Sample size re-estimation for survival data in clinical trials with an adaptive design

Pharmaceutical Statistics
Kanae Togo, Manabu Iwasaki

Abstract

In clinical trials with survival data, investigators may wish to re-estimate the sample size based on the observed effect size while the trial is ongoing. Besides the inflation of the type-I error rate due to sample size re-estimation, the method for calculating the sample size in an interim analysis should be carefully considered because the data in each stage are mutually dependent in trials with survival data. Although the interim hazard estimate is commonly used to re-estimate the sample size, the estimate can sometimes be considerably higher or lower than the hypothesized hazard by chance. We propose an interim hazard ratio estimate that can be used to re-estimate the sample size under those circumstances. The proposed method was demonstrated through a simulation study and an actual clinical trial as an example. The effect of the shape parameter for the Weibull survival distribution on the sample size re-estimation is presented.

References

Feb 13, 2001·Statistics in Medicine·J WhiteheadM R Sooriyarachchi
Feb 27, 2001·Statistics in Medicine·W J Shih
Nov 5, 2002·Journal of Biopharmaceutical Statistics·John Lawrence
Apr 2, 2003·The New England Journal of Medicine·Bertram PittUNKNOWN Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators
Jul 19, 2005·Journal of Biopharmaceutical Statistics·Gang LiYining Wang
Jun 6, 2006·Contemporary Clinical Trials·Michael A Proschan, Eric S Leifer
Jun 20, 2007·Statistics in Medicine·K Desseaux, R Porcher

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Citations

Aug 4, 2018·Biometrical Journal. Biometrische Zeitschrift·Michael J GraylingJames M S Wason
Jun 12, 2013·American Journal of Therapeutics·Sanjay G Gokhale, Sankalp Gokhale

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