Wang Zhi-Fei, Zhang Qiang, Xie Yan-Ming
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2022 Mar;47(6):1484-1492. doi: 10.19540/j.cnki.cjcmm.20211124.501.
Based on Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), this study aims to sort out the clinical evidence of Huangkui Capsules(HC) in the treatment of chronic kidney diseases in aspects of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) from real-world data, secondary literature evaluations, questionnaires, and public data, with the methods in evidence-based medicine, epidemiology, pharmacoeconomics, and health technology. Furthermore, with multi-criteria decision analysis(MCDA) model and CSC v2.0, the clinical value of the medicine is comprehensively assessed. All the above are to highlight the advantages and characteristics of HC and lay a basis for scientific decision-making by the medical management department. The dimensions are graded A, B, C, or D. According to the conclusions from phase Ⅳ clinical trial, spontaneous reporting system(SRS), systematic review and Meta-analysis, acute toxicity and long-term toxicity tests, it mainly results in the adverse reactions of nausea, abdominal distension, vomiting, pruritus, rash, and good prognosis in patients. According to the available research, the safety evidence is sufficient and the risk is controllable, so the safety of this medicine is grade B. According to Meta-analysis, HC in combination with conventional drugs in the treatment of chronic kidney disease is superior to conventional drugs alone in reducing urinary protein, serum creatinine concentration, and blood urea nitrogen. In addition, HC combined angiotensin receptor blocker(ARB) or angiotensin converting enzyme inhibitor(ACEI) is outstanding in improving total clinical effective rate, reducing 24 h urinary protein quantity, urinary albumin excretion rate, serum creatinine concentration, triglyceride, and total cholesterol in the treatment of diabetic nephropathy as compared with ARB or ACEI alone. As for chronic nephritis, the application together with ARB or ACEI can raise the total effective rate, reduce 24 h urinary protein content, serum creatinine concentration, and blood urea nitrogen, and delay the progress of the disease. HC boasts high-quality evidence in treating chronic kidney disease, diabetic nephropathy, and chronic nephritis. It has obvious clinical significance in treating chronic kidney disease and thus its efficacy in this aspect is grade B. It has outstanding clinical significance for diabetic nephropathy and chronic nephritis and corresponding and the effectiveness is grade A. As for the pharmacoeconomic value, HC combined with ARB or ACEI is more economical in the treatment of chronic kidney disease than Bailing Capsules combined with ARB or ACEI, with high-quality evidence, and thus the economy of the formula is grade B. HC is a key solution to the high urinary protein in patients with hypotension and chronic kidney disease. The innovation is evidenced by the methods to ensuring drug supply, community-level supply, drug safety, effectiveness, and reasonable price, as wells as the aspects of enterprise philosophy, equipment management, research and development in process and technology, enterprise management and marketing. Thus, the prescription is grade A in innovation. The suitability, as evidenced in drug administration, technical management, drug storage, information service, and medication, is grade B. The course of the medicine is affordable, and it is accessible in a wide range of areas and hospitals. Thus, the accessibility is grade A. HC was developed from an in-hospital preparation, with application in numerous patients and thus large-scale real-world data. As a result, HC is grade B in terms of characteristics of traditional Chinese medicine. After comprehensive evaluation, the clinical value of HC in treating chronic kidney disease is class B, and that for diabetic nephropathy and chronic nephritis is class A. The result is of great reference value for the basic clinical medication management.
基于《药物临床综合评价管理指南（2021年试行版）》，本研究旨在从真实世界数据、二次文献评价、问卷调查及公共数据等方面，运用循证医学、流行病学、药物经济学及卫生技术等方法，梳理黄葵胶囊（HC）在治疗慢性肾脏病方面的安全性、有效性、经济性、创新性、适宜性、可及性及中医药特色（“6 + 1”维度）的临床证据。此外，运用多准则决策分析（MCDA）模型及CSC v2.0对该药物的临床价值进行综合评估。以上所有均为突出HC的优势与特色，为医疗管理部门的科学决策奠定基础。各维度分为A、B、C或D级。根据Ⅳ期临床试验、自发报告系统（SRS）、系统评价及Meta分析、急性毒性和长期毒性试验的结论，其主要不良反应有恶心、腹胀、呕吐、瘙痒、皮疹，患者预后良好。根据现有研究，安全性证据充分，风险可控，故该药物的安全性为B级。根据Meta分析，HC联合传统药物治疗慢性肾脏病在降低尿蛋白、血清肌酐浓度及血尿素氮方面优于单纯使用传统药物。此外，在治疗糖尿病肾病方面，HC联合血管紧张素受体阻滞剂（ARB）或血管紧张素转换酶抑制剂（ACEI）与单独使用ARB或ACEI相比，在提高临床总有效率、降低24小时尿蛋白量、尿白蛋白排泄率、血清肌酐浓度、甘油三酯及总胆固醇方面表现突出。对于慢性肾炎，与ARB或ACEI联合应用可提高总有效率，降低24小时尿蛋白含量、血清肌酐浓度及血尿素氮，并延缓疾病进展。HC在治疗慢性肾脏病、糖尿病肾病及慢性肾炎方面拥有高质量证据。其在治疗慢性肾脏病方面具有明显临床意义，因此该方面疗效为B级。对糖尿病肾病和慢性肾炎具有突出临床意义，相应有效性为A级。在药物经济学价值方面，HC联合ARB或ACEI治疗慢性肾脏病比百令胶囊联合ARB或ACEI更具经济性，证据质量高，故该配方的经济性为B级。HC是治疗低血压合并慢性肾脏病患者高尿蛋白的关键解决方案。其创新性体现在确保药物供应、社区层面供应、药物安全、有效性及合理价格的方法，以及企业理念、设备管理、研发过程与技术、企业管理及营销等方面。因此，该处方的创新性为A级。在给药、技术管理、药品储存、信息服务及用药等方面体现的适宜性为B级。该药物疗程费用可承受，在广泛地区和医院均可获得。因此，可及性为A级。HC由院内制剂研发而来，应用于众多患者，拥有大规模真实世界数据。因此，在中医药特色方面为B级。综合评价后，HC治疗慢性肾脏病的临床价值为B级，治疗糖尿病肾病和慢性肾炎的临床价值为A级。该结果对基层临床用药管理具有重要参考价值。
