临床试验不同区域间疗效方向性差异的因素分析

Analysis of influencing factors on observed regional difference in treatment effects in clinical trial

目的分析临床试验中不同区域间疗效的方向性差异的影响因素,为设计更合理的临床试验提供建议。方法从试验设计角度分别在假设事实疗效一致与不一致的条件下,采用数学推导来推算观察到不一致临床试验结果的概率,用求导及SAS编程分析其每一个随机因素对不一致概率的影响,并分析该如何控制这些影响因素。结果不同区域间疗效的方向性差异的影响因素主要有试验样本量、各区域标准化事实疗效、各区域人数比例和区域数目。通过在原地区增加样本量、增加疗效绝对值小的区域人数比例和减少区域数目等方法可减小随机因素的影响,使得临床试验中观察到的结果更接近于真实状况。结论优化样本量、区域人数比例和区域数目等设计因素,可降低临床试验中随机因素造成的疗效不一致。

AIM To explore factors affecting the probability of observing qualitatively inconsistent effects in clinical trials, and provide recommendations on designing more reliable clinical trials. METHODS Under the condition of consistent or inconsistent regional true effects, calculate the probability of observing inconsistent effects with using both mathematical and numerical （SAS） methods, to analyze the impact of various factors on this probability. RESULTS Factors affecting the probability of observing inconsistent results were sample size, regional standardized effect size, regional proportion and number of regions. Increasing sample size, increasing the proportion of patients in region with a smaller effect in absolute value and reducing the number of regions could reduce the impact of chance factors to make any observed result more likely the reflection of true effects. CONCLUSION Optimizing the sample size, regional proportion of patients, and number of regions can reduce inconsistency due to chance factor, and then make trial results more reliable.