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).
QuickTime™ and aPhoto - JPEG decompressor
are needed to see this picture.
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