STANDARDISATION, HARMONISATION AND TRACEABILITY - PowerPoint Presentation

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STANDARDISATION, HARMONISATION AND TRACEABILITY

Dr A

A

KHINE

DIVISION OF CHEMICAL PATHOLOGY

NHLS TYGERBERG

STELLENBOSCH UNIVERSITY

Laboratory Management workshop 3-6 June 2019

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Good laboratory practice requires

E

rror of measurement must be small enough that a result reflects a patient’s biological condition.

Comparable results that are independent of:

Where and when a test was performed

The measurement procedure used

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Total Error

Calibration bias to an accepted reference ( and also includes bias from calibrator lot-to-lot variability)

Imprecision in a measurement procedure

Sample specific influences

non-specificity for the

measurand

interfering substances

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Why We Need Comparable Results?

If different measurements give different results for the same patient sample:

Clinical practice guidelines become less useful.

Patients may receive incorrect treatment.

Patients may be moving around, thus specimens sent to various labs

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Three areas of standardization in the clinicallaboratory

procedures that are followed before analysis

How sample is analysed (test methods used)

What calibrator is used and how it is traceable

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Standardisation versus harmonisation

Standardization:

Same method or same instrument used

Using calibrator with a traceability ref number

Results are uniform among measurement procedures

Reporting units are the same

Harmonization:

Different methods are used but results are not uniform but comparable

Reporting units may not be the same originally but conversions help to make comparable (SI units)

No reference measurement procedure and no “pure substance” reference material

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How To Achieve Comparable Results?

Laboratories using a common traceable calibrator or different calibrators with the same traceability ref number

Performance is monitored and maintained by surveillance using proficiency testing (PT), external quality assessment (EQA), or a certification program.

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Metrological traceability

True value is not known unless it is attached to a reference so that value can be assigned

is defined as “the property of a measurement result whereby the result can be related to a reference through a documented unbroken chain of calibrations, each contributing to the measurement uncertainty”.

Traceability is established to SI using a reference calibrator and reference measurement procedure

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Metrology traceability chain

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COMMUTABILITY ISSUES

Commutable means that

the ref material reacts with the reagents in the ref method and other methods in the same way that analyte in the patient sample would

Thus, values obtained from the

calibration material and

from

native

clinical samples

have the same relationship

across measurement

procedures for

the same

measurand

.

Ideally a reference material should be validated for commutability against all field methods and types of samples but it is rarely the case

Poor commutability means there is matrix effect affecting reaction between reagent and

measurand

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When there is no or poor commutability

A manufacturer uses a “master lot of calibrator” that may be traceable to a non-commutable reference material, then the Traceability chain is broken

Even though manufacturers claim traceability, the process fails to provide equivalent results for patient samples when different measurement procedures are used.

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Calibration Traceability Does Not Ensure Accuracy for an Individual Patient Sample

Measurement procedure may not be specific for the

measurand

.

Measurand

may not be well defined.

Molecular form(s) of clinical interest

Interfering substances present in a patient’s sample may influence the result

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Use of a Non-commutable Material forCalibration Will Cause

Incorrect value assignment for the manufacturer’s calibrator

Incorrect results for patient samples

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Calibrators in the routine laboratory

A manufacturer's calibrator is proprietary (patented)- intended for use with a specific measurement procedure.

It cannot be used with a different manufacturer’s measurement procedure

This is because the company has validated its commutability only with their own reagent

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Change in Practice Needed

In the business of producing and marketing PRM, SRM and TRM, there must be requirement to submit commutability validation against

Reference methods

Manufacturer’s methods and reagents

Routine clinical laboratory procedures and reagents

A guideline for validating commutability is available: CLSI C53-A-Characterization and Qualification of Commutable Reference Materials for Laboratory Medicine (2010)

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No traceability

No reference measurement procedure or

No reference material

Can there be harmonisation?

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Barriers to Harmonization

Lack of a systematic process to identify and prioritize measurands

Materials labelled as “reference materials” that have not been validated to be commutable for the intended measurement procedures

Inadequate definition of the

measurand

Inadequate analytical specificity for the

measurand

Lack of systematic procedures to implement harmonization, in particular:

When there is no reference measurement procedure

When there is no reference material

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Initiatives in establishing S and H

IFCC has been a key leader in developing science in developing PRMs and RMPs.

Many national and international groups are engaged

JCTLM (joint committee for traceability in lab measurements) composed of three organizations:

International Committee of Weights and Measures

International Federation of Clinical Chemistry and Laboratory Medicine

International Laboratory Accreditation Cooperation

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Functions of JCTLM

Maintain the list of reviewed and approved

Reference measurement procedures

Reference laboratories

Reference materials

Commutability requirements are being addressed.

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Possibilities for consideration:

T

raceable to an all methods mean (outliers removed) of a panel of patient samples

Traceable to a designated measurement procedure (arbitrary, but which has good correlation with clinical outcome)

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References

Mary Lou

Gantzer

, PhD, FACB. President, CLSI, CEO,

BioCore

Diagnostics. Laboratory Standardization: Bringing Order to Chaos

Standardization –the theory and practice-Jill Tate, M

Panteghini

The JCTML- A global approach to promote standardization of clinical laboratory test results

Traceability, Reference systems and result comparability- Clin

Biochem

reviews- 28Aug 2007

ISO 17511

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EXERCISE

What are the analytes in routine chemistry that have been standardized using both ref material and ref method procedure?

What are the analytes that have been standardized through development of primary ref material but not all routine laboratories use the reference method procedure?

What are the analytes that have been standardized through development of primary ref material but lacking method standardization?

What are the analytes that have not been standardized through both development of primary ref material or method standardization?

How has NHLS tried to harmonise the analytes under 2, 3, 4 and 5?