Quality Control Measurements Yield Similar Variation Below and Above Limit of Quantification for High-Sensitivity Cardiac Troponin I Assays

There has been much focus on what constitutes an “undetectable” high-sensitivity cardiac troponin (hs-cTn) level. The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers (IFCC C-CB) uses the limit of detection (LOD), in part, to aid in classifying an assay as a high-sensitivity assay. However, some regulatory bodies (i.e., United States Food and Drug Administration [FDA]) limit reporting of hs-cTn assays to values at or above the limit of quantification (LOQ) (1). How these metrics are derived varies between manufacturers; different approaches are proposed by different groups, with a 20% coefficient of variation (CV) often used to designate the LOQ (1). Assessing variability via %CV at low concentrations (i.e., <10 ng/L) may not capture acceptable variation, where absolute analytical variation of ±3 ng/L has been proposed as an analytical goal (2). Use of this analytical variability metric has support from different external proficiency testing schemes and has minimal impact (via simulation) on myocardial infarction diagnosis in the emergency setting (3, 4). For a ±3 ng/L analytical limit, a standard deviation (SD) of ≤1 ng/L would be suitable. However, this has not been formally evaluated at concentrations below the LOQ, especially with commercial quality control (QC) material. In the present analysis, we evaluated imprecision (SD and %CV) with a commercial QC material that yielded concentrations below and above the LOQ for different hs-cTn assays.