负二项回归在新药安全性评价中的应用

目的: 将负二项回归用于新药的安全性评价,以此分析评价不良事件的发生情况.方法: 结合罗格列酮治疗Ⅱ型糖尿病患者的Ⅲ期临床试验实例,以年龄、性别等为影响因素,以不良事件的发生次数为反应变量拟合Poisson回归模型和负二项回归模型.结果: 负二项回归模型拟合其值与自由度之比为0.9995,效果要优于Poisson回归模型,"性别"和"处理"进入回归模型,"年龄"未进入.拟合的回归模型具有统计学意义.结论: 负二项回归模型作为一种新的方法可尝试应用于新药的安全性评价中,以拓展新药的安全性评价,解决传统新药安全性评价仅考虑不良事件发生例数而不考虑例次及基线因素的弊端.

Application of negative binomial model for safety assessment in new drug

AIM: To apply negative binomial model for the safety assessment of a new drug, so as to analyze the occurrence of adverse events. METHODS: Using the data from one phase-III clinical trial of Rosiglitazone in treating type-2 diabetes, we fitted the poisson regression model and the negative binomial regression model, with the frequency of adverse events as response variable, and sex, age as well as many other factors as independent variables. The fitting effectiveness of the models and the statistical significance of the factors were analyzed. RESULTS: The negative binomial regression model proved satisfactory and its fitting effectiveness was better than that of the poisson model. Two factors, sex and treatment, were found significant and were included in the regression model. No significance was found in the factor of age, and it was not include in the regression model. CONCLUSION: It is a new and better choice to apply the negative binomial regression model to drug safety assessment, which not only analyzes the frequency of adverse events but also assesses the effects of covariates.