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Abstract：
BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) assays have been developed that quantify lower cTnI concentrations with better precision versus earlier generation assays. hs-cTnI assays allow improved clinical utility for diagnosis and risk stratification in patients presenting to the emergency department with suspected acute myocardial infarction. We describe the High-Sensitivity Cardiac Troponin I Assays in the United States (HIGH-US) study design used to conduct studies for characterizing the analytical and clinical performance of hs-cTnI assays, as required by the US Food and Drug Administration for a 510(k) clearance application. This study was non-interventional and therefore it was not registered at clinicaltrials.gov.
METHODS: We conducted analytic studies utilizing Clinical and Laboratory Standards Institute guidance that included limit of blank, limit of detection, limit of quantitation, linearity, within-run and between run imprecision and reproducibility as well as potential interferences and high dose hook effect. A sample set collected from healthy females and males was used to determine the overall and sex-specific cTnI 99th percentile upper reference limits (URL). The total coefficient of variation at the female 99th percentile URL and a universally available American Association for Clinical Chemistry sample set (AACC Universal Sample Bank) from healthy females and males was used to examine high-sensitivity (hs) performance of the cTnI assays. Clinical diagnosis of enrolled subjects was adjudicated by expert cardiologists and emergency medicine physicians. Assessment of temporal diagnostic accuracy including sensitivity, specificity, positive predictive value, and negative predictive value were determined at presentation and collection times thereafter. The prognostic performance at one-year after presentation to the emergency department was also performed. This design is appropriate to describe analytical characterization and clinical performance, and allows for acute myocardial infarction diagnosis and risk assessment.
METHODS: We conducted analytic studies utilizing Clinical and Laboratory Standards Institute guidance that included limit of blank, limit of detection, limit of quantitation, linearity, within-run and between run imprecision and reproducibility as well as potential interferences and high dose hook effect. A sample set collected from healthy females and males was used to determine the overall and sex-specific cTnI 99th percentile upper reference limits (URL). The total coefficient of variation at the female 99th percentile URL and a universally available American Association for Clinical Chemistry sample set (AACC Universal Sample Bank) from healthy females and males was used to examine high-sensitivity (hs) performance of the cTnI assays. Clinical diagnosis of enrolled subjects was adjudicated by expert cardiologists and emergency medicine physicians. Assessment of temporal diagnostic accuracy including sensitivity, specificity, positive predictive value, and negative predictive value were determined at presentation and collection times thereafter. The prognostic performance at one-year after presentation to the emergency department was also performed. This design is appropriate to describe analytical characterization and clinical performance, and allows for acute myocardial infarction diagnosis and risk assessment.
摘要：
背景：已经开发了高灵敏度的心肌肌钙蛋白I（hs-cTnI）测定法，该测定法与较早的测定法相比以更好的精度定量较低的cTnI浓度。hs-cTnI测定可以改善向急诊科就诊的疑似急性心肌梗塞患者的诊断和风险分层的临床实用性。我们描述了美国的高灵敏度心脏肌钙蛋白I测定（HIGH-US）研究设计，用于进行表征hs-cTnI测定的分析和临床表现的研究。根据美国食品和药物管理局510（k）许可申请的要求。这项研究是非干预性的，因此没有在临床试验中注册。
方法：我们利用临床和实验室标准研究所指南进行了分析研究，其中包括空白，检测限，定量极限，线性度运行内和运行之间的不精确性和可重复性以及潜在的干扰和高剂量钩效应。从健康女性和男性收集的样品集用于确定总体和性别特异性cTnI第99百分位数参考上限(URL)。使用女性第99百分位数URL处的总变异系数和来自健康女性和男性的普遍可用的美国临床化学协会样品集(AACC通用样品库)来检查cTnI测定的高灵敏度(hs)性能。入选受试者的临床诊断由心脏病专家和急诊医师裁定。时间诊断准确性评估，包括灵敏度，特异性，正预测值，和阴性预测值在之后的展示和收集时间确定。还进行了向急诊科就诊后一年的预后表现。此设计适用于描述分析表征和临床表现，并允许急性心肌梗死的诊断和风险评估。
方法：我们利用临床和实验室标准研究所指南进行了分析研究，其中包括空白，检测限，定量极限，线性度运行内和运行之间的不精确性和可重复性以及潜在的干扰和高剂量钩效应。从健康女性和男性收集的样品集用于确定总体和性别特异性cTnI第99百分位数参考上限(URL)。使用女性第99百分位数URL处的总变异系数和来自健康女性和男性的普遍可用的美国临床化学协会样品集(AACC通用样品库)来检查cTnI测定的高灵敏度(hs)性能。入选受试者的临床诊断由心脏病专家和急诊医师裁定。时间诊断准确性评估，包括灵敏度，特异性，正预测值，和阴性预测值在之后的展示和收集时间确定。还进行了向急诊科就诊后一年的预后表现。此设计适用于描述分析表征和临床表现，并允许急性心肌梗死的诊断和风险评估。
