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ISO/DIS 15189.2 Medical laboratories - Particular requirements for quality and competence. Burnett D. Understanding accreditation in laboratory medicine. – PowerPoint PPT presentation

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Title: Content

Content Annex
  • Checklists
  • Glossary of terms
  • References

Annex Checklists
  • IQC software
  • Administrative capabilities
  • -Easy set-up and modification
  • -Online (real time) connection with LIS
  • -Full sample IQC traceability
  • -Accreditation-conform documentation
  • -Up-to-date data safety
  • IQC-capabilities
  • -Transparent efficient data presentation
  • -Great variety of rules
  • -Rule selection logic
  • -Automatic release
  • -Automatic flags and remedial action
  • (but with open decision logic)
  • IQC-sample
  • Nature
  • Correspond with patient sample
  • Compatible with the test

Annex Checklists
  • Stable imprecision
  • Instrument stability (general system robustness),
  • Pipetting
  • Temperature
  • Photometer (wavelength/intensity/sensor)
  • Test stability reproducibility (individual test
  • Total/within-day CV (CVa,tot/CVa,w ratio)
  • Calibration tolerance (within/between lot),
  • Reagent (within/between lot)
  • Test robustness
  • Note Ideally, a GUM-type variance analysis of
    all elements should be available.
  • ? Decide about approaching the variation by IQC
    and/or quality assurance

Annex Checklists
  • IQC-measurement-frequency and location
  • Minimum 2 samples per run
  • Desirable 1-2 of patient samples
  • -Make a cost/benefit calculation
  • Frequency should be related to test stability
    requires knowledge of instrument and test
  • Consider dummy measurements before 1st IQC
  • Frequency may depend on the control rule
  • Block Maximizes chance of assignable cause of
    variability between subgroups
  • Continuous Maximizes chance of assignable cause
    of variability within subgroups
  • Basic statistics
  • Calculations
  • Mean
  • SD
  • CV
  • Gaussian (normal) distribution
  • Graphic of the usual the cumulated
  • Probabilities within certain distances (s) of
    the mean
  • Probabilities outside certain distances (s) of
    the mean

Annex Checklists
  • TEa
  • Apply TEa values from the following hierarchy
  • 1. Clinical models (e.g., cholesterol glucose)
  • 2. Biological variation (obtain the database)
  • -Bottom-line values
  • No numbers from 1-2 3. Expert models
  • No numbers from 1-3 4. Regulation
  • No numbers from 1-4 5. Better state-of-the-art
  • Note Critically review the proposed numbers.
  • Rule selection
  • Statistical basis A rule is chosen based on Pfr
    and Ped. SD-limits are taken from stable
  • TEa basis From a specification for TEa,
    critical error values can be calculated.
  • From the critical error values, adequate IQC
    rules can be selected, naturally, on statistical
  • Selection tools power functions, OPSpecs, the
    TEa/CVa,tot ratio the IQC decision tool
  • Power of control rules
  • Ped should be 90
  • Realistic errors to be detected by IQC are

Annex Checklists
  • Input elements for a successful IQC policy
  • The guiding rule (regulation)
  • Knowledge
  • Basic statistics
  • Power functions
  • TE error concept (metrology)
  • TEa (critical errors, specifications)
  • Selection of TEa values (and problems)
  • IQC Software
  • Additional rule selection tools
  • Adequate samples
  • Adequate frequency (and location) policy
  • Cost/benefit calculations
  • Instrument stability data
  • Test stability and reproducibility data
  • Integrated rule selection (TEa statistics
  • Release of patient data
  • Process control
  • Remedial actions policy

Glossary (and abbreviations) of terms IQC
Annex Glossary of terms
  • Ped probability of error detection
  • Pfr probability of false rejection
  • TEa total allowable error
  • DSEcrit, critical systematic error the amount
    of systematic error that places 5 of results
    outside TEa
  • DREcrit, critical random error the amount of
    random error that places 5 of results outside
  • ARL, average run length the average number of
    runs that occur before a run is rejected by the
    IQC procedure
  • Glossary of terms IQC rules
  • Control rules with a fixed limit 
  • a) Control rules in the form of Nzs (N is the
    number of observations, zs is a certain number
    of standard deviations of the Gaussian
    distribution, commonly used are 2s, 2.5s, or 3s).
  • 13s refers to a control rule where action is
    taken when one measurement falls outside the 3s
    range around the target value.
  • 22s refers to the situation where action is
    taken when two consecutive measurements exceed
    the same limit, either the 2s or -2s range.
  • b) Range rules
  • R4s refers to a situation where action is taken
    when the absolute difference between the highest
    and the lowest result exceeds 4 s (Westgard
    interpretation one gt2s, the other lt-2s).

Glossary of terms IQC rules
Annex Glossary of terms
  • Control rules with variable limit (depending on
    the number of observations N), however, a fixed
    probability of false rejections (Pfr) XPfr
  • 10.05 1 control measurement in a group of N
    measurements exceeds a limit based on a Pfr of
    0.05. The limit widens when N increases (tables
    are available).
  • X0.05 The mean of a group of N measurements
    exceeds a limit based on a Pfr of 0.05 (also
    called "mean" rules). The limit decreases when N
    increases (tables are available).
  • R0.05 The range in a group of N measurements
    exceeds a limit based on a Pfr of 0.05. The limit
    increases when N increases (tables are
  • Chi20.05 The ratio s2obs(N-1)/s2 exceeds the
    critical chi-square value at a Pfr of 0.05 (sobs
    is the standard deviation calculated from the
    control measurements, s is the intrinsic standard
    deviation) (also called "variance" rules). The
    limit increases when N increases (tables are
  • CS ("CUSUM") The difference between individual
    results and the mean is summed up and plotted.
    Interpretation is either graphical ("V" mask) or
    with a numerical limit.

Annex References
  • Statistical textbooks
  • Basic
  • Miller JC, Miller JN. Statistics for analytical
    chemistry. 3rd ed. Chichester (UK) Ellis
    Horwood, 1993.
  • Advanced
  • Sokal RR, Rohlf FJ. Biometry. 3rd ed. New York
    W. H. Freeman and Company, 1995.
  • Altman DG. Practical Statistics for medical
    research. Chapman Hall, London, 1991.
  • Electronic textbook
  • http//
  • Software for laboratory statistics
  • IQC-websites

Annex References
  • IQC-general
  • National Committee for Clinical Laboratory
    Standards (NCCLS).C24-A2. Statistical quality
    control for quantitative measurements Principles
    and definitions Approved Guideline 2nd ed
  • Westgard JO, Barry PL. Cost-effective quality
    control. AACC Press, 1995
  • Shewart WA. Economic control of manufactured
    products. Van Nostrand 1931.
  • Levey S, Jennings ER. The use of control charts
    in the clinical laboratory. Am J Clin Pathol
  • Westgard JO, Groth T, Aronsson T, Falk H, de
    Verdier C-H. Performance characteristics of rules
    for internal quality control probabilities for
    false rejection and error detection. Clin Chem
  • Hyltoft Petersen P, Ricós C, Stöckl D, Libeer
    J-C, Baadenhuijsen H, Fraser CG, Thienpont LM.
    Proposed guidelines for the internal quality
    control of analytical results in the medical
    laboratory. Eur J Clin Chem Clin Biochem
  • Linnet K. Mean and variance rules are more
    powerful or selective than quality control rules
    based on individual values. Eur J Clin Chem Clin
    Biochem 199129417-24.
  • IQC-practice surveys
  • Steindel SJ, Tetrault G. Quality control
    practices for calcium, cholesterol, digoxin, and
    hemoglobin. A College of American Pathologists
    Q-probes study in 505 hospital laboratories. Arch
    Pathol Lab Med 1998122401-8 Recommend 2.5
    2.7s rule
  • Tetrault GA. QC in the clinical lab 6 questions
    for the pathologist. CAP Today 1995 (April)60-1
    Recommends 3.5 s rule
  • Steindel SJ. Quality control systems in the
    clinical laboratory. A survey on implementation
    in 505 hospital laboratories. Labmedica Int
    1999168-12 Recommends 2.5 2.7s rule
  • Krishnan S, Webb S, Henderson AR, Cheung CM,
    Nazir DJ, Richardson H. An overview of quality
    control practices in Ontario with particular
    reference to cholesterol analysis. Clin Biochem

Annex References
  • Quality management
  • ISO 8402 1994. Quality management and quality
    assurance - Vocabulary
  • National Committee for Clinical Laboratory
    Standards (NCCLS). HS1-A (replaces GP26-A). A
    quality system model for health care Approved
    guideline (2002).
  • ISO/DIS 15189.2 Medical laboratories -
    Particular requirements for quality and
  • Burnett D. Understanding accreditation in
    laboratory medicine. ACB Venture Publications.
    London Association of Clinical Biochemists,
  • Stewart CE, Koepke JA. Basic quality assurance
    practices for clinical laboratories. Philadelphia
    (USA) J. B. Lippincott Company, 1987.
  • Garfield FM. Quality assurance principles for
    analytical laboratories. AOAC International
  • St John A. Critical care testing. Quality
    assurance. Mannheim Roche Diagnostics, 2001.
  • Nilsen CL. Managing the analytical laboratory
    plain and simple. Buffalo Grove (IL) Interpharm
    Press, 1996.
  • Metrology
  • ISO VIM. Vocabulaire international des terms
    fondamentaux et généraux de métrologie.
  • ISO GUM. Guide to the expression of uncertainty
    in measurement
  • ISO 5725-1. Accuracy (trueness and precision) of
    measurement methods and results.
  • Stöckl D. Metrology and analysis in laboratory
    medicine a criticism from the workbench. Scand J
    Clin Lab Invest 199656193-7.

Annex References
  • Regulation
  • Praktijkrichtlijn voor het opzetten van een
    kwaliteitshandboek in erkende klinische
    laboratoria werkzaam binnen het kader van het
  • Royal Decree from December 3 1999 regarding the
    authorization of clinical chemical laboratories.
    Moniteur Belge. December 30, 1999. Implementation
    document Praktijkrichtlijn (Practice guideline)
  • Guidelines of the German Medical Association
    (Bundesärztekammer) regarding the quality
    assurance in medical laboratories (RILIBÄK).
    Deutsches Ärzteblatt 200198, 42A 2747-59
    200299, 17 A 1187.
  • QC - THE REGULATIONS. Sharon S. Ehrmeyer, Ph.D.
  • Directive 98/79/EC of the European Parliament
    and of the Council of 27 October 1998 on in vitro
    diagnostic medical devices. Official Journal of
    the European Communities 1998 (Dec 7)L 331/1-L
  • CEN prEN ISO 17511 (draft Dec 2000) in vitro
    diagnostic medical devices - Measurement of
    quantities in samples of biological origin -
    Metrological traceability of values assigned to
    calibrators and control materials (ISO/DIS
  • CEN prEN 13612 (final draft September 2001)
    Performance evaluation of in vitro diagnostic
    medical devices.
  • ISO/DIS 15198 (April 2001). Clinical laboratory
    medicine - Validation of manufacturers
    recommendations for user quality control.
  • CEN EN 591 (2001) Instructions for use for in
    vitro diagnostic instruments for professional
  • CEN EN 375 (2001) Information supplied by the
    manufacturer with in vitro diagnostic reagents
    for professional use.
  • CEN prEN 14136 (draft March 2001) Use of
    external quality assessment schemes in the
    assessment of the performance of in vitro
    diagnostic procedures.
  • ISO/IEC 17025 1999 - General requirements for
    the competence of testing and calibration
    laboratories (former EN 45001).
  • ISO/DIS 15189.2 Medical laboratories
    particular requirements for quality and
  • ISO/AWI 22869 Clinical laboratory testing --
    Guidance on application of ISO 15189.
  • NCCLS EP11-P Uniformity of claims for in vitro
    diagnostic tests Proposed guideline (1996).
  • NCCLS EP15-P User demonstration of performance
    for precision and accuracy Proposed guideline

Annex References
  • Dignostic value of tests
  • Büttner J. Diagnostic validity as a theoretical
    concept and as measurable quantity. Clin Chim
    Acta 1998260131-43.
  • Linnet K. A review on the methodology for
    assessing diagnostic tests. Clin Chem
  • National Committee for Clinical Laboratory
    Standards. Assessment of clinical accuracy of
    laboratory tests using receiver operating
    characteristics (ROC) plots approved guideline.
    NCCLS publication GP10-A. Wayne, PA NCCLS 1995.
  • The Bayes Library of Diagnostic Studies and
    Reviews. 2nd edition 2002. http//www.ispm.unibe.c
  • Henderson AR. Assessing test accuracy and its
    clinical consequences a primer for receiver
    operating characteristic curve analysis Review.
    Ann Clin Biochem 199330521-39.
  • Performance specifications
  • Stöckl D, Baadenhuijsen H, Fraser CG, Libeer
    J-C, Hyltoft Petersen P, Ricós C. Desirable
    routine analytical goals for quantities assayed
    in serum. Eur J Clin Chem Clin Biochem
  • Stöckl D. Desirable Performance criteria for
    quantitative measurements in medical laboratories
    based on biological analyte variation -
    hindrances to reaching some and reasons to
    surpass some. Clin Chem 199339913-4.
  • Strategies to set global analytical quality
    specifications in laboratory medicine. Consensus
    Statement, Stockholm 1999. Scand J Clin Lab
    Invest 199959585.
  • Hyltoft Petersen, P. Quality specifications
    based on analysis of effects of performance on
    clinical decision making. Scand J Clin Lab Invest
  • ISO 15196/CD Identification and determination of
    analytical and clinical performance goals for
    laboratory methodologies

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