中药治疗新型冠状病毒肺炎临床研究文献的质量评价

目的 对迄今发表的中药治疗新型冠状病毒肺炎临床研究文献进行质量评价，找出其中的不足并提出相应的建议，以期推广中药在新冠肺炎治疗中的应用。方法 检索中国知网和PubMed数据库，用“COVID-19” “新冠病毒肺炎” “TCM” “中医药” “Clinical trial” “临床试验” “Lianhua Qingwen” “连花清瘟” “Huoxiang Zhengqi” “藿香正气” “Jinhua Qinggan” “金花清感”等关键词进行搜索，获得所有有关中药治疗新冠肺炎的相关文献，通过对比实验方法、临床疗效、主要症状消失率、体征消失率等指标，对其质量进行评价。结果 共得到中药治疗新冠肺炎相关论文463篇，剔除441篇中药治疗新冠肺炎的网络药理学理论研究文献。在纳入质量分析的22篇中药临床试验研究文献中，有随机对照研究3篇，多中心前瞻性随机对照试验1篇，病例报告2篇，无对照单臂研究5篇，对照试验4篇，回顾性研究7篇。疫情发生至今，虽然已经陆续发表了不少中药治疗新冠肺炎的临床试验文献，但多数工作不够规范，存在着部分试验没有设计对照组、样本量过低、没有设盲等问题，这些问题还需进一步改进和完善。结论 中药治疗新冠肺炎仍然需要进行更多的、设计规范的临床试验验证，产生强有力的循证医学证据，例如，增设对照组、增加样本量、采用盲法等，以此增加临床试验的可信度。     

中药新药防治儿童功能性便秘的临床研究技术要点

基于国内、外文献并结合作者的临床科研实践,在试验目的与试验设计、受试者的选择、治疗方案、试验流程、有效性评价、安全性评价、试验的质量控制和保证等方面,总结了中药新药防治儿童功能性便秘的临床研究技术要点,以期为本病的中药新药临床试验设计提供借鉴。     

符合中医药特点的中药新药评价思路探讨

目的：探讨中药新药区别于化学药新药的评价思路。方法：以真实世界证据为工具,以整体证据评价为方法,以电子化的患者报告结局为技术支持,创新中药新药评价思路。结果：1)提出中药新药质量控制中的质量一致性评价思路。在单一角度对中药新药质量一致性无法评价的前提下,采用整体证据方法这种多角度的审评观念,用真实世界证据评价多批次药品的疗效一致性,适当放宽中药新药质量一致性的要求,使中药新药的疗效一致性评价作为质量一致性评价的有力补充。2)提出中药新药临床疗效评价思路。在传统临床试验的评价基础上,以患者为中心进行临床试验设计,创建电子化的患者报告结局,关注患者生活质量改善,形成临床疗效的支持性证据。结论：鼓励采用新工具、新方法、新技术、新思路,在中药新药评价中充分体现中药临床疗效评价方法的开创性,创新中药新药评价思路。     

中药治疗儿童支原体肺炎临床试验设计述要

肺炎支原体肺炎是儿科临床常见的呼吸道感染性疾病。在参考国内外有关儿童支原体肺炎的诊疗指南、临床评价指南及临床试验相关文献的基础上,结合作者多年从事中药新药临床试验的实践经验,从试验目的、试验设计、诊断标准、辨证标准、受试者的选择、治疗方案、试验流程、有效性评价、安全性观察、试验的质量控制等方面,系统阐述了中药治疗儿童支原体肺炎临床试验设计要点,以期丰富儿科疾病中药临床评价的方法学内容。     

中医药治疗黄疸型病毒性肝炎临床研究文献的质量评价

目的:评价自1994年以来我国关于黄疸型病毒性肝炎中医药研究已发表文献的质量.方法:计算机检索MEDLINE,CBMdisk,CMCC,CMAC,CNKI,VIP等数据库,凡文中有"随机"或"随机分组","随机对照"字样,以黄疸型病毒性肝炎为治疗疾病的研究,均予纳入,并对其质量进行评价.结果:检索出文献185篇.符合纳入标准的109篇文献中,有7篇简单描述了随机分组方法,没有一篇提及分配隐藏、样本含量估算依据、盲法,仅有1篇提及失访,但未进行意向治疗分析(ITT).结论:目前中医药治疗的临床试验设计仍存在一些问题,高质量的随机对照试验(RCT)数量较少,研究的总体水平有待提高.     

安慰剂对中药新药临床试验的影响及相关建议

由于方法学和中药新药临床特点，中药安慰剂在临床研究使用较为广泛。中药安慰剂质量和模拟效果，影响整个中药新药临床研究的质量和有效性评价的客观性与准确性。从中药安慰剂制作的技术难度，与受试药物相似性，客观化、规范化模拟效果评价，服用依从性等方面探讨目前中药新药临床试验中安慰剂的主要问题。在此基础上，提出了加强安慰剂制作技术和可用原辅料研究；出台安慰剂模拟效果评估指导原则，引导研发企业加强相关研究；增加客观性评价指标设置，提高临床研究结果的可信度；根据不同研究阶段、剂型和给药方式，通过流程设计和管理，弥补中药安慰剂模拟效果不佳等缺陷的建议和思考。     

中药注射剂应用存在问题及对策

目的:促进中药注射剂安全、有效、合理使用.方法:使用文献综述的方法,对中药注射剂临床应用的现状及存在的问题进行分析,提出相应的对策.结果:中药注射剂临床使用日趋广泛,在疾病的治疗中发挥了较好的作用.主要存在安全性评价及上市后再评价机制缺乏、质量和临床疗效不稳定、中药西化、配伍不合理、不良反应发生频繁等问题,应从政策、企业、科研、临床医务人员及患者等多个层面解决相应的问题.结论:中药注射剂应用存在一些问题,需要多方面的不懈努力才能确保中药注射剂的安全、有效、经济和合理使用,促进中药注射剂健康发展.     

Revascularization treatment of stable coronary artery disease

INTRODUCTION: Coronary artery disease (CAD) is the leading cause of mortality in developed countries. Angina, myocardial infarction, heart failure and other clinical manifestations of coronary atherosclerosis lead to considerable patient morbidity and constitute an increasingly heavy burden on health systems worldwide. AREAS COVERED: This article reviews the recent major developments in the treatment of CAD, which can be achieved using medical therapy either in isolation or in combination with revascularization, performed via coronary artery bypass surgery (CABG) or percutaneous coronary intervention (PCI). There is no dispute that optimal medical treatment is the cornerstone of CAD management; however, timely revascularization offers superior symptom control in patients with severe symptoms and may also offer a survival advantage in some patients with diffuse disease and diabetes. Importantly, the advances in PCI technology, especially with the introduction of drug-eluting stents has narrowed the gap between CABG and PCI for the treatment of CAD. EXPERT OPINION: The continuous developments in diagnosis and treatment of CAD call for contemporary trials with detailed analysis to provide evidence that will help in the choice of the best and most cost-effective treatment strategy.     

临床试验随机化的质量保证

随机对照临床试验的随机化是减少选择偏倚的有效措施之一,因此如何保证随机化的质量也就成为提高临床试验质量的关键。成功实施临床试验的随机化有两个重要的环节：一是采用随机的方法产生不可预测的随机分配序列,二是采用分配隐蔽的方法保证随机分配序列的执行。本文在介绍随机化的概念和质量保证要求的基础上,分别就随机分配和分配隐蔽的质量保证方法进行阐述,同时也从报告随机对照试验的角度介绍了随机化的具体报告内容和要求,期望进一步规范我国临床试验随机化的实施,以达到不断提高我国临床试验质量的目的。     

中药安全性监测评价新方法对降低中药不良反应的影响

随着中药应用的日益广泛和公众用药安全意识的普遍提升,有关中药不良反应(ADR)的问题日益凸显;如何客观认识、分析和评价中药的安全性问题,不仅可以提高中药疗效、为评价和控制风险提供科学依据,同时也关系到中医药事业的发展.本文主要介绍药物警戒和数据挖掘技术这两种中药安全性监测新方法在中药ADR研究领域的应用现状.     

胰激肽释放酶治疗糖尿病视网膜病变的系统评价

目的：评价胰激肽释放酶治疗糖尿病视网膜病变的疗效与安全性。方法：检索MEDLINE（1977～2008）、EMBASE（1989～2008）、Cochrane临床试验数据库、CBMdisc（1978～2008）和CNKI（1979～2008）等文献数据库，收集胰激肽释放酶治疗糖尿病视网膜病变的临床研究，进行质量评价，并对符合纳入标准的临床研究进行Meta分析。结果：共纳入4项随机、对照研究，全部为中文，未检索到关于此题目的其他语种研究报告。4项研究的质量均较低，4项研究Juni评分为C级。所有研究均未对远期效果进行评价。有1项研究未提到随机分组，其他3项研究提到采用随机分组，但未描述具体的随机方法，未进行分配方案的隐藏。所有研究均未使用盲法，也未进行随访。由于缺乏高质量的临床研究，上述Meta分析未进行敏感性分析。结论：胰激肽释放酶可能对糖尿病视网膜病有一定的疗效。由于目前的临床研究质量较低，且未对远期疗效进行评价，胰激肽释放酶对于糖尿病视网膜病变的疗效还需要进行大规模及高质量的随机对照研究加以证实。     

Sample Size Determination for Three-Level Randomized Clinical Trials with Randomization at the First or Second Level

Clinical trials in the context of comparative effectiveness research (CER) are often conducted to evaluate health outcomes under real-world conditions and standard health care settings. In such settings, three-level hierarchical study designs are increasingly common. For example, patients may be nested within treating physicians, who in turn are nested within an urgent care center or hospital. While many trials randomize the third-level units (e.g., centers) to intervention, in some cases randomization may occur at lower levels of the hierarchy, such as patients or physicians. In this article, we present and verify explicit closed-form sample size and power formulas for three-level designs assuming randomization is at the first or second level. The formulas are based on maximum likelihood estimates from mixed-effect linear models and verified by simulation studies. Results indicate that even with smaller sample sizes, theoretical power derived with known variances is nearly identical to empirically estimated power for the more realistic setting when variances are unknown. In addition, we show that randomization at the second or first level of the hierarchy provides an increasingly statistically efficient alternative to third-level randomization. Power to detect a treatment effect under second-level randomization approaches that of patient-level randomization when there are few patients within each randomized second-level cluster and, most importantly, when the correlation attributable to second-level variation is a small proportion of the overall correlation between patient outcomes.     

中药新药治疗小儿厌食临床研究设计技术要点

本文立足国内研究进展和实践经验,对中药新药治疗小儿厌食临床研究方案设计过程中的关键问题,从试验目的与总体设计、诊断标准、中医辨证标准、受试者的选择、对照药的选择、导入期、疗程及随访、有效性评价、安全性评价、合并用药、质量控制等各个方面,阐述了作者的认识,为中药新药治疗小儿厌食的临床研究设计提出了具体的思路,也为中药新药的临床研究设计与评价方法提供了借鉴。     

干细胞临床研究及管理的现状与未来

干细胞研究和临床试验发展迅速,目前全球干细胞临床研究排名前三的国家或地区分别是美国、欧洲和中国,干细胞治疗种类以造血干细胞为主,间充质干细胞日益增长,神经干细胞和多能干细胞的临床试验也相对较多。目前全球已有14款干细胞药物上市,超过一半以上是间充质干细胞治疗产品。中国共有87个干细胞临床项目完成备案,其中间充质干细胞备案项目最多。细胞治疗是按照医疗技术还是药品来监管,世界各国有所不同。在美国按细胞组织类产品风险高低进行归类监管,欧盟以先进技术治疗医学产品归类监管,日本按照再生医学产品管理,中国目前进行机构和项目双备案制度。在严格分类管理的基础上,无论欧盟的医院豁免制度、日本的条件限制性准入政策,还是中国从药品-第三类医疗技术-备案制管理政策的变迁,都为干细胞及其他细胞治疗产品的研究和应用提供了科学而快速发展的政策保障。对国内外干细胞临床研究及应用的发展现状进行综述,同时分析各国干细胞临床研究相关的法律法规与质量控制监管政策。     

Quality of life in children and adolescents with cystic fibrosis: implications for optimizing treatments and clinical trial design

Health related quality of life (QOL) as an outcome measure in clinical trials is becoming increasingly important. Trials should not only be able to demonstrate the pharmacologic activity of a therapy, but of equal importance, they should demonstrate clinical effectiveness that is of significant benefit to the patient. QOL measurement provides a way of incorporating the child/parent's perspective of how cystic fibrosis (CF) and its therapies impact on their lives. Several validated generic instruments have been employed to measure QOL in adolescents and adults. QOL assessment is more difficult in children and, therefore, has been employed less often in children with CF. Difficulties arise with the issue of whether children can report their own experiences directly, or whether a parent or clinician should report on behalf of the child. A child-centered approach is imperative since the literature indicates that children are able to report on their own QOL. An additional complication has been the use of adult measures with children. These are often inappropriate in their complexity, use of language, response scales, and time frame. The evaluation of pharmacologic therapies can profit from QOL measurement. The effectiveness of a drug and any adverse effects that impact on daily life can be assessed from the child/parent's viewpoint. Home therapy versus hospital therapy and drug delivery systems, are additional areas where QOL as an outcome measure is valuable. There have been relatively few appropriately powered trials in CF, and only a minority of these have evaluated QOL as an outcome measure. This review highlights areas where QOL measurement is appropriate. It focuses on the pharmacologic trials that have employed QOL assessment for antibiotic, mucociliary clearance, anti-inflammatory, and nutritional therapies. Methodological issues of incorporating QOL assessment into trials center on cross-cultural and data interpretation issues. QOL measurement in CF has been patchy and largely unreliable. The notion that improved symptoms equate with improved QOL is erroneous. Measurement of how symptoms impact on QOL is essential. Currently, the development and validation of CF specific measures (across the CF age range) provides optimism for appropriate QOL measurement in clinical trials, and for future meta-analysis and systematic reviews.     

发展监管科学，促进中药产业传承创新

2008年新药创制重大专项启动实施以来的10多年间,紧密围绕构建国家药物创新技术体系目标,为我国新药研发和公众用药安全提供了重要的保障,获得重大进展。药品监管科学是近十几年发展形成的前沿学科,受到世界科学界和管理界的重视。本文秉着中药监管科学发展与现实存在问题,需要理论创新、药物创新、技术创新、方法创新和应用创新。中药监管科学研究计划是国家推进的9个监管科学行动计划之一。启动以中药临床为导向的中药安全性评价研究,构建中药安全性和质量控制体系。作者认为通过监管科学研究,制定科学规范的中药质量标准和评价指导原则和技术指南,推进中药材、中药饮片和中成药,特别是经典名方制剂品种示范研究,有利于中药产业健康科学发展。在本文中还结合当前的中药监管科学问题,加强药材和饮片的基础研究、中药注射剂质量疗效的再评价研究、经典名方的开发和简化申请的监管科学研究,提出监管科学研究顶层设计建议,制定技术原则与技术指南,有利于药典品种和市场产品的质量和临床有效性再评价。     

儿童湿疹/特应性皮炎药物临床试验评价指标的研究进展

湿疹是儿科临床常见的皮肤病,特应性皮炎是其中最常见的一种.《儿童湿疹/特应性皮炎中药临床试验设计与评价技术指南》已正式发布,其中提到湿疹/特应性皮炎临床试验的核心指标集,包括客观体征、主观症状、生活质量和长期控制4个核心领域,并参考核心指标集所述,制定了疗效评价指标.综述国内外湿疹/特应性皮炎临床试验中关于上述4个核心...     

中医药国际临床研究的探索与展望

本文简述了国内中医药临床试验研究的现状,简要总结了中医药国际多中心临床研究的概况,分析了中医药走出国门参与国际多中心临床评价所面临和亟待解决的一些问题,试图为推动中医药国际化进程提供新的思路和参考.     

Bayesian clinical trials

Bayesian statistical methods are being used increasingly in clinical research because the Bayesian approach is ideally suited to adapting to information that accrues during a trial, potentially allowing for smaller more informative trials and for patients to receive better treatment. Accumulating results can be assessed at any time, including continually, with the possibility of modifying the design of the trial, for example, by slowing (or stopping) or expanding accrual, imbalancing randomization to favour better-performing therapies, dropping or adding treatment arms, and changing the trial population to focus on patient subsets that are responding better to the experimental therapies. Bayesian analyses use available patient-outcome information, including biomarkers that accumulating data indicate might be related to clinical outcome. They also allow for the use of historical information and for synthesizing results of relevant trials. Here, I explain the rationale underlying Bayesian clinical trials, and discuss the potential of such trials to improve the effectiveness of drug development.