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Biological Variation, A Practical Review, DR C. Ricos
Biological Variation, A Practical Review, DR C. Ricos
a practical review
Carmen Ricós
Brussels & Amsterdam
2010 Bio-Rad_QC Seminars
C Ricós
2010 QC Seminars
Within-subject
biological variation
• Age, sex
• Diet, physic exercise
• Pathology, treatment
• Within-day variation, season
variation
• Homeostasis
Fraser CG. Biological Variation: from theory to practice. AACC press, 2001
C Ricós
2010 QC Seminars
Within-subject
biological variation
Fluctuation of the
concentration
of blody fluid components
around the setting point
Fraser CG. Biological Variation: from theory to practice. AACC press, 2001
C Ricós
2010 QC Seminars
Between-subject
biological variation
Differences in concentration
of the components of
biologic fluids
among persons
Fraser CG. Biological Variation: from theory to practice. AACC press, 2001
C Ricós
2010 QC Seminars
How to estimate the
components of BV
Fraser CG. Biological Variation: from theory to practice. AACC press, 2001
C Ricós
2010 QC Seminars
How to estimate the
components of BV
2. To eliminate outliers
Cochran test outlier values
Reed test outlier individuals
C Ricós
2010 QC Seminars
How to estimate the
components of BV
C Ricós
2010 QC Seminars
Compilation of data on
Biological variation
C Ricós
2010 QC Seminars
What else?
a DATABASE
• selective
• permanently updated
C Ricós
2010 QC Seminars
Why?
To give information on
quality specifications for
• Imprecision (CV,%)
• Bias (SE,%)
• Total error (TE,%)
C Ricós
2010 QC Seminars
Material
1. PAPERS SEARCH: BIOS, CURRENT CONTENTS,
EMBASE, MEDLINE, PUBMED
- Calculations Individuality,
Critical differences
C Ricós
2010 QC Seminars
Method (1)
1. EXCLUSSIONS
• Papers with too high analytical variation
(CVA> 0.5 CVW)
• Papers not specifically designed to estimate CVW
and CVG
C Ricós
2010 QC Seminars
Method (2)
2. EXPRESSION (for each analyte)
• Papers in ascending order according to the CVW
• Search for relationships between CVW and
number of subjects, sex, health status, fasting;
number of samples per subject, time span of the
study…
• If no relationships are observed: calculation of
the median of CVW and CVG values from all
papers compiled
C Ricós
2010 QC Seminars
Example: s- Glucose
CVW CVG CVA N Td Ss Mean Unit Year
C Ricós
2010 QC Seminars
Method (3)
3. CALCULATION OF SPECIFICATIONS
C Ricós
2010 QC Seminars
Results
(Database, 2010 update)
319 analytes
59 journals
C Ricós
2010 QC Seminars
Database 2010 update
Example
C Ricós
2010 QC Seminars
Database 2010 update
References
C Ricós
2010 QC Seminars
Database - contras
analytes
C Ricós
2010 QC Seminars
Database - pros
C Ricós
2010 QC Seminars
Database - Applications
Quality specifications
Delta check
Reference change value
C Ricós
2010 QC Seminars
Quality specifications
Stockholm international consensus
1999
Professional recommendations
1:2s N=1
(2-3) 1:3 N=2
1:3,5s N=4
1;2,5s N=1
>3 1:3s N=2
1:3,5s N=4
Hyltoft P et al. Strategies to set global analytical quality specifications
in laboratory medicine. Scand J Clin Lab Invest 1999;57,7
C Ricós
2010 QC Seminars
Use of Q specifications
2. to evaluate internal QC results
C Ricós
2010 QC Seminars
Use of Q specifications
3. to evaluate EQA results
C Ricós
2010 QC Seminars
Use of Q specifications
3. to evaluate EQA results
- SEQC
C Ricós
2010 QC Seminars
Use of Q specifications
3. to evaluate EQA results
- SEQC
% of results reaching specifications based on BV
C Ricós
2010 QC Seminars
Delta Check
C Ricós
2010 QC Seminars
Reference change value
Fraser CG. Biological variation: from principles to practice. Washington DC. AACC Press ,2001
C Ricós
2010 QC Seminars
Reference change value
SOULD BE USED
• For analytes with high individuality
CVI/CVG<0.6
Fraser CG. Biological variation: from principles to practice. Washington DC. AACC Press ,2001
C Ricós
2010 QC Seminars
Reference change value
SHOULD BE USED
• In 276 of the 319 analytes
from the current database
C Ricós
2010 QC Seminars
Reference change value
Fraser CG. Biological variation: from principles to practice. Washington DC. AACC Press ,2001
C Ricós
2010 QC Seminars
Reference change vlaue
Fraser CG. Biological variation: from principles to practice. Washington DC. AACC Press ,2001
C Ricós
2010 QC Seminars
Reference change value
- reporting
NINEWELLS HOSPITAL AND MEDICAL SCHOOL
Result Units Ref.
values
Sodium 138 * mmol/L 135-147
Potassium 5.0 mmol/L 3.5-5.0
Urea 9.5 ** mmol/L 3.3-6.6
Creatinine 137 > mmol/L 50-100
Bilirubins 100 >> mmol/L NAME
Albumin 23 << g/L 36-50
Calcium 2.27 ** mmol/L 2.1-2.6
Fraser CG. Biological Variation: From Principles to Practice. Washington, DC, AACC Press, 2001
C Ricós
2010 QC Seminars
Reference change value
- in pathology
Pathology Analyte CVI (%)
Cancer ovarium CA 125 46
Cancer mamarian CA 15.3 17
C. colorectal CEA 45
Diabetes HbA1C 9
mellitus Microalbumin 36
Hepatic disease α-fetoprotein 40
Paget Alkaline phos. 12
Ricós C et al. Ann Clin Biochem 2007; 44: 343–352
Reference change value
- two analytes combined
VRC combinado
100
Uratos Diferencias (%)
50
-50
-100
-100 -50 0 50 100 150
Creatinina Diferencias (%)
C Ricós
2010 QC Seminars
References (2)
• Hyltoft Petersen P, Sandberg S, Fraser CG, Goldsmith H.
Influence of index of individuality on false positives in repeated
sampling from healthy individuals. Clin Chem Lab med
2001;391:160-165
• Comité de garantía de la Calidad y Acreditación de
Laboratorios. Comisión de Calidad analítica. Base de datos de
Variación biológica. Actualización del año 2010.
http://www.seqc.es/es/Sociedad/51/102
• Fraser CG, Stevenson HP, Kennedy IMG. Biological variation
data are necessary prerequisites for objective autoverification
of clinical laboratory data. Accred Qual Assur 2002;7:455-460.
• Biosca C, Ricós C, Lauzurica R, Galimany R et al. Reference
Change Value Concept Combining Two Delta Values to Predict
Crises in Renal Posttransplantation. Clin Chem 2001;47:2146-8
C Ricós
2010 QC Seminars
C Ricós
2010 QC Seminars