Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Division of Cancer Medicine, Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Division of Pathology/Lab Medicine, Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Clin Epidemiol. 2024 Nov;175:111540. doi: 10.1016/j.jclinepi.2024.111540. Epub 2024 Sep 21.
Randomized noncomparative trials (RNCTs) promise reduced accrual requirements vs randomized controlled comparative trials because RNCTs do not enroll a control group and instead compare outcomes to historical controls or prespecified estimates. We hypothesized that RNCTs often suffer from two methodological concerns: (1) lack of interpretability due to group-specific inferences in nonrandomly selected samples and (2) misinterpretation due to unlicensed between-group comparisons lacking prespecification. The purpose of this study was to characterize RNCTs and the incidence of these two methodological concerns.
We queried PubMed and Web of Science on September 14, 2023, to conduct a meta-epidemiological analysis of published RNCTs in any field of medicine. Trial characteristics and the incidence of methodological concerns were manually recorded.
We identified 70 RNCTs published from 2002 to 2023. RNCTs have been increasingly published over time (slope = 0.28, 95% CI 0.17-0.39, P < .001). Sixty trials (60/70, 86%) had a lack of interpretability for the primary endpoint due to group-specific inferences. Unlicensed between-group comparisons were present in 36 trials (36/70, 51%), including in the primary conclusion of 31 trials (31/70, 44%), and were accompanied by significance testing in 20 trials (20/70, 29%). Only five (5/70, 7%) trials were found to have neither of these flaws.
Although RNCTs are increasingly published over time, the primary analysis of nearly all published RNCTs in the medical literature was unsupported by their fundamental underlying methodological assumptions. RNCTs promise group-specific inference, which they are unable to deliver, and undermine the primary advantage of randomization, which is comparative inference. The ongoing use of the RNCT design in lieu of a traditional randomized controlled comparative trial should therefore be reconsidered.
与随机对照临床试验相比，随机非对照试验（RNCT）承诺减少入组要求，因为 RNCT 不招募对照组，而是将结果与历史对照或预设估计值进行比较。我们假设 RNCT 通常存在两个方法学问题：（1）由于非随机选择的样本中的组特异性推断，缺乏可解释性；（2）由于缺乏许可的组间比较且没有预先指定，导致误解。本研究的目的是描述 RNCT 及其这两个方法学问题的发生率。
我们于 2023 年 9 月 14 日在 PubMed 和 Web of Science 上进行了查询，以对任何医学领域发表的 RNCT 进行荟萃流行病学分析。手动记录试验特征和方法学问题的发生率。
我们确定了 2002 年至 2023 年期间发表的 70 项 RNCT。随着时间的推移，RNCT 的发表数量逐渐增加（斜率=0.28，95%CI 0.17-0.39，P<0.001）。60 项试验（60/70，86%）由于组特异性推断，主要终点的解释性不足。36 项试验（36/70，51%）存在未经许可的组间比较，其中 31 项试验（31/70，44%）的主要结论中存在未经许可的组间比较，20 项试验（20/70，29%）进行了显著性检验。只有 5 项（5/70，7%）试验既没有这两个缺陷。
尽管随着时间的推移，RNCT 的发表数量逐渐增加，但几乎所有发表在医学文献中的 RNCT 的主要分析都没有得到其基本方法学假设的支持。RNCT 承诺进行组特异性推断，但实际上无法实现，破坏了随机化的主要优势，即比较推断。因此，应重新考虑在传统的随机对照临床试验中使用 RNCT 设计。
