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Backfilling cohorts in phase I dose-escalation studies.
Barnett, Helen; Boix, Oliver; Kontos, Dimitris; Jaki, Thomas.
Afiliação
  • Barnett H; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK.
  • Boix O; Lancaster University, Lancaster, UK.
  • Kontos D; Bayer AG, Leverkusen, Germany.
  • Jaki T; ClinBAY, Limassol, Cyprus.
Clin Trials ; 20(3): 261-268, 2023 Jun.
Article em En | MEDLINE | ID: mdl-36951478
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.
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Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Ano de publicação: 2023 Tipo de documento: Article