We present, as a pure Prolog program, the first executable specification of the 3 + 3 dose-escalation protocol commonly used in early-phase oncology drug development. In this program, the imperative operations of the protocol emerge as consequences of clinically meaningful anticipatory-regret scenarios that are declared as CLP(Z) constraints. This 'regret-constrained' (RC) specification yields a robust formulation which can be used to prove clinically meaningful safety and liveness properties of the protocol before incorporating it into a trial, and then as an on-line decision support system while the trial is underway. Our RC specification also readily accommodates certain pragmatic modifications to trial enrollment which severely strain traditionally imperative formulations. The features of modern Prolog systems let us describe the 3 + 3 protocol with a short and general program that has desirable algebraic properties and can therefore be used, tested and reasoned about in several different ways.

翻译：我们以纯Prolog程序形式，首次实现了早期肿瘤药物开发中常用的3+3剂量递增方案的可执行规范。在该程序中，方案的过程性操作表现为基于临床意义的预期-遗憾场景的逻辑结果，这些场景被声明为CLP(Z)约束。这种"遗憾约束"规范提供了稳健的公式化表达，既可在临床试验实施前用于证明方案具有临床意义的安全性与活性属性，又可在试验进行时作为在线决策支持系统。我们的遗憾约束规范还能灵活适应某些严重挑战传统过程性公式化的试验入组实践性修改。现代Prolog系统的特性使我们能够用简短且通用的程序描述3+3方案，该程序具备理想的代数性质，因此可通过多种不同方式进行使用、测试和推理。