title: Two-stage seamless transition design from open-label single-arm to randomized double-arm clinical trials.
abstract: Conventional phase II clinical trials use either a single- or multi-arm comparison scheme to examine the therapeutic effects of the experimental drug. Both single- and multi-arm evaluations have their own merits; for example, single-arm phase II trials are easy to conduct and often require a smaller sample size, while multiarm trials are randomized and typically lead to a more objective comparison. To bridge the single- and double-arm schemes in one trial, we propose a two-stage design, in which the first stage takes a single-arm comparison of the experimental drug with the standard response rate (no concurrent treatment) and the second stage imposes a two-arm comparison by adding an active control arm. The design is calibrated using a new concept, the detectable treatment difference, to balance the trade-offs between futility termination, power, and sample size. We conduct extensive simulation studies to examine the operating characteristics of the proposed method and provide an illustrative example of our design.
authors.affiliation: Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong.
authors.forename: Haolun
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Statistics and Actuarial Science, The University of Hong Kong, Hong Kong.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yin
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D017322:Clinical Trials, Phase II as Topic / Q000379:methods; D023381:Endpoint Determination; D018447:Medical Futility; D012107:Research Design; D018401:Sample Size; D016896:Treatment Outcome
keywords: Detectable treatment difference; expected sample size; futility termination; proof of concept; randomization; two-stage design