Privacy-Preserving Framework for Multi-Institutional Medical Time-Series Analysis via Homomorphic Encryption: Design and Development Study.

Background: The development of robust medical AI for knowledge discovery and decision support commonly necessitates large-scale datasets from multiple institutions. However, such data aggregation is severely constrained by privacy regulations and the inherent risk of sensitive information leakage, making it difficult to navigate the utility-privacy trade-off. Objective: We aimed to design a secure multiparty deep learning system that enables privacy-preserving modeling from distributed medical time-series data without centralizing raw information or exposing model parameters. Our goal was to achieve predictive accuracy comparable to nonsecure models while providing strong security and efficiency. Methods: We developed a framework using threshold homomorphic encryption to securely train recurrent neural networks on distributed longitudinal data. To improve the efficiency, we proposed an optimized encrypted matrix multiplication scheme, a secure ciphertext refresh protocol, and used lightweight encryption parameters and low-degree approximated activation polynomials. The system was evaluated on 4 real-world intensive care unit datasets for tasks like mortality and sepsis prediction. Results: The system demonstrated practical efficiency, requiring approximately 1 minute per training iteration for processing 125 local batches over 39 variables and 48 time steps, and scaling well with data size and participant number. Securely trained models achieved predictive performance that was comparable to, and in some cases superior to, nonsecure centralized models, highlighting their ability to learn generalizable patterns in different unseen data distributions. For example, on the PhysioNet Challenge 2012 dataset, our secure model achieved an area under the curve (AUC) of 0.8480, outperforming the nonsecure baseline AUC of 0.8404. Conclusions: This work provides a viable and efficient solution for cross-institutional, privacy-preserving analysis of longitudinal medical data. The framework successfully bridges the utility-privacy gap, facilitating safer collaborative research and enabling robust knowledge discovery and decision support while adhering to strict data protection standards.