cs.LGNov 3, 2026

Post-Inference Model Chaining: A Problem Statement and a Model-based Bootstrap for Training End-to-End Digital Twins

Authors: Lukas Madenach, Timo Bailer, Tobias Eilert

Organizations: CMC Statistics BioPharma, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany

Abstract

End-to-end digital twins can be constructed by fitting separate stage models and connecting them after inference. We investigate the Frequentist prediction properties of a commonly used Monte Carlo simulation scheme that forwards complete predictive draws through such a chain when measured stage outputs contain independent normal errors, but the latent stage means are deterministic. Analytical two-stage examples show persistent asymptotic interval and coverage inflation and, with quadratic propagation, mean bias dependent on the parameters to be estimated. Simulations of four- and eight-stage linear-quadratic univariate chains with 7, 15 or 30 training runs demonstrate pronounced input-dependent distortions. A diagnostic using error-free latent training predictors shows that the effect is mainly not attributable to errors in variables, but to the MCSim approach even showing underestimation of coverage. We propose a model-based bootstrap: an initial chain forwards fitted means, bootstrap chains are refitted on fixed-center bootstrap data while forwarding their mean prediction, and a target-stage future error enters a studentized prediction root. Across the investigated scenarios, relative mean bias is substantially reduced, and coverage is closer to the nominal 90%. At sample size 30, the eight-stage bootstrap has mean width ratios of 1.16-1.42 relative to the known-parameter normal reference, compared with 4.11-4.97 for observed-to-observed MCSim. These results support improved endpoint prediction in the tested setting. Further investigations of the bootstrap scheme in the supplement for a bivariate 6-stage process show similar satisfactory results.

Explore similar work

Apr 24, 2026

Optimal sequential decision-making for error propagation mitigation in digital twins

Here, we explore the problem of error propagation mitigation in modular digital twins as a sequential decision process. Building on a companion study that used a Hidden Markov Model (HMM) to infer latent error regimes from surrogate-physics residuals, we develop a Markov Decision Process (MDP) in which the inferred regimes serve as states, corrective interventions serve as actions, and a scalar reward that takes into consideration the cost-benefit tradeoff between system fidelity and maintenance expense. The baseline transition matrix is extracted from the HMM-learned parameters. We then extend the formulation to a Partially Observable MDP (POMDP) that accounts for the imperfect nature of regime classification by maintaining a belief distribution updated via Bayesian filtering, with the HMM confusion matrix serving as the observation model. Both formulations are solved via dynamic programming and validated through Gillespie stochastic simulation. We then benchmark two model-free reinforcement learning algorithms, Q-learning and REINFORCE, to assess whether effective policies can be learned without explicit model knowledge. A systematic comparison of different intervention policies demonstrates that the MDP policy achieves the highest cumulative reward and fraction of time in nominal operation, while the POMDP recovers approximately 95% of MDP performance under realistic observation noise. Sensitivity analyses across observation quality, repair probability, and discount factor confirm the robustness of these conclusions, and the major gaps in the policy hierarchy are statistically significant at p<0.001p < 0.001. The gap between MDP and POMDP performance quantifies the value of information providing a principled criterion for investing in improved classification accuracy.
Apr 1, 2026

The Digital Twin Counterfactual Framework: A Validation Architecture for Simulated Potential Outcomes

The fundamental problem of causal inference - that the counterfactual outcome for any individual is never observed - has shaped the entire methodology of the field. Every existing approach substitutes assumptions for missing data: ignorability, parallel trends, exclusion restrictions. None produces the counterfactual itself. This paper proposes the Digital Twin Counterfactual Framework (DTCF): rather than estimating the counterfactual statistically, we simulate it using a digital twin and subject the simulation to a hierarchical validation regime. We formalize the digital twin simulator as a stochastic mapping within the potential outcomes framework and introduce a hierarchy of twin fidelity assumptions - from marginal fidelity through joint fidelity to structural fidelity - each unlocking a progressively richer class of estimands. The central contribution is threefold. First, a five-level validation architecture converts the unfalsifiable claim that the simulator produces correct counterfactuals into falsifiable tests against observable data. Second, a formal decomposition separates causal quantities into those that are marginally validated (ATE, CATE, QTE - testable through observable-arm comparison) and those that are copula-dependent (the ITE distribution, probability of benefit/harm, variance of treatment effects - permanently reliant on the unobservable within-individual dependence structure). Third, bounding, sensitivity, and uncertainty quantification tools make the copula dependence explicit. The DTCF does not resolve the fundamental problem of causal inference. What it provides is a framework in which marginal causal claims become increasingly testable, joint causal claims become explicitly assumption-indexed, and the gap between the two is formally characterized.
Jul 23, 2026

Equilibrium Causal Digital Twins: Validation, Transport, and Identification Limits

Digital twins are often used to predict how a system would respond to an intervention. In systems with feedback, a twin must reproduce an equilibrium counterfactual, and a twin developed in one domain may fail after mechanisms change. We study when these predictions can be validated and transported. For equilibrium causal games, we give conditions on the mechanisms, equilibrium selection, and intervention design under which agreement with experimental distributions identifies the counterfactual of interest. We show why agreement of means and covariances is insufficient for distributional queries. We then introduce cyclic selection diagrams and derive criteria for direct reuse and for hybrid models that combine invariant source mechanisms with target information. An impossibility result constructs systems that agree under every experiment in a finite design but disagree on the target counterfactual, showing that validation requires structural assumptions. For linear models, we derive intervention requirements that depend on the mechanisms that changed, the observation model, and graph support. When point identification fails, we characterize the remaining range of query values. We also provide statistical tests for reconstructed means and covariances and illustrate the theory in synthetic feedback systems.