A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

Abstract

BackgroundPostnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies.MethodsWe conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications.ResultsThe basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall.ConclusionsCurrently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale introduction in England and Wales. Only minor savings are calculated and, balanced against this, the predicted increase in maternal sensitisations may be unacceptably high. Reliability of NIPD assays still needs to be demonstrated rigorously in different ethnic minority populations. First trimester testing is unlikely to alter this picture significantly although other emerging technologies may.

High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD-negative women not known to be sensitised to the RhD antigen: a systematic review and economic evaluation

“…Macher et al 70 and Hawk et al 72 stated that their analysis considered RhD-negative pregnant women but they were not clear about women's sensitisation status at study entry. Only two studies 68,73 explicitly stated that a high-throughput NIPT method was being used for the comparative assessment, although for the other studies this was considered implicit, as the test diagnostic performance was considered similar to the high-throughput studies. One study 71 explicitly focused on providing NIPT to all RhD-negative women, as the test for sensitisation was conducted only if the NIPT result was positive.…”

“…Of those, seven met the selection criteria and were included in the review. 58,[68][69][70][71][72][73] A flow diagram of the selection process is reported in Figure 10.…”

“…Most studies 58,68,[71][72][73] evaluated the cost-effectiveness of introducing NIPT in the management pathway of RhD-negative pregnant women compared with alternative strategies. These studies explored a range of alternative strategies to prevent sensitisation.…”

“…These studies explored a range of alternative strategies to prevent sensitisation. Except for Szczepura et al 68 Total full papers screened (n = 10)…”

“…Three studies 58,68,73 aimed to evaluate the short-term costs and consequences of sensitisation in RhD-negative women. Duplantie et al 71 and Hawk et al, 72 however, estimated long-term outcomes relating to morbidity and mortality attributable to haemolytic disease of the fetus and/or newborn infant.…”