Digital intensive genomic medicine: is data driven medicine changing the

values and the practices of medicine? Anne Cambon-Thomsen, MD, emeritus research director CNRS,

UMR1027 Inserm & Université Toulouse III Paul Sabatier: Epidemiology and Public health analyses, Toulouse, France

Co-leader of the working group ELSI of the French plan for genomic medicine (PFGM 2025)

Member of the European group on ethics of science and new technologies

anne.cambon-thomsen@univ-tlse3.fr

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Innovation & Values Schumpeter (1930): “Innovation changes

the values onto which the system is based“

The Cassandra Complex

or

“Ethicists” considered as being too negative or too late

Adapted from A Soulier and S. Leonard

The evidentiary time-lag ? Guidelines introduced

Technology introduced

Problems encountered Evidence gathered

High throughput technologies entering medical genetics practice

• Efficient for diagnostics in context of uncertainty on gene(s) involved

• (Will) become technically and economically interesting

BUT

• Generate unsought for information

• Complexity : different levels of capacity of interpretation and clinical significance

• Right to know and not to know becomes more complex to address

• Anonymization becomes a fiction.

3 CHALLENGE platform meeting - Copenhagen, DK 25/04/2019

Blurring several limits

• Specific clinical question/ genome exploration

• Clinical care/ research

• Protocol of research/ database driven discovery

• Health information/ non health information

• Body elements / information

• Clinical utility /personal utility (curiosity)

Creating continuum instead of discrete categories

• Evolving capacity of data interpretation

• Evolving level of identifiability

• Right to know/not to know generally do not apply the same way to all kinds of information

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Transforming established concepts

• Generating a world of documented uncertainty • Autonomy in the context of an evolving uncertainty?

• Meaning of « best interest »?

• Responsibility towards own health/family

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And why is all this very pertinent nationally in France? Notably because since 2016 a National Genomic medicine plan 2025 is planned and has started.

Patient/doctor dialogue Shared decisions

Request for exam Agreement

Pre-analytic sampling

National database of

Clinico-biological Meta-data

Technical validation

Sequencing / Analyses

INTEGRATE SEQUENCING INTO A GENERIC HEALTHCARE PATHWAY

DEVELOP A NATIONAL GENOMIC MEDICINE SECTOR

Support for the therapeutic

decision

Clinical data Genomic data

“Diagnostic Laboratory”

Support tools for analysis

Biological validation and interpretation

Support for the diagnostic decision

AMBITION OF THE FRENCH INITIATIVE

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Sending & collecting

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CAD

AURAGEN SeqOIA

Clinical data

GLOBAL VISION OF THE IMPLEMENTED TOOLS

Network of sequencing platforms

Central Analyzer of Data (CAD) Center of reference, innovation, expertise and transfer (CRefiX)

Sampling

200,000 genomes sequenced per year from 2025

A co-constructed 10-year national plan

• 3 main streams, 14 actions

• I- SET UP THE TOOLS FOR A GENOMIC HEALTHCARE PATHWAY:

• II- ENSURE THESE DEVELOPMENTS IN A SAFE TECHNICAL & ETHICAL

FRAMEWORK:

Action ⑧ Integrate ethical aspects related to the processing of clinical & genomic data

• III - IMPLEMENT MONITORING AND MANAGEMENT TOOLS:

Action ⑬ Organize information, consultation, and involvement of concerned stakeholders in society

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THE FIRST 2 SEQUENCING PLATFORMS

Standardized procedures & processes

Sampling

Sequencing

platforms

Reference

center

(CRefIX)

Sample transfer

Variant Call File (VCF) transfer

CAD

June 2019

AUvergne Rhône Alpes

GENomique

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4 CLINICAL PILOT PROJECTS

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Rare Disease: DEFIDIAG Intellectual Disability

Cancer : MULTIPLI Sarcoma (Multisarc trial) or metastatic

Colorectal Cancers (Acompli trial)

Common disease: GLUCOGENE Atypical forms of Diabetes

General Population: POPGEN

CLINICAL PILOT PROJECTS

ETHICS, REGULATORY ASPECTS AND SOCIETY

Patient information and consent : about ready !

Methodology

– Hearing of national and international stakeholders

– Collecting different clinical care/research frameworks (information and consent, including incidental findings)

– Exchanges/confrontations with pilot projects

Working group: Researchers (included human and social sciences), Ministries (Health, Justice), Patient/user associations, Different institutional levels (Health insurance, Health Agencies), Professional and scientific genetic societies

Data protection : storage and processing modalities of personal data resulting from

sequencing

Human and Social Sciences researches

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Thank you for your attention

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