Determining Cost-Optimal Next-Generation Sequencing Panels for Rare Disease and Pharmacogenomics Testing

Abstract Background Multi–gene panel sequencing using next-generation sequencing (NGS) methods is a key tool for genomic medicine. However, with an estimated 140 000 genomic tests available, current system inefficiencies result in high genetic-testing costs. Reduced testing costs are needed to expand the availability of genomic medicine. One solution to improve efficiency and lower costs is to calculate the most cost-effective set of panels for a typical pattern of test requests. Methods We compiled rare diseases, associated genes, point prevalence, and test-order frequencies from a representative laboratory. We then modeled the costs of the relevant steps in the NGS process in detail. Using a simulated annealing-based optimization procedure, we determined panel sets that were more cost-optimal than whole exome sequencing (WES) or clinical exome sequencing (CES). Finally, we repeated this methodology to cost-optimize pharmacogenomics (PGx) testing. Results For rare disease testing, we show that an optimal choice of 4–6 panels, uniquely covering genes that comprise 95% of the total prevalence of monogenic diseases, saves $257–304 per sample compared with WES, and $66–135 per sample compared with CES. For PGx, we show that the optimal multipanel solution saves $6–7 (27%–40%) over a single panel covering all relevant gene–drug associations. Conclusions Laboratories can reduce costs using the proposed method to obtain and run a cost-optimal set of panels for specific test requests. In addition, payers can use this method to inform reimbursement policy.