title: Cell-free fetal DNA screening in the USA: a cost analysis of screening strategies.
abstract: OBJECTIVE
  To determine whether implementation of primary cell-free fetal DNA (cffDNA) screening would be cost-effective in the USA and to evaluate potential lower-cost alternatives.
  
  
  METHODS
  Three strategies to screen for trisomy 21 were evaluated using decision tree analysis: 1) a primary strategy in which cffDNA screening was offered to all patients, 2) a contingent strategy in which cffDNA screening was offered only to patients who were high risk on traditional first-trimester screening and 3) a hybrid strategy in which cffDNA screening was offered to all patients ≥ 35 years of age and only to patients < 35 years who were high risk after first-trimester screening. Four traditional screening protocols were evaluated, each assessing nuchal translucency (NT) and pregnancy-associated plasma protein-A (PAPP-A) along with either free or total beta-human chorionic gonadotropin (β-hCG), with or without nasal bone (NB) assessment.
  
  
  RESULTS
  Utilizing a primary cffDNA screening strategy, the cost per patient was 1017 US$. With a traditional screening protocol using free β-hCG, PAPP-A and NT assessment as part of a hybrid screening strategy, a contingent strategy with a 1/300 cut-off and a contingent strategy with a 1/1000 cut-off, the cost per patient was 474, 430 and 409 US$, respectively. Findings were similar using the other traditional screening protocols. Marginal cost per viable case detected for the primary screening strategy as compared to the other strategies was 3-16 times greater than the cost of care for a missed case.
  
  
  CONCLUSIONS
  Primary cffDNA screening is not currently a cost-effective strategy. The contingent strategy was the lowest-cost alternative, especially with a risk cut-off of 1/1000. The hybrid strategy, although less costly than primary cffDNA screening, was more costly than the contingent strategy.
authors.affiliation: Comprehensive Genetics, New York, NY, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Evans
authors.forename: J D
authors.initials: JD
authors.lastname: Sonek
authors.forename: T W
authors.initials: TW
authors.lastname: Hallahan
authors.forename: D A
authors.initials: DA
authors.lastname: Krantz
mesh_terms: D000328:Adult; D002474:Cell-Free System; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D003362:Cost-Benefit Analysis; D003365:Costs and Cost Analysis; D004247:DNA / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D008423:Maternal Age; D048208:Nuchal Translucency Measurement / Q000191:economics; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism; D011296:Prenatal Diagnosis / Q000191:economics*; D014314:Trisomy / Q000175:diagnosis*; D016216:Ultrasonography, Prenatal / Q000191:economics*; D014481:United States
chemical_list: D018997:Chorionic Gonadotropin, beta Subunit, Human; D004247:DNA; D011266:Pregnancy-Associated Plasma Protein-A
keywords: Down syndrome screening; aneuploidy serum markers; cell-free fetal DNA; cost analysis; nasal bone; nuchal translucency