我院药物临床试验实施中方案偏离的回顾性研究

Retrospective Study on the Protocol Deviation in Drug Clinical Trial Implementation of Our Hospital

目的:研究药物临床试验实施中方案偏离的影响要素,为提高药物临床试验的质量提供参考。方法:对重庆医科大学附属第一医院2010-2016年开展的药物临床试验项目进行质量核查,对各年度方案偏离进行回顾性研究并归类分析,探讨方案偏离的类别、例数,并比较国际与国内试验项目以及是否有专职研究护士参与试验管理后方案偏离的差异,并提出改进措施。结果:我院2010-2016年开展药物临床试验27项涉及949例病案,方案偏离发生176例,占比18.55%;7年间方案偏离发生比例逐年降低。发生的方案偏离类别主要为观察/评价记录不全(30.11%)、检查漏项/"超窗"(28.41%)、不良事件及合并用药不当(14.20%)和药物管理存在疏漏(11.93%);有专职研究护士参与的项目方案偏离发生比例低于没有专职研究护士参与的项目(11.11%vs.28.67%,P<0.01);国际多中心项目方案偏离发生比例低于国内项目(6.60%vs.28.84%,P<0.01)。结论:建议应有针对性地加强药物临床试验中的薄弱环节,如临床试验机构应建立临床试验数据留存制度,电子数据及时异地备份等。此外,临床试验机构应尽量配备各专业专职研究护士,学习和借鉴国际多中心临床试验项目试验设计严谨科学、操作流程标准化及数据处理真实等做法,以切实减少方案偏离的发生,提高药物临床试验的质量。

OBJECTIVE： To study the influencing factors of protocol deviation in drug clinical trial implementation, and pro- vide reference for improving the quality of drug clinical trial. METHODS： Quality verification was conducted for the drug clinical trial projects in the First Affiliated Hospital of Chongqing Medical University during 2010-2016, and protocol deviations in each year were retrospectively studied, classified and analyzed. Category, frequency, international and domestic pilot projects and the differences of protocol deviation after full-time research nurse participating in trail management were explored, and the measures were put forward. RESULTS： 27 drug clinical trials were implemented in our hospital during 2010-2016, including 949 cases, 176 cases with protocol deviation, accounting for 18.55%. Deviation protocol in drug clinical trial was decreased year by year for 7 years. The categories were mainly incompleteness of observation/records （30.11%）, checking omission/＂broaden the window＂ （28.41%）, adverse drug events and improper combined medication （14.20%） and omission in drug management （11.93%）. The proportion of protocol deviation with full-time research nurse participated was lower than the projects without full-time research nurse （11.11% vs. 28.67 %, P〈0.01）, and proportion of deviation protocol in international multi-center project was lower than the domestic projects （6.60% vs. 28.84%, P〈0.01）. CONCLUSIONS： It is suggested to pointedly strengthen the weak links of drug clinical trial. For example, clinical trial institutions should establish the clinical trial data retention system, electronic data should be timely backed up in a different places, etc. Besides, clinical trial institutions should equip professional full-time research nurses as much as possible, learn the rigorous scientific experimental design, standard operational procedures and the authenticity of data pro- cessing from the international multi-center clinical trial projects to effectively reduce the incidence of deviation protocol and im- prove the quality of drug clinical trials.