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.

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 18/9/08joan.forsyth@bwhct.nhs.uk

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 2002

• 2003 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 2003-16 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 2006- 5 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. 2005 Sep;7(7):495-500

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. 2005 Sep;7(7):495-500 Sanderson S, Zimmern R, Kroese M, Higgins J, Patch C, Emery J.

• www.ukgtn.nhs.uk.

•