Department of Emergency Medicine, University of Minnesota, Minneapolis, MN, USA.
Am Heart J. 2013 Mar;165(3):273-279.e1. doi: 10.1016/j.ahj.2012.12.012. Epub 2013 Jan 26.
The impact of regulatory requirements, which require central adjudication for the diagnosis of acute myocardial infarction (AMI) in cardiac biomarker studies, is unclear. We determined the impact of local (at the site of subject enrollment) versus central adjudication of AMI on final diagnosis.
This is a retrospective analysis of data from the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study, an 18-center prospective study of patients with suspected acute coronary syndromes, with enrollment from December 19, 2006, to September 20, 2007. Local adjudication of AMI was performed by a single site investigator at each center following the protocol-specified definition and according to the year 2000 definition of AMI, which based cardiac troponin (cTn) elevation on local cut points for each of the 13 different assays. After completion of the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study primary analysis and to evaluate a new troponin assay, a Food and Drug Administration-mandated central adjudication was performed by 3 investigators at different institutions. This adjudication used the 2007 Universal Definition of AMI, which differs by use of the manufacturer's 99th percentile cTn cut point. We describe the outcome of this process and compare it with the local adjudication. Central adjudicators were not blinded to local adjudications. For central adjudication, discrepant diagnoses were resolved by consensus. Local versus central cTn cut points differed for 6 assays. Both definitions required a rise and/or fall of cTn. Discrepant cases were reviewed by the lead author. Difficult cases were defined as having a difference between local and central adjudication, an elevated cTn with a temporal rise and fall, and a negative or absent risk stratification test. Statistics were by χ(2), κ, and logistic regression.
Of 1,107 patients enrolled, 11 had indeterminate central adjudication, leaving 1,096 for analysis. In spite of high agreement across central versus local adjudicators, κ = 0.79 (95% CI [0.73, 0.85]), AMI was diagnosed more often by central adjudication, 134 (12.2%) versus 104 (9.5%), with 44 local diagnoses (4%) changed from non-AMI to AMI (n = 37) or AMI to non-AMI (n = 7) (P < .001). These 44 represented 34% (95% CI 26%-42%) of 141 cases in which either central or local adjudication was AMI. Of diagnoses changed to AMI, 3 reasons contributed approximately one-third each: the local use of a non-99th percentile cTn cutoff (32%), the possibility of human error (34%), and difficult cases (34%).
Despite an acceptable κ, over a third of patients with a diagnosis of AMI were not assigned that diagnosis by both sets of adjudicators. This supports the importance of 1 standard method for diagnosis of AMI.
监管要求对心肌梗死（AMI）诊断的影响尚不明确，这些要求需要中心裁定来确诊 AMI。我们旨在明确本地（在受试者登记点）和中心裁定 AMI 对最终诊断的影响。
本研究是对疑似急性冠状动脉综合征患者进行的一项多中心前瞻性研究（Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study）数据的回顾性分析，该研究于 2006 年 12 月 19 日至 2007 年 9 月 20 日期间入组了 18 个中心的患者。根据方案规定的定义和 2000 年 AMI 定义，每个中心的一位本地研究者对 AMI 进行裁定，该定义基于当地的心肌肌钙蛋白（cTn）升高切点，适用于 13 种不同检测方法中的每一种。完成 Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study 的主要分析后，为评估新的肌钙蛋白检测方法，由 3 名来自不同机构的研究者进行了 FDA 授权的中心裁定。该裁定采用了 2007 年 AMI 的通用定义，该定义与制造商的 99 百分位 cTn 切点的使用不同。我们描述了这个过程的结果，并与本地裁定进行了比较。中心裁定者并未对本地裁定进行盲法评估。对于中心裁定，不一致的诊断通过共识解决。有 6 种检测方法的本地和中心 cTn 切点不同。两种定义都需要 cTn 的升高和/或降低。对有分歧的病例由主要作者进行了审查。困难病例被定义为：本地和中心裁定之间存在差异，cTn 升高和降低，阴性或无风险分层检测。统计方法采用 χ(2)、κ 和逻辑回归。
在入组的 1107 例患者中，有 11 例的中心裁定不确定，因此有 1096 例可供分析。尽管中心和本地裁定者之间有高度一致性，κ=0.79（95%CI [0.73, 0.85]），但中心裁定 AMI 的诊断更常见，134 例（12.2%）比 104 例（9.5%）多，44 例（4%）本地诊断（n=37）或 AMI 诊断（n=7）发生变化（n=44）（P<.001）。这些病例占 141 例 AMI 诊断的 34%（95%CI 26%-42%）。被诊断为 AMI 的病例中，有 3 个原因各占约三分之一：本地使用非 99 百分位 cTn 切点（32%）、可能存在人为错误（34%）和困难病例（34%）。
尽管 κ 值可接受，但仍有超过三分之一的 AMI 诊断患者未被两组裁定者诊断为 AMI。这支持了采用 1 种标准方法诊断 AMI 的重要性。
