Costs and cost-effectiveness of returning secondary findings from genomic sequencing based on the return of additional findings in the 100,000 Genomes Project

Purpose

To assess costs and cost-effectiveness of returning additional findings from genome sequencing using data from the 100,000 Genomes Project (100kGP).

Methods

A model-based cost-utility analysis combining yield, consent rates, and cost data from the 100kGP with published estimates of downstream costs and quality-adjusted life years expected to accrue over a lifetime, after the identification of a pathogenic variant.

Results

The cost of returning additional findings to participants in the 100kGP was £7.1m or £81 per participant, with a yield of 0.85% for consented participants. The estimated lifetime incremental cost per participant was £125 and quality-adjusted life years 0.004, giving an incremental cost-effectiveness ratio of £28,830. Implementing a policy of returning additional findings is unlikely to be cost-effective (ie, 13%) at a willingness-to-pay threshold of £20,000. A short-term cost of returning findings of £43 per participant or lower (compared with the base case of £81) would result in an incremental cost-effectiveness ratio of less than £20,000. Alternatively, cost-effectiveness may be improved by returning additional findings to younger patient populations.

Conclusion

Return of additional findings following genome sequencing for this group of conditions may not be a cost-effective use of health care system resources. Our cost-effectiveness outcomes rely on published estimates and should be validated through long-term follow-up data.