Background Clinical decision-making for risk stratification for possible myocardial infarction (MI) uses high-sensitivity cardiac troponin (hs-cTn) thresholds that range from the limit of detection to several-fold higher than the upper reference limit (URL). To establish a minimum analytical variation standard, we can quantify the effect of variation on the population clinical measures of safety (sensitivity) and effectiveness [proportion below threshold, or positive predictive value (PPV)]. Methods From large datasets of patients investigated for possible MI with the Abbott hs-cTnI and Roche hs-cTnT assays, we synthesized datasets of 1 000 000 simulated patients. Troponin concentrations were randomly varied several times based on absolute deviations of 0.5 to 3 ng/L and relative changes of 2% to 20% around the low-risk threshold (5 ng/L) and URLs, respectively. Results For both assays at the low-risk thresholds, there were negligible differences in sensitivity (<0.3%) with increasing analytical variation. The proportion of patients characterized as low risk reduced by 30% to 29% (Roche) and 53% to 44% (Abbott). At the URL, increasing analytical variation also did not change sensitivity; the PPV fell by less than 3%. For risk stratification, increased delta thresholds (change between serial troponin concentrations) increased sensitivity at the cost of a decreased percentage of patients below the delta threshold, with the largest changes at the greatest analytical variation. Conclusions At the low-risk threshold, analytical variation up to 3 ng/L minimally impacted the safety metric (sensitivity) but marginally reduced effectiveness. Similarly, at the URL even relative variation up to 25% minimally impacted safety metrics and effectiveness. Analytical variation for delta thresholds did not negatively impact sensitivity but decreased effectiveness.

中文翻译：

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确定临床可接受的心肌肌钙蛋白在决策阈值的分析变异

背景 对可能的心肌梗死 (MI) 进行风险分层的临床决策使用高敏心肌肌钙蛋白 (hs-cTn) 阈值，其范围从检测限到比参考上限 (URL) 高几倍。为了建立最小分析变异标准，我们可以量化变异对群体临床安全性（敏感性）和有效性指标的影响[低于阈值的比例，或阳性预测值（PPV）]。方法 从使用 Abbott hs-cTnI 和 Roche hs-cTnT 检测调查可能发生 MI 的患者的大型数据集中，我们合成了 1 000 000 名模拟患者的数据集。肌钙蛋白浓度分别根据低风险阈值 (5 ng/L) 和 URL 周围 0.5 至 3 ng/L 的绝对偏差和 2% 至 20% 的相对变化随机变化数次。结果 对于低风险阈值下的两种测定，随着分析变异的增加，灵敏度的差异可以忽略不计(＜0.​​3％)。低风险患者比例减少了 30% 至 29%（罗氏）和 53% 至 44%（雅培）。在 URL 处，增加分析变异也不会改变灵敏度； PPV下降了不到3%。对于风险分层，增加 Delta 阈值（连续肌钙蛋白浓度之间的变化）可以提高敏感性，但代价是低于 Delta 阈值的患者比例下降，分析变异最大时变化最大。结论 在低风险阈值下，高达 3 ng/L 的分析变异对安全指标（灵敏度）的影响最小，但有效性略有降低。同样，在 URL 处，即使相对变化高达 25%，对安全指标和有效性的影响也最小。增量阈值的分析变化不会对灵敏度产生负面影响，但会降低有效性。