2024/02/13 by David C. Norris, Norris, David C., Markus Triska +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Mathematics · Medicine · #Cancer Genomics and Diagnostics #Medical Imaging Techniques and Applications #Statistical Methods in Clinical Trials #cs.PL
paper · pdf · doi:10.48550/arxiv.2402.08334
openalex publication_date 2024/02/13 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
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.