Genetics Quality and Accreditation workshop Manchester 17 th May 2017

Transcription

1 Genetics Quality and Accreditation workshop Manchester 17 th May 2017 Katrina Rack Oxford

2 CEQAS What is CEQAS Types of schemes Scheme update Highlights 2016 Key recommendations

3 CEQAS Background External Quality Assessment scheme assesses laboratories analytical and interpretive performance compared to other laboratories by testing the accuracy and quality of the results Part of the UK NEQAS Consortium Not for profit organisation Accredited EQAs (ISO17043)

4 CEQAS : what we do Largest European Cytogenetic Scheme Widest repertoire of cytogenomic EQAs 35 EQAs cytogenetics, molecular cytogenetics, PGD, NIPT, acquired disorders, clinical genetics

5 EQAs 2017 Constitutional Amniotic fluid Blood Chorionic villus FISH rapid aneuploidy Molecular rapid aneuploidy Products of conception(2) Prenatal Microarray Postnatal Microarray Pilot NIPT Pilot Breakage Genetic Counselling Cardiovascular genetics Monogenetic disorder Dysmorphology Oncogenetics Acquired Acute lymphoblastic Leukaemia CNS tumours - 1p/19q co-deletion, MGMT, IDH Myeloid Disorders Mature B&T Cell Neoplasms(2) Microarray for acquired disorder Myeloma Sarcoma (FFPE FISH & RT-PCR) Neuroblastoma pilot Renal Carcinoma pilot Lymphoma pilot (FFPE FISH) Preimplantation Genetic diagnosis PGD array/ngs (blastomere/trophectoderm/pb) aneuploidy and rearrangement (3) PGD FISH (blastomere) PGD Sperm FISH

6 CEQAS : EQA organisation Submission in 5 European Languages Submissions assessed against European Cytogenetic and reporting Guidelines ISCN 2016 ISO15189 CEQAS offers EQAs to laboratories worldwide

7 CEQAS : Participants Genetic laboratories Molecular pathology laboratories Haematology laboratories Prenatal diagnostic testing laboratories and companies Clinical genetic centres

8 Participating labs countries 34 European countries 6 continents

9 Total number of EQA enrolments Number of laboratories Enrolled Laboratories & EQAs Enrolled laboratories Total EQA Enrolments

10 EQA Types of tests offered Historically EQAs provided for cytogenetic analysis and FISH. As new technologies introduced in the laboratories EQAs evolved to incorporate these: Arrays, NGS As complementary tests introduced or required as part of the diagnostic or work up procedure EQAs evolved to include mutation screening and epigenetic changes Traditional cytogenetic/molecular genetic boundaries are disappearing in the laboratories requires EQA providers to respond to this. CEQAS runs joint EQAs with both UK NEQAS for molecular genetics and EMQN. Will mean closer collaboration needed in the future

11 EQA Techniques assessed Karyotyping FISH QF-PCR MLPA Arrays NGS copy number analysis Gene mutation analysis and epigenetic changes (1) RT-PCR for cancer fusion genes

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

13 CEQAS : How are EQAs run Each EQA assessedby a group of assessors Experienced clinical scientists, clinicians or pathologists with necessary competency in relevant genetic testing field 85 Assessors from 15 countries Agreed Marking Criteria and Performance Criteria Two performance designations: Satisfactory Poor

14 Scientific Advisory Board (SAB) Prenatal Constitutional SAG Amniotic fluid CVS Prenatal Microarray Products of conception (G) Products of conception (Arr/MLPA/PCR) Postnatal Constitutional SAG Blood Microarray (postnatal) Breakage Haematology SAG ALL Myeloid Mature B&T x2 (G or FISH) Microarray for acquired disorders Myeloma Lymphoma pilot (FFPE FISH) Rapid Prenatal SAG FISH rapid aneuploidy Molecular rapid aneuploidy (QF-PCR/ MLPA/BoBs) Pilot NIPT PGD SAG PGD array/ngs aneuploidy rearrangement PGD FISH (blastomere) PGD Sperm FISH Oncology SAG CNS Sarcoma Neuro- blastoma Renal Carcinoma Genetic Counselling SAG Cardiovascular genetics Monogenetic disorder Dysmorphology Oncogenetics Joint SAGs with UK NEQAS molecular biology

15 New EQAs : On going development Genetic counselling Educational EQA Aimed at Clinical Geneticists Developed at the request of ESHG Will expand to include genetic counsellors

16 Consists of an unfolding case scenario Sequential EQA stepwise access to case details dependant on completion of each stage Each stage requires counsellor to outline what questions to ask, what to discuss and what tests to request Stage 1: 1st consultation Referral letter, examination, family history, genetic testing requests based on differential diagnosis Stage 2/3: 2 nd /3 rd consultations. Feedback of initial results. Request further patient or family testing as required. Advice to patients and other family members

17 Case scenarios based on real life consultations Specialities covered Dysmorphology Cardiology Cancer genetics Monogenic disorders Future: Provision of EQA for Genetic counsellors

18 Scheme update 2016 New EQAs Neuroblastoma (Array, FISH) Renal cell carcinomas (retrospective)- development to include mutation screening NIPT Breakage syndromes Lymphoma

19 Aims of EQA Highlight areas of concern where laboratories are struggling What essential tests to perform Best technique to use How to interpret results particularly atypical results What to include in a report clarity, is it clear and concise EQA providers can facilitate this Provide experience of EQA outcome Capability of bringing together the experience of large number of laboratories Independent Results in Best practice meetings and establishment of guidelines and recommendations.

20 Best Practice meetings: Sperm FISH 04/04/2017 Feedback from EQA What parameters to report Cut offs to apply to distinguish normal and abnormal results No specific guidelines Now in preparation

21 Best Practice meetings: Prenatal array 20/04/2017 No European guidelines, some national guidelines Feedback from EQA Different reporting strategies of CNVs Unsure how to report absence of heterogeneity (AOH) Survey on interpretation of pathogenicity of CNVs. Good consensus for pathogenic and benign CNVs. Variation classification intermediate groups Another survey planned Findings will be presented at ACGS meeting

22 Best Practice meetings: CNS tumours 10/05/2017 Feedback from EQA Difficulties in reporting atypical FISH patterns: report or not? is it important? Methylation studies- variable number of sites Variable cut offs, how to establish internal validation No specific guidelines New WHO classification system to integrate

23 Best Practice meetings: PGD December 2017 Feedback from array/ngs Polarbody blastomere/trophectoderm aneuploidy/rearrangement EQAs How to describe results in the context of a haploid genotype (Polar Body) Interpretation of results relationship of abnormal results to chromosome abnormalities and therefore correct advice No specific guidelines

24 Best Practice Guidelines Guidelines in preparation Update Haematology Update Constitutional Sperm FISH Oligodendroglioma (CNS) Array/NGS PDG NIPT guidelines genetic testing, in press To start Lymphoma

25 Whats happening 2017 Survey labs aim development new EQAs or reorganisation of existent EQAs Working more closely with UK NEQAS for Molecular Genetics to develop further EQAs. Joint PGD SAG and Joint Rapid prenatal SAG. New Joint Oncology SAG. Will facilitate better provision of EQAs to participants.

26 Key recommendations How to be successful at EQA Don t deviate from normal procedure Don t over interpret results Keep reports concise Put all essential test results in a prominent position in report, ideally in a summary box Take on board any comments learn from others Recognise that errors can occur in any laboratories despite rigorous procedure