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TITE-gBOIN: Time-to-event Bayesian optimal interval design to accelerate dose-finding accounting for toxicity grades
Kentaro Takeda1, Qing Xia2, Shufang Liu1
1Data Science, Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA.
Pharmaceutical Statistics
|December 4, 2021
Summary
This study introduces the TITE-gBOIN design to improve early-stage oncology trials. This novel Bayesian approach accelerates dose-finding by effectively managing complex toxicity data, leading to faster identification of maximum tolerated doses (MTDs).
Area of Science:
- Oncology
- Clinical Trial Design
- Biostatistics
Background:
- Novel cancer therapeutics (molecular targeted agents, immuno-oncology) often present complex toxicity profiles beyond traditional dose-limiting toxicities.
- Challenges in adaptive dose escalation/de-escalation arise from rapid patient accrual and late-onset toxicities, potentially delaying trials.
- Current dose-finding trial designs struggle to efficiently adapt to the nuanced toxicity patterns of new cancer therapies.
Purpose of the Study:
- To propose a novel time-to-event Bayesian optimal interval design, TITE-gBOIN, for accelerating early-stage oncology dose-finding trials.
- To address the limitations of traditional designs in managing complex and time-dependent toxicities associated with new therapeutic agents.
- To enhance the efficiency and accuracy of identifying maximum tolerated doses (MTDs) in early-phase clinical studies.
Main Methods:
- Development of the TITE-gBOIN (Time-To-Event Bayesian Optimal Interval) design, a nonparametric and model-assisted approach.
- The design integrates both cumulative and pending toxicity outcomes, utilizing time-to-event modeling.
- Utilized simulation studies to evaluate the performance of the TITE-gBOIN design against existing methodologies.
Main Results:
- The TITE-gBOIN design demonstrated a higher probability of correctly identifying the maximum tolerated doses (MTDs).
- A greater proportion of patients were allocated to MTDs across various simulated scenarios.
- The TITE-gBOIN design significantly reduced overall trial duration compared to traditional methods.
Conclusions:
- The TITE-gBOIN design offers a robust, simple, and implementable solution for oncology dose-finding trials.
- This innovative design accelerates the dose-finding process by efficiently utilizing toxicity data.
- TITE-gBOIN facilitates faster progression of early-stage clinical trials for novel cancer therapeutics.
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