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Population-Based Newborn Screening for Germline TP53 Variants: Clinical Benefits, Cost-Effectiveness, and Value of
Natalia Kunst1, Natasha K Stout1, Grace O'Brien2
1Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Insights
Newborn screening for TP53 variants (TP53-NBS) could be cost-effective for Li-Fraumeni syndrome, potentially reducing cancer deaths through early detection. Further research is recommended to refine outcomes and costs associated with this screening approach.
Area of Science:
- Genetics and Genomics
- Pediatric Oncology
- Public Health
Background:
- Li-Fraumeni syndrome (LFS) identification enables tumor surveillance and early cancer detection in children.
- Assessing the clinical benefits and cost-effectiveness of population-wide newborn screening for TP53 variants (TP53-NBS) is crucial.
Purpose of the Study:
- To evaluate the clinical benefits and cost-effectiveness of implementing TP53-NBS in the US.
- To simulate the impact of TP53-NBS on pediatric cancer incidence, mortality, and healthcare costs.
Main Methods:
- A simulation model was used, incorporating data on TP53-associated pediatric cancers and pathogenic/likely pathogenic (P/LP) TP53 variants.
- Annual US birth cohorts under usual care and TP53-NBS were simulated to estimate clinical outcomes and costs.
Main Results:
- TP53-NBS identified more individuals with P/LP TP53 variants, leading to a 7.2% reduction in cancer deaths via early detection.
- The incremental cost-effectiveness ratio for TP53-NBS was $106,009 per life-year gained, with a 40% probability of being cost-effective at a $100,000 threshold.
Conclusions:
- TP53-NBS demonstrates potential cost-effectiveness for Li-Fraumeni syndrome screening.
- Further research, particularly on TP53 variant prevalence in rhabdomyosarcoma, is needed to reduce uncertainty in health outcomes and costs.
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.
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