Tse Siu Keung, Chow Shein Chung, Lu Qingshu, Cosmatos Dennis
Department of Management Sciences, City University of Hong Kong, Kowloon, Hong Kong.
Biom J. 2009 Feb;51(1):159-70. doi: 10.1002/bimj.200710490.
The problem of testing treatment difference in the occurrence of a safety parameter in a randomized parallel-group comparative clinical trial under the assumption that the number of occurrence follows a zero-inflated Poisson (ZIP) distribution is considered. Likelihood ratio tests (LRT) for homogeneity of two ZIP populations are derived under the hypotheses that (i) there is no difference in inflation parameters, (ii) there is no difference in non-zero means; and (iii) there is no difference in both inflation parameters and non-zero means. Approximate formulas for sample size calculation are also obtained for achieving a desired power for detecting a clinically meaningful difference under the corresponding alternative hypotheses. An example concerning the assessment of the gastrointestinal (GI) safety in terms of the number of erosion counts of a newly developed compound for the treatment of osteoarthritis and rheumatoid arthritis is given for illustration purpose.
考虑在随机平行组比较临床试验中，假设安全参数发生次数服从零膨胀泊松（ZIP）分布时，检验治疗差异的问题。在以下假设下推导了两个ZIP总体同质性的似然比检验（LRT）：（i）膨胀参数无差异；（ii）非零均值无差异；以及（iii）膨胀参数和非零均值均无差异。还获得了样本量计算的近似公式，以便在相应的备择假设下实现检测临床有意义差异的所需功效。为说明目的，给出了一个关于评估一种新开发的用于治疗骨关节炎和类风湿关节炎的化合物的胃肠道（GI）安全性（根据糜烂计数）的示例。
