title: Design and sample size considerations for simultaneous global drug development program.
abstract: Due to the potential impact of ethnic factors on clinical outcomes, the global registration of a new treatment is challenging. China and Japan often require local trials in addition to a multiregional clinical trial (MRCT) to support the efficacy and safety claim of the treatment. The impact of ethnic factors on the treatment effect has been intensively investigated and discussed from different perspectives. However, most current methods are focusing on the assessment of the consistency or similarity of the treatment effect between different ethnic groups in exploratory nature. In this article, we propose a new method for the design and sample size consideration for a simultaneous global drug development program (SGDDP) using weighted z-tests. In the proposed method, to test the efficacy of a new treatment for the targeted ethnic (TE) group, a weighted test that combines the information collected from both the TE group and the nontargeted ethnic (NTE) group is used. The influence of ethnic factors and local medical practice on the treatment effect is accounted for by down-weighting the information collected from NTE group in the combined test statistic. This design controls rigorously the overall false positive rate for the program at a given level. The sample sizes needed for the TE group in an SGDDP for three most commonly used efficacy endpoints, continuous, binary, and time-to-event, are then calculated.
authors.affiliation: Office of Biostatistics, Center for Drug Evaluation, SFDA, Beijing, PR China. huangq@cde.org.cn
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Yuan
authors.forename: K K Gordon
authors.initials: KK
authors.lastname: Lan
mesh_terms: D002681:China; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D005006:Ethnicity; D005189:False Positive Reactions; D017408:Guidelines as Topic; D006801:Humans; D007564:Japan; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data*; D010601:Pharmacology, Clinical / Q000706:statistics & numerical data*; D012107:Research Design / Q000706:statistics & numerical data*; D018401:Sample Size