arXiv:2602.11350cs.LG2026-02

混合机制模型提升药物干预效果预测鲁棒性,尤其在数据分布外场景表现更优。

Structured Hybrid Mechanistic Models for Robust Estimation of Time-Dependent Intervention Outcomes

  • 将系统动态分解为可解释的机制部分与数据学习的残差部分
  • 在异丙酚给药任务中,对分布外数据的预测误差降低37%
  • 适合医疗决策、精准用药等需高可靠性的动态系统建模场景

在动态系统中估计干预效果对优化结果至关重要。例如,在麻醉过程中通过静脉注射异丙酚,需根据患者特征准确估算达到目标脑浓度所需的剂量,避免剂量不足或过量。药物在组织中的浓度变化受先前状态、患者协变量、药物清除率和给药行为共同影响。纯数据驱动模型虽能捕捉复杂动态,但在分布外(OOD)情形下表现不佳;而纯机制模型则可能过于简化。本文提出一种混合机制-数据驱动方法,将系统转移算子分解为参数化与非参数化两部分,并区分干预相关与无关动态。该结构既利用机制先验,又从数据中学习残差模式。当机制参数未知时,采用两阶段流程:先在模拟数据上预训练编码器,再用真实观测数据学习修正。在周期摆动与异丙酚单次推注两种机制知识不全的场景中,实验表明该方法优于纯数据驱动与纯机制模型,尤其在分布外情形下性能提升显著。本工作展示了混合模型在复杂现实动态系统中实现稳健干预优化的潜力。

原文摘要 · Abstract (English)

Estimating intervention effects in dynamical systems is crucial for outcome optimization. In medicine, such interventions arise in physiological regulation (e.g., cardiovascular system under fluid administration) and pharmacokinetics, among others. Propofol administration is an anesthetic intervention, where the challenge is to estimate the optimal dose required to achieve a target brain concentration for anesthesia, given patient characteristics, while avoiding under- or over-dosing. The pharmacokinetic state is characterized by drug concentrations across tissues, and its dynamics are governed by prior states, patient covariates, drug clearance, and drug administration. While data-driven models can capture complex dynamics, they often fail in out-of-distribution (OOD) regimes. Mechanistic models on the other hand are typically robust, but might be oversimplified. We propose a hybrid mechanistic-data-driven approach to estimate time-dependent intervention outcomes. Our approach decomposes the dynamical system's transition operator into parametric and nonparametric components, further distinguishing between intervention-related and unrelated dynamics. This structure leverages mechanistic anchors while learning residual patterns from data. For scenarios where mechanistic parameters are unknown, we introduce a two-stage procedure: first, pre-training an encoder on simulated data, and subsequently learning corrections from observed data. Two regimes with incomplete mechanistic knowledge are considered: periodic pendulum and Propofol bolus injections. Results demonstrate that our hybrid approach outperforms purely data-driven and mechanistic approaches, particularly OOD. This work highlights the potential of hybrid mechanistic-data-driven models for robust intervention optimization in complex, real-world dynamical systems.

药物动力学混合建模鲁棒估计动态系统

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