CART@GENEThe CART@GENE project is a population genomics project that aims to understand and guide the application of the Human Genome Project and new technologies in the maintenance of health and in susceptibility to common diseases such as cancer, diabetes, hypertension, arthritis, and others.

WHAT IS CART@GENE?

• A resource of health, environmental and genetic information to be widely used by the Quebec, Canadian and worldwide research communities interested in human genetics and public health.

• An unbiased, random sample of the heterogeneous Quebec population

• A double-coded, semi-longitudinal survey.• 50,000 adults between 25-74 years of age representing

≈1.2% in that age group. (Phase A = 20,000 over 3 years).

CART@GENE will:

• provide a public resource (e.g. CEPH Model) for the research community, through an Open Selection Process

• allow studies of genetic and environmental factors (and their interactions) that modify disease risk.

• serve for the validation for candidate gene studies.• serve as a baseline study for the development of

pharmacogenetics and public health programmes (education, promotion, prevention, policymaking and health services).

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Advantages of doing a population genomics project in Quebec: Universal health care system, managed by a central body (RAMQ) and regional boards.

1. Unique Health Insurance Number2. Name and Surname at Birth3. Date of birth and sex4. Expiration date5. Personal Identifier

1996

Table 1: CARTaGENE Project Recruitment and Enrolment PhasesPhase Contact

TargetTarget

EnrollmentRationale

Phase A(ICIProject)

30,000 to45,000

20,000 Participants near major university-hospitalcentres including: Montreal, Quebec City,Saguenay -Lac St-Jean, Sherbrooke

Figure 1: Phase ARecruitment

Phase B 45,000 to70,000

30,250 Western areas of Montreal, St-Lawrence RiverBasin, Outaouais River and Montérégie,Laurentide and other outlying regions.

Pri

nci

ple

s

• Individuality• Diversity • Complexity• Reciprocity• Solidarity• Security • Accountability • Equity • Citizenry • Universality

IPEG Institute of Populations, Ethics and Governance*

Who: Not-for Profit CorporationBoard of public representatives

Why: Independent ethical governance of population tissue/ databases including:

BiobanksOrphan populations/banksLarge cohorts

Public information on the ethical collection/uses of such tissues/databases

Mandate: Establish an ethical framework for collection/uses Periodic public information and periodic auditsEnsure optimal uses for the public goodIdentify and manage conflicts of interests

* Three Founders (Not to be represented on the Board):University of Montreal (representing Quebec Universities)FRSQ (Quebec Health Research Funding Agency)Genome Quebec

DOUBLE-CODING - RAMQ: • ICD-9 Codes (public); medication codes• Right to withdrawal• Follow-up on health and lifestyle events• Specific “new” questionnaires

RECRUITMENT BY MRC: • (More community-based than FSA)• Expertise from ISQ and Santé-Québec• No more recruitment of regional “trios”

SELF-QUESTIONNAIRES: • Logistic Help: 1-800- phone line (5/7 days)• Mainly socio-demographic data

IMMEDIATE RESULTS: • Physical, physiological and biological• Given to participant and/or transmitted to participant’s personal M.D.

CONSENT: (for 50 years) • Research on genetic diversity in relation to health or disease and the human evolution.•Transfer of “public” codes such as ICD-9 & medication; recontact/follow-up on health and lifestyle events (v.g. death); and, for genealogical reconstruction.

IPEG: Complete governance of CARTaGENE

Age = 25-75

N = 50,000

CaG Clinical Team (CCT)CaG Clinical Team (CCT)

RAMQRAMQ

RAMQRAMQ

#RAMQNom. info

Generation of a random data

subset for CaG + encryption of

#RAMQ

Sampling, Logistic and Dispatching Office (SLDO)Sampling, Logistic and Dispatching Office (SLDO)

Preparation of the stratification / sampling. Request RAMQ to conduct the search

Generation of data subset for RIC

Contact participants, flags refusals and

acceptance

SLDOSLDO

#RAMQcNom. info

Recruitment Information Center (RIC)Recruitment Information Center (RIC)

Consents

Generation of data subsets for CCT (for each site / MRC)

CCTCCT

#RAMQcNom. info

RICRIC

#RAMQcNom. info

Contact participants,Send questionnaires and

consents, manage refusals

Meeting with subject / Validation of participant identity, consents forms

Attribution of #CaG

COCO

#RAMQc#CaG

RAMQc

Fills questionnaires and clinical forms.

Update / longitudinal data

CaG Data CenterCaG Data Center

COCO

#RAMQc#CaG

Attribution of #CO

Separation

CO-CaGCO-CaG

#CO#CaG

Coding Office (IPEG)Coding Office (IPEG)

CaG BiobankCaG Biobank

Flag participant as participating, delete

nominative information

CO-SLDOCO-SLDO

#RAMQc#CO

Genealogies platformGenealogies platform

Fills genealogy questionnaire, identified with #RAMQc

BALSACBALSAC

#RAMQcGenealogies

BALSACBALSAC

#RAMQcNames

Reconstitution of genealogies

CaG DBCaG DB

#CaG#CaG

Take blood sample, samples identification,…

GVGV

#CaG#CaG

Translate #RAMQc into #CO

Translate #COinto #CaG

SLDO/CCTSLDO/CCT

SOP and tools production

CCT Training

Monitoring + quality control

1

3

4

5

6

7

8

9

11

12

13 14 18

17

15

16

2

19

20

21

22

10 P1.1

P2

P3

P2

P4

Op1

Op2

Op3

Op1.1

P8

Op1.2

P5

Figure 1: GenVault: DNA automated storageand retrieval system

Figure 2: Robotic samplepreparation and GenPlate

Saguenay-Lac-St-Jean Biobank

Quebec Health Survey

• First “use” of CARTaGENE

• Early emphasis on CDV, diabetes and obesity related phenotypes:- anthropometric measures, blood pressure- fasting and 2-hour glucose- bio-impedance, measures of arterial stiffness- transcutaenous cholesterol measures - (automated report to patient and his physician)- blood phenotypes: lipid profile, ApoB, homcystinemia,

HS-CRP, glycated hemoglobin, vitamin B-complex-genotyping of 100 SNPs in apolipoproteins, PPARs,

LDLR, apoE, LPL, ACE, etc.

GOVERNANCE Coding Office IPEG Board Ethics Committee

ADVISORY

Scientific Advisory

Board

Research Management

Committee (RMC)

Executive Committees

? Finance Audit ? Project QA ? HR

M ANAGEMENT Scientific Director Assoc. Sci. Director HOST

INSTITUTION

COO Partnerships Manager Project Coord.

Financial Coord. (Genome Quebec)

UdeM

Logistics Committee

OPERATION S Project Study Nurse and Project Data Monitor (QA/QC)

1. Participants & Recruitment

2. Enrolment & Consent Mgmt

3. Clinical & Social Data, Blood Samples

Coordinators Operation Coord. Recruitment Coord. Clinical Site Nurse CCT Team CaG

Sites: Quebec (CHUL); Montreal (CHUM, ICM, IRCM); Saguenay (CHS)

PLATFORMS

1.1 IT/ Bioinformatics

2. Demographics 3.1 SOP Production & Training

4. Biobank 5. Genealogy 6. Public Engagement

1.2 Longitudinal Data (RAMQ)

3.2 Phenotyping SOP 4.1 Blood /DNA Sample Storage

7. Ethics

0.00 $0.50 $1.00 $1.50 $2.00 $2.50 $3.00 $3.50 $4.00 $4.50 $

SamplingRecruitment

Clinical activities

InformaticsDemographics

Public Engagement

Ethics

GeneaologiesManagement

SalariesConsumablesG&AEquipment

CARTaGENE COST BREAKDOWN

Phase A: Budget: 20 770 080 $Phase B: Estimate: 20 M

Saguenay DNA Bankto serve CARTaGENE Phase A, B and other projects

Total: $ 5 771 572

GENVAULT80%

Renovation20% DEC

35%

MDERR40%

GENVAULT19%

CHS6%

Components Potential Funding Sources

Quebec Health Survey Costs

21%

79%

0%SalariesConsumablesG&AEquipmentServices from others

Budget: 1 579 436 $

Potential Funding Source: MSSS

QUANTITATIVE STUDY: Two-phase telephone survey

PHASE 1PHASE 1 • 1,800 interviews held between Nov. 7 and Dec. 7, 2003• 1,800 interviews held between Nov. 7 and Dec. 7, 2003

Mailout of Cart@gene documents to 1,394 people (77,5%) having priorly agreed to

receive them

Mailout of Cart@gene documents to 1,394 people (77,5%) having priorly agreed to

receive them

PHASE 2PHASE 2803 interviews (68%) held

between Nov.19 and Dec.19

803 interviews (68%) held between Nov.19 and Dec.19

FINDINGFINDINGThe high proportion of people accepting to

receive Cart@gene info (77,5%) & the high rate of participation in the second phase (68%)

reveal the interest in the project.

The high proportion of people accepting to receive Cart@gene info (77,5%) & the high rate

of participation in the second phase (68%) reveal the interest in the project.

Cart@gene accorded ''qualified'' support

3%

18%

4%

45%

30%

0% 20% 40% 60%

A lot ofapprehension

Someapprehension

Neitherenthusiam norapprehension

Some enthusiasm

A lot ofenthusiasm

Respondents had the following reactions to the project:

Close to half of respondents showed ''some enthusiasm''.Close to half of respondents showed ''some enthusiasm''.

Estimation of the rate of participation

SegmentProportion of the

Quebec populationRate of participation (inside the segment)

Rate of participation (in relation to the targeted

population)

1- The uninterested 13% 22% 3%

2- The educated

enthusiasts26% 65% 17%

3- The wait and seers 24% 50% 10%

4- The apprehensive resisters

18% 10% 2%

5- The converted 19% 80% 16%

Estimation of the rate of participation:

48%

The estimation of the rate of participation is based on our current state of

knowledge (project to date). With a wide, efficient and targeted communication

strategy, the goal of achieving a higher participation rate seems feasible.

The estimation of the rate of participation is based on our current state of

knowledge (project to date). With a wide, efficient and targeted communication

strategy, the goal of achieving a higher participation rate seems feasible.

Factorial correspondence analysis: to identify and quantify different segments of individuals who differentiate themselves in regard to their particular responses among all the questions of the survey.

Team Leaders

• Laberge Claude Genetics Laval U• Gaudet Daniel GeneticsSaguenay• Knoppers Bartha Maria Ethics Montreal U• Hudson Thomas J Genomics McGill• Labuda Damian GeneticsMontreal U• Couture Patrick Medicine Laval U• Hamet Pavel GeneticsMontreal U• Bouchard Gérard Genealogy Chicoutimi U• Bergeron Pierre Stats Stat Inst.• Vézina Hélène Demography Chicoutimi U• Godard Béatrice Ethics Montreal U• Arsenault Steve Informatics Chicoutimi• Francois Rousseau Biochem Laval U• Julian Little Epidemiology Ottawa U

CARTaGENE schedule• > 3 years of planning (2002-2005)• Statements of Principles of the RMGA:

– Sampling/Access– Populations

• Public consultation of the public: qualitative and quantitative phases.• Funding applications --------------------------------------------------------• Spring 2005: Authorization from Quebec’s Access Commission and

from a “national” REB.• Fall 2005: Trial phase to recruit participants according to CaG standard

procedures.• 2006-2008: 20,000 participants• 2008-2011: 30,000 participants