Linda M Thienpont1,2, Katleen Van Uytfanghe3, Linde A C De Grande4, Dries Reynders5, Barnali Das6, James D Faix7, Finlay MacKenzie8, Brigitte Decallonne9, Akira Hishinuma10, Bruno Lapauw11, Paul Taelman12, Paul Van Crombrugge13, Annick Van den Bruel14, Brigitte Velkeniers15, Paul Williams16. 1. Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium; linda.thienpont@ugent.be. 2. Current affiliation: Thienpont & Stöckl Wissenschaftliches Consulting GbR, Rennertshofen (OT Bertoldsheim), Germany. 3. Ref4U, Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. 4. Department of Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. 5. Department of Applied Mathematics, Computer Science, and Statistics, Faculty of Sciences, Ghent University, Ghent, Belgium. 6. Biochemistry and Immunology Laboratory, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, India. 7. Clinical Chemistry and Immunology, Montefiore Medical Center, and Department of Pathology, Albert Einstein School of Medicine, New York, NY. 8. Birmingham Quality/UK NEQAS, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 9. Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium. 10. Department of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, Japan. 11. Department of Endocrinology, Ghent University Hospital, Ghent, Belgium. 12. Laboratory of Endocrinology, Department of Laboratory Medicine, AZ Maria-Middelares Sint-Jozef, Campus Maria-Middelares, Ghent, Belgium. 13. Department of Endocrinology, OLV Ziekenhuis Aalst-Asse-Ninove, Aalst, Belgium. 14. Department of Endocrinology, General Hospital Sint Jan, Bruges, Belgium. 15. Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium. 16. Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, Australia.
Abstract
BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests developed a global harmonization approach for thyroid-stimulating hormone measurements. It is based on a multiassay method comparison study with clinical serum samples and target setting with a robust factor analysis method. Here we describe the Phase IV method comparison and reference interval (RI) studies conducted with the objective to recalibrate the participating assays and demonstrate the proof-of-concept. METHODS: Fourteen manufacturers measured the harmonization and RI panel; 4 of them quantified the harmonization and first follow-up panel in parallel. All recalibrated their assays to the statistically inferred targets. For validation, we used desirable specifications from the biological variation for the bias and total error (TE). The RI measurements were done with the assays' current calibrators, but data were also reported after transformation to the new calibration status. We estimated the pre- and postrecalibration RIs with a nonparametric bootstrap procedure. RESULTS: After recalibration, 14 of 15 assays met the bias specification with 95% confidence; 8 assays complied with the TE specification. The CV of the assay means for the harmonization panel was reduced from 9.5% to 4.2%. The RI study showed improved uniformity after recalibration: the ranges (i.e., maximum differences) exhibited by the assay-specific 2.5th, 50th, and 97.5th percentile estimates were reduced from 0.27, 0.89, and 2.13 mIU/L to 0.12, 0.29, and 0.77 mIU/L. CONCLUSIONS: We showed that harmonization increased the agreement of results from the participating immunoassays, and may allow them to adopt a more uniform RI in the future.
BACKGROUND: The IFCC Committee for Standardization of Thyroid Function Tests developed a global harmonization approach for thyroid-stimulating hormone measurements. It is based on a multiassay method comparison study with clinical serum samples and target setting with a robust factor analysis method. Here we describe the Phase IV method comparison and reference interval (RI) studies conducted with the objective to recalibrate the participating assays and demonstrate the proof-of-concept. METHODS: Fourteen manufacturers measured the harmonization and RI panel; 4 of them quantified the harmonization and first follow-up panel in parallel. All recalibrated their assays to the statistically inferred targets. For validation, we used desirable specifications from the biological variation for the bias and total error (TE). The RI measurements were done with the assays' current calibrators, but data were also reported after transformation to the new calibration status. We estimated the pre- and postrecalibration RIs with a nonparametric bootstrap procedure. RESULTS: After recalibration, 14 of 15 assays met the bias specification with 95% confidence; 8 assays complied with the TE specification. The CV of the assay means for the harmonization panel was reduced from 9.5% to 4.2%. The RI study showed improved uniformity after recalibration: the ranges (i.e., maximum differences) exhibited by the assay-specific 2.5th, 50th, and 97.5th percentile estimates were reduced from 0.27, 0.89, and 2.13 mIU/L to 0.12, 0.29, and 0.77 mIU/L. CONCLUSIONS: We showed that harmonization increased the agreement of results from the participating immunoassays, and may allow them to adopt a more uniform RI in the future.
Authors: Charles Austin Pickens; Maya Sternberg; Mary Seeterlin; Víctor R De Jesús; Mark Morrissey; Adrienne Manning; Sonal Bhakta; Patrice K Held; Joanne Mei; Carla Cuthbert; Konstantinos Petritis Journal: Int J Neonatal Screen Date: 2020-09-17