Conditionally unbiased and near unbiased estimation of the selected treatment mean for multistage drop-the-losers trials

Biometrical Journal. Biometrische Zeitschrift
Jack Bowden, Ekkehard Glimm

Abstract

The two-stage drop-the-loser design provides a framework for selecting the most promising of K experimental treatments in stage one, in order to test it against a control in a confirmatory analysis at stage two. The multistage drop-the-losers design is both a natural extension of the original two-stage design, and a special case of the more general framework of Stallard & Friede () (Stat. Med. 27, 6209-6227). It may be a useful strategy if deselecting all but the best performing treatment after one interim analysis is thought to pose an unacceptable risk of dropping the truly best treatment. However, estimation has yet to be considered for this design. Building on the work of Cohen & Sackrowitz () (Stat. Prob. Lett. 8, 273-278), we derive unbiased and near-unbiased estimates in the multistage setting. Complications caused by the multistage selection process are shown to hinder a simple identification of the multistage uniform minimum variance conditionally unbiased estimate (UMVCUE); two separate but related estimators are therefore proposed, each containing some of the UMVCUEs theoretical characteristics. For a specific example of a three-stage drop-the-losers trial, we compare their performance against several alternative est...Continue Reading

References

Aug 2, 2005·Biometrical Journal. Biometrische Zeitschrift·Allan R Sampson, Michael W Sill
Jul 30, 2008·Biometrical Journal. Biometrische Zeitschrift·Jack Bowden, Ekkehard Glimm
Sep 16, 2008·Statistics in Medicine·Nigel Stallard, Tim Friede
Jan 19, 2010·Pulmonary Pharmacology & Therapeutics·Peter J BarnesDavid Lawrence
Sep 8, 2010·Biometrical Journal. Biometrische Zeitschrift·Ionut BebuVladimir Dragalin
Jan 13, 2012·Statistics in Medicine·Joseph S KoopmeinersMargaret Sullivan Pepe
Jun 30, 2012·Statistics in Medicine·Máximo Carreras, Werner Brannath
Aug 25, 2012·Trials·John A KairallaKeith E Muller
Feb 16, 2013·Statistics in Medicine·Peter K KimaniNigel Stallard
Sep 18, 2014·Statistical Methods in Medical Research·James WasonChristopher Jennison

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Citations

Mar 18, 2015·Statistics in Medicine·Peter BauerGernot Wassmer
Jun 7, 2016·Pharmaceutical Statistics·Gaohong Dong, Marc Vandemeulebroecke
Sep 18, 2014·Statistical Methods in Medical Research·James WasonChristopher Jennison
Aug 13, 2015·Statistical Methods in Medical Research·Jack Bowden, Lorenzo Trippa
Feb 13, 2020·Statistics in Medicine·Pranab GhoshCyrus Mehta
Mar 25, 2020·Statistics in Medicine·John WhiteheadThomas Jaki
Aug 28, 2019·Journal of Biopharmaceutical Statistics·Hongjian ZhuLixin Zhang
Mar 17, 2016·Statistical Methods in Medical Research·Xiaomin LuSamuel S Wu
Jan 19, 2017·Biometrics·Per Broberg, Frank Miller
Jun 15, 2017·Statistics in Medicine·Matthias BrücknerThomas Jaki

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