Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Howard Cuckle ◽  
Seppo Heinonen ◽  
Anna-Kaisa Anttonen ◽  
Vedran Stefanovic

Abstract Introduction A financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies. Materials and methods Three cell-free DNA screening strategies are considered: Primary, all women; Secondary, those with positive Combined test; and Contingent, the 10–30% with the highest Combined test risks. Three costs are estimated: additional cost for 10,000 pregnancies compared with the Combined test; ‘marginal’ cost of avoiding a Down syndrome birth which occurs in a pregnancy that would have been false-negative using the Combined test; and marginal cost of preventing the iatrogenic loss of a non-Down syndrome birth which occurs in a pregnancy that would have been false-positive. Results Primary cell-free DNA will require additional funds of €250,000. The marginal cost per Down syndrome birth avoided is considerably less than the lifetime medical and indirect cost; the marginal cost per unaffected iatrogenic fetal loss prevented is higher than one benefit measure but lower than another. If the ultrasound component of the Combined test is retained, as would be in Finland, the additional funds required rise to €992,000. Secondary cell-free DNA is cost-saving as is a Contingent strategy with 10% selected but whilst when 20–30% costs rise they are much less than for the Primary strategy and are cost-beneficial. Conclusions When considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits. Under most assumptions the balance is favorable for Contingent screening.

2018 ◽  
Vol 26 (10) ◽  
pp. 1490-1496 ◽  
Author(s):  
Karin Huijsdens-van Amsterdam ◽  
Lieve Page-Christiaens ◽  
Nicola Flowers ◽  
Michael D Bonifacio ◽  
Katie M Battese Ellis ◽  
...  

2019 ◽  
Vol 220 (1) ◽  
pp. S583-S584
Author(s):  
Maeve Hopkins ◽  
Lorraine Dugoff ◽  
Celeste Durnwald ◽  
Laura Havrilesky ◽  
Sarah Dotters-Katz

2015 ◽  
Vol 35 (5) ◽  
pp. 440-446 ◽  
Author(s):  
Brandon S. Walker ◽  
Brian R. Jackson ◽  
Danielle LaGrave ◽  
Edward R. Ashwood ◽  
Robert L. Schmidt

2016 ◽  
Vol 30 (20) ◽  
pp. 2476-2482 ◽  
Author(s):  
M. M. Gil ◽  
M. Brik ◽  
C. Casanova ◽  
R. Martin-Alonso ◽  
M. Verdejo ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Yang Cao ◽  
Nicole L. Hoppman ◽  
Sarah E. Kerr ◽  
Christopher A. Sattler ◽  
Kristi S. Borowski ◽  
...  

Background.Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy.Results.We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism.Conclusions.Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.


2021 ◽  
pp. 921-930
Author(s):  
Catherine B. Meador ◽  
Marina S. D. Milan ◽  
Emmy Y. Hu ◽  
Mark M. Awad ◽  
Michael S. Rabin ◽  
...  

PURPOSE Plasma cell-free DNA (cfDNA) sequencing is a compelling diagnostic tool in solid tumors and has been shown to have high positive predictive value. However, limited assay sensitivity means that negative plasma genotyping, or the absence of detection of mutation of interest, still requires reflex tumor biopsy. METHODS We analyzed two independent cohorts of patients with advanced non–small-cell lung cancer (NSCLC) with known canonical driver and resistance mutations who underwent plasma cfDNA genotyping. We measured quantitative features, such as maximum allelic frequency (mAF), as clinically available measures of cfDNA tumor content, and studied their relationship with assay sensitivity. RESULTS In patients with EGFR-mutant NSCLC harboring EGFR T790M, detection of driver mutation at > 1% AF conferred a sensitivity of 97% (368/380) for detection of T790M across three cfDNA genotyping platforms. Similarly, in a second cohort of patients with EGFR or KRAS driver mutations, when the mAF of nontarget mutations was > 1%, sensitivity for driver mutation detection was 100% (43/43). Combining the two NSCLC patient cohorts, the presence of nontarget mutations at mAF > 1% predicts for high sensitivity (> 95%) for identifying the presence of the known driver mutation, whereas mAF of ≤ 1% confers sensitivity of only 26%-54% across platforms. Focusing on 21 false-negative cases where the driver mutation was not detected on plasma next-generation sequencing, other mutations (presumably clonal hematopoiesis) were detected at ≤ 1% AF in 14 (67%). CONCLUSION Plasma cfDNA genotyping is highly sensitive when adequate tumor DNA content is present. The likelihood of a false-negative cfDNA genotyping result is low in a sample with evidence of > 1% tumor content. Bioinformatic approaches are needed to further optimize the assessment of cfDNA tumor content in plasma genotyping assays.


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