Causally interpretable meta-analysis combining aggregate and individual participant data.

Recent work in causally-interpretable meta-analysis (CIMA) has bridged the gap between traditional meta-analysis and causal inference. While traditional meta-analysis results generally do not apply to any well-defined population, CIMA approaches specify a target population to which meta-analytic treatment effect estimates are transported. While theoretically attractive, these approaches currently have some practical limitations. Most assume that all studies in the meta-analysis have individual participant data (IPD), which is rare in practice because most trials share only aggregate data. We propose a method to perform CIMA using a combination of aggregate data and IPD. This method borrows information from studies with IPD to augment the aggregate data and create aggregate-matched synthetic IPD (AMSIPD), which can be used readily in the existing CIMA framework. By allowing use of both aggregate data and IPD, the method opens CIMA to more applications and can avoid biases arising from using only studies with IPD. We present a case study and simulations showing the AMSIPD approach is promising and merits further investigation as an advancement of CIMA.

The Intersections of COVID-19, HIV, and Race/Ethnicity: Machine Learning Methods to Identify and Model Risk Factors for Severe COVID-19 in a Large U.S. National Dataset.

We investigate risk factors for severe COVID-19 in persons living with HIV (PWH), including among racialized PWH, using the U.S. population-sampled National COVID Cohort Collaborative (N3C) data released from January 1, 2020 to October 10, 2022. We defined severe COVID-19 as hospitalized with invasive mechanical ventilation, extracorporeal membrane oxygenation, discharge to hospice or death. We used machine learning methods to identify highly ranked, uncorrelated factors predicting severe COVID-19, and used multivariable logistic regression models to assess the associations of these variables with severe COVID-19 in several models, including race-stratified models. There were 3 241 627 individuals with incident COVID-19 cases and 81 549 (2.5%) with severe COVID-19, of which 17 445 incident COVID-19 and 1 020 (5.8%) severe cases were among PWH. The top highly ranked factors of severe COVID-19 were age, congestive heart failure (CHF), dementia, renal disease, sodium concentration, smoking status, and sex. Among PWH, age and sodium concentration were important predictors of COVID-19 severity, and the effect of sodium concentration was more pronounced in Hispanics (aOR 4.11 compared to aOR range: 1.47-1.88 for Black, White, and Other non-Hispanics). Dementia, CHF, and renal disease was associated with higher odds of severe COVID-19 among Black, Hispanic, and Other non-Hispanics PWH, respectively. Our findings suggest that the impact of factors, especially clinical comorbidities, predictive of severe COVID-19 among PWH varies by racialized groups, highlighting a need to account for race and comorbidity burden when assessing the risk of PWH developing severe COVID-19.

Causally interpretable meta-analysis: Clearly defined causal effects and two case studies.

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.

Bayesian meta-analysis using SAS PROC BGLIMM.

Meta-analysis is commonly used to compare two treatments. Network meta-analysis (NMA) is a powerful extension for comparing and contrasting multiple treatments simultaneously in a systematic review of multiple clinical trials. Although the practical utility of meta-analysis is apparent, it is not always straightforward to implement, especially for those interested in a Bayesian approach. This paper demonstrates that the recently-developed SAS procedure BGLIMM provides an intuitive and computationally efficient means for conducting Bayesian meta-analysis in SAS, using a worked example of a smoking cessation NMA data set. BGLIMM gives practitioners an effective and simple way to implement Bayesian meta-analysis (pairwise and network, either contrast-based or arm-based) without requiring significant background in coding or statistical modeling. Those familiar with generalized linear mixed models, and especially the SAS procedure GLIMMIX, will find this tutorial a useful introduction to Bayesian meta-analysis in SAS.