Dataset Information

Using dichotomized survival data to construct a prior distribution for a Bayesian seamless Phase II/III clinical trial.

ABSTRACT: Master protocol designs allow for simultaneous comparison of multiple treatments or disease subgroups. Master protocols can also be designed as seamless studies, in which two or more clinical phases are considered within the same trial. They can be divided into two categories: operationally seamless, in which the two phases are separated into two independent studies, and inferentially seamless, in which the interim analysis is considered an adaptation of the study. Bayesian designs are scarcely studied. Our aim is to propose and compare Bayesian operationally seamless Phase II/III designs using a binary endpoint for the first stage and a time-to-event endpoint for the second stage. At the end of Phase II, arm selection is based on posterior (futility) and predictive (selection) probabilities. The results of the first phase are then incorporated into prior distributions of a time-to-event model. Simulation studies showed that Bayesian operationally seamless designs can approach the inferentially seamless counterpart, allowing for an increasing simulated power with respect to the operationally frequentist design.

SUBMITTER: Duputel B

PROVIDER: S-EPMC10521165 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Using dichotomized survival data to construct a prior distribution for a Bayesian seamless Phase II/III clinical trial.

Duputel Benjamin B Stallard Nigel N Montestruc François F Zohar Sarah S Ursino Moreno M

Statistical methods in medical research 20230315 5

Master protocol designs allow for simultaneous comparison of multiple treatments or disease subgroups. Master protocols can also be designed as seamless studies, in which two or more clinical phases are considered within the same trial. They can be divided into two categories: operationally seamless, in which the two phases are separated into two independent studies, and inferentially seamless, in which the interim analysis is considered an adaptation of the study. Bayesian designs are scarcely ...[more]

PMID: 36919403

Similar Datasets

Project description:BackgroundThe phase III TIVO-3 study demonstrated improvement in progression-free survival (PFS) with tivozanib compared with sorafenib in patients with 2-3 prior systemic regimens for metastatic renal cell carcinoma (mRCC).MethodsThe TIVO-3 trial enrolled patients with measurable mRCC who had received 2 or more prior systemic therapies, including a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Patients were stratified by International Metastatic RCC Database Consortium risk score and type of prior treatment and were randomized 1:1 to receive tivozanib or sorafenib. Efficacy was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 criteria, with PFS as the primary endpoint. Safety was evaluated using Common Terminology Criteria for Adverse Events version v4.03, and statistical analyses included Cox regression for overall survival (OS) and descriptive statistics for duration of response (DOR). The current post-hoc long-term follow-up analysis consists of an assessment of OS in the previously stratified subpopulation of patients with prior CPI exposure.ResultsBetween May 2016, and August 2017, 350 patients were randomized, of which 26% had prior CPI exposure, with final analysis data cut off on June 21, 2021. In patients previously treated with CPIs (n = 91), the median PFS of tivozanib was 7.3 months versus 5.1 months with sorafenib and hazard ratio (HR) of 0.55 (95% CI, 0.32-0.94). The OS HR in the CPI-treated subset was 0.69 (95% CI, 0.43-1.11, P =.0992) favoring tivozanib, although with a median OS of 18.1 and 20.9 months, for tivozanib and sorafenib, respectively. Tivozanib demonstrated a longer median DOR of 20.3 versus 5.7 months for sorafenib in the subset previously treated with CPIs. The safety profile favored tivozanib, with lower rates of VEGF-TKI class-related grade ≥3 adverse events compared with sorafenib. However, in the subset of patients previously treated with CPIs, the incidence of grade ≥3 adverse events was higher, at 58% for tivozanib and 67% for sorafenib, compared with the ITT population, at 46% and 55%, respectively.ConclusionsIn this long-term post-hoc update of the TIVO-3 trial, we show that in CPI-resistant mRCC, the PFS benefit of tivozanib over sorafenib is accompanied with improved OS data, although not statistically significant, and durable responses.

Dataset Information

Using dichotomized survival data to construct a prior distribution for a Bayesian seamless Phase II/III clinical trial.

Publications

Using dichotomized survival data to construct a prior distribution for a Bayesian seamless Phase II/III clinical trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets