Privacy-Preserving Matching for Federated Causal Inference in Multicentre Patient Cohorts

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Abstract
Motivation: Causal effect estimates can often be biased in clinical and epidemiological studies as patient cohorts frequently exhibit substantial covariate imbalances between treated and control groups, often amplified in multicentre studies due to heterogeneous recruitment, clinical practice, and case mix. Covariate balancing methods are therefore essential for valid causal inference. However, their application becomes challenging when data are distributed across cohorts and cannot be pooled because of privacy, legal, or institutional constraints, leaving a gap in practical methods for causal effect estimation in federated and imbalanced clinical data settings. Results: We develop a privacy-preserving framework for covariate balancing and causal effect estimation across distributed data providers, combining federated aggregation with differential privacy to enable propensity score subclassification and matching without sharing individual-level records. Matching relies on non-disclosive quantities and differentially private distance evaluation, and the resulting matched subsets remain local to each server. Balance can be assessed through federated diagnostics and privacy-preserving visualisations, and we provide secure estimators for average treatment effects with associated uncertainty quantification. We implement this framework in the DataSHIELD federated analysis platform via 2 R packages. In simulations, we demonstrate agreement between federated and centralised analyses in the absence of privacy noise and quantify the bias–variance trade-offs induced by differential privacy. We illustrate applicability in two multinational settings—a Long COVID cohort and very preterm birth cohorts—showing that the approach enables practical causal analyses under real-world data protection constraints. Availability and Implementation: The DataSHIELD packages are available on Github ( https://github.com/roygusinow/dsMatchingClient , https://github.com/roygusinow/dsMatching ). Additional methodological details are provided in the Supplementary Material. Contact: Jan Hasenauer: jan.hasenauer@uni-bonn.de
Funding Information
  • Deutsche Forschungsgemeinschaft (EXC 2047—390685813)
  • Deutsche Forschungsgemeinschaft (EXC 2151-390873048)
  • Horizon Europe research and innovation programme (101016167)
  • Horizon Europe research and innovation programme (733280)

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