Commissie voor Klinische BiologieCommission de Biologie Clinique
EXTERNAL EVALUATION PROGRAM FORImmmunoassays - Chemistry
TRENDS IN TIME
CM Van Campenhout – N Hamers – JC Libeer WIV/ISP/IPH – Clinical Biology
Brussels - BELGIUM
• EQA PROGRAMS - STATISTICAL EVALUATION
• GENERAL CHANGES
• EVOLUTIONS IN IMMUNOASSAYS
• EVOLUTIONS IN CHEMISTRY
• EQA PROGRAMS – THE PLAYERS
• CONCLUSION
EQA PROGRAMS
• CLINICAL CHEMISTRY - ELECTROPHORESIS
• IMMUNOASSAYS
• HEMATOLOGY
• COAGULATION
• IMMUNOHEMATOLOGY
• FLOW CYTOMETRY
• NON INFECTIOUS SEROLOGY
• PCR / ONCO-HEMATO / MICROBIOLOGY
• HEAVY METALS
• ALLERGY
• SPERM
• HbA1c
• ALCOHOL
• POCT GLUCOSE
• MICROBIOLOGY
• PARASITOLOGY
• INFECTIOUS SEROLOGY
• THERAPEUTIC MONITORING
TYPES OF CONTROL MATERIAL
• COMMERCIAL LYOPHYLIZED (human)
• COMMERCIAL LIQUID (human)
• PATIENT SAMPLES - pools- single donation
• MICRO-ORGANISMS
• RELATIVE IMPRECISIONRELATIVE IMPRECISION (own peer group) CRITERIA
M - RZ-SCORE = --------- limit = 3Z (3SD)
SD
• RELATIVE ACCURACYRELATIVE ACCURACY (own peer group)
M - RU-SCORE = --------- x 100 limit = “d” (%)
M Based on biological variability
STATISTICAL non parametricANALYSIS OF QUANTITATIVE RESULTS
SD = P75 – P25 / 1,349
NUMBER OF RESULTS EXCEEDING THE LIMITS FOR IMPRECISION AND ACCURACY ARE ADDED
IMPRECISION (relative) ACCURACY (relative)
Z > 3SD (own peer group) U > d (fixed limit)method dependent non method dependent
LABORATORY EVALUATION FORQUANTITATIVE RESULTS
- ANNUAL REPORT-
NZ NuPercentages of Nz (=Pz) and Nu (Pu) for each laboratory are calculated
PRECISION (relative) ACCURACY (relative)
(%) 100N
NP ZZ ×⎟
⎠⎞
⎜⎝⎛= (%) 100
NNP U
U ×⎟⎠⎞
⎜⎝⎛=
90th percentile (P90) of the distribution of all Pz and all Pu values of all laboratories is calculated criterion for performance evaluation.
Pz > P(90) z Poor performance for PRECISION
Pu > P(90)u Poor performance for ACCURACY
LABORATORY EVALUATION FORQUANTITATIVE RESULTS
- ANNUAL REPORT-
Cumulative Pz- en Pu-distribution for alllaboratories - EQA CHEMISTRY 2009 - (N=213)
0
20
40
60
80
100
120
0 5 10 15 20 25 30 35Percentage z-scores and u-scores "out of limit values"
Cum
ulat
ive
freq
dis
trib
.o
Pz
Pu
• EQA PROGRAMS - STATISTICAL EVALUATION
• GENERAL CHANGES
• EVOLUTIONS IN IMMUNOASSAYS
• EVOLUTIONS IN CHEMISTRY
• EQA PROGRAMS – THE PLAYERS
• CONCLUSION
CHANGES OVER TIME - GENERAL
• CHANGES IN NUMBER OF PARTICIPATING LABORATORIES
• CHANGES IN REQUESTED ANALYTES
• MAJOR CHANGES IN METHODOLOGIES
• MAJOR CHANGES IN REPORTING EQA RESULTS
050
100150200250300350400450
BIOCHEMISTRY IMMUNOASSAY
19952008
EVOLUTION OF PARTICIPATING LABORATORIES
• INCREASE IN REQUESTED ANALYTES
• CHANGES IN METHODOLOGY
EVOLUTION IN EQA IMMUNOASSAYS
VancomycinValproic acidTheophyllinePhenytoinPhenobarbitalParacetamolLithiumGentamicinDigoxinCarbamazepinAmikacinSalicylate
Anti TG/TPOVitamin B12TSHThyroglobulinTestosteronPSAProlactineProgesteroneParathormoneOestradiolNSELHInsulinIgE
hGHhCGFT4FT3FSHFolateFerritineDHEA-Sc-PeptideCortisolCEACA 19.9CA 15.3CA 125AFP
REQUESTED ANALYTES EQA IMMUNASSAYS
1995
VancomycinValproic acidTheophyllinePhenytoinPhenobarbitalParacetamolLithiumGentamicinDigoxinCarbamazepinAmikacinSalicylate
Anti TG/TPOVitamin B12TSHThyroglobulinTestosteronPSAProlactineProgesteroneParathormoneOestradiolNSELHInsulinIgE
hGHhCGFT4FT3FSHFolateFerritineDHEA-Sc-PeptideCortisolCEACA 19.9CA 15.3CA 125AFP
REQUESTED ANALYTES EQA IMMUNASSAYS
1995 - 2008
0.0
20.0
40.0
60.0
80.0
100.0
%RIA % non RIA
EXAMPLE FOR PROGESTERON
1996 1997 1998 1999 2000 2001 2002 2003
CHANGES IN METHODOLOGY
from RIA to non RIA METHODS
0102030405060708090
RIA non RIA
20%28%
CV(%) IN FUNCTION OF TIME
RIA and non RIA METHODS
CV(%)
1996 1997 1998 1999
EXAMPLE FOR PROGESTERON
0
5
10
15
20
25
30
35
40
Immunotech(4)
Siemens(coat-a-
count) (9)
Access (6)
Liaison (6)
Elecsys Cobas e
(29)
Immulite (38)
Global (102)
Patient 1.68 µmol/LBiorad 1.69 µmol/LPatient 1.69 µmol/LBiorad 14.20 µmol/LRandox 25.00 µmol/L
DHEA-S CV (%)
CV(%) IN FUNCTION OF METHODS
Analytical systems
(n=4) Coat-a-count(n=9) (n=6)
(n=29)(n=38) (n=102)(n=6)
05
101520253035404550
AFP*
CEA
*
Cortisol
Ferritine
FSH
FT3*
FT4*
hCG
IgE
LH Progesteron
Prolactine*
PSA
Testosteron*
TSH
Vit B12
d (%)1993/2004*d (%) 2008TE-WESTGARD
EVOLUTION OF FIXED LIMITS “d” IN TIME
0
5
10
15
20
25
30
Am
ikacine*
Digoxine
Theophylline
Valproïnezuur*
Vancom
ycine* d (%)1993/2004*d (%) 2005 d (%) 2008
EVOLUTION OF FIXED LIMITS “d” IN TIME
1994 1996 1998 2000 2002 2004 2006 2008
14
12
10
8
6
4
CYCLE
P(90
) Z
1994 1996 1998 2000 2002 2004 2006 2008
18
16
14
12
10
8
6
4
CYCLE
P(90
) U
INTRODUCTION OF NEW
PARAMETERS
CHANGES IN CONCENTRATIONS
(e.g. low values)
EVOLUTION OF
PU and Pz IN TIME
P(90)U
P(90)Z
• INCREASE IN REQUESTED ANALYTES
• CHANGES IN METHODOLOGY
EVOLUTION IN EQA CHEMISTRY
eGFR*γ GTCREATININECHOLESTEROL TOTALCHOLESTEROL – HDL*CHLORIDESCALCIUMBILIRUBINE TOTAL*BILIRUBINE DIRECTE*AST*AMYALSEALTALBUMIN*
REQUESTED ANALYTES EQA CHEMISTRY
1995
GLUCOSEIgAIgGIRONLDHMAGNESIUMPHOSPHORUS*POTASSIUMSODIUMTOTAL PROTEINTRIGLYCERIDESURIC ACIDUREA
eGFR*γ GTCREATININECHOLESTEROL TOTALCHOLESTEROL – HDL*CHLORIDESCALCIUMBILIRUBIN TOTAL*BILIRUBIN DIRECT*AST*AMYLASEALTALBUMIN*
REQUESTED ANALYTES EQA CHEMISTRY
1995 - 2008
GLUCOSEIgAIgGIRONLDHMAGNESIUMPHOSPHORUS*POTASSIUMSODIUMTOTAL PROTEINTRIGLYCERIDESURIC ACIDUREA
CHANGES IN METHODOLOGIES
• UNIFORMIZATION OF TEMPERATURE FOR ENZYMES
• ELECTROLYTES: Flame photometry POTENTIOMETRY
• STANDARIZATION OF SERUM PROTEINS (CRM 470)
• STANDARDIZATION OF CREATININE (IDMS)
ELECTROLYTES
• SODIUM
• POTASSIUM
• CHLORIDES
• CALCIUM
POTASSIUM (mmol/L)
NCV(%)MEDIANSURVEY
3681.72.0
4.906.41
1994/04
3791.83.0
6.427.39
1994/03
3932.92.6
3.805.80
1994/02
3842.92.2
5.207.00
1994/01
NCV(%)MEDIANSURVEY
2102.20.9
6.284.00
2009/01
2041.71.3
4.805.10
2008/03
2072.21.4
3.306.22
2008/02
2101.51.2
4.006.26
2008/01
CHLORIDES (mmol/L)
NCV(%)MEDIANSURVEY
2083.22.3
116.098.7
2009/01
2074.31.9
86.0116.8
2008/02
2103.22.8
116.099.0
2008/01
2111.92.9
116.0103.0
2007/03
NCV(%)MEDIANSURVEY
3592.84.0
107.0111.0
1994/04
3674.06.0
111.0126.0
1994/03
3825.14.4
102.085.0
1994/02
3736.34.2
70.588.0
1994/01
SODIUM (mmol/L)
NCV(%)MEDIANSURVEY
2092.11.5
142.0144.6
2009/01
2041.71.5
151.0150.0
2008/03
2061.81.9
122.0160.0
2008/02
2092.11.5
141.8145.0
2008/01
NCV(%)MEDIANSURVEY
3681.82.7
145.0138.0
1994/04
3792.71.3
138.0171.0
1994/03
3931.61.7
136.0111.0
1994/02
3842.91.6
107.2121.0
1994/01
CALCIUM (mmol/L)
NCV(%)MEDIANSURVEY
2092.62.4
3.152.35
2008/04(Serum)
2042.63.2
2.352.35
2008/03
2073.32.6
2.083.15
2008/02
2092.92.9
3.182.38
2008/01
NCV(%)MEDIANSURVEY
3833.53.6
3.292.45
1994/04
3913.84.1
3.303.05
1994/03
4114.63.5
2.082.93
1994/02
3983.53.3
3.222.50
1994/01
0,00
1,00
2,00
3,00
4,00
5,00
6,00
1999
1999
2000
2000
2001
2001
2002
2002
2003
2003
2004
2004
2005
2005
2006
2006
2007
2007
2008
2008
Arsenazo O-Cresol Indirect Pot.
EVOLUTION OF CV(%) for CALCIUM OVER TIME
CHANGES IN METHODOLOGIES
• UNIFORMIZATION OF TEMPERATURE FOR ENZYMES
• ELECTOLYTES: Flame photometry POTENTIOMETRY
• STANDARIZATION OF SERUM PROTEINS (CRM 470) - 1994
• STANDARDIZATION OF CREATININE (IDMS)
IgG (g/L)
NCV(%)MEDIANSURVEY
1656.66.4
7.816.21
2008/02
1667.26.8
6.805.90
2007/04
1645.14.9
7.317.32
2007/02
1646.46.2
11.757.86
2007/01
NCV(%)MEDIANSURVEY
34415.816.0
7.8711.30
1993/04
35318.217.6
10.208.39
1993/03
35214.817.4
9.327.53
1992/04
35415.518.2
5.9412.28
1992/01
BEFORE BEFORE CRM 470 AFTERAFTER CRM 470
IgA (g/L)
NCV(%)MEDIANSURVEY
1658.67.9
1.551.32
2008/02
1667.47.7
1.461.34
2007/04
1647.87.3
1.521.52
2007/02
1666.47.8
2.901.62
2007/01 35417.823.2
1.292.47
1992/01
NCV(%)MEDIANSURVEY
34218.319.0
1.702.50
1993/04
35223.819.9
2.221.90
1993/03
36220.319.3
1.892.08
1992/03
BEFOREBEFORE CRM 470 AFTERAFTER CRM 470
0,00
5,00
10,00
15,00
20,00
25,00
30,00
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
EVOLUTION of CV(%) over time
Introduction of CRM 470CRM 470
CRM 470
IgA
0,00
5,00
10,00
15,00
20,00
25,00
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
CRM 470
IgG
CREATININE(µmol/L)
NCV(%)MEDIANSURVEY
2105.15.3
128.0347.0
2009/01
2048.27.1
72.273.2
2008/03
2079.74.2
102.0362.0
2008/02
2095.14.7
128.0347.0
2008/01
NCV(%)MEDIANSURVEY
4175.85.6
167.0344.0
1994/04
4236.25.7
344.0189.0
1994/03
44618.77.0
115.0597.0
1994/02
4345.66.3
212.0307.0
1994/01
EVOLUTION OF FIXED LIMITS “d” IN TIME
0
5
10
15
20
25
30
35
40
45
50
Album
in*
ALA
T
Am
ylase
ASA
T*
Bilirubin direct*
Bilirubin total*
Calcium
Cholesterol
Chloride
Creatinine
Phosphorus*
g GG
T
Glucose
HD
L-Cholesterol *
IgA
IgG
Iron
Potassium
LDH
Magnesium
Sodium
Protein total
Triglycerides
Urea
Uric A
cid
d (%) 1993/2004*d (%) 2008TE - WESTGARD
1992 1994 1996 1998 2000 2002 2004 2006 2008
35
30
25
20
15
10
5
P(90
) U
1992 1994 1996 1998 2000 2002 2004 2006 2008
18
16
14
12
10
8
6
4
P(90
) Z
EVOLUTION OF
PU and Pz IN TIME
P(90)U
P(90)Z
• 2006 - Changes in fixed limit “d”• Amylase• K• Mg• Cholesterol tot/HDL• Glucose• LDH• Uric acid• Iron• Urea
5,43,922,22020gGT
1,51,210,210,210,2Phosporus*
2,99,38,28,38,3Creatinine
2,617,41,533Chlorides
2,41,68,5910,5Cholesterol tot..
1,58,92,44,54,5Ca
3,410,931,116,216,2Bilirubin tot.*
8,39,644,524,124,1Bilirubin dir.*
2,64,515,215,215,2AST*
2,51,614,61517Amylase
2,812,632,12020ALT
4,215,73,96,26,2Albumin*
Z > 3%
U > d%
TE -WESTGARD
d (%) 2008
d(%) 1993 2004*
ANALYTE
4,21,512,411,915Uric acid
1,50,615,715,721Ureum
5,80,227,92020Triglyc.
2,14,83,45,55,5Proteins tot.
2,414,20,922Na
3,12,54,88,89,5Mg
3,71,011,411,414LDH
6,91,45,85,88K
2,32,230,79,520Ijzer
2,94,0811,511,5IgG
4,21,013,51919IgA
3,04,411,113,415HDL-Chol.*
1,91,56,96,914Glucose
Z >3%
U > d%
TE -WESTGARD
d (%) 2008
d(%)1993
2004*ANALYTE
FIXED LIMITS (d) - TEa - U > d (%) - Z > 3 (%)
FIXED LIMITS ARE BASED ON Westgard TEa or on the 90th percentile of intra-laboratory CV’s (multiplied by 3) of about 10 laboratories using different techniques
CHANGES OVER TIME - GENERAL
DECREASE IN NUMBER OF PARTICIPATING LABORATORIES
INCREASE IN REQUESTED ANALYTES
MAJOR CHANGES IN METHODOLOGIES
MAJOR CHANGES IN REPORTING EQA RESULTS
CHANGES OVER TIME - GENERAL
AMELIORATION OF RELATIVE ACCURACY
AMELIORATION OF RELATIVE PRECISION
MAJOR CHANGES IN METHODOLOGIES dedicated systems generally lesser method principles (ex enzymes, electrolytes,…)
MAJOR CHANGES IN REPORTING EQA RESULTS more documented reports – educative messages – graphs - …….
EQA PROGRAMS - THE PLAYERS
PARTICIPANTS = LABORATORIES
ORGANIZERS = WIV/ISP
EQUIPEMENT/REAGENTS = MANUFACTURERS
ALL PLAYERS AFFECT THE RESULTS OF EQA SURVEYS
LABORATORIES
MANUFACTURERS
EQA ORGANIZERSWIV/ISP
INCORRECT choice of units (e.g. mg/dL – mmol/L)
INCORRECT choice of method
INCORRECT interpretation of “limit of detection” and limit of quantification (LOQ ≠ LOD)
INCORRECT SAMPLE IDENTIFICATION
PARTICIPANTS - LABORATORIES
ORGANIZERS = WIV/ISP
CHOICE OF CONTROL MATERIAL
CONCENTRATION RANGES
FIXATION OF LIMIT “d”
PARTITION OF METHODS AND METHOD GROUPSMEASURING PRINCIPLEMANUFACTURER
2084.40 3.4%0.05 1.42 Global results (all methods and all measuring systems)
64.43 1.70.02 1.43 310 Unreduced phosphomolyb./ UV-Siemens (Bayer)
574.41 1.70.02 1.42 309 Unreduced phosphomolyb./ UV-Roche (Hit/Modular)
594.30 3.40.05 1.39 308 Unreduced phosphomolyb./ UV-Roche (Cobas/Integra)
124.40 3.00.04 1.42 307 Unreduced phosphomolyb./ UV-Olympus
64.27 3.50.05 1.38 306 Unreduced phosphomolyb./ UV-Siemens (Dade)
164.83 3.10.05 1.56 305 Unreduced phosphomolyb./ UV-Coulter (Beckman)
154.30 2.60.04 1.39 304 Unreduced phosphomolyb./ UV-Abbott
354.50 3.20.05 1.45 303 Reflectometry - OCD
2********1.48 - 1.54 301 Unreduced phosphomolyb./ UV-Other
N labsMedianmg/dL
CV%
SDmmol/L
Medianmmol/L METHOD
C/8202 (2009/01)PHOSPHORUS - d (%) : 10.2
C/8181 (2008/01)PHOSPHORUS - d (%) : 10.2
4.41
4.41
4.41
Medianmg/dL
2093.4%0.051.42Global results (all methods and all measuring systems)
351.7%0.021.42003 Reflectometry - OCD
2********1.41-1.45002 Reduced phosphomolybdate complex / VIS
1723.4%0.051.42001 Unreduced phosphomolybdate complex / UV
No.labsCV%SDMedian
Mmol/LMETHOD
C/8181 METHOD 11,65
1,55
1,45
1,35
1,25
MANUFACTURER
PH
OS
PH
OR
US
(m
mol
/L)
1 2 3 4 5 6 7
PHOSPHORUS – 2008/01
C/81818/19 labs U > d (=10,5%) 12/19 labs R > 3Z
001 Unreduced phosphomolybdate complex / UV
310 Unreduced phosphomolyb./ UV-Siemens (Bayer)
309 Unreduced phosphomolyb./ UV-Roche (Hit/Modular)
308 Unreduced phosphomolyb./ UV-Roche (Cobas/Integra)
307 Unreduced phosphomolyb./ UV-Olympus
306 Unreduced phosphomolyb./ UV-Siemens (Dade)
305 Unreduced phosphomolyb./ UV-Coulter (Beckman)
304 Unreduced phosphomolyb./ UV-Abbott
303 Reflectometry - OCD
301 Unreduced phosphomolyb./ UV-Other
413416N
2,664,33P Z (%)
1,456,40P U (%)
2009/012008/01
INFLUENCE OF PEER GROUPING ON p U(%)
% citations for U > d; relative accuracy
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
ALBUMIN ALT
AMYLA
SE AST
BILIRUB
IN TOTA
L CA
LCIUM
CH
LORIDE
CHOLEST
EROL-HDL
CHOLEST
EROL-Tota
lCREA
TININE
GGT
GLUCOSE
IGA
IGG
IRON
LDH
MAGNES
IUM
PHOSPHORUS POTA
SSIUM
SODIUM
TOTA
L PROTE
IN
TRIG
LYCERID
ES UR
ATE
UREA
p U% 2008/1p U% 2009/1
INFLUENCE OF PEER GROUPING ON p Z(%)
0%
1%
2%
3%
4%
5%
6%
7%
8%
ALBUMINALT
AMYL
ASE
AST
BILIRUBIN TO
TAL
CALCIUM
CHLORIDE
CHOLEST
EROL-H
DL
CHOLEST
EROL-T
otal
CREATIN
INEGGT
GLUCOSE IGA
IGG IRON LD
H MAGNES
IUMPH
OSPHORUS
POTA
SSIUM
SODIUM
TOTA
L PROTE
IN
TRIGLY
CERIDESURATE
UREA
p Z% 2008/1p Z% 2009/1
% citations for Z > 3; relative imprecision
EQUIPEMENT/REAGENTS = MANUFACTURERS
INFORMATION ON NEW or CHANGED REAGENT / EQUIPEMENT
MEASURING PRINCIPLECALIBRATION
INFORMATION ON CALIBRATION / LINEARITY
CORRECT AND FULLY DOCUMENTED INSERTS
COMMUNICATION WITH WIV/ISP ON EPXIRED REAGENTS/EQUIPEMENT
BILIRUBIN TOTAL (21670) µmol/l C/7521 METHOD Median SD CV No.labs
1 Diazo sulfanilic acid 85.50 5.45 6.4% 97 2 Diazo sulfanilic acid (blue color) 83.79 2.09 2.5% 19 4 Dichloraniline 89.18 4.82 5.4% 6 5 Diphenyldiazonium (DPD) 84.47 3.80 4.5% 42 6 Reflectometry 75.41 3.11 4.1% 35 7 Reduction (biliverdin) 78.15 3.04 3.9% 9 obal results (all methods and all measuring systems) 83.70 5.39 6.4% 208
B IL IR U B IN T O T A L - d (% ) : 1 6 .2 C o n ve rs io n fa c to r : µ m o l/L / 1 7 .1 = m g /d L C /7 5 22
M E T H O D M e d ia nµ m o l/L
S D µ m o l/L
C V %
M e d ia nm g /d L N lab s
3 01 D ia zo su lfa n ilic a c id -S ie m e n s (D a d e ) 7 6 .9 5 0 .2 5 0 .3 4 .5 0 6 3 02 D ia zo su lfa n ilic a c id (b lue co lo r)-C o u lte r 8 3 .1 1 1 .8 4 2 .2 4 .8 6 16 3 03 D ia zo su lfa n ilic a c id -O the r 8 7 .2 1 - 8 5 .1 5 2 3 04 D ich lo ra n iline - A bbo tt 7 0 .1 1 5 .0 7 7 .2 4 .1 0 13 3 05 D ip h en y ld ia zo n iu m (D P D )-O lym pu s 8 5 .8 4 1 .8 7 2 .2 5 .0 2 12 3 06 R e fle c to m etry-O C D 7 3 .1 9 3 .7 4 5 .1 4 .2 8 35 3 07 R ed u ction (b ilive rd in )-S ie m e n s (B a ye r) 7 7 .8 9 2 .6 6 3 .4 4 .5 5 6 3 09 R ed u ction (b ilive rd in )-A b b o tt 7 4 .5 6 - 7 7 .6 3 2 3 10 D ia zo su lfa n ilic a c id -R o ch e (C o b as/In teg ra ) 7 9 .1 7 7 .6 1 9 .6 4 .6 3 17 3 11 D ia zo su lfa n ilic a c id -R o ch e (H it/M o du la r) 7 3 .8 7 6 .6 5 9 .0 4 .3 2 55 3 12 D ip h en y ld ia zo n iu m (D P D )-R o ch e (C o b a s) 7 5 .5 0 6 .9 7 9 .2 4 .4 1 42 G lo b a l re s u lts (a ll m e th o d s an d a ll m e a s u rin g s ys te m s ) 7 5 .6 7 7 .1 0 9 .4 4 .4 2 2 0 6
?
EQA is not just statistics !
LABORATORIES
MANUFACTURERS
EQA ORGANIZERSWIV/ISP
evaluation - amelioration - education – communication Having confidence is good, to check your confidence is better…
Coming up soon – 2009 / 2010
•DOA – urine
•Cardiac markers
•Specific proteins
•CRP
With sincere thanks to all laboratories for their willing collaborationN Hamers – Y Lenga – C Van Campenhout – P Van de Walle
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