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Updated: Jul 18, 2025

Evidence-based Knowledge Synthesis and Hypothesis Validation: Navigating Biomedical Knowledge Bases via Explainable AI and Agentic Systems
Published on: June 13, 2025
Padé approximant meets federated learning: A nearly lossless, one-shot algorithm for evidence synthesis in
Qiong Wu1, Martijn J Schuemie2, Marc A Suchard3
1Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Objective:
We developed and evaluated a novel one-shot distributed algorithm for evidence synthesis in distributed research networks with rare outcomes.
Materials And Methods:
Fed-Padé, motivated by a classic mathematical tool, Padé approximants, reconstructs the multi-site data likelihood via Padé approximant whose key parameters can be computed distributively. Thanks to the simplicity of [2,2] Padé approximant, Fed-Padé requests an extremely simple task and low communication cost for data partners. Specifically, each data partner only needs to compute and share the log-likelihood and its first 4 gradients evaluated at an initial estimator. We evaluated the performance of our algorithm with extensive simulation studies and four observational healthcare databases.
Results:
Our simulation studies revealed that a [2,2]-Padé approximant can well reconstruct the multi-site likelihood so that Fed-Padé produces nearly identical estimates to the pooled analysis. Across all simulation scenarios considered, the median of relative bias and rate of instability of our Fed-Padé are both <0.1%, whereas meta-analysis estimates have bias up to 50% and instability up to 75%. Furthermore, the confidence intervals derived from the Fed-Padé algorithm showed better coverage of the truth than confidence intervals based on the meta-analysis. In real data analysis, the Fed-Padé has a relative bias of <1% for all three comparisons for risks of acute liver injury and decreased libido, whereas the meta-analysis estimates have a substantially higher bias (around 10%).
Conclusion:
The Fed-Padé algorithm is nearly lossless, stable, communication-efficient, and easy to implement for models with rare outcomes. It provides an extremely suitable and convenient approach for synthesizing evidence in distributed research networks with rare outcomes.
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