Genet Med. 2014 Nov 13. doi: 10.1038/gim.2014.156. [Epub ahead of print]

The cost-effectiveness of returning incidental findings from next-generation genomic sequencing.

Bennette CS1, Gallego CJ2, Burke W3, Jarvik GP4, Veenstra DL5.

Author information

• 1Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington, USA.
• 21] Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington, USA [2] Department of Medicine and Genome Sciences, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
• 3Department of Bioethics and Humanities, University of Washington, Seattle, Washington, USA.
• 4Department of Medicine and Genome Sciences, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
• 51] Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington, USA [2] Institute for Public Health Genetics, University of Washington, Seattle, Washington, USA.

Abstract

Purpose:The American College of Medical Genetics and Genomics (ACMG) recommended that clinical laboratories performing next-generation sequencing analyze and return pathogenic variants for 56 specific genes it considered medically actionable. Our objective was to evaluate the clinical and economic impact of returning these results.Methods:We developed a decision-analytic policy model to project the quality-adjusted life-years and lifetime costs associated with returning ACMG-recommended incidental findings in three hypothetical cohorts of 10,000 patients.Results:Returning incidental findings to cardiomyopathy patients, colorectal cancer patients, or healthy individuals would increase costs by $896,000, $2.9 million, and $3.9 million, respectively, and would increase quality-adjusted life-years by 20, 25.4, and 67 years, respectively, for incremental cost-effectiveness ratios of $44,800, $115,020, and $58,600, respectively. In probabilistic analyses, returning incidental findings cost less than $100,000/quality-adjusted life-year gained in 85, 28, and 91%, respectively, of simulations. Assuming next-generation sequencing costs $500, the incremental cost-effectiveness ratio for primary screening of healthy individuals was $133,400 (<$100,000/quality-adjusted life-year gained in 10% of simulations). Results were sensitive to the cohort age and assumptions about gene penetrance.Conclusion:Returning incidental findings is likely cost-effective for certain patient populations. Screening of generally healthy individuals is likely not cost-effective based on current data, unless next-generation sequencing costs less than $500.