Supplementary analysis of probabilities at the termination of a group sequential phase II trial.
We consider estimation of various probabilities after termination of a group sequential phase II trial. A motivating example is that the stopping rule of a phase II oncologic trial is determined solely based on response to a drug treatment, and at the end of the trial estimating the rate of toxicity and response is desirable. The conventional maximum likelihood estimator (sample proportion) of a probability is shown to be biased, and two alternative estimators are proposed to correct for bias, a bias-reduced estimator obtained by using Whitehead's bias-adjusted approach, and an unbiased estimator from the Rao-Blackwell method of conditioning. All three estimation procedures are shown to have certain invariance property in bias. Moreover, estimators of a probability and their bias and precision can be evaluated through the observed response rate and the stage at which the trial stops, thus avoiding extensive computation.
Liu
Aiyi
A
Biometry and Mathematical Statistics Branch, Department of Health and Human Services, National Institute of Child Health and Human Development, 6100 Executive Boulevard, Rockville, MD 20892, USA. liua@mail.nih.gov
Wu
Chengqing
C
Yu
Kai F
KF
Gehan
Edmund
E
D015982:Bias; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008954:Models, Biological