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Optimal seamless phase 2/3 oncology trial designs based on Probability of Success (PoS)
Zhaoyang Teng1, Liang Liang2, Guohui Liu1
1Takeda Pharmaceuticals, Cambridge, Massachusetts.
Abstract:
In recent years, there has been an increasing trend in conducting seamless phase 2/3 clinical trials for drug development in the pharmaceutical industry due to the visible advantages compared with traditional approaches for separate phase 2 and 3 development. Innovative study designs have been proposed for seamless phase 2/3 trials, which mainly focus on the traditional aspects of study design, such as how to control the Type I error rate, sample size re-estimation after the phase 2 portion, and how to make treatment selection at the end of the phase 2 portion. However, there are still some questions unresolved such as how to determine the go/no-go boundary and how to plan the phase 2 portion sample size. In this paper, we discuss how to determine the phase 2 portion and phase 3 portion sample sizes as well as the corresponding go/no-go criteria for a seamless phase 2/3 oncology trial based on Probability of Success. In addition, we further expand the methodology to include designs with an interim look within the phase 2 portion to speed up the go/no-go decision-making process. In case of overwhelming efficacy, this design would further shorten the overall trial duration. In case of inefficacy, this design can stop the trial earlier without exposing more patients to inefficacious treatment.
Insights
Seamless phase 2/3 clinical trials offer advantages for drug development. This study proposes methods for determining sample sizes and go/no-go criteria in oncology trials, enhancing decision-making and efficiency.
Area of Science:
- Clinical trial design
- Pharmaceutical drug development
- Oncology research
Background:
- Seamless phase 2/3 trials are increasingly adopted in pharmaceutical development for their efficiency over traditional separate phase 2 and 3 studies.
- Existing seamless trial designs address Type I error control, sample size re-estimation, and treatment selection, but lack clear methods for go/no-go boundaries and phase 2 sample size determination.
- Unresolved questions in seamless trial design include establishing go/no-go decision points and planning phase 2 sample sizes.
Purpose of the Study:
- To propose a methodology for determining phase 2 and phase 3 sample sizes in seamless oncology trials.
- To establish go/no-go criteria for seamless phase 2/3 oncology trials based on the Probability of Success.
- To extend the methodology to incorporate interim analyses within the phase 2 portion for accelerated decision-making.
Main Methods:
- The study focuses on determining sample sizes for both phase 2 and phase 3 portions of seamless trials.
- It utilizes the Probability of Success metric to define go/no-go criteria.
- The methodology is expanded to include interim looks within the phase 2 portion to expedite go/no-go decisions.
Main Results:
- The proposed methods provide a framework for calculating optimal sample sizes for phase 2 and phase 3 components.
- Defined go/no-go criteria facilitate objective decision-making regarding trial progression.
- Incorporating interim looks can significantly shorten overall trial duration in cases of clear efficacy or inefficacy.
Conclusions:
- The developed approach addresses critical gaps in seamless phase 2/3 trial design, particularly for oncology studies.
- Determining sample sizes and go/no-go criteria using Probability of Success enhances trial efficiency and patient safety.
- Interim analyses within phase 2 can lead to faster drug development timelines and reduced patient exposure to ineffective treatments.
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