Integration of Whole genome sequencing in pediatric healthcare: an Italian HTA

Abstract Diagnosing pediatric rare diseases poses challenges due to ambiguous symptoms and genetic complexities. Next-generation sequencing (NGS) technologies, like Whole exome sequencing (WES) and Whole genome sequencing (WGS), offer faster and more accurate diagnoses, enhancing clinical utility. However, WGS implementation faces hurdles including complexity and socio-economic impacts. This Health Technology Assessment (HTA) aims to evaluate the integration of WGS, compared to WES, into the Italian NHS for pediatric genetic disorder diagnosis, considering diverse stakeholders and value generation. The EUnetHTA Core Model 3.0 was the primary framework for evaluations. Various methodologies, such as narrative, scoping, and systematic reviews, meta-analysis, GRADE assessment were employed to assess existing evidence. Bayesian cost-effectiveness analyses were adopted for the economic aspects. Summative thematic analysis was used to evaluate organizational aspects of implementing WGS. In respect to non-clinical domains, organizational differences between WES and WGS implementation were seen in respect to procedural steps (i.e., genome rearrangement analysis, data storage) albeit both reduce the need for additional tests. WGS is cost-effective, with Bayesian analysis revealing incremental cost per additional diagnosis lower than the threshold. Ethically, WGS benefits outweigh risks, but comprehensive genetic counseling should address concerns like unsolicited findings and misattributed parentage. Timely genetic diagnosis through genomic technologies may shorten the diagnostic odyssey ensuring brighter futures for children and advancing health care equity. Nevertheless, the implementation of genomic knowledge in clinical practice brings organizational, economic, and ethical issues urging critical reflection in HTA evaluations and a multi-stakeholders involvement. Speakers/Panelists Gianfranco Damiani Università Cattolica del Sacro Cuore, Rome, Italy Els Maeckelberghe University Medical Center Groningen, Groningen, Netherlands João Vasco Santos University of Porto, CINTESIS, ARS Norte, Porto, Portugal Sandra García Armesto Agència de Qualitat i Avaluació Sanitàries de Catalunya, AQuAS, Barcelona, Spain