Optimizing Digital Therapeutic Interventions: Online Learning under Endogenous Adherence
Authors: Eric Pulick, Stephanie Carpenter, Matthew Buman, Yonatan Mintz
Organizations: Department of Industrial and Systems Engineering, University of Wisconsin-Madison · College of Health Solutions, Arizona State University
Abstract
A critical challenge facing clinicians managing chronic disease interventions is sustaining long-run patient health given limited information and resources. Digital therapeutics (DTs) provide a cost-effective way to manage interventions at scale through repeated interactions (e.g. daily treatment recommendations), but patient success is highly dependent on their adherence. Behavioral psychology suggests that both treatment recommendations and past adherence affect future adherence, yet existing decision support frameworks for DTs model only recommendation effects or treat adherence as exogenous context, leaving a key gap in model and algorithm development. To address this gap, we present a DT decision support framework that captures both recommendation and adherence effects, allowing clinicians to better plan treatment recommendations. We model a patient's time-varying capacity for engagement with treatment using a linear dynamical system (LDS) that captures both recommendation and adherence effects, endogenously connected to adherence behavior with a logit link. We establish finite-time identification guarantees for this model, extending LDS results to our setting. Next, we propose an optimism-based algorithm, UCB-BOLD, for online treatment selection and prove that it achieves sublinear regret. We evaluate UCB-BOLD against benchmarks via ablation studies on a synthetic patient cohort generated using micro-randomized trial data. DT decision support tools can include dynamical models to enable decision makers to efficiently use the data in DT settings to improve patient health through effective resource allocation. While myopic or heuristic approaches suffice for some patient types, the benefits of explicitly planning around recommendation and adherence effects are significant for others; UCB-BOLD achieves 2-3x lower conditional value-at-risk regret than the next-best benchmark.
Treatment allocation under budget constraints is a central challenge in digital advertising: advertisers must decide which users to show ads to while spending a limited budget wisely. The standard approach follows a two-stage offline pipeline - first collect historical data to estimate heterogeneous treatment effects (HTE), then solve a constrained optimization to allocate the budget. This works well with abundant data, but fails in cold-start settings such as new campaigns, new markets, or new customer segments where little historical data exists. We propose Budget-Constrained Causal Bandits (BCCB), an online framework that learns which users respond to ads while simultaneously spending the budget, making treatment decisions one user at a time. BCCB unifies three components into a single sequential process: learning individual-level ad effectiveness, exploring users whose response is uncertain, and pacing the budget over time. We evaluated on the Criteo Uplift dataset, a large-scale advertising dataset from a real randomized controlled trial. Our key finding is a data-efficiency crossover: offline methods require approximately 10,000 historical observations to produce reliable results, while BCCB operates effectively from the very first user. Furthermore, BCCB exhibits 3-5x lower performance variance between runs, making it more practical for real campaign planning. Among purely online methods, BCCB consistently outperforms standard Thompson Sampling, budgeted Thompson Sampling, and greedy HTE estimation across all budget levels tested.
Personalized models are essential in digital health because individuals exhibit substantial physiological and behavioral heterogeneity. Yet personalization is limited by scarce and noisy user-specific data. Most existing methods rely on population pretraining or data from similar users only, which can lead to biased transfer and weak generalization. We propose a unified personalization framework that trains a personal model using adaptively weighted support users, including both similar and dissimilar individuals. The objective integrates personal loss, similarity-weighted transfer from similar users, and contrastive regularization from dissimilar users to suppress misleading correlations. An iterative optimization algorithm jointly updates model parameters and user similarity weights. Experiments on six tasks across four real-world digital health datasets show consistent improvements over population and personalized baselines. The method achieves up to 10% lower RMSE on large-scale datasets and approximately 25% lower RMSE in low-data settings. The learned adaptive weights improve data efficiency and provide interpretable guidance for targeted data selection.
Clinical decision support AI systems (CDSASs) must adapt to evolving patient conditions in real-time while adhering to strict safety constraints. We present an online adaptive framework that integrates Treatment Effect (TE) estimation to quantify clinical benefits, a patient Digital Twin (DT) to simulate treatment trajectories, and Reinforcement Learning (RL) for sequential decision-making. The AI system is initially trained on historical medical records and operates in a continuous learning loop. To ensure safety, a rule-based module monitors vital signs and blocks contraindicated treatments. Cases with strong internal model disagreement are flagged for clinician review, simulated in our experiments via a pre-trained outcome model. We validate our framework using both a synthetic clinical simulator and a real-world ovarian cancer dataset from The Cancer Genome Atlas (TCGA). In both simulated and clinical settings, our method demonstrated superior effectiveness and stability in recommending treatments compared to standard computational baselines. Furthermore, the AI system maintains low latency and requires expert consultation for only a minority of cases in our experimental validation, demonstrating its potential as a safe, clinician-supervised tool for personalized medicine that continuously improves through practical use.