ABSTRACT
We discuss how to structure large pharmaceutical projects that include a relatively large number of clinical sub-trials, of which basket, umbrella, and platform trials provide popular examples. Such trials may be unified under the concept of a cluster trial, and subsequently similar design methods can be applied to all of them. While presenting two approaches rooted in combinatorial and model-based design paradigms, we focus on early phase studies for screening across various combinations of treatments, diseases sub-types, genotypes, or phenotypes. It appears that combinatorial techniques complemented by factorial design methods work well for holistic structuring of cluster trials, while model-based design methods are essential for dose finding. The fusion of the two approaches is promising but can be computationally challenging. The latter motivated us to explore quantum annealing algorithms while running iterative numerical methods for optimal design construction. The quantum annealing component was implemented on D-Wave computer in the framework of the ICON – Lockheed Martin “proof-of-concept” collaboration project.
