Genomic testing for the diagnosis of heritable cardiomyopathies

Tamblyn D, Vogan A, Parsons J, Carter D, Schubert C, Bellman S
Record ID 32018002418
Original Title: MSAC application 1599
Authors' objectives: To assess the safety, clinical effectiveness and cost-effectiveness of genetic testing for heritable cardiomyopathies in affected individuals, as well as cascade testing in biological relatives and in reproductive partners of people with recessively inherited variants. Data re-analysis was also considered. The test comprised a panel of 22 genes associated with cardiomyopathies. Three types of cardiomyopathy were considered: hypertrophic (HCM), dialated (DCM) and arrythmogenic (ACM). This HTA was conducted for the Australian Government to inform decision making regarding the public funding of the test through the Medicare Benefits Schedule.
Authors' results and conclusions: Safety: Genetic testing was non-inferior to no genetic testing. Effectiveness: The clinical effectiveness of the test was deemed to be non-inferior to no genetic testing in affected patients, as genotyping usually does not change clinical management. For some rare variants, genotype will change management, for example through the implantation of an implantable cardioverter-defibrillator. However the evidence informing this change of management is of poor quality, with the key uncertainty being if the ICD is implanted based on the genotype or on the basis of phenotypic findings. In family members, genetic testing was found to have non-inferior safety and superior effectiveness; this is because the key benefit of genetic testing compared to no testing was realised in cascade testing, where individuals at future risk of cardiomyopathy can be identified and monitored, with possible early intervention offered. Conversely, monitoring can be avoided by those without the variant. Key uncertainties remained around whether genetic testing increased compliance with ongoing monitoring or if monitoring had an impact on health outcomes. Cost-effectiveness: cost-effectiveness and cost-utility analyses were conducted. The analyses found that the cost of genetic testing was largely offset by monitoring costs in relatives found to be genotype-negative. It was noted that the change in management of the small number of patients with actionable variants contributed to only a relatively small incremental QALY gain (spread across the total eligible population), and the model was most sensitive to choice of discount rate, model time horizon, yield in affected cases, number of relatives eligible for testing, uptake of periodic monitoring, the treatment effect of ICDs modelled and the inclusion of a utility benefit in genotype-negative relatives. The test was approved for public funding at the Medical Services Advisory Committee meeting in April 2021.
Authors' methods: A systematic review to assess the safety and clinical effectiveness of genetic testing for cardiomyopathies was undertaken. The PPICO criteria guided the review. There were 142 studies included in the systematic review across clinical validity and clinical utility in the index patient, and clinical validity and clinical utility in the cascade population. The economic analysis comprised a cost-utility analysis, with sensitivity analyses.
Project Status: Completed
Year Published: 2021
English language abstract: An English language summary is available
Publication Type: Not Assigned
Country: Australia
MeSH Terms
  • Genetic Testing
  • Cardiomyopathies
  • Cardiomyopathy, Hypertrophic
  • Genomics
  • Diagnostic Techniques, Cardiovascular
  • cardiomyopathy
  • hypertrophic cardiomyopathy
  • dilated cardiomyopathy
  • arrythmogenic cardiomyopathy
  • genetic test
  • genotyping
  • cascade testing
Organisation Name: Adelaide Health Technology Assessment
Contact Address: School of Public Health, Mail Drop 545, University of Adelaide, Adelaide SA 5005, AUSTRALIA, Tel: +61 8 8313 4617
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Adelaide Health Technology Assessment (AHTA) on behalf of NICS

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