Balancing How Much We Want to Know with What We Are Willing to Pay: A Comparative Cost Analysis of Prenatal...

Introduction: Invasive prenatal diagnostic tests have higher detection rates than screening tests. Cell-free DNA (cfDNA) screening has higher detection than combined testing (CT). We estimated the cost per cytogenetic abnormality diagnosed for prenatal testing and screening methods (US data).

We compared seven strategies: universal diagnosis with microarray and karyotype; cfDNA screening with four methodologies: Digital Analysis of Selected Regions (DANSR), massively parallel shotgun sequencing (MPSS), single-nucleotide polymorphisms (SNPs), and rolling circle amplification (RCA); and CT. Five abnormality groupings were considered: common autosomal trisomies (21,18,13), sex chromosome aneusomies, triploidy, clinically significant sub-chromosome changes, and copy number variants. Prevalence, detection, false-positive rates, and unit costs (literature) were obtained. The detection rate was aggregated across groups as were costs, including diagnostic tests following positive screening results.

All six high detection strategies had greater cost per abnormality diagnosed than CT (USD 26,100). The costliest was cfDNA using MPSS (USD 96,100), followed by universal karyotyping (USD 95,900), cfDNA using SNPs, DANSR (USD 94,800-USD 92,800), universal microarray (USD 56,600), and cfDNA with RCA (USD 32,200). The additional cost per extra abnormality diagnosed compared to CT ("marginal" cost) was the lowest for cfDNA with RCA (USD 45,000); others were considerably higher (USD 59,400-USD 160,700).

Preferred prenatal strategies vary among stakeholders. However, as monopolies (large systems and Accountable Care Organizations) now control the majority of American healthcare policy decisions, the lowest cost cfDNA screening will likely prevail in actual practice.