Target toxicity design for phase I dose-finding
We propose a new two-/three-stage dose-finding design called Target Toxicity (TT) for phase I clinical trials, where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test. The power to detect excessive toxicity is also given. This solves the problem of wh...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-04-01
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| Series: | Statistical Theory and Related Fields |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/24754269.2020.1800331 |
| _version_ | 1797677111860789248 |
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| author | Wenchuan Guo Bob Zhong |
| author_facet | Wenchuan Guo Bob Zhong |
| author_sort | Wenchuan Guo |
| collection | DOAJ |
| description | We propose a new two-/three-stage dose-finding design called Target Toxicity (TT) for phase I clinical trials, where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test. The power to detect excessive toxicity is also given. This solves the problem of why the minimal number of patients is needed for the selected dose level. Our method provides a statistical explanation of traditional ‘3+3’ design using frequentist framework. The proposed method is very flexible and it incorporates other interval-based decision rules through different parameter settings. We provide the decision tables to guide investigators when to decrease, increase or repeat a dose for next cohort of subjects. Simulation experiments were conducted to compare the performance of the proposed method with other dose-finding designs. A free open source R package tsdf is available on CRAN. It is dedicated to deriving two-/three-stage design decision tables and perform dose-finding simulations. |
| first_indexed | 2024-03-11T22:39:16Z |
| format | Article |
| id | doaj.art-ded1eae824ff490fad22a09466101964 |
| institution | Directory Open Access Journal |
| issn | 2475-4269 2475-4277 |
| language | English |
| last_indexed | 2024-03-11T22:39:16Z |
| publishDate | 2021-04-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Statistical Theory and Related Fields |
| spelling | doaj.art-ded1eae824ff490fad22a094661019642023-09-22T09:19:45ZengTaylor & Francis GroupStatistical Theory and Related Fields2475-42692475-42772021-04-015214916110.1080/24754269.2020.18003311800331Target toxicity design for phase I dose-findingWenchuan Guo0Bob Zhong1Global Biometric Sciences, Bristol-Myers Squibb CompanyNektar TherapeuticsWe propose a new two-/three-stage dose-finding design called Target Toxicity (TT) for phase I clinical trials, where we link the decision rules in the dose-finding process with the conclusions from a hypothesis test. The power to detect excessive toxicity is also given. This solves the problem of why the minimal number of patients is needed for the selected dose level. Our method provides a statistical explanation of traditional ‘3+3’ design using frequentist framework. The proposed method is very flexible and it incorporates other interval-based decision rules through different parameter settings. We provide the decision tables to guide investigators when to decrease, increase or repeat a dose for next cohort of subjects. Simulation experiments were conducted to compare the performance of the proposed method with other dose-finding designs. A free open source R package tsdf is available on CRAN. It is dedicated to deriving two-/three-stage design decision tables and perform dose-finding simulations.http://dx.doi.org/10.1080/24754269.2020.1800331group-sequential-like designsdose-findingphase imtdrecommended phase ii dosespower |
| spellingShingle | Wenchuan Guo Bob Zhong Target toxicity design for phase I dose-finding Statistical Theory and Related Fields group-sequential-like designs dose-finding phase i mtd recommended phase ii doses power |
| title | Target toxicity design for phase I dose-finding |
| title_full | Target toxicity design for phase I dose-finding |
| title_fullStr | Target toxicity design for phase I dose-finding |
| title_full_unstemmed | Target toxicity design for phase I dose-finding |
| title_short | Target toxicity design for phase I dose-finding |
| title_sort | target toxicity design for phase i dose finding |
| topic | group-sequential-like designs dose-finding phase i mtd recommended phase ii doses power |
| url | http://dx.doi.org/10.1080/24754269.2020.1800331 |
| work_keys_str_mv | AT wenchuanguo targettoxicitydesignforphaseidosefinding AT bobzhong targettoxicitydesignforphaseidosefinding |