新药临床试验数据盲态审核中常见方案偏离情况分析

Protocol deviations in clinical trials of new drug application

目的:了解国内新药临床试验数据盲态审核中常见的方案偏离情况,为提高临床研究实施质量提供一定的参考依据。方法:选取36个已完成的新药Ⅱ,Ⅲ期临床试验,对数据管理中盲态审核中出现的方案偏离情况进行编码。结果:临床方案偏离情况与临床项目特征关系不大,方案偏离类型主要为失访(27.73%)、不符合入排标准(14.43%)、合并使用影响疗效判定的其他药物(14.05%)、未按方案用药或依从性差(11.42%)和因不良事件中止(10.92%)等,影响FAS和PPS人群划分的方案偏离类型主要是失访、不符合入排标准等;影响SS人群划分的方案偏离类型主要原因是失访。结论:造成方案偏离的原因中多数和研究的质量控制有关,仅少数由药物或治疗本身特性决定,因此需要在临床研究的整个过程中分别从研究者的角度、监察员的角度对相应的问题采取有效的措施,从而提高研究的质量。

Objective： To reveal the status of protocol deviations in clinical trials of new drug application, and to give reference information to improve the quality of clinical trials. Methods： Thirty six clinical trials of phase II and phase III were collected and the reasons of deviation from design were coded. Results ： The deviations were little associated with the basic information of these trials. The most important types were lost （27.73%） , not accord with inclusion and exclusion criteria （14.43%） , the combined medicine use that influence the efficacy of drugs （14.05%）, poor compliance （11.42% ）, withdrawal because of adverse event （10.92%）, and so on. The most important types of deviation affecting population dividing into FAS and PPS were loss of follow-up, and incor- rect inclusion and exclusion criteria. For SS, it was lost to follow-up, and the SS set was lost also. Conclusion： Most of the reasons that lead to the plan deviations is associated with the implementation quality of the trials, only a little are related to the characteristics of the drug itself. It is very important to take measures to improve the quality of the study by the sponsors and monitors in their own aspects.