We consider a control theory approach to adaptive dose allocation of anticoagulants, based on an analysis of records of 152 patients on long‐term warfarin treatment. We consider a selection of statistical models for the relationship between the dose of drug and subsequent blood clotting speed, measured through the international normalized ratio. Our main focus is on subsequent use of the model in guiding the choice of the next dose adaptively as patient‐specific information accrues. We compare a naive long‐term approach with a proportional‐integral‐plus method, with parameters estimated by either linear quadratic optimization or by stochastic resource allocation. We demonstrate advantages of the control approaches in comparison with a naive approach in simulations and through calculation of robust stability margins for the observed data.

中文翻译：

---

强大的自适应抗凝控制

我们根据对长期华法林治疗的152例患者的记录进行分析，考虑采用一种控制理论方法来自适应分配抗凝剂。我们考虑选择一种统计模型，用于通过国际标准化比率衡量的药物剂量与随后的血液凝固速度之间的关系。我们的主要关注点是该模型的后续使用，以随着患者特定信息的累积而自适应地指导选择下一剂药物。我们将天真的长期方法与比例积分加方法进行了比较，并采用了线性二次优化或随机资源分配来估算参数。我们在仿真中以及通过计算观察数据的鲁棒稳定性裕度，证明了与朴素方法相比，控制方法的优势。