific populations. Seventy-four (46.8%) review authors were women, while 84 (53.2%) were men. Most review authors were primarily affiliated with institutions in the European Region (85, 53.8%) or The Americas (55, 34.8%), while none were primarily affiliated with institutions in Africa or low-income countries. Most RCTs were conducted in The Americas (32.8%) European Region (27.9%), or in high-income countries (72.1%). While most RCTs reported gender or sex of participants (107, 87.7%), only half reported race or ethnicity (61, 50.0%). No RCTs reported place of residence, occupation, socioeconomic status, or social capital of participants. Approximately half (51.7%) of the participants in these RCTs were female.

Conclusions: Equity considerations can be better addressed in research on glaucoma. Reporting of patient sociodemographic in RCTs, particularly race and ethnicity, as well as global representation was insufficient. This may limit generalizability and applicability of intervention efficacy to populations experiencing inequities and people from low-income countries.

Objective: While subgroup analyses are common in epidemiologic research, restriction to subgroup members can yield imprecise estimates. We aimed to demonstrate how methods extending inferences to external targets improve precision of subgroup estimates under the major assumption effects differ between subgroup members and non-members due to measured effect measure modifiers (EMMs) and membership is independent of the effect after conditioning on EMMs.

Study design and setting: We applied this approach in the Panitumumab Randomized Trial in Combination with Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME). Assuming Hispanic vs non-Hispanic ethnicity was independent of the effect conditional on measured EMMs, we weighted non-Hispanic White participants to resemble Hispanic participants in EMMs, assigned Hispanic participants weights of 1, and estimated weighted 9-month progression-free survival differences (PFSDs) with 95% confidence limits from 2,000 bootstraps. We also explored outcome-based approaches. Finally, we examined a situation where the method generates biased estimates (targeting participants with mutant-type KRAS, which determines efficacy).

Results: While the Hispanic participant-only analysis estimated a 9-month panitumumab PFSD of -7.1% (95% C.I. -32%, 19%), the weighted combined estimate targeting Hispanic participants was much more precise (-3.7%, 95% CI -16%, 9.2%). Other analytic approaches yielded similar results. Meanwhile, the weighted combined estimate targeting mutant-type KRAS participants appeared biased (-2.2%, 95% CI: -7.5%, 3.3%) vs the subgroup-only estimate (-11%, 95% CI: -18%, -2.3%).

Conclusions: While extending inferences from study populations to specific targets can improve the precision of estimates in small subgroups, violating key assumptions creates bias for many subgroups of interest.

Objectives: Improving clinical trial inclusivity for diverse populations, including people with disabilities, is crucial. Ethical considerations emphasise the need for trial enrollment to mirror the potential trial users' diversity, yet underrepresentation persists due to direct and indirect exclusions. The purpose of our study was to determine if trial teams collect data on people with disabilities for diversity monitoring purposes. We also examined how they collect disability and report it.

Study design and setting: We reviewed trial reports for randomised controlled trials published in the UK National Institute of Health Research library from 2016 to 2021. We extracted data on disability, including if, how and when it was collected, who collected it, the measurements used, and the results presented.

Results: We extracted data from 407 trial reports. Disability was not collected as a demographic characteristic in any trial. 27% (109/407) collected some disability data for other purposes, e.g., eligibility, a measure of functional outcome or serious adverse events. Disability was most commonly assessed through questionnaires (65%; 71/109), clinical assessment (17%; 19/109), and interviews (8%; 9/109). A variety of measures were used to collect disability information. In 109 trial reports, the most common was a measure of cognitive function, the Mini Mental State Examination (MMSE), which accounted for 15% overall.

Conclusions: Disability is not just under recorded or underreported, it is ignored, in trials. As disability is not collected as a demographic characteristic, people with disabilities remain underserved in trials. Given 16% of the global population live with a disability, it is a threat to the generalisability of all trials and risks exacerbating health inequalities of people with a disability.

Scoping reviews have been identified as appropriate methodologies to contribute to our knowledge. The objective of this review is to summarise how scoping reviews can be used to identify research priorities. Based on our experience as evidence synthesis methodologists and researchers, the JBI scoping review methodology group, have identified the potential roles of scoping reviews in identification of research priorities. Scoping reviews typically ask broad questions that allow researchers to obtain an overview or map of the existing evidence. Scoping reviews also incorporate multiple levels of evidence that enriches the strength of the knowledge that is gained. This value is revealed by the use of scoping reviews to contribute to and perform the following functions: 1) Map a research area and identify gaps that need to be addressed; 2) prioritize research topics by identifying key issues to investigate; 3) identify the type of study designs that have been used to investigate a particular topic, and or the range of outcomes measured following a specific intervention; 4) identify the essential contextual factors that are relevant to the study of a particular research topic; 5) identify equity issues in the research field; 6) assist in engaging stakeholders and or experts in the field by facilitating the inclusion of these stakeholders within the research process; and 7) provide the relevant new knowledge to enhance and support applications for funding. To ensure this contribution to identifying research priorities is reliable, scoping reviews must be performed following the existing rigorous methodological processes and adhere to the currently available reporting guidelines. By doing so, scoping reviews have great potential to identify research priorities, to guide the expansion of research and the generation of new knowledge.