A Framework for Evaluating Predictive Models Using Synthetic Image Covariates and Longitudinal Data

We present a novel framework for synthesizing patient data with complex covariates (e.g., eye scans) paired with longitudinal observations (e.g., visual acuity over time), addressing privacy concerns in healthcare research. Our approach introduces controlled association in latent spaces generating each data modality, enabling the creation of complex covariate-longitudinal observation pairs. This framework facilitates the development of predictive models and provides openly available benchmarking datasets for healthcare research. We demonstrate our framework using optical coherence tomography (OCT) scans, though it is applicable across domains. Using 109,309 2D OCT scan slices, we trained an image generative model combining a variational autoencoder and a diffusion model. Longitudinal observations were simulated using a nonlinear mixed effect (NLME) model from a low-dimensional space of random effects. We generated 1.1M OCT scan slices paired with five sets of longitudinal observations at controlled association levels (100%, 50%, 10%, 5.26%, and 2% of between-subject variability). To assess the framework, we modeled synthetic longitudinal observations with another NLME model, computed empirical Bayes estimates of random effects, and trained a ResNet to predict these estimates from synthetic OCT scans. We then incorporated ResNet predictions into the NLME model for patient-individualized predictions. Prediction accuracy on withheld data declined as intended with reduced association between images and longitudinal measurements. Notably, in all but the 2% case, we achieved within 50% of the theoretical best possible prediction on withheld data, demonstrating our ability to detect even weak signals. This confirms the effectiveness of our framework in generating synthetic data with controlled levels of association, providing a valuable tool for healthcare research.

A Practitioner's Guide to Bayesian Inference in Pharmacometrics using Pumas

This paper provides a comprehensive tutorial for Bayesian practitioners in pharmacometrics using Pumas workflows. We start by giving a brief motivation of Bayesian inference for pharmacometrics highlighting limitations in existing software that Pumas addresses. We then follow by a description of all the steps of a standard Bayesian workflow for pharmacometrics using code snippets and examples. This includes: model definition, prior selection, sampling from the posterior, prior and posterior simulations and predictions, counter-factual simulations and predictions, convergence diagnostics, visual predictive checks, and finally model comparison with cross-validation. Finally, the background and intuition behind many advanced concepts in Bayesian statistics are explained in simple language. This includes many important ideas and precautions that users need to keep in mind when performing Bayesian analysis. Many of the algorithms, codes, and ideas presented in this paper are highly applicable to clinical research and statistical learning at large but we chose to focus our discussions on pharmacometrics in this paper to have a narrower scope in mind and given the nature of Pumas as a software primarily for pharmacometricians.