INTEGRATED QUALITY CONTROL,

THE GRAZ SYSTEM

Prof. Dr. med. habil. FRCPA

Markus Herrmann
Klinisches Institut f. Medizinische u. Chemische Labordiagnostik
Medizinische Universität of Graz

BIORAD, QC Masterclass 2022

A true story from 2012 …..

Boss, we have a problem!

2
Grossly erratic electrolyte results …..

Over 2 days one of our chemistry analysers produced >600 erratic electrolyte results

Results already released to requesting doctors

Na+ (mmol/l)
Original Re-Test
Sample 1 125 134
Sample 2 132 139
Sample 3 146 156
Sample 4 139 156

Risk of inappropriate
max
= 17 mmol/L Patient management
3
 Grossly erratic electrolyte results …..

What is your procedure We don‘t need to do anything

for such cases? because the requesting doctors
have already sent fresh samples.

Unfortunately we can‘t retrieve

the samples because we don‘t
have a central specimen
Re-test all samples and generate
storage where the position of
corrected reports for samples with
each sample is logged.
Na+ Δ > 5mmol/L. 4
How could this happen?

➢ An inexperienced scientist misplaced a sample mixer during instrument maintenance

➢ Sample mixing varied randomly

➢ Inadequate quality control rules

➢ Staff not sufficiently competent

➢ Insufficient postanalytical process (validation and correction of reports)

➢ Insufficient communication inside the lab and with requesting doctors 5

How could this happen?

Hematology

Biochemistry Coagulation

Non-standardized QC procedures that were not in

accordance with modern standards

Proteins
STAT Lab

6
Immunoassays
How could this happen?

Na+ - QC-Data (instrument print-out)

155.58
112.73
128.00(+2SD
(+2SD
(+2SD)))

ΔΔΔ444SD
SD
SD===4.44
2.04
15.00

160.02
114.77
113.00(-2SD
(-2SD
(-2SD)))

➢ No central QC-management (chief scientist with limited knowledge in QC standards)

➢ QC targets transcribed from pack insert (very wide)

➢ Lab used only 2s, 2x2s and 3s

7
Lacking integration of internal and external QC

8
 Another problem….

Different instruments for the same test without cross-comparison

Routine-Labor Notfall-Labor
27/4/12 27/4/12
08:33 10:27
WBC (*103/µl) 11.57 Δ=17% 13.80 (4.80 - 10.80)
ERY (*106/µl) 4.94 5.11 (4.20 - 6.10)
HB (g/dl) 15.3 16.4 (12 - 18)
Siemens Advia Beckman Coulter
Systematic difference between instruments
or change in patient’s status?

Discrepant results = clinical risk 9

Revision of QC-Managements

The Graz System

10
Aims

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Installation of centralized QC-management

Internal QC
External QC

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Aims of new QC-Management

1) Improvement of analytical quality through state-of-the-art QC-standards

2) Improvement of QC competence in the entire team

➢ Support of all staff through competent QC-management team

➢ Interpretation and archiving of all internal QCs by smart QC software

➢ Test-specific acceptance criteria based on labs own performance

➢ Harmonization of EQA programs

➢ Uniform interpretation and documentation of all EQAs

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Implementation of highly specialized QC-team

➢ Advanced competence in QC Marko Horvat

(BSc)
(ideally more competent than lab director)

➢ High motivation and proactive approach

PD Dr. Tatjana Stojakovic
(Senior consultant)
➢ Organisational talent

➢ Communication talent

Dr. Gerald Markus Eibinger

(Consultant)

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Job description QC-manager

➢ Implementation of QC standards set out by the lab management

➢ Planning and implementation of measures for efficent operation of QC system

➢ Implementation of QC software, interfacing of instruments

➢ Programming of analytes and controls, definition von targets and acceptance criteria

➢ Performance of supervisor reviews

➢ Troubleshooting

➢ Information and training of staff in all aspects of QC

➢ Drafting and review of QC documents

➢ ……………………………..
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Implementation of highly specialized QC-team

➢ Determines frequency and type of QCs

➢ Interfacing of instruments with Unity RT

➢ Implementation and adminsitration of Unity RT

➢ Selection of QC rules for each Analyte

QC manger
➢ Staff training

➢ Supervisor review

➢ Ordering and administration of EQAs

➢ Preparation and analysis of QC

➢ Validation of QC / Bench Review

all scientists ➢ Troubleshooting

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Specialized QC software

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Implementation of smart QC software
QC software - interfacing of all instruments & workstations
QC software – intuitive presentation
and easy localization of QC

Intuitive presentation of lab

section and instruments

Easy localization of QC
materials and analytes

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QC software - ISO 15189 aligned archiving of QC data

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QC software – intuitive and flexible visualization of QC data

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QC software - intuitive and flexible visualization of QC data

COBAS 1 – Level 1 & 3

COBAS 2 – Level 1 & 3

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QC software – test-specific QC rules

Warning- and rejection rules

can be chosen freely

for each test

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QC software – real time comparison with other laboratories

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QC software – two level validation

Bench-Review (bench staff)

• Review of daily QC data (table)
• Review of Levey-Jennings graphs
• Commenting on daily QC data
• Decision if results are acceptable

Validation of analytical run

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QC software – two level validation

Supervisor-Review
(QC manager and scientists with advanced knowledge)

• Performed periodically (weekly, monthly)

• Check if bench reviews have been performed correctly
• Identification of trends and measures to address them

Validation of the system

Precocious identification of QC problems
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QC software – user-friendly administration of QC problems

Einfache und übersichtliche

Einfache Abklärung von Validierung in 2 Ebenen
Regelverletzungen

Selection of predefined (common) actions

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 QC software – variable vs. fixed meant

184,87

157,28
MW 154,00 MW 151,61
145,94

123,33

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QC-Software – Arbeiten mit analytischen Zielen

➢ Biological variability
➢ Intra-individual variability
➢ Inter-individual variability
➢ Analytical variability
➢ Systemic bias
➢ Total error

Ricos, C. et al. (1999): Current databases on biological variation: pros, cons and progress,
Scand J Clin Lab Invest; 59: 491-500.
Europäischen Föderation für klinische Chemie und Labormedizin (EFLM) 2021

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QC software – working with analytical goals

The variability
Analyte of a biological
with low result depends on analytical
variability
imprecision andhas
Low precision biological variability
great impact
on interpretation of results
The lower the biological variability
the greater the impact of imprecision

Practical consequence:
Analyte with great biological variability
Violation of Westgard rules may be accepted
Low precision has small impact
when impact on total variability is low
on interpretation of results

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QC software – working with analytical goals

1-3S violation: repeat No!!! Because result

all patient samples since inside analytical goals
last valid control?

32
QC software – easy calculation of measurement uncertainty

Day 1 Day 2 Day 3

Na = 143 mmol/l Na = 145 mmol/l Na = 148 mmol/l

Analyzer 1 Analyzer 2 Analyzer 3

MU = 2 x CV
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QC software – easy calculation of measurement uncertainty

ISO 15189 requires determination of measurement uncertainty (MU)

• For all methods
• With appropriate limits that are acceptable
• Regular re-evaluation of MU
QC software summary

➢ Archiving of all QC results with associated information

➢ Automated calculation of mean and SD

➢ Comparison with international peer-group

➢ Flexible graphical visualization of QC data

➢ Test-specific rules for interpretation of QC results

➢ Two level validation (Bench-Review and Supervisor Review)

➢ User-friendly validation of QC results using Westgard rules or analytical goals

➢ User-friendly cross-comparison of instruments

➢ User-friendly calculation of measurement uncertainty

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External QC

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EQA –archiving and interpretation

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Harmonization of EQA programs

Key points

➢ Ensure adequate frequency of EQA

➢ Reduce complexity

➢ Simplify data management

➢ Simplify interpretation of reports

➢ Reduce human error

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EQA – Harmonized reports facilitate review process

Cholesterol (mg/dL)

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EQA – standardized
presentation of relevant
information

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EQA - Example

✓ User friendly comparison of own result with:

- all participants

- users of the same method

- Users of the same analytical system and method (peer group) 41

EQA – easy assessment of long-term performance

➢ Comparator Mean displayed at top of the chart

➢ Each samples Z-score and comparator is displayed

➢ Date in bottom scale of chart

➢ Works across cycles

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EQA – easy assessment of linearity and bias

Trendline

➢ Plotting of concentration versus bias

➢ Good chart to detect linearity or bias problems

➢ Works across cycles

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EQA – easy performance assessment at a glance

➢ All results acceptable

(within 2 Z-score-range)

➢ Negative bias
(acceptable)

➢ Linearity problem

➢ Higher levels cause

negative bias

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EQA – additional information about other systems/methods

➢ list of other instruments with

method and reagent details

➢ displays number of participants incl.

mean, CV and uncertainty.

➢ Nice tool to compare own system

with others

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EQA – KPIs allow identification of strengths and weaknesses

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EQA – end-of-cycle-report provides additional information

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EQA – end-of-cycle-report provides additional information

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EQA – end-of-cycle-report provides additional information

Summary Data - Cholesterol (mg/dL)

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End-of-cycle report –
cumulative performance
information
End-of-cycle report – cumulative performance information

➢ Provides overall assessment

of your laboratory’s performance
in terms of bias, distribution of
Z-scores, National and Worldwide
peer performance scores.
EQA, medical
competence

52
QC – enough is never enough…….

✓ approx. 2800 QCs / day

✓ approx. 9600 EQAs / year

✓ Monthly interim reports

✓ End-of-cycle reports twice per year

Lab Total QC Erratic Corrective action Cause not

Area Analysis EQAs No Yes identified
Chemistry 4578 64 4 3 57
Hematology 3422 54 6 30 18
TDM 416 11 1 9 1
Proteins 76 1 0 0 1
Coagulation 432 27 8 16 3
Molecular Genetics 67 0 0 0 0
Lipids 28 0 0 0 0
VTM 580 11 0 3 8
Total 9599 168 19 61 88 53
Summary

✓ Modern QC standards, necessity to ensure patient safety

✓ Centralized QC management, prerequisite for harmonized QC standards in all areas

✓ Qualified QC manager, guarantees full implementation in all lab areas

✓ Smart QC software, tool for data administration, interpretation and risk management

✓ Smart EQA programs, exteral control of analytical quality

✓ Smart EQA programs, comparison with other labs and test systems

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Thanks For Your
Attention
&
Hasta La Vista,
Folks
EQAS – Method
summary report

➢ overall assessment
of performance for all
methods in the program