Genetics Quality and Accreditation workshop Manchester ... · PDF fileGenetics Quality and...
Transcript of Genetics Quality and Accreditation workshop Manchester ... · PDF fileGenetics Quality and...
CEQAS is a member of the consortium
Genetics Quality and Accreditation workshop
Manchester 17th May 2017
Katrina Rack
Oxford
CEQAS is a member of the consortium
____________________________________________________________________________________________________________ CEQAS
What is CEQAS
Types of schemes
Scheme update
Highlights 2016
Key recommendations
CEQAS is a member of the consortium
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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)
CEQAS is a member of the consortium
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CEQAS : what we do
Largest European Cytogenetic Scheme
Widest repertoire of cytogenomic EQAs
35 EQAs – cytogenetics, molecular cytogenetics, PGD,
NIPT, acquired disorders, clinical genetics
CEQAS is a member of the consortium
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EQAs 2017
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
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
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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
CEQAS is a member of the consortium
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CEQAS : Participants
Genetic laboratories
Molecular pathology laboratories
Haematology laboratories
Prenatal diagnostic testing laboratories and
companies
Clinical genetic centres
CEQAS is a member of the consortium
Participating labs 2016
51 countries
34 European countries
6 continents
CEQAS is a member of the consortium
____________________________________________________________________________________________________________ Enrolled Laboratories & EQAs
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2010 2011 2012 2013 2014 2015 2016
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Total EQA Enrolments 2010 - 20160
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2010 2011 2012 2013 2014 2015 2016
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Enrolled laboratories 2010 - 2016
CEQAS is a member of the consortium
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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
CEQAS is a member of the consortium
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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
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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
CEQAS is a member of the consortium
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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
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Prenatal
Constitutional
SAG
Amniotic fluid
CVS
Prenatal
Microarray
Products of
conception (G)
Products of
conception
(Arr/MLPA/PCR)
Scientific Advisory Board (SAB)
PGD SAG
PGD
array/NGS
aneuploidy
rearrangement
PGD FISH
(blastomere)
PGD Sperm
FISH
Rapid
Prenatal
SAG
FISH rapid
aneuploidy
Molecular
rapid
aneuploidy
(QF-PCR/
MLPA/BoBs)
Pilot NIPT
Postnatal
Constitutional
SAG
Blood
Microarray
(postnatal)
Breakage
Genetic
Counselling
SAG
Cardiovascular
genetics
Monogenetic
disorder
Dysmorphology
Oncogenetics
Haematology
SAG
ALL
Myeloid
Mature B&T
x2 (G or FISH)
Microarray
for acquired
disorders
Myeloma
Lymphoma
pilot (FFPE
FISH)
Oncology
SAG
CNS
Sarcoma
Neuro-
blastoma
Renal
Carcinoma
Joint SAGs with UK
NEQAS molecular biology
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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
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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: 2nd/3rd consultations.
Feedback of initial results. Request further patient or
family testing as required. Advice to patients and other
family members
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Case scenarios based on real life consultations
Specialities covered
Dysmorphology
Cardiology
Cancer genetics
Monogenic disorders
Future: Provision of EQA for Genetic
counsellors
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Scheme update 2016
New EQAs
Neuroblastoma (Array, FISH)
Renal cell carcinomas (retrospective)-
development to include mutation
screening
NIPT
Breakage syndromes
Lymphoma
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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.
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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
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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
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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
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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
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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
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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.
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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