Tianhua Huang1, Wendy S Meschino2, Mari Teitelbaum3, Shelley Dougan4, Nan Okun5. 1. Genetics Program, North York General Hospital, Toronto, ON; Better Outcomes Registry & Network (BORN) Ontario, Ottawa, ON; The Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON. Electronic address: tianhua.huang@nygh.on.ca. 2. Genetics Program, North York General Hospital, Toronto, ON; Department of Paediatrics, University of Toronto, Toronto, ON. 3. Better Outcomes Registry & Network (BORN) Ontario, Ottawa, ON; Children's Hospital of Eastern Ontario, Ottawa, ON. 4. Better Outcomes Registry & Network (BORN) Ontario, Ottawa, ON. 5. Maternal Fetal Medicine Program, Mount Sinai Hospital, University of Toronto, Toronto, ON.
Abstract
OBJECTIVE: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system. METHODS: Using performance and cost parameters from published literature, four prenatal screening strategies were compared. Scenario 1 modelled integrated prenatal screening (first trimester nuchal translucency and biochemical markers from both the first and second trimesters) with no cffDNA. Scenarios 2 and 3 modelled first trimester combined screening (FTS) and "enhanced FTS" (adding serum placental growth factor and alpha fetoprotein to FTS), respectively, with contingent cffDNA following a positive result. Scenario 4 modelled cffDNA as the primary screening test. RESULTS: Scenario 1 provides a known detection rate (DR) of 88%, with a false positive rate (FPR) of 3.3%. Scenarios 2 and 3 result in a DR of 94% and overall FPR of 0.59% and 0.33%, respectively, comparable to the DR of 96% and FPR of 0.1% with primary cffDNA (assuming the published test failure rate of 3%). The total cost, cost per woman screened, and cost per case of trisomy 21 detected were lower with scenario 3 (enhanced FTS with contingent cffDNA) compared with primary cffDNA or scenario 2 (FTS with contingent cffDNA). CONCLUSION: Enhanced FTS with contingent cffDNA following a positive result provides a similar performance to that of primary cffDNA at a substantially lower cost.
OBJECTIVE: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system. METHODS: Using performance and cost parameters from published literature, four prenatal screening strategies were compared. Scenario 1 modelled integrated prenatal screening (first trimester nuchal translucency and biochemical markers from both the first and second trimesters) with no cffDNA. Scenarios 2 and 3 modelled first trimester combined screening (FTS) and "enhanced FTS" (adding serum placental growth factor and alpha fetoprotein to FTS), respectively, with contingent cffDNA following a positive result. Scenario 4 modelled cffDNA as the primary screening test. RESULTS: Scenario 1 provides a known detection rate (DR) of 88%, with a false positive rate (FPR) of 3.3%. Scenarios 2 and 3 result in a DR of 94% and overall FPR of 0.59% and 0.33%, respectively, comparable to the DR of 96% and FPR of 0.1% with primary cffDNA (assuming the published test failure rate of 3%). The total cost, cost per woman screened, and cost per case of trisomy 21 detected were lower with scenario 3 (enhanced FTS with contingent cffDNA) compared with primary cffDNA or scenario 2 (FTS with contingent cffDNA). CONCLUSION: Enhanced FTS with contingent cffDNA following a positive result provides a similar performance to that of primary cffDNA at a substantially lower cost.
Authors: Altug Koc; Ozge Ozer Kaya; Berk Ozyilmaz; Yasar B Kutbay; Ozgur Kirbiyik; Taha R Ozdemir; Kadri M Erdogan; Merve Saka Guvenc; Deniz C Oztekin; Mehmet Ozeren; Halil G Pala; Atalay Ekin; Cenk Gezer; Alkim G Sahingoz Yildirim; Bahar Konuralp Atakul; Secil Kurtulmus; Ugur Turhan; Cuneyt E Taner Journal: Mol Genet Genomic Med Date: 2019-05-08 Impact factor: 2.183
Authors: Malia S Q Murphy; Deshayne B Fell; Ann E Sprague; Daniel J Corsi; Shelley Dougan; Sandra I Dunn; Vivian Holmberg; Tianhua Huang; Moya Johnson; Michael Kotuba; Lise Bisnaire; Pranesh Chakraborty; Susan Richardson; Mari Teitelbaum; Mark C Walker Journal: Int J Epidemiol Date: 2021-11-10 Impact factor: 7.196