Background: Developing effective and generalizable predictive models is critical for disease prediction and clinical decision-making, often requiring diverse samples to mitigate population bias and address algorithmic fairness. However, a major challenge is to retrieve learning models across multiple institutions without bringing in local biases and inequity, while preserving individual patients' privacy at each site.

Objective: This study aims to understand the issues of bias and fairness in the machine learning process used in the predictive health care domain. We proposed a software architecture that integrates federated learning and blockchain to improve fairness, while maintaining acceptable prediction accuracy and minimizing overhead costs.

Methods: We improved existing federated learning platforms by integrating blockchain through an iterative design approach. We used the design science research method, which involves 2 design cycles (federated learning for bias mitigation and decentralized architecture). The design involves a bias-mitigation process within the blockchain-empowered federated learning framework based on a novel architecture. Under this architecture, multiple medical institutions can jointly train predictive models using their privacy-protected data effectively and efficiently and ultimately achieve fairness in decision-making in the health care domain.

Results: We designed and implemented our solution using the Aplos smart contract, microservices, Rahasak blockchain, and Apache Cassandra-based distributed storage. By conducting 20,000 local model training iterations and 1000 federated model training iterations across 5 simulated medical centers as peers in the Rahasak blockchain network, we demonstrated how our solution with an improved fairness mechanism can enhance the accuracy of predictive diagnosis.

Conclusions: Our study identified the technical challenges of prediction biases faced by existing predictive models in the health care domain. To overcome these challenges, we presented an innovative design solution using federated learning and blockchain, along with the adoption of a unique distributed architecture for a fairness-aware system. We have illustrated how this design can address privacy, security, prediction accuracy, and scalability challenges, ultimately improving fairness and equity in the predictive health care domain.