临床试验中心对可疑且非预期严重不良反应报告的管理现状

Management status of suspected unexpected serious adverse reaction reports in clinical trial sites

目的了解2020版《药物临床试验质量管理规范》(新版GCP)发布后我国临床试验中心(中心)对可疑且非预期严重不良反应(SUSAR)报告的管理现状。方法登录药研社APP的"新版GCP下全国各家中心SAE/SUSAR报告要求汇总"平台,下载截至2021年6月30日汇集的各中心严重不良事件(SAE)/SUSAR报告要求,从SUSAR报告要求中提取中心关于SUSAR报告管理的要求,包括对临床试验申办者提交SUSAR报告的受理流程以及接收报告后的处理流程(是否要求研究者签收阅读和评估SUSAR报告,研究者向临床试验机构和伦理委员会提交SUSAR报告的时限和形式/格式,以及临床试验机构和伦理委员会接收研究者所提交SUSAR报告后的处理方式)。对收集到的数据进行描述性统计分析。结果纳入分析的SUSAR报告要求来自全国30个省级行政区的194家中心。对申办者提交SUSAR报告的受理流程,69.6%(135/194)的中心要求研究者签收阅读和评估SUSAR报告,24.2%(47/194)要求申办者将SUSAR报告提交给临床试验机构和/或伦理委员会,6.2%(12/194)无明确要求。对接收报告后的处理流程,85.1%(165/194)的中心要求研究者收到SUSAR报告后同时提交给临床试验机构和伦理委员会,13.4%(26/194)只要求向伦理委员会提交,1.5%(3/194)无明确要求。对致死/危及生命的SUSAR报告要求研究者在7 d内、按月度、按季度提交和无明确要求的中心分别占94.3%(183/194)、2.6%(5/194)、2.1%(4/194)和1.0%(2/194),对非致死/危及生命的SUSAR报告要求研究者在15 d内、按月度、按季度、每半年提交和无明确要求的中心分别占54.6%(106/194)、12.9%(25/194)、29.4%(57/194)、0.5%(1/194)和2.6%(5/194)。各中心对研究者提交SUSAR报告的形式/格式的要求不尽一致。关于伦理委员会对SUSAR报告的处理,仅12.9%(25/194)的中心要求以备案或上会方式处理,5.7%(11/194)的中心要求反馈处理意见。结论各中心SUSAR报告要求存在较大差异,部分中心对SUSAR报告的管理存在不符合新版GCP要求的问题,可能影响药物临床试验的风险防控,需要进一步予以规范。

Objective To understand the management status of suspected unexpected serious adverse reaction(SUSAR)reports in clinical trial sites in China after the release of the 2020 edition of Good Clinical Practice(new GCP).Methods The serious adverse event(SAE)/SUSAR reporting requirements files in each site as of June 30,2021 were downloaded after logging into the"summary of SAE/SUSAR reporting requirements in national sites under the new GCP"platform on an APP named Yaoyanshe(药研社).The requirements on SUSAR reporting management from above files in each site were extracted,including the acceptance process of the SUSAR reports submitted by the clinical trial sponsor and the processing process after receiving the reports(whether the investigator is required to sign for reading and evaluating the SUSAR reports,the time limit and form/format for the investigator to submit the SUSAR reports to the clinical trial institution and the ethics committee,and the processing method in the clinical trial institution and the ethics committee after receiving the SUSAR reports).The collected data were analyzed by descriptive statistics.Results The SUSAR reporting requirements files in the analysis were collected from 194-sites in 30 provincial administrative regions across the country.In the acceptance process of SUSAR reports submitted by the sponsor,69.6%(135/194)of the sites required the investigators to sign for reading and evaluating the SUSAR reports,24.2%(47/194)required the sponsor to submit the SUSAR reports to the clinical trial institution and/or ethics committee,and 6.2%(12/194)had no clear requirements.In the processing process after receiving the reports,85.1%(165/194)of the sites required the investigators to submit the SUSAR reports to the clinical trial institution and the ethics committee at the same time,13.4%(26/194)only required the investigators to submit them to the ethics committee,and 1.5%(3/194)had no clear requirements.Except that 1.0%(2/194)sites had no explicit requirements,for lethal/life-threatening SUSAR,94.3%(183/194),2.6%(5/194),and 2.1%(4/194)sites required investigators to submit the reports within 7 days,monthly,and quarterly,respectively.Except that 2.6%(5/194)sites had no explicit requirements,for non lethal/life-threatening SUSAR,54.6%(106/194),12.9%(25/194),29.4%(57/194),and 0.5%(1/194)sites required investigators to submit the reports within 15 d,monthly,quarterly,and semiannually,respectively.Requirements on the form/format of SUSAR reports for investigators in submitting were different among sites.Only 12.9%(25/194)of the sites required the ethics committee to filing or meeting in handling of SUSAR reports,and 5.7%(11/194)required feedback on the handling opinions from the ethics committee.Conclusions Requirements on SUSAR reporting are of great differences among sites.The management of SUSAR reports in some sites does not meet the requirements in the new GCP,which may affect the risk control in clinical trials and need to be further standardized.