Optimised point estimators for multi-stage single-arm phase II oncology trials

ABSTRACT

The uniform minimum variance unbiased estimator (UMVUE) is, by definition, a solution to removing bias in estimation following a multi-stage single-arm trial with a primary dichotomous outcome. However, the UMVUE is known to have large residual mean squared error (RMSE). Therefore, we develop an optimisation approach to finding estimators with reduced RMSE for many response rates, which attain low bias. We demonstrate that careful choice of the optimisation parameters can lead to an estimator with often substantially reduced RMSE, without the introduction of appreciable bias.

KEYWORDS:

• Adaptive design
• group sequential
• interim analysis
• UMVUE
• unbiased estimation

Data availability statement

Code to reproduce all results given in this manuscript is available from https://github.com/mjg211/article_code.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

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Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.