A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results.
A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results.
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DOI：
10.1186/s13063-015-1023-4
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发表时间：
2015-11-03
期刊：
影响因子：
2.5
通讯作者：
Johnston J
中科院分区：
文献类型：
--
作者：
Kennedy-Martin T;Curtis S;Faries D;Robinson S;Johnston J
随机对照试验（RCTs）是在理想化和严格控制的条件下进行的，可能会损害其外部有效性。通过比较rct中报告药物干预的患者样本与日常临床实践的患者，我们对已发表的英文文章进行了文献回顾，这些文章报道了通过比较rct中报告药物干预的患者样本来评估外部有效性的研究结果。该综述主要关注心脏病学、精神健康和肿瘤学领域的出版物。检索了一系列数据库（MEDLINE； EMBASE; Science Citation Index; Cochrane Methodology Register）。按照协议规范进行双摘要评审和数据提取。在5456篇去重复摘要中，52项研究符合纳入标准（心脏病学，n = 20；精神健康，n = 17；肿瘤学，n = 15）。研究要么对RCT入组患者的基线特征（人口学、社会经济和临床参数）与现实人群进行分析，要么在应用RCT纳入/排除标准后评估符合RCT纳入条件的现实患者的比例。许多纳入的研究得出结论，RCT样本经过高度筛选，其风险状况低于现实人群，经常排除老年患者和合并症患者。个别研究中不合格率的计算表明，一般疾病人群中有很大一部分经常被排除在试验之外。大多数研究（n = 37[71.2%]）明确得出结论，RCT样本不能广泛代表现实世界的患者，这可能限制了RCT的外部有效性。作者提出了一些建议，以提高外部有效性。本综述的研究结果表明，有必要提高随机对照试验的外部有效性，以便医生在现实环境中治疗患者时有适当的证据作为临床决策的基础。通过修改试验设计以纳入更具代表性的患者样本，以及用观察性研究的数据补充RCT证据，可以实现这一目标。一般来说，需要一种深思熟虑的临床证据生成方法，其中以整体和平衡的方式考虑内部和外部有效性之间的权衡。本文的在线版本（doi:10.1186/s13063-015-1023-4）包含补充材料，仅供授权用户使用。
Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner. The online version of this article (doi:10.1186/s13063-015-1023-4) contains supplementary material, which is available to authorized users.
影响因子：
1.7
作者：
Talamo, Alessandra;Baldessarini, Ross J.;Centorrino, Franca
通讯作者：
Centorrino, Franca