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.
An Executable Specification of Oncology Dose-Escalation Protocols with Prolog
Can Logic Programming Be Liberated from Predicates and Backtracking?
Applying Constraint Programming to Minimal Lottery Designs
We develop and deploy a set of constraints for the purpose of calculating minimal sizes of lottery designs. Specifically, we find the minimum number of tickets of size six which are needed to match at least two balls on any draw of size six, whenever there are at most 70 balls.