1. QA of screening for downs

WHAT, WHY AND

HOW?

WHAT:

Some background

Probability

Model

Age risk model

Risk

MoM values

Marker values (PAPP-A, free hCG, NT)

Gestational age (from CRL)

Maternal weight

Smoking

Ethnicity

The process

Standardisation

Standardisation

Ideally markers should be independent of other variables such as gestation, weight, ethnicity, .. so that interpretation is easy The reality is that marker levels depend, to various degrees, on:

• Gestation • Maternal weight • Ethnicity • Smoking status • Multiple pregnancy • IVF • Machine • Laboratory • Reagent lot • etc.

We standardise into MoM values to remove the effects of these characteristics.

4

PAPP-A

0 5 10 15

PAPP-A

0 5 10 15

PAPP-A

0 5 10 15

Illustration PAPP-A 11w+3d

12w+3d

13w+3d

PAPP-A

0 5 10 15

PAPP-A

0 5 10 15

PAPP-A

0 5 10 15

11w+3d

12w+3d

13w+3d

PAPP-A

0 5 10 150.5 1.0 2.0

PAPP-A

0 5 10 150.5 1.0 2.0

PAPP-A

0 5 10 150.5 1.0 2.0

11w+3d

12w+3d

13w+3d

PAPP-A MoM

0 1 2 3 4 5

PAPP-A MoM

0 1 2 3 4 5

PAPP-A MoM

0 1 2 3 4 5

MoMs 11w+3d

12w+3d

13w+3d

PAPP-A MoM - log scale

0.1 0.5 1.0 2.0 10.0


0.1 0.5 1.0 2.0 10.0


0.1 0.5 1.0 2.0 10.0

Log (MoMs)

11w+3d

12w+3d

13w+3d

11w+3d

12w+3d

13w+3d


0.1 0.5 1.0 2.0 10.0


0.1 0.5 1.0 2.0 10.0


0.1 0.5 1.0 2.0 10.0

PAPP-A

Gestation (days)

PA

PP

-A (

iU/l)

50 60 70 80 90 100

0.1

0.2

0.5

1.0

2.0

5.0Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

Weight (kg)

PA

PP

-A M

oM

40 50 60 70 80 90 100 110 120 130 140 150

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

11

Effects on PAPP-A

MoM PAPP-A

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21 - Wk 11-13

T risomy 18

T risomy 13

Afro-Caribbean

Asian

Oriental

Smoking

11 12 13

PAPP-A

12

Free β-hCG (T1)

Gestation (days)

hC

G b

eta

50 60 70 80 90 100

5

10

20

30

40

5060

80

100

150

200

250

Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

Gestation (days)

Fre

e b

eta

hC

G

100 110 120 130 140 150

5

10

15

20

25

30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

Weight (kg)

Fre

e b

eta

MoM

40 50 60 70 80 90 100 110 120 130 140 150

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

Fre

e b

eta

hC

G

100 110 120 130 140 150

5

10

15

20

25

30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

13

Free β-hCG (T1) Effects on Free ß-hCG (T1)

MoM Free ß-hCG (T1)

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

Afro-Caribbean

Asian

Oriental

Smoking

11 12 13

14

AFP

Weight (kg)

AF

P M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

AF

P

100 110 120 130 140 150

20

30

40

50

60

70

80 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

15

AFP Effects on AFP

MoM AFP

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

African

Caribbean

Chinese

Oriental

Asian

Bangladeshi

Indian

Pakistani

Smoking

16

uE3

Weight (kg)

uE

3 M

oM

40 50 60 70 80 90 110 130 150

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

uE

3

100 110 120 130 140 150

1

2

3

4

5

6

78

10

15

20 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

17

Effects on uE3

MoM uE3

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

African

Caribbean

Chinese

Oriental

Asian

Bangladeshi

Indian

Pakistani

Smoking

uE3

18

hCG

Weight (kg)

hC

G M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

hC

G

100 110 120 130 140 150

10

20

30

40

50 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

19

hCG Effects on hCG

MoM hCG

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

African

Caribbean

Chinese

Asian

Indian

Pakistani

Smoking

20

Free β-hCG (T2)

Weight (kg)

Fre

e b

eta

hC

G M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

Fre

e b

eta

hC

G

100 110 120 130 140 150

5

10

15

20

25

30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

21



0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

African

Caribbean

Black Other

Asian

Bangladeshi

Indian

Pakistani

Other Asian

Chinese

Oriental

Smoking

22

Gestation (days)

Inhib

in

100 110 120 130 140 150

100

150

200

250

300

Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

Weight (kg)

Inhib

in M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Inhibin

23

Effects on Inhibin

MoM Inhibin

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

Asian

Caribbean

Smoking

Inhibin

24

Nuchal

Translucency

NT

Crown-rump length (mm)

Nu

ch

al tr

an

slu

ce

ncy (

mm

)

45 50 55 60 65 70 75 80 85

0.5

1

2

3

4

5

6

78

WHY : the effect of

errors on the

screening program

Standardisation

• MoM values should be centred on 1.0 when viewed together, by gestation, by weight, by smoking status, by ethnicity …

• What if this is not true?

28

Inputs and parameter estimates

Risk

DR/FPR/SPR

Process

Amplification of errors

Effects of bias – biochemistry

(NT and biochemistry at 12 weeks risk cut-off 1 in 150 at term)

A 27% increase in SPR with 70 more ‘positive’ results per 10,000

screening tests than expected.

PAPP-A hCG β

1 1 2.6% 85%

0.9 1 3.3% 87%

1 0.9 2.0% 83%

1.1 1 2.0% 83%

1 1.1 3.1% 86%

0.9 0.9 2.7% 85%

1.1 1.1 2.4% 84%

0.9 1.1 4.0% 88%

1.1 0.9 1.7% 81%

Median MoM FPR (%) DR (%)

The importance

of crown rump

length

The (near) perfect world of biochemistry

Cyprus

Gestation (weeks)

PA

PP

-A M

oM

7 8 9 10 11 12 13

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

n= 1

n= 812

n= 4787 n= 4231n= 1426

n= 311

n= 72

n= 2

Median Standard

The median MoM

value for any sub-

population defined by

time period, gestational

age, maternal weight,

smoking status and

ethnicity should lie

within 5% of the target

value of 1.

Median MoM by

gestation

Operator

hC

G b

eta

Mo

M

######

######

######

######

######

######

######

######

######

######

###

0.8

1.0

1.2

n = 2 7

n = 2 9

n = 3 3n = 3 4

n = 3 5

n = 3 7

n = 3 8

n = 4 7

n = 6 6

n = 6 8

n = 7 0

n = 7 5

n = 7 7

n = 7 9

n = 8 0

n = 9 9

n = 1 0 4

n = 1 0 4

n = 1 0 9

n = 1 5 3

n = 1 8 6

OperatorP

AP

P-A

Mo

M

######

######

######

######

######

######

######

######

######

######

###

0.8

1.0

1.2 n = 2 7

n = 2 9

n = 3 3

n = 3 4

n = 3 5

n = 3 7

n = 3 8

n = 4 7

n = 6 6

n = 6 8

n = 7 0

n = 7 5

n = 7 7

n = 7 9

n = 8 0

n = 9 9

n = 1 0 4

n = 1 0 4

n = 1 0 9

n = 1 5 3

n = 1 8 6

PA

PP

-A M

oM

h

CG

β M

oM

Operator

Operator

Why operator effects on biochemistry?

• Causes include

– case mix

– sample preparation

– storage

– transportation

– CRL measurement

PAPP-A by gestation

Gestation (days)

PA

PP

-A

50 60 70 80 90 100

0.1

0.2

0.5

1.0

2.0

5.0Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

PAPP-A by gestation

Gestation (days)

PA

PP

-A

50 60 70 80 90 100

0.1

0.2

0.5

1.0

2.0

5.0Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

MoM = 1

PAPP-A by gestation

Gestation (days)

PA

PP

-A

50 60 70 80 90 100

0.1

0.2

0.5

1.0

2.0

5.0Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

MoM = 1

MoM = 0.57

Free β-hCG by gestation

Gestation (days)

hC

G b

eta

50 60 70 80 90 100

5

10

20

30

40

5060

80

100

150

200

250

Wk 7 Wk 8 Wk 9 Wk 10 Wk 11 Wk 12 Wk 13

MoM = 1

MoM =1.2

Effects of Crown Rump Length (CRL) biases on biochemistry MoM values

(NT and biochemistry at 12 weeks risk cut-off 1 in 150 at term)

CRL Error Error in GA Median MoM

(mm) (days) PAPP-A hCG beta DR FPR

-5 -2.7 1.17 0.93 80% 1.4%

-4 -2.2 1.13 0.94 81% 1.6%

-3 -1.6 1.10 0.96 82% 1.9%

-2 -1.1 1.06 0.97 83% 2.0%

-1 -0.5 1.03 0.99 84% 2.4%

0 0.0 1.00 1.00 85% 2.7%

1 0.5 0.97 1.01 86% 3.1%

2 1.0 0.94 1.03 86% 3.7%

3 1.6 0.92 1.04 87% 4.1%

4 2.1 0.89 1.06 88% 4.8%

5 2.6 0.87 1.07 89% 5.5%

Down’s syndrome presents as biochemical immaturity so effects of errors on PAPP-A and free β-hCG combine.


Nu

ch

al tr

an

slu

ce

ncy (

mm

)

45 50 55 60 65 70 75 80 85

0.5

1

2

3

4

5

6

78

Impact of NT on risks


Nu

ch

al tr

an

slu

ce

ncy (

mm

)

45 50 55 60 65 70 75 80 85

0.5

1

2

3

4

5

6

78




Nu

ch

al tr

an

slu

ce

ncy (

mm

)

45 50 55 60 65 70 75 80 85

0.5

1

2

3

4

5

6

78

How : DQASS

DQASS

• The aim is to monitor and support the quality and

effectiveness of screening

• Provide feedback on all aspects of the test to laboratories,

ultrasound departments and commercial suppliers.

• Through meta-analyses DQASS provides information on

effects of factors such a smoking that can be used to

improve screening performance.

Report production

Feedback

& advice Improvements

Data submissions

Lab reports ~40 per year

Cycle reports

A Two Day Workshop

Thursday 17 and Friday 18 January 2008

DQASS Workshop on

Standardisation, Monitoring and

Updating Medians: Why, When

and How?

Presented by:

Amy Baker

Barry Nix

Dave Worthington

Dave Wright

Workshops

Individualised feedback to all sonographers on all scan measurements ~20002 (from April 2010)

Nu

ch

al

Tra

ns

luc

en

cy

(m

m)

ID: 49057 (n = 184)


Cycle 5

From: 16/05/2008

To: 31/10/2008

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

68 (37%)

116 (63%)Bias = 0.08mm

4 NT values greater than 4mm shown as 4mm

Nu

cha

l T

ran

slu

ce

nc

y (

mm

)

ID: 49057 (n = 184)


Cycle 5

From: 16/05/2008

To: 31/10/2008

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

68 (37%)

116 (63%)Bias = 0.08mm


Nu

ch

al

Tra

ns

luc

en

cy

(m

m)

ID: 49057 (n = 184)


Cycle 5

From: 16/05/2008

To: 31/10/2008

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

68 (37%)

116 (63%)Bias = 0.08mm


Nu

ch

al

Tra

ns

luc

en

cy

(m

m)

ID: 49057 (n = 184)


Cycle 5

From: 16/05/2008

To: 31/10/2008

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

68 (37%)

116 (63%)Bias = 0.08mm


DQASS

Monitoring SPR

DQASS diagnostics for

biochemistry

• MoM values should be centred on 1.0 when viewed together, by gestation, by weight, by smoking status, by ethnicity …

• Small deviations from this target can have important implications for screening

Gestational age

Gestation (weeks)

MoM

PA

PP

-A

10 11 12 13 14

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

n= 1

n= 28

n= 227

n= 1137

n= 3710 n= 2539

n= 11

Gestation (weeks)

MoM

PA

PP

-A

10 11 12 13 14

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

n= 2066n= 6793 n= 3234

n= 25

Cycle 2

Cycle 7

48

Maternal weight

Weight group

MoM

Fre

e b

eta

-hC

G

<50kg

50-60kg

60-70kg

70-80kg

80-90kg

90-100kg

100-110kg

110-120kg>120kg

0.7

0.8

0.9

1.0

1.1

1.2

1.3n= 368

n= 1818 n= 2404n= 1409

n= 706n= 385

n= 170

n= 88

n= 46

Weight group

MoM

Fre

e b

eta

-hC

G

<50kg

50-60kg

60-70kg

70-80kg

80-90kg

90-100kg

100-110kg

110-120kg

>120kg

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

n=638n=3043

n=3870 n=2326 n=1211

n=614 n=273

n=136n=88

Cycle 2

Cycle 7

49

Smoking status Cycle 2

Cycle 7

Smoking status

MoM

Inhib

in

No Yes

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

n= 4729

n= 1119

Smoking status

MoM

Inhib

in

Non-Smoker Smoker

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

n= 2821

n= 563

50

Ethnicity Cycle 2

Cycle 7 Ethnic origin

MoM

PA

PP

-A

Caucasian

Afro-Caribbean

AsianMixed

Oriental

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

1.6

1.7

n= 7907

n= 2054

n= 563

n= 373

n= 176

Ethnic origin

MoM

PA

PP

-A

Caucasian

Afro-CaribbeanAsian

OrientalOther

0.7

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

n=7881n=1979

n=1608 n=263

n=469

51

CUSUM

52

Time 1 2 3 4 5 6 7 8 9 10

Deviation from target 0 0 0 0 0.5 0.5 0.5 0.5 0.5 0.5

Cumulative sum 0 0 0 0 0.5 1 1.5 2 2.5 3

0

0.5

1

1.5

2

2.5

3

3.5

0 2 4 6 8 10 12

CU

SUM

Time

Change points

A change of -10% was

introduced around the

middle of September.

This is detected

relatively quickly.

A change of -5% was

introduced around the

middle of September.

This takes longer to

detect.

53

CUSUM charts for detecting change points

Diagnostics for NT

Nu

cha

l T

ran

slu

ce

nc

y (

mm

)

ID: 49057 (n = 184)


Cycle 5

From: 16/05/2008

To: 31/10/2008

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

68 (37%)

116 (63%)Bias = 0.08mm


Expected relationship with CRL

Expected degree of scatter about the curve

DQASS Diagnostics: Nuchal Translucency

Nu

ch

al T

ran

slu

ce

ncy (

mm

)ID: Sample (n = 300)


Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

152 (51%)

148 (49%)Bias = 0mm

Nu

ch

al T

ran

slu

ce

ncy (

mm

)

ID: Sample (n = 300)


Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

152 (51%)

148 (49%)Bias = 0mm

Nuchal T

ranslu

cency (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

287 (96%)

13 (4%)Bias = -0.58mm

Bias

Nu

ch

al T

ran

slu

ce

ncy (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

152 (51%)

148 (49%)Bias = 0mm

Bias

Nuchal T

ranslu

cency (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

12 (4%)

288 (96%)Bias = 0.55mm

1 NT value greater than 4mm shown as 4mm

Cycle Reports

Pareto Charts

Sonography

0.0 0.1 0.2 0.3 0.4 0.5 0.6

020

40

60

80

100

Bias

(mm)

Pro

port

ion

of

tests

10% of all scans, bias of 0.60mm

Illustration (n = 4 sonographers)

0.0 0.1 0.2 0.3 0.4 0.5 0.6

Bias

(mm)

Pro

port

ion

of

tests



020

40

60

80

100

0.0 0.1 0.2 0.3 0.4 0.5 0.6

020

40

60

80

100

Bias

(mm)

Pro

port

ion

of

tests

Area = Average bias


0.0 0.1 0.2 0.3 0.4 0.5 0.6

Bias

(mm)

Pro

port

ion

of

tests


020

40

60

80

100

0.0 0.1 0.2 0.3 0.4 0.5 0.6

0

20

40

60

80

100

Bias

(mm)

Pro

port

ion

of

tests


Cycle 18

Other outputs from DQASS

Parameter estimates for configuring the screening program. Example: Twin effect for Inhibin-A.

MoM

1.4 1.6 1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4

Cycle 18

Cycle 19

Pooled

Thank you!

END OF PRESENTATION

Nu

ch

al T

ran

slu

ce

ncy (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

152 (51%)

148 (49%)Bias = 0mm

Spread

Nu

cha

l T

ran

slu

ce

nc

y (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

159 (53%)

141 (47%)Bias = -0.01mm

Spread decreased: 0.43

Nu

ch

al T

ran

slu

ce

ncy (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

152 (51%)

148 (49%)Bias = 0mm

Trend

Nu

cha

l T

ran

slu

ce

nc

y (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

130 (43%)

170 (57%)Bias = 0.09mm

Trend deviation


Nu

ch

al T

ran

slu

ce

ncy (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

152 (51%)

148 (49%)Bias = 0mm

Trend

Nuchal T

ranslu

cency (

mm

)



Cycle

From: NA

To: NA

40 45 50 55 60 65 70 75 80 85 90

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

168 (56%)

132 (44%)Bias = -0.07mm

Trend deviation

1 NT value greater than 4mm shown as 4mm

Hospital Summary Report


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Cycle reports

End of cycle reports

Cycle 14 report

April 2013 to September 2013

Cycle reports for biochemistry-

PAPP-A

Estimated proportion of median MoMs outside 5%

Best

Worst

DQASS 88

DQASS 99

Cycle reports for NT - National

Cycle reports for NT - Region x

Laboratory

throughput

Rationale

• Need for sufficient precision to estimate

performance (standardised SPR)

• To enable monitoring of laboratory

medians and early detection of change

points

• For proficiency/expertise

log

(M

oM

)

-50

-40

-30

-20

-10

0

10

20

log

(M

oM

)

-50

-40

-30

-20

-10

0

10

20

log

(M

oM

)

-50

-40

-30

-20

-10

0

10

20

log

(M

oM

)

-50

-40

-30

-20

-10

0

10

20

Sample

log

(M

oM

)

-50

-40

-30

-20

-10

0

10

20

0 200 400 600 800 1000

Sample

log

(MoM

)-250

-200

-150

-100

-50

0

50

0 2500 5000

5 labs 1,000 samples

1 lab5,000 samples

DQASS

• Feedback and support to sonographers laboratories, hospitals and suppliers

• Monitoring at the local and national level

• A national database: evidence on screening parameters, effects of smoking ethnicity etc

Thank you!

MONITORING PROGRESS

REGIONALLY AND

NATIONALLY

Laboratory

Cycle by cycle feedback to individual

laboratories

0

10

20

30

40

50

60

AFP hCG uE3 Inhibin

Esti

mate

d p

rop

ort

ion

(%

) of M

oM

valu

es

ou

tsid

e 5

%

Cycle 1 Cycle 2 Cycle 3

Sonography

0.0 0.1 0.2 0.3 0.4 0.5 0.6

020

40

60

80

100

Bias

(mm)

Pro

port

ion

of

tests



0.0 0.1 0.2 0.3 0.4 0.5 0.6

Bias

(mm)

Pro

port

ion

of

tests



020

40

60

80

100

0.0 0.1 0.2 0.3 0.4 0.5 0.6

020

40

60

80

100

Bias

(mm)

Pro

port

ion

of

tests

Area = Average bias


0.0 0.1 0.2 0.3 0.4 0.5 0.6

Bias

(mm)

Pro

port

ion

of

tests


020

40

60

80

100

0.0 0.1 0.2 0.3 0.4 0.5 0.6

0

20

40

60

80

100

Bias

(mm)

Pro

port

ion

of

tests


0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

0

10

20

30

40

50

60

70

80

90

100

Bias (mm)

Pro

po

rtio

n o

f W

om

en

Scre

en

ed

National

Cycle 8: Reference

Cycle 12:

Cycle 11:

Cycle 10:

Cycle 12:

1841 Sonographers

203601 Scans

1.24% < 25 scans

Cycle 11:

1759 Sonographers

188472 Scans

1.37% < 25 scans

Cycle 10:

1599 Sonographers

167944 Scans

1.91% < 25 scans

46.92% 42.38% 6.91% 3.79%

57.55% 38.40% 3.29% 0.77%

60.94% 36.39% 2.08% 0.59%

DQASS NT-QA

Highlights

• Consistency of provision

• Evidenced improvement is quality

• Improved outcomes

Consistent provision

March 2007: SPR 5.9% September 2012: SPR 2.5%

Combined15%

Quadruple9%

Triple48%

Double27%

Integrated1%

Combined

Quadruple

Triple

Double

IntegratedCombined

80%

Quadruple19%

Integrated1%

Combined

Quadruple

Integrated

Cycle Scans (000,s) Sonograhers (n) Green (%)8 (Apr-Sep 2010) 102 884 35

9 128 1,160 39

10 168 1,599 47

11 188 1,759 58

12 (Apr-Sep 2012) 204 1,841 61

Improving Quality

0

10

20

30

40

50

60

70

80

90

100

8 9 10 11 12

Pro

po

rtio

n g

ree

n (%

)

Cycle

Improving Quality

All

regions

What Next

• Choice of screening test

• Choice of risk cut-off

• QA of screening (what, why, how)

• DQASS Reports

• Monitoring program performance

CHOICE OF

SCREENING TEST

AND RISK CUT-OFF

Double Test: AFP + hCG

False Positive Rate (%)

De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 150

1 in 200

1 in 250

Double Test: AFP + free beta hCG


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 150

1 in 2001 in 250

Triple Test: AFP + hCG + uE3


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 150

1 in 2001 in 250

Triple Test: AFP + free beta hCG + uE3


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 1501 in 200

1 in 250

Combined Test: NT + free beta hCG + PAPP-A

Week 11False Positive Rate (%)

De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 150

1 in 2001 in 250



De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 150

1 in 2001 in 250



De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 150

1 in 2001 in 250

Quad test (hCG)


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 1501 in 200

1 in 250

Quad test (free beta hCG)


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 1501 in 200

1 in 250

Integrated Test


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 1001 in 150

1 in 2001 in 250

Integrated Test


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 1501 in 200

1 in 250

Integrated Test


De

tectio

n R

ate

(%

)

0 2 4 6 8 10

02

04

06

08

01

00

1 in 100

1 in 1501 in 200

1 in 250

QA OF SCREENING

WHAT, WHY, HOW

Overview

• What

– Quick overview of first and second trimester

screening

• Why

– The effects of errors from different sources

• How

– The DQASS process

DQASS A service, funded by the NHS, to

support the improvement of quality

and effectiveness of prenatal

screening in the UK

Based in Plymouth, Devon

Louise Armitage

Amy Baker

Andy Baker*

Nathan Eastwood*

Barry Nix

Paul Newell*

Dave Worthington

Dave Wright

Jade

Report production

Feedback Improvements

Data submissions

Quality Assurance Support Service

People (2.8 full time equivalents):

Louise Armitage (admin) Amy Baker Andy Bailey Paul Newell Dave Wright Dave Worthington (Biochemist) Barry Nix (Statistician)

Statisticians DQASS

Cycle 1 Cycle 2 Cycle 3 Cycle 4 Cycle 5 Cycle 6 Cycle 7 Cycle 8 Cycle 9

Oct-06 Mar 07 Apr 07 Sep-07 Oct-07 Mar-08 Apr 08 Sep-08 Oct-08 Mar-09 Apr 09 Sep-09 Oct-09 Mar-10 Apr 10 Sep-10 Oct-10 Mar-11

2008 2011

PND

type

Number

2003/2004

Number

2004/2005

Number

2005/2006

Number

2006/2007

Number

2007/2008

Number

2008/2009

Number

2009/2010

Amnio 28,700 24,349 22,625 14,733 12,932 12,145 9,894

CVS 8,268 7,980 7,819 4, 781 4,681 3,520 3,701

*TOTA

L 36,968 32,329 30,444 19,514 17,613 15,665 13,595

Total screening tests

PND as % of screening tests

Total births

Percentage acceptance

365,775

4.81%

409,346

3.83%

427,527

3.18%

690,721 708, 711 706,248

52.95% 57.76% 60.53%

Improved Outcomes: Invasive Tests

0 1000 2000 3000 4000 5000

-10

0-5

00

50

Sample

log

(M

oM

)

Second trimester triple and

quadruple test

AFP

Weight (kg)

AF

P M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

AF

P

100 110 120 130 140 150

20

30

40

50

60

70

80 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

123

AFP Effects on AFP

MoM AFP

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

African

Caribbean

Chinese

Oriental

Asian

Bangladeshi

Indian

Pakistani

Smoking

124

uE3

Weight (kg)

uE

3 M

oM

40 50 60 70 80 90 110 130 150

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

uE

3

100 110 120 130 140 150

1

2

3

4

5

6

78

10

15

20 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

125

Effects on uE3

MoM uE3

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

African

Caribbean

Chinese

Oriental

Asian

Bangladeshi

Indian

Pakistani

Smoking

uE3

126

hCG

Weight (kg)

hC

G M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

hC

G

100 110 120 130 140 150

10

20

30

40

50 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

127

hCG Effects on hCG

MoM hCG

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

T risomy 18

T risomy 13

African

Caribbean

Chinese

Asian

Indian

Pakistani

Smoking

128

Free β-hCG (T2)

Weight (kg)

Fre

e b

eta

hC

G M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Gestation (days)

Fre

e b

eta

hC

G

100 110 120 130 140 150

5

10

15

20

25

30 Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

129



0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

African

Caribbean

Black Other

Asian

Bangladeshi

Indian

Pakistani

Other Asian

Chinese

Oriental

Smoking

130

Gestation (days)

Inhib

in

100 110 120 130 140 150

100

150

200

250

300

Wk 15 Wk 16 Wk 17 Wk 18 Wk 19 Wk 20

Weight (kg)

Inhib

in M

oM

40 50 60 70 80 90 100 120 140

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

Inhibin

131

Effects on Inhibin

MoM Inhibin

0.1 0.5 1.0 1.5 2.0 3.0

T risomy 21

Asian

Caribbean

Smoking

Inhibin

132

Crown rump length

The (near) perfect world of biochemistry

Cyprus

Gestation (weeks)

PA

PP

-A M

oM

7 8 9 10 11 12 13

0.8

0.9

1.0

1.1

1.2

1.3

1.4

1.5

n= 1

n= 812

n= 4787 n= 4231n= 1426

n= 311

n= 72

n= 2

Median Standard

The median MoM value for any sub-population defined by time period, gestational age, maternal weight, smoking status and ethnicity should lie within 5% of the target value of 1.

Median MoM by gestation

Communication with sonographers

DQASS

Screening support sonographers (165)

Sonographers (1,950)

Sonographer reports

Hospital reports

Cycle reports

Regional reports

Training

Regional meeting

Annual meetings

Healthcare

1. QA of screening for downs