Optimal risk cut-off of sequential screening for Down syndrome: a cost-effectiveness analysis / 中华围产医学杂志

ABSTRACT

Objective:To investigate the optimal cut-off of sequential screening for Down syndrome (DS) with a cost-effectiveness analysis.Methods:A theoretical model, covering 1 000 000 singleton pregnancies, was established with the parameters from published articles and on-the-spot investigation. Two screening strategies were involved and both required conventional second-trimester serum triple screening first. For the next step, strategyⅠ was followed by cell-free fetal DNA (cffDNA) testing if the cut-offs were higher than 1/300 (Ⅰ-1) or 1/1 000 (Ⅰ-2), and if cffDNA testing indicated high risk, prenatal diagnostic testing would be performed. While strategy Ⅱ was followed by prenatal diagnostic testing in high-risk populations with cut-offs higher than 1/10 (Ⅱ-1), 1/50 (Ⅱ-2), 1/100 (Ⅱ-3), 1/150 (Ⅱ-4), 1/200 (Ⅱ-5), 1/250 (Ⅱ-6) or 1/300 (Ⅱ-7), or cffDNA testing for those with intermediate risks. The primary outcome was an incremental cost analysis on the baseline and alternative assumptions. The strategy was defined as "appropriate" when the incremental cost was less than the cost of raising one DS child. The secondary outcomes included total cost, cost-effectiveness analysis, cost-benefit analysis, and screening efficiency.Results:(1) More DS cases and less survived miss-diagnosed cases were detected by strategy Ⅱthan strategyⅠ (Ⅰ-1 1 921, Ⅰ-2 2 199 vs Ⅱ-1 to Ⅱ-7 2 202-2 212; Ⅰ-1 312; Ⅰ-2 100 vs Ⅱ-1 to Ⅱ-7 98-90). The total prenatal diagnosis cases and the number of case requring prenatal diagnosis for detecting one DS case were the lowest in strategy Ⅰ-1 group (2 081; 1.1, 2 081/1 921) and were the highest in Strategy Ⅱ-7 group (82 385; 37.2, 82 385/2 212). (2) Strategy Ⅰ-1 was the most cost-effective approach with the lowest total cost (￥928.896 million) and cost-effectiveness (￥237 000), and the highest benefit/cost ratio (4.90), followed by strategy Ⅱ-7 (￥957.380 million, ￥371 000 and 3.11). The most costly strategy was Ⅰ-2 (￥1 040.883 million, ￥404 000 and 2.85). (3) Setting strategyⅠ-1 as the baseline, strategyⅠ-2 had the highest incremental cost (￥1.580 million). The incremental cost of strategy Ⅱ ranged from ￥1.535 million (Ⅱ-1) to ￥1.259 million (Ⅱ-7), close to or less than the cost of raising a DS child (￥1.52 million). (4) The cost of cffDNA was a major factor in decision-making based on sensitivity analysis. When the price went down to ￥1 075, the incremental cost of strategy Ⅱ-1 was the lowest (￥757 000). If it further lowered to ￥697, strategy Ⅰ-2 was optimal (lower than ￥523 000). (5) The sensitivity analysis also suggested that the acceptance rate of cffDNA testing had no influence on the incremental cost-related findings (incremental cost in strategy Ⅱ-7 was least and less than costs for one Down Syndrome patient). When the acceptance rate of prenatal diagnostic testing was lower than 80%, the incremental cost of strategy Ⅱ-7 (￥1.669 million) was the lowest, which was higher than raising a DS child.Conclusions:cffDNA testing in high-risk populations (strategyⅠ-1) could significantly reduce unnecessary diagnostic tests and is appropriate in total cost, cost-effectiveness and cost-benefit analysis, but misses more DS livebirths. Implementing prenatal diagnostic testing among pregnancies with risk cut-offs higher than 1/300 (strategy Ⅱ-7) could improve screening efficiency and reduce incremental costs, but require more cases to be tested. The cost of cffDNA testing is the most important influencing factor. On the premise of achieving substantial screening efficiency, strategy Ⅱ-1 and Ⅰ-2 are optimal with the lowest incremental costs if cffDNA testing cost drops to ￥1 075 and ￥697, respectively. Lower acceptance of prenatal diagnostic testing is accompanied by less detected DS cases and increased incremental costs than the baseline, which is not conducive to the prevention of birth defects.