Content

1
Content
Content Annex

• Checklists
• Glossary of terms
• References

2
Checklists
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

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Checklists
Annex Checklists

• Stable imprecision
• Instrument stability (general system robustness),
  e.g.
• Pipetting
• Temperature
• Photometer (wavelength/intensity/sensor)
• Test stability reproducibility (individual test
  robustness)
• Total/within-day CV (CVa,tot/CVa,w ratio)
• Calibration tolerance (within/between lot),
  -function
• 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

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Checklists
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
  distribution
• Probabilities within certain distances (s) of
  the mean
• Probabilities outside certain distances (s) of
  the mean

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Checklists
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
  performance.
• 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
  basis.
• 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

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Checklists
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
  costs)
• Release of patient data
• Process control
• Remedial actions policy

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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
  TEa
• 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).

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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
  available).
• 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
  available).
• 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.

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References
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
• www.statsoft.com/textbook/stathome.htm
• http//faculty.vassar.edu/lowry/VassarStats.html
• Software for laboratory statistics
• www.cbstat.com
• www.medcalc.be
• www.marquis-soft.com
• IQC-websites
• www.westgard.com
• www.marquis-soft.com

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References
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
  (1999).
• 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
  1950201059-66.
• 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
  1977231857-67.
• 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
  199634983-99.
• 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
  19993293-9.

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References
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
  competence.
• Burnett D. Understanding accreditation in
  laboratory medicine. ACB Venture Publications.
  London Association of Clinical Biochemists,
  1996.
• 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
  1994.
• 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.

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References
Annex References

• Regulation
• Praktijkrichtlijn voor het opzetten van een
  kwaliteitshandboek in erkende klinische
  laboratoria werkzaam binnen het kader van het
  RIZIV.
• Royal Decree from December 3 1999 regarding the
  authorization of clinical chemical laboratories.
  Moniteur Belge. December 30, 1999. Implementation
  document Praktijkrichtlijn (Practice guideline)
  www.iph.fgov.be/Clinbiol/NL/index.htm.
• 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. www.bundesaerztekammer.de/30/
  -Richtlinien/Richtidx/Labor2002/index.html.
• QC - THE REGULATIONS. Sharon S. Ehrmeyer, Ph.D.
  www.westgard.com/guest8.htm.
• 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
  331/37.
• 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
  175112000).
• 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
  use.
• 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
  competence
• 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
  (1998).

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References
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
  1988341379-86.
• 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
  h/files/file/261.Bayes_library_handbook.pdf
• 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
  199533157-69.
• 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.
• www.westgard.com
• 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
  199959517-22.
• ISO 15196/CD Identification and determination of
  analytical and clinical performance goals for
  laboratory methodologies

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Annex