Zang, YongThall, Peter F.Yuan, Ying2025-03-212025-03-212024Zang Y, Thall PF, Yuan Y. A generalized phase 1-2-3 design integrating dose optimization with confirmatory treatment comparison. Biometrics. 2024;80(1):ujad022. doi:10.1093/biomtc/ujad022https://hdl.handle.net/1805/46458A 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 by 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. In stage 1, it uses phase 1-2 criteria to identify a set of candidate doses rather than 1 dose. In stage 2, which is intermediate 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 from both stage 1 and stage 2 patients to select an optimal dose. It then makes a Go/No Go decision of whether or not to conduct phase 3 based on the predictive probability that the selected optimal dose will provide a specified substantive improvement in survival time over the control. A simulation study shows that the Gen 1-2-3 design has desirable operating characteristics compared to the CT design and 2 conventional designs.en-USPublisher PolicyBayesian designCell therapyDose findingPhase 1-2 clinical trialPhase 1-2-3 clinical trialArticle