新版GCP施行后临床试验机构严重不良事件/可疑非预期严重不良反应报告现状分析与建议

Present situation analysis and suggestions for clinical trial SAE/SUSAR reports after the implementation of new edition of GCP

目的:分析新版药物临床试验质量管理规范(GCP)施行后,不同申办者严重不良事件(SAE)报告要求及可疑非预期严重不良反应(SUSAR)报告递交的现状和存在问题,探讨机构中完善SAE/SUSAR管理的可能环节,为指导试验各方进一步做好药物试验安全警戒工作,做好临床试验风险把控提出建议。方法:汇总分析某医院2020年7月1日—2020年12月31日期间,60家申办者的SAE报告表和64家申办者的SUSAR报告;按照同个申办者同种格式递交算1个研究样本,最终确定有效原始SAE报告表62份,SUSAR报告87份。结果:申办者所使用的SAE表中,61.3%为申办者自行设计模板,32.3%使用原国家食品药品监督管理总局(CFDA)SAE报告模板,6.4%使用电子数据采集(EDC)直接导出的SAE报告表;不同申办者提供的SAE表格存在差异,部分SAE表格设计存在字段重复设计、字段选项设置不合理、逻辑性问题、必要字段缺失、手写填报、表格设计不美观(字体较小等)等问题。机构接收的SUSAR中,有38家申办者进行过单个的个例SUSAR报告,其中使用自制表格模板的申办者共5家(13.116%),使用原CFDA表格模板的申办者共10家(26.31%),使用CIOMS表格模板的申办者共23家(60.53%)。统计结果显示目前递交单个个例报告主要采用CIOMS模板,而递交过行列汇总表的49家申办者使用行列格式、字段和递交频率均不相同,有待进一步统一规范。结论:业内暂无SAE报告表统一模板,申办者需加强对SAE报告表的规范设计和填写指引,提高研究者填写SAE报告的效率和个例安全性报告的数据质量。不同申办者递交机构和伦理的SUSAR存在较大差异,部分表格不足以支持安全信息审查要求,且递交SUSAR报告的时限和频率存在差异,以致机构和伦理委员会可能无法准确判断试验和受试者的风险程度。

Objective:To analyze the requirements of different sponsors for serious adverse event(SAE)reporting in clinical trials and the existing problems of suspected unexpected serious adverse reaction(SUSAR)report submission after the implementation of new edition of GCP thus to give possible suggestions to guide the trial parties in drug trial safety alert work and clinical trial risk control and improve the management of SAE/SUSAR.Methods:SAE reports of 60 applicants and SUSAR reports of 64 applicants from July 1,2020 to December 31,2020 were collected.Taking the report submitted by the same sponsor in the same format as one valid study sample,62 valid original SAE reports and 87 SUSAR reports were included for the analysis.Results:In the submitted SAE forms,61.3%used the template designed by the sponsors,32.3%used the original CFDA SAE report template,6.4%used SAE reports derived directly from EDC.Differences existed in SAE forms provided by different sponsors.For the design of these SAE forms,there were problems such as field duplicate,unreasonable setting of field options,logistic problems,missing necessary fields,handwritten filling out,unclear fonts,and so on.Among the SUSAR reports received by the institute,38 applicants reported individual SUSAR cases,5 out of which(13.116%)used self-made form templates,10 out of which used the original CFDA form template(26.31%),and 23 sponsors using the CIOMS form template(60.53%),showing that CIOMS template was the most commonly used for case reports.The 49 sponsors who submitted the column matrix used different formats,fields,and varied in time of submission.Conclusion:There is no unified template for the SAE report form in the industry.Sponsors need to strengthen the normative design and filling guidelines for the SAE report form,so that the researchers can fill out the SAE report more efficiently and ensure the data quality of individual case safety reports.There are significant differences in the SUSAR reports submitted to institutions and ethics committees among different applicants.Some forms are not sufficient to meet the requirements of security information review,and the time limit and frequency of submitting SUSAR reports are different.Under the above-mentioned situation institutions and ethics committees may not be able to accurately determine the risk levels of the clinical trials and subjects.So the SAE/SUSAR report forms need to be further unified and standardized.