Proposal for size justification of expanded cohort at phase-2-recommended dose
- 2 February 2010
- journal article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 29 (4), 713-715
- https://doi.org/10.1007/s10637-009-9385-7
Abstract
Purpose Most current dose-seeking phase 1 trials include an expanded cohort at phase-2-recommended dose (P2RD) to better characterize the drug safety or to obtain a better estimate of secondary endpoints. Nevertheless, the sample size of this expanded cohort has generally not been justified. Materials and methods We reviewed 330 phase 1 trials (1998–2008). We estimated the rate of patients experiencing dose-limiting toxicity (DLT) at P2RD. Next, we estimated the probability of observing 1, 2 or 3 DLT in different fictive cohorts (from 8 to 22 patients). Results In the literature, the rate of patients experiencing DLT at P2RD was 367/2433, or 15.0%. We drew a table estimating the probability of observing 1, 2 or 3 DLTs in the different fictive cohorts. For example, in a cohort of 16 patients, the probabilities of observing 1, 2 or 3 DLTs are about 92.6%, 91.3 and 91.1% respectively. Conclusion This simple tool could provide a justification for the sample size of an expanded cohort when DLT remains the metric for dose-seeking.Keywords
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