Background: Patient-focused drug development (PFDD) is an important direction in the field of medical research and is of great significance to the development of medicine. In recent years, PFDD and real-world study (RWS) have gained much interest, of which both have their advantages. This study aims to promote research methods innovation and optimize clinical research design and implementation. Methods: After a brief introduction of PFDD and RWS, this review focused on the comparison of clinical trials of PFDD and RWS in terms of objectives, Population, Intervention, Comparator, Outcome (PICO) elements, research team members, data acquisition, and research key points, and clarified the feasibility and significance of “patient-focused RWS” research model. Results: PFDD emphasized that patients’ needs as well as the willingness and satisfaction of patients should be considered throughout the whole research process and the patient experience data should be collected during the study development and drug use. RWS emphasized the facticity of research implementation environment and the breadth of patient sources, which concerned the problem of the extrapolation of study results, the clinical localization, and patient applicability of the target drug. However, there is a connection between both of the above. Both clinical trials of PFDD and RWS bring benefits to patients. Conclusions: Combining PFDD idea and RWS research method to carry out new research will maximize the benefits for patients. The study model combining the PFDD concept with RWS can facilitate drug development and dissemination, which can be popularized and applied in various research areas. This study can innovate research methods and provide new ideas for future research.

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.

Objective: This study aimed to systematically review and depict the current studies of traditional Chinese medicine for the mental health of patients with coronavirus disease 2019 (COVID-19).Methods: A scoping review was conducted by searching PubMed, Web of Science, CNKI, Wanfang database, VIP database, and SinoMed, with the retrieval time being from the establishment of the database to April 18, 2022. The basic information of the included studies, objective, design, types of patients, interventions, outcomes, etc., was reviewed and summarized narratively. Method:ological quality was assessed using the Cochrane Risk of Bias assessment tool, the methodological index for non-randomized studies or the Newcastle-Ottawa scale.Results: We identified 30 traditional Chinese medicine (TCM) studies from six databases. Among them, finished randomized controlled trials (n = 16) accounted for most of the studies, followed by single-arm studies (n = 9). In terms of study theme, 20 studies defined the mental health of patients with COVID-19 as the research theme. Psychological assessment was included in the inclusion criteria (performed before participation) of nine studies, whereas the other studies only mentioned the mental outcomes. TCM interventions included TCM exercises (Yijinjing, Baduanjin, Liuzijue, Taichi), acupoint stimulation (auricular and body points), moxibustion, decoction, or granules based on TCM syndrome differentiation, decoction, or granules with fixed formulae (Baidu Jieduan granules, Xuanfei Baidu decoction, and Qingfei Paidu decoction), Chinese patent medicine (Jinhua Qinggan granules), TCM psychological therapy (TCM ideological therapy, TCM five-tone therapy, and TCM psychological sand table), and TCM nursing (dialectical care, dialectical diet, and psychological counseling). Anxiety and depression were the main outcomes evaluated in regard to mental health in patients with COVID-19. The limitations of methodological quality were predominantly from follow-up, blinding, and registration. Positive results were reported by 27 studies (90%, n = 30).Conclusion: We summarized the existing literature about the impact of TCM on mental health in patients with COVID-19. The number of studies evaluating the impact of TCM on mental health is encouraging, but overall methodological quality was low. Several TCM interventions warrant further evaluation, particularly among populations outside of China, for the purpose of establishing supporting evidence. More importantly, research with stronger methodological quality needs to be developed.

核心指标集是通过一系列规范的研制过程,形成某种疾病所有相关临床试验必须报告的、统一的、标准化的最小指标集合.确定哪些指标为核心结局指标,需要经过不同利益群体的高级代表一致性认定、达成共识.共识方法设计的科学性和实施的透明化,决定了最终形成的核心指标集的质量.因此,在中医药核心指标集(Core Outcome Set for Traditional Chinese Medicine,COS-TCM)研制过程中共识过程的设计和实施至关重要.本文对COS-TCM研制中共识方法的实施要点进行归纳总结,以期为中医药核心指标集研究的开展提供方法学借鉴.

Background Treatment of chronic pulmonary heart disease (CPHD), a common disease, has over recent years been studied using traditional Chinese medicine (TCM) due to many high-profile benefits. These can be evaluated by the measurement and analysis of related outcomes. Because of selective reporting bias and the heterogeneity of study outcomes, it is not possible to combine similar studies in a meta-analysis. Consequently, not only does the low quality of original studies fails to support evidence-based decision-making, but also the value of those clinical studies cannot be evaluated. To solve these problems, the development of a core outcome set for traditional Chinese medicines for the treatment of chronic pulmonary heart disease (COS-TCM-CPHD) is required. Methods The development is conducted in five steps: (1) a library of outcomes through systematic review, the retrieval of libraries from two clinical trials registries, and semistructured interviews is established; (2) following data extraction and analysis of the library of outcomes, each outcome can be classified into seven outcome domains, including TCM disease, symptoms/signs, physical and chemical testing, quality of life, long-term prognosis, economic evaluation, and adverse events to form a preliminary list of outcomes; (3) stakeholder groups for participation are selected; (4) stakeholder groups are invited to participate in two rounds of Delphi surveys to score outcomes and provide additional outcomes; (5) a consensus meeting is organized to produce the final COS-TCM-CPHD. Discussion. The protocol is consistent with the guidelines defined by the Core Outcome Set-STAndardised Protocol (COS-STAP) statement and formulated with reference to Core Outcome Set-STAndards for development (COS-STAD). The COS-TCM-CPHD will improve the consistency of study reports and reduce publication bias, thereby improving the quality of TCM clinical trials and decision-making for evidence-based medicine. The study has been registered on the COMET website (http://www.comet-initiative.org/Studies/Details/1677).

[目的]基于中医药系统评价/Meta分析证据库(SMD-TCM),对口服益气活血类中成药治疗冠心病心绞痛的系统评价/Meta分析进行再评价,并验证SMD-TCM各部分功能.[方法]计算机检索SMD-TCM,获取并筛选文献,借助SMD-TCM对口服益气活血类中成药治疗冠心病心绞痛的系统评价/Meta分析进行再评价.[结果]纳入符合标准的系统评价/Meta分析26篇,再评价结果显示:疗效方面,纳入研究均报告口服益气活血类中成药治疗冠心病心绞痛具有疗效;安全性方面,19篇研究对安全性进行了相关报告,7篇未报告,且存在报告不清晰、未明确区分组别、未报告发生患者例数等问题;方法学质量和报告规范方面,纳入研究均存在一定的不足,具有一定改善空间.[结论]当前,SMD-TCM各项功能运行正常,将系统评价再评价研究的时间大幅缩短,切实提升了科研效率,节约了时间及人力成本.

核心指标集(Core Outcome Set,COS)的研制是解决当前临床试验结局指标异质性大、发表偏倚、不重要、不公认等共性问题的关键途径.为推动核心指标集研究发展,中国临床试验核心指标集研究中心(Chinese Clinical Trial Core Outcome Set,ChiCOS)建立了专业化数据库平台.本文从ChiCOS数据库平台的架构设计、平台功能与有效性试验核心结局指标(Core Outcome Measures in Effectiveness Trials,COMET)数据平台特点比较等方面,对ChiCOS数据库平台进行介绍,以期更好地为核心指标集研究提供技术支持.

目的 评价中药治疗室性早搏系统评价或Meta分析的方法学质量和结局指标的证据质量,以期为中药治疗室性早搏提供一定证据支持.方法 计算机检索知网、万方、维普、SinoMed、PubMed、The Cochrane library和EMbase数据库,搜集已发表的中药治疗室性早搏的系统评价或Meta分析,检索时限从建库至2020年9月29日.有2名研究员应用AMSTAR2量表、GRADE评分分别评价其方法学质量和证据质量.结果 共筛选出13篇中药治疗室性早搏系统评价/Meta分析,AMSTAR2量表方法学评价整体偏低,只有1篇评价为中级,其余2篇评价为低、10篇评价为极低.GRADE对结局指标证据评价:5个结局指标评为中级,16个结局指标评为低级,21个结局指标评为极低级.结论 中药治疗室性早搏具有一定临床疗效,能够明显降低室早频数,改善室早心悸、胸闷等症状,且不良反应发生率低.但中药治疗室性早搏的系统评价/Meta分析存在方法学质量问题,结局指标的证据质量偏低,建议临床研究人员重视方法学的培训和应用,以期有高质量的原始研究和系统评价的产出,从而能够更好的为临床提供循证证据支持.

To systematically evaluate the efficacy and safety of Gongxuening Capsules in the treatment of abnormal vaginal bleeding after medical abortion. CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to comprehensively collect the clinical randomized controlled trials(RCTs) of Gongxuening Capsules for treatment of abnormal vaginal bleeding after medical abortion from the establishment of the databases to October 10, 2020. Literature screening, data extraction and quality evaluation were conducted independently by two system reviewers according to the inclusion and exclusion criteria. Cochrane Handbook bias risk assessment tool was used for the literature methodology quality evaluation, RevMan 5.3 software was used for Meta-analysis, and the evidence quality of outcomes was evaluated by the evidence quality grading system(GRADE). A total of 16 RCTs were inclu-ded. The results of Meta-analysis showed that as compared with the western medicine treatment alone, the addition of Gongxuening Capsules to the western medicine treatment can reduce the amount of vaginal bleeding(RR=1.23, 95%CI[1.19, 1.27], P<0.000 01), shorten vaginal bleeding time(RR_(≤15 d number of people)=1.39, 95%CI[1.31, 1.48], P<0.000 01; MD_(number ofdays)=-1.20, 95%CI[-1.66,-0.74],P<0.000 01). However, there was no obvious advantage in abortion effect(RR=1.02, 95%CI[0.99, 1.06], P=0.14) and menstrual recovery(MD=-0.35, 95%CI[-0.96, 0.25], P=0.25). The results of GRADE showed that the grading level was low for vaginal bleeding volume and vaginal bleeding time, and extremely low for abortion effect and mens-trual recovery. In terms of safety, 16 studies reported adverse events. Only one study showed no adverse events and the rest showed transient nausea, vomiting, stomach burning, upper abdominal discomfort and other gastrointestinal symptoms. The results show that the addition of Gongxuening Capsules to the application of western medicine in treatment of drug abortion can reduce the amount of vaginal bleeding and shorten vaginal bleeding time, but the abortion effect and menstrual recovery have no obvious advantages. The use of Gongxuening Capsules helps to achieve less adverse reactions and higher safety. Due to the small sample size of the included studies and many methodological quality problems, no conclusions with clinical guidance value can be obtained. Large sample-zise, high-qua-lity randomized controlled trials are still needed for further verification.

[目的]通过整理中药治疗慢性肺源性心脏病临床随机对照试验的结局指标,为制定慢性肺源性心脏病的核心指标集提供基础数据.[方法]计算机检索中国知网(CNKI)、万方(WanFang)、维普(VIP)、中国生物医学文献服务系统(SinoMed)、PubMed、Cochrane Library和Embase数据库,收集中药干预治疗慢性肺源性心脏病随机对照试验数据.论文发表时间限定为2018年.由两位作者严格按照纳入和排除标准独立筛选文献,提取资料,若有分歧,经商讨决定.[结果]经筛选最终纳入68篇慢性肺源性心脏病随机对照试验,共采用49个结局指标.根据指标功能属性,分为中医症状/证候、症状体征、理化检查、生活质量、远期预后、经济学评估和安全性事件7个指标域.排前15位的结局指标依次为临床有效率、血气分析、超声心动图、不良反应、脑钠肽、肺功能指标、中医证候积分、血液流变学、肺动脉压、生活质量、6 min步行试验、心功能分级、血清学指标、症状缓解时间、C-反应蛋白.[结论]中药治疗慢性肺源性心脏病的临床试验采用的结局指标存在差异性大、报告不规范等问题,需要开展核心指标集研究,提高临床研究的价值.

Background Traditional Chinese medicine (TCM) plays an important role in contributing to the public health in China. However, non-standardized outcomes in TCM related studies posed great difficulty in data synthesis for healthcare decisions. An agreed set of standardized outcomes, or termed as a core outcome set (COS), can solve this existing problem of outcome heterogeneity. This review aimed to analyze outcome heterogeneity, assess the quality of outcome reporting and providing a list of potential outcomes for COS development of SAP using TCM. Methods 8 literature databases were searched to identify clinical studies about TCM for SAP (SAP-TCM) of yearly samples of 2005, 2010, 2015, 2016, 2018 and 2019. 2 clinical registry databases were searched from inception to October 2020. Outcomes definition, measurement methods and time-point were extracted and categorized into 7 themes which include clinical symptoms and signs, physical and chemical examination, TCM-related outcomes, adverse events, quality of life, long-term prognosis and economic evaluation. Timing and quality assessment of the outcomes reported were analyzed and evaluated. Results A total of 1166 studies were included from 12962 potential studies, involving 111426 patients. 231 outcomes were identified and a total of 89 outcomes reported at least twice in the studies. The most commonly reported theme was clinical symptoms and signs. The most frequently reported outcomes were total rate of ECG efficiency and angina attack in clinical studies of published literature and clinical registries databases respectively. Outcomes reported in a single study ranged from 1 to 15, and 5 outcomes on average per study. 80% of the studies lack reporting of primary outcomes. A wide variation of measurement instruments or methods was used. A range of 1–17 measurement time-points were recorded. Quality assessment of outcome reporting was generally low, with 65.6% of the studies scoring 3 to 4 points. Conclusion Outcomes reported in studies on SAP-TCM are heterogeneous. A lack of standardization complicates comparisons of outcomes across studies. Developing a COS for SAP-TCM could contribute to the standardization of outcome reporting and offer a stronger evidence for health decision-making.

临床研究设计中选择合适的结局指标对评价干预措施的作用至关重要.在同类疾病相关临床试验中建立必须报告的、统一的、标准化的最小指标集合,即核心指标集(COS),是规范指标使用的关键途径.回顾COS产生背景和发展历程,揭示COS研究的重要意义,并结合实际情况介绍COMET及ChiCOS两大数据库注册平台的各自特点和局限性,对不同数据库平台的合理选择使用进行分析.目前COS研制方法尚不成熟,结合中医药研究的特殊性,阐述了中医药COS研制难点在于原始结局指标需标准化、指标分类之间存在交叉性、广泛征求国际性共识实施困难大、中医药疗效特色指标在COS中体现不足等,以期为我国临床试验COS各利益相关群体提供参考.

德尔菲调查是核心指标集研究中共识环节的重要群体决策方法.中医药核心指标集研究中德尔菲实施过程规范性很重要,实施过程质控不严会影响中医药核心指标集(Core Outcome Set of Traditional Chinese Medicine,COS-TCM)研究的可靠性.为此,本文将对COS-TCM研制中德尔菲调查研究实施过程中问卷的设计、调查方式、平台、轮次、指标遴选原则、条目变动原则、评分与反馈机制、偏倚及丢失数据的控制、参与者等要点进行总结,以期为其他COS-TCM研究德尔菲法的开展提供方法学指导.

Introduction Chronic heart failure (CHF) is a serious and advanced stage of various cardiovascular diseases and portends poor prognosis. An increase in clinical studies has reported the effectiveness of traditional Chinese medicine (TCM). For example, intravenous Chinese medicine can significantly improve cardiac function and biomarkers in patients with CHF. However, there exists inconsistency, lack of practicality and unclear reporting of outcomes in these clinical trials causing difficulty in the comparison of results across similar studies during data synthesis. A core outcome set (COS) can help in the standardisation of outcomes reported across studies from the same healthcare area. The aim of this study is to develop a COS on TCM for CHF (COS-TCM-CHF) to reduce heterogeneity in reporting and improve quality assessment in clinical trials to support data synthesis in addressing the effectiveness of TCM treatment. Methods and analysis This study will include constructing an outcome pool which will identify potential outcomes through systematic reviews of TCM randomised clinical trials, two clinical registry databases, semi-structured interviews of patients and the clinicians’ questionnaire. According to the characteristics of TCM and a taxonomy recommended by the Core Outcome Measures in Effectiveness Trials (COMET) initiative, all outcomes in the outcome pool will be classified into different domains. A preliminary list of outcomes which will then be used in the Delphi survey is generated using a certain criteria based on the length of the pool. The Delphi survey will include two rounds with seven key stakeholder groups to select candidate items for a consensus meeting. A final COS-TCM-CHF will be developed at a face-to-face consensus meeting involving representatives from the different stakeholders. Ethics and dissemination Ethical approval of this study has been granted by Evidence-based Medicine Centre of Tianjin University of Traditional Chinese Medicine Research Ethics Committee (TJUTCMEC201200002). We will disseminate our research findings of the final COS on the website of Chinese Clinical Trials for Core Outcome Set, with open access publications and present at international conferences to reach a wide range of knowledge users. Trial registration number http://www.comet-initiative.org/studies/details/1486.

[目的]分析中药注射剂治疗非小细胞肺癌随机对照试验(RCT)的结局指标,为构建肺癌临床试验的核心指标集提供基础.[方法]计算机检索中国知网数据库(CNKI),万方数据(WanFang),维普数据库(VIP),中国生物医学文献服务系统(SinoMed),Embase,Cochrane library,Web of Science和PubMed 8个数据库.以2018年发表的文献为样本,由2位作者严格按照纳入与排除标准独立筛选文献、提取资料,如有分歧,经讨论解决.[结果]纳入94个RCT研究中共包含8450位患者,共采用64种结局指标.单个研究指标数量最少为1个,最多达10个,平均每个研究结局指标的数量为3.3个.使用频次排前10位的结局指标依次为:临床疗效、不良反应、生活质量、免疫功能、肿瘤标志物水平、卡氏(KPS)评分、毒副作用、T细胞亚群变化、中医证候积分、总生存期.94个RCT研究普遍存在结局指标临床相关性差、缺少中医药特色指标、指标组合随意、指标测量时点多样、时间跨度较大、指标测量工具不一致等问题.[结论]中医药治疗非小细胞肺癌临床试验结局指标存在较多问题,需要建立核心指标集提高相关临床研究质量.

疗效评价指标是影响中医药临床研究质量的一个重要因素.自2011年将核心指标集(Core Outcome Set,COS)的概念引入中医药研究,已经开展了多项实践研究,中医药核心指标集(Core Outcome Set of Traditional Chinese Medicine,COS-TCM)的研究方法逐渐发展.本文分析COS-TCM的研究现状,总结各项工作开展情况,为下一阶段的发展提供基础和方向.

To systemically evaluate the efficacy and safety of Maxing Shigan Decoction in the treatment of community acquired pneumonia(CAP) and provide a reference for the treatment of CAP. Databases of CNKI, Wanfang, VIP, SinoMed, EMbase, Cochrane Library, Web of Science and PubMed were searched(from inception to May 30, 2020) to screen the randomized controlled trials(RCTs) of Maxing Shigan Decoction in treating CAP. Two authors independently screened and selected relevant literature and extracted data based on the inclusion and exclusion criteria. Any disagreement or differences was resolved through discussion. The bias risk assessment tool recommended by Cochrane handbook was used to evaluate the quality of the included studies, and RevMan 5.3 software was used for data analysis. Seventeen RCTs were finally included, involving 1 309 patients. Meta-analysis showed that Maxing Shigan Decoction combined with conventional Western medicine treatment could improve clinical efficacy in patients with CAP more effectively as compared with conventional Western medicine treatment alone, mainly in terms of anti-inflammatory effects, a decrease in C-reactive protein(CRP) content(MD=-6.01, 95%CI[-10.95,-1.06], P=0.02)and white blood cell(WBC) count, a decrease in procalcitonin(PCT) level(MD=-0.74, 95%CI[-0.77,-0.71], P<0.000 1), and shortened recovery time of cough and fever. Maxing Shigan Decoction has certain curative effect on CAP, but there are problems in the methodology of included studies. High-quality stu-dies are still needed for further verification.

目前,临床试验中的结局指标在选择、测量与报告三个环节中普遍存在不一致、不实用、不规范、发表偏倚等问题.导致同类研究结果不能合并或比较,大量研究资源被浪费.建立同类病证中医药临床试验均应该报告的、最小的指标集合,即核心指标集(COS),是规范中医临床试验结局指标,解决以上问题的关键.研制COS工作的第一步需要收集所有现存临床研究报告的结局指标,即构建中医临床试验结局指标池.指标池是研制核心指标集的基础,因此,遵循严格、科学的方法学进行构建至关重要.本文以已发表文献、试验注册方案、临床医生和患者调查问卷4种途径,收集中医临床试验结局指标构建指标池,总结指标池构建的影响因素及各个环节的注意事项,以期为中医药临床试验COS的研制提供指导和参考.

有效性试验核心结局指标(Core Outcome Measures in Effectiveness Trials,COMET)小组为推动核心指标集(Core Outcome Set,COS)研究的规范化,发布了核心指标集报告规范(Core Outcome Set-STAndards for Reporting,COS-STAR)和核心指标集研究研制规范(Core Outcome Set-STAndards for Development,COS-STAD).2019年COMET工作组发布了核心指标集标准方案声明(Core Outcome Set-STAndardised Protocol Items:COS-STAP statement),用以指导研究方案的规范化.COS-STAP声明包括6个主题、13个条目.本文对COS-STAP声明相关条目进行解读,并就中医药核心指标集研究方案需要重视的问题,进行简要分析,以期为核心指标集方案制定提供参考.

目的 对已公开发表的新冠肺炎核心指标集及其研究方法进行比较分析,为临床试验和证据转化研究提供参考信息.方法 计算机检索COMET数据库,并补充检索CNKI、WanFang、PubMed、Web of Science、The Cochrane Library等数据库,收集发表的新型冠状病毒肺炎(Coronavirus Disease 2019,COVID-19)核心指标集(Core Outcome Set,COS)研究,检索时间截至为2021年3月31日.按照纳入排除标准筛选文献,并提取研究基本信息、研究方法及指标数据,对其进行描述性分析.结果 共纳入5项COVID-19核心指标集相关研究(4项为COVID-19-COS研究,1项为COVID-19核心指标测量工具研究).相同的结局指标包括死亡率、病毒核酸检测、临床进展、恢复期、临床症状评分及临床分型等.指标来源主要来自临床试验注册平台和问卷调查;达成共识的方法主要采用共识会议;利益相关群体中临床专家、方法学专家和医疗管理人员涉及较多.结论 不同的新冠肺炎核心指标集研究有一定的共性,但由于应用场景不同,也存在一定差异.随着对疾病认识的深化,相关COVID-19核心指标需要加强测量方法和疗程推荐.