The Backfill i3+3 Design for Dose-Finding Trials in Oncology
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arXiv
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| Autori principali: | , , , |
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| Natura: | Preprint |
| Pubblicazione: |
2023
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| _version_ | 1866916188103114752 |
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| author | Liu, Jiaxin Yuan, Shijie Bekele, B. Nebiyou Ji, Yuan |
| author_facet | Liu, Jiaxin Yuan, Shijie Bekele, B. Nebiyou Ji, Yuan |
| contents | We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose optimization. The proposed design, called Bi3+3, combines the simple dose-escalation algorithm in the i3+3 design and a model-based inference under the framework of probability of decisions (POD), both previously published. As a result, Bi3+3 provides a simple algorithm for backfilling patients to lower doses in a dose-finding trial once these doses exhibit safety profile in patients. The POD framework allows dosing decisions to be made when some backfill patients are still being followed with incomplete toxicity outcomes, thereby potentially expediting the clinical trial. At the end of the trial, Bi3+3 uses both toxicity and efficacy outcomes to estimate an optimal biological dose (OBD). The proposed inference is based on a dose-response model that takes into account either a monotone or plateau dose-efficacy relationship, which are frequently encountered in modern oncology drug development. Simulation studies show promising operating characteristics of the Bi3+3 design in comparison to existing designs. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2303_15798 |
| institution | arXiv |
| publishDate | 2023 |
| record_format | arxiv |
| spellingShingle | The Backfill i3+3 Design for Dose-Finding Trials in Oncology Liu, Jiaxin Yuan, Shijie Bekele, B. Nebiyou Ji, Yuan Applications We consider a formal statistical design that allows simultaneous enrollment of a main cohort and a backfill cohort of patients in a dose-finding trial. The goal is to accumulate more information at various doses to facilitate dose optimization. The proposed design, called Bi3+3, combines the simple dose-escalation algorithm in the i3+3 design and a model-based inference under the framework of probability of decisions (POD), both previously published. As a result, Bi3+3 provides a simple algorithm for backfilling patients to lower doses in a dose-finding trial once these doses exhibit safety profile in patients. The POD framework allows dosing decisions to be made when some backfill patients are still being followed with incomplete toxicity outcomes, thereby potentially expediting the clinical trial. At the end of the trial, Bi3+3 uses both toxicity and efficacy outcomes to estimate an optimal biological dose (OBD). The proposed inference is based on a dose-response model that takes into account either a monotone or plateau dose-efficacy relationship, which are frequently encountered in modern oncology drug development. Simulation studies show promising operating characteristics of the Bi3+3 design in comparison to existing designs. |
| title | The Backfill i3+3 Design for Dose-Finding Trials in Oncology |
| topic | Applications |
| url | https://arxiv.org/abs/2303.15798 |