Department of Cardiology and Angiology, Cardiovascular Clinical Research Center, University Heart Center Freiburg-Bad Krozingen, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Institute of Medical Biometry and Medical Informatics, University Medical Center Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
JAMA Netw Open. 2024 Apr 1;7(4):e248818. doi: 10.1001/jamanetworkopen.2024.8818.
For the design of a randomized clinical trial (RCT), estimation of the expected event rate and effect size of an intervention is needed to calculate the sample size. Overestimation may lead to an underpowered trial.
To evaluate the accuracy of published estimates of event rate and effect size in contemporary cardiovascular RCTs.
A systematic search was conducted in MEDLINE for multicenter cardiovascular RCTs associated with MeSH (Medical Subject Headings) terms for cardiovascular diseases published in the New England Journal of Medicine, JAMA, or the Lancet between January 1, 2010, and December 31, 2019. Identified trials underwent abstract review; eligible trials then underwent full review, and those with insufficiently reported data were excluded. Data were extracted from the original publication or the study protocol, and a random-effects model was used for data pooling. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline. The primary outcome was the accuracy of event rate and effect size estimation. Accuracy was determined by comparing the observed event rate in the control group and the effect size with their hypothesized values. Linear regression was used to determine the association between estimation accuracy and trial characteristics.
Of the 873 RCTs identified, 374 underwent full review and 30 were subsequently excluded, resulting in 344 trials for analysis. The median observed event rate was 9.0% (IQR, 4.3% to 21.4%), which was significantly lower than the estimated event rate of 11.0% (IQR, 6.0% to 25.0%) with a median deviation of -12.3% (95% CI, -16.4% to -5.6%; P < .001). More than half of the trials (196 [61.1%]) overestimated the expected event rate. Accuracy of event rate estimation was associated with a higher likelihood of refuting the null hypothesis (0.13 [95% CI, 0.01 to 0.25]; P = .03). The median observed effect size in superiority trials was 0.91 (IQR, 0.74 to 0.99), which was significantly lower than the estimated effect size of 0.72 (IQR, 0.60 to 0.80), indicating a median overestimation of 23.1% (95% CI, 17.9% to 28.3%). A total of 216 trials (82.1%) overestimated the effect size.
In this systematic review of contemporary cardiovascular RCTs, event rates of the primary end point and effect sizes of an intervention were frequently overestimated. This overestimation may have contributed to the inability to adequately test the trial hypothesis.
为了设计一项随机临床试验 (RCT)，需要估计干预措施的预期事件发生率和效应大小，以计算样本量。高估可能导致试验效能不足。
评估当代心血管 RCT 中已发表的事件发生率和效应大小估计的准确性。
系统检索了 MEDLINE 中与心血管疾病相关的多中心心血管 RCT，这些 RCT 与 MeSH（医学主题词）术语相关，发表在《新英格兰医学杂志》、《美国医学会杂志》或《柳叶刀》上，时间为 2010 年 1 月 1 日至 2019 年 12 月 31 日。确定的试验进行了摘要审查；合格的试验随后进行了全面审查，那些数据报告不充分的试验被排除在外。数据从原始出版物或研究方案中提取，并使用随机效应模型进行数据合并。本综述按照系统评价和荟萃分析报告的首选报告项目进行。主要结果是事件发生率和效应大小估计的准确性。准确性通过比较对照组的观察事件发生率和效应大小与其假设值来确定。线性回归用于确定估计准确性与试验特征之间的关系。
在确定的 873 项 RCT 中，374 项进行了全面审查，随后有 30 项被排除在外，最终有 344 项试验进行了分析。中位观察到的事件发生率为 9.0%（IQR，4.3%至 21.4%），显著低于估计的 11.0%（IQR，6.0%至 25.0%），中位偏差为-12.3%（95%CI，-16.4%至-5.6%；P<0.001）。超过一半的试验（196 [61.1%]）高估了预期的事件发生率。事件发生率估计的准确性与更有可能反驳零假设有关（0.13 [95%CI，0.01 至 0.25]；P=0.03）。优势试验中观察到的中位效应大小为 0.91（IQR，0.74 至 0.99），显著低于估计的效应大小 0.72（IQR，0.60 至 0.80），表明中位高估 23.1%（95%CI，17.9%至 28.3%）。共有 216 项试验（82.1%）高估了效应大小。
在这项对当代心血管 RCT 的系统评价中，主要终点的事件发生率和干预措施的效应大小经常被高估。这种高估可能导致无法充分检验试验假设。
