“真实世界研究”——中医药科研新思路

[目的]研究“真实世界研究”（real—worldstudy,Rws）方法,使RWS走进医学研究人员视野,为中医药科研探索新方向。[方法]回顾近年来国外开展的RWS,通过与“随机对照试验”（Randomizedcontrolledtrial,RCT）对比,总结RWS的特征,讨论运用RCT、RWS开展中医药科研的局限性和优势。[结果]RWS与RCT在临床研究目的、纳入和排除标准、样本量、干预情况、评价时间及评价指标、数据采集、管理及统计分析方法等方面存在差异。[结论]与RCT比较,RWS更契合中医“整体观念”及“辨证论治”的基本特征,有利于保存中医特色,为中医药科研指明新方向。     

实施针灸临床随机对照研究的体会

临床试验是一种经过精心设计的医学研究方法,常用来评价药物、疗法和预防性干预措施的效果,同时也是医生将临床工作中摸索的经验或假设转化为理论,进而得到同行认可并推广实践的重要手段.随着中医从业人员对方法学认识的提高,越来越多的临床医生在临床设计时,选择了设计严谨、证据强度较高的随机对照试验(randomized controlled trial,RCT).     

我国中医药临床对照试验文献发表趋势分析

目的：分析近20年内国内期刊发表的中医临床对照试验文献的现状及其发展趋势。方法：选择＂中文科技期刊数据库＂,对1989—2009年11月国内正式发表的中医临床对照试验文献进行检索,按照文献计量学方法,分析历年对照试验文献的数量及其构成比变化。结果：共检索出中医药临床对照试验33399篇,其中随机对照试验（randomized controlled trial,RCT）19234篇（占57.59%）,非随机对照试验（non-randomized controlled trial,non-RCT）14165篇（占42.41%）,RCT文献的数量和构成比呈逐年递增趋势,non-RCT文献的构成比呈逐年递减趋势,二者构成比及比值经Runs游程检验显示差异有统计学意义（P=0.003）。结论：中医药临床对照研究的文献数量呈逐年增长趋势,非随机对照研究文献数量逐渐减少,而随机对照研究文献逐年增加。     

比较效果研究常用方法之一:实用型随机对照试验设计

比较效果研究(comparative effectiveness research,CER)是在注重不同干预措施临床效果间比较的基础上,得出相对的临床效果,为指导临床决策提供依据。因此"效果"是此类研究评价和关注的焦点,与传统的解释性随机对照试验(randomized controlled trial,RCT)所评价的"效力"不同[1]。"效果"(effectiveness)是指一种特定的医疗干预措施在现实环境中针对某一特定人群的实际效果或作用程     

队列研究与随机对照试验的方法学比较

在临床科研中．在考虑到所要研究的相关因素后，研究者据此所采用的研究设计的强度在临床科研中即成为医学证据的重要方面。我们通常用随机对照试验（randomized controlled trial，RCT）来提供治疗和预防的证据，而对病因学的研究等则用观察性研究而非随机对照试验。例如作为仅次于RCT证据的队列研究（cohort study）可以减少选择和测量偏倚。     

针灸研究中组间症状积分的定量比较与组内分级定性法利弊的探讨

近年来,在中医针灸随机对照临床试验（randomized controlled trial,RCT）中恰当地应用统计学方法日益受到重视。基于假设检验的统计推断是临床试验与循证医学的基础,根据临床试验设计的基本统计原则,本文探讨了中西方文献中针灸RCT设计与分析方法学的差异。国内针刺临床试验多采用3级或4级定性法进行临床统计分析,而国外的临床试验则多采用组间症状积分的定量比较。本文以针刺治疗疼痛的临床试验为例,讨论了两种分析方法的利弊。我们认为两种方法可以兼用,但应以定量分析方法为主,分级定性法为辅,以取各自方法的所长。本文的目的是希望通过提出问题来抛砖引玉,以期引起更多的学术讨论,从而提高中医针灸临床研究的科学性和严谨性。     

国内癌因性疲劳中医药相关临床试验注册现状分析

目的 通过分析中国临床试验注册中心(Chinese clinical trial registry，ChiCTR)注册的与中医药干预癌因性疲劳(cancer-related fatigue，CRF)相关的临床试验，探讨其试验注册现状。方法 检索ChiCTR数据库收录的从建库至2022年6月2日与中医药相关的CRF临床研究注册试验，对检索结果进行筛选并提取所需数据信息，运用WPS Office软件的表格功能对纳入研究数据进行统计分析，并归纳临床试验特征。结果 最终纳入36项CRF中医药相关临床试验，覆盖全国6个省、3个直辖市，其中包括干预性研究34项，观察性研究2项，招募样本量5 327例，干预措施包括内服药物疗法、中药注射液、外治法和中医传统功法。结论 目前有关CRF中医药临床试验注册数量总体呈上升趋势，试验以随机对照试验(randomized controlled trial, RCT)研究居多，干预性研究为主，其空间分布欠均衡，且注册信息的严谨性与结局指标的规范性待进一步提高。     

临床研究的新路径:基于专业特长的随机对照试验

当今是循证医学时代,随机对照试验(randomized controlled trials,RCT)被誉为临床试验的最佳方法和金标准[1],一项设计和实施优良的RCT所能提供的证据作为循证医学的最高等级证据已毋容置疑。然而,随着临床研究发展需要,尽管常规的RCT用于评价药物干预方法的效果     

重视循证医学证据,合理评价和选择抗高血压药物

随机对照临床试验（randomized clinical trial，RCT）是循证医学的基础，也是制定指南的重要依据，而指南又是我们临床实践的金标准。迄今为止，上百项大型高血压RCT的结果为高血压的干预提供了两方面的证据。[第一段]     

单病例随机对照试验在中医药临床疗效评价中的应用与思考

目的对比单病例随机对照试验(N-of-1)、随机对照试验(RCT)、真实世界研究(RWS) 3种临床研究方法在中医药领域的优劣,并寻找出更适用于中医药临床疗效评价的研究方法。方法查阅国内外相关文献和最新版指南,对3种研究方法进行比较。结果中医学临床研究强调个体化,N-of-1能够科学合理地与中医自身规律有机结合,核心思想与中医临床诊疗模式相同。结论通过N-of-1是对中医诊疗个案研究的科学提炼与完善,通过对所得数据的系统评价,不仅能够获得对中医诊疗的疗效、治则等的科学评价,更能够为中医个体化诊疗提供有效的验证方式,在中医药临床研究中有极好的应用前景。     

以证据医学(EBM)为基础的谷氨酰胺和肠通透性的临床研究

以证据医学(evidence-based medicine)为基础的临床研究并不是取代所有的传统临床研究模式,但它将是2l世纪临床研究的发展方向。证据医学着重以客观的终点指标、病人的预后(病死率、并发症发生率和住院时间等)、生活质量及如功／耗比等来评价某一种治疗方法或某一种药物的效果。证据医学以病人获得实际益处为中心,如降低死亡率,减少并发症,提高病人的生活质量等。该评价方法已日益增多地应用于发达国家的临床研究中,对我们的临床研究有重要指导意义。文献附有观察谷氨酰胺双肽对肠道粘膜通透性,术后与感染有关的并发症及住院时间等影响的实例。观察到谷氨酰胺双肽强化的肠外营养有助于肠粘膜通透性的维持,减少与感染有关的并发症及缩短住院日等效应。     

Principle of evidence-based medicine and its application in clinical trial practice for glutamine and gut permeability

Evidence-based medicine (EBM) was developed from the progress of traditional clinical model trial patterns. EBM was based on well-designed, randomized, double blind, controlled, multiple center trails in order to assess end pont parameters, prognosis parameters (as: mortality, morbidity of complications and hospital stay etc.), quality of life and cost/effect ratio. It has been accepted in developed countries and could be the guidelines for Chinese clinical trials in the future. This article summarized the principle of EBM and attached with a clinical trial sample about effects of glutamine dipeptide on gut barrier function, post-operative complications and the hospital stay.     

Update on intravenous tissue plasminogen activator for acute stroke: from clinical trials to clinical practice

TISSUE PLASMINOGEN ACTIVATOR (TPA) INJECTED INTRAVENOUSLY within 3 hours of symptom onset has emerged as a treatment option for acute ischemic stroke. Although controversial and not universally accepted, its use in carefully selected patients is supported by evidence from randomized controlled trials and by mounting community experience. In this paper we review the literature published in the past 5 years regarding the safety, clinical trial efficacy and real-world effectiveness of intravenous tPA for stroke. First we review data from the phase III clinical trials on which approval for tPA is based. Then we summarize a growing literature of postmarketing phase IV studies and discuss the limitations and challenges that lie ahead. Our aim is to provide clinicians with an overview of this evolving therapy.     

心肺复苏的新观念

在过去30年中人们对心肺复苏和心血管急救方法进行了广泛的研究，特别是近10年在大量的多中心、随机、对照临床试验基础上，以循证医学为依据，对心肺复苏的观念进行了较大的改进。笔者就以下几个方面进行了论述：①CPR指南；②CPR的ABC顺序；②CPR指南的伦理学。另外笔者就超长心肺复苏观念以及药物肾上腺素、碳酸氢钠及多巴胺在心肺复苏中应用方面也进行了论述。     

Population diversity of cardiovascular outcome trials and real-world patients with diabetes in a Chinese tertiary hospital

Background:Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.Methods:This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.Results:We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the real-world inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.Conclusions:The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.     

姑息化疗和最佳支持治疗在晚期胰腺癌中的比较

目的 评价姑息化疗在提高晚期胰腺癌病人生存期方面的意义，本文所指的姑息化疗均是以5—FU为基础的。方法通过MEDLINE、EMBASE等数据库检索国内外已发表和未发表的相关文献。选择治疗组为姑息化疗并对症支持治疗，对照组为只给予对症支持治疗的晚期胰腺癌的随机对照试验。由2位评价者分别按上述检索策略收集资料，按选择标准入选，主要对半年生存率及1年生存率进行Meta分析。结果 姑息化疗与最佳支持治疗对比，治疗晚期胰腺癌使半年生存率提高21％，使1年生存率提高6％，但均无统计学意义。结论 目前姑息化疗可以选择性地用于晚期胰腺癌，部分病人可能获益，但仍不能作为标准治疗。     

常见的患者偏好随机对照试验方法介绍与评价

为了解决传统的随机对照试验在临床实际操作过程中面临的患者的偏好、伦理和依从性等,研究者们提出了患者偏好随机对照试验。介绍几种常用的患者偏好设计方案:患者偏好二阶段设计(Wennberg设计、Rücker设计)、全面队列设计(Brewin设计和Olschewski设计)、预随机设计和Korn设计等,并评价各个设计方案的优缺点,以便研究人员和临床医生根据研究目的、疾病特点等特征选择合适的方案。     

Real world clinical performance of the zotarolimus eluting coronary stent system in Chinese patients: a prospective, multicenter registry study

Background  Early clinical trials with the Endeavor zotarolimus eluting stent (ZES) in western populations demonstrated low rates of target lesion revascularization with a favorable safety profile including low late stent thrombosis with up to 5 years of follow-up. The aim of this clinical registry study was to evaluate real world clinical performance of the ZES coronary system in Chinese patients.

Methods  The China Endeavor Registry is a prospective, multicenter registry assessing the safety of the ZES system in a real world patient population. It was conducted at 46 centers in China in routine treatment of patients with coronary artery stenosis, including patients with clinical characteristics or lesion types that are often excluded from randomized controlled trials. The registry included 2210 adult patients who underwent single-vessel or multi-vessel percutaneous coronary intervention. The primary end point was the rate of major adverse cardiac events (MACE) at 12 months.

Results  The 12-month rate of MACE for all patients in the registry was 3.03%. Cardiac death or myocardial infarction rate was 1.28% and target lesion revascularization rate was 1.66%, non-target lesion target vessel revascularization (TVR) was 0.52%, TVR was 2.18%, and target vessel failure was 3.22%. There was only one case of emergent cardiac bypass surgery. The 12-month overall incidence of all Academic Research Consortium (ARC)-defined stent thrombosis was 0.43%.

Conclusion  Mid-term results from the real-world China Endeavor Registry suggest that Endeavor ZES was safe and effective in Chinese patients.

     

针刺减肥的随机对照试验方法学和报告质量评估

目的评价全世界针刺减肥的随机对照试验的方法学质量和报告质量.方法没有语言限制地系统、全面检索全世界针刺减肥的随机对照试验文献,利用循证医学的质量标准对试验的方法学进行评估;并参照CONSORT和STRICT清单对试验报告的质量进行评估.结果共获得7篇随机对照试验.1篇方法学质量等级为A,2篇方法学质量等级为B,4篇方法学质量等级为C.所有随机对照试验的报告质量等级均为C.结论目前全世界针刺减肥的随机对照试验质量不高,尚不能为临床实践提供强有力的证据.针刺减肥的随机对照试验报告写作质量差,不能充分反映试验所有有用的信息.     

国产重组人促红细胞生成素临床疗效观察

采用随机对照的方法，观察了２５例（对照）和２４例（开放）国产重组人促红细胞生成素（ＥＰＯ）的对慢性肾功能衰竭肾性贫血患者的疗效和副作用，结果表明，采用皮下和静脉给药的方法，用国产ＥＰＯ治疗慢性肾功能不全肾性贫血患者总有效率为９３．９％，显效率为６７．３％，有效率为２６．５％，无效率为６．１％，与进口ＥＰＯ疗效相当。国产ＥＰＯ不良反应，透析器凝血发生率为４．０％，内瘘堵塞发生率为８．５％，与进口ＥＰ