Privacy-by-Design Approach to Generate Two Virtual Clinical Trials for Multiple Sclerosis and Release Them as Open Datasets: Evaluation Study.

Background: Sharing information derived from individual patient data is restricted by regulatory frameworks due to privacy concerns. Generative artificial intelligence can generate shareable virtual patient populations as proxies for sensitive reference datasets. Explicit demonstration of privacy is demanded. Objective: This study evaluated whether a privacy-by-design technique called "avatars" can generate synthetic datasets replicating all reported information from randomized clinical trials (RCTs). Methods: We generated 2160 synthetic datasets from two phase 3 RCTs for patients with multiple sclerosis (NCT00213135 and NCT00906399; n=865 and 1516 patients) with different configurations to select one synthetic dataset with optimal privacy and utility for each. Several privacy metrics were computed, including protection against distance-based membership inference attacks. We assessed fidelity by comparing variable distributions and assessed utility by checking that all end points reported in the publications had the same effect directions, were within the reported 95% CIs, and had the same statistical significance. Results: Protection against membership inference attacks was the hardest privacy metric to optimize, but the technique yielded robust privacy and replication of the primary end points (in 72.5% and 80.8% of the 1080 generated datasets). Utility was uneven across the variables and end points, such that information about some end points could not be captured. With optimized generation configurations, we selected one dataset from each RCT replicating all efficacy end points of the placebo and approved treatment arms while maintaining satisfactory privacy (hidden rate: 85.0% and 93.2%). Conclusions: Generating synthetic RCT datasets replicating primary and secondary efficacy end points is possible while achieving a satisfactory and explicit level of privacy. To show the potential of this method to unlock health data sharing, we released both placebo arms as open datasets.