THE NGS CONVENTION FOR ONCOLOGY IN BELGIUM€¦ · The clinical report should contain the following...

THE NGS CONVENTION FOR ONCOLOGY IN BELGIUM:P I L O T I N G M O L E C U L A R D I A G N O S T I C S I N T O T H E 2 1 S T C E N T U R Y W I T H

A N E Y E O N E U R O P E

M A R C VA N D E N B U L C K E

C A N C E R C E N T R E , S C I E N S A N O

B G D O , M A I L L E N , 2 6 A P R I L , 2 0 1 9

NGS convention

ComPerMed actvities

EC Pre-commerciam Procurement project oncNGS

EC 1.000.000 genomes initiative

Topics

Walli Van DorenNational Institute for Health and Disability Insurance Belgium

The introduction of NGS panel tests in the Belgian healthcare system

07-11-2017 3

Context

Already in 2015 there was a clear political will tointroduce the innovative targeted ‘Next-Generation-Sequencing’ (NGS) into the Belgian healthcare system

The Ministry of health gave a mandate to the Cancer Center (WIV-ISP) to develop a Roadbook PersonalisedMedicine

“Introduction of Next-Generation-Sequencing in routine diagnostics in oncology and hemato-oncology”.

4

Preliminary steps

Pilot project

Preliminary steps:– Evidence-based guidelines– Specific criteria for the use of NGS– Selection of patients– Benchmarking study for the participating labs– Dataregistration– Training…..

5

The convention: objectives

To implement NGS under controlled conditions and tomonitor closely

Technical aspects– The implementation of a quality control system– The selection of patients for which the new technology

represents an added value– To collect data (registration is mandatory)– Guidelines:updated by COMPERMED

6


Regulatory aspects:- The creation of NGS networks

Budgettary aspects– Costeffectiveness of the new technique– To investigate the budgettary impact under specific and

verifiable conditions

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• At the end of the pilotstudy a thorough evaluationwill reveal whether this new molecular technologyhas improved diagnostics within the (hemato) oncology (therapy, survival rates….)

• At the end of the study we will be able to identify the bottlenecks– How to improve the data collection system?

Can NGS be integrated in the nomenclature andgeneralised?

8

Convention budget

• Partly financed through article 33bis and article33ter:– NGS will replace a combination of single more

classical tests/routine tests (sequential tests)• Partly financed by a forfait through article 56 of the

convention– 2 million €

Per indication: specific nomenclature codes can beused

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Expertise within the network

• Medical Oncologists (two)• Clinical Biologist or a Pathologist competent in NGS for

the specific tumortype• Onco-geneticist (hereditary impact like BRCA)• Biomedical sciences (or equivalent, 4 years of relevant

experience)(two)• (Bio) Computer-scientist (or equivalent, 2 years of

relevant experience) and a substitute within the network• Bachelor in medical lab technology (one and a

substitute)

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Start: 1st June 2019

• 10 networks with 24 labs (7 Vl, 1 Bxl, 2W)

• MOC range: 1200 - 5800

• NW size: 5 – 26 Hospitals

• About 25% of MOCs would include NGS analysis(close to 15000 NGS analyses)

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Monitoring and evaluation

Implementation (Y1)RUN NGSCollect data

NGS in nomenclature by 202?

Analyse (Y2)scopebudget

Adapt (Y2/3)data collection procesindicationsNGS platforms

COMPERMED

NGS GUIDELINES

First version published in 2017 in the Belgian Journal of Medical Oncology

• The chapters ‘variant interpretation’ and ‘NGS report content’ were further

developed.

• Documents taken up by Belac

NGS GUIDELINES – Variant interpretation

Workflow and scoring system uniform somatic variant biological classification

NGS GUIDELINES – NGS report content

Biological classes

- Pathogenic must be reported

- Probably pathogenic must be reported

- VUS must be reported (separated)

- Probably benign should not be reported

- Benign should not be reported


Clinical classes:

- Tier I: Strong clinical significance must be reported

- Tier II: Potential clinical significance must be reported

- Tier III: Unknown clinical significance must be reported

- Tier IV: variants deemed benign or likely benign should not be reported


The clinical report should contain the following information:

1. Laboratory, patient and physician identification

2. Medical information

Primary tumor type and histology e.g. NSCLC, adenocarcinoma

e.g. Acute myeloid leukemia

Clinical Information and Request e. g. stage of tumor, treatment phase, therapy considered, …


3. Sample information

Sample ID (primary lab) XXXX

Sampling date e.g. 24-09-2018

Date of sample received e.g. 01-10-2018

Sample tumoral stage Primary/metastasis

Sample anatomic site e.g. colon, lung, liver, blood, pleural cavity, bone marrow, axillarylymph node …

Sample type eg. Resection, (endoscopic) biopsy, fluid, aspirate, trephinebiopsy …

Sample procedure e.g. FFPE, frozen tissue, fresh tissue;…

Neoplastic cells (%) e.g. 10

Sample quality Disclaimer if sample does not fulfill pre-analytical requirements


4. Test results

5. Conclusions and interpretation of the report

6. Methods

Gene name at coding DNA level at protein level Biologicalclasses

Allelic frequency (%)

EGFR c.2573T>G p.(Leu858Arg)* Pathogenic 5

MOLECULAR TESTING IN (HAEMATO)-ONCOLOGY

(ALGORITHMS)

A L I N E H E B R A N T – E L S VA N VA L C K E N B O R G H

C A N C E R C E N T R E , S C I E N S A N O

MOLECULAR TESTING ALGORITHMS

AIM:

Propose workflows (algorithms) of molecular tests to be performed for a

particular cancer with regard to their clinical utility (diagnosis, prognosis or

therapy) to guarantee good clinical practice

Information available on the website: www.compermed.be

MOLECULAR TESTING ALGORITHMS -Molecular test levels

MOLECULAR TESTING ALGORITHMS -website


- CRC- Gastric cancers- Pancreatic cancers- GIST- Breast

- Develop algorithms for other solid tumors (lung, melanoma, brain,…)

Published in BJMO in 2018 by A. Hébrant

SOLID TUMORS:


Submitted in BJMO, A. Hébrant

- Lung- Melanoma- Brain- Endometrium- Ovary- Head and neck- Soft tissue- Thyroid

- Update of the different algorithms

SOLID TUMORS :

NGS BENCHMARKING TRIALS

A L I N E A N TO N I O U

Q U A L I T Y O F L A B O R ATO R I E S D E P T.

Assess the quality of NGS tests carried out by the participatinglaboratories:

Examine the ability of the validated/accredited NGS assays toaccurately and reproducibly detect mutations

Next step:• Develop a national EQA program

Aim

Participation was open to all Belgian laboratories which meet theactual legal obligations:

• Licensed (pathology, clinical biology, centre of humangenetics)

• Accredited or in process to be accredited for NGS testing(ISO 15189)

Methods: Participants

Well-characterized genomic DNA from tumor cell lines:mixture of different cell lines

Reference samples produced externally according to our customdesign and validated by NGS and ddPCR (HORIZON, accredited ISO9001 and 13485) :• Type and number of variants/sample• Allele frequency between 3 and 50%• Clinically relevant mutations• Variety of mutation types: missense, frameshift and indels

Methods: Reference samples

Methods: Data analysis

1. Summary of laboratories’ methods2. Analysis of all unexpected results 3. Bioinformatics analysis of all participants' raw data (Thomas

Delcourt)4. Variant interpretation collection

Individual report and global report

• Numerous differences observed between NGS methods used inBelgium

• Good global success rate for the assessed variants

• No uniformity in sequence annotation and in gene references used

• No uniformity in the choice of which variants must be present in theclinical report and in their interpretation (biological classes/clinicalclasses)

Since February 2018, ComPerMed expert group for variantinterpretation and clinical report content

publication of Belgian guidelines

32

General Conclusions

2019 Perspectives:

•2019/1: Benchmarking trial case studies on solid tumors (20 participants)

•2019/2 : Benchmarking trial case studies on hematological tumors (23 participants)

•2019/3: Benchmarking trial on FFPE real solid tumors Formalin-Fixed Paraffin-Embedded (FFPE)

Next steps and perspectives

INFORMED CONSENT, LEGAL AND ETHICAL IMPLICATIONS OF NGS USE

Wannes Van HoofCANCER CENTRE, SCIENSANO

1 test focus group (n=9)5 focus groups in Dutch (n=37)5 focus groups in French (n=24)• Respondents: aged 32-75 (54.5); suffering from breast/ ovarian/ lung/

colorectal/ skin (melanoma) cancer• Recruited through patient organizations, social networks and hospitals

Information video on Youtube channel Belgian Cancer Center: https://www.youtube.com/channel/UC2C-15GeaC-zxoqFffcbJnQ

8 assertions containing value laden statements about precision medicine = the thread for the group discussions

Focus Group Study

1. UNCERTAINTY• Genes• Research (practices, databases, outcomes, …)• Privacy protection• Data ownership• Future use (fear of ‘something’ untowards happening with ‘my’ data)

Key findings

• Informed consent is an illusion: ‘when you have cancer, when you are sick, you are not really yourself’

• Personalized informed consent process

• Important to respect the goals and values of patients• Often not aligned with research interests• Sense of community amongst cancer patients• Fear of unjustified use of patient data

• TRUST: the foundation for cancer patients’ trust iscurrently thin, more openness and transparency isrequired to maintain social support for increasinglyexpensive and complex new treatments and diagnostics

Key messages and recommendations

HEALTHDATA

NGS / PITTER / PRECISION

Nicolas RosewickHealthdata, Sciendano

HD4DPHD4RES

HD4BCR

Healthdata datawarehouse

Belgian Cancer Registry

Data collection Data transfer

Analysis

HOSPITAL & LAB

TECHNICAL PLATFORM

REGISTRATIONS (TPR)

Green = uncoded dataRed = coded dataPurple = coded, aggregated data

LEGEND

eHBox codage eHBox

decodage

Electronic Patient Dossier

Dataflow

Dataflow

Lab HD BCR

PRECISION

NGS

PITTER

RN1

Diapositive 40

RN1 Rosewick, Nicolas; 18/03/2019

Healthdata.be status

- PRECISION- Onboarding of all data providers finished- Data collection start 03/2019

- NGS / PITTER- Internal load testing of VCF attachment performed- Pilot phase started (5 labs)

- Duration : 03/2019 – 04/2019- Goal :

- Test data flow Lab -> Healthdata- Understand VCF storage at lab side

- Production 05-06/2019- Perspective :

- Healthdata architecture 2.0 (2020) : S2S

GLANCE TO EUROPE 21ST CENTURY

INNOVATIVE PARTNERSHIP FOR ACTION AGAINST CANCER (iPAAC)

Official iPAAC Joint Action presentation

GENERAL INFORMATION

• The Innovative Partnership for Action Against Cancer (iPAAC) Joint Action, which has been selected for funding under the Third Health Programme (2014–2020), brings together 44 partners from 24 European countries.

• It aims to build upon the outcomes of previous EPAAC and CANCON Joint Actions and is coordinated by the National Institute of Public Health of the Republic ofSlovenia (NIJZ).

• The iPAAC Joint Action has officiallystarted on 1st April 2018and will last for three years.


iPAAC BUDGET: 5.625.000 EUR 4.500.000 EUR co‐funding by EC (80 %)

iPAAC STRUCTURE

Innovative Partnership for Action Against Cancer (iPAAC) is the third consecutive Joint Action dedicated to cancer control.

iPAAC WORK PACKAGES:

WP 1 – CoordinationNational Institute of Public Health of Slovenia (NIJZ)

WP 2 – DisseminationInstitute of Health Information and Statistics of the Czech Republic (UZIS)

WP 3 – EvaluationCroatian National Institute of Public Health (HZJZ)

WP 4 – Integration in National Policies and Sustainability Belgian Cancer Centre, Sciensano (SC)


WP4 WORK PROGRESS

Belgian Cancer Center Sciensano

ROADMAP

iPAAC STRUCTURE

WP 5 – Prevention and ScreeningCancer Society of Finland (CSF)

WP 6 – Genomics in Cancer Control and CareBelgian Cancer Centre, Sciensano (SC)

WP 7 – Cancer Information and RegistrationItalian National Institute of Public Health (ISS)

WP 8 – Challenges in Cancer Care Catalan Institute of Oncology (ICO)

WP 9 – Innovative Therapies in CancerFrench National Institute of Cancer (INCa)

WP 10 – Governance of Integrated and Comprehensive Cancer CareGerman Federal Ministry of Health and German Cancer Society (DKG)


PCP: Next‐Generation‐Sequencing in Healthcare applications(acronym: Onco‐NGS)

Marc Van den BulckeCancer Centre, Sciensano

ComPerMed, 19 January, 2019

Scope of EC‐PCP NGS in HealthcareScope:

The objective is to implement NGS in routine diagnostics for personalised medicine and scale up demand‐driven innovation for healthcare systems.

This includes organisational, economical, technical and clinical aspects.

It should lead to NGS tests, clinically validated procedures (including sex analysis), quality assurance schemes, tools and methods for data collection, management, analysis and interpretation, with a view to assist clinical decision‐making and foster medical research and innovation.

Transferability and cloud based NGS data analyses should be considered, as appropriate.

Input from initiatives like the EJP Cofund on rare diseases and ERNs should be considered when relevant.

Ethical issues should be addressed.

EC‐PCP NGS in Healthcare (Horizon 2020 program)

Scope: develop integrated solution for testing, analysing, reporting and storage of Next‐Generation‐Sequencing medical data within routine healthcare diagnostics

4 target domains:‐ Metastatic cancers‐ Immunotherapies‐ Genetics‐ Hospital‐borne infections

Domains are only indicative – others are allowed

Key challenges Accessibility to all citizens

Standardization from “Analyte to DATA”

Timely platform conversion

IP/Regulatory compliance (FtO, IVD, GDPR, ISO,…)

Interdisciplinarity

Private Public Partnership

Cost

PCP partnership• EU Member States (MS)

PCP requirement: at least 3 EU MSProposal: Be, Fr, It, Sp and Ger

• MS stakeholders (= Test payers) Be: NIHDI; France: INCA, Aviesan, … It, GER, Sp: regional

auth.

• Procures (= Test buyers) At least two local hospitals or private licensed medical

labs

open market consultation with the industry, including on technical and service readiness analysis of the suitable testing environments analysis of differences in legal public procurement framework for the participating procurers in health and social care,market analysis and analysis of potential barriers (standardisation, certification, regulatory requirements, intellectual property rights, contracting models, payment schemes) consultations with relevant stakeholders, end‐users (consumer organisations, reimbursement bodies) to prepare for a future market uptake of the solutions

Intellectual property

Coordination

Market scan

HCS Integration(reimbursement, legal,

accreditation, registration, …)

Tec

Infectious diseases

Cancer

Genetics

Technical Specifications

IVD properties

PPI partnership

others

ELSI aspects

Onco‐PCP Players

BUYERS (Lead procurer and procurer)Supporting entities, third parties, interested entitiesTENDER

EconomicOperators

A

EconomicOperators

B

EconomicOperators

C

EconomicOperators

D

D

A

B

C

A

D

C

Chip

ClinVal

IT

WP1 and WP6

Phase 0

TECH specIP ‐ FTO

Business CasePrior Notification

StrategyCE‐IVD strategy

GDPR implicationsTender

Eval. Com (citeria, members)

Dessimination

PRE CO

MMER

CIAL

TEN

DER

Phase 1Solution design

Sup ASup BSup CSup D

DesignEvaluationCommittee(D‐EVC)

Phase 2Prototype development

‐Analytical testing

Sup ASup CSup D

Phase 3Pre‐commercial

device‐

Clinical testing

Sup ASup D

Anal. testEvaluationCommittee(A‐EVC)

PrototypeEvaluationCommittee(P‐EVC)

Y01 Y04Y03Y02 Y05

WP3

WP2WP5

WP4WP3

WP5

WP4WP3

WP5

WP4

WP3

WP5

PCP Onco‐NGS

Proposal organisation

WP1 : Coordination WP2 : Preparation of procurement WP3 : Tendering WP4 : Contract implementation WP5 : Communication, Exploitation and Dissemination WP6 : Ethical, Legal, privacy and IPR

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