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An adaptive two-stage dose-response design method for establishing proof of concept
Yoko Franchetti1, Stewart J Anderson, Allan R Sampson
1Department of Biostatistics and Computational Biology, Dana-Faber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02215, USA. yoko.tnk@gmail.com
Abstract:
We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.
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Crossover Experiments
Crossover designs are performed even with smaller sample sizes since the samples can act as their controls. These are better than simple randomized trials since patients are exposed to all the treatments.

