We have often said that one of the greatest benefits of an adaptive clinical trial is the flexibility it affords for decision-making [1]. Often this flexibility is taken to mean that sponsors have some leeway to accommodate events - foreseen or unforeseen, challenging or advantageous - midway through a trial. However, when designing a trial, it is often possible to leverage this flexibility towards the sponsor's advantage.
Recently, a client approached us, determined to select the best of eight candidate doses to move forward into a pivotal Phase 3 trial. Like many in their situation, our client worried that testing all eight doses would require unnecessary time and expense. However, given a variety of other constraints, a subpar Phase 3 dose was simply not an option.
Our first recommendation was to combine our client's proof-of-concept and dose-finding trials into a single adaptive study. Several candidate doses would be tested for proof-of-concept prior to the interim look. The trial would then become a dose-finding trial after consultation with the DMC.
Secondly, we designed the adaptive trial to be a multi-arm study which began with four doses prior to interim analysis. The design allowed for the option to add other candidate doses after the interim look, or to drop doses as seemed fitting .
Third, our team of consultants devised a customized clinical utility function to support the DMC's decision-making. As the trial played out, the flexibility and choice afforded in such decision-making meant that the trial continued with two active arms after the interim look.
The result: This combined study reduced the trial time by an estimated 9 to 12 months, and required 100 fewer patients.
Related Items of Interest
[2] Impact of Study Design and Development Strategy on Pharmaceutical Programs and Portfolios
[3] Adaptive Clinical Trial Strategies for the Limited Early Phase Budget
