Espeland M A, Craven T E, Riley W A, Corson J, Romont A, Furberg C D
Department of Public Health Sciences, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC, USA.
Stroke. 1996 Mar;27(3):480-5. doi: 10.1161/01.str.27.3.480.
Serial ultrasonic B-mode measurements of intimal-medial thickness (IMT) of the carotid artery are commonly used as surrogates for describing atherosclerosis progression. This report describes the longitudinal reliability of IMT measurement during a multicenter clinical trial, quantifies the error attributable to differences among readers, and discusses how studies can be efficiently designed.
Serial B-mode measurements of carotid IMT from the 3-year Asymptomatic Carotid Artery Progression Study (ACAPS; formerly Asymptomatic Carotid Artery Plaque Study) were used to estimate the contributions to longitudinal measurement error of systematic reader effects, nonvisualization, and nonsystematic error and to describe the distribution of "true" progression rates that underlie the observed data. Variance components were estimated from random-effects models fitted to outcome measures formed by averaging IMTs from different sets of carotid artery walls. These were used to contrast the relative efficiency of study designs.
Of the total variance of measured IMT, 11% was attributable to systematic differences among readers. Nonvisualization contributed less than 7%. Thus, the predominant source of error was unaccounted for (ie, random error or "noise," which in our analyses included any drift, nonlinearity, and sonographer differences). For studies with measurement protocols similar to ACAPS, follow-up times of 2 years or more are desirable for describing the mean progression rates of cohorts, and of 6 years or more for categorizing progression within individuals. In 3-year studies, sample sizes as low as 237 provide 90% statistical power for detecting risk factors that have correlations with IMT progression of .50 or greater.
The ACAPS measurement protocol provided highly reliable serial IMT data. Moderate-sized multicenter studies using B-mode outcomes are feasible.
对颈动脉内膜中层厚度（IMT）进行连续超声B模式测量，通常被用作描述动脉粥样硬化进展的替代指标。本报告描述了在一项多中心临床试验中IMT测量的纵向可靠性，量化了因读者之间差异导致的误差，并讨论了如何高效设计研究。
利用来自为期3年的无症状颈动脉进展研究（ACAPS；原无症状颈动脉斑块研究）的颈动脉IMT连续B模式测量数据，来估计系统读者效应、不可见性和非系统误差对纵向测量误差的影响，并描述观察数据背后“真实”进展率的分布情况。方差成分是根据随机效应模型估计得出的，该模型适用于通过对不同组颈动脉壁的IMT进行平均而形成的结局测量指标。这些方差成分被用于对比研究设计的相对效率。
在测量的IMT总方差中，11%归因于读者之间的系统差异。不可见性的贡献小于7%。因此，主要的误差来源未得到解释（即随机误差或“噪声”，在我们的分析中包括任何漂移、非线性以及超声检查者差异）。对于测量方案与ACAPS相似的研究，描述队列的平均进展率需要2年或更长时间的随访，而对个体进展进行分类则需要6年或更长时间的随访。在为期3年的研究中，低至237的样本量为检测与IMT进展相关性为0.50或更高的危险因素提供了90%的统计效力。
ACAPS测量方案提供了高度可靠的连续IMT数据。使用B模式结局的中等规模多中心研究是可行的。
