Bayesian Inference-Based Gaussian Mixture Models With Optimal Components Estimation Towards Large-Scale Synthetic Data Generation for <italic>In Silico</italic> 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.

Keywords

• Gaussian Mixture Models
• synthetic data generator
• $in silico$ clinical trials%22%2C%22default_operator%22%3A%22AND%22%7D%7D%7D"> <named-content xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" content-type="math" xlink:type="simple"> <inline-formula> <tex-math notation="LaTeX">$in silico$</tex-math> </inline-formula> </named-content> clinical trials
• computational complexity
• hypertrophic cardiomyopathy