抗肿瘤药物临床试验方案偏离的原因分析及管理对策探讨

Analysis of the causes of deviation of clinical trial protocol of anti-tumor drugs and discussion of management countermeasures

目的分析抗肿瘤药物临床试验方案偏离的原因,并探讨相应的管理对策。方法选择2021年1月~2023年10月徐州医科大学附属医院进行的药物临床试验560项,回顾性分析抗肿瘤药物临床试验的方案偏离的原因,针对可能的原因制定相应的管理对策。结果在560项临床试验方案中,抗肿瘤药物临床试验出现偏离方案231例次,占41.25%,前三位原因分别为:标准操作规程(SOP)不依从(31.60%),检验、检查方式及评估等超窗(27.27%),抗肿瘤药物用法及用量不依从(18.61%)。在抗肿瘤药物临床试验偏离方案危害性评估中,65.80%的试验存在持续违背方案的情况,虽然不属于重大方案违背,但是反复、多次违背方案;26.84%的试验对违规事件不予以纠正。在综合评估中,A级风险28项(占12.12%,需采取相应措施并持续关注)、B级风险140项(占60.61%,需密切关注)、C类风险63项(占27.27%,风险在可控范围内)。结论抗肿瘤药物临床试验中,标准操作规程不依从,检验、检查方式及评估等超窗,抗肿瘤药物用法及用量不依从是导致方案偏离的主要原因。方案偏离的主体包括申办者、研究者、受试者等,且具有诸多危害性,相关部门应引起重视,动态监测项目风险等级取向,提高抗肿瘤药物使用合理性。

Objective To analyze the causes of protocol deviation in clinical trial of anti-tumor drugs,and to explore the corresponding management countermeasures.Methods A total of 560 drug clinical trials conducted in the Affiliated Hospital of Xuzhou Medical University from January 2021 to October 2023 were selected,and the causes of protocol deviation in clinical trials of anti-tumor drugs were retrospectively analyzed,and corresponding management countermeasures were formulated according to possible reasons.Results Among 560 clinical trials,231 cases(41.25%)were protocols deviation of anti-tumor drugs clinical trials,.The top three reasons were:Non-compliance with(SOP)(31.60%,),overwindow of inspection methods and evaluation(27.27%),non-compliance with the usage and dosage of anti-tumor drugs(18.61%).Among the harm of anti-tumor drug clinical trial deviation from the protocol,65.80%of the trials had continued violation of the protocol,which was not a major protocol violation,but repeated and multiple violations;26.84%of the trials did not correct the violation events.In comprehensive assessment,there were 28 A-level risks(12.12%,requiring using corresponding measures and continuous attention),140 B-level risks(60.61%,requiring close attention),and 63 C-level risks(27.27%,the risks were controllable range).Conclusion In clinical trials of anti-tumor drugs,noncompliance with SOP,over-window of inspection methods and evaluation,and non-compliance with the usage and dosage of anti-tumor drugs are the main reasons leading to the deviation of the program.The subjects of the deviation include sponsors,researchers,subjects,etc.,and it has many harms.Relevant departments should pay attention to the deviation and dynamically monitor the risk grade orientation of the project,and mprove the rationality of the use of antitumor drugs.