Uniformly minimum variance conditionally unbiased estimation in multi-arm multi-stage clinical trials

Nigel Stallard, Peter K. Kimani

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Multi-arm multi-stage clinical trials compare several experimental treatments with a control treatment, with poorly performing treatments dropped at interim analyses. This leads to inferential challenges, including the construction of unbiased treatment effect estimators. A number of estimators which are unbiased conditional on treatment selection have been proposed, but are specific to certain selection rules, may ignore the comparison to the control and are not all minimum variance. We obtain estimators for treatment effects compared to the control that are uniformly minimum variance unbiased conditional on selection with any specified rule or stopping for futility.

Original languageEnglish
Pages (from-to)495-501
Number of pages7
JournalBiometrika
Volume105
Issue number2
DOIs
Publication statusPublished - 1 Jun 2018
Externally publishedYes

Keywords

  • Adaptive seamless design
  • Drop-the-loser design
  • Point estimation
  • Treatment selection

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