Original Title: Análisis de ADN fetal en sangre materna para la detección de trisomías 21, 18 y 13

Authors' objectives: MAIN OBJECTIVES: • To review the validity of the NIPT for the detection of trisomies in chromosomes 21, 18 and 13 in the fetus. • To review the cost-effectiveness of the NIPT for the detection of trisomies in chromosomes 21, 18 and 13. • To assess the cost-effectiveness of the screening strategy that includes the NIPT for the detection of trisomies 21, 18 and 13 in the fetus versus the usual prenatal screening program from the National Health System (NHS) perspective in Spain. SECONDARY OBJECTIVE: • To report on aspects related to ethical, organizational, legal, and other domains with the aim of informing the decision making.

Authors' results and conclusions: RESULTS: DIAGNOSIS TEST STUDIES: A total of 49 articles were included in this review, 41 studies already included in the review by Taylor-Phillips et al. and 8 studies found during the update. Most of the studies had a cohort design with prospective collection of data and single pregnancies. High-risk pregnancies were included in 26 studies. Only 8 studies included only women in their first trimester. T21 was analyzed in 48 studies, T18 in 44 studies, and T13 in 36 studies. The risk of bias was high in most of the studies. According to our meta-analyses, the global sensitivity and specificity of NIPT was estimated at 99.76% and 99.96%, respectively, for T21; 96.49% and 99.93% for T18; 96.19% and 99.94% for T13. The subgroup analyses showed that the best results are found for high-risk populations. COST-EFFECTIVENESS STUDIES: We identified 12 studies that fulfilled the inclusion criteria. Three studies conducted in the USA assessed the three trisomies. Two of them, with limited transparency, concluded that contingent NIPT is cost-effective. The third study, with better methodological quality, concluded that universal NIPT dominated the other alternatives from the societal perspective, whereas from the payer perspective contingent NIPT finds more cases and is more costly than the usual screening. The other economic evaluations only assessed T21, finding heterogeneous results. OSTEBA conducted a study in Spain from the NHS perspective that found contingent NIPT less costly and with a reduced number of invasive test-related fetal losses, although it detects fewer T21 cases than the usual screening. ECONOMIC EVALUATION: The prenatal screening with contingent NIPT is less costly and less effective in terms of the number of cases with trisomies (T21, T18, and T13) with a correct diagnosis. The estimated ICER was €234,596 per correctly diagnosed case. The prenatal screening with contingent NIPT has the advantage of a reduced number of invasive test-related fetal losses. The probabilistic sensitivity analysis confirmed the results of the base case. BUDGET IMPACT: In a scenario with constant annual pregnancies in Spain (325,373), assuming an increase in the percentage of pregnancies monitored by the public healthcare system (from 80% to 85%), and for a price of NIPT of €289, the net budget impact for the NHS is estimated to be more than €12 million per year. CONCLUSIONS: • The sensitivity of NIPT for the detection of T21, T18 or T13 in general population is 94.5%, 89.77% y 61.47%, respectively (Quality of evidence: low or very low). • The specificity of NIPT for the detection of T21, T18 or T13 in general population is higher than 99% (Quality of evidence: moderate to high). • In populations with high risk better estimations are obtained. • The economic evaluations show heterogeneous results. A Spanish study concluded that contingent NIPT is less costly and less effective in terms of T21 cases than the usual screening, although it reduces the number of invasive test related fetal losses. • The economic evaluation included in this report found that contingent NIPT is less costly for the NHS and less effective in terms of T21, T18 and T13 cases than the usual screening in Spain, although it reduces the number of invasive test related fetal losses. • The budget impact of including NIPT in the NHS depends on the price of NIPT or the number of pregnancies monitored by the public healthcare system. • The inclusion of NIPT in the NHS requires considerations related to technical, organizational, legal and informational aspects.

Authors' methods: SYSTEMATIC REVIEW OF DIAGNOSIS TEST STUDIES: A previous systematic review by Taylor-Phillips et al. was updated. The selection criteria were: • Types of participants: Women with single or multiple pregnancies that participate in a prenatal screening program due to a potential risk of anomalies in the fetus or without that risk. • Types of interventions (index test): NIPT for the detection of trisomies in chromosomes 21, 18, and 13 (T21, T18, and T13). • Type of comparators (standard of reference): Invasive tests such as amniocentesis, CVS, and cordocentesis, post-mortem examinations, phenotypic analysis. The analysis of the fetal sample should be made by means of usual methods such as karyotype, FISH, or QF-PCR. • Types of outcomes: To be included, the study had to report the sensitivity and specificity of the test, or at least, the true positives, false positives, true negatives, and false negatives. Every woman had to be tested with NIPT and with the standard independently of the result in each test. • Types of studies: Every type of design. Case-control studies with less than 15 cases and cohort studies with less than 500 women were excluded. • Type of report and languages: We included studies published in English or Spanish. We excluded protocols of studies without results, conference abstracts, letters, editorials, and discussion papers. We conducted a systematic search in MEDLINE and PreMEDLINE, EMBASE, and Cochrane Library (DARE, HTA, NHS EED) from January 2006, without language restrictions. Two independent reviewers selected the studies. The assessment of bias was conducted by two reviewers by means of the QUADAS-2 instrument. The data extraction of the included studies was carried out by one reviewer and verified by a second reviewer. The differences between reviewers were resolved through discussion and/or with a third reviewer. The information gathered was summarized through a narrative synthesis, and the results were shown in tables, informing separately of results related to T21, T18, and T13. We conducted meta-analyses of the yield of NIPT for the detection of each trisomy by means of a bivariate random effects model. Quality of the evidence and strength of recommendations were assessed using the GRADE methodology. SYSTEMATIC REVIEW OF COST-EFFECTIVENESS: The selection criteria of economic evaluations were similar to the selection criteria of diagnosis test studies. Briefly, we included full economic evaluations that compared a screening strategy that included NIPT to detect T21, T18, and T13 in the fetus with a screening strategy not including NIPT or the alternative ‘no screening’. The studies had to report detected cases and the costs of each alternative or the incremental cost-effectiveness ratios (ICER). The search strategy of diagnosis test studies was used. The assessment of the methodological quality was conducted by means of the tool by López-Bastida et al. The synthesis of the cost-effectiveness studies was only narrative. ECONOMIC EVALUATION: We conducted an economic evaluation where we compared detected cases of T21, T18, and T13 and costs of two screening strategies, the usual screening (first or second trimester screening) vs. the screening where NIPT is a contingent test. Experts and a review of literature were used to define the strategies, the clinical course, and the resource use of every strategy. The values of sensitivity and specificity used were the results of the meta-analyses conducted for this review in high-risk population. A decision tree was designed with a short-term horizon, until birth. The analysis was conducted for a cohort of 100,000 pregnant women and from the point of view of the NHS, therefore only direct medical costs in Spain were included. The costs were expressed in EUROS 2016. Costs and effectiveness of each alternative and ICERs were estimated. We also estimated the number of invasive test-related fetal losses. We conducted deterministic and probabilistic sensitivity analyses. BUDGET IMPACT ANALYSIS: It was estimated the annual budget impact if the NIPT for the detection of trisomies in high-risk pregnancies were included in the NHS. The number of pregnant women is estimated from national statistics and assumptions, excluding twins or multiple pregnancies. The net impact was estimated for several scenarios depending on the price of NIPT and the percentage of women attending the public healthcare.

Project Status: Completed

Year Published: 2016

URL for published report: https://sescs.es/analisis-de-adn-fetal-en-sangre-materna-para-la-deteccion-de-trisomias-21-18-y-13/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Spain

Organisation Name: Canary Health Service

Contact Address: Dirección del Servicio. Servicio Canario de la Salud, Camino Candelaria 44, 1ª planta, 38109 El Rosario, Santa Cruz de Tenerife

Contact Name: sescs@sescs.es

Contact Email: sescs@sescs.es