Presentation on theme: "You have recently set up a new disease service in your laboratory. What is the role of the UKGTN? Describe the process involved in submission & evaluation."— Presentation transcript:
You have recently set up a new disease service in your laboratory. What is the role of the UKGTN? Describe the process involved in submission & evaluation of a gene dossier. Joan Forsyth 18/9/08
What is the UK Genetic Testing Network (UKGTN) Collaborative network of NHS labs that offer tests for human single gene germ disorders Aims to provide high quality and equitable laboratory services for patients and their families who require genetic advice, diagnosis and management. DoH supported establishment of UKGTN in UKGTN established the NHS directory of Molecular Genetic Testing –Allow equity in access to genetic testing across NHS –Funding responsibility of local specialist groups (purchasers of healthcare).
Core functions UKGTN Approval of labs for membership & audit of services provided –Dev simple methods/documentation to collect relevant lab data, produce annual reports Evaluation & recommendation of new genetic tests to be included/deleted from directory –constant review of gene dossiers Establish robust arrangements for the provision of molecular genetic services –Review of new developments & impact on NHS services, & identify commissioning mechanisms/procedures/policies Provide information on services of members Monitor, develop & manage UKGTN website & include a directory of test (levels of service) –ensuring fit for use by all relevant users & has appropriate links Evaluation of service development
How is the UKGTN organised? Network managed by UKTGN Steering Group –Members from a number of disciplines (clinical & molecular genetic, cytogenetics,DOH representatives, Genetic interest grps, NHS healthcare purchasers public health, Clinical Chemistry, Pathology, Biochemistry,Haematology, & reference labs) Subgroup of & accountable to National Genetics Commissioning Advisory Group (GenCAG)
UKGTN project team Pilot in labs submitted 85 GD, unexpected high number. To allow more time to consider applications a Project team introduced Includes project director, Lab coordinator, commissioning co- ordinator & 3 specialist advisors From working groups have supported the steering group, each with members from relevant professional & patient groups
Evaluation of new genetic tests UKGTN defines a genetic test as tests for single gene, germ line disorders where nucleic acid is the analyte Gene dossier (GD) process developed & a GD needs to be submitted for all tests the member wishes to offer to the network Standardised for the presentation of key information about the genetic test
ACCE model GD based on four components evaluated (ACCE model) & the Canadian experience of genetic test evaluation: Analytical validity Clinical validity Clinical utility Ethical, legal and social issues (ELSi) Genet Med Sep;7(7):
Analytical Validity Defines the ability of a test to accurately and reliably measure the genotype(s) of interest –Sensitivity – probability the test will be positive when the mutation is present –Specificity – probability the test will be negative when the mutation is not present Linked to quality assurance (QA) –Internal – reference standards, SNP checking, transfer checks –External – QA schemes, CPA registered laboratory
Clinical Validity Defines ability to detect/predict the presence or absence of the phenotype or clinical disease –Sensitivity – probability the test will be positive in an affected individual –Specificity – probability the test will be negative in an unaffected individual
Clinical Utility Defines the likelihood the test will lead to an improved outcome, & includes financial costs –Assessment or risk/benefits of genetic testing –Economic evaluation (business case)
ELSi Implications for relatives Insurance discrimination Stigmatisation based on genotype rather than phenotype
The criteria used by the Evaluation Panel Clinical details/prevalence of the condition Particular purpose of the test –diagnosis, treatment, prognosis and management, presymptomatic testing, risk assessment the complexity of the test Test criteria, clinical context in which test will be done- referrals from/population groups to be tested
The criteria used by the Evaluation Panel ACCE framework –the clinical sensitivity, specificity and predictive value of test –the utility of the test – how it adds to patient management and the availability of alternative diagnostic procedures –ethical, legal and social considerations Cost of the test
Process GD subgrp provides a summary back to steering group, which makes the final decision on dossier. Issues encountered with gene dossier applications include: –Use of published data rather than actual lab data in analytical evaluation –Lack of knowledge/technical limitations so only a proportion mutations identified by on test –Lack of analytical/validity data for significant no tests, because rare single gene disorder –Absence of controls in pilot studies/target pop poorly defined/estimates of disease prevalence of disease in target pop not provided –Financial data difficult to obtain –Limited discussion of Elsi issues List of approved tests placed before GenCAG for acceptance into directory & request made to healthcare purchasers to consider funding these tests
References How can genetic tests be evaluated for clinical use? Experience of the UK Genetic Testing Network. European Journal of Human Genetics (2007) 15, 917–921.Mark Kroese, Ron L Zimmern, Peter Farndon, Fiona Stewart and Joanne Whittaker How can the evaluation of genetic tests be enhanced? Lessons learned from the ACCE framework and evaluating genetic tests in the United Kingdom. Genet Med Sep;7(7): Sanderson S, Zimmern R, Kroese M, Higgins J, Patch C, Emery J.