Early completion based on adjacent dose information for model-assisted designs to accelerate maximum tolerated dose finding

Phase I trials aim to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or a Phase II trial to assess the efficacy of the treatment. We present an early completion method based on multiple dosages (adjacent dose information) to accelerate the identification of the MTD in model-assisted designs. By using not only toxicity data for the current dose but also toxicity data for the next higher and lower doses, the MTD can be identified early without compromising accuracy. The early completion method is performed based on dose-assignment probabilities for multiple dosages. These probabilities are straightforward to calculate. We evaluated the early completion method using from an actual clinical trial. In a simulation study, we evaluated the percentage of correct MTD selection and the impact of early completion on trial outcomes. The results indicate that our proposed early completion method maintains a high level of accuracy in MTD selection, with minimal reduction compared to the standard approach. In certain scenarios, the accuracy of MTD selection even improves under the early completion framework. We conclude that the use of this early completion method poses no issue when applied to model-assisted designs.

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Publication Details

Journal
The International Journal of Biostatistics
Published
2025-06-03
DOI
https://doi.org/10.1515/ijb-2023-0040
Primary Topic
Optimal Experimental Design Methods
Type
article
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article

Early completion based on adjacent dose information for model-assisted designs to accelerate maximum tolerated dose finding

Masahiro Kojima
The International Journal of Biostatistics
Optimal Experimental Design Methods
article

Early completion based on adjacent dose information for model-assisted designs to accelerate maximum tolerated dose finding

Masahiro Kojima
article en

Abstract

Phase I trials aim to identify the maximum tolerated dose (MTD) early and proceed quickly to an expansion cohort or a Phase II trial to assess the efficacy of the treatment. We present an early completion method based on multiple dosages (adjacent dose information) to accelerate the identification of the MTD in model-assisted designs. By using not only toxicity data for the current dose but also toxicity data for the next higher and lower doses, the MTD can be identified early without compromising accuracy. The early completion method is performed based on dose-assignment probabilities for multiple dosages. These probabilities are straightforward to calculate. We evaluated the early completion method using from an actual clinical trial. In a simulation study, we evaluated the percentage of correct MTD selection and the impact of early completion on trial outcomes. The results indicate that our proposed early completion method maintains a high level of accuracy in MTD selection, with minimal reduction compared to the standard approach. In certain scenarios, the accuracy of MTD selection even improves under the early completion framework. We conclude that the use of this early completion method poses no issue when applied to model-assisted designs.

The International Journal of BiostatisticsVol. 21(2)
The Graduate University for Advanced Studies, SOKENDAI (JP), Kyowa Kirin (Japan) (JP)
Openalex Percentile: Top 86%
Optimal Experimental Design Methods
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Early completion based on adjacent dose information for model-assisted designs to accelerate maximum tolerated dose finding — Masahiro Kojima · The International Journal of Biostatistics (2025) | TGRS Research Map | TGRS