1. Genetic testing and the United Kingdom Genetic Testing Network Professor Peter Farndon Chair UKGTN Presentation with images removed

2. Genetic testing and the UK What is a genetic test? Do they require special consideration compared with other tests? How are they best provided? How can we encourage appropriate use?

3. What is a genetic test? UKGTN remit: tests for germ line disorders where nucleic acid is the analyte

4. Genetic testing and the UK What is a genetic test? Do they require special consideration compared with other tests? How are they best provided? How can we encourage appropriate use?

5. Some characteristics of genetic testing technology straightforward but sequencing (“gold standard”) may not be the answer relatively low throughout relatively high cost interpretation of sequence changes may require specialist knowledge of disease/gene specialist staff: can’t “borrow” staff from pathology

6. Some characteristics of genetic testing overall incidence of genetic diseases known but local incidence varies widely from year to year capacity to provide a particular service needs to be available for when it is required

7. Some characteristics of genetic testing family based in most instances testing people without disease to generate information for an affected family member family study may be required to determine significance of mutation result

8. Centrally organised (funded) national service/network Some characteristics of genetic testing overall incidence of genetic diseases known but local incidence varies widely from year to year capacity to provide a particular service needs to be available for when it is required relatively low throughout relatively high cost family based in most instances testing people without disease to generate information for an affected family member family study may be required to determine significance of mutation result specialist staff: can’t “borrow” staff from pathology How can one plan and fund such a service?

9. OMIM January 25, 2006 Genes with known sequence 10,552 Phenotypes known for 386 Known phenotypes 5,572 Known molecular basis 1,831 Unknown molecular basis 3,741

10. Genetic testing and the UK What is a genetic test? Do they require special consideration compared with other tests? How are they best provided? How can we encourage appropriate use?

11. Research projects Research laboratories NHS service laboratories Funding Continuity of service Timescale Quality 1985+ Planning and funding for specialist services was through Regional Health Authorities on five-year rolling programmes

12. Aberdeen Glasgow Dundee Edinburgh Newcastle Liverpool Leeds Manchester Sheffield Nottingham Leicester Oxford Cambridge London Northwick Park Gt. Ormond St. Guy’s St. Georges Southampton Exeter Cardiff Belfast Bristol Birmingham Regional genetics centres provide integrated clinical and laboratory services Most serve 2 to 3 million people (range 0.5 to 5)

13. Genetic testing services Clinicians Generating requests for tests Enthusiastic about scientific advances Patient groups Equity of access to clinicians and tests Continuity of service Commissioners Potential huge demand Limited funds Conflicting priorities Cost/volume considerations Minimal beaurocracy Laboratories Network Equipment Staff Development

14. Speech by the Secretary of State for Health, Alan Milburn, 2001 Genetic Network (clinical and laboratory), Green Paper £30 million investment The values of Britain's NHS mean citizens can choose to take genetic tests free from the fear that should they test positive they face an enormous bill for insurance or treatment or become priced out of care or cover altogether. Properly exploited, genetics strengthens the case for the values of the NHS. Of course there will be up front costs if the NHS is to spread the benefits of genetic developments. But, down the line, there could be significant financial gains to put alongside major health gains. Speech by Rt Hon Alan Milburn MP, Secretary of State for Health at the international conference Genetics and Health - a Decade of Opportunity 16 January 2002

15. 2000: UK co-ordination of clinical and laboratory services Genetics Commissioning Advisory Group formed Subgroup of National Specialist Commissioning Advisory Group (NSCAG) Responsible through NSCAG to ministers Commissioners, providers and patients Progress!

16. 2002: GenCAG Commissioners gone! Set up Genetic Testing Network Steering Group Paper to PCTs about priorities for genetic services Commitment by commissioners to fund service under whatever arrangements emerge Commissioners form themselves into “Friends” group to enable consensus over commissioning and maintain expertise

17. UKGTN: The driving force “The fundamental underlying principle is that of geographical equity. Patients and their families who require genetics advice, diagnosis and management should be able to access a range of expert advice and appropriate tests via local genetics centres which provide the clinical interface and act as a gateway to a coordinated network of laboratory services throughout the UK.” Framework for delivering the UK GTN

18. UKGTN: collaborative group of laboratories and commissioners informed by patients Steering group, project team, working groups

19. UKGTN quality criteria for laboratory membership Laboratory accreditation Target turn-around times Support from host institution and host commissioners (including RSCGs and consortia) Information for monitoring Robust and sustainable service provision Technical, scientific and clinical environment Audit Research Dissemination of information on availability of service

20. UKGTN laboratory members 2005 UKGTN Diagnostic Service Laboratory laboratories offer molecular genetic analysis, clinical interpretation and reporting. conform to clinical governance standards clinical accreditation such as CPA. UKGTN Technical Service Laboratory laboratories provide an analytical service for UKGTN diagnostic service laboratories. do not provide the clinical interpretation but report directly to the referring Network laboratory. comply with standards such as ISO 17025 A clinician referring a sample directly takes complete responsibility for the quality of the clinical interpretation. The status of UKGTN membership applies only when a technical service laboratory is providing a service to a UKGTN diagnostic laboratory.

21. Identify need Prepare “gene dossier” Clinical indications Target population Specificity and sensitivity Technical details Costs Patient groups; clinicians; laboratories; Clinical users’ group UK GTN assessment and prioritisation Accepted into NHS portfolio of tests Funding decision: RSCG/PCTs Recommend to GenCAG that “test” considered for funding

22. Gene Dossier – mechanism to add genetic tests to service Assessed by a working group, ratified by whole Steering Group through consensus against published criteria Seriousness of condition Prevalence Purpose of test Population group Sensitivity, specificity and predictive value Utility Ethical, legal, social considerations Cost

23. NHS Directory of molecular genetic testing 325 diseases/tests for which testing is available/appropriate (published list at April 2005) Testing supported by research funding/ available as part of DH funded initiatives Statement on need to send some tests to non UKGTN or international laboratories

24. www.ukgtn.nhs.uk

25. Genetic testing and the UK What is a genetic test? Do they require special consideration compared with other tests? How are they best provided? How can we encourage appropriate use?

26. Considerations in ordering a DNA test Same test: different clinical utility in different clinical situations a) Diagnosis b) Treatment c) Prognosis and Management d) Presymptomatic Diagnostic Screening e) Genetic Risk assessment. Clinical judgement: DNA vs other testing Each test request on a case by case basis Priority under NHS funding for testing which directly affects clinical management

27. d) Presymptomatic Diagnostic Screening Will a positive molecular result accurately predict future disease and alter management? Will a negative molecular result be definitive (ie: further tests do not need to be carried out)? e) Genetic Risk Assessment Will molecular diagnosis in the affected person reduce the needs for tests in the rest of the family? Will molecular diagnosis resolve the mode of inheritance? (eg: HMSN) Will molecular diagnosis provide a means of pre-natal diagnosis or carrier detection? Will molecular diagnosis allow pre-symptomatic testing for other family members? Examples of questions to ask when considering ordering a genetic test

28. Genetic testing and the UK What is a genetic test? Do they require special consideration compared with other tests? How are they best provided? How can we encourage appropriate use? Challenges

29. QUESTIONS STILL REMAINING 1. Technology affecting pace and nature of service developments 4. Public Reaction to genetics-based technology ethical, legal, social concerns 3. Policy/ Supply Of Services organisation and availability of services marketing of services cost (free, payment) regulation/legislation 2. Information natural history of disease genetic heterogeneity mutation spectrum risk refinement bioinformatics

30. Challenges ? Access improved ? Tests into practice Provision of development/set up costs for tests Funding mechanisms Is the philosophy of a shared national network at variance with local decision making? Effect of “Payment by Results” Using the ordering of a genetic test as an opportunity for genetic education

31. Challenges Interface with FISH/array cytogenetics tests

32. What is a genetic test? UKGTN working definition: test for a genetic variant (or set of variants) for a particular disease in a particular population for a particular purpose