心血管病中西药联用临床安全性评价医患共建必备指标的优选方法

There are some problems in clinical safety assessment of clinical trials for traditional Chinese medicine (TCM). First, it is difficult to determine TCM’s clinical safety when it is combined with western medicine. Second, the patient-reported adverse events/effects reporting is insufficient. Third, clinical safety outcome reporting is diverse in similar clinical trials. These problems lead to some clinical trials cannot provide sufficient evidence to clinical practice. Based on the previous research experience in developing core outcome set for beneficial outcomes evaluation, this project proposes to develop the preferred method for the doctor-patient co-operated necessary outcomes in clinical safety evaluation of integrated traditional Chinese and western medicine. Based on the known adverse effects of western medicine, it will help researchers assess if TCM has the effect of attenuating or increasing adverse events/effects when Chinese medicine is combined with western medicine. Doctor-patient co-operated core outcome set for safety assessment will improve the reliability of symptomatic adverse events/effects reporting. The core outcome set and its measurement instrument for clinical safety evaluation will decrease the heterogeneity of safety outcomes reporting, so that more clinical trials may be included in systematic reviews to provide evidence for clinical practice. This project takes cardiovascular disease as an example to explore the method of developing doctor-patient co-operated necessary outcomes for safety evaluation. The research methods of developing doctor-reported core outcome set for safety evaluation and the patient-reported core symptom set for adverse events/effects and their measurement instruments include systematic review, semi-structured interview, Delphi survey, consensus meeting and so on. Semi-structured interview and cross-sectional survey will be conducted thereafter to assess the validity and reliability of measurement instruments. This project may bring new ideas for safety evaluation of integrated traditional Chinese and western medicine’s clinical trials.

中医临床研究中安全性评价存在的主要问题有：中西药联用难以真实反映中药不良反应；患者报告的不良事件/反应不充分；同类临床研究中安全性评价指标差异大。这些问题导致诸多临床研究不能为中药临床安全应用提供证据。在前期有效性评价核心指标集研究基础上，本项目将探索中西药联用临床安全性评价医患共建必备指标的优选方法。通过报告西药已知不良事件/反应，帮助研究者相对真实地评估中西药联用是否增加不良事件/反应的发生；医患共建能提高症状性不良事件/反应报告的可靠性；临床安全性评价核心指标集及评价工具可提高同类临床研究中安全性指标报告的一致性，使更多研究能纳入系统评价。本项目以心血管病为例，通过系统评价、半结构化访谈、德尔菲调查、共识会议等方法，形成医生报告的临床安全性评价核心指标集和患者报告的不良事件/反应核心症状集及相应的评价工具；通过半结构化访谈和横断面调查评估工具性能，为中西药联用临床安全性评价提供方法。

中医临床研究中安全性评价存在的主要问题有：中西药联用难以真实反映中药不良反应；.患者报告的不良事件/反应不充分；同类临床研究中安全性评价指标差异大。这些问题导致.多临床研究不能为中药临床安全应用提供证据。本项目以心血管病（房颤、高血压、心绞痛、心肌梗死、心力衰竭、缓慢型心律失常等）为例，探索了中西药联用临床安全性评价医患共建必备指标的优选方法。本项目通过系统评价、半结构化访谈、德尔菲调查、共识会议等方法形成医生报告的临床安全性评价核心指标集。其中医生报告核心不良事件如下：①所有心血管病的核心不良事件：过敏反应、心律失常、心脏骤停、低血压、死亡、出血（除外中枢神经系统）。②房颤核心不良事件：血栓栓塞事件、颅内出血、缺血性脑卒中、短暂性脑缺血发作、心力衰竭、急性心肌梗死。③高血压核心不良事件：急性心肌梗死、高钾血症、急性肾损伤、缺血性脑卒中。④冠心病核心不良事件：血栓栓塞事件、休克。其中心绞痛的核心不良事件为颅内出血，心肌梗死的核心不良事件为心源性休克、再发心肌梗死，心力衰竭的核心不良事件为肾功能不全、心源性休克、不稳定性心绞痛、急性心肌梗死。⑤高血压核心不良事件：急性心肌梗死。患者报告的核心症状如下：①所有心血管病的核心症状：心悸、胸闷、头晕、晕厥。②房颤的核心症状：胸痛、恶心、呕吐。③高血压的核心症状：胸痛、头痛、乏力、全身性水肿、局限性水肿、呼吸困难、失眠、皮疹、视力模糊、耳鸣。④冠心病核心症状：胸痛、头痛、腹痛。⑤缓慢型心律失常核心症状：乏力、多汗、烦躁。在此基础上，本研究进一步形成了医患评价标准。通过医患共建形成的核心不良事件集及评价标准，可以帮助研究者相对真实地评估中西药联用是否增加不良事件/反应的发生；医患共建能提高症状性不良事件/反应报告的可靠性；临床安全性评价核心指标集及评价工具可提高同类临床研究中安全性指标报告的一致性，使更多研究能纳入系统评价，提高研究价值。