Using the 'Leapfrog' Design as a Simple Form of Adaptive Platform Trial to Develop, Test, and Implement Treatment Personalization Methods in Routine Practice

Abstract

The route for the development, evaluation and dissemination of personalized psychological therapies is complex and challenging. In particular, the large sample sizes needed to provide adequately powered trials of newly-developed personalization approaches means that the traditional treatment development route is extremely inefficient. This paper outlines the promise of adaptive platform trials (APT) embedded within routine practice as a method to streamline development and testing of personalized psychological therapies, and close the gap to implementation in real-world settings. It focuses in particular on a recently-developed simplified APT design, the 'leapfrog' trial, illustrating via simulation how such a trial may proceed and the advantages it can bring, for example in terms of reduced sample sizes. Finally it discusses models of how such trials could be implemented in routine practice, including potential challenges and caveats, alongside a longer-term perspective on the development of personalized psychological treatments.

Keywords: Adaptive platform trial; Bayes factor; Leapfrog trial; Sequential analysis; Treatment personalization.

Fig. 1

Illustration of a hypothetical trial using the leapfrog design. Each triangle depicts a study arm, with the height of the triangle indicating the number of participants recruited. The comparator arm is indicated by the dark grey shading of the triangle, and the initial comparator arm is designated “C”

Fig. 2

Schematic overview of integration of the leapfrog design into routine practice across multiple sites