title: Cost-effectiveness of MODY genetic testing: translating genomic advances into practical health applications.
abstract: OBJECTIVE To evaluate the cost-effectiveness of a genetic testing policy for HNF1A-, HNF4A-, and GCK-MODY in a hypothetical cohort of type 2 diabetic patients 25-40 years old with a MODY prevalence of 2%. RESEARCH DESIGN AND METHODS We used a simulation model of type 2 diabetes complications based on UK Prospective Diabetes Study data, modified to account for the natural history of disease by genetic subtype to compare a policy of genetic testing at diabetes diagnosis versus a policy of no testing. Under the screening policy, successful sulfonylurea treatment of HNF1A-MODY and HNF4A-MODY was modeled to produce a glycosylated hemoglobin reduction of -1.5% compared with usual care. GCK-MODY received no therapy. Main outcome measures were costs and quality-adjusted life years (QALYs) based on lifetime risk of complications and treatments, expressed as the incremental cost-effectiveness ratio (ICER) (USD/QALY). RESULTS The testing policy yielded an average gain of 0.012 QALYs and resulted in an ICER of 205,000 USD. Sensitivity analysis showed that if the MODY prevalence was 6%, the ICER would be ~50,000 USD. If MODY prevalence was >30%, the testing policy was cost saving. Reducing genetic testing costs to 700 USD also resulted in an ICER of ~50,000 USD. CONCLUSIONS Our simulated model suggests that a policy of testing for MODY in selected populations is cost-effective for the U.S. based on contemporary ICER thresholds. Higher prevalence of MODY in the tested population or decreased testing costs would enhance cost-effectiveness. Our results make a compelling argument for routine coverage of genetic testing in patients with high clinical suspicion of MODY.
authors.affiliation: Corresponding author: Rochelle N. Naylor, rnaylor@bsd.uchicago.edu.
authors.forename: Rochelle N
authors.initials: RN
authors.lastname: Naylor
authors.forename: Priya M
authors.initials: PM
authors.lastname: John
authors.forename: Aaron N
authors.initials: AN
authors.lastname: Winn
authors.forename: David
authors.initials: D
authors.lastname: Carmody
authors.forename: Siri Atma W
authors.initials: SA
authors.lastname: Greeley
authors.forename: Louis H
authors.initials: LH
authors.lastname: Philipson
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: Elbert S
authors.initials: ES
authors.lastname: Huang
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003362:Cost-Benefit Analysis; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000191:economics*; D023281:Genomics / Q000639:trends*; D000081410:Germinal Center Kinases; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D008297:Male; D008962:Models, Theoretical; D017063:Outcome Assessment, Health Care; D057285:Precision Medicine; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D019057:Quality-Adjusted Life Years; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D057170:Translational Research, Biomedical / Q000639:trends*; D014481:United States
chemical_list: D000081410:Germinal Center Kinases; C496487:HNF1A protein, human; C496592:HNF4A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; D013453:Sulfonylurea Compounds; D017346:Protein Serine-Threonine Kinases
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