Molecular Genetics Services: The National Context

1. Molecular Genetics Services: The National Context Maggie Williams Consultant Clinical Scientist

2. UK Genetic Services Network 22 Regional Genetic Services 8 Molecular Genetic Clusters. Cytogenetics Clinical Diagnosis Counselling Research Two National Genetics Reference Laboratories UK Genetic Testing Network Genetic Knowledge Parks National Genetics Education and Development Centre

3. Britain must be at the leading edge of genetics - Milburn 16 January 2002 • To help prepare the NHS for the genetics revolution, Mr Milburn today announced details of a range of new centres of excellence for genetics. • Two new National Genetics Reference Laboratories to be based in Salisbury and Manchester specialising in assessing and developing new genetic tests and technologies for the benefit of patients - each receiving £500,000 funding a year.

4. Britain must be at the leading edge of genetics - Milburn 16 January 2002 • Six new Genetics Knowledge Parks in Oxford, Cambridge, London, the North West and Newcastle. • The new Genetics Knowledge Parks will bring together on a single site, or in collaboration between sites, clinicians, scientists, academics and industrial researchers. They will be centres of clinical and scientific excellence seeking to improve the diagnosis, treatment and counselling of patients. • The Genetics Knowledge challenge fund of £10 million and the DTI contribution of £5million allocated

5. NHS National Genetics Education and Development Centre – Birmingham www.geneticseducation.nhs.uk/ • working with a range of groups throughout the UK to facilitate the integration of genetics education into all levels of education and training for all NHS health professionals. • Provide leadership in genetics education • Help to raise the awareness of genetics • Involve patients and their families in informing all aspects of our work • Identify the genetics knowledge, skills and attitudes useful for clinical roles • Develop a framework for competences in genetics • Facilitate the integration of genetics into curricula and courses • Identify and develop resources appropriate to the needs of health professionals (and their trainers) • Support and disseminate learning from service development initiatives in genetics

6. Genetic testing in the UK Cardiff SAS Porphyria Service London Haemoglobinopathies UCL National Haemoglobinopathy Reference Lab Royal Marsden Cancer Genetics Laboratory Regional Genetics Centres Specialist Labs GENETIC TESTING IN UK Other pathology departments Privatelabs London Kings Haematology London UCL Hospitals Clinical Biochemistry N. West Biochemical Genetics Unit (Willink) West Midlands Inherited Metabolic Disorders

7. Genetics White Paper June 2003 Genetics Laboratories Performance Targets Service Developments Integrating Genetics Future Proofing

8. Genetics White Paper June 2003 "Our inheritance, our future - realising the potential of genetics in the NHS" 2.20 High-throughput automated testing technology, often operated round the clock, will become essential to deliver quality results quickly. Robotics and other automation will mean that testing at vastly increased speeds and the ability to do more tests at once will be possible, and the cost per test reduced considerably • 2.26 ….by 2006 genetic test results should be available to the following standards: • within three days for urgent samples • within eight weeks for unknown mutations in a large gene.

9. Investment

10. NHS Genetics Laboratories - Challenges • Re-configuration of services • increase capacity for new tests • respond to National Guidance (NICE/RCPath) • maximise quality • future proof • Reduce reporting times • ‘Urgent’ eg prenatal - 3 days • ‘known mutation’ - 10 days • ‘unknown mutation’ - 40 days • Clinical Waiting Time targets –14 weeks

11. GeneticsClusters / “Consortia” Leeds / Newcastle Liverpool / Manchester Nottingham /Sheffield Birmingham Salisbury/Cambridge/Oxford/Bristol/Exeter/Cardiff London labs Scottish labs Northern Ireland -Belfast

12. SCOBEC Collaboration • Automated HT central facility • BRCA backlog cleared screens within 8 weeks • Rationalisation • Improvement in reporting times • Development of new tests • Per review to improve quality • Pathology integration

13. Genetics…. Past, Present and Future !

14. UK Genetic Testing Network ‘The United Kingdom Genetic Testing Network (UKGTN) is a collaborative group of laboratories and their clinicians, commissioners and patient representatives.  The UKGTN is involved in supporting the provision of genetic tests for inherited disorders in order to promote equity of access.’ www.ukgtn.org

15. UK Genetic Testing Network Department of Health Genetics Commissioning Advisory Group UK Genetic Testing Network UK GTN Steering Group

16. UK Genetic Testing Network • Formalised in 2003, funded by the DH • Promote equity of access to genetic tests in the UK • Remit is limited to single gene, germline disorders where nucleic acid is the analyte • Online Directory and Database of member laboratories and the service levels provided for each disease/gene • www.ukgtn.nhs.uk

17. UKGTN Membership • 1st wave: • all regional molecular genetics laboratories • specialist molecular genetics laboratories • 2nd wave: • technical providers but only in partnership with a RGC • 3rd wave: • cytogenetics laboratories

18. Genetic Test Definition • UKGTN • ‘‘tests for single gene germline disorders where nucleic acid is the analyte’’ For example Cystic fibrosis: CFTR Familial Breast Cancer: BrCa1 and BrCa2

19. Gene Dossier ( 1/05/09 ) • Details and prevalence of the condition • Target population • Complexity of the test • Clinical context in which the test is to be used • Analytical validity • Clinical validity and utility • Cost • Referral pathway and referral criteria

20. Disease gene discovered Translation by RGC in association with research lab Evidence for a New Test • Clinical scientists in RGC’s as job role • Funded by host Trusts • Research / NHS partnerships • Eg Genetics Knowledge Parks ( pre 2007) • Sudden cardiac death ( Oxford) • Reference Labs / Research • Autosomal Dominant Retinitis Pigmentosa (Manchester) Local clinical interest and literature review

21. Gene dossier: Long QT syndrome

22. Referral Pathway Template – . Population A Individuals with a clinical diagnosis or probable clinical diagnosis of LongQT syndrome. Population B At risk relatives in families where a pathogenic mutation has been identified in the proband. Population A Referrals accepted from: Clinical Genetics Departments Consultant Adult and Paediatric Cardiologists in liaison with their local Clinical Genetics Department Coroners and Pathologists Population B Referrals accepted from: -Clinical Genetics Departments -Minimal referral criteria will be set. -Referrals will be assessed by the SCD Team (Clinical scientist in charge of disease, Consultant Clinical Geneticist [Dr E. Blair], Cardiovascular Genetic Counsellor and Consultant Cardiologist [Professor H. Watkins]) 300 Gene Screen 300 Single mutation tests (Presymptomatic and Diagnostic)

23. Translation to Commissioning Disease genediscovered Translation by RGC in association with research lab Gene Dossier submitted to UKGTN Gene Dossier accepted by UKGTN GenCAG recommends test is funded ** Test appears on UKGTN directory

24. Translation cont GenCAG recommends test is funded GenCAG advises Commisisoners to fund tests for local population and informs of cost of test for population LSCG’s decide whether to fund test for local population and increase budgets of RGC’s

25. Gene dossier: rejections Common problems: • May have limited clinical utility • May still really be in the research phase • May have poor sensitivity and specificity • Referral pathway and testing criteria may not be thought out

26. Issues and problems for laboratories • UKGTN is not a statutory regulatory body, it is a network of laboratories and has an advisory role to the DH: • Lever for change • It is often not possible to undertake rigorous test evaluation especially for sensitivity and specificity • Translation and UKGTN process may be successful but may not be supported by local commissioners • Equity of access

27. The future role for UKGTN in test evaluation • Currently addresses inherited or heritable disorders where DNA is the analyte • Should it broaden it’s scope to more complex disorders? • Should it confine itself to DNA as the analyte?

28. Thanks • Anneke Seller/Jo Whittaker • SCOBEC labs • Sarah Warburton