Reflex single-gene non-invasive prenatal testing is associated with markedly better detection of fetuses affected with single-gene recessive disorders at lower cost

Abstract

Objective

To evaluate the clinical benefits and achievable cost savings associated with the adoption of a carrier screen with reflex single-gene non-invasive prenatal test (sgNIPT) in prenatal care.

Method

A decision-analytic model was developed to compare carrier screen with reflex sgNIPT (maternal carrier status and fetal risk reported together) as first-line carrier screening to the traditional carrier screening workflow (positive maternal carrier screen followed by paternal screening to evaluate fetal risk). The model compared the clinical outcomes and healthcare costs associated with the two screening methods. These results were used to simulate appropriate pricing for reflex sgNIPT.

Results

Reflex sgNIPT carrier screening-detected 108 of 110 affected pregnancies per 100,000 births (98.5% sensitivity), whereas traditional carrier screening-detected 46 of 110 affected pregnancies (41.5% sensitivity). The cost to identify one affected pregnancy was reduced by 62% in the reflex sgNIPT scenario compared to the traditional scenario. Adding together the testing cost savings and the savings from earlier clinical intervention made possible by reflex sgNIPT, the total cost savings was $37.6 million per 100,000 pregnancies. Based on these cost savings, we simulated appropriate reflex sgNIPT pricing range: if the cost to identify one affected pregnancy is the unit cost, carrier screening with reflex sgNIPT can be priced up to $1,859 per test (or $7,233 if sgNIPT is billed separately); if the cost per 100,000 pregnancies is the unit cost, carrier screening with sgNIPT can be priced up to $1,070 per test (or $2,336 if sgNIPT is billed separately).

Conclusion

Using the carrier screen with reflex sgNIPT as first-line screening improves the detection of affected fetuses by 2.4-fold and can save costs for the healthcare system. A real-life experience will be needed to assess the clinical utility and exact cost savings of carrier screen with reflex sgNIPT.

Keywords:

• Carrier screening
• genetic disorders
• pregnancy healthcare costs
• decision-analytical model
• cystic fibrosis
• spinal muscular atrophy
• thalassemia
• sickle cell disease
• genetic counseling
• cell-free DNA

JEL CLASSIFICATION CODES:

• C51
• C5
• C
• I10
• I1
• I
• I19

Transparency

Declaration of funding

BillionToOne, Inc. provided financial support for the conduct of the research and preparation of the article.

Declaration of financial/other relationships

S.R. and J.H. are employees of BillionToOne (or a subsidiary) and hold stock or options to hold stock in the company. J.A.C. is compensated by BillionToOne. H.H. serves on the Advisory Board for BillionToOne and does not hold stock or option to hold stocks.

Peer reviewers on this manuscript have received an honorarium from JME for their review work but have no other relevant financial relationships to disclose.

The Deputy Editor in Chief helped with adjudicating the final decision on this paper.

Author contributions

S.R. built the decision-analytical model. S.R. and J.A.C analyzed data. All authors wrote and edited the manuscript.

Acknowledgements

We thank Dr. Oguzhan Atay, Dr. John ten Bosch, and Carrie McGehee for providing valuable inputs to the decision-analytic model, and Dr. Rong Mao for providing editorial support for this manuscript.