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

Genet Med. 2015 Jul;17(7):587-95. doi: 10.1038/gim.2014.156. Epub 2014 Nov 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cost-Benefit Analysis
  • Decision Support Techniques
  • Female
  • Genomics / economics*
  • Genomics / methods*
  • High-Throughput Nucleotide Sequencing / economics*
  • High-Throughput Nucleotide Sequencing / methods*
  • Humans
  • Incidental Findings
  • Male
  • Models, Statistical
  • Quality-Adjusted Life Years
  • United States