Health Technology Assessment of genetic testing for susceptibility to Venous Thromboembolism in Italy

Venous Thromboembolism (VTE) is one of the leading causes of mortality and morbidity in the developed world. Factor II (PTM) G20210A, factor V Leiden (FVL) G1691A and Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms are the most common inherited risk factors for VTE. Oral contraceptives (OC) users among carriers of these polymorphic variants show a particularly increased risk of VTE. The aim of the study was to realize a Health Technology Assessment (HTA) report on genetic testing for susceptibility to VTE. Methods To evaluate all the implications regarding the use of genetic susceptibility tests for VTE, the ACCE model was used, which considers four main dimensions of evaluation: Analytic validity (A), Clinical validity (C), Clinical utility (C) and Ethical (E), legal and social implications. A survey to describe the Italian scenario of genetic testing provision strategies was performed using a questionnaire ad hoc. Clinical validity of tests was assessed through meta-pooled analysis of the literature. A meta-analysis was carried out to evaluate the risk of VTE among OC users, in order to assess clinical utility. Additionally, for the economic evaluation, a cost-effectiveness analysis was performed. An expert opinion was sought for a comprehensive ethical evaluation. Results In Italy the screening for PTM, FVL and MTHFR polymorphisms accounts for around 25% of all genetic tests performed in adults, with a growing trend in recent years. Results of the meta- pooled analysis showed a significantly increased risk of VTE for the carriers of FVL and PTM polymorphism. Odds Ratios (OR) and 95%Confidence Intervals were as follows: OR= 3.51 (2.53–4.87) for FVL and OR= 2.47 (1.86–3.29) for PTM. Among women with one of the thrombogenic mutations, those using OCs had a significantly higher risk of developing VTE. Currently, performing these genetic tests does not seem to be cost-effective in Italy. Minor ethical issues were raised regarding the prescription of these tests. Conclusions The evaluation of genetic testing for VTE suffer from a lack of evidence. Given this limitation, a comprehensive approach like HTA is important to address the decision making process and to make possible to translate the human genome discoveries into public health practice.