Table 9:

Results of Economic Literature Review—Summary

				Results
Author, Year, Country	Study Designa and Perspective	Population/Target Fetal Aneuploidies	Intervention/Comparatorb	Health Outcomesc	Costsd	Conclusionse
Nshimyumukiza et al, 2018,74 Canada	Type of economic analysis: cost-effectiveness analysis Study design: decision-analytic model Perspective: public payer Time horizon: duration of pregnancy	Pregnancies in Quebec (6% per year of 1,879,872 people 15–49 years old) with an uptake of 70% Trisomies 21, 18, and 13	FTS (risk cutoff 1:300 for trisomy 21) MSS (risk cutoff 1:300 for trisomy 21) FTS + NIPT MSS + NIPT Universal NIPT Note: the authors included 13 screening strategies; we have reported the 5 most relevant to this review	Cases identified, n (trisomy 21; trisomies 18 and 13): FTS: 281 (184; 97) MSS: 240 (173; 67) FTS + NIPT: 251 (163; 88) MSS + NIPT: 210 (155; 55) Universal NIPT: 314 (216; 98) Diagnostic tests, n: FTS: 2,659 MSS: 3,146 FTS + NIPT: 292 MSS + NIPT: 253 Universal NIPT: 539	CAD; fiscal year 2014/15 Cost of NIPT: $795 FTS: $16.9 M MSS: $11.9 M FTS + NIPT: $15.0 M MSS + NIPT: $10.4 M Universal NIPT: $66.6 M	Compared with FTS, first-tier NIPT would cost $1.5 M to detect 1 additional case of trisomy 21 Compared with traditional prenatal screening, NIPT as a second-tier test for high-risk pregnant people was likely to be cost-effective
Huang et al, 2017,75 Canada	Type of economic analysis: cost-effectiveness analysis Study design: decision-analytic model Perspective: public payer Time horizon: duration of pregnancy	Cohort of 97,385 pregnancies screened annually in Ontario (total annual pregnancies 142,376) Trisomy 21	IPS (risk cutoff 1:200) FTS (risk cutoff 1:1,500) + NIPT eFTS (risk cutoff 1:1,000) + NIPT Universal NIPT(a): 100% of those with NIPT test failures would have diagnostic testing Universal NIPT(b): 0% of those with NIPT test failures would have diagnostic testing	Cases identified, n: IPS: 135 FTS + NIPT: 238 eFTS + NIPT: 238 Universal NIPT(a): 251 Universal NIPT(b): 243 Diagnostic tests, n: IPS: 3,190 FTS + NIPT: 813 eFTS + NIPT: 563 Universal NIPT(a): 3,259 Universal NIPT(b): 338 False-positive rate, %: IPS: 3.30 FTS + NIPT: 0.59 eFTS + NIPT: 0.33 Universal NIPT(a): 3.09 Universal NIPT(b): 0.10	CAD; costing year not reported Cost of NIPT: $550 IPS: $17.3 M FTS + NIPT: $21.8 M eFTS + NIPT: $18.6 M Universal NIPT(a): $59.4 M Universal NIPT(b): $54.1 M Cost of NIPT: $400 IPS: $17.3 M FTS + NIPT: $19.0 M eFTS + NIPT: $17.0 M Universal NIPT(a): $44.8 M Universal NIPT(b): $39.6 M Cost of NIPT: $200 IPS: $17.3 M FTS + NIPT: $15.2 M eFTS + NIPT: $14.8 M Universal NIPT(a): $25.3 M Universal NIPT(b): $20.1 M	eFTS with second-tier NIPT provided performance similar to that of universal NIPT at a substantially lower cost
Maxwell et al, 2017,76 Australia	Type of economic analysis: cost-effectiveness analysis Study design: decision-analytic model Perspective: public payer Time horizon: duration of pregnancy	Cohort of 300,000 screened pregnancies representing the approximate number of live births annually in Australia Trisomy 21	FTS (risk cutoff 1:300) FTS + NIPT (risk cutoff 1:300 for NIPT, 1:5 for diagnostic testing) FTS + NIPT (risk cutoff 1:1,000 for NIPT, 1:10 for diagnostic testing) Note: this article included 25 second-tier NIPT models. We have reported results from 2 models and the traditional prenatal screening model	Detection rate, %: FTS: 82.0 FTS + NIPT (risk cutoff 1:300): 81.3 FTS + NIPT (risk cutoff 1:1,000): 90.1 Diagnostic tests per diagnosis, n: FTS: 14.18 FTS + NIPT (risk cutoff 1:300): 1.7 FTS + NIPT (risk cutoff 1:1,000): 2.03	Australian dollars; 2014 Cost of NIPT: $400 FTS: $38.2 M FTS + NIPT (risk cutoff, 1:300): $36.0 M FTS + NIPT (risk cutoff, 1:1,000): $42.9 M	Compared with FTS, second-tier NIPT models using more sensitive risk cutoffs improved the detection rate for trisomy 21, reduced procedure-related pregnancy loss and could be provided at a lower cost per diagnosis
Colosi et al, 2017,77 Italy	Type of economic analysis: cost-effectiveness analysis Study design: decision-analytic model Perspective: health care sector Time horizon: duration of pregnancy	Singleton pregnancies in Tuscany, Italy: 20,831 people Trisomies 21, 18, and 13	FTS (risk cutoff 1:250) FTS + NIPT with nasal bone evaluation (risk cutoff 1:10–1:1,000 for NIPT, 1:10 for diagnostic testing) FTS + NIPT without nasal bone evaluation (risk cutoff 1:10–1:1,000 for NIPT, 1:10 for diagnostic testing) Universal NIPT	Detection rate, %: FTS: 94.92 FTS + NIPT without nasal bone evaluation: 97.82 FTS + NIPT with nasal bone evaluation: 97.82 Universal NIPT: 97.82 Note: no breakdown on detection rate of trisomies 21, 18, or 13 Diagnostic tests, n: FTS: 1,313 FTS + NIPT without nasal bone evaluation: 339 FTS + NIPT with nasal bone evaluation: 285 Universal NIPT: 760 (positive NIPT results and NIPT test failures received diagnostic testing) False-positive rate, %: FTS: 5.63 FTS + NIPT and without nasal bone evaluation: 0.85 FTS + NIPT and nasal bone evaluation: 0.85 Universal NIPT: 0.43	Euro; cost year not reported Cost of NIPT: 260 € FTS: €2.4 M FTS + NIPT without nasal bone evaluation: €2.8 M FTS + NIPT with nasal bone evaluation: €2.3 M Universal NIPT: €5.8 M	Second-tier NIPT could be a cost-efficient and feasible first-trimester screening test for aneuploidies in the public health system
Chitty et al, 2016,78 United Kingdom	Type of economic analysis: cost-effectiveness analysis Study design: decision-analytic model Perspective: United Kingdom National Screening Committee Time horizon: duration of pregnancy	Cohort of 698,500 pregnancies, based on annual live births in England and Wales and an uptake rate of 66% Trisomy 21	Traditional prenatal screening—FTS (86.9%) and MSS (13.1%; risk cutoff 1:150) FTS/MSS + NIPT(a): pregnant people can have diagnostic testing directly without NIPT first (risk cutoff 1:150) FTS/MSS + NIPT(b): pregnant people cannot have diagnostic testing directly (risk cutoff 1:150) Note: this article also reported results at risk cutoffs of 1:500 and 1:1,000	Cases identified, n: FTS/MSS: 577 FTS/MSS + NIPT(a): 688 FTS/MSS + NIPT(b): 556 Note: We have presented the number of positive findings confirmed by diagnostic testing Diagnostic tests, n: FTS/MSS: 5,743 FTS/MSS + NIPT(a): 2,375 FTS/MSS + NIPT(b): 615	GBP; 2012/13 Cost of NIPT: £250 FTS/MSS: $17.0 M FTS/MSS + NIPT(a): $17.0 M FTS/MSS + NIPT(b): $16.4 M	Second-tier NIPT improved the overall performance of prenatal screening without increasing costs
Fairbrother et al, 2016,79 United States	Type of economic analysis: cost-effectiveness analysis Study design: decision-analytic model Perspective: societalf Time horizon: lifetime	General pregnancy population based on annual live births in the United States (4,000,000) and an uptake rate of 70% Trisomies 21, 18 and 13	FTS Universal NIPT	Total cases identified, n (trisomy 21; trisomy 18; trisomy 13): FTS: 7,799 (4,768; 2,356; 674) Universal NIPT: 8,993 (5,544; 2,710; 738) Diagnostic tests, n: FTS: 147,311 Universal NIPT: 17,303	USD; 2014 FTS: $3.88 B Universal NIPT: when the NIPT unit cost was $453 or less, NIPT resulted in cost savings over FTS Discounting not reported	First-tier NIPT resulted in more trisomy cases detected than FTS, and was more economical at a NIPT unit cost of $453

Abbreviations: B, billion; eFTS, enhanced first-trimester screening; FTS, first-trimester screening; ICER, incremental cost-effectiveness ratio; IPS, integrated prenatal screening; MSS, maternal serum screening (also known as quadruple screening); M, million; NIPT, noninvasive prenatal testing; NT, nuchal translucency.

^aThe included studies used different terms (e.g., cost-effectiveness analysis⁷⁴ and cost analysis^75,76) in their titles. Since all included studies reported both health outcomes and costs, we used the term “cost-effectiveness analysis” in this review. Moreover, some studies can be categorized as cost–consequence studies, since they did not report cost per case detected or incremental cost per case detected.

^bThe intervention and comparator refer to NIPT strategies (i.e., first-tier or second-tier NIPT). When studies included numerous strategies, we reported the results from the strategies most relevant to this review:

• FTS, IPS, eFTS and MSS: traditional prenatal screening without NIPT
• FTS/IPS/eFTS/MSS + NIPT: second-tier NIPT
• Universal NIPT: first-tier NIPT

^cPublished studies presented various health outcomes. We reported three health outcomes: the number of trisomy cases identified (or detection rate), the number of invasive diagnostic tests (or invasive diagnostic tests per diagnosis), and false-positive rate. We kept the original measures (e.g., the number of case identified or the detection rate) reported in these studies. Invasive diagnostic tests refers to amniocentesis or chorionic villus sampling.

^dThe costs refer to the total costs of implementing each screening strategy for the entire hypothetical cohort, including the cost of traditional prenatal screening, NIPT, and diagnostic testing.

^eWe summarized the conclusions from authors in each economic evaluation. We did not calculate the ICER (incremental cost per case detected or diagnostic test avoided) if it was not reported in the study.

^fAuthors did not clearly state the perspective. Because this study included both direct medical costs and indirect costs for a given trisomy birth, we assumed that the study was conducted from a societal perspective with a lifetime horizon.