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. 2021 Mar;20(2):390-412.
doi: 10.1002/pst.2084. Epub 2020 Dec 7.

Early stopping in seamless phase I/II clinical trials

Noor M Khan  1 , M Iftakhar Alam  1
Affiliations

Early stopping in seamless phase I/II clinical trials

Noor M Khan et al. Pharm Stat. 2021 Mar.

Abstract

In recent years, seamless phase I/II clinical trials have drawn much attention, as they consider both toxicity and efficacy endpoints in finding an optimal dose (OD). Engaging an appropriate number of patients in a trial is a challenging task. This paper attempts a dynamic stopping rule to save resources in phase I/II trials. That is, the stopping rule aims to save patients from unnecessary toxic or subtherapeutic doses. We allow a trial to stop early when widths of the confidence intervals for the dose-response parameters become narrower or when the sample size is equal to a predefined size, whichever comes first. The simulation study of dose-response scenarios in various settings demonstrates that the proposed stopping rule can engage an appropriate number of patients. Therefore, we suggest its use in clinical trials.

Keywords: continuation ratio model; early stopping; optimum dose; seamless phase I/II trial.

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References

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