title: Group sequential monitoring based on the weighted log-rank test statistic with the Fleming-Harrington class of weights in cancer vaccine studies.
abstract: In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log-rank tests with the Fleming-Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming-Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long-term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log-rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Biostatistics Department, Shionogi & Co., Ltd. 12F, Hankyu Terminal Bldg., 1-4, Shibata 1-chome, Kita-ku, Osaka, 530-0012, Japan. takahiro.hasegawa@shionogi.co.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D019496:Cancer Vaccines / Q000008:administration & dosage*; D003606:Dacarbazine / Q000008:administration & dosage; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality*; D000077594:Nivolumab; D016032:Randomized Controlled Trials as Topic / Q000379:methods / Q000706:statistics & numerical data*; D015996:Survival Rate / Q000639:trends
chemical_list: D000911:Antibodies, Monoclonal; D019496:Cancer Vaccines; D000077594:Nivolumab; D003606:Dacarbazine
keywords: delayed treatment effect; group sequential; information fraction; long-term survivals; weighted log-rank test statistic