儿童药物临床试验方案违背现状及对策探讨

Exploration on the current status of protocol violations in pediatric drug clinical trials and corresponding countermeasures

摘要

目的: 剖析儿童药物临床试验中方案违背的现状及成因,构建预防与减少方案违背的应对策略,为儿童药物临床试验的规范开展提供参考依据。方法: 收集某三甲专科妇儿医院2022年1月—2025年6月儿科药物临床试验中方案违背案例,回顾性分析方案违背的类型、责任主体及具体诱因,并据此制定针对性的改进措施。结果: 24项儿童药物临床试验共发生186例次方案违背,主要类型包括样本相关违背、访视相关违背、药物相关违背、检查检验相关违背等;责任主体按发生频次依次为受试者及监护人、研究者、临床试验协调员、申办方及其他因素。结论: 儿童药物临床试验需在试验全流程中持续开展总结与优化工作,针对各责任主体制定对应策略有效降低方案违背发生率,为提升儿童类临床试验质量提供实践借鉴。

Abstract

Objective: To analyze the current situation and causes of protocol violations in pediatric drug clinical trials, develop strategies to prevent and reduce them, and provide a reference for standardized implementation of pediatric drug clinical trials. Methods: Cases of protocol violations in pediatric drug clinical trials at a Grade Ⅲ Level A specialized women and children's hospital from January 2022 to June 2025 were collected. A retrospective analysis of the types of protocol violations, responsible entities, and specific causes was performed, and targeted improvement measures were formulated accordingly. Results: Across 24 pediatric drug clinical trials, a total of 186 occurrences of protocol violations were recorded. The primary types included sample-related violations, visit-related violations, medication-related violations, and examination/test-related violations. When classified by the responsible entity and ranked by frequency of occurrence, the order was: subjects/guardians, investigators, clinical research coordinators, sponsors, and other factors. Conclusion: Throughout the entire process of pediatric drug clinical trials, continuous summary and optimization work should be carried out, and corresponding strategies should be formulated for each responsible entity to effectively reduce the incidence of protocol violations, thereby providing practical reference for improving the quality of pediatric clinical trials.

关键词

儿童 / 药物临床试验 / 方案违背 / 对策

Key words

children / drug clinical trials / protocol violations / countermeasure

[1] 中华人民共和国国家卫生和计划生育委员会. 关于保障儿童用药的若干意见[EB/OL].(2014-05-30)[2025-09-09].https://www.nhc.gov.cn/zwgkzt/pzcyj/201405/e51354d631944fa68aac0c4d9585f291.shtml.
[2] 国家卫生健康委员会. 关于印发第五批鼓励研发申报儿童药品清单的通知[EB/OL].(2024-08-30)[2025-07-25].http://www.gov.cn/zhengce/zhengceku/202409/content_6973293.html.
[3] 国务院妇女儿童工作委员会. 中国儿童发展纲要(2021—2030年)[EB/OL].(2021-09-27)[2025-09-09].https://www.nwccw.gov.cn/2021/09/27/99338976.html.
[4] 国家药品监督管理局药品审评中心. 儿科人群药物临床试验技术指导原则[EB/OL].(2016-03-01)[2025-09-09].https://www.cde.org.cn/zdyz/domesticinfopagezdyzIdCODE=e20e9bd309366a800d3b0cda9f2d9359.
[5] 叶朝辉, 严荧燕, 朱卓儿, 等. 儿童药物临床试验免费检查开具及结算信息系统的设计与应用[J]. 中国现代应用药学, 2024, 41(3): 393-397.
[6] 国家卫生健康委医学伦理专家委员会办公室, 中国医院协会. 涉及人的临床研究伦理审查委员会建设指南(2023版)[EB/OL].(2023-06-28)[2025-07-06].https://www.cha.org.cn/site/content/393b419e529469ef3f4c0ddaddb347ca.html.
[7] 李亚男, 吴大维, 孟丽君, 等. 新备案临床试验机构方案偏离的问题研究[J]. 中国医疗管理科学, 2025, 15(1): 24-29.
[8] 王谦, 丁倩, 郭春彦, 等. 我国儿科人群多中心药物临床试验机构合作关系网络分析[J]. 中国医院用药评价与分析, 2024, 24(3): 257-260, 264.
[9] 熊宁宁, 刘海涛, 胡晋红, 等. 伦理委员会制度与操作规程[M]. 4版. 北京: 科学出版社, 2021: 184-195.
[10] 李吉, 漆林艳, 毛建华, 等. 儿科临床试验违背方案分析及应对措施[J]. 中国医学伦理学, 2023, 36(8): 847-852.
[11] 王璐, 黄哲. 真实世界证据改善儿童药物临床试验障碍的对策研究[J]. 中国新药杂志, 2022, 31(19): 1872-1875.
[12] 国家药品监督管理局药品审评中心. 儿童药物临床试验安全信息评估与报告技术指导原则(试行)[EB/OL].(2025-05-29)[2025-09-11].https://www.cde.org.cn/main/news/viewInfoCommon/d3762909c55ef21c7fc533d8ba826d40.
[13] 最高人民检察院. 深化最有利于未成年人原则适用最大限度保护未成年人合法权益[EB/OL].(2025-04-19)[2025-09-11].https://www.spp.gov.cn/spp/llyj/202504/t20250419_693466.shtml.
[14] 钟一鸣, 张天义, 郭文. 中美儿科临床试验管理的比较研究[J]. 中国新药杂志, 2021, 30(14): 1302-1308.
[15] 张红三, 刘慧兰, 卜志军, 等. 单臂设计在中医儿科临床研究中的应用[J]. 世界中医药, 2025, 20(10): 1784-1789.
[16] KOHARA N, KANEKO M, NARUKAWA M. Investigation of the study characteristics affecting clinical trial quality using the protocol deviations leading to exclusion of subjects from the per protocol set data in studies for new drug application: a retrospective analysis[J]. Ther Innov Regul Sci, 2019, 53(1): 45-51.
[17] 翟羽佳, 莫小兰, 何艳玲, 等. 儿科临床药师用药指导实践与思考[J]. 今日药学, 2025, 35(4): 312-315.