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


CONCLUSIONS
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.
Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington, USA.
Caroline S
CS
Bennette
1] 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.
Carlos J
CJ
Gallego
Department of Bioethics and Humanities, University of Washington, Seattle, Washington, USA.
Wylie
W
Burke
Department of Medicine and Genome Sciences, Division of Medical Genetics, University of Washington, Seattle, Washington, USA.
Gail P
GP
Jarvik
1] Pharmaceutical Outcomes Research and Policy Program, University of Washington, Seattle, Washington, USA [2] Institute for Public Health Genetics, University of Washington, Seattle, Washington, USA.
David L
0000000267108708
DL
Veenstra
D003362:Cost-Benefit Analysis; D003661:Decision Support Techniques; D005260:Female; D023281:Genomics / Q000191:economics* / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000191:economics* / Q000379:methods*; D006801:Humans; D033162:Incidental Findings; D008297:Male; D015233:Models, Statistical; D019057:Quality-Adjusted Life Years; D014481:United States