title: The bias of the sample proportion following a group sequential phase II clinical trial.
abstract: Group sequential testing procedures have seen wide use in Phase II clinical trials. The sample proportion p of responders is the commonly used estimator for the binomial response probability p. It can be shown that p is the maximum likelihood estimator (MLE) of p. It is well known that MLE can be in general (Whitehead) and p in particular (Dupont) biased estimators, if ther computation follows a group sequential procedure. In this paper we numerically investigate the bias of p. We find that the magnitude of the bias of p is less than 0.025 in all cases we investigated. We apply the idea in Whitehead to propose a bias-adjusted estimator that reduces the bias substantially and reduces the mean square error as well in a certain range of p. We also evaluate the uniformly minimum variance unbiased (UMVU) estimator. If one does not mind a bias of 0.025, one may find the sample proportion a suitable estimator for p because of its simplicity and easy explanation. If one is concerned with bias, the bias-adjusted estimator may be a good choice.
authors.affiliation: Department of Statistics, University of Florida, Gainesville 32611.
authors.forename: M N
authors.initials: MN
authors.lastname: Chang
authors.forename: H S
authors.initials: HS
authors.lastname: Wieand
authors.forename: V T
authors.initials: VT
authors.lastname: Chang
mesh_terms: D004341:Drug Evaluation / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011336:Probability; D012107:Research Design; D013997:Time Factors