|
|||||
|
|
An Adaptive Two-Stage Dose-Response Design Method for Establishing Proof of Concept |
|
| Authors: | Yoko Franchetti Stewart J. Anderson Allan R. Sampson |
| Affiliation: | 1. Department of Biostatistics and Computational Biology , Dana-Faber Cancer Institute and Harvard School of Public Health , Boston , Massachusetts , USA yoko.tnk@gmail.com;3. Department of Biostatistics, Graduate School of Public Health , University of Pittsburgh , Pittsburgh , Pennsylvania , USA;4. Department of Statistics, School of Arts and Sciences , University of Pittsburgh , Pittsburgh , Pennsylvania , USA |
| 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. |
| Keywords: | Adding and/or dropping treatment arms Drug development Proof of concept Two-stage adaptive design xMCP-Mod |