| dc.description.abstract | Summary Introduction: Down syndrome (DS) is a condition when a child is born with all or part of a third copy of chromosome 21 in some or all the body cells and is the most frequent chromosomal abnormality in humans and affects anywhere between one in 400 to 1500 pregnancies. DS can be fatal or result in various kinds of disabilities. DS can be identified early in the pre-natal stage of pregnancy through various screening tests with varying accuracy which helps a woman make a decision to avoid a pregnancy with DS or not. Objectives: The objective of this study was to evaluate the cost-effectiveness of various prenatal screening methods for DS in terms of cost per number of cases detected compared to no screening from a health care perspective. Methods: Various screening tests like maternal serum marker tests, NIPT and nuchal translucency (NT), were compared to no screening. The total costs and the number of cases detected were calculated using a decision tree for three different age groups of singleton pregnant women (15-49 years, 35 years or above, and 40 years and above) and one special scenario (40 years and above with coinsurance). Sensitivity analyses (one-way, two-way and scenario analysis) and probabilistic analysis (PA) were conducted to validate the findings of the deterministic analysis. The results from cost-effectiveness analysis (CEA) was also supplemented by safety related outcomes like safety index and harm to benefit analysis, and budget impact analysis. Finally, a value of information (VOI) analysis through expected value of perfect information (EVPI) and expected value of partial perfect information (EVPPI) was also carried out to explore the possibility of collection of information of input parameters. Results: The cost per detected case of DS ranged from $37661, $11794, $8940 (general population, >35 years and >40 years) for NT to $343473, $102306, $70688 (general population, >35 years and >40 years) for NIPT. The number of fetal losses due to amniocentesis varied from 12, 8, 18 (general population, >35 years and >40 years) for NIPT to 552, 173, 113 (general population, >35 years and >40 years) for QT. No screening strategy was found to be cost-effective at a threshold of $3,000 per incremental case detected regardless of the age group. NIPT was the safest strategy in terms of the number of fetal loss, but CUB had the best combination of cost, case detected, and the number of fetal loss. However, NT was found to be cost-effective in a special scenario for women 40 years or older, where the cost is decreased by 70%. One way of achieving this is introduction of coinsurance (30% for health payer-70% for the individual), with an ICER (same as CER) of $2689 per additional case detected (52% probability of being cost-effective from PA analysis). Sensitivity analyses (both one-way and two-way) showed that incidence of DS, cost of individual, cost of amniocentesis, and respective test sensitivities affected the CER and ICER values. However, no interventions were cost-effective for any of the age-groups even in the best case-scenario at the current willingness to pay (WTP) threshold. VOI analysis for all the three age groups show that there is no value added by the collection of perfect information of all the input parameters (EVPI=0) at the current WTP threshold. However, collection of perfect information on all the parameters can be worthwhile and help in making decision with more certainty population EVPI=$124,700 per year). Similarly, collection of information on probabilities of spontaneous miscarriages and foetal loss due to amniocentesis (population EVVPI= $118,020 per year) would bring the most value in decision making followed by test input values i.e. sensitivities and false-positive rates (population EVVPI= $47,530 per year). Information on acceptance rates of screening and diagnostic tests is worthwhile if the total cost of research does not exceed $27,584 per year (population EVVPI= $27,584 per year). Lastly, NT had the lowest budget (in millions) over the course of five years i.e. $78.66, $24.63 and $16.35 (general population, >35 years and >40 years) with NIPT being the costliest intervention to implement with more than ten times the cost of NT. Conclusion: The choice of prenatal screening strategies for Nepal at the current willingness to pay threshold is straightforward, i.e., no screening regardless of the age group. NT can be introduced as a screening strategy only if provided to women 40 years and older if the cost is decreased by 70%. One way of achieving this is introduction of coinsurance where the cost of NT is divided between the health system and individual. VOI analysis shows that the collection of further information is worthwhile for some group of parameters for this special scenario. | eng |