Kost Gerald J
Pathology and Laboratory Medicine, School of Medicine, University of California, Davis, CA 95616, USA.
Point-of-Care Testing Center for Teaching and Research (POCT•CTR), Knowledge Optimization, Davis, CA 95616, USA.
Diagnostics (Basel). 2023 Oct 16;13(20):3223. doi: 10.3390/diagnostics13203223.
A prevalence boundary (PB) marks the point in prevalence in which the false omission rate, R = FN/(TN + FN), exceeds the tolerance limit for missed diagnoses. The objectives were to mathematically analyze rapid antigen test (RAgT) performance, determine why PBs are breeched, and evaluate the merits of testing three times over five days, now required by the US Food and Drug Administration for asymptomatic persons. Equations were derived to compare test performance patterns, calculate PBs, and perform recursive computations. An independent July 2023 FDA-NIH-university-commercial evaluation of RAgTs provided performance data used in theoretical calculations. Tiered sensitivity/specificity comprise the following: tier (1) 90%, 95%; tier (2) 95%, 97.5%; and tier (3) 100%, ≥99%. Repeating a T2 test improves the PB from 44.6% to 95.2% (R 5%). In the FDA-NIH-university-commercial evaluation, RAgTs generated a sensitivity of 34.4%, which improved to 55.3% when repeated, and then improved to 68.5% with the third test. With R = 5%, PBs are 7.37/10.46/14.22%, respectively. PB analysis suggests that RAgTs should achieve a clinically proven sensitivity of 91.0-91.4%. When prevalence exceeds PBs, missed diagnoses can perpetuate virus transmission. Repeating low-sensitivity RAgTs delays diagnosis. In homes, high-risk settings, and hotspots, PB breaches may prolong contagion, defeat mitigation, facilitate new variants, and transform outbreaks into endemic disease. Molecular diagnostics can help avoid these potential vicious cycles.
流行率边界（PB）标志着流行率达到这样一个点，即假漏诊率R = FN/(TN + FN)超过漏诊诊断的容忍限度。目的是对快速抗原检测（RAgT）性能进行数学分析，确定PB被突破的原因，并评估美国食品药品监督管理局目前要求无症状者在五天内进行三次检测的优点。推导了方程以比较检测性能模式、计算PB并进行递归计算。2023年7月美国食品药品监督管理局、美国国立卫生研究院、大学和商业机构对RAgT进行的独立评估提供了用于理论计算的性能数据。分级灵敏度/特异性包括以下几种：第（1）级90%，95%；第（2）级95%，97.5%；第（3）级100%，≥99%。重复进行T2检测可将PB从44.6%提高到95.2%（R为5%）。在美国食品药品监督管理局、美国国立卫生研究院、大学和商业机构的评估中，RAgT的灵敏度为34.4%，重复检测时提高到55.3%，第三次检测时提高到68.5%。当R = 5%时，PB分别为7.37%/10.46%/14.22%。PB分析表明，RAgT应达到经临床验证的91.0 - 91.4%的灵敏度。当流行率超过PB时，漏诊诊断可能会使病毒传播持续下去。重复进行低灵敏度的RAgT会延迟诊断。在家庭、高风险场所和热点地区，PB被突破可能会延长传染期、破坏缓解措施、助长新变种出现并将疫情转变为地方病。分子诊断有助于避免这些潜在的恶性循环。
