Warfarin is a widely used anticoagulant, and has a narrow therapeutic range. Dosing of warfarin should be individualized, since slight overdosing or underdosing can have catastrophic or even fatal consequences. Despite much research on warfarin dosing, current dosing protocols do not live up to expectations, especially for patients sensitive to warfarin. We propose a deep reinforcement learning-based dosing model for warfarin. To overcome the issue of relatively small sample sizes in dosing trials, we use a Pharmacokinetic/ Pharmacodynamic (PK/PD) model of warfarin to simulate dose-responses of virtual patients. Applying the proposed algorithm on virtual test patients shows that this model outperforms a set of clinically accepted dosing protocols by a wide margin. We tested the robustness of our dosing protocol on a second PK/PD model and showed that its performance is comparable to the set of baseline protocols.
翻译:华法林是一种广泛使用的抗冷凝剂,其治疗范围狭窄。 华法林的剂量应该被个性化, 因为轻微过量或过量可能带来灾难性甚至致命的后果。 尽管对华法林剂量做了大量研究,但目前的剂量协议并不符合人们的期望, 特别是对沃法林敏感的病人而言。 我们为华法林提出了一个深度强化的基于学习的剂量模式。 为了克服剂量试验中样本体积相对较小的问题, 我们使用药用基因/药用动力学(PK/PD)模型模拟虚拟病人的剂量反应。 对虚拟试验病人应用拟议的算法表明,这种模式在广泛的范围内超越了一套临床上接受的剂量协议。 我们在第二个PK/药用模型上测试了我们的剂量协议的稳健性,并表明其性能与一套基线协议相当。