Sequential Testing in Clinical Trials with Repeated Measurements
针对每个治疗组受试者数量固定、在等间隔时间点重复测量的临床试验，提出一种序贯检验方法，用于检验两种治疗平均效果无差异的零假设，并通过模拟验证其整体显著性水平接近预设值。
In some clinical trials, the number of subjects on each treatment is fixed and at successive equally-spaced time points each subject yields a measurement which reflects response to treatment. A model is presented for such repeated measurements data. A sequential procedure is proposed for testing the null hypothesis of no difference in mean effect between two treatments. In this procedure, the maximum number of measurements per subject and absorption probabilities for intermediate significance tests are preassigned to yield a required approximate overall significance level. The jth significance test follows thejth measurement on each subject, and the test depends on values of model parameters estimated from all the data available so far. Simulations show that the proposed procedure yields overall significance levels close to 5% when required, for data from a variety of models.