SD @ IFCC General Conference Report.pdf · 4-Variable Equation for Estimating GFR (Levey AS et al.,...
Transcript of SD @ IFCC General Conference Report.pdf · 4-Variable Equation for Estimating GFR (Levey AS et al.,...
Term and Time of Office M PANTEGHINI (IT) (Chair) 1st 2006 01 - 2008 12 I YOUNG (UK) (Vice-Chair) 1st 2006 01 - 2008 12 H MORRIS (AU) (Secretary) 2nd 2006 01 - 2008 12 P GILLERY (FR) 1st 2006 01 - 2008 12 L SIEKMANN (DE) 1st 2006 01 - 2008 12 U-H STENMAN (FI) 2nd 2006 01 - 2008 12 G BROTEA (US) (Corporate Repr) 1st 2007 01 - 2009 12 D BUNK (NIST Repr) Consultant H SCHIMMEL (IRMM Repr) Consultant J-C FOREST (JCTLM Repr) Consultant MM MÜLLER EB Liaison
2005 Glagow, UK May SD 35 Milan, Italy September SD 36 2006 Damascus, Syria April SD 37 Milan, Italy September SD 38
2007 Amsterdam, NL June SD 39 Milan, Italy September SD 40 2008 Antalya, Turkey April SD 41
Chair (appointed by EB)
4 full members (call for nominations)
Corresponding members
• COMMITTEES (8): Theme-orientated
Chair (appointed by SD)
Members (appointed by WG’s chair)
• WORKING GROUPS (14): Task-orientated
C-NPU Nomenclature, Properties and Units F. Pontet (FR)
C-MD Molecular Diagnostics F. Rousseau (CA)
C-PP Plasma Proteins G. Merlini (IT)
C-SMCD Standardization of Markers of Cardiac
Damage
F. Apple (US)
C-RSE Reference Systems of Enzymes G. Schumann
(DE)
C-POCT Point-of-Care Testing A. Okorodudu
(US)
C-TLM Traceability in Laboratory Medicine A. Kessler (DE)
C-RIDL Reference Intervals and Decision Limits F. Ceriotti (IT)
WG-SEB Selective Electrodes and Biosensors A. Lewenstam (FI)
WG-A Apolipoproteins G. Myers (US)
WG-SHCG Standardization of Human Chorionic
Gonadotropin
C. Sturgeon (UK)
WG-HbAlc Standardization of Hemoglobin A1c G. John (UK)
WG-STFT Standardization of Thyroid Function
Tests
L. Thienpoint (BE)
WG-HbA2 Standardization of Hemoglobin A2 A. Mosca (IT)
WG-CDT Standardization of Carbohydrate-
Deficient Transferrin
A. Helander (SE)
cont’d
WG-SCC Standardization of Cystatin C A. Grubb (SE)
WG-GFRA Standardization of Glomerular Filtration
Rate Assessment
N. Greenberg (US)
WG-SAU Standardization of Albumin Assays in
Urine
G. Miller (US)
WG-
PAPPA
Standardization of Pregnancy-Associated
Plasma Protein A (PAPP-A)
K. Pettersson (FI)
WG-GH Growth Hormone M. Bildlingmaier
(DE)
WG-SIA Standardization of Insulin Assays M. Steffes (US)
WG-TNI Standardization of Troponin I J. Tate (AU)
IMPLEMENTATION OF STANDARDIZATION IN LABORATORY MEDICINE
Reference Materials
Reference Measurement Procedures
Networks of Reference Laboratories
Reference Intervals & Decision Limits
SCIENTIFIC PUBLICATIONS & PARTICIPATION TO REGIONAL IFCC CONGRESSES AND MASTER DISCUSSIONS
COLLABORATIONS & PARTNERSHIP WITH OTHER INTERNATIONAL ORGANIZATIONS
The benefit of standardization
Comparability of results over time and space
would significantly contribute to
improvements in healthcare, since results of
clinical studies undertaken in different
locations or times could be universally
applied
Standardize clinical decision limits
(i.e. cutpoints for intervention)
Effective application of
evidence-based medicine
Need for Internationally Recognized Reference Measurement Systems
Original Test
RS-USA RS-EU RS-J
USA-Test EU-Test Japan-Test
RS-Global
Global Test
XUSA XEU XJ Xglobal
Tracing back the calibration to a
Reference System (RS)
Results
Different test results
high costs impaired medical reliability
Universally comparable test results lower costs
increased clinical reliability
HbA1c
COLLABORATION WITH INTERNATIONAL ORGANIZATIONS
ADA
BIPM (JCTLM, JCGM)
CDC
CLSI (NCCLS)
IRMM
ILAC (JCTLM)
IUPAC
NIBSC
NKDEP (NIH)
NIST
WHO
Declaration of co-operation
establishing
A framework for the international recognition of available higher-order reference materials,
measurement procedures and reference measurement laboratories
Objectives and Purpose
To support comparability and equivalence of measurement results in Laboratory Medicine for the purpose of improving healthcare, through worldwide accepted traceability effort
following the principles of metrology
To support IVD manufacturers in registration and licensing the CE label conforming with the EU directive
What has JCTLM delivered?
The World’s only quality-assured database of:
a) Higher Order Reference Materials b) Higher Order Reference Measurement Procedures c) Laboratory Reference Measurement Services
http://www.bipm.org/en/committees/jc/jctlm/jctlm-db/
For use by (primarily):
a) IVD industry (to ensure that results produced by
IVDs are traceable to) b) Regulators (to verify that results produced by IVDs are traceable to)
Reference System for HbA1c
1. Definition of the analyte as hemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose to the N-terminal valine of the hemoglobin -chain (N-1-deoxyfructosyl-hemoglobin);
2. Unit [according to International System (SI)] mmol/mol 3. Establishment of validated reference method:
• Specifically measure the glycated N-terminal hexapeptide of the -chain of Hb;
• The assay principle is peptide mapping after proteolytic cleavage of the molecule and measurement of the ratio of the glycated and non-glycated -N-terminal hexapeptide by HPLC/MS or HPLC/CE
4. Development of appropriate reference materials
5. Implementation of a reference laboratory network
6. Definition of reference intervals & decision limits
WG-HbA1c
Reliable linear relationships between results traceable to the IFCC reference system for HbA1c and previous national and regional recommended methods have been demonstrated, allowing the conversion of analytical and clinical data from one system to another.
The grey zones are the 95% confidence intervals
of the equation
IFCC HbA1c concentration = 53 mmol/mol
1.9 2.0 2.1 2.2 2.3 2.4
Intercept [%NGSP-HbA1c]
2001-1
2001-2
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0.88 0.90 0.92 0.94 0.96
Slope
2001-1
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6.90 6.95 7.00 7.05 7.10
%NGSP-HbA1c
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2001-2
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1.4 1.6 1.8 2.0
Intercept [%Japan-HbA1c]
2001-1
2001-2
2002-1
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0.86 0.90 0.94 0.98
Slope
2001-1
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6.5 6.6 6.7 6.8
%Japan-HbA1c
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2001-2
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0.6 0.8 1.0 1.2
Intercept [%Sw eden-HbA1c]
2001-1
2001-2
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2003-1
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2004-1
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0.92 0.96 1.00 1.04
Slope
2001-1
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5.9 6.0 6.1 6.2 6.3
%Sw eden-HbA1c
2001-1
2001-2
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1.9 2.0 2.1 2.2 2.3 2.4
Intercept [%NGSP-HbA1c]
2001-1
2001-2
2002-1
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2003-1
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2004-1
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0.88 0.90 0.92 0.94 0.96
Slope
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2001-2
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6.90 6.95 7.00 7.05 7.10
%NGSP-HbA1c
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2001-2
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1.4 1.6 1.8 2.0
Intercept [%Japan-HbA1c]
2001-1
2001-2
2002-1
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2003-2
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0.86 0.90 0.94 0.98
Slope
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6.5 6.6 6.7 6.8
%Japan-HbA1c
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2001-2
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2003-2
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0.6 0.8 1.0 1.2
Intercept [%Sw eden-HbA1c]
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2001-2
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0.92 0.96 1.00 1.04
Slope
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5.9 6.0 6.1 6.2 6.3
%Sw eden-HbA1c
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1.9 2.0 2.1 2.2 2.3 2.4
Intercept [%NGSP-HbA1c]
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2001-2
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0.88 0.90 0.92 0.94 0.96
Slope
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2001-2
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6.90 6.95 7.00 7.05 7.10
%NGSP-HbA1c
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2001-2
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1.4 1.6 1.8 2.0
Intercept [%Japan-HbA1c]
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0.86 0.90 0.94 0.98
Slope
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6.5 6.6 6.7 6.8
%Japan-HbA1c
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0.6 0.8 1.0 1.2
Intercept [%Sw eden-HbA1c]
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0.92 0.96 1.00 1.04
Slope
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5.9 6.0 6.1 6.2 6.3
%Sw eden-HbA1c
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Relationship: y=0.0915x+2.152
The transformation based on the “master equation” adds further uncertainty to the derived values [0.05% to 2%, depending from the HbA1c concentration]
The knowledge about the clinical validity of HbA1c and the decision-making criteria used by physicians in different parts of the world are however based on data, which were generated with routine tests which were not standardized.
WG-HbA1c
Suggested units and target values for HbA1c when measured with methods traceable to the IFCC reference system.
A comparison with the current figures is also given
IFCC traceable methods
Currenta
Reference interval (non-diabetics) 20-42 mmol/mol
4-6%
Target for treatment in diabeticsb <53 mmol/mol
<7%
Change of therapy in diabeticsb >64 mmol/mol
>8%
a refer to methods aligned to the US NGSP. b as recommended by American Diabetes Association.
[Panteghini M & John G, CCLM 2007;45:942 ]
1. The HbA1c results should be standardized worldwide, including the reference system and results reporting.
2. The IFCC reference system for HbA1c represents the only valid anchor to implement standardization of the measurement.
3. The HbA1c assay results are to be reported worldwide in IFCC unit (mmol/mol) and derived NGSP unit (%), using the IFCC-NGSP master equation.
4. If the ongoing “average plasma glucose study” fulfills its a priori specified criteria, an HbA1c-derived average glucose (ADAG) value will also be reported as an interpretation of the HbA1c result.
5. Glycemic goals appearing in clinical guidelines should be expressed in IFCC units, derived NGSP units, and as ADAG.
Diabetes Care 2007;30:2399 & Diabetologia 2007;50:2042
Implementation of standardization of HbA1c measurement Meeting with manufacturers (Dec 12, 2007)
- Main outcomes - All manufacturers should implement worldwide assays for HbA1c
giving results traceable to the IFCC reference system. The deadline for implementing traceability to the IFCC reference
system will be Dec 31st, 2009 for all the instruments in current use. All new instruments sold after January 1st, 2011 will report both SI
(mmol/mol – no decimals) and NGSP derived units (percentage – one decimal) for results of HbA1c tests, in agreement with the Consensus Statement.
The implementation of HbA1c results in terms of eAG will be discussed after the “A1c-derived average glucose” (ADAG) results of the ongoing clinical trial are published. However, this will not be an issue for analytical systems, but for the computer-based systems used to calculate ADAG (e.g, LIS vendors).
External Quality Assessment programs must be introduced for HbA1c testing that use commutable control materials with target values assigned using the IFCC reference measurement procedure and provide a clear definition of the allowable total error of measurements.
Available at http://www.ifcc.org/Report%20of%20HbA1c_Meeting.pdf
ALT
AST
LDH
GT
Amylase
CK
Reference Measurement Procedures
Reference Materials
Reference Laboratories
Reference Systems for Enzymes
Committee on Reference Systems for Enzymes (C-RSE)
Protocol for collaborative experiments on the establishment of reference values using assays traceable to reference systems
Production of “standardized” common reference intervals for AST, ALT, and GT
Multicentre Reference Interval Study for AST, ALT & GT
Committee on Reference Intervals and Decision Limits (C-RIDL)
Reference System for Creatinine
Working Group on Standardization of GFR Assessment (WG-GFRA)
eGFR (mL/min 1.73 m2) =
175 x (s-Cr)-1.154
x (Age)-0.203
x (0.742 if Female) x
(1.210 if African American)
IDMS-traceable MDRD Study
4-Variable Equation for Estimating GFR (Levey AS et al., Clin Chem 2007)
By using this equation and a standardized
creatinine assay, clinical laboratories can report
estimated GFR more uniformly and accurately.
Working Group on Standardization of GFR Assessment (WG-GFRA)
The use of assays that are more specific for serum creatinine determination, such as those based on enzymatic reactions, may provide more reliable eGFR values.
Supporting the choice of more specific assays by clinical laboratories represents one of the main tasks of our profession in order to report an accurate eGFR in all pertinent clinical situations.
Scientific Division
Traceability to the reference system as a mean to obtain worldwide useful reference intervals for
creatinine
Committee on Reference Intervals and Decision Limits (C-RIDL)
The work of the SD stretches across the full remit of Laboratory Medicine and seeks to address the issues of
greatest importance to the profession, laboratory users and patients.
Members of the SD are always happy to discuss ongoing or future projects with all of you and suggestions as to
other areas which the SD might address in the future are welcome.
Thanks to more than 500 specialists in Laboratory Medicine, coming from diverse organisations around the world (Hospitals, Universities, Manufacturers, Regulatory and Governmental Bodies) who contribute to the
IFCC SD activities.
