IFCC Committee for Standardization of Thyroid Function Tests C-STFT- Update on the project

Transcription

1 IFCC Committee for Standardization of Thyroid Function Tests C-STFT- Update on the project Maria-Magdalena Patru, MD, PhD Director, Medical and Scientific Affairs, Ortho Clinical Diagnostics, Member C-STFT

2 2 Disclaimer I am an employee of Ortho Clinical Diagnostics, the manufacturer of VITROS TSH and VITROS FT4 assays.

3 C-STFT Scientific Committee 3 Name Position Country Term Time in Office L. Thienpont Chair BE 2nd B. Das Member IN 2nd J.D. Faix Member US 2nd F. MacKenzie Member UK 2nd M.M. Patru Member/OCUS 1st D F. Quinn Consultant US M. Consultant DE Rottmann K. Van Consultant BE Uytfanghe Accessed May 2017

4 List of Corresponding Members 4 Nominated by National Societies Paul Williams Australasian Assocition of Clinical Biochemists (AACB) Pierre Carayon Société Française de Biologie Clinique (SFBC) M. Reza Bakhtiari Iranian Association of Clinical Laboratory Doctors Akira Hishinuma Japan Society of Clinical Chemistry (JSCC) Simeon Adebisi Association of Clinical Chemists Nigeria (ACCN) Jens Berg Norwegian Society of Medical Biochemistry Lakminda Thilakarathna Association for Clinical Biochemistry, Sri Lanka Sevgi Eskiocak Turkish Biochemical Society (TBS) David Halsall Association for Clinical Biochemistry (ACB) - UK Nominated by Corporate Members Gordon Avery ABBOTT Diagnostics Annette Adelmann BECKMAN COULTER Paul Sibley SIEMENS Accessed May 2017

5 Traceability- patient results are linked to an accepted reference Definition: Property of a measurement result whereby the result can be related to a stated reference through a documented unbroken chain of calibrations, each contributing to the measurement uncertainty." Goal: to link measurement results from a patient sample to a commonly accepted reference, making them comparable across measurement systems, location, and time. International Vocabulary of Basic and General Terms in Metrology (VIM)

6 Standardization- patient results are traceable to a standard reference Definition: When results for a measurand are equivalent and, in addition, the results are traceable to the International System of Units (SE) through a higherorder primary (pure substance) reference material and/or reference measurement procedure. Clin Chem 57:87: (2011)

7 The concept of standardization Accessed May 2017

8 Harmonization-patient results are traceable to allmethods mean in the absence of a reference standard Definition: When results are equivalent either by being traceable to a reference material or based on a consensus approach, such as agreement to an all-methods mean, but neither a higher-order primary reference material nor a reference measurement procedure exist. Clin Chem 57:87: (2011)

9 Main Outcomes of the TFT Standardization/Harmonization Project Common reference intervals and/or clinical practice decision limits 9 Combine laboratory data across studies to translate research into patient care & disease prevention activities Develop evidence-based clinical practice guidelines Include laboratory test results in electronic patient records Accessed May 2017

10 Milestones of the TFT Project 10 The conventional RMP for standardization of FT4 measurements The APTM for harmonization of TSH measurements The method comparison studies The Phase IV Study Accessed May 2017

11 The conventional reference measurement procedure (crmp) for FT4 Accessed May 2017

12 Harmonization of TSH to an All Procedure Trimmed Mean 12 The C-STFT decided to preserve the traceability of TSH assays to the WHO IRP in their proposed harmonization process, and recommends the All Procedure Trimmed Mean (APTM, expressed in IU) statistically inferred by a robust factor analysis model as surrogate RMP. The APTM is derived from data of a dedicated method comparison study with native human samples, in which as many TSH assays as possible participate. This APTM targeted panel becomes the key tool in the harmonization process. All follow-up panels need to be made traceable to it (process to do this is in place and was used for the first follow-up panel). Accessed May 2017

13 Phase III-Status of TSH assays 13

14 Phase III: status of the FT4 assay 14

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19 Pre- (green) and post-(blue) recalibration reference intervals of the individual immunoassays to the overall RI Thienpont et al, Thienpont et al, Harmonization of serum thyroid-stimulating hormone measurements paves the way for the adoption of a more uniform reference interval- technical report.unpublished data, Manuscript accepted to Clin Chem.

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21 Stability of performance- The Percentiler 21 Analyte Analyte Analyte Stable Drift shift Moving median calculated from daily medians of outpatient results must be stable within preset limits Van Houcke SK, Stepman HC, Thienpont LM, Fiers T, Stove V, Couck P, Anckaert E, Gorus F. Long-term stability of laboratory tests and practical implications for quality management. Clin Chem Lab Med 2013;51: IFCC C-STFT - July 2014

22 FT4 standardization- Will it happen? 22

23 The Standardized Reference Intervals for Thyroid Testing Survey C-STFT has asked input from different stakeholders on the: - Estimated risks to patient safety as a consequence of changing the reference interval for patients with thyroid disorders, -Measures your laboratory would take to minimize these risks experts in laboratory endocrinology >95% having an academic degree (MD, PhD, MD/PhD) responded. 78% : hospital, academic, core lab or private practice setting, 11% industry, 11% government/military-, managed care-, and research 70%: director/administrator 11% consultants 19% : supervisor/team leader, or coordinator, clinical lab scientist/medical technologist, educator/trainer, clinical fellow. Endocrinology Division News Volume 2 Issue 2 Jul 2016

24 Survey Results 24 Patient safety after a considerable change in reference intervals 50% of the responders say that they estimate the risk for misinterpretation not likely 50% do because physicians sometimes misunderstand reference intervals, or are so used to certain numbers that they are reluctant to changes Measures taken by the laboratory to avoid misinterpretation by clinicians: 85% confirm the establishment of a communication policy Although it is difficult to convey information to busy physicians the larger the medical center, the higher the likelihood of misinterpretations after changes, because it is difficult to communicate with every clinician on time. Endocrinology Division News Volume 2 Issue 2 Jul 2016

25 Phase IV Publications Submitted 25 Thienpont et al., Harmonization of serum thyroid-stimulating hormone measurements paves the way for the adoption of a more uniform reference interval- technical report. De Grande et al., IFCC report on global standardization of free thyroxine immunoassays and its impact on future reference intervals

26 Standardization/Harmonization-Way Forward Liaise with key stakeholders to implement the use of methods traceable to agreed reference methods in routine clinical practice Through collaboration with IFCC EMD to provide educational materials for manufacturers, clinicians and patients which will support the implementation of traceable methods Accessed May 2017

27 Thank You

28 VITROS TSH and FT4 assays

29 VITROS TSH Assay 29

30 VITROS FT4 Assay 30

31 VITROS TSH Assay Performance Pre-Harmonization 31 Results from testing of IFCC C-STFT Phase IV patient sample panel in VITROS TSH Assay. IFCC Panel 101 TSH Samples, Approx.: 40 Hypothyroid, 30 Euthyroid & 30 Hyperthyroid Testing of the IFCC patient sample panel in the VITROS TSH assay indicates that there is under recovery at doses below the clinical decision threshold of 0.10 miu/l. At TSH concentrations of 0.10 miu/l and above, the assay shows good alignment to the APTM values (both APTM(4)* and APTM(11)**). *All Procedure Trimmed Mean (4) - Values determined from four major IVD manufacturers (Identities not disclosed). ** All Procedure Trimmed Mean (11) Values determined from all 11 participating IVD manufacturers. PR Poster presented at AACC, Philadelphia, July 2016

32 VITROS TSH Assay Results Post Harmonization 32 Results from testing of IFCC C-STFT Phase IV patient sample panel in VITROS TSH Assay with revised master reference calibrator set. IFCC Panel, 100 TSH Samples: 40 Hypothyroid, 30 Euthyroid and 30 Hyperthyroid Testing of the revised master reference calibrator set shows the improved agreement of the VITROS TSH assay to the IFCC patient sample panel APTM(4)* values across the whole of the assays measuring range ( mIU/L). *All Procedure Trimmed Mean (4) - Values determined from four major IVD manufacturers (Identities not disclosed) PR Poster presented at AACC, Philadelphia, July 2016

33 VITROS FT4 Assay Performance Pre-Standardization Testing of IFCC C-STFT Phase IV patient sample panel in the VITROS FT4 Assay. IFCC Panel 91 FT4 Samples, Approx: 30 Hypothyroid, 30 Euthyroid & 30 Hyperthyroid 33 Comparison of results generated indicates that the VITROS FT4 assay under recovers across the range tested versus the IFCC crmp values (ED ID- LC/MS/MS), as indicated by the correlation slope of However significant bias was observed for all participating FT4 immunoassays when compared to the crmp L.M. Thienpont.: A Progress Report of the IFCC Committee for Standardization of Thyroid Function Tests. Eur Thyroid J. 3, ;2014 PR Poster presented at AACC, Philadelphia, July 2016

34 VITROS FT4 Assay Standardization Methods & Results The existing VITROS FT4 master reference calibrator values were adjusted to achieve the optimal fit to the IFCC Panel reference method (ED ID-LC/MS/MS) results. 34 Testing of the revised master reference calibrator set shows the improved agreement of VITROS FT4 assay to the IFCC patient sample panel crmp values (ED ID-LC/MS/MS). the The changes to the assigned values of master reference calibrators has resulted in an increase of the measurable (reportable) range of the assay from to pmol/L. PR Poster presented at AACC, Philadelphia, July 2016

35 Conclusion 35 VITROS TSH Feasibility testing in the VITROS TSH Assay with the revised master reference calibrator set indicates that the functional sensitivity achieved is consistent with 3 rd Generation TSH immunoassay performance 3. Very good agreement with the APTM pre-and post harmonization in the clinical range. VITROS FT4 Adjustment of the VITROS FT4 Assigned master reference calibrator values achieves good agreement to the IFCC conventional reference method procedure (crmp, ED ID-LC/MS/MS). The VITROS FT4 assay is a true free hormone assay, which is currently well aligned with other FT4 immunoassays. Any future changes to the calibration of the VITROS FT4 assay will be based on recommendations of the C-STFT. PR Poster presented at AACC, Philadelphia, July 2016

36 Thank You