Page 23 - 2020年17期

2010－2019年某CRO公司药物临床试验项目盲态审核中方案偏

离的相关数据分析 Δ

#
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董玉君 ，王 蓉，余秋钿，程国华（暨南大学药学院，广州 510632）
中图分类号 R951；R969.4 文献标志码 A 文章编号 1001-0408（2020）17-2065-06
DOI 10.6039/j.issn.1001-0408.2020.17.04

摘 要 目的：研究方案偏离对药物临床试验结果的影响，为提高药物临床试验的质量管理水平提供参考。方法：收集广州某合
同研究组织（CRO）公司2010－2019年药物临床试验的盲态数据审核表，分析方案偏离总体特征、“722公告”（指国家食品药品监
督管理总局2015年7月22日发布《关于开展药物临床试验数据自查核查工作的公告》）前后的方案偏离情况以及方案偏离对全分
析集（FAS）人群划分的影响，并提出相应建议。结果：最终纳入45个试验项目，涉及454个中心、14 304例病例和5 562例次方案
偏离。最常见的方案偏离类型依次是超窗、违背纳入与排除标准、脱落，分别占方案偏离的36.88％、20.71％、18.43％。不同试验
分期和不同药物类型的项目发生方案偏离的程度无统计学意义（P＞0.05），而“722公告”前后不同阶段项目发生方案偏离的程度
有显著性差异（P＜0.05）；“722公告”后的超窗、违背纳入与排除标准和服药依从性的偏离发生率有所升高。发生方案偏离的病例
有82.07％可以进入FAS，纳入FAS且未进入符合方案集（PPS）的人群占总体偏离人群的53.99％，其中脱落、合并用药偏离分别占
19.51％、4.29％，服药依从性偏离的人群均未进入PPS。结论：脱落、违背纳入与排除标准、超窗是造成临床试验方案偏离的主要
因素。“722公告”对药物临床试验人员的质量管理意识的提高起到了一定的促进作用。建议应选择恰当的统计方法控制偏倚，从
试验设计、人员培训及机构管理建设各方面加强药物临床试验质量管理，减少方案偏离的发生。
关键词 方案偏离；药物临床试验；盲态审核；质量管理

Data Analysis on Protocol Deviation in Blind Review of Drug Clinical Trials of a CRO Company from
2010 to 2019
DONG Yujun，WANG Rong，YU Qiutian，CHENG Guohua（College of Pharmacy，Jinan University，Guangzhou
510632，China）

ABSTRACT OBJECTIVE：To study the effects of protocol deviation on the results of clinical trials，and to provide reference for
rising the quality management of drug clinical trials. METHODS：Blind data review forms for clinical trials of a contract research
organzation （CRO） company in Guangzhou from 2010 to 2019 were collected to analyze general characteristics of protocol
deviation， the situation of protocol deviation before and after the “722 announcement”（Announcement on Carrying Out
Self-inspection and Verification of Drug Clinical Trial Data issued by CFDA on July 22，2015）as well as the effects of protocol
deviation on full analysis set（FAS）population division. The suggestions were put forward. RESULTS：A total of 45 trials were
included，involving 454 centers，14 304 disease cases and 5 562 cases of protocol deviation. The most common types of protocol
deviations were over-window，violation of criteria of the inclusion and exclusion，and drop-out，which accounted for 36.88％，
20.71％ and 18.43％ respectively. There was no statistical significance in protocol deviation degree of clinical trials with different
stages or drug types（P＞0.05）；there was significant difference in the degree of protocol deviations in clinical trials with different
stages before and after the“722 announcement”（P＜0.05）；the incidence of deviations from over-window，violation of cirteria of
the inclusion and exclusion，and medication compliance had increased after the“722 announcement”；82.07％ of cases with
protocol deviations could enter FAS，and the population who included in FAS but did not enter per protocol set（PPS）accounted
for 53.99％ of the total deviation，of which deviations from drop-out and combined medication accounted for 19.51％ and 4.29％
respectively. All cases with deviation from medication compliance did not enter PPS. CONCLUSIONS：Drop-out，violation of
criteria of the inclusion and exclusion，and over-window are the main factors that cause clinical trial protocol deviations. The“722
announcement”played a certain role on improving the quality management awareness of the personnel in drug clinical trial.
Appropriate statistical methods should be selected to control bias，and to strengthen the quality management of drug clinical trials
and reduce protocol deviations，by paying attention to trial
Δ 基金项目：广东省省级科技计划项目（No.2015B090901053）
design， staff training， institutional management and
＊硕士研究生。研究方向：药物临床试验管理。电话：020-
construction.
85223869。E-mail：302959184@qq.com
# 通信作者：教授，硕士生导师，博士。研究方向：药物临床试验 KEYWORDS Protocol deviation；Drug clinical trial；Blind
管理。电话：020-85223869。E-mail：ghcheng661203@126.com review；Quality management

中国药房 2020年第31卷第17期 China Pharmacy 2020 Vol. 31 No. 17 ·2065 ·