External quality assessment-based tumor marker harmonization simulation; insights in achievable harmonization for CA 15-3 and CEA

Clinical Chemistry and Laboratory Medicine (CCLM), vol. 63, pp. 410–421

Abstract

Abstract Objectives CA 15-3 and CEA are tumor markers used in routine clinical care for breast cancer and colorectal cancer, among others. Current measurement procedures (MP) for these tumor markers are considered to be insufficiently harmonized. This study investigated the achievable harmonization for CA 15-3 and CEA by using an in silico simulation of external quality assessment (EQA) data from multiple EQA programs using patient-pool based samples. Methods CA 15-3 and CEA data from SKML (2021), UK NEQAS (2020–2021) and KEQAS (2020–2021) were used. A harmonization protocol was defined in which MPs that were considered equivalent were used to value assign EQA samples, and recalibration was only required if the MP had a bias of >5 % with value assigned EQA. Harmonization status was assessed by determining the mean level of agreement and residual variation by CV (%). Results Only MPs from Abbott, Beckman, Roche and Siemens were available in all EQA programs. For CA 15-3, recalibration was proposed for Beckman MP only and for CEA, recalibration was proposed for Siemens MP only. When the harmonization procedures were applied, for CA 15-3 the pre-harmonization mean bias range per MP was reduced from −29.28 to 9.86 %, into −0.09–0.12 % after harmonization. For CEA, the mean bias range per MP was reduced from −23.78 to 2.00 % pre-harmonization to −3.13–1.42 % post-harmonization. Conclusions The present study suggests that a significant improvement in the harmonization status of CA 15-3 and CEA may be achieved by recalibration of a limited number of MPs.

Authors 14

1. Huub H. van Rossum

   The Netherlands Cancer Institute

   Affiliation as printed

   Department of Laboratory Medicine , Netherlands Cancer Institute , Amsterdam , The Netherlands

2. Stefan Holdenrieder

   Deutsches Herzzentrum München · Institut für Laboratoriumsmedizin

   Affiliation as printed

   Institute of Laboratory Medicine, Munich Biomarker Research Center , Deutsches Herzzentrum , Munich , Germany

3. Yeo‐Min Yun

   Konkuk University Medical Center

   Affiliation as printed

   Department of Laboratory Medicine , Konkuk University Medical Center , Seoul , Republic of South Korea

4. Dina Patel

   Northern General Hospital

   Affiliation as printed

   UK NEQAS Immunology, Immunochemistry & Allergy , Northern General Hospital , Sheffield , UK

5. Marc Thelen

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Laboratory Medicine of the Radboud University Medical Center , Nijmegen , The Netherlands

   SKML , Nijmegen , The Netherlands

6. Junghan Song

   Seoul National University · Seoul National University Bundang Hospital

   Affiliation as printed

   Department of Laboratory Medicine , Seoul National University Bundang Hospital and College of Medicine , Seongnam , Republic of South Korea

7. Nick Unsworth

   Edinburgh Royal Infirmary

   Affiliation as printed

   UK NEQAS [Edinburgh], Department of Laboratory Medicine , Royal Infirmary of Edinburgh , Edinburgh , UK

8. Katherine Partridge

   Medicines and Healthcare products Regulatory Agency

   Affiliation as printed

   Therapeutic Reference Materials,Medicines and Healthcare Products Regulatory Agency (MHRA) , South Mimms , Hertfordshire , UK

9. Wei Cui

   Chinese Academy of Medical Sciences & Peking Union Medical College · Cancer Hospital of Chinese Academy of Medical Sciences

   Affiliation as printed

   Department of Laboratory Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China

10. Lakshmi V. Ramanathan

    Memorial Sloan Kettering Cancer Center

    Affiliation as printed

    Clinical Chemistry Service, Department of Laboratory Medicine , Memorial Sloan Kettering Cancer Center , New York , NY , USA

11. Qing H. Meng

    The University of Texas MD Anderson Cancer Center

    Affiliation as printed

    Department of Laboratory Medicine, Division of Pathology and Laboratory Medicine , The University of Texas MD Anderson Cancer Center , Houston , TX , USA

12. Bart E.P.B. Ballieux Aachen Department of Clinical Chemistry

    Leiden University Medical Center

    Affiliation as printed

    Department of Clinical Chemistry , Leiden University Medical Center , Leiden , The Netherlands

13. Catharine M. Sturgeon

    Edinburgh Royal Infirmary

    Affiliation as printed

    UK NEQAS [Edinburgh], Department of Laboratory Medicine , Royal Infirmary of Edinburgh , Edinburgh , UK

14. Hubert W. Vesper

    Centers for Disease Control and Prevention · National Center for Environmental Health

    Affiliation as printed

    Division of Laboratory Sciences, National Center for Environmental Health , Centers for Disease Control and Prevention , Atlanta , GA , USA