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.     

鱼油和ω-3多不饱和脂肪酸在冠心病防治中的作用

鱼油和ω-3多不饱和脂肪酸在冠心病防治中的价值,历经临床流行病研究、队列研究、基础研究和临床多中心随机对照研究,积累了大量的证据,并形成了一定的共识,但由于近年来几个大型双肓临床多中心随机对照试验结果不一致,目前的结论仍需要今后高质量的研究工作证实.     

统计学小知识

1.EER循证医学中预防和治疗性试验中,将发生率可细分为EER和CER两类。EER(experimental event rate),即试验组的某事件发生率。2.CER CER(control event rate),即对照组的某事件发生率,常用于临床对某病不采取防治措施或采用阳性对照措施的发生率。在两平行组的临床试验中,还经常需要比较两组某个指标是否有差异,常用两组该指标的比值或差值来反映两组试验效应的差异。     

运动干预对超重肥胖儿童青少年身体成分影响的网状Meta分析

目的 采用网状Meta分析方法比较有氧、抗阻、有氧结合抗阻3种运动方式对超重/肥胖儿童、青少年身体成分的影响,为儿童青少年超重/肥胖干预研究和实践提供更全面有效的证据.方法 检索中国知网、维普网、万方、PubMed、Web of Science数据库公开发表的与"运动干预对超重/肥胖儿童青少年体成分"相关的随机对照试验...     

2001-2005年《广东医学》临床用药研究论文的分析评价

目的 了解广东省临床用药研究现状,提高临床用药研究水平,保证研究结果的真实性.方法 按照循证医学标准,对2001-2005年<广东医学>临床用药研究论文进行分析,重点评价随机对照试验论文的质量.结果 2001-2005年<广东医学>临床用药研究论文共计381篇,其中随机对照试验论文239篇(占62.73%).只有17篇(占7.11%)论文简单描述了随机方法,有159篇(占66.53%)论文进行了组间基线资料比较,仅有7篇(占2.93%)论文采用了盲法,有169篇(占70.71%)论文报道了药物不良反应.总样本量最大为966、最小为25、平均为107;一般对计量资料用t检验,计数资料用x2检验.结论 近5年<广东医学>临床用药研究论文总体质量较好,但研究方法不够严谨,影响了研究结果的真实性.今后必须进一步加强临床医学工作者的循证医学培训,组织多中心的临床医学研究,提高科研管理水平和论文编审质量.     

中医药治疗子宫内膜异位症临床疗效

目的对中医药治疗子宫内膜异位症的临床随机对照试验的科研设计质量进行系统评价。方法主要治疗方法为中医、中药或中西医结合疗法的临床研究;随机对照试验或临床对照试验,试验纳入一平行的对照组接受安慰剂、西药（丹那唑、内美通、三苯氧胺等）治疗或不治疗。中药联合西药与单用西药对照比较的随机试验也被纳入。结果采用了随机对照方法的研究文献占64％,但随机对照的质量欠佳;大部分研究缺乏诊疗标准或标准不一。结论中医药治疗子宫内膜异位症的临床试验的设计和实施还存在很多不足。     

临床真实世界研究中的实验性研究设计

真实世界研究作为解释性随机对照试验在医疗实践中评价干预措施效果的进一步验证和补充已成为医疗卫生领域关注的焦点。但是也存在错误将真实世界研究等同于观察性研究,认为真实世界研究不能实施人为干预,更不能采取随机化。实际上,真实世界研究的基本设计既可以是观察性的,也可以是实验性的。其中真实世界研究的实验性研究设计主要是指实用性随机对照试验和基于注册登记研究的随机对照试验,也可采用非随机对照、自适应设计等其他研究设计方案。     

拓普替康治疗卵巢癌的循证评价

目的采用循证医学的方法评价拓普替康治疗卵巢癌的效果和安全性。方法采用Cochrane系统评价方法，检索Cochrane图书馆，MEDLINE，CENTRAL，CNKI，VIP，CBMDISC等电子资料库，搜集关于拓普替康治疗卵巢癌的系统评价、临床随机对照试验等，并对所获取的证据进行质量评价。结果检索并纳入7篇临床随机对照试验，1篇系统评价。根据临床问题，对所查证据进行了评价。结论拓普替康与紫杉醇、甲基化脂质体阿霉素、吉西他滨等化疗药具有相似的治疗作用，是一种有效的治疗卵巢癌的二线化疗药物。     

2012年循证医学与实效研究方法学研讨会第一轮通知

由中国医师协会循证医学专业委员会主办,北京大学循证医学中心协办的"循证医学与实效研究方法学研讨会"即将于2012年10月18-20日在北京召开,诚挚地邀请您莅临会议。循证医学强调证据分级,在评价疗效时"最佳证据"主要来自随机对照试验(randomized controlled trial,RCT)及其荟萃分析。但经典的RCT通常要求研究对象患单一疾病,采用标准治疗和单一干预措施,从而评价干预措施在理想状态下所能达到     

Principles of evidence-based medicine; merits and pitfalls

Historical background, main principles, methodology of evidence based medicine (EBM) and prospective randomized trials (incl. megatrials) are reviewed. EBM has a significant beneficial influence on medical activities as follows: improving efficacy of medical therapy, generation of new research trends, optimizing decision making in clinical settings of incomplete pathophysiological background, exploring new associations can be found beyond the individual clinician's scope, regular financial support of gradual, postgradual medical training, medical research and international scientific programs. Potential adverse influences related to EBM are: weakening position of individual (versus modus) patient-oriented approach in medical care, diminution of pathophysiology- (versus product-) oriented medical research, reevaluation of medical, scientific activity, interrelations between medical doctors and patients. Potential misuse of statistical methods in evaluation of megatrials is briefly discussed. A combination of benefits related to EBM and traditional elements of classical medical care, clinical research is needed to establish a more improved medical care for the individual patient.     

Why observational studies should be among the tools used in comparative effectiveness research

Doctors, patients, and other decision makers need access to the best available clinical evidence, which can come from systematic reviews, experimental trials, and observational research. Despite methodological challenges, high-quality observational studies have an important role in comparative effectiveness research because they can address issues that are otherwise difficult or impossible to study. In addition, many clinical and policy decisions do not require the very high levels of certainty provided by large, rigorous randomized trials. This paper provides insights and a framework to guide good decision making that involves the full range of high-quality comparative effectiveness research techniques, including observational research.     

The critical role of observational evidence in comparative effectiveness research

Although not the gold standard of clinical research, observational studies can play a central role as the nation's health care system embraces comparative effectiveness research. Investigators generally prefer randomized trials to observational studies because the former are less subject to bias. Randomized studies, however, often don't represent real-world patient populations, while observational studies can offer quicker results and the opportunity to investigate large numbers of interventions and outcomes among diverse populations--sometimes at lower costs. But some decisions based on observational studies have turned out to be wrong. We recommend that researchers adopt a "body of evidence" approach that includes both randomized and observational evidence.     

The art of quality assessment of RCTs included in systematic reviews.

The best evidence on the efficacy of medical interventions is provided by high-quality trials summarized in high-quality systematic reviews or meta-analyses. The methodological quality of studies included in a systematic review can have a substantial impact on the estimates of the treatment effect and therefore on the conclusions of such a review. But what is the empirical evidence to support quality assessment of randomized clinical trials (RCTs)? We elaborate on questions such as: what is the concept of quality of individual studies (RCTs), can quality be measured validly and reliably? Plans for future research on this issue are proposed.     

Analyses of Cost Data in Economic Evaluations Conducted Alongside Randomized Controlled Trials

OBJECTIVE: The adoption and diffusion of new medical treatments depend increasingly on evidence of costs and cost-effectiveness. This evidence is increasingly being generated from economic data collected in randomized clinical trials. The objective of this article is to evaluate the statistical methods used for analysis of cost data in economic evaluations conducted alongside randomized controlled trials. METHODS: Systematic review of economic evaluations based on patient-level cost or resource-use data collected in randomized trials was published in 2003. One hundred fifteen articles were identified from the MEDLINE database. The use of statistical methods for 1) joint comparison of costs and effects and assessment of stochastic uncertainty, 2) incremental cost estimation, and 3) handling of incomplete or censored cost data was evaluated. RESULTS: Only 42 (37%) of the 115 economic evaluations presented a cost-effectiveness ratio or estimated net benefits and 24 (57%) of these reported the uncertainty of this statistic. A comparison of costs alone was more common with 92 (80%) of the 115 studies statistically comparing costs between treatment groups. Of these, about two-thirds (62; 68%) used at least one statistical test appropriate for drawing inferences for arithmetic means. Incomplete cost data were reported in 67 (58%) studies with only two using a published statistical approach for handling censored cost data. CONCLUSION: The quality of statistical methods used in economic evaluations conducted alongside randomized controlled trials was poor in the majority of studies published in 2003. Adoption of appropriate statistical methods is required before the results from such studies can consistently provide valid information to decision-makers.     

Reports of clinical trials should begin and end with up-to-date systematic reviews of other relevant evidence: a status report

OBJECTIVE: Scientific and ethical justification for new clinical trials requires them to have been designed in the light of scientifically defensible assessments of relevant previous research. Reliable interpretation of the results of new clinical trials entails setting them in the context of updates of the reviews upon which they were deemed scientifically and ethically justifiable. We have shown previously that most reports of randomized trials published in five general medical journals in May 1997 and in May 2001 failed to set their results in the context of the findings from similar research. In the current study, we assess whether there had been progress in this respect in 2005 and also investigate the extent to which reports begin by referring to systematic reviews providing the justification for the new research reported. DESIGN: Assessment of the Introduction and Discussion sections in all reports of randomized trials published during May 2005 in five general medical journals. SETTING: Reports of randomized trials in five general medical journals. PARTICIPANTS: Annals of Internal Medicine, BMJ, JAMA, Lancet and New England Journal of Medicine. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The inclusion or mention of one or more systematic reviews in the Introduction or Discussion section of each report assessed. RESULTS: We found 18 reports of randomized trials. The Introduction sections referred to systematic reviews in five (27%) of these reports. None of the discussion sections of the 15 reports of trials that were not the first published trials to address the question studied placed the results of the new trial in the context of an updated systematic review of other research. Although reference was made to relevant systematic reviews in five of these 15 reports, there was no integration - quantitative or qualitative - of the results of the new trials in an update of these reviews. In the remaining ten reports there was no evidence that any systematic attempt had been made to set the new results in the context of previous trials. CONCLUSIONS: There is no evidence of progress between 1997 and 2005 in the proportion of reports of trials published in general medical journals which discussed new results within the context of up-to-date systematic reviews of relevant evidence from other controlled trials. Although the proportion of trials referring to systematic reviews in Discussion sections has increased, the majority of reports continued to fail even to do this. Similarly, most researchers appear not to have considered a systematic review when designing their trial. Researchers and journal editors do a disservice to the interests of the public and others involved in healthcare decision-making by acquiescing in this situation.     

Study design,statistical method,and level of evidence in Japanese and American clinical journals

Clinical articles published in Japanese journals are said to be characterized by poor study design, less sophisticated statistics, and producing few high-grade clinical evidences. Two American and two Japanese medical journals, published in 1990, 1993, 1996, and 1999 were compared to find out the differences regarding study design, statistical methods, and level of clinical evidence of original articles and synthetic studies. There were 1689 original articles in American and 308 in Japanese joumals. Regarding study design, American articles contributed much more to randomized controlled trials/controlled trials/clinical trials (27.9% vs. 14.3%, p=0.001), cohort studies (21.6% vs. 6.2%, p=0.001), and case-control studies (6.5% vs.0.3 %, p=0.000). Among original articles in American and Japanese journals, mean number of statistical methods used were 2.4 and 1.7 per article (p=0.000), respectively. Articles providing high grade clinical evidence (grade Ia, Ib & IIa) were much greater in proportion in American journals than Japanese journals (31.1% vs. 12.7%, p=0.001). The overall picture of Japanese medical articles seems to be improving recently, at least in terms of statistical methods toward more diversified and sophisticated way of use, compared to the previous data.     

THE ROLE OF META-ANALYSIS IN MONITORING CLINICAL TRIALS

The randomized clinical trial is the gold standard methodology for evaluating treatment interventions. The randomized trial is a prospective experimental study, the embodiment of the scientific method applied to the clinic. Both organizational and ethical considerations encourage the use of formal criteria for termination. Such criteria, typically based on an overall 5 per cent significance test, are frequently portrayed as guidelines, but none the less usually succeed in focusing the debate on termination decisions and thus facilitate decision making. The use of the 5 per cent criterion is entirely arbitrary and is not based in any way on optimality considerations. No credible model for optimizing the decision to terminate trials has been developed. Meta-analysis is an evolving technique for evaluating the totality of the evidence on general treatment strategies. It has enjoyed considerable success in influencing medical opinion and treatment practice in selected areas. Its role is in establishing proof of concept of general treatment strategies, and is thus a consensus builder, making use of data from trials which may be heterogeneous in the details of treatment administration and patient selection, but similar in conceptual intent. The level of evidence required for consensus is not well understood and cannot be defined precisely. The retrospective nature of meta-analysis and the risks of biased data acquisition mandate a conservative approach to data analysis and interpretation. Randomized trials and meta-analyses have distinct but complementary goals. Meta-analysis can be used productively in planning new clinical trials, and in supplying updated information to study monitors in the course of a trial. However, it is not advisable to employ meta-analysis in formal statistical procedures for terminating clinical trials.     

Research methods for obtaining primary evidence

The use of new therapeutic and diagnostic technologies has become commonplace in modern medical practice. To avoid both clinical disappointment and the waste of money, health, and lives, the introduction of these technologies will have to be based on evidence that these technologies will do more good than harm. The evidence supporting their use should be derived using research methods designed to deal with placebo effects, confounders, and biases. Some of these methods, and the rationale for their use, are discussed in this article. Although the value of evidence derived from randomized controlled trials is stressed, the importance of reviewing critically the methodological details of such trials and interpreting their results with caution is emphasized. The benefits and risks of relying on case-control and cohort studies are reviewed.