Impact and Cost-effectiveness of Newborn Screening

Chris Vorster

(nothing to declare)

North-West University

NBS @ RareX 2016 – A recap

Why should we screen our newborns

• SA constitution, UN convention etc.

• No discrimination based on diseases incidence

• Optimal resource allocation

• NBS is not only cost-effective but in fact cost-minimizing and the right thing to do.

Arguments (lame excuses) against newborn screening

• Lack of infrastructure

• Lack of expertise

• Lost to follow-up

• Lack of treatment options

• Burden of False Positives

• Not willing to deal with what we do not know and understand

NBS @ RareX 2018 – What is new

• Better estimates of Cost-effectiveness of NBS

• Precision NBS with assistance from Mayo Clinic• False positive rate below 1% (in fact way below)

• Screening at 24hrs after birth (can we go lower)

• Program expansion

• Call to patient advocacy groups

Region NBS Coverage Expanded NBS coverage

North America Universal Yes

Europe 47/48 regions Most

Asia pacific 13/24 Increasing

Middle east and North Africa 14/21 regions(4/21 in 2007)

Limited

Latin America 15/20 Most

Sub-Saharan Africa No national programmesScattered efforts

Total 140,000 Newborn screens per day37% of global births

𝐶𝑈𝐴 =𝐶𝑜𝑠𝑡

𝑄𝐴𝐿𝑌

CUAScreen < CUANo Screen

CUAScreen < GDP per Capita

ICPLM: Economic feasibility of Newborn Screening

Public Health Care

Private Health Care

Results

Public Sector Private Sector

Base Scenario Screen No Screen Screen No Screen

CUA R23,000 R106,000 R38,000 R190,000

Total Cost per annum R660 M R2,000 M R220 M R720 M

Alternative Scenarios (CUA) Screen No Screen Screen No Screen

Other cost not included R23,000 R32,000

Medical insurer perspective R38,000 R4,000

Incidence = 1:10,000 R114,000 R106,000 R190,000 R189,000

Conclusion and Recommendations

• CUAScreen < CUANo Screen & CUAScreen < GDP per Capita

• NBS is likely to be cost saving

• Incidence is less of a barrier to implementation than initially thought

• South Africa should utilize the tools provided by WHO-COICE to enable best possible utilization of health resources.

….but what about the False Positives

Phenylketonuria

• Prevalence = 1 in 10 000

• Specificity 99.9%, Sensitivity 100%

• Specificity• Probability of a negative result given disease absence • 0.999 * 9999 = 9989• 9989/(9989 + 10) TN/(TN+FP)

• Sensitivity• Probability of a positive result given disease• 1 * 1 = 1• 1/ (1+0) TP/(TP+FN)

• PPV = TP/(TP+FP) = 1/(1+10) = 9%

• NPV = TN/(TN+FN) = 9989/(9989+0) = 100%

The curse of cumulative probabilities

Number of Analytes Reference percentile at 97.5% Reference percentile Typeequation here.at 99%

1 3% 1%

5 12% 2%

10 22% 5%

50 72% 22%

100 92% 39%

400 100% 87%

1000 100% 99%

𝑃1 = 1 − 𝑃𝑛𝑜𝑛𝑒𝑇𝑒𝑠𝑡𝑠

https://news.mayomedicallaboratories.com/2016/12/12/advancing-a-new-standard-of-care-for-newborn-screening/

Precision newborn screening

Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)• 1:10,000-20,000• Clinical

• Hypoglycaemic encephalopathy• Liver dysfunction• Sudden death

• Treatment• Avoid fasting and MCT• Riboflavin

Conclusions and beyond

• Newborn Screening is cost-effective and probably cost saving

• Precision newborn screening:• Greatly increases cost-effectiveness• Screening at 24hrs after birth• Expanded newborn screening

• Rapid increase in treatment options for rare diseases but…• Early diagnosis is essential

• Patient advocacy groups please assist!

AcknowledgementsStaff and colleagues of the NWU• Marli Dercksen• Brenda Klopper• Eugenei Modikoe• Mari van Reenen• Elmarie Davoren• Tania Grobler• Dalene van der Walt• Ansie Mienie• Yolanda Kruger• Jano Jacobs• Grant Maasdorp• Derylize Beukes-Maasdorp• Japie Mienie

Next BiosciencesYvonne HoltBronwyn LendrumKim Hulett

Past contributors to Newborn ScreeningCarools ReineckeDetlef KnollLinda MalanMarietjie MeyerJennifer CartwrightMany others

Mayo ClinicPiero Rinaldo

Program supportersMany cliniciansAmpathLancetPathcare

Disease NCongenital hypothyroidism 4

Propionic acidemia 2

Galactosemia 2

Biotinidase deficiency 2

Methylmalonic acidemia 1

Isovaleric acidemia 1

Phenylketonuria 1

Cystic fibrosis 1*

Citrullinemia I 1

Total 15

Total Screened 16,754

Predicted incidence 1:1100

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