Barnett, Helen and Boix, Oliver and Kontos, Dimitris and Jaki, Thomas (2023) Backfilling cohorts in phase I dose-escalation studies. CLINICAL TRIALS, 20 (3). pp. 261-268. ISSN 1740-7745, 1740-7753
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Background: The use of 'backfilling', assigning additional patients to doses deemed safe, in phase I dose-escalation studies has been used in practice to collect additional information on the safety profile, pharmacokinetics and activity of a drug. These additional patients help ensure that the maximum tolerated dose is reliably estimated and give additional information to determine the recommended phase II dose. Methods: In this article, we study the effect of employing backfilling in a phase I trial on the estimation of the maximum tolerated dose and the duration of the study. We consider the situation where only one cycle of follow-up is used for escalation as well as the case where there may be delayed onset toxicities. Results: We find that, over a range of scenarios, the use of backfilling gives an increase in the percentage of correct selections by up to 9%. On average, for a treatment with a cycle length of 6 weeks, each additional backfilling patient reduces the trial duration by half a week. Conclusions: Backfilling in phase I dose-escalation studies can substantially increase the accuracy of estimation of the maximum tolerated dose, with a larger impact in the setting with a dose-limiting toxicity event assessment period of only one cycle. This increased accuracy and reduction in the trial duration are at the cost of increased sample size.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Dose-finding; dose-escalation; backfilling; phase I trials; model-based; late-onset toxicity |
| Subjects: | 000 Computer science, information & general works > 004 Computer science 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Informatics and Data Science > Department Machine Learning & Data Science > Lehrstuhl für Computational Statistics (Prof. Dr. Thomas Jaki) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Mar 2024 11:36 |
| Last Modified: | 14 Mar 2024 11:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60089 |
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