OBJECTIVES: To estimate the costs and benefits of implementing cfDNA for T21 in prenatal screening to support recommendations on its use in France.

METHODS: A model was developed to simulate outcomes (detected foetal T21s, miscarriages avoided, false and true negatives, screening withdrawals and test failures) and costs of using standard first trimester T21 screening in France, compared to screening strategies that include cfDNA with different T21 risk thresholds (i.e. 1/250, 1/1000 and 1/2500). The time horizon used for the model was less than one year. Methodological choices were based on HAS guidelines, a systematic literature review of health economics studies, and expert consultation. Data was derived from national datasets and completed with international studies, where needed. Sensitivity analyses and validation against international study results were carried out.

RESULTS: Integrating cfDNA in T21 prenatal screening strategy prior to invasive diagnosis for pregnant women with a risk threshold of at least 1/250, leads to an additional cost of €440,000, while improving the number of detected prenatal T21s by more than 40, and reducing the number of invasive procedures by 13 300 and the number of related miscarriages by 18. When comparing the modelling strategies integrating cfDNA, the low bounds of 1/250 and 1/1000, and the high bounds of 1 and 1/50, appear to be the most relevant choices based on non-weighted outcomes.

CONCLUSIONS: Implementation of cfDNA as a contingent test in prenatal screening can improve foetal T21s detection while avoiding procedure related miscarriages. From a health economic point of view, implementation of cfDNA in France seems to be most relevant for threshold risks ranging between [1/250; 1[, [1/1000; 1[, or [1/1000; 1/50[. Final HAS recommendations were based on model results, as well as on ethical, preferential and organisational aspects and expert opinion.