A-027 Analytical and clinical performance of VITROS™ Immunodiagnostic Products hs Troponin I Assay in United States Patients

Abstract

The study objectives were: 1) establish 99th percentile upper reference limits (URL) for the VITROS™ Immunodiagnostic Products hs Troponin I (VITROS hsTnI) Assay, 2) confirm VITROS hsTnI Assay meets analytical performance criteria for a high-sensitivity cardiac troponin assay established by the IFCC Task Force on Cardiac Bio-markers (TF-CB), and 3) evaluate clinical performance for aiding in diagnosis of myocardial infarction (MI). Overall and sex-specific 99th percentile URLs were established with lithium heparin plasma samples from a healthy U.S. reference population (N = 952, aged 22–91 years) including 486 females and 466 males. Subjects were pre-screened via questionnaire, followed by biomarker-based screening per IFCC TF-CB recommendations. VITROS hsTnI Assay results were assessed to verify detectable troponin concentrations at or above the limit of detection (LoD [0.59 ng/L]) in >=50% of healthy males and females. Analytical imprecision (% coefficient of variation [%CV]) was determined at overall and sex-specific cutoffs. The clinical performance study enrolled subjects 22 years and older, presenting with symptoms consistent with acute coronary syndrome at 24 U.S. emergency departments (ED). Each subject’s diagnosis was determined by an independent adjudication committee consisting of cardiologists and according to the Fourth Universal Definition of Myocardial Infarction. Serial lithium heparin plasma specimens were tested with VITROS hsTnI Assay in four time brackets relative to patients’ ED presentation (0–2 hours, >=2–4 hours, >=4–6 hours, and >=6–11 hours). Sensitivity, specificity, positive and negative predictive values (PPV and NPV) were determined for each time bracket. Testing was performed on VITROS 5600 Integrated System. Comparable assay performance has been demonstrated across VITROS 3600 Immunodiagnostic and XT 7600 Integrated Systems. The overall 99th percentile URL was determined to be 11 ng/L (90% CI, 8.2–14.3 ng/L); the female-specific URL was 9 ng/L (90% CI, 3.9–17.5 ng/L); and the male-specific URL was 12 ng/L (90% CI, 8.8–20.9 ng/L). Analytical imprecision was 4.7%CV at the female-specific URL, 4.5%CV at the male-specific URL, and 4.5%CV at the overall URL. VITROS hsTnI Assay detected troponin concentrations at or above the LoD in 659/952 healthy subjects (69.2%), 282/486 (58.0%) females and 377/466 (80.9%) males. The prevalence of adjudicated MI in the study was 8.16% (175/2145). Using the overall URL, clinical sensitivity of VITROS hsTnI Assay for all subjects ranged from 85.64%–93.30% across all time brackets. Specificity ranged from 78.55%–86.60%. NPVs were >=98.57% and PPVs ranged from 35.80%–40.14%. For females, using the sex-specific URL, sensitivity and specificity ranged from 88.71–97.62% and 84.76–90.31%, respectively. NPV was >99% for all time brackets while PPV ranged from 36.67–45.11%. For males, sensitivity and specificity ranged from 84.03–93.16% and 75.07–83.11%, respectively. NPVs were >=97.95% and PPVs ranged from 35.06–39.07%. The VITROS hsTnI Assay meets the analytical performance criteria for a high-sensitivity cardiac troponin assay, demonstrating acceptable precision at the 99th percentile URLs and detection rates >50% in a healthy reference population. The clinical performance assessment demonstrated the assay effectively aids in diagnosis of MI in a U.S. population when used in conjunction with other clinical information.