Quality Assurance for Multiplex Quantitative Clinical Chemistry Proteomics in Large Clinical Trials.

IF 1.8 Q3 MEDICAL LABORATORY TECHNOLOGY Journal of Applied Laboratory Medicine Pub Date : 2024-11-04 DOI:10.1093/jalm/jfae092
Esther Reijnders, Fred P H T M Romijn, Figen Arslan, Julien J J Georges, Mervin M Pieterse, Edwin R Schipper, Sonja Didden-Buitendijk, Machteld C Martherus-Bultman, Nico P M Smit, Nina M Diederiks, Maxim M Treep, J Wouter Jukema, Christa M Cobbaert, L Renee Ruhaak
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Abstract

Background: To evaluate the clinical performance and effectiveness of a multiplex apolipoprotein panel in the context of cardiovascular precision diagnostics, clinical samples of patients with recent acute coronary syndrome in the ODYSSEY OUTCOMES trial were measured by quantitative clinical chemistry proteomics (qCCP). The ISO15189-accredited laboratory setting, including the total testing process (TTP), served as a foundation for this study. Consequently, tailored quality assurance measures needed to be designed and implemented to suit the demands of a multiplex LC-MS/MS test.

Methods: Nine serum apolipoproteins were measured in 23 376 samples with a laboratory-developed multiplex apolipoprotein test on 4 Agilent 6495 LC-MS/MS systems. A fit-for-purpose process was designed with tailored additions enhancing the accredited laboratory infrastructure and the TTP. Quality assurance was organized in 3 steps: system suitability testing (SST), internal quality control (IQC) evaluation with adjusted Westgard rules to fit a multiplex test, and interpeptide agreement analysis. Data was semi-automatically evaluated with a custom R script.

Results: LC-MS/MS analyses were performed with the following between-run CVs: for apolipoprotein (Apo) (a) 6.2%, Apo A-I 2.3%, Apo A-II 2.1%, Apo A-IV 2.9%, Apo B 1.9%, Apo C-I 3.3%, Apo C-II 3.3%, Apo C-III 2.7%, and for Apo E 3.3% and an average interpeptide agreement Pearson r of 0.981.

Conclusions: This is the first study of its kind in which qCCP was performed at this scale. This research successfully demonstrates the feasibility of high-throughput LC-MS/MS applications in large clinical trials. ClinicalTrials.gov Registration Number: NCT01663402.

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大型临床试验中多重定量临床化学蛋白质组学的质量保证。
背景:为了评估心血管精准诊断中多重载脂蛋白面板的临床性能和有效性,我们采用定量临床化学蛋白质组学(qCCP)方法测量了ODYSSEY OUTCOMES试验中近期急性冠状动脉综合征患者的临床样本。通过 ISO15189 认证的实验室环境(包括整个检测流程 (TTP))是本研究的基础。因此,需要设计和实施量身定制的质量保证措施,以适应多重 LC-MS/MS 检测的要求:方法:在 4 套 Agilent 6495 LC-MS/MS 系统上使用实验室开发的多重脂蛋白检测方法对 23 376 份样本中的 9 种血清脂蛋白进行了检测。设计了一个适合目的的流程,并根据需要增加了增强认可实验室基础设施和 TTP 的内容。质量保证分为 3 个步骤:系统适用性测试 (SST)、使用调整后的 Westgard 规则进行内部质量控制 (IQC) 评估以适应多重检测,以及肽间一致性分析。数据通过定制的 R 脚本进行半自动评估:结果:LC-MS/MS分析的运行间变异系数如下:载脂蛋白(载脂蛋白A)(a)6.2%、载脂蛋白A-I 2.3%、载脂蛋白A-II 2.1%、载脂蛋白A-IV 2.9%、载脂蛋白B 1.9%、载脂蛋白C-I 3.3%、载脂蛋白C-II 3.3%、载脂蛋白C-III 2.7%、载脂蛋白E 3.3%,平均肽间一致性Pearson r为0.981:这是首次在如此大规模上进行 qCCP 的同类研究。这项研究成功证明了高通量 LC-MS/MS 应用于大型临床试验的可行性。ClinicalTrials.gov 注册号:NCT01663402:NCT01663402。
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来源期刊
Journal of Applied Laboratory Medicine
Journal of Applied Laboratory Medicine MEDICAL LABORATORY TECHNOLOGY-
CiteScore
3.70
自引率
5.00%
发文量
137
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