抗逆转录病毒药物临床药理学质量保证能力验证计划中性能评估的变异性和准确性的来源。

Sources of Variability and Accuracy of Performance Assessment in the Clinical Pharmacology Quality Assurance Proficiency Testing Program for Antiretrovirals.

机构信息

Department of Biotechnical and Clinical Laboratory Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.

Frontier Science Technology and Research Foundation, Amherst, New York.

出版信息

Ther Drug Monit. 2019 Aug;41(4):452-458. doi: 10.1097/FTD.0000000000000612.

DOI:10.1097/FTD.0000000000000612

PMID:30829950

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6629475/

Abstract

BACKGROUND

The Clinical Pharmacology Quality Assurance (CPQA) program provides semiannual proficiency testing (PT) of antiretroviral analytes for 11 US and international clinical pharmacology laboratories (CPLs) to ensure interlaboratory comparability. In this article, we provide estimates of the main sources of variability and assess the accuracy of the algorithm for the assessment of performance.

METHODS

Descriptive statistics are reported from 13 PT rounds from 2010 to 2016. Eight of the most common antiretroviral analytes were examined. Variance components analysis was used to rank the relative contributions of CPLs, antiretroviral analyte, and concentration category (low, medium, and high) to bias and variability using mixed models. Binary classification metrics of the PT assessment algorithm are calculated in comparison with a model using 95% prediction limits around estimated regression equations.

RESULTS

CPLs provided 4109 reported concentrations of 65 unique samples for each of the 8 antiretroviral analytes across 13 PT rounds. Individual CPL accounted for the greatest amount of total variability (4.4%). Individual CPL and analyte combination (interaction) accounted for the greatest amount of bias (8.1%). Analyte alone accounted for 0.5% or less for total variability and bias. Overall, using a ±20% acceptance window around the final target, 97% of individual reported concentrations were scored acceptable, and 96% of antiretroviral/round scores were deemed satisfactory. Comparison with the regression model gave 100% sensitivity but only 34.47% specificity. Narrowing the acceptance window to ±15% improved specificity to 84.47% while maintaining a 99.17% sensitivity.

CONCLUSIONS

The current CPQA PT scoring algorithm that use a ±20% acceptance window seems to suffer from a low specificity and may be too lenient. A stricter ±15% acceptance window would increase specificity and overall accuracy while lowering the overall pass rate by only 3%.

摘要

背景

临床药理学质量保证（CPQA）计划为 11 个美国和国际临床药理学实验室（CPL）提供半年一次的抗逆转录病毒分析物能力验证（PT），以确保实验室间的可比性。在本文中，我们提供了变异的主要来源的估计，并评估了用于评估性能的算法的准确性。

方法

报告了 2010 年至 2016 年 13 个 PT 轮次的描述性统计数据。检查了 8 种最常见的抗逆转录病毒分析物。方差分量分析用于使用混合模型，根据实验室、抗逆转录病毒分析物和浓度类别（低、中、高）对偏倚和变异的相对贡献对等级进行排名。与使用估计回归方程周围 95%预测限的模型相比，计算了 PT 评估算法的二元分类指标。

结果

在 13 个 PT 轮次中，每个实验室对 8 种抗逆转录病毒分析物的 65 个独特样本中的 65 个样本提供了 4109 个报告浓度。单个 CPL 占总变异的最大比例（4.4%）。单个 CPL 和分析物组合（相互作用）占偏倚的最大比例（8.1%）。分析物本身仅占总变异和偏倚的 0.5%或更小。总体而言，在最终目标周围使用±20%的接受窗口，97%的个体报告浓度的评分可接受，96%的抗逆转录病毒/轮次评分令人满意。与回归模型的比较产生了 100%的灵敏度，但只有 34.47%的特异性。将接受窗口缩小到±15%可以将特异性提高到 84.47%，同时保持 99.17%的灵敏度。