中药复方治疗脑小血管病相关认知功能障碍随机对照试验的结局指标分析

Analysis of outcomes of randomized controlled trial on compound Chinese herbal medicine formulas in treatment of vascular cognitive impairment caused by cerebral small vessel

该研究旨在分析中药复方治疗脑小血管病相关认知功能障碍(vascular cognitive impairment caused by cerebral small vessel disease,CSVD-VCI)的随机对照试验(randomized controlled trial,RCT)结局指标,并针对不足提出发展建议。预先制定检索式,全面检索3个英文数据库,4个中文数据库和2个临床研究线上注册网站。筛选近十年相关RCT,提取信息,评估偏倚风险,分析其结局指标。检索获文献10461篇,剔重后余8681篇,筛选后纳入41篇RCTs,偏倚风险总体较高。其结局指标分为9大类,即临床症状指标、神经影像学指标、神经电生理指标、血液生化学指标、血液流变学指标、体征、中医证候积分、临床有效率、安全性指标。其中被纳入RCT报告频次最高的是血液生化学指标,报告率最高的是临床症状指标,有9个RCTs以中医证候积分为结局指标并报告相应评价标准。经分析,该领域RCT结局指标的应用目前存在着临床上的合理性和局限性,且在研究设计层面有所不足,即结局指标主次不分、设盲不足、报告不详、测量工具不统一、轻视"终点指标"。这些局限性和不足影响了中药复方治疗CSVD-VCI的RCT质量。建议未来研究者在顶层设计阶段做好有所依据的准备,并积极开展该领域核心指标集的筹建工作,最终提升临床研究质量。

The purpose of the study is to analyze the outcomes of randomized controlled trial(RCT)of Chinese herbal medicine formula(CHMF)in the treatment of vascular cognitive impairment caused by cerebral small vessel disease(CSVD-VCI),and provide suggestions for future studies in this field.Three English databases,four Chinese databases,and two online registration websites of clinical trials were searched with use of the search strategy established in advance.Relevant RCTs published in recent ten years were screened,and necessary information was extracted to assess the risk of bias and analyze the outcomes of these RCTs.As a result,a total of 10461 articles were retrieved,of which 8681 were kept after de-duplication,and 41 RCTs were included after screening,with a generally higher risk of bias.The outcomes of included RCTs were classified into 9 categories,namely,clinical symptom outcomes,neuroimaging outcomes,neuroelectrophysiological outcomes,blood biochemical outcomes,hemorheology outcomes,physical signs,syndrome scores of traditional Chinese medicine(TCM),clinical effective rate,and safety outcomes.Among them,the most frequently reported outcomes of included RCTs were blood biochemical outcomes,and clinical symptom outcomes showed the highest reporting rate.Besides,9 RCTs reported syndrome scores of TCM as the outcomes and illustrated corresponding evaluation criteria.The analysis showed that the application of RCT outcomes in this field had clinical rationality and limitations,and there were also some deficiencies in the trial design level,namely,no distinction between primary and secondary outcomes,insufficient blind methods,not detailed description of outcomes,disunity of evaluation tools,and despised endpoint outcomes.These limitations and deficiencies were negatively affecting the quality of RCTs of CHMF in the treatment of CSVD-VCI.Therefore,we suggest that future researchers should be well prepared in the top-level design stage,and actively construct the core outcome set of this field,so as to improve the quality of clinical trials.