Reporting HbA1c Task Force for HbA1c

Cas Weykamp, Secretary

IFCC General Conference, Kuala Lumpur, Malaysia, 19 November 2012

Development Reference Method

IFCC

IFCC Scientific Division

Working Group HbA1c Chair: Garry John

Network HbA1c Coordinator: Cas Weykamp

2009: Evaluation

Analytical The IFCC Reference Measurement Procedure for HbA1c

is accepted worldwide as the only valid anchor for the

standardisation of HbA1c and should be maintained

in a Network of reference laboratories

Reporting Units and Use HbA1c Reporting of HbA1c in SI units (mmol/mol) and use

of HbA1c for diagnosis and screening is discussed

worldwide and Education should be intensified

Disband Working Group….

IFCC

IFCC Scientific Division

Working Group HbA1c Chair: Garry John

Network HbA1c Coordinator: Cas Weykamp

….Reorganise

IFCC

IFCC Scientific Division

IFCC C-TLM

Network HbA1c Coordinator: Cas Weykamp

Integrated Project HbA1c Chair: Garry John

Metrological Aspects Educational/Clinical Aspects

Definition The Task Force for HbA1c is an Integrated Project that

involves input from a number of IFCC functional units

and also from clinical experts in the field of Diabetes

Task Force HbA1c

Definition The Task Force for HbA1c is an Integrated Project that

involves input from a number of IFCC functional units

and also from clinical experts in the field of Diabetes

Aim To establish an interface between IFCC and its National

/Corporate members and the clinical users of HbA1c to

enable the implementation of a scientifically sound reporting

structure for HbA1c standardised to the

IFCC Reference Measurement Procedure

Task Force HbA1c

Group Experts

Analytical * Advisory Board Network Reference Labs

* Scientific Links between National networks

* Work with Manufacturers

Units and Education * Links Professional Bodies Transition Units

* Help Implementation Consensus Statement

* Monitor introduction Consensus Statement

Quality Targets monitoring, diagnosis, screening

Objectives Task Force HbA1c

Group Experts Prof. G. John Chair UK

Dr. C. Weykamp Secretary NL

Prof. L. Ji Member CN

Prof. I Takei Member JP

Dr. D. Sacks Member US

Dr. R. Little Member US

Dr. E. Lenters Member NL

Prof. P. Gillery SD Liaison FR

Dr. R. Hinzmann EMD Liaison DE

Dr. G. Sypniewska CPD Liaison PL

Objectives Task Force HbA1c

Group Experts

Analytical * Advisory Board Network Reference Labs

* Scientific Links between National networks

* Work with Manufacturers

Units and Education * Links Professional Bodies Tranisition Units

* Help Implementation Consensus Statement

* Monitor introduction Consensus Statement

Quality Targets monitoring, diagnosis, screening

Objectives Task Force HbA1c

US

US JP JP

JP

NL NL

I

D F

D US

CH KO

IN

Approved Approved 2012 Candidate

IFCC Network Labs

?

Tasks Network

Warrant Availability

Tools

Continuity Traceability

Warrant Network

Quality HbA1c worldwide IFCC

Traceable

SOP

Calibrator Sets

Rules

Statistics

Approval Candidates

Re-Approval Network Labs

Manufacturers

EQA/PT Organisers

DCM’s

Control Sets

Organisation Others

Candidate Shanghai Approved

Approval Lab Elliptic (Study Cape Town)

-4

-3

-2

-1

0

1

2

3

4

-0,06 -0,04 -0,02 0 0,02 0,04 0,06

Proportional Bias

Syste

mati

c B

ias

lab_01

lab_02

lab_03

lab_05

lab_06

lab_08

lab_11

lab_12

lab_14

lab_15

lab_16

lab_17

lab_18

Periodical Re-Approval Network Labs

Clin Chem

2008;54:240-8

The IFCC Reference Measurement System for HbA1c:

A 6-Year Progress Report

Cas Weykamp (1*), W. Garry John (2), Andrea Mosca (3)

Tadao Hoshino (4), Randie Little (5), Jan-Olof Jeppsson (6)

Kor Miedema (8), Gary Myers (9), Hans Reinauer (10)

David Sacks (11), Robbert Slingerland (8), Carla Siebelder (1)

Link National Networks:Master Equations

IFCC

NGSP

Japan Scandin.

We can tranfer

All old

Clinical

Studies To the new

IFCC

Reference

Method

-0,70

-0,60

-0,50

-0,40

-0,30

-0,20

-0,10

0,00

0,10

0,20

0,30

½ 1 1½ 2 2½ 3 3½ 4 4½ 5 5½ 6 6½ 7 7½ 8 9 10

% N

GS

P

NGSP

Scientific Link Network US Master Equation IFCC – NGSP over 10 years

Green = Low HbA1c Level Blue = High HbA1c level

Scientific Link Network Japan Master Equation IFCC – JDS/JSCC over 10 years

Green = Low HbA1c Level Blue = High HbA1c level

Work with Manufacturers

Group Experts

Analytical * Advisory Board Network Reference Labs

* Scientific Links between National networks

* Work with Manufacturers

Units and Education * Links Professional Bodies Transition Units

* Help Implementation Consensus Statement

* Monitor introduction Consensus Statement

Quality Targets monitoring, diagnosis, screening

Objectives Task Force HbA1c

1. HbA1c Standardised Worldwide

2. IFCC is the Anchor

3. HbA1c reported IFCC and NGSP

5. IFCC, NGSP in Guidelines

6. Implementation Soon

Essention Consensus Statement IDF – ADA – EASD - IFCC

Links: Meetings

• Update Consensus Statement,Dubai (GJ)

• Workshop Brazilian Society, Salvador (GJ + CW)

• IDF-WPR Congress and AASD Kyoto (GJ)

• Manufacturer Forum AACC Los Angeles (GJ + CW)

• WHO: hbA1c in developing countries

Links: Survey

Mean Labs 10

Reference Method 7

Manufacturer 2

Example Transition

Campaign Netherlands -Collaboration Professionals

-Publication Campaign

(support Ministry Health)

Group Experts

Analytical * Advisory Board Network Reference Labs

* Scientific Links between National networks

* Work with Manufacturers

Units and Education * Links Professional Bodies Transition Units

* Help Implementation Consensus Statement

* Monitor introduction Consensus Statement

Quality Targets monitoring, diagnosis, screening

Objectives Task Force HbA1c

Use of HbA1c

1. Monitoring Therapy Diabetes Type I

(DCCT Study)

2. Monitoring Therapy Diabetes Type II

(UKPDS Study)

3. Diagnosis and Screening?

Norms Diagnosis Diabetes

Year Authority

1979 NDDG (USA) and WHO

1997 ECDC (USA) and WHO

2009 IEC (ADA – EASD – IDF)

1979 WHO 1997 WHO 2009 IEC

Gold Glucose Fasting

Standard Tolerance Plasma HbA1c

Test Glucose

Concept Glucose Long Term Long Term

Concentration Complications Complicatis

Norms FPG >140 FPG >125 HbA1c

2HPG >200 2HPG >200 >6.4%

FPG <140 FPG 110-125 HbA1c

2HPG 140-200 5.8 – 6.4%

Terminology Impaired Impaired Increasing

“Doubt” Glucose Fasting Risk

Tolerance Glucose

2009 IEC

Guided by the successfull

Standardisation of HbA1c

the Committee investigated

HbA1c as tool for diagnosis

and concluded:

“HbA1c is the Gold Standard

For Diagnosis and Screening”

2009: IEC (ADA – EASD –IDF) Leading Concept Long Term Complications

Gold Standard HbA1c

Parameter HbA1c HbA1c

mmol/mol %

Diabetes >46 >6.4

Increasing Risk 40 – 46 5.8 – 6.4

Normal <40 <5.8

IEC = International Expert Committee IDF = International Diabetes Federation

ADA = American Diabetes Organisation HbA1c = Hemoglobin A1c

EASD = European Association Study diabetes

HbA1c

>46 mmol

HbA1c

<40 mmol

46 mmol

HbA1c

40 mmol

Diabetes

Increased Risk

Developing

Diabetes

Low Risk

Experts: Diagnosis and Screening

Diagnosis

Screening

This is the Picture

But is the Quality of HbA1c

good enough

for Diagnosis and Screening?

Norms?

Calibration

Reproducibility

Erythrocyte

Lifespan

Global Standardisation

IFCC Working Group

Good Calibrators

Manufacturers

EQA Organisers

Accuracy Based

Individual laboratories

Attend Calibration

Calibration Improved

Calibration

Reproducibility

Erythrocyte

Lifespan

Better instruments

Manuafacturers

Attention

EQA Organisers

Attention

Individual Labs

Reproducibility Improved

Calibration

Reproducibility

Erythrocyte

Lifespan

Calibration Reproducibility

Erythrocyte

Lifespan

1998 2012

Contribution Uncertainty Interpretation HbA1c

Calibration Reproducibility

Erythrocyte

Lifespan

If

High Quality HbA1c Assay

Is used…….

……Erythrocyte

Lifespan

Major source

Uncertainty in

Interpretation

Erythrocyte Lifespan

If Erythrocyte Lifespan (EL) is 10% shorter….

…. HbA1c will be 10% lower

Example

Two persons, same glycaemic status

A: Normal EL: HbA1c = 6.5%

B: 10% Shorter EL: HbA1c = 5.9%

Interpretation of HbA1c of Person B

Will lead to wrong interpretation of

Glycaemic status

Calibration Reproducibility

Erythrocyte

Lifespan

Biological Variation

- Inter Individual?

- Intra individual?

- Ill Non diabetics

-Ethnic Groups

Not many Data

“Not too big a problem”

Large Study required

Future Plans Task Force

Symposium IFCC WorldLab Istanbul June 2014

* Quality specifications Monitoring/Diagnosis

* Status Implementation Consensus Statement

* View HbA1c for Diagnosis/Screening

Meetings

* IDF Sydney (revision Consensus Statement)

* IP meeting EuroMedLab Milan

Various

* Review Paper

* Survey 2 collaboration WHO

Discussion

Reporting HbA1c……..

………..IFCC and NGSP units?

HbA1c for Diagnosis……

……fit for purpose?

Emerging use HbA1c…..

…. In non-diabetic (cardiovascular)?

Your View