Public health genomics research in Italy: an overview of ongoing projects.

Public health genomics (PHG) aims to integrate advances in genomic sciences into healthcare for the benefit of the general population. As in many countries, there are various research initiatives in this field in Italy, but a clear picture of the national research portfolio has never been sketched. Thus, we aimed to provide an overview of current PHG research projects at the national or international level by consultation with Italian institutional and academic experts. We included 68 PHG projects: the majority were international projects in which Italian researchers participated (n = 43), mainly funded by the European Commission, while the remainder were national initiatives (N = 25), mainly funded by central government. Funding varied considerably, from € 50,000 to € 80,803,177. Three main research themes were identified: governance (N = 20); precision medicine (PM; N = 46); and precision public health (N = 2). We found that research activities are preferentially aimed at the clinical application of PM, while other efforts deal with the governance of the complex translation of genomic innovation into clinical and public health practice. To align such activities with national and international priorities, the development of an updated research agenda for PHG is needed.

Managing the introduction of genomic applications into the National Health Service: A special challenge for health technology assessment in Italy.

In recent years, the rapid proliferation of genomic tests for use in clinical practice has prompted healthcare systems to use a health technology assessment (HTA) approach to distinguish valuable from unwarranted applications. In this study, we narratively review the Italian HTA mechanisms for medical devices (MDs), both at the national and regional levels, and discuss the opportunity and benefits of extending them to genomic technologies, for which a dedicated assessment path was advocated by the National Plan for Public Health Genomics in 2017. We found that the National Health Technology Assessment Program for MDs, completed in 2019, had developed a structured pathway for the HTA of MDs; it established a hub-and-spoke structure, run by a governmental institution, and put in place transparent methodological procedures to cover all four HTA phases (i.e., proposal and prioritization, assessment, appraisal, and dissemination). However, several factors have hindered its adoption, and the regions are at different stages of its implementation. For these reasons, efforts should be made to ensure its effective deployment, both at national and regional levels. In addition, we argue that to harmonize the institutional roles and methodological procedures adopted, the time has come to concentrate resources on a single pathway for the assessment of all technologies that include both MDs and genomic applications.

Time to Align: A Call for Consensus on the Assessment of Genetic Testing.

In this paper, we updated our 2018 systematic review aimed to identify and compare ad hoc designed frameworks for genetic testing evaluation. Overall, we identified 30 frameworks (29 in the first systematic review and one in the update): they were mainly based on the ACCE model, whereas a minority were adjustments of the more traditional Health Technology Assessment (HTA) approach. After discussing the strengths and weaknesses of the retrieved frameworks, this perspective calls for consensus on the assessment of genetic testing. In line with the recent European recommendations that encouraged the generation of comparable evidence across Member States, we believe that the time has come to align all the ideas that have emerged over the last few decades and find a sustainable and sharable tool for the evaluation of genetic and genomic applications. Therefore, we suggest stopping the evaluation of such technologies using ad hoc strategies-affected by validation, implementation, and adoption issues-and we propose to use a general HTA approach, particularly the European reference tool for the assessment of health technologies, the EUnetHTA HTA core model, that is built on solid theoretical and methodological principles and provides a comprehensive assessment of the technologies value.

How Public Health Professionals View Mandatory Vaccination in Italy-A Cross-Sectional Survey.

In response to the decline in child vaccination coverage and the subsequent occurrence of large vaccine-preventable disease outbreaks, in 2017 Italy introduced a new law that made ten vaccines mandatory for children aged 0-16 years. The policy change initiated an ongoing debate among the general public, as well as in the political arena and the scientific community, over this major public health concern. Hence, we conducted a survey aimed at assessing Italian public health professionals' attitudes towards and opinions on mandatory vaccination. A validated online questionnaire was administered to 1350 members of the Italian Society of Hygiene, Preventive Medicine and Public Health. Among the 1044 responders (response rate 77%), a large majority were in favour of the Italian mandatory vaccination law (91%) and against its repeal (74%). Nevertheless, according to our sample, maintaining a high level of vaccination coverage without the need to mandate would be preferable, and thus efforts to promote vaccine confidence and proactive vaccine uptake are still needed.

Precision Medicine and Public Health: New Challenges for Effective and Sustainable Health.

The development of high-throughput omics technologies represents an unmissable opportunity for evidence-based prevention of adverse effects on human health. However, the applicability and access to multi-omics tests are limited. In Italy, this is due to the rapid increase of knowledge and the high levels of skill and economic investment initially necessary. The fields of human genetics and public health have highlighted the relevance of an implementation strategy at a national level in Italy, including integration in sanitary regulations and governance instruments. In this review, the emerging field of public health genomics is discussed, including the polygenic scores approach, epigenetic modulation, nutrigenomics, and microbiomes implications. Moreover, the Italian state of implementation is presented. The omics sciences have important implications for the prevention of both communicable and noncommunicable diseases, especially because they can be used to assess the health status during the whole course of life. An effective population health gain is possible if omics tools are implemented for each person after a preliminary assessment of effectiveness in the medium to long term.

Genomics knowledge and attitudes among European public health professionals: Results of a cross-sectional survey.

BACKGROUND: The international public health (PH) community is debating the opportunity to incorporate genomic technologies into PH practice. A survey was conducted to assess attitudes of the European Public Health Association (EUPHA) members towards their role in the implementation of public health genomics (PHG), and their knowledge and attitudes towards genetic testing and the delivery of genetic services. METHODS: EUPHA members were invited via monthly newsletter and e-mail to take part in an online survey from February 2017 to January 2018. A descriptive analysis of knowledge and attitudes was conducted, along with a univariate and multivariate analysis of their determinants. RESULTS: Five hundred and two people completed the questionnaire, 17.9% were involved in PHG activities. Only 28.9% correctly identified all medical conditions for which there is (or not) evidence for implementing genetic testing; over 60% thought that investing in genomics may divert economic resources from social and environmental determinants of health. The majority agreed that PH professionals may play different roles in incorporating genomics into their activities. Better knowledge was associated with positive attitudes towards the use of genetic testing and the delivery of genetic services in PH (OR = 1.48; 95% CI 1.01-2.18). CONCLUSIONS: Our study revealed quite positive attitudes, but also a need to increase awareness on genomics among European PH professionals. Those directly involved in PHG activities tend to have a more positive attitude and better knowledge; however, gaps are also evident in this group, suggesting the need to harmonize practice and encourage greater exchange of knowledge among professionals.

Cost-Effectiveness of RAS Genetic Testing Strategies in Patients With Metastatic Colorectal Cancer: A Systematic Review.

BACKGROUND: Monoclonal antibodies against epidermal growth factor receptor (EGFR) have proved beneficial for the treatment of metastatic colorectal cancer (mCRC), particularly when combined with predictive biomarkers of response. International guidelines recommend anti-EGFR therapy only for RAS (NRAS,KRAS) wild-type tumors because tumors with RAS mutations are unlikely to benefit. OBJECTIVES: We aimed to review the cost-effectiveness of RAS testing in mCRC patients before anti-EGFR therapy and to assess how well economic evaluations adhere to guidelines. METHODS: A systematic review of full economic evaluations comparing RAS testing with no testing was performed for articles published in English between 2000 and 2018. Study quality was assessed using the Quality of Health Economic Studies scale, and the British Medical Journal and the Philips checklists. RESULTS: Six economic evaluations (2 cost-effectiveness analyses, 2 cost-utility analyses, and 2 combined cost-effectiveness and cost-utility analyses) were included. All studies were of good quality and adopted the perspective of the healthcare system/payer; accordingly, only direct medical costs were considered. Four studies presented testing strategies with a favorable incremental cost-effectiveness ratio under the National Institute for Clinical Excellence (£20 000-£30 000/QALY) and the US ($50 000-$100 000/QALY) thresholds. CONCLUSIONS: Testing mCRC patients for RAS status and administering EGFR inhibitors only to patients with RAS wild-type tumors is a more cost-effective strategy than treating all patients without testing. The treatment of mCRC is becoming more personalized, which is essential to avoid inappropriate therapy and unnecessarily high healthcare costs. Future economic assessments should take into account other parameters that reflect the real world (eg, NRAS mutation analysis, toxicity of biological agents, genetic test sensitivity and specificity).

Factors affecting the vaccination choices of pregnant women for their children: a systematic review of the literature.

In recent years, an increase in vaccine hesitancy has led to a decrease in vaccination coverage in several countries. We conducted a systematic review of studies that assessed knowledge of and attitudes toward pediatric vaccinations, and the vaccination choices and their determinants among pregnant women. A total of 6,277 records were retrieved, and 16 full texts were included in the narrative synthesis. The published literature on the topic shows that, overall, pregnant women believe that vaccines are important for the protection of their children and the community, but various concerns and misunderstandings persist around vaccine safety and efficacy, which reduce the trust of expectant mothers in immunization. Nevertheless, such attitudes and choices vary depending on the vaccine being considered and the corresponding determinants should therefore be studied in the context of each specific vaccination. Further research on this topic is needed, particularly in non-western countries.

Value-based genomic screening: exploring genomic screening for chronic diseases using triple value principles.

BACKGROUND: Genomic screening has unique challenges which makes it difficult to easily implement on a wide scale. If the costs, benefits and tradeoffs of investing in genomic screening are not evaluated properly, there is a risk of wasting finite healthcare resources and also causing avoidable harm. MAIN TEXT: If healthcare professionals - including policy makers, payers and providers - wish to incorporate genomic screening into healthcare while minimizing waste, maximizing benefits, and considering results that matter to patients, using the principles of triple value (allocative, technical, and personal value) could help them to evaluate tough decisions and tradeoffs. Allocative value focuses on the optimal distribution of limited healthcare resources to maximize the health benefits to the entire population while also accounting for all the costs of care delivery. Technical value ensures that for any given condition, the right intervention is chosen and delivered in the right way. Various methods (e.g. ACCE, HTA, and Wilson and Jungner screening criteria) exist that can help identify appropriate genomic applications. Personal value incorporates preference based informed decision making to ensure that patients are informed about the benefits and harms of the choices available to them and to ensure they make choices based on their values and preferences. CONCLUSIONS: Using triple value principles can help healthcare professionals make reasoned and tough judgements about benefits and tradeoffs when they are exploring the role genomic screening for chronic diseases could play in improving the health of their patients and populations.

A proposal of a new evaluation framework towards implementation of genetic tests.

BACKGROUND: The existing frameworks for the evaluation of genetic and genomic applications clearly address the technical and clinical value of a test, but are less concerned with the way genetic services are delivered and organized. We therefore aimed to develop a comprehensive new framework that includes an assessment of service delivery. METHODS: A new framework was built on the evaluation dimensions identified through a systematic review of the existing frameworks and a Delphi survey of Italian experts in public health genomics. RESULTS: Our framework has four sections. The first two sections, respectively, guide the evidence collection process for the genetic test (analytic validity; clinical validity; clinical utility; personal utility) and its delivery models (organizational aspects; economic evaluation; ethical, legal and social implications; patient perspective). The third section guides the formulation of the research priorities to be addressed in future research. Finally, the fourth section suggests three criteria to summarize the collected evidence (net benefit, cost-effectiveness, feasibility). CONCLUSION: We have successfully developed an evaluation framework for the evaluation of genetic tests that includes an assessment of service delivery. It also introduces some neglected evaluation dimensions such as personal utility and patient perspective.

Current Genetic Service Delivery Models for the Provision of Genetic Testing in Europe: A Systematic Review of the Literature.

Background: The provision of genetic services, along with research in the fields of genomics and genetics, has evolved in recent years to meet the increasing demand of consumers interested in prediction of genetic diseases and various inherited traits. The aim of this study is to evaluate genetic services in order to identify and classify delivery models for the provision of genetic testing in European and in extra-European countries. Methods: A systematic review of the literature was conducted using five electronic resources. Inclusion criteria were that studies be published in English or Italian during the period 2000-2015 and carried out in European or extra-European countries (Canada, USA, Australia, or New Zealand). Results: 148 genetic programs were identified in 117 articles and were delivered mostly in the UK (59, 40%), USA (35, 24%) or Australia (16, 11%). The programs were available nationally (66; 45%), regionally (49; 33%) or in urban areas (21, 14%). Ninety-six (64%) of the programs were integrated into healthcare systems, 48 (32.21%) were pilot programs and five (3%) were direct-to-consumer genetic services. The genetic tests offered were mainly for BRCA1/2 (59, 40%), Lynch syndrome (23, 16%), and newborn screening (18, 12%). Healthcare professionals with different backgrounds are increasingly engaged in the provision of genetic services. Based on which healthcare professionals have prominent roles in the respective patient care pathways, genetic programs were classified into five models: (i) the geneticists model; (ii) the primary care model; (iii) the medical specialist model; (iv) the population screening programs model; and (v) the direct-to-consumer model. Conclusions: New models of genetic service delivery are currently under development worldwide to address the increasing demand for accessible and affordable services. These models require the integration of genetics into all medical specialties, collaboration among different healthcare professionals, and the redistribution of professional roles. An appropriate model for genetic service provision in a specific setting should ideally be defined according to the type of healthcare system, the genetic test provided within a genetic program, and the cost-effectiveness of the intervention. Only applications with proven efficacy and cost-effectiveness should be implemented in healthcare systems and made available to all citizens.

Correction: Patient experience and utility of genetic information: a cross-sectional study among patients tested for cancer susceptibility and thrombophilia.

This article was originally published under an incorrect license. This has now been amended and is available under a CC BY-NC-ND 4.0 license. The PDF and HTML versions of the paper have been modified accordingly.

How is genetic testing evaluated? A systematic review of the literature.

Given the rapid development of genetic tests, an assessment of their benefits, risks, and limitations is crucial for public health practice. We performed a systematic review aimed at identifying and comparing the existing evaluation frameworks for genetic tests. We searched PUBMED, SCOPUS, ISI Web of Knowledge, Google Scholar, Google, and gray literature sources for any documents describing such frameworks. We identified 29 evaluation frameworks published between 2000 and 2017, mostly based on the ACCE Framework (n = 13 models), or on the HTA process (n = 6), or both (n = 2). Others refer to the Wilson and Jungner screening criteria (n = 3) or to a mixture of different criteria (n = 5). Due to the widespread use of the ACCE Framework, the most frequently used evaluation criteria are analytic and clinical validity, clinical utility and ethical, legal and social implications. Less attention is given to the context of implementation. An economic dimension is always considered, but not in great detail. Consideration of delivery models, organizational aspects, and consumer viewpoint is often lacking. A deeper analysis of such context-related evaluation dimensions may strengthen a comprehensive evaluation of genetic tests and support the decision-making process.

Patient experience and utility of genetic information: a cross-sectional study among patients tested for cancer susceptibility and thrombophilia.

We evaluated whether genetic tests with evidence of clinical and personal utility (i.e. APC and BRCA1/2 tests) are associated with higher satisfaction and a more positive perception of care experience than those with undefined utility (i.e. tests for thrombophilia). A cross-sectional survey was performed through telephone interviews to patients tested for deleterious variants in APC or BRCA1/2 genes, or for inherited thrombophilia (FV Leiden and/or FIIG20210A) during a 5-year period (2008-2012). Three aspects of patient experience were assessed: effective communication through pre- and post-test genetic counselling; collaboration between caregivers on the management of patient care; and impact of genetic testing on quality of life. Overall 237 patients had telephone interviews. Multivariate logistic regression analyses showed that patients tested for APC or BRCA1/2 variants were more likely to be satisfied with both pre- and post-test counselling than those tested for inherited thrombophilia (APC vs. thrombophilia, p = 0.039 and 0.005; BRCA1/2 vs. thrombophilia, p = 0.030 and <0.001). Patients tested for APC were more likely to report an improvement in quality of life than those for thrombophilia (OR = 2.97, 95%CI 1.14, 7.72; p = 0.025). A positive association was observed between patients who underwent BRCA1/2 testing, and self-perceived improvement in quality of life (OR = 1.41, 95%CI 0.74, 2.69; p = 0.294). Tests of undefined clinical and personal utility are associated with a lower degree of patient satisfaction with genetic counselling and no clear opinions on changes in quality of life compared with those with well-defined utility.