Abstract | BACKGROUND: OBJECTIVE: The objective was to evaluate the potential clinical, patient, and economic outcomes associated with the use of A1555G testing in a cystic fibrosis population, and explore data gaps and uncertainty in its clinical implementation. METHODS: We developed a decision-analytic model to evaluate a hypothetical cohort of patients with cystic fibrosis from a societal perspective. Clinical and economic data were derived primarily from a critical literature review. The incidence of aminoglycoside-induced severe hearing loss, quality-adjusted life-years, and total health care costs were evaluated. Sensitivity analyses were conducted to evaluate uncertainty in our results. RESULTS: In the base-case analysis, A1555G testing decreased the risk of severe aminoglycoside-induced hearing loss by 0.12% in the cystic fibrosis population. The discounted incremental cost per quality-adjusted life-years gained was $79,300, but varied widely from $33,000 to testing being dominated by the no testing strategy (higher costs and lower quality-adjusted life-years with testing) in sensitivity analyses. If avoidance of aminoglycosides in patients testing positive leads to an absolute increase in the lifetime risk of death from Pseudomonas infection of 0.8% or greater, A1555G testing would lead to a decrease in quality-adjusted life-years. CONCLUSIONS: The results of our analysis suggest that there are significant data gaps and uncertainty in the outcomes with A1555G testing, but it is not likely cost-effective, and could lead to worse patient outcomes due to avoidance of first-line therapy in the >95% of patients who are false-positives. Additional research is needed before pharmacogenetic testing for the A1555G mitochondrial mutation can be recommended, even in a population with a high likelihood of exposure to aminoglycosides.
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Authors | David L Veenstra, Julie Harris, Ronald L Gibson, Margaret Rosenfeld, Wylie Burke, Carolyn Watts |
Journal | Genetics in medicine : official journal of the American College of Medical Genetics
(Genet Med)
Vol. 9
Issue 10
Pg. 695-704
(Oct 2007)
ISSN: 1530-0366 [Electronic] United States |
PMID | 18073583
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Aminoglycosides
- Anti-Bacterial Agents
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Topics |
- Adolescent
- Adult
- Aminoglycosides
(adverse effects)
- Anti-Bacterial Agents
(adverse effects)
- Child
- Cohort Studies
- Cost-Benefit Analysis
- Cystic Fibrosis
(complications, economics)
- Genetic Predisposition to Disease
- Hearing Loss
(chemically induced, prevention & control)
- Humans
- Mitochondria
(genetics)
- Mutation
- Outcome Assessment, Health Care
- Pharmacogenetics
- Quality-Adjusted Life Years
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