Position statement from the Italian Society of Human Genetics (SIGU) on the implementation of germline pharmacogenetic testing

The Italian Society of Human Genetics (SIGU) Working Group on Pharmacogenomics has released recommendations for the implementation, interpretation and reporting of germline pharmacogenetic testing in clinical practice within the Italian National Health Service (SSN). These guidelines outline the key principles for the responsible use, reporting, and interpretation of pharmacogenetic data, emphasizing clinical validity, clinical utility, cost-effectiveness, and ethical considerations. With the aim of promoting a systematic standardized, and evidence-based implementation of germline pharmacogenetic testing in Italy, SIGU strongly recommends addressing the following points: (1) Pharmacogenetic testing should be performed based on validated scientific evidence, primarily following Association for Molecular Pathology (AMP) and Dutch Pharmacogenetics Working Group (DPWG) guidelines, and restricted to gene-drug pairs with ClinPGx clinical annotation level 1 A. (2) Patients must be appropriately informed and provide specific consent, particularly when pharmacogenetic data are derived as secondary findings from diagnostic next generation sequencing (NGS) analyses. (3) Testing should prioritize clinically actionable variants that influence therapeutic efficacy or prevent severe adverse drug reactions. (4) The interpretation and reporting of results must be carried out by a qualified geneticist in collaboration with clinical pharmacologists to ensure appropriate therapeutic recommendations. (5) The implementation of pharmacogenetic testing should be supported by robust quality assurance procedures in laboratories, in line with international standards. (6) The inclusion of pharmacogenetic tests in the Italian LEA (Essential Levels of Assistance) should be updated in accordance with international evidence and EMA-AIFA recommendations. (7) Further pharmaco-economic and psychosocial research is needed to evaluate the impact of pre-emptive versus reactive testing strategies on patient outcomes and healthcare sustainability.