Collegamento a: http://enews.clsi.org/clsi/issues/2006-05-01/1.html

Expression of Measurement Uncertainty in Laboratory Medicine (C51-P)
Background, methods, and examples explored in upcoming release of
proposed-level CLSI guideline
Measurement uncertainty is defined in the International Vocabulary of Basic
and General Terms in Metrology (VIM93) as "the parameter, associated with
the result of a measurement, that characterizes the dispersion of the values
that could reasonably be attributed to the measurand." As further stated in
International Organization for Standardization (ISO) document, Laboratory
medicine - Requirement for reference measurement laboratories (ISO 15195),
the parameter may be, for example, a standard deviation (or a given multiple
of it), or the half-width of an interval having a stated level of
confidence.
Overall, measurement uncertainty estimates are used to determine the quality
of test results, contribute to improved interpretation of patient data, and
allow for optimal comparison of results across time and place.

Best Practices Outlined in CLSI Guideline
Laboratories are being encouraged to evaluate uncertainty, in order to
assess the quality of their results and to determine whether the result is
close to any specified limit. Currently, "There is no standard written in
the language of the clinical laboratorian providing instructions as to how
to estimate, report, or utilize uncertainty. There is an ISO document called
the Guide to Uncertainty in Measurement (GUM); however, this document is
primarily written by people who were doing physical measurements, such as
wave-length or a steel gauge block, and they were able to collect the right
kinds of information relatively easily," says Richard Miller, Dade Behring,
Inc., and Chairholder of the CLSI subcommittee that is developing the C51
guideline. There is an expressed need for specific "how to" guidance for
measuring uncertainty that translates to laboratory medicine.
This year, CLSI is scheduled to publish Expression of Measurement
Uncertainty in Laboratory Medicine; Proposed Guideline (C51-P). The focus of
the guideline is to describe a practical approach to developing relevant and
useful estimates of measurement uncertainty and for using the information to
maintain and improve the quality and application of clinical laboratory
measurements.
The guideline gives recommendations for defining the measurand, listing
sources of uncertainty, generating statistical estimates of combined
uncertainty, and general guidance for reporting uncertainty to users of the
results. In addition, commonly used practical strategies for producing
estimates in the clinical laboratory are included, such as use of quality
control data, information from manufacturers, and method validation results.
David L. Duewer, PhD, National Institute of Standards and Technology, and
C51 subcommittee member, describes the document as providing "1) a broad
overview "why" estimating measurement uncertainty is useful and 2)
sufficient "how" detail to identify the necessary information and make the
estimates. This is done by both providing instructions and a number of fully
worked examples. The document is intended to help put the why and how of
measurement uncertainty estimation into a practical, assessable clinical
laboratory context."

Essential Resource for Various Users
As stated in the C51-P guideline, the recommendations are intended for use
by the following parties:
those involved in generating and applying estimates of the uncertainty of
measurement in the clinical laboratory;
those concerned with oversight of laboratory quality (such as government
regulatory
and accreditation bodies); and providers of laboratory products that
influence the uncertainty of measurement, such
as:
o manufacturers of in vitro diagnostic medical devices,
o producers of reagents and reference materials, and
o providers of external quality assessment / proficiency testing schemes.

Miller explains, "For auditors, the CLSI document provides a mechanism to
understand how the laboratory that wishes to be compliant with ISO 15189
should be calculating uncertainty.
For in vitro diagnostic (IVD) manufacturers, Miller says, "This document
delineates the responsibilities for providing information to the clinical
laboratory that is calculating the uncertainty.
"For clinical laboratories, this document outlines practical techniques for
how to perform the new and unusual task of measuring uncertainty," says
Miller. Dr. Duewer agrees, (C51 is) "the only 'measurement uncertainty'
guide that explicitly addresses problems that clinical scientists consider
relevant."
"Many external quality assessment organizations at the present time are
moving towards traceable systems. Part of a traceable system is the need to
understand the uncertainty of values assigned to external quality assessment
materials. Secondly, in theory, the medical laboratory that provides the
result should be providing an uncertainty. Pass/fail requirements may be
based on that uncertainty. Providers of external quality assessments have an
interest as well because they need to know the uncertainty that they are
introducing into the system, as well as whether the laboratory is capable of
providing acceptable results," comments Miller.
Linda Thienpont, PhD, University of Ghent, and C51 document development
subcommittee member adds, "The demand to know the uncertainty of measurement
extends to all parties concerned with physicochemical laboratory analyses
(environmental analysis, toxicology, food chemistry, etc.)."

Global and Accreditation Aspects
Accreditation bodies are responsible for ensuring that accredited
laboratories meet the requirements of Medical laboratories - Particular
requirements for quality and competence (ISO 15189) and/or General
requirements for the competence of testing and calibration laboratories
(ISO/IEC 17025). Both ISO/IEC 17025 and ISO 15189 cite the GUM as an
acceptable model for estimating uncertainty. GUM, jointly published by BIPM,
IEC, ISO, IUPAC, IUPAP, and IFCC, is a broad-based, widely used, and
accepted method of calculating uncertainty.
The recommendations provided in C51-P are consistent with ISO as expressed
in the GUM, and with documents concerned with laboratory accreditation,
namely, ISO 15189 and ISO/IEC 17025.
Miller explains, "C51-P will provide laboratories with a mechanism to meet
one of the essential requirements of ISO 15189. It also provides each
individual laboratory a mechanism for estimating and understanding how
reproducible and comparable their results are with laboratories in other
parts of the world."
At the present time, Miller says, "If a patient has the same test done in
more than one laboratory, perhaps in different countries, estimates for
comparability of results would be doubtful. C51 will help users understand
the level of variability in the results."

When asked how C51-P differs from the ISO documents and GUM, Miller says,
"In general, the ISO standards are a list of minimum requirements without
much description about how to implement. CLSI documents include more
in-depth explanation of 'how to' and 'why.' As a result, the ISO and CLSI
documents are complementary resources."
Dr. Thienpont elaborates, "Laboratories all over the world are faced with
the demand of estimating the uncertainty of their measurements. The
rationale behind that demand is that the uncertainty of measurement affects
clinical decision making and a means of judging the fitness for purpose of a
measurement procedure. National regulations or regulations with regard to
laboratory accreditation may be at the basis of this demand. Namely, to
comply with ISO 15189 or ISO/IEC 17025, a laboratory must provide the
uncertainty of a measurement. Although everyone recognizes that the
estimation should be done consistent with the GUM, it is extremely
complicated to know which input elements to include. Consequently, today,
there is no coherence with regard to estimating uncertainty; hence, the
numbers generated may not be realistic or reliable. Since the forthcoming
CLSI document C51 will formulate clear recommendations in this respect,
enforced by real life examples, it is a document that the laboratory
director should have on his/her desk."
Proper Uncertainty Measurement Improves Quality and Reliability of Results
Making estimates of the measurement uncertainty of routine methods is an
essential step for clinical laboratories when evaluating methods to ensure
they produce patient results that are fit for clinical use. Estimating
measurement uncertainties also provides laboratories with a better
understanding of the performance characteristics and limitations of their
methods, and may identify technical steps where uncertainty can be reduced.
Dr. Theinpont says, "I think that a correct estimation of the uncertainty
will indirectly improve the quality of the work/products in laboratory
medicine. The interesting aspect of correctly estimating the input elements
to uncertainty is that one can infer which part of the analysis or a product
contributes most. In this way, I suppose that, when necessary, a respectable
laboratory director or manufacturer of in vitro diagnostic medical devices
will try to improve the analysis or the product in order to decrease the
uncertainty to an acceptable level."
Miller concludes, "The uncertainty concept is one that provides the good,
clear understanding of the interchangeability of laboratory results by
different laboratories, in different geographic areas, as well as by using
different methods. In order to have results that are consistent, which is
becoming increasingly important, we have to understand when they are
comparable and when they are not. This new CLSI guideline provides the
comparison criteria so that somebody can understand and recognize whether
results from a Beckman system, or an Abbott system, or a Dade Behring
system, for example, would be comparable. It also provides an understanding
of whether they would be comparable in Europe vs. Asia or North America."
A proper measurement of uncertainty is good professional practice and can
provide laboratories and patients around the world with valuable information
about the quality, reliability, and comparability of results.



CLSI offers numerous related documents that complement the new proposed
C51-P guideline including: Evaluation of Precision Performance of
Quantitative Measurement Methods; Approved Guideline- Second Edition
(EP5-A2); Evaluation of the Linearity of Quantitative Measurement
Procedures: A Statistical Approach; Approved Guideline (EP6-A); Method
Comparison and Bias Estimation Using Patient Samples; Approved
Guideline-Second Edition (EP9-A2); Preliminary Evaluation of Quantitative
Clinical Laboratory Methods; Approved Guideline-Second Edition (EP10-A2);
and Estimation of Total Analytical Error for Clinical Laboratory Methods;
Approved Guideline (EP21-A).
For more information about related documents and products, visit
www.clsi.org.