Petersen John L, Haque Ghazala, Hellkamp Anne S, Flaker Greg C, Mark Estes N A, Marchlinski Francis E, McAnulty John H, Greenspon Arnold J, Marinchak Roger A, Lee Kerry L, Lamas Gervasio A, Mahaffey Kenneth W
Duke Clinical Research Institute, Duke University Medical Center, Durham, NC 27710, USA.
Contemp Clin Trials. 2006 Jun;27(3):260-8. doi: 10.1016/j.cct.2006.02.002. Epub 2006 Mar 29.
Clinical events committees (CECs) are the current standard for endpoint adjudication in clinical trials. However, little data exist with which to compare CEC and site investigator determinations or to evaluate internal agreement among CEC members. Using data from the Mode Selection Trial in Sinus Node Dysfunction (MOST), we analyzed classifications of death in order to compare internal agreement among CEC physician reviewers and agreement between the CEC and site investigators. Death was classified at 2 levels: by major cause (cardiac, noncardiac, or unknown) and by minor subclassification of the major classifications. Reviewer agreement was tabulated at the major and minor levels, and standard and weighted kappa statistics were calculated. Disagreement at both levels was also determined. Individual decision-making was tabulated in terms of frequency in classifying death as unknown. All 404 deaths were classified by the CEC. Site investigators determined major classifications in 382 cases and minor classification in 379 cases. The CEC and the site investigators disagreed in classifying 41 cases (10.7%) at the major level and 117 (30.9%) at the minor level. CEC reviewers disagreed internally at the major level in 64 cases (15.8%), at the minor level in 63 cases (15.6%), and at any level in 127 cases (31.4%) (kappa = 0.60, 95% confidence interval (CI) [0.55, 0.66]; weighted kappa = 0.66, 95% CI [0.62, 0.75]). In resolving internal disagreements, the full CEC agreed with 1 of 2 CEC reviewers in 85.9% of cases. Disagreements occurred between site investigators and CEC reviewers in classifying deaths. Endpoint determination and decision-making varied among individual CEC reviewers, but second-tier reviews by the full CEC resolved all disagreements. These findings support continued use of CECs for endpoint adjudication in clinical trials.
临床事件委员会（CECs）是目前临床试验中终点判定的标准。然而，几乎没有数据可用于比较CEC与研究点研究者的判定结果，或评估CEC成员之间的内部一致性。利用来自窦房结功能障碍模式选择试验（MOST）的数据，我们分析了死亡分类情况，以比较CEC内科评审员之间的内部一致性以及CEC与研究点研究者之间的一致性。死亡分为两个层次：主要原因（心脏性、非心脏性或不明）以及主要分类下的次要亚分类。在主要和次要层次上列出评审员的一致性情况，并计算标准kappa统计量和加权kappa统计量。还确定了两个层次上的不一致情况。将个体在将死亡分类为不明方面的决策情况按频率列出。CEC对所有404例死亡进行了分类。研究点研究者确定了382例的主要分类和379例的次要分类。CEC与研究点研究者在主要层次上对41例（10.7%）的分类存在分歧，在次要层次上对117例（30.9%）的分类存在分歧。CEC评审员在主要层次上内部存在64例（15.8%）分歧，在次要层次上存在63例（15.6%）分歧，在任何层次上存在127例（31.4%）分歧（kappa = 0.60，95%置信区间（CI）[0.55, 0.66]；加权kappa = 0.66，95% CI [0.62, 0.75]）。在解决内部分歧时，全体CEC在85.9%的情况下与两名CEC评审员中的一名达成一致。在死亡分类方面，研究点研究者与CEC评审员之间存在分歧。终点判定和决策在个体CEC评审员之间存在差异，但全体CEC的二级评审解决了所有分歧。这些发现支持在临床试验中继续使用CEC进行终点判定。
