An economic evaluation of functional genomics testing for individuals with undiagnosed rare disorders

PURPOSE: Functional genomics (FG) approaches, such as RNA-sequencing and proteomics, offer a complementary diagnostic modality for individuals whose cases remain unsolved after genomic sequencing. This study evaluates the cost-effectiveness and cost-benefit of FG for individuals with suspected monogenic disorders relative to the manual reanalysis of genomic data at 18 months. METHODS: A decision tree model compared the costs and outcomes of FG and 18-month reanalysis using data from 2 Australian Undiagnosed Disease Programs. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: With a diagnostic yield of 13%, FG enabled 4 additional diagnoses per 100 individuals tested at an additional cost of $390 (US$240), resulting in an incremental cost-effectiveness ratio of $8550 (US$5313) and an 85% probability of being cost-effective. CONCLUSION: FG enables timely diagnosis for individuals with suspected monogenic disorders by evaluating the functional impact of variants of uncertain significance, offering an advantage over reanalyzing genomic data at 18 months. Integration into the Australian health care system, supported by collaborative networks and secure data-sharing infrastructure, coupled with addressing barriers to accessing funded genomic testing, could lead to an annual net benefit of up to $1.1 million ($0.7 million).