体现患者重要结局的中成药临床效应个性化比较效果评价方法

Previous development of Chinese patent medicine has been criticised for their vaguely and broadly-defined indications and the repeated development of similar drugs, as well as for the simple mechnism of evaluating drug efficacy by monitoring the diesease or syndrom changes. To solve this problem, we introduced the concept of Comarative Effectiveness Research (CER) and established a new way of assessing drug efficacy in a clinical trial to test the effectiveness of chinese patent drugs in improving angina symptoms and patients' life quality. We recruited patients diagnosed with angina and grouped them according to different TCM syndroms and symptoms. Some studies included angina patients of the same syndrom, while others included patients with different syndroms. In both trials, drug's effects on disease and on the TCM syndrom were considered. Furthermore, Patient Important Outcome (PIO) as well as Patient Report Outcome (PRO) were reported and analysed with an anchor-based approach of defining the Minimal Clinically Important Difference (MCID). Also a unordered R×C contingency table was used to assess the heterogenity of the drugs' effects. Trough comparison we intended to find the best indications for a certain Chinese patent drug and the best timing in a disease progression for the drug to intervene. And finally we aim to set up and popularize an individualized CER evaluation method that highlights consideration for the drug's effects on disease as well as on the TCM syndrom and the assessment of PIO for clinical use of Chinese patent medicines.

临床定位不清、同类品种过多、适应症宽泛是目前中成药普遍存在的问题；单纯以"疾病"或"证候"为核心进行评价还难以全面阐释中成药的确切疗效。针对以上问题，本课题引入国际先进的比较效果研究理念，以改善冠心病心绞痛患者的主要症状和生活质量为目标，结合疾病效应和证侯效应，从"病同证同"和"病同证异"两个角度同时开展临床试验：采用"以病为纲，以证为类，以症为比"的方法进行患者的分类募集；融合患者重要结局与患者报告结局相结合的模式进行主要指标的建立和提取；利用"标准测量误差"法对"最小临床意义变化值"进行测量，实现主要结局的定性、定量分析；运用"双向无序R×C症状-用药列联"法开展中成药症状疗效的异质性分析和多层面评价。通过中成药优势症状群的比较和发现，明确各自功能主治定位，探索形成体现 "病证结合，病症并重"的评价模式，建立中成药患者重要结局临床效应个性化比较效果评价方法，并转化应用。

背景：证候是中医的精髓，任何中医治疗必须基于辨证论治基础上才能发挥确切的疗效；中成药是中医的现代药物剂型，中成药的临床应用也必须在中医证候的理论指导下合理应用。目前，由于大量非中医人员对中成药的非对证使用，严重影响了中成药临床疗效的发挥和评价。长期以来，中医对稳定性心绞痛（SAP）的发病和治疗积累了一定的经验且疗效明确，据统计，我国超过70%的冠心病患者长期使用中成药进行治疗，而我国批准治疗冠心病的中成药多达349种，剔除同名同方而剂型不同的品种，尚有207种。因此，如何对不同品种的中成药进行合理的选择和应用成为日益突出的临床问题。研究内容：本课题以SAP患者为研究对象，拟通过两个探索性的试验建立中成药个性化效应CER评价方法：试验1，基于“气虚血瘀”的辨证，选取芪参益气滴丸和通心络胶囊开展“病同证同”研究；试验2，基于“气虚血瘀”和“气滞血瘀”的辨证，选取芪参益气滴丸和复方丹参滴丸开展“病同证异”研究。方法：本课题将采用标准测量误差法（SEM），针对患者重要性临床结局（PIO），测量最小临床意义变化值（MCID），通过个性比较、综合分析，实现不同药物疗效间的比较效果分析（CER）和单个药物绝对疗效的患者报告结局评价（PRO），最终实现中成药个性化临床效应的多层面评价。结果：通过本课题的研究，已经对治疗SAP3种中成药的治疗特点分别进行了独立和比较评价，并形成了同类中成药个性疗效CER评价方法；意义：本课题基于“病证结合”理论和CER理念，以患者的症状疗效为突破口，以治疗SAP上市后中成药2个临床试验为研究载体，旨在构建中成药个性疗效的CER评价方法，为进一步区分同类中成药的疗效特点，促进临床合理用药发挥作用。