Unconfounded Meta-analytical Frameworks for Multivariate Outcomes in Multigroup Observational Studies using Concordant Weights

Abstract: While meta-analyzing retrospective cancer patient cohorts, an investigation of differences in the expressions of target oncogenes across cancer subtypes is of substantial interest because the results may uncover novel tumorigenesis mechanisms and improve screening and treatment strategies. Weighting methods facilitate unconfounded comparisons of multigroup potential outcomes in multiple observational studies. For example, Guha et al. (2022) introduced concordant weights, allowing integrative analyses of survival outcomes by maximizing the effective sample size. However, it remains unclear how to use this or other weighting approaches to analyze a variety of continuous, categorical, ordinal, or multivariate outcomes, especially when research interests prioritize uncommon or unplanned estimands suggested by post hoc analyses; examples include percentiles and moments of group potential outcomes and pairwise correlations of multivariate outcomes. This paper proposes a unified meta-analytical approach accommodating various types of endpoints and fosters new estimators compatible with most weighting frameworks. Asymptotic properties of the estimators are investigated under mild assumptions. For undersampled groups, we devise small-sample procedures for quantifying estimation uncertainty. We meta-analyze multi-site TCGA breast cancer data, shedding light on the differential mRNA expression patterns of eight targeted genes for the subtypes infiltrating ductal carcinoma and infiltrating lobular carcinoma.