1106 Cost-Effectiveness analysis of genetic testing for stillbirth: balancing cost and diagnostic rate

Abstract

Whole exome sequencing (WES) has recently been shown to be useful in determining genetic causes of stillbirth, further adding complexity to currently available technologies. We aim to perform cost-effectiveness analysis of algorithms in genetic testing for stillbirth. Literature review was performed to obtain data regarding the performance of karyotype, chromosomal microarray (CMA) and WES on stillbirth. We created 10 approaches for various testing algorithms using karyotype, CMA and WES. Reflex testing is defined as testing if the previous result was negative OR failed to yield results. Point simulations using these 12 different algorithms were done to calculate expected annual total diagnosis, hit-rate, cost/diagnosis and missed diagnosis assuming national birth rate of 3,788,235 births/year and stillbirth rate of 0.6% (Table 1). We then selected four algorithms with the highest hit-rate without WES and the two algorithms with WES and performed Monte Carlo simulations by letting the parameters vary to provide cost/diagnosis ranges estimate for each selected algorithm. One-way ANOVA was used to compare cost/diagnosis for each algorithm. The results of the point simulations were shown in Table 1. Figure 1 shows the result of Monte Carlo simulation of cost/diagnosis for the 6 selected algorithms. Universal karyotype with reflex CMA for culture failure only and universal CMA only have the lowest median cost/diagnosis at $7,122.61 and $9,863.61, respectively. Despite being used frequently, reflex CMA with culture failure OR normal karyotype does not appear to be cost-effective. At present, the cost of WES is likely still prohibitive for its widespread usage in stillbirth. The option of which algorithm to use could vary from one place and another depending on the willingness to pay and desired hit rate. To aid health systems and policy makers, we have created a calculator to show the calculation result using different birth rate and cost of testing. http://bit.ly/StillBirthCalc (download and click to open the file to access the calculator).View Large Image Figure ViewerDownload Hi-res image Download (PPT)