抗肿瘤药物临床试验受试者筛选失败原因及方案纳排指标分析  

Analysis of the Causes of Subject Screening Failures in Clinical Trials of Antineoplastic Drugs and Protocol Nerfing Indicators

作　　者：贾硕鹏 马海兰 黄慧瑶 朱敬肖 于安琪 侯怡如 唐玉 房虹 李宁 JIA Shuopeng;MA Hailan;HUANG Huiyao;ZHU Jingxiao;YU Anqi;HOU Yiru;TANG Yu;FANG Hong;LI Ning(Clinical Trials Center,National Cancer Center,National Cancer Clinical Medical Research Center,Cancer Hospital of Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100021,China;School of Basic Medical and Clinical Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院药物临床试验研究中心,北京100021 [2]中国药科大学基础医学与临床药学学院,南京211198

出　　处：《医药导报》2025年第3期497-502,共6页Herald of Medicine

摘　　要：目的分析抗肿瘤药物临床试验受试者筛选失败的原因以及纳排标准对受试者进入临床试验的影响,探讨提高受试者成功筛选入组的策略,为研究机构和申办方制定纳排标准提供参考依据。方法选取2016年1月1日—2022年6月30日中国医学科学院北京协和医学院肿瘤医院药物临床试验研究中心开展的40项药物临床试验资料,通过频数、百分构成比对收集到的受试者筛选失败数据和方案中的纳排指标进行统计描述。结果在涵盖8个瘤种的40个抗肿瘤药物临床试验项目中,筛选失败受试者425例,<65岁受试者居多(333例,78.4%),筛选失败的主要原因包括受试者自愿退出(71例,16.7%)、基因突变不符合(61例,14.3%)、肿瘤转移(52例,12.2%)、其他疾病治疗未恢复(38例,8.9%)、骨髓功能未达标(19例,4.5%)、肝功能不符合要求(15例,3.5%)。在纳排指标中,对受试者年龄(100%)、美国东部肿瘤协作组(ECOG)评分(97.5%)、骨髓功能[中性粒细胞绝对计数(ANC):95.0%、血小板计数(PLT):97.5%、血红蛋白(HB):97.5%]、肝功能[总胆红素(T-BiL):95.0%、丙氨酸氨基转移酶(ALT):87.5%、天冬氨酸氨基转移酶(AST):95.0%]、肾功能[肌酐(Cr):80.0%,以及病毒筛查(人体免疫缺陷病毒(HIV):80.0%、乙型肝炎病毒(HBV):70.0%、丙型肝炎病毒(HCV):62.5%]的要求相对严格。结论该院抗肿瘤药物临床试验中受试者筛选失败的主要原因是受试者自愿退出、肿瘤脑转移以及生化检测指标不合格,这与临床试验纳排标准的设定密切相关。深入了解受试者特征,精准设定合适纳排标准,持续改进试验设计,加强与受试者沟通,提供更多相关信息,有助于提高抗肿瘤药物临床试验筛选成功率。Objective To analyze the reasons for the failure of subject screening in clinical trials of antineoplastic drugs and the impact of natriuretic criteria on the entry of subjects into clinical trials,to explore the strategies to improve the successful enrolment of screened subjects,and to provide reference bases for research institutes and sponsors in the formulation of natriuretic criteria.Methods This study selected data from 40 drug clinical trials conducted at the Drug Clinical Trial Research Center of the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1,2016,to June 30,2022.It statistically described the collected data on the frequency and percentage composition of screening failures among participants and the inclusion and exclusion criteria in the protocols.Results A total of 425 subjects were screened out of 40 clinical trial programmers covering 8 tumor types,with the majority being<65 years of age(333,78.4%),of which the most important reasons included voluntary withdrawal(71,16.7%),tumor metastasis(52,12.2%),failure to recover from treatment of pre-existing disease(38,8.9%),failure of bone marrow function(19,4.5%),and non-compliant liver function(15,3.5%).Among the nadir indicators,the age of the subjects(100%),ECOG score(97.5%),bone marrow function(ANC:95.0%,PLT:97.5%,HB:97.5%),liver function(T-BiL:95.0%,ALT:87.5%,AST:95.0%),renal function(CR:80.0%),and viral screening(HIV:80.0%,HBV:70.0%,HCV:62.5%)were relatively stringent.Conclusion The main reasons for subject screening failure in clinical trials in oncology in our hospital are voluntary withdrawal,brain metastasis,and failure of their biochemical test standards,which are closely related to the setting of clinical trial nadir criteria.Therefore,an in-depth understanding of subjects'characteristics,accurate setting of appropriate nadir criteria,continuous improvement of trial design,and strengthening of communication with subjects to provide more relevant information will help to improve the screening success rate of clinical

关 键 词：抗肿瘤药物 临床试验方案 纳排标准 筛选失败原因 受试者 

分 类 号：R95[医药卫生—药学]