Page 24 - 《中国药房》2022年13期

药物临床试验中常见方案偏离及改进措施 Δ

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谢江川 ，谢林利，曹丽亚，潘辛梅，马 攀，陈勇川（陆军军医大学第一附属医院药学部，重庆 400038）
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中图分类号 R95 文献标志码 A 文章编号 1001-0408（2022）13-1554-05
DOI 10.6039/j.issn.1001-0408.2022.13.04

摘 要 目的 了解药物临床试验过程中常见的方案偏离（PD）并探讨预防和减少 PD 的措施，为药物临床试验的规范化提供参
考。方法 以《药物临床试验质量管理规范》《关于发布药物临床试验数据管理与统计分析的计划和报告指导原则的通告》《药物临
床试验伦理审查工作指导原则》、人用药品注册技术要求国际协调会议（ICH）E3、ICH E6（R2）等法规为参照，对笔者2017年3月－
2022年2月负责管理的相关项目中上报的PD，以及在递交材料、项目质控中发现的PD进行梳理和统计分析。结果与结论 共纳入
39 个药物临床试验项目，有 212 名受试者入选。在所有项目中，共上报 PD 258 条，包括重大 PD 28 条（占比为 10.85％）、常规 PD
230条（占比为89.15％）。PD上报频率较高的为检查/检验缺失（93条，占比为36.05％）、访视缺失（36条，占比为13.95％）、访视超
窗（29条，占比为11.24％）、试验药物使用及剂量（28条，占比为10.85％）、药品超温/温度缺失（21条，占比为8.14％）等。避免和减
少PD的发生需要多方努力：申办方应听取多方意见后设计合理且访视频率和窗口期适宜的方案；研究者和临床研究协调员应加
强自身学习和培训，熟悉方案、《药物临床试验质量管理规范》和相应法规；应加强受试者的依从性教育；机构办公室和伦理委员会
在药物临床试验立项时、进行中、结题时应进行多角度、全过程的监督和管理，保障受试者的安全权益和临床试验的质量。在此基
础上，各参与方应做好有效沟通，发现PD及时上报，并针对已发生的重大PD和容易发生PD的关键环节进行专项学习。
关键词 药物临床试验；方案偏离；质量管理；规范化；改进措施

Common protocol deviations and improvement methods and precautions in drug clinical trials
XIE Jiangchuan，XIE Linli，CAO Liya，PAN Xinmei，MA Pan，CHEN Yongchuan（Dept. of Pharmacy，the First

Affiliated Hospital of Army Medical University，Chongqing 400038，China）

ABSTRACT OBJECTIVE To learn the common protocol deviation（PD）in the process of drug clinical trials and discuss the
methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials.
METHODS According to Good Clinical Practice，Notice on Issuing Guidelines for Planning and Reporting of Data Management
and Statistical Analysis of Drug Clinical Trials，Guidelines for Ethical Review of Drug Clinical Trials，ICH E3，ICH E6（R2）and
other regulations，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as
the PD found in the submission materials and project quality control，were sorted out and statistically analyzed. RESULTS &
CONCLUSIONS A total of 39 drug clinical trials were included，and 212 subjects were selected. In all projects，258 PDs were
reported，including 28 major PD （accounting for 10.85％） and 230 ordinary PD （accounting for 89.15％）. The report of PD
mainly included missed inspections/tests（93 reports，accounting for 36.05％），lack of visits（36 reports，accounting for 13.95％），
inspection/testing out-of-window（29 reports，accounting for 11.24％），dosage and usage of test drugs（28 reports，accounting for
10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the
occurrence of PD requires the efforts of multiple parties：the sponsor designs a reasonable protocol with appropriate interview rate
and window period after listening to the opinions of multiple parties；the investigators and clinical research coordinator should
strengthen their own learning and training， and be familiar with the protocol， Good Clinical Practice and corresponding
regulations；the compliance education of the subjects should be strengthened；the institutional offices and ethics committees should
conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved，in progress，and
Δ 基金项目 重庆市技术预见与制度创新项目（No.cstc2018jsyj- concluded，to ensure the safety rights and interests of the
zdcxX0079） subjects and the quality of clinical trials. On this basis，all
＊第一作者 主管药师，硕士。研究方向：临床试验质控及管理、药 parties should communicate effectively and timely，report PD
物新剂型与新技术。电话：023-68766776。E-mail：15828676406@163. in time，and conduct special studies on major PD that have
com
occurred and key links that are prone to PD.
# 通信作者 副主任药师，硕士。研究方向：临床试验及伦理管理、
KEYWORDS drug clinical trials； protocol deviation；
临床药理学和药代动力学。电话：023-68766776。E-mail：zwmcyc@
quality management；standardization；improvement measures
163.com

·1554 · China Pharmacy 2022 Vol. 33 No. 13 中国药房 2022年第33卷第13期