title: Optimal two-stage designs allowing flexibility in number of subjects for phase II clinical trials.
abstract: Phase II clinical trials are conducted to test whether a drug has a minimum desired effect and to assess whether further development of the drug is warranted. They are often designed as one-arm trials with response rate as the primary endpoint, and a two-stage design is often used to ensure early termination of the trial for futility. To control the type I error rate and guarantee the specified power of the study, planned sample sizes for both stages must be rigidly followed, but a literature review suggests that actual sample size often differs from that planned. We propose to extend simple two-stage designs to allow more flexible sampling plans in both stages. Our designs are preferable to similar extensions proposed to control type I and II error probabilities. Additionally, our assumptions regarding distribution of the actual sample size at the end of stage 1 are more lenient. A list of optimal designs for typical error rates and the selected null and alternative response rates is presented.
authors.affiliation: Department of Biostatistics, Bristol-Myers K.K, Tokyo, Japan. nobuyuki.masaki@bms.com
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Masaki
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Koyama
authors.forename: Isao
authors.initials: I
authors.lastname: Yoshimura
authors.forename: Chikuma
authors.initials: C
authors.lastname: Hamada
mesh_terms: D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data*; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D006801:Humans; D015233:Models, Statistical; D018401:Sample Size; D016896:Treatment Outcome