Research Synthesis Methods最新文献

Conventional random-effects models in meta-analysis rely on large sample approximations instead of exact small sample results. While random-effects methods produce efficient estimates and confidence intervals for the summary effect have correct coverage when the number of studies is sufficiently large, we demonstrate that conventional methods result in confidence intervals that are not wide enough when the number of studies is small, depending on the configuration of sample sizes across studies, the degree of true heterogeneity and number of studies. We introduce two alternative variance estimators with better small sample properties, investigate degrees of freedom adjustments for computing confidence intervals, and study their effectiveness via simulation studies.

Individual participant data meta-analyses (IPD-MAs) have several benefits over standard aggregate data meta-analyses, including the consideration of additional participants, follow-up time, and the joint consideration of study- and participant-level heterogeneity for improved diagnostic and prognostic model development and evaluation. However, IPD-MAs are resource-intensive and require careful budgeting of time from data contributing groups, a dedicated management team, diversity of expertise, clearly documented data sharing and authorship agreements, and consistent and clear communication. We present a toolkit to facilitate the implementation and management of IPD-MAs, from study recruitment to retrospective harmonization. The toolkit was developed and refined over our work on multiple multinational IPD-MA projects over the last 13 years. The toolkit's budget and email templates, agreements, project management spreadsheets, and standard operating procedures are meant to facilitate routine IPD-MA tasks to expedite implementing and managing future IPD-MA projects.

Rapid review methodology aims to facilitate faster conduct of systematic reviews to meet the needs of the decision-maker, while also maintaining quality and credibility. This systematic review aimed to determine the impact of different methodological shortcuts for undertaking rapid reviews on the risk of bias (RoB) of the results of the review. Review stages for which reviews and primary studies were sought included the preparation of a protocol, question formulation, inclusion criteria, searching, selection, data extraction, RoB assessment, synthesis, and reporting. We searched 11 electronic databases in April 2022, and conducted some supplementary searching. Reviewers worked in pairs to screen, select, extract data, and assess the RoB of included reviews and studies. We included 15 systematic reviews, 7 scoping reviews, and 65 primary studies. We found that several commonly used shortcuts in rapid reviews are likely to increase the RoB in the results. These include restrictions based on publication date, use of a single electronic database as a source of studies, and use of a single reviewer for screening titles and abstracts, selecting studies based on the full-text, and for extracting data. Authors of rapid reviews should be transparent in reporting their use of these shortcuts and acknowledge the possibility of them causing bias in the results. This review also highlights shortcuts that can save time without increasing the risk of bias. Further research is needed for both systematic and rapid reviews on faster methods for accurate data extraction and RoB assessment, and on development of more precise search strategies.

Meta-analysis is commonly used to combine results from multiple clinical trials, but traditional meta-analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently-introduced causally interpretable meta-analysis methods and apply their treatment effect estimators to two individual-participant data sets. These estimators transport estimated treatment effects from studies in the meta-analysis to a specified target population using the individuals' potentially effect-modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated-data meta-analysis methods. In our applications, certain versions of the causally interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally interpretable approach gives meta-analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments.

The Systematic Review Toolbox aims provide a web-based catalogue of tools that support various tasks within the systematic review and wider evidence synthesis process. Identifying publications surrounding specific systematic review tools is currently challenging, leading to a high screening burden for few eligible records. We aimed to develop a search strategy that could be regularly and automatically run to identify eligible records for the SR Toolbox, thus reducing time on task and burden for those involved. We undertook a mapping exercise to identify the PubMed IDs of papers indexed within the SR Toolbox. We then used the Yale MeSH Analyser and Visualisation of Similarities (VOS) Viewer text-mining software to identify the most commonly used MeSH terms and text words within the eligible records. These MeSH terms and text words were combined using Boolean Operators into a search strategy for Ovid MEDLINE. Prior to the mapping exercise and search strategy development, 81 software tools and 55 ‘Other’ tools were included within the SR Toolbox. Since implementation of the search strategy, 146 tools have been added. There has been an increase in tools added to the toolbox since the search was developed and its corresponding auto-alert in MEDLINE was originally set up. Developing a search strategy based on a mapping exercise is an effective way of identifying new tools to support the systematic review process. Further research could be conducted to help prioritise records for screening to reduce reviewer burden further and to adapt the strategy for disciplines beyond healthcare.

Meta-analysis of diagnostic test accuracy (DTA) is a powerful statistical method for synthesizing and evaluating the diagnostic capacity of medical tests and has been extensively used by clinical physicians and healthcare decision-makers. However, publication bias (PB) threatens the validity of meta-analysis of DTA. Some statistical methods have been developed to deal with PB in meta-analysis of DTA, but implementing these methods requires high-level statistical knowledge and programming skill. To assist non-technical users in running most routines in meta-analysis of DTA and handling with PB, we developed an interactive application, DTAmetasa. DTAmetasa is developed as a web-based graphical user interface based on the R shiny framework. It allows users to upload data and conduct meta-analysis of DTA by “point and click” operations. Moreover, DTAmetasa provides the sensitivity analysis of PB and presents the graphical results to evaluate the magnitude of the PB under various publication mechanisms. In this study, we introduce the functionalities of DTAmetasa and use the real-world meta-analysis to show its capacity for dealing with PB.

Individual participant data meta-analysis (IPDMA) projects obtain, check, harmonise and synthesise raw data from multiple studies. When undertaking the meta-analysis, researchers must decide between a two-stage or a one-stage approach. In a two-stage approach, the IPD are first analysed separately within each study to obtain aggregate data (e.g., treatment effect estimates and standard errors); then, in the second stage, these aggregate data are combined in a standard meta-analysis model (e.g., common-effect or random-effects). In a one-stage approach, the IPD from all studies are analysed in a single step using an appropriate model that accounts for clustering of participants within studies and, potentially, between-study heterogeneity (e.g., a general or generalised linear mixed model). The best approach to take is debated in the literature, and so here we provide clearer guidance for a broad audience. Both approaches are important tools for IPDMA researchers and neither are a panacea. If most studies in the IPDMA are small (few participants or events), a one-stage approach is recommended due to using a more exact likelihood. However, in other situations, researchers can choose either approach, carefully following best practice. Some previous claims recommending to always use a one-stage approach are misleading, and the two-stage approach will often suffice for most researchers. When differences do arise between the two approaches, often it is caused by researchers using different modelling assumptions or estimation methods, rather than using one or two stages per se.

In meta-analyses of rare events, it can be challenging to obtain a reliable estimate of the pooled effect, in particular when the meta-analysis is based on a small number of studies. Recent simulation studies have shown that the beta-binomial model is a promising candidate in this situation, but have thus far only investigated its performance in a frequentist framework. In this study, we aim to make the beta-binomial model for meta-analysis of rare events amenable to Bayesian inference by proposing prior distributions for the effect parameter and investigating the models' robustness to different specifications of priors for the scale parameter. To evaluate the performance of Bayesian beta-binomial models with different priors, we conducted a simulation study with two different data generating models in which we varied the size of the pooled effect, the degree of heterogeneity, the baseline probability, and the sample size. Our results show that while some caution must be exercised when using the Bayesian beta-binomial in meta-analyses with extremely sparse data, the use of a weakly informative prior for the effect parameter is beneficial in terms of mean bias, mean squared error, and coverage. For the scale parameter, half-normal and exponential distributions are identified as candidate priors in meta-analysis of rare events using the Bayesian beta-binomial model.

Extracting data from studies is the norm in meta-analyses, enabling researchers to generate effect sizes when raw data are otherwise not available. While there has been a general push for increased reproducibility in meta-analysis, the transparency and reproducibility of the data extraction phase is still lagging behind. Unfortunately, there is little guidance of how to make this process more transparent and shareable. To address this, we provide several steps to help increase the reproducibility of data extraction in meta-analysis. We also provide suggestions of R software that can further help with reproducible data policies: the shinyDigitise and juicr packages. Adopting the guiding principles listed here and using the appropriate software will provide a more transparent form of data extraction in meta-analyses.

Missing data complicates statistical analyses in multi-site studies, especially when it is not feasible to centrally pool individual-level data across sites. We combined meta-analysis with within-site multiple imputation for one-step estimation of the average causal effect (ACE) of a target population comprised of all individuals from all data-contributing sites within a multi-site distributed data network, without the need for sharing individual-level data to handle missing data. We considered two orders of combination and three choices of weights for meta-analysis, resulting in six approaches. The first three approaches, denoted as RR + metaF, RR + metaR and RR + std, first combined results from imputed data sets within each site using Rubin's rules and then meta-analyzed the combined results across sites using fixed-effect, random-effects and sample-standardization weights, respectively. The last three approaches, denoted as metaF + RR, metaR + RR and std + RR, first meta-analyzed results across sites separately for each imputation and then combined the meta-analysis results using Rubin's rules. Simulation results confirmed very good performance of RR + std and std + RR under various missing completely at random and missing at random settings. A direct application of the inverse-variance weighted meta-analysis based on site-specific ACEs can lead to biased results for the targeted network-wide ACE in the presence of treatment effect heterogeneity by site, demonstrating the need to clearly specify the target population and estimand and properly account for potential site heterogeneity in meta-analyses seeking to draw causal interpretations. An illustration using a large administrative claims database is presented.