Yong Zang, Ph.D., Department of Biostatistics and Health Data Science, Indiana University

"A Generalized Phase 1-2-3 Design integrating Dose Optimization with Confirmatory Treatment Comparison"

A generalized phase 1-2-3 design, Gen 1-2-3, that includes all phases of clinical treatment evaluation is proposed. The design extends and modifies the design of Chapple and Thall (2019), denoted as CT. Both designs begin with a phase 1-2 trial including dose acceptability and optimality criteria, and both select an optimal dose for phase 3. The Gen 1-2-3 design has the following key differences. It uses phase 1-2 criteria to identify a set of candidate doses rather than one dose. In an intermediate stage between phase 1-2 and phase 3, it randomizes additional patients fairly among the candidate doses and an active control treatment arm and uses survival time data to select an optimal dose. It makes a Go / No Go decision of whether or not to conduct phase 3 based on a predictive probability that the optimal dose will provide a substantive improvement over the control in survival time. A simulation study shows that the Gen 1-2-3 design has desirable operating characteristics compared to the CT design and two conventional designs.

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