Multimodal Empirical Bayes Variational Autoencoders for Joint Longitudinal and Time-to-Event Modeling
Authors: Anders Sjöberg, Nils Olsson, Marcus Baaz, Mats Jirstrand
Organizations: Fraunhofer-Chalmers Centre, Gothenburg, SE-412 88, Sweden · Department of Electrical Engineering, Chalmers University of Technology, Gothenburg, SE-412 96, Sweden
Longitudinal tumor measurements, dropout information, and genetic covariates provide complementary information about treatment response, but integrating these data sources within a single population modeling framework remains challenging. We extend the empirical Bayes variational autoencoder (EB-VAE) framework to joint longitudinal and time-to-event modeling and evaluate it on tumor growth data. The framework represents inter-individual variability using latent individual effects regularized by a covariate-conditioned empirical Bayes prior, while a decoder maps these latent effects to tumor-volume trajectories. To account for informative dropout, the decoder was augmented with a hazard model, yielding joint predictions of tumor growth and time to dropout. We further compared fully neural and hybrid semi-mechanistic decoder formulations and incorporated genomic covariates through a genetics-conditioned prior adaptation. The hybrid decoder recovered treatment-effect parameters broadly consistent with previously reported nonlinear mixed-effects estimates, while achieving prior predictive performance comparable to the neural decoder. The joint model reproduced both tumor-volume distributions and dropout patterns in held-out individuals, and genetic conditioning improved individual-level prior predictions in both cutaneous melanoma and breast cancer experiments. Stability selection identified several biologically plausible genetic indicators, including alterations in BRAF, NRAS, NF1, and MDM2. These results demonstrate that EB-VAE provides a flexible probabilistic framework for combining neural dynamics, mechanistic structure, time-to-event modeling, and high-dimensional covariates in pharmacometric applications.
Predicting customers' long-term revenue from sparse and irregular transaction data is central to marketing resource allocation in non-contractual settings, yet existing approaches face a trade-off. Traditional probabilistic customer base models deliver robust long-horizon forecasts by imposing strong structural assumptions, while flexible machine-learning models often require substantial training data and careful tuning. We propose a variational-autoencoder-based model that preserves the process-based likelihood of established attrition-transaction-spend models conditional on customer heterogeneity, but replaces the restrictive parametric mixing distribution with a flexible latent representation learned by encoder-decoder networks. The resulting approach (i) provides a single model for customer attrition, transactions and spending, (ii) remains reliable when contextual covariates are unavailable, and (iii) flexibly incorporates rich covariates and nonlinear effects when they are available. This design balances structural stability with the flexibility needed to capture complex purchase dynamics. Across multiple real-world datasets and prediction horizons, the proposed model improves upon the latest benchmarks. Businesses benefit directly, as a better assessment of customers' future revenues improves the efficiency of campaign targeting. For research, this work provides guidance on how to embed domain-specific models into the variational autoencoder framework, enabling flexible representation learning while retaining an econometrically meaningful process structure.
Scalable Bayesian inference for generalized linear mixed models (GLMMs) provides uncertainty-aware analysis of correlated longitudinal data, but existing scalable approaches largely assume low-dimensional tabular predictors and do not directly accommodate high-dimensional modalities such as images and text. We address this limitation by learning one or more modality-specific neural encoders jointly with a GLMM objective, then performing variance-corrected stochasticgradient MCMC for the GLMM parameters conditional on the learned representation. This conditional-Bayes design combines supervised representation learning with posterior uncertainty quantification for population-level effects, subjectspecific heterogeneity, and modality-level random slopes. The resulting model preserves interpretable fixed and random effects for structured covariates and learned modalities while scaling gracefully to large longitudinal datasets. In simulation studies, our method recovers posterior means and variance estimates from full-data MCMC benchmarks after covariance correction. We further evaluate uncertainty through parameter-level interval coverage in simulations and predictive calibration on held-out data. Applications to glaucoma progression and adolescent mental health demonstrate that the framework allows nuanced assessment of the relative importance of each modality on both individual and population levels without sacrificing predictive performance.
Yuankang Zhao, Youngsoo Baek, Felipe A. Medeiros +2
Despite their ubiquity, variational autoencoders (VAEs) inherently suffer from posterior collapse, a failure mode in which latent variables are effectively ignored. This failure arises because explicit prior imposition drives optimization toward loss landscape regions corresponding to uninformative latent representations. Here, we introduce Entropic Autoencoders (EAEs), a framework in which reconstruction loss is the only explicit objective, and entropy generates the latent variables' prior implicitly through a free energy-minimizing ensemble of encoders. This ensemble biases learning toward high-volume regions of near-optimal solutions, while decoder updates direct the search trajectories toward informative latent representations. We demonstrate that EAEs mitigate posterior collapse by learning non-Gaussian, multimodal latent distributions that yield diverse, data-consistent generations and preserve different forms of underlying structure in the data. As a proof-of-concept, we show that an EAE captures a superposition of the known low-dimensional dynamics of a reaction-diffusion process. Then, we show that an EAE identifies implicit categorical distinctions in MNIST latent representations, and displays a hierarchical understanding of facial structure on the CelebA dataset, from an "all-human" face to individual-dependent features.