临床随机对照试验的外部真实性及其评价的探讨

一、临床试验及其真实性 临床随机对照试验(RCT)严格遵循随机、对照、盲法等三大设计原则,并在试验过程中有效控制了潜在的混杂与偏倚,从而保证试验结果的真实可靠.现已成为验证临床药物或某项干预措施是否安全有效的重要研究手段.     

临床随机对照试验的外部真实性及其评价的探讨

一、临床试验及其真实性临床随机对照试验(RCT)严格遵循随机、对照、盲法等三大设计原则,并在试验过程中有效控制了潜在的混杂与偏倚,从而保证试验结果的真实可靠.现已成为验证临床药物或某项干预措施是否安全有效的重要研究手段.     

碘盐预防碘缺乏病随机对照试验的系统评价

目的 评价碘盐预防碘缺乏病的效果。方法 采用Cochrane系统评价的方法。结果 全世界约500篇相关文献中，4项研究为随机对照试验，符合纳入标准，按照年龄，干预措施和对照措施的不同进行亚组分析，8-12岁儿童组使用分发碘盐和市场碘盐加碘油胶囊均能有效降低甲状腺肿患病率（甲肿率），接近5%控制线，并明显优于市场碘盐（OR=0.10,95%CI:0.02-0.17)；市场碘盐虽能使甲肿率下降，但仍不能达到甲肿率控制线（14.7%)，使用市场碘盐时，儿童尿碘日排量在不同地区有不同结果，中国的研究结果尿碘水平随市场碘盐浓度的变化而变化，一般能达到100μg/L以上；德国和印度尼西亚的研究结果均不能达到碘缺乏病控制线，孕妇组使用市场碘盐预防碘营养不足基本有效，但仍应注意有相当部分孕妇达不到碘营养标准。结论 严格控制质量的碘盐和市场碘盐加碘油制剂能有效消除碘缺乏病；但对于市场碘盐消除碘缺乏病，尤其是消除儿童的碘缺乏病的效果评价。尚需更充分的证据。     

真实世界研究与随机对照试验、单病例随机对照试验在临床治疗性研究中的关系比较

真实世界研究、随机对照试验及单病例随机对照试验在设计及具体的实施环节上存在明显不同.随机对照试验属于新治疗措施实施前的研究,真实世界研究属于新治疗措施实施后的研究.两者不是对同一个问题的平行论证,而是承启关系.精心设计的随机对照试验是临床上任何干预措施效果评价的基础,其结果需要真实世界研究的进一步验证及拓展补充,综合考虑二者才是最佳的选择.单病例随机对照试验更易在短时间内获得一些特殊病例的信息,是随机对照试验结果的良好补充,也是一定条件下最经济的真实世界研究.临床工作及其研究是十分复杂的过程.不同个体虽患同种疾病,但临床表现互有差异,且临床反应的变化也不尽相同.因此,无法获得同一干预措施下不同个体的相同治疗效果;加之有的治疗措施缺乏真实性和实用价值,从而使得疗效评价成为一个难题.近些年来,普遍采用试验性的研究结果作为证据指导临床实践活动,其中以随机对照试验(RCT)最为受到重视,但由于RCT属于药物面市前研究,对研究对象的选择、治疗措施的应用等均有严格的限定.     

真实世界研究与随机对照试验、单病例随机对照试验在临床治疗性研究中的关系比较

真实世界研究、随机对照试验及单病例随机对照试验在设计及具体的实施环节上存在明显不同.随机对照试验属于新治疗措施实施前的研究,真实世界研究属于新治疗措施实施后的研究.两者不是对同一个问题的平行论证,而是承启关系.精心设计的随机对照试验是临床上任何干预措施效果评价的基础,其结果需要真实世界研究的进一步验证及拓展补充,综合考虑二者才是最佳的选择.单病例随机对照试验更易在短时间内获得一些特殊病例的信息,是随机对照试验结果的良好补充,也是一定条件下最经济的真实世界研究.临床工作及其研究是十分复杂的过程.不同个体虽患同种疾病,但临床表现互有差异,且临床反应的变化也不尽相同.因此,无法获得同一干预措施下不同个体的相同治疗效果;加之有的治疗措施缺乏真实性和实用价值,从而使得疗效评价成为一个难题.近些年来,普遍采用试验性的研究结果作为证据指导临床实践活动,其中以随机对照试验(RCT)最为受到重视,但由于RCT属于药物面市前研究,对研究对象的选择、治疗措施的应用等均有严格的限定.     

重复性和真实性的评价方法

重复性和真实性的评价方法文万青在流行病学和其他医学研究中，经常需要对两组研究资料间的一致性进行评价。用同一方法对同一变量的重复测量结果之间的一致性称为重复性￣［１］；某种新的测量或研究方法与已建立的“黄金标准”方法之间的一致性称为真实性￣［１］。一般...     

临床营养研究中随机对照研究质量评价

目的评价两种主要临床营养期刊中随机对照试验（RCT）的质量。方法查阅2000～2008年《中国临床营养杂志》和《肠外与肠内营养》发表的RCT研究，按Cochrane协作网标准评价，并进行Jadad评分。结果两种期刊共发表238篇RCT研究，Jadad评分为（1．65±0．82）分。高质量RCT仅28篇（11．76％），评分为满分5分的仅5篇（2．10％）。随机分组的方法、组间可比性、纳入排除标准、盲法、撤除和退出的数量和理由、样本含量等方面存在各种问题。结论国内临床营养领域RCT研究的设计和质量控制还存在不足或欠缺，水平尚待提高。     

临床营养研究中随机对照研究质量评价

Objective To evaluate the quality of the randomized controlled trials (RCTs) published in two key Chineze journals on clinical nutrition.Methods The articles published in CHINESE JOURNAL OF CLIN-ICAL NUTRlTION and PARENTERAL & ENTERAL NUTRITION from 2000 to 2008 were reviewed and the RCTs were identified according to criteria of the handbook of Cochrane Collaboration.The Jadad scale was used to evalu-ate the quality of these RCTs.Results Totally 238 RCT articles were published in these two journals in this peri-od.The Jadad score of all RCT articles was 1.65±0.82.Twenty-eight articles (11.76%) were of high quality and only 5 articles (2.10%) were identified 5 points.There were some problems in the RCTs design,conduction and analyses included unclear randomization methods,poor comparison,lack of inclusion and exclusion criteria.less blinding employment,unclear withdrawals and dropouts,and improper sample size.Conclusion The design and quality control of Chinese clinical nutrition RCTs still have some problems and require further improvement.     

医学随机对照试验论文存在的几个问题

随机对照试验 (randomizedcontrolledtrials ,RCTs)在医学论文中使用较为广泛 ,是现阶段公认较为理想的医学实验类型 ,著名的报告试验强化标准 (CONSORT)声明专门对如何报道RCTs列出了2 2条项目 ,该声明目前已得到诸如国际医学期刊编辑委员会 ,世界医学编辑学会等编辑学组织和一些医药卫生期刊的认同[1] 。可见 ,科学合理报告RCTs的论文具有准确性和可靠性 ,能使整篇文章可信度和科学性大大提高。但是笔者在编辑工作中审阅RCTs论文时常发现存在诸如比较方法交代不清 ,统计方法未交代或不正确等等问题 ,为了解这些问题的存在是否具有…     

随机对照临床试验论文统计质量评价量表的建立

目的 编制随机对照临床试验论文统计质量评价量表,并对量表进行信度、效度和可接受性评价.方法 采用Delphi法和小组讨论法确定量表的条目池及评分标准,采用分层随机抽样的方法,分别从2008年发表的随机对照临床试验论文中,选取非核心期刊论文50篇,核心期刊论文50篇,SCI论文34篇.对量表进行内部一致性信度、重测信度、评价者间一致性信度和区分效度的考核.结果 量表的内部一致性信度系数为0.801,各条目重测信度和测评者间信度测定kappa一致性系数均大于0.75.量表区分效度较好,能够将3种类型的期刊论文区分开来(F=173.81,P<0.001),非核心期刊论文(60.20±4.68)分,核心期刊论文(65.68±8.44)分,SCI期刊论文(86.91±6.06)分.结论 该研究形成的量表信度、效度和可接受性均较好,可用于随机对照临床试验论文的统计质量评价,也可为科研工作者撰写规范的制订提供借鉴.     

Comparison of balanced and random allocation in clinical trials: A simulation study

Background: Before analysing the results of a randomised controlled clinical trial in which 200 children were balanced over five prognostic factors, we wanted to know the efficiency of balanced allocation compared to simple randomisation as well as the efficiency of adjusted as compared to unadjusted statistical analysis in small and large sample sizes. Methods: A simulation study with 1000 replications of each assignment was performed for both relatively large trials (n = 100) and for small trials (n = 20). Four options for the design and analysis were studied: (1) simple randomisation with simple univariate analysis, (2) simple randomisation with multivariate modelling, (3) balanced allocation with simple univariate analysis and (4) balanced allocation with multivariate modelling. In addition, we also considered the effect of an unmeasured covariable, which was either uncorrelated or correlated with another covariate. Results/conclusion: The simulations show that a combination of balanced allocation and multivariate analysis as compared to simple randomisation and multivariate analysis leads to more valid and precise treatment effects as well as to smaller confidence intervals, especially in small trials (n = 20). Multivariate analysis with all known prognostic factors produces on average smaller Type I errors and Type II errors in balanced allocation compared to simple randomisation. If an unmeasured covariate is strongly correlated with another covariate the treatment effect is estimated more precisely as compared to an unmeasured covariate that is not correlate or less strongly correlated.     

Economic evaluation in long-term clinical trials

Economic endpoints have been increasingly included in long-term clinical trials, but they pose several methodologic challenges, including how best to collect, describe, analyse and interpret medical cost data. Cost of care can be measured by converting billed charges, performing detailed micro-costing studies, or by measuring use of key resources and assigning cost weights to each resource. The latter method is most commonly used, with cost weights based either on empirical regression models or administratively determined reimbursement rates. In long-term studies, monetary units should be adjusted to reflect cost inflation and discounting. The temporal pattern of accumulating costs can be described using a modification of the Kaplan-Meier curve. Regression analyses to evaluate factors associated with cost are best performed on the log of costs due to their typically skewed distribution.Cost-effectiveness analysis attempts to measure the value of a new therapy by calculating the difference in cost between the new therapy and the standard therapy, divided by the difference in benefit between the new therapy and the standard therapy. The cost-effectiveness ratio based on the results of a randomized trial may change substantially with longer follow-up intervals, particularly for therapies that are initially expensive but eventually improve survival. A model that projects long-term patterns of cost and survival expected beyond the end of completed follow-up can provide an important perspective in the setting of limited trial duration.     

中国四个大规模抗高血压临床试验Meta分析

目的评估中国四个大规模抗高血压临床试验的疗效。方法采用固定效应模型进行数据分析。结果分析显示平均治疗时间为3．7a，血压平均降低9／4mmHg。脑卒中危险降低36％（95％CI为25％～46％，P〈0．001），心血管死亡和总死亡减少22％和20％（P〈0．05），总的心血管事件减少33％（P〈0．001）。冠心病事件减少无显著性差异（P〉0．05）。结论抗高血压治疗的效果很大程度上源于脑卒中事件的减少。     

多中心临床随机对照试验的Meta分析

目的探讨解决多中心临床随机对照试验中心效应差异的统计分析问题。方法以两项多中心临床随机对照试验数据为例,运用协方差分析及Meta分析。结果协方差分析中心间效应值差异均有统计学意义,行Meta分析,项目1异质性检验差异无统计学意义(P>0.05),采用固定效应模型分析合并效应值组间差异有统计学意义(P<0.05)。项目2异质性检验差异有统计学意义(P<0.05),采用随机效应模型分析合并效应值组间差异无统计学意义(P>0.05)。结论多中心临床随机对照试验研究中,如果存在中心间以及中心与分组间交互效应差异有统计学意义时,可根据Meta分析异质性检验结果选择适合的模型进行合并效应值的组间比较,如果协方差与Meta分析结果不一致时,建议选择Meta分析的结果较为稳妥。     

Critical evaluation of clinical trials

The primary source of scientific evidence are well designed and well executed randomised controlled clinical trials. However, the sources of scientific evidence are multifaceted. The concept of evidence based medicine is wider, encompassing the best available scientific data, the preference of patients and the professional experience of physicians. Decisions on therapies or other types of interventions are based on these three components. The authors give an overview of the evaluation of the results of randomised controlled clinical trials and present an easily applicable assessment list for practising physicians.     

Internet-based trials and the creation of health consumers

In this paper we document the experience of participating in novel randomised controlled trials for panic disorder – where face-to-face and Internet delivery of cognitive behavioural therapy are compared. Our analysis is based on 18 months of observation and in-depth interviews with 10 trial participants and 8 trialists in Victoria, Australia. We argue that the participants are positioned as active health consumers and approach the trial as they would other self-help practices. High levels of individual responsibility are assumed of participants in these trials, which they accept by approaching the trials reflexively and searching for information and strategies they can employ while building their health literacy on panic disorder. Although the researchers set the parameters of the treatment and interaction, increasingly the participants choose the extent to which they will comply with their defined role. For the participants the trial is one of the ‘pick and mix’ options of available treatment and we suggest it is a compelling example of contemporary health consumption.