Li Qing, Jin Xin-Yao, Zhou Xia, Pang Wen-Tai, Wang Ke-Yi, Li Nan, Zheng Wen-Ke
Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.
Tianjin University of Traditional Chinese Medicine Tianjin 301617, China Evidence-based Medicine Center, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.
Zhongguo Zhong Yao Za Zhi. 2021 Feb;46(3):712-721. doi: 10.19540/j.cnki.cjcmm.20201015.501.
This study aimed to comprehensively analyze and compare the differences of different clinical study types currently published in the safety evaluation of Xuebijing Injection. Six databases, namely the Cochrane Library, PubMed, EMbase, CNKI, VIP and Wanfang database, were electronically retrieved to collect all types of studies on the safety of Xuebijing Injection, including randomized controlled trials, case-controlled studies, cohort studies, systematic reviews, and centralized monitoring studies of clinical safety(hospital), in order to comprehensively and objectively evaluate the safety of Xuebijing Injection, and analyze the differences of different research results. A total of 211 literatures were included, involving a total of 46 384 patients treated with Xuebijing Injection, and 423 adverse reactions(ADRs) occurred. They included 191 randomized controlled trials, 3 cohort studies, 15 systematic reviews, and 2 centralized monitoring studies of clinical safety(hospital), and the incidence of adverse reactions was 2.54%(common), 2.31%(common), 0.95%(occasionally), and 0.50%(occasionally). More than half of the 423 cases of ADRs occurred in skin and adnexal system(151 cases) and gastrointestinal system(65 cases), including such manifestations as rash, skin itching, nausea and vomiting, diarrhea. The degree of ADRs was mild. Randomized controlled trials showed that the incidence of ADR was the highest when Xuebijing Injection was used for malignant tumor and multiple organ failure. And the systematic evaluation showed that the incidence of ADR was the highest when Xuebijing Injection was used for spontaneous peritonitis of liver cirrhosis. In conclusion, different study types could lead to significant differences in the results of drug safety evaluation. Sample size, study type, and quality control are the main factors for biased results. Due to large sample size and high-quality, centralized monitoring studies become the better clinical safety evaluation model of drugs at present, and full life cycle management could more objectively reflect drug safety and guide clinical rational drug use.
本研究旨在全面分析和比较目前已发表的不同临床研究类型在血必净注射液安全性评价中的差异。通过电子检索Cochrane图书馆、PubMed、EMbase、中国知网、维普和万方数据库这6个数据库，收集血必净注射液安全性的各类研究，包括随机对照试验、病例对照研究、队列研究、系统评价以及临床安全性集中监测研究（医院），以全面、客观地评价血必净注射液的安全性，并分析不同研究结果的差异。共纳入211篇文献，涉及使用血必净注射液治疗的患者共46384例，发生不良反应423例。其中包括191项随机对照试验、3项队列研究、15项系统评价以及2项临床安全性集中监测研究（医院），不良反应发生率分别为2.54%（常见）、2.31%（常见）、0.95%（偶见）和0.50%（偶见）。423例不良反应中，超过半数发生在皮肤及附件系统（151例）和胃肠道系统（65例），表现为皮疹、皮肤瘙痒、恶心呕吐、腹泻等。不良反应程度较轻。随机对照试验显示，血必净注射液用于恶性肿瘤和多器官功能衰竭时不良反应发生率最高。而系统评价显示，血必净注射液用于肝硬化自发性腹膜炎时不良反应发生率最高。综上所述，不同研究类型会导致药物安全性评价结果存在显著差异。样本量、研究类型和质量控制是导致结果偏倚的主要因素。由于样本量大且质量高，临床安全性集中监测研究成为目前较好的药物临床安全性评价模式，全生命周期管理能更客观地反映药物安全性并指导临床合理用药。
