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Update Screening performance
• T21, T18 and T13
• Combined test
• Quadruple test
NIPT • Current & proposed pathway
• Changes in choice behaviour
• Modelled performance
• Positive predictive values
• Changes to the cut-off
Twins • Vanishing twins
• Quad test twin factors
DQASS reports • Reporting T13/T18
• Changes to diagnostics
NIPT
Current policy
IPD
Combined test
Offer IPD
No further testing
Offer combined test
IPD
Combined test
Offer IPD or cf DNA No
further testing
cf DNA test
Offer IPD
Offer combined test
Choice
Screening result
Proposed policy
Choice
Screening result
Change
Existing Policy New Policy
Discussion: What changes to choice behaviour would we expect
Choice
Screening result
Change
Existing Policy New Policy
Choice behaviour
Current policy
Starting with 100,000 accepting testing here
• Assume a population of 100,000 screened at 12 weeks using the combined test
• Maternal age distribution of England and Wales 2011
• Expected number of trisomies at screening • Trisomy 21 271 • Trisomy 18 116 • Trisomy 13 37
Composition of screened population
Choice behaviour after a +ve result: modelled results
RiskP
r[A
ccept|R
isk]
0.0
0.2
0.4
0.6
0.8
1.0
1/150 1/50 1/20 1/10 1/5 1/2
Outcome N +ve N %
Normal 99,576 2,104 1,236 59
T21 271 234 137 59
T18 116 97 57 59
T13 37 27 16 59
100,000 2,462 1,446
Accept IPD
Age distribution of E&W 2011
Most of the previous work assumes that the proportions accepting IPD following a high risk results are independent of outcome. In practice the pregnancies with trisomies are the ones with higher risks so they choose IPD more often.
Choice behaviour after a +ve result: modelled results
Risk
Pr[
Accept|R
isk]
0.0
0.2
0.4
0.6
0.8
1.0
1/150 1/50 1/20 1/10 1/5 1/2
Outcome N +ve N %
Normal 99,576 2,104 1,143 54
T21 271 234 198 85
T18 116 97 84 86
T13 37 27 21 80
100,000 2,462 1,446 59
Accept IPD
Outcome N +ve N %
Normal 99,576 2,104 1,236 59
T21 271 234 137 59
T18 116 97 57 59
T13 37 27 16 59
100,000 2,462 1,446
Accept IPD
Choice depends on risk
Unrealistic assumptions
Realistic assumptions
Choice behaviour after a +ve result: modelled results
Risk
Pr[
Accept|R
isk]
0.0
0.2
0.4
0.6
0.8
1.0
1/150 1/50 1/20 1/10 1/5 1/2
Outcome N +ve N %
Normal 99,576 2,104 1,143 54
T21 271 234 198 85
T18 116 97 84 86
T13 37 27 21 80
100,000 2,462 1,446 59
Accept IPD
Outcome N +ve N %
Normal 99,576 2,104 1,236 59
T21 271 234 137 59
T18 116 97 57 59
T13 37 27 16 59
100,000 2,462 1,446
Accept IPD
Fewer IPDs in normal pregnancies
Unrealistic assumptions
Realistic assumptions
Choice behaviour dependent on risk: modelled results
Risk
Pr[
Accept|R
isk]
0.0
0.2
0.4
0.6
0.8
1.0
1/150 1/50 1/20 1/10 1/5 1/2
Outcome N +ve N %
Normal 99,576 2,104 1,143 54
T21 271 234 198 85
T18 116 97 84 86
T13 37 27 21 80
100,000 2,462 1,446 59
Accept IPD
Outcome N +ve N %
Normal 99,576 2,104 1,236 59
T21 271 234 137 59
T18 116 97 57 59
T13 37 27 16 59
100,000 2,462 1,446
Accept IPD
More women with affected pregnancies choose IPD
Unrealistic assumptions
Realistic assumptions
Choice behaviour new policy
IPD
Combined test
Offer IPD or cfDNA No further testing
cf DNA test
Offer IPD
Offer combined test
Risk
Pr[
Accept|R
isk]
0.0
0.2
0.4
0.6
0.8
1.0
1/150 1/50 1/20 1/10 1/5 1/2
IPD
IPD is chosen less often. cfDNA is chosen instead. Less harm.
Cf DNA instead
Choice behaviour new policy
IPD
Combined test
Offer IPD or cfDNA No further testing
cf DNA test
Offer IPD
Offer combined test
Risk
Pr[
Accept|R
isk]
0.0
0.2
0.4
0.6
0.8
1.0
1/150 1/50 1/20 1/10 1/5 1/2
No further testing
Cf DNA
IPD
Many choose cf DNA instead of nothing. More information.
Modelling
Numbers based on a population of 100,000 accepting screening
IPD
Combined test
Offer IPD or cfDNA No further testing
cf DNA test
Offer IPD
Offer combined test
Starting with 100,000 accepting testing here
Offer choice of cfDNA or IPD: modelled results
Outcome N +ve N %
Normal 99,576 2,104 1,143 54
T21 271 234 198 85
T18 116 97 84 86
T13 37 27 21 80
100,000 2,462 1,446 59
Accept IPD
Outcome N +ve N % N % N %
Normal 99,576 2,104 702 33 1,355 64 2,057 98
T21 271 234 170 73 58 25 228 98
T18 116 97 74 76 21 21 95 98
T13 37 27 18 66 9 32 26 98
100,000 2,462 964 39 1,443 59 2,407 98
Accept IPD Accept cfDNA Accept IPD or cfDNA
Offer IPD only (Current)
Offer choice of cfDNA or IPD
Offer choice of cfDNA or IPD: modelled results
Outcome N +ve N %
Normal 99,576 2,104 1,143 54
T21 271 234 198 85
T18 116 97 84 86
T13 37 27 21 80
100,000 2,462 1,446 59
Accept IPD
Outcome N +ve N % N % N %
Normal 99,576 2,104 702 33 1,355 64 2,057 98
T21 271 234 170 73 58 25 228 98
T18 116 97 74 76 21 21 95 98
T13 37 27 18 66 9 32 26 98
100,000 2,462 964 39 1,443 59 2,407 98
Accept IPD Accept cfDNA Accept IPD or cfDNA
Offer IPD only (Current)
Offer choice of cfDNA or IPD
Fewer IPDs in unaffected pregnancies
Offer choice of cfDNA or IPD: modelled results
Outcome N +ve N %
Normal 99,576 2,104 1,143 54
T21 271 234 198 85
T18 116 97 84 86
T13 37 27 21 80
100,000 2,462 1,446 59
Accept IPD
Outcome N +ve N % N % N %
Normal 99,576 2,104 702 33 1,355 64 2,057 98
T21 271 234 170 73 58 25 228 98
T18 116 97 74 76 21 21 95 98
T13 37 27 18 66 9 32 26 98
100,000 2,462 964 39 1,443 59 2,407 98
Accept IPD Accept cfDNA Accept IPD or cfDNA
More information about trisomies
Offer IPD only (Current)
Offer choice of cfDNA or IPD
Positive predictive values
Prevalence 0.3% FPR = 0.2% DR = 100%
Screened population of 1,000 Screen positives
Positive predictive values
PPV = 3/5 = 60%
Practical Session: PPV of NIPT in the high risk group
• The prevalence of trisomies in the combined tests with risks if 1 in 150 or higher is estimated to be 7.5%
• Assume that the FPR of cfDNA is 0.2% and its DR is 99%
• What is the PPV of cf DNA?
Prevalence 7.5% FPR = 0.2% DR = 99%
Combined/Quadruple test risk ≥ 1 in 150
Practical Session: PPV of NIPT in the high risk group