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


Journal

The journal of applied laboratory medicine
ISSN: 2576-9456
Titre abrégé: J Appl Lab Med
Pays: England
ID NLM: 101693884

Informations de publication

Date de publication:
06 Sep 2024
Historique:
received: 01 03 2024
accepted: 20 06 2024
medline: 6 9 2024
pubmed: 6 9 2024
entrez: 6 9 2024
Statut: aheadofprint

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND 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 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 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 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.

Identifiants

pubmed: 39239905
pii: 7750195
doi: 10.1093/jalm/jfae092
pii:
doi:

Banques de données

ClinicalTrials.gov
['NCT01663402']

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Association for Diagnostics & Laboratory Medicine 2024.

Auteurs

Esther Reijnders (E)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Fred P H T M Romijn (FPHTM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Figen Arslan (F)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Julien J J Georges (JJJ)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Mervin M Pieterse (MM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Edwin R Schipper (ER)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Sonja Didden-Buitendijk (S)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Machteld C Martherus-Bultman (MC)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Nico P M Smit (NPM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Nina M Diederiks (NM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Maxim M Treep (MM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

J Wouter Jukema (JW)

Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Netherlands Heart Institute, Utrecht, the Netherlands.

Christa M Cobbaert (CM)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

L Renee Ruhaak (LR)

Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands.

Classifications MeSH