1. EMGO Institute for Health and Care Research Quality of Care Martina Cornel Professor of Community Genetics & Public Health Genomics Next generation genomics: translation into clinically useful applications in health care Community Genetics, Dept Clinical Genetics Leiden 10 years CMSB 14th October 2013

2. CMSB: the goal The Centre for Medical Systems Biology (CMSB) is a joint activity of Leiden University Medical Center, Leiden University, VU University Medical Center and Free University Amsterdam, Erasmus MC Rotterdam and TNO Leiden, aiming to apply innovative multidisciplinary genomics and bioinformatics approaches to improve diagnosis, therapy and prevention of common and rare diseases Photo: http://www.cad-company.nl/2013/09/05/10-tips-voor-de-reis-naar-bim/

3. The activities of CMSB Identifying genes and biological pathways involved in onset and severity of disease Alzheimer’s disease, arthritis, depression, diabetes, migraine, immune disorders and cancer This suggests the existence of biological master switches in the human body www.cmsb.nl

4. From knowledge to implementation … remember that genomics obeys the First Law of Technology: we invariably overestimate the short- term impacts of new technologies and underestimate their longer-term effects. The decade from 2000 to 2010 was characterized by breathtaking acceleration in genome science The consequences for clinical medicine, however, have thus far been modest. Collins 2010 Nature

5. After proof of principle… Khoury 2007 Genetics in Medicine

6. The continuum of translation Khoury 2007 Genetics in Medicine

7. Be prepared to involve… Modified from Achterbergh 2007

8. And assess… clinical utility? Genetic risk prediction… Mihaescu, Janssens et al Updating risk factors may produce contradictory information about an individual's risk status over time, which is undesirable if lifestyle and nutritional recommendations vary accordingly. Genet Med. 2009 Genetic testing of multiple SNPs is considered a potentially useful tool for early detection of individuals at high diabetes risk leading to improved targeting of preventive interventions. PLoS Curr 2011

9. Clinical utility - Diabetes Web-based familial risk information reduced worry related to diabetes risk and decreased saturated fat intake of those at greatest need of preventative care. However, the intervention was not effective for the total study population on improving risk-reducing behaviour. The emphasis on familial risk does not seem to result in false reassurance among individuals without family history. Additionally, a detailed family history questionnaire identifies more individuals at familial risk than a simple enquiry. Wijdenes 2013 BMC Public Health

10. Assess… patients/consumers interest? Parental Opinions about the Expansion of the Neonatal Screening Programme. Detmar et al. Community Genetics 2008 The divergence in attitudes and preferences we found in this study reflected the complexity inherent in any consideration of screening for additional conditions. To implement such options successfully and to direct applied research in genomics, it is important to develop a better understanding of the thinking of target groups, namely parents.

11. Assess… legal issues? Which lessons can we learn from the European Union legal framework of medicines for the regulation of direct-to-consumer genetic tests? The EU laws governing medicines can, notwithstanding their shortcomings, serve as an example for (central) authorising the marketing of DTC genetic tests on the internal market in accordance with strict criteria regarding predictive value and clinical usefulness. Van Hellemondt R et al. Rev Derecho Genoma Hum. 2012

12. Assess… ethical issues? Informed consent DTC testing The quantity and the complexity of risk information pose challenges to adequate pre- test and post-test information provision and informed consent. Bunnik 2013 EJHG

13. Be prepared to involve… Modified from Achterbergh 2007

14. Proposed roadmap (Houwink 2013)

15. Assess… learning needs MDs Focus group study: (1) genetics knowledge (2) family history (3) ethical dilemmas and psychosocial effects in relation to genetics and (4) insight into the organisation and role of clinical genetics services. Houwink 2011 BMC Family Practice

16. Develop modules oncogenetics Genetics e-learning Continuing Professional Development (CPD) module Houwink EJHG 2013 4h consultation skills training, evaluated with unannounced standardized patients visits Houwink GIM 2013 Website www.huisartsengenetica.nl eCPD: at 6 months follow up increased knowledge scores Face-to-face skills training: Key consultation skills significantly and substantially improved, moderate effect size

17. Proposed roadmap (Houwink 2013)

18. Improve genomic literacy by training & education Improve possibility to register family history (ICPC)

19. 3. (Access to) up-to-date and unambiguous guidelines. 4. (Apps to) self-register family history such as familyhealthware.com 5. Proactive genetic services integrated in GP service facilitated by ICT multidisciplinary; from tissue sample in pathology to clinical geneticist & patient

20. Next generation genomics: -› translation into clinically useful applications in health care! What is clinically useful? What do patients/citizens need? What is allowed? Acceptable? Develop guidelines Train Live longer & healthier!

21. THANK YOU FOR YOUR ATTENTION