Variational Bayes latent class analysis for EHR-based phenotyping with large real-world data

Introduction Bayesian approaches to patient phenotyping in clinical observational studies have been limited by the computational challenges associated with applying the Markov Chain Monte Carlo (MCMC) approach to real-world data. Approximate Bayesian inference via optimization of the variational evidence lower bound, variational Bayes (VB), has been successfully demonstrated for other applications.Methods We investigate the performance and characteristics of currently available VB and MCMC software to explore the practicability of available approaches and provide guidance for clinical practitioners. Two case studies are used to fully explore the methods covering a variety of real-world data. First, we use the publicly available Pima Indian diabetes data to comprehensively compare VB implementations of logistic regression. Second, a large real-world data set, Optum (TM) EHR with approximately one million diabetes patients extended the analysis to large, highly unbalanced data containing discrete and continuous variables. A Bayesian patient phenotyping composite model incorporating latent class analysis (LCA) and regression was implemented with the second case study.Results We find that several data characteristics common in clinical data, such as sparsity, significantly affect the posterior accuracy of automatic VB methods compared with conditionally conjugate mean-field methods. We find that for both models, automatic VB approaches require more effort and technical knowledge to set up for accurate posterior estimation and are very sensitive to stopping time compared with closed-form VB methods.Discussion Our results indicate that the patient phenotyping composite Bayes model is more easily usable for real-world studies if Monte Carlo is replaced with VB. It can potentially become a uniquely useful tool for decision support, especially for rare diseases where gold-standard biomarker data are sparse but prior knowledge can be used to assist model diagnosis and may suggest when biomarker tests are warranted.