Fed-ComBat: A Generalized Federated Framework for Batch Effect Harmonization in Collaborative Studies.

The use of multi-centric analyses is crucial for obtaining sufficient sample sizes and representative clinical populations in experimental studies. In this setting, data harmonization techniques are typically employed to address systematic biases and ensure the interoperability of the data. State-of-the-art harmonisation approaches are based on the statistical theory of random effect modeling, allowing to account for either linear of non-linear biases and batch effects. However, optimizing these statistical methods generally requires data centralization at some point during the analysis pipeline, therefore introducing the risk of exposing individual patient information while posing significant data governance issues. To overcome this challenge, in this paper we present Fed-ComBat, a federated framework for batch effect harmonization on decentralized data. Fed-ComBat enables the preservation of nonlinear covariate effects without requiring centralization of data and without prior parametric hypothesis on the variables to account for. We demonstrate the effectiveness of Fed-ComBat against a comprehensive panel of existing approaches based on the state-of-the-art ComBat, along with distributed and nonlinear variants. Our experiments are based on extensive simulated data, and on the analysis of multiple cohorts based on 7 neuroimaging studies comprising healthy controls (CI) and subjects with various disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD). Our results show that in a federated settings, Fed-ComBat harmonization exhibits comparable results to centralized methods for both linear and nonlinear cases. On real data, harmonized trajectories of the thickness ofthe right hippocampus across lifespan measured on a set of 7 public studies show comparable results between centralized and federated models and are consistent with the literature when using a nonlinear model. The code is publicly available at: https://gitlab.inria.fr/greguig/fedcombat.