Ensuring high quality genomic testing Dr Katrina Rack GenQA, John Radcliffe Hospital, Oxford

GenQA Self funding, not for profit organisation External Quality Assessment scheme Self funding, not for profit organisation ISO 17043 accredited EQA schemes Member of the UK NEQAS consortium Participants worldwide

What is EQA Process that assesses laboratories analytical and interpretive skills compared to other laboratories by testing the accuracy and quality of their results.

External verification of quality of service Improve quality of care Aim Educational External verification of quality of service Improve quality of care Not To judge centres 4 4

Why EQA is important Ensure quality across national borders Harmonise the quality of genetic diagnostic services Ensure quality across national borders Establish continuous quality improvement Helps centres to stay up-to-date Identifies imperfect practice and improves quality Patient safety 5 5

Principles of EQA Same samples/data set sent to all participating laboratories Samples either ‘real’ or mimic real cases Independent validation using range of methods Assessed for - genotyping/analytical accuracy - interpretation of the result - clerical accuracy of the report Continual performance monitoring Provides feedback on any potential issues

From 1st January 2018 78 Hosted by NHS Lothian within Laboratory Medicine, Royal Infirmary, Edinburgh 78 Hosted by OUH NHS Foundation Trust in Women’s Centre, John Radcliffe Hospital, Oxford

Why the new partnership Historically the 2 schemes provided either cytogenetic or molecular genetic EQAs. Progressively new technologies replacing traditional techniques Traditional cytogenetic/molecular genetic boundaries have disappeared in laboratories EQA providers needed to respond to this change. Development of joint EQAs

GenQA - Aim Join forces to offer a comprehensive genetic EQA Scheme EQA to assess laboratories analytical and interpretation skills Tool for Individual training and competency assessment Educational EQAs

End to end testing

Benefits for Participants Single access point to website to streamline EQA management Access to more EQA schemes through one provider Reduced costs Assurance of delivery of high quality EQAs through UK NEQAS Consortium membership

Benefits for GenQA Aids development of EQAs that are open to different technologies Draw on expertise of both EQA schemes and have access to a large number of expert advisors (approximately 200) Reduce website development costs Long term stability to enable developments and meet needs of participants

Offers 78 EQAs for genetic/genomic testing More EQAs planned for 2019

Offers 74 EQAs for genetic testing Institution competency Offers 74 EQAs for genetic testing Reflect analytical and interpretation processes Reflect training policies Individual competency Offers 4 Educational EQAs for Clinical Genetics Offers – a training and competency tool for laboratory staff 14 14

Tumour Assessment Training/ Competency Clinical Genetics Educational Newborn screening Pre-implantation Genetic Testing DNA extraction and quality measurement Haematology Next Generation Sequencing Rapid Prenatal testing/screening inc. NIPT/D Molecular Genetics core diseases Constitutional - postnatal Molecular Pathology Constitutional - prenatal Tumour Assessment Training/ Competency Clinical Genetics Educational

Types of EQA Sample Distribution of samples for analysis (DNA, amplified DNA, fixed cells, FFPE slides) Online datasets Analysis of G-band and FISH images online Serial EQA for Clinical Genetics Educational case scenarios

Types of EQA Analytical and interpretation Interpretation only Analytical only Analytical and interpretation Interpretation only Variety of EQA types required as they assess different parts of the testing process

EQA Techniques assessed Chromosome banding analysis FISH QF-PCR MLPA Arrays/NGS Gene mutation analysis - single genes/gene panels/NGS RT-PCR for cancer fusion genes

How are EQAs run Each EQA marked by a group of assessors Experienced clinical scientists, clinicians or pathologists with necessary competency in relevant genetic testing field >200 Assessors from 18 countries Agreed Marking and Performance Criteria Two EQA performance designations: Satisfactory Poor

Tumour Assessment Training/ Competency Clinical Genetics Educational Newborn screening Pre-implantation Genetic Testing DNA extraction and quality measurement Haematology Next Generation Sequencing Rapid Prenatal testing/screening inc. NIPT/D Molecular Genetics core diseases Constitutional - postnatal Molecular Pathology Constitutional - prenatal Tumour Assessment Training/ Competency Clinical Genetics Educational

Going forward, What’s planned? Continuation of existing schemes Develop new EQAs and evolve existing EQAs, where appropriate, to respond to genetic service requirements Diversify into individual-based assessments e.g. G-TACT and Tissue-i Extend repertoire of educational EQAs Increased staffing means that we will be able to provide a better service

Going forward, What’s planned? Continuation of existing schemes Develop new EQAs and evolve existing EQAs, where appropriate, to respond to genetic service requirements Diversify into individual-based assessments e.g. G-TACT and Tissue-i Extend repertoire of educational EQAs Increased staffing means that we will be able to provide a better service

National test directory - need for new EQAs Principles of the National Genomic Testing Strategy Creation of a national network of genomic laboratories to ensure equity and consistent availability of testing All genetic and genomic testing for cancer and constitutional set out and specified in a single national test directory – mandated in standard NHS contract Outlines the appropriate genetic tests for different indications Directory specifies technology, targets, scope, indication with any qualifiers with aim/utility of testing – most cancer is for large panels Peer reviewed and updated annually to keep up with technological advance – expect scope of WGS to extend

National Genomic Testing Directory Clinical Indication Setting Test Scope Target/Gene Technology Non-squamous non-small cell lung cancer Prognostic/ Predictive Small variant detection EGFR Small panel Opportunity to scope, develop and implement future EQAs

Going forward, What’s new? Continuation of existing schemes Develop new EQAs and evolve existing EQAs, where appropriate, to respond to genetic service requirements Diversify into individual-based assessments e.g. G-TACT and Tissue-i Extend repertoire of educational EQAs

Individual training assessment and competency tool Genomics Training Assessment & Competency Tool

ISO 15189:2012

G-TACT virtual laboratory GenQA website access Individual participation Comprises different modules Task scenarios randomly generated Automated assessment Complete at your own pace (12 mths) Sample Reception Duty Scientist Tumour content assessment Test data analysis Sequence variant interpretation Report authorisation Sample Reception Duty Scientist Tumour content assessment Test data analysis Sequence variant interpretation Report authorisation Sample Reception Duty Scientist Tumour content assessment Test data analysis Sequence variant interpretation Report authorisation

Process of variant classification   In development In development In development Chromosome analysis CNV classification   Trial mode   Process of variant classification BRCA variant classification in ovarian cancer Including CNVs

How is it assessed? Performance not monitored by GenQA Monitored by Institution Automatic responses can be over ridden by Institution Training and performance reviews

Going forward, What’s planned? Continuation of existing schemes Develop new EQAs and evolve existing EQAs, where appropriate, to respond to genetic service requirements Diversify into individual-based assessments e.g. G- TACT and Tissue-i Extend repertoire of educational EQAs

Clinical genetics Currently running 4 educational EQAs for Clinical Genetics Cardio genetics Dysmorphology Monogenic disorders Oncogenetics Comprised of case scenarios based on sequential consultations including Family history Test requests and test results Counselling EQA for genetic counsellors planned for 2019

Laboratories Acknowledgements GenQA Staff Assessors SAG members ____________________________________________________________________________________________________________ Acknowledgements GenQA Staff Assessors SAG members but most of all the Laboratories