Validation of the Cobas/Ssdw system for trisomy 21 ...€¦ · Swiss MedLab 2012 June 12 4 Snijders...

Validation of the Cobas/Ssdw system

for trisomy 21 screening in the first

trimester of pregnancy:

Comparison with the Kryptor/

FastScreen combination

MF Rossier, N Beloeil, J Hediger-Bonfantini, S Dahoun,

R Stricker, E Dayer, O Irion, DF Hochstrasser, and I Kern

Dr M.F. Rossier Institut Central (ICHV)

Service de Chimie

clinique & Toxicologie

|

Introduction

June 12 2 Swiss MedLab 2012

Source: Merck Manual of Medical Information

0

1

2

3

4

5

6

7

Ris

k o

f D

ow

n s

yn

dro

me i

n

live b

irth

s (

%)

20 24 28 32 36 40 44 48

Maternal age (years)

Risk assessment

1 in

1667

1 in

769

1 in 14

1 in 38

1 in

1061 in

1250

1 in

1053

1 in

294

0

1

2

3

4

5

6

7

Ris

k o

f D

ow

n s

yn

dro

me i

n

live b

irth

s (

%)

20 24 28 32 36 40 44 48

Maternal age (years)

Risk assessment

1 in

1667

1 in

769

1 in 14

1 in 38

1 in

1061 in

1250

1 in

1053

1 in

294

Prenatal Screening Increasing Down syndrome risk with increasing maternal age

|

Introduction


Nuchal Translucency

(NT)

|

Introduction


Snijders et al.,Lancet 1998;351:343.

Sensitivity

False positives

(5 %)

Nuchal Translucency (NT) is

increased in case of Down

Syndrome, congenital heart

defects, other syndromes and

conditions.

Sens = 77 % at Spec = 95 %

(NT + maternal age, medians

according to gestational age and

embryo size)

|

Introduction


Risk Assessment Comparison of detection rates of different screening methods

Comparison of the detection

rates (DR), for a false

positive rate (FPR) of 5% of different screening

methods for trisomy 21 in

prenatal screening.

Source: FMF, London 2004

|

Instruments for free b-hCG and PAPP-A determination

Cobas 6000 <e601> (Roche)

(FMF certified since 2010)

Kryptor (Brahms/Thermo)

(reference method)

Program Furnisher Ref Instrument Statistics Calculated

risk

Certification

required

Recommendation

*FastScreen (2009 - V.1.1.3.2)

Brahms Kryptor DoE At sampling FMF (D) Recommended in

Switzerland

Prisca (2004 – V.4.0.20.4)

Siemens Kryptor or

Immulite

MoM At term or at

sampling

no Alternative to

FastScreen

Astraia (2009)

Astraia MoM At term FMF (UK) Recommended in

Switzerland

*Ssdw Lab

(2007 – V.5)

Roche Cobas MoM At sampling

or at term

no In process


Softwares for risk assessment

|

0 5000 10000 15000

0

5000

10000

15000

Passing-Bablok

regression anal.

y=0.915x+60.7

r=0.973, n=209

PAPP-A vs Lab1

vs Lab2

Co

ba

s 6

00

0 P

AP

P-A

(m

UI/L

)

Kryptor PAPP-A (mUI/L)


Instrument comparisons

|

1000 10000

1000

10000

Passing-Bablok

regression anal.

y=0.915x+60.7

r=0.973, n=209

PAPP-A vs Lab1

vs Lab2

Co

ba

s 6

00

0 P

AP

P-A

(m

UI/L

)

Kryptor PAPP-A (mUI/L)



|

10 100

10

100

vs Lab1

vs Lab2

Co

ba

s 6

00

0 fre

e b

-hC

G (

ng

/ml)

Kryptor free b-hCG (ng/ml)

free b-hCG

Passing-Bablok

regression anal.

y=0.970x-1.251

r=0.983, n=209



|

Cohort: 143 pregnancies including

- 40 cases of trisomy 21, plus

- 103 consecutive controls

Analysis: ROC curve characteristics

Sensitivity and specificity

Illegitimate combinations

Influence of nuchal translucency


Performance evaluation

|

0.0 0.2 0.4 0.6 0.8 1.0

0.0

0.2

0.4

0.6

0.8

1.0

S

en

sit

ivit

y

1 - Specificity (FPR)

Kryptor / FastScreen

AUC = 99%

Se = 95% at 5% FPR

Cobas / Ssdw

AUC = 99%

Se = 95% at 5% FPR

Analysis on

- 40 T21 cases

- 103 controls

ROC curve analysis


| June 12 12 Swiss MedLab 2012

Comparison Kryptor/FastScreen and Cobas/Ssdw

1 10 100 1000 10000

10

100

1000

10000

Sen : 88% (35/40)

Spe : 98% (101/103)

Sen : 90% (36/40)

Spe : 98% (101/103)

Controls (103)

Affected (40)

Cobas /

Ssdw

ris

k a

t sam

plin

g (

odds r

atio)

Kryptor / FastScreen risk at sampling (odds ratio)


1 10 100 1000 10000

1

10

100

1000

10000

Sen : 88% (35/40)

Spe : 100% (103/103)

Sen : 88% (35/40)

Spe : 98% (101/103)

Controls (103)

Affected (40)

juillet 2011

Co

ba

s / F

astS

cre

en

ris

k a

t sa

mp

ling

(o

dd

s r

atio

)

Kryptor / FastScreen risk at sampling (odds ratio)

Comparison of instruments using FastScreen


10 100 1000 10000

10

100

1000

10000Sen : 90% (36/40)

Spe : 100% (103/103)

Sen : 88% (35/40)

Spe : 100% (103/103)

Controls (103)

Affected (40)

Cobas /

Ssdw

ris

k a

t te

rm (

odds r

atio)

Kryptor / Ssdw risk at term (odds ratio)

Comparison of instruments using Ssdw

| 15 June 12 Swiss MedLab 2012

Comparison of softwares using Cobas

1 10 100 1000 10000

10

100

1000

10000

Sen : 90% (36/40)

Spe : 98% (101/103)

Sen : 88% (35/40)

Spe : 100% (103/103)

Controls (103)

Affected (40)

Co

ba

s /

Ssd

w r

isk a

t sa

mp

ling

(o

dd

s r

atio

)

Cobas / FastScreen risk at sampling (odds ratio)

|

1.0 1.5 2.0 2.5 3.0 3.5 4.0

1

10

100

1000

10000

odd

s r

atio

NT (mm)

Ssdw

FastScreen

Prisca

Cisline

1.0 1.5 2.0 2.5 3.0 3.5 4.0

1

10

100

1000

10000

NT (mm)

Cobas

Kryptor


Weight of nuchal translucency in risk assessment

|

Case 1 Case 3 Case 2


1.0 1.5 2.0 2.5 3.0 3.5 4.0

10

100

1000

10000

odd

s r

atio

NT (mm)

Ssdw

FastScreen

Prisca

Cisline

1.0 1.5 2.0 2.5 3.0 3.5 4.0

1

10

100

1000

10000

NT (mm)

1.0 1.5 2.0 2.5 3.0 3.5 4.0

1

10

100

1000

10000

NT (mm)

Weight of nuchal translucency in risk assessment

|

Conclusion

In our limited cohort, the Cobas/Ssdw system performed as well as

the Kryptor/FastScreen system and therefore could be considered as

a new alternative in Switzerland for risk assessment in the first

trimester of pregnancy

PAPP-A and free b-hCG determinations in biological

samples were similar with the Kryptor and the Cobas e-601

In our cohort, both systems predicted the presence of

trisomy 21 with similar sensitivity and specificity

Variability between systems was mostly due to the software,

not to the analytical instrument

The weight of the nuchal translucency in the risk assessment

was similar in the four tested softwares


|

Acknowledgements

Central Institute (ICHV)

Nicole Beloeil*

Eric Dayer

Univ. Hosp. Geneva (HUG)

Jocelyne Hediger*

Sophie Dahoun

Olivier Irion

Denis Hochstrasser

Ilse Kern*

Dianalabs

Reto Stricker

Disclosure: Cobas reagents were provided by Roche


Validation of the Cobas/Ssdw system for trisomy 21 ...€¦ · Swiss MedLab 2012 June 12 4 Snijders...

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Transcript of Validation of the Cobas/Ssdw system for trisomy 21 ...€¦ · Swiss MedLab 2012 June 12 4 Snijders...