Bayesian Inference-Based Gaussian Mixture Models with Optimal Components Estimation Towards Large-Scale Synthetic Data Generation for in Silico Clinical Trials

Abstract

Goal: To develop a computationally efficient and unbiased synthetic data generator for large-scale in silico clinical trials (CTs). Methods: We propose the BGMM-OCE, an extension of the conventional BGMM (Bayesian Gaussian Mixture Models) algorithm to provide unbiased estimations regarding the optimal number of Gaussian components and yield high-quality, large-scale synthetic data at reduced computational complexity. Spectral clustering with efficient eigenvalue decomposition is applied to estimate the hyperparameters of the generator. A case study is conducted to compare the performance of BGMM-OCE against four straightforward synthetic data generators for in silico CTs in hypertrophic cardiomyopathy (HCM). Results: The BGMM-OCE generated 30000 virtual patient profiles having the lowest coefficient-of-variation (0.046), inter- and intra-correlation differences (0.017, and 0.016, respectively) with the real ones in reduced execution time. Conclusions: BGMM-OCE overcomes the lack of population size in HCM which obscures the development of targeted therapies and robust risk stratification models.