Background:
Molecular genetic diagnostics (GDx) is an increasingly important tool in the so called personalised medicine or precision healthcare. With the discovery of functional gene sequences that cause familial hypercholesterolaemia (FH) (LDLR, ApoB, PCSK9), GDx has also gained importance in endocrinology and internal medicine, particularly as a triage mechanism for risk stratification in the prevention of arteriosclerosis and coronary heart disease.

Method:
The overview of recommended or implemented (inter)national FH test strategies was based on an iterative manual literature search. Expert interviews were conducted to answer questions on the Austrian situation and Austrian-specific organisational aspects. Ethical aspects of (predictive) genetic diagnostics were identified using Hofmann's questionnaire. In order to assess the economic implications, a resource impact analysis (RIA) from the perspective of public funding agencies was conducted for a one-year time horizon based on the FH model of the National Institute for Health and Care Excellence (NICE).

Results:
Numerous characteristic treatment components in internationally recommended or already implemented test strategies for the diagnosis of FH could be identified. These include the method for identifying so called FH index patients, the clinical criteria for diagnosis, the use of GDx and recommendations for cascade screening and genetic counselling. In Austria, a systematically organised FH testing strategy is currently neither formally recommended nor actually implemented. From an ethical point of view, genetic counselling is particularly relevant, since the complex decisions that patients have to make require professional support. With regard to resource impact analysis, the largest cost factor seems to be the molecular genetic test, but a number of other cost components must be taken into account.

Conclusion:
The report shows, regardless of the respective FH test strategy, that the (systematic) implementation of GDx entails a number of organisational challenges, such as the definition of concrete steps of action and responsible personnel, as well as the provision of sufficient and well-trained genetic counsellors and their close logistical connection to the clinical and laboratory processes of genetic diagnosis. Moreover, the organised introduction of GDx can lead to considerable cost increases, which are significantly higher than those of the actual test itself. A thorough effectiveness and cost-effectiveness analysis for the Austrian context should therefore be carried out before implementation.