Population-Based Newborn Screening for Germline TP53 Variants: Clinical Benefits, Cost-Effectiveness, and Value of Further Research

Natalia Kunst; Natasha K Stout; Grace O'Brien; Kurt D Christensen; Pamela M McMahon; Ann Chen Wu; Lisa R Diller; Jennifer M Yeh

doi:10.1093/jnci/djac013

Population-Based Newborn Screening for Germline TP53 Variants: Clinical Benefits, Cost-Effectiveness, and Value of Further Research

Natalia Kunst^*, Natasha K Stout, Grace O'Brien, Kurt D Christensen, Pamela M McMahon, Ann Chen Wu, Lisa R Diller, Jennifer M Yeh

^*Corresponding author for this work

Centre for Health Economics

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).

METHODS: We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS.

RESULTS: Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI = 4.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106 009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100 000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).

CONCLUSIONS: We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.

Original language	English
Pages (from-to)	722-731
Number of pages	10
Journal	Journal of the National Cancer Institute
Volume	114
Issue number	5
Early online date	19 Jan 2022
DOIs	https://doi.org/10.1093/jnci/djac013
Publication status	Published - 1 May 2022

Bibliographical note

Keywords

Child
Cost-Benefit Analysis
Early Detection of Cancer
Germ Cells
Humans
Infant
Infant, Newborn
Li-Fraumeni Syndrome/diagnosis
Neonatal Screening
Tumor Suppressor Protein p53/genetics
Young Adult

Access to Document

10.1093/jnci/djac013

Cite this

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title = "Population-Based Newborn Screening for Germline TP53 Variants: Clinical Benefits, Cost-Effectiveness, and Value of Further Research",

abstract = "BACKGROUND: Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).METHODS: We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS.RESULTS: Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI = 4.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106 009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100 000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).CONCLUSIONS: We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.",

keywords = "Child, Cost-Benefit Analysis, Early Detection of Cancer, Germ Cells, Humans, Infant, Infant, Newborn, Li-Fraumeni Syndrome/diagnosis, Neonatal Screening, Tumor Suppressor Protein p53/genetics, Young Adult",

author = "Natalia Kunst and Stout, {Natasha K} and Grace O'Brien and Christensen, {Kurt D} and McMahon, {Pamela M} and Wu, {Ann Chen} and Diller, {Lisa R} and Yeh, {Jennifer M}",

note = "{\textcopyright} The Author(s) 2022.",

year = "2022",

month = may,

day = "1",

doi = "10.1093/jnci/djac013",

language = "English",

volume = "114",

pages = "722--731",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

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TY - JOUR

T1 - Population-Based Newborn Screening for Germline TP53 Variants

T2 - Clinical Benefits, Cost-Effectiveness, and Value of Further Research

AU - Kunst, Natalia

AU - Stout, Natasha K

AU - O'Brien, Grace

AU - Christensen, Kurt D

AU - McMahon, Pamela M

AU - Wu, Ann Chen

AU - Diller, Lisa R

AU - Yeh, Jennifer M

N1 - © The Author(s) 2022.

PY - 2022/5/1

Y1 - 2022/5/1

N2 - BACKGROUND: Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).METHODS: We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS.RESULTS: Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI = 4.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106 009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100 000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).CONCLUSIONS: We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.

AB - BACKGROUND: Identification of children and infants with Li-Fraumeni syndrome prompts tumor surveillance and allows potential early cancer detection. We assessed the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS).METHODS: We simulated the impact of TP53-NBS using data regarding TP53-associated pediatric cancers and pathogenic or likely pathogenic (P/LP) TP53 variants from Surveillance, Epidemiology, and End Results; ClinVar and gnomAD; and clinical studies. We simulated an annual US birth cohort under usual care and TP53-NBS and estimated clinical benefits, life-years, and costs associated with usual care and TP53-NBS.RESULTS: Under usual care, of 4 million newborns, 608 (uncertainty interval [UI] = 581-636) individuals would develop TP53-associated cancers before age 20 years. Under TP53-NBS, 894 individuals would have P/LP TP53 variants detected. These individuals would undergo routine surveillance after detection of P/LP TP53 variants decreasing the number of cancer-related deaths by 7.2% (UI = 4.0%-12.1%) overall via early malignancy detection. Compared with usual care, TP53-NBS had an incremental cost-effectiveness ratio of $106 009 per life-year gained. Probabilistic analysis estimated a 40% probability that TP53-NBS would be cost-effective given a $100 000 per life-year gained willingness-to-pay threshold. Using this threshold, a value of information analysis found that additional research on the prevalence of TP53 variants among rhabdomyosarcoma cases would resolve most of the decision uncertainty, resulting in an expected benefit of 349 life-years gained (or $36.6 million).CONCLUSIONS: We found that TP53-NBS could be cost-effective; however, our findings suggest that further research is needed to reduce the uncertainty in the potential health outcomes and costs associated with TP53-NBS.

KW - Child

KW - Cost-Benefit Analysis

KW - Early Detection of Cancer

KW - Germ Cells

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Li-Fraumeni Syndrome/diagnosis

KW - Neonatal Screening

KW - Tumor Suppressor Protein p53/genetics

KW - Young Adult

U2 - 10.1093/jnci/djac013

DO - 10.1093/jnci/djac013

M3 - Article

C2 - 35043946

SN - 0027-8874

VL - 114

SP - 722

EP - 731

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 5

ER -