AdaPCLA framework is proposed, which enables generative models to adaptively fit and generate EHR data through a data distribution-aware training strategy; this is achieved by internalizing data knowledge parameters by simulated annealing training.
Abstract
Generative modeling of longitudinal Electronic Health Records is increasingly important for privacy-preserving research, yet standard autoregressive models tend to underrepresent the co-occurrence structure of tail events (i.e., diseases, symptoms), reducing the fidelity and faithfulness of generated data for rare subpopulations. To this end, we propose AdaPCLA framework, which enables generative models to adaptively fit and generate EHR data through a data distribution-aware training strategy; this is achieved by internalizing data knowledge parameters by simulated annealing training. It also supports training-free adaptation to a diverse clinical population for generation through zero-shot distribution control. Moreover, our theoretical analysis characterizes rare-code logit updates through the label-wise empirical NTK and derives a prior-internalization bound for how annealing speed and NTK conditioning affect retained prior signals. Experiments on real-world data show that AdaPCLA achieves consistent gains in tail plausibility, downstream utility, and zero-shot control; in particular, it improves TailPairSeen over HALO by 114.2% on MIMIC-III and 65.1% on MIMIC-IV, outperforms GPT-style generation by 3.5% F1 for zero-shot cross-population adaptation.
Estimating conditional average treatment effects (CATE) enables efficient targeting of interventions, but many applications have limited experimental samples, making it difficult to estimate heterogeneous effects from high-dimensional covariates. In such settings, policymakers and medical practitioners often succumb to the curse of dimensionality or apply off-the-shelf dimension reduction methods that may not preserve treatment heterogeneity. Yet these domains often come with large historical datasets measuring a wide range of outcomes -- a source of supervision that is rarely exploited in practice. Following causal representation learning, we hypothesize that such domains with high-dimensional covariates have lower-dimensional underlying dynamics. We can thus leverage the diverse outcomes measured in historical data to learn a lower-dimensional representation of the covariates. Theoretically, we prove that when the auxiliary outcomes satisfy a set of surrogacy conditions and the representation retains relevant covariate information, the original CATE is identified when the high-dimensional covariates are replaced by the learned representation. Combined with existing dimension-dependent rates for CATE estimation, the result implies greater sample-efficiency on the same experimental sample. Additionally, we characterize the bias-variance tradeoff when the assumptions do not hold perfectly, and show that the representation-based estimator can still achieve lower error when the reduction in estimator variance outweighs the bias due to compression. Empirically, we evaluate the method on synthetic data and semi-synthetic medical data.
Maitreyi Swaroop, Shikha Bhat, Samantha Rodriguez et al.· 0 citations
Synthetic data generation is increasingly used to enable data sharing and secondary analysis while protecting participant privacy, particularly for longitudinal tabular health data, where repeated measures per subject create within-subject dependence that most synthetic data methods are not designed to preserve. Existing generative methods, particularly generative adversarial network (GAN)-based approaches, can model complex distributions, but their estimated dependence structures are often difficult to interpret and their performance may be unstable or prone to overfitting in modestly sized datasets. Here we show that eCDF-copula, a statistically rooted approach using the empirical cumulative distribution function (eCDF) and copula modeling, preserves within- and between-visit dependence structure. To handle pervasive missing data, we propose a two-stage strategy combining multiple imputation with copula-based synthesis, enabling a variance decomposition that quantifies replication variability across methods. We benchmarked the proposed approach against four established methods on two longitudinal clinical datasets spanning markedly different sample sizes (n = 120 vs. n = 3, 612). eCDF-copula achieved resemblance and utility exceeding those of state-of-the-art synthetic data methods, while maintaining comparable privacy.
Hanchang Cai, Wen-Shan Yu, Ruijin Lu et al.· bioRxiv· 0 citations
Self-supervised Causal Effects Estimation is proposed, a novel framework that integrates causal priors with self-supervised learning to construct balanced and predictive representations for causal effects estimation that consistently outperforms state-of-the-art methods.
Xin-Shu Li, Shiyi Yang, Venus Haghighi et al.· ACM Transactions on Intellig...· 0 citations
Modern generative models increasingly produce distribution-valued outputs, such as predicted cellular responses to genetic perturbations in single-cell genomics. While these models provide valuable auxiliary information, they are inherently imperfect, creating a need for statistical methods that leverage their predictions without relying on their correctness. We propose generation-powered inference (GPI), a general framework for improving inference on distribution-valued parameters using auxiliary generative models. Focusing on Wasserstein barycenters and related distributional functionals, we introduce a function-valued bridge representation that transforms inference in the nonlinear Wasserstein space into estimation of a mean function in a Hilbert space, enabling an augmented estimation framework analogous to prediction-powered inference. We develop a family of GPI estimators with optimal information borrowing, establish consistency, asymptotic normality, and simultaneous confidence bands, and derive valid inference for linear functionals and Wasserstein distances. Simulation studies demonstrate efficiency gains over labeled-data-only methods and robust performance under generative model misspecification. We illustrate the proposed framework using a Perturb-seq study of K562 cells, where synthetic perturbation responses generated by the State foundation model are used to improve inference for pathway-level consensus gene expression distributions associated with perturbations of the 40S ribosome module.
Estimating counterfactual outcomes over time from longitudinal observational data is central to clinical decision support. Existing methods rely on domain confusion -- adversarial training that renders representations invariant to treatment assignment -- yet this invariance creates a mutual information conflict: it suppresses treatment-correlated covariate signals necessary for accurate outcome prediction. We formalise this tension via a Jensen-Shannon divergence bound on counterfactual prediction error and develop two complementary models. CSSD (Causal State-Space model with Direct decoder) adapts selective State Space Models with a parallel multi-step decoder that eliminates accumulated rollout error by producing all prediction horizons simultaneously in a single forward pass. CSSPD (Causal State-Space model with Predictive regularisation and Direct decoder) augments CSSD with Contrastive Predictive Coding and Local Information Maximisation to reinforce temporal predictability in the balancing representation and recover local covariate information destroyed by domain confusion. On MIMIC-III, CSSPD achieves lower counterfactual RMSE than the Causal Transformer at every horizon tau>= 2 at O(T) encoder cost, with gains from 0.02 (2-step) to 0.07 (6-step). On Cancer Simulation across confounding strengths gamma in {0,1,2,3,4}, CSSPD outperforms CT at gamma<= 3 (margins 25.9%--37.0%), and CSSD achieves the lowest overall average RMSE (12.7% reduction over CT), confirming the MI conflict analysis. To our knowledge, this is the first work to formalise the balancing-prediction MI conflict and propose a structured resolution through complementary predictive and information-theoretic training objectives.
The combined objective is derived, which proof steps transfer from the classification setting without modification and which require adaptation, and which require adaptation on the PhysioNet 2019 Sepsis Challenge, treating the two hospital systems as sequential training fragments and the unseen system as an out-of-distribution test.
Behraj Khan, Shabir Ahmad, S. Bukhari et al.· arXiv.org· 1 citation
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