Transforming Health Care Through Personalized

Medicine

Catherine A. McCarty, PhD, MPHSenior Research Scientist

Interim Director, Center for Human Genetics

Personalized Medicine Research Project

Ultimate Goal:– Translate genetic data into specific

knowledge about disease that is clinically relevant and will enhance patient care

• Short term Goal:– Establish database to allow research in

genetic epidemiology, pharmacogenetics, population genetics

Personalized Medicine Research Project

• Phase I: Consultation and initial enrollment, completed April 2004

• Phase II: Creating the infrastructure for a national resource and expanding the database

• Phase III: Genetic discovery projects, community and physician education and consultation

Consultation

• Community Advisory Group• Scientific Advisory Board• Ethics and Security Advisory Board• Focus group discussions• Community talks• Media releases

Why Marshfield? Marshfield

Epidemiologic Study Area (MESA)– Well studied

population– Primarily

Marshfield Clinic patients

– Many families have lived in MESA for many generations

Why Marshfield? Marshfield Clinic system of care Extensive Electronic Medical Record for

two decades MECCA disease lexicon Electronic prescription data

Research Foundation with strong programs in genomics and clinical research

Security Health Plan to capture diagnoses outside the Marshfield Clinic 55% overall

Study Logistics MESA residents aged 18+ contacted by letter and

telephone (600-1000 letters per week)• 30-90 participants per day (30 minute appts) Written informed consent and questionnaire

Allows sharing of samples and data Consenting participants donate blood for DNA

extraction, storage of plasma and serum $20 reimbursement for expenses (10% return)

Dietary history questionnaire and Baecke physical activity questionnaire ($10)

Participant/Non-Participant Comparison

19,723 enrolled 6-1-08

Variable Participants Non-Participants

Mean age (range)

47.5 (18-98.5)

47.7 (18-101)

Percent female 57.2% 49.4%

Number of unique diagnoses in 2002

14.3 (11.3) 12.2 (11.2)

Mean diagnosis records in 2002

34.4 (44.1) 30.4 (46.1)

Participant Demographics

• RaceCaucasian, 98.2%American Indian, 0.9%Hispanic, 1.1%Asian, 0.5%Other, 0.3%African American, 0.3%

• EthnicityGerman, 76.2%Irish, 17.3%English, 16.6%Other, 16.6%Polish, 12.6%Norwegian, 11.9%French, 9.8%Swedish, 6.8%Dutch, 6.4%Czech, 3.8%

Participant Residence

• Current– Working farm, 7.9%– Rural home or hobby farm, 30.2%– Suburb, city, village, 61.8%– Other, 0.1%

• Ever lived on a working farm, 51.7%

Participant Exposure Status• Smoking status:

– Current, 19.1% (22% in Wisconsin, 2003)– Past, 27.0%– Never, 53.4%

• Personal and/or family history of adverse drug reactions, 14%– 55.3% rash– 22.3% swelling– 19.3% breathing problems– 15.7% hospitalized (n=427)

Opt-out on Consent form

• 168/19,692 (0.9%) participants ask to not be contacted for future studies

– 65% agreed to complete dietary and physical activity questionnaires when asked

Distribution of Years of Health Information

Available

0

20

40

60

80

100

Age (years)

Per

cen

tag

e

20+ years 15-19 years 10-14 years

5-9 years < 5 years

Majority has 20+ years of health data

Process to Access Samples

• Feasibility request for phenotype• Scientific merit review

– External peer-reviewed funding mechanism OR Marshfield Clinic Research Committee

• IRB review/approval for all studies• Oversight Committee to release

samples• Funding is required for phenotyping and

identification and retrieval of samples• Data deposit within 6 months after

completing analyses

Pharmacogenetics Projects

• Statin efficacy and adverse reactions• Warfarin (blood thinner)• Topical beta-blockers for glaucoma• Metformin for diabetes• Tamoxifen in breast cancer

Genetic Epidemiology Projects• Alzheimer’s Disease

• Multiple sclerosis• Vertebral malformations• Fibromyalgia syndrome• Osteoporosis• Cataract and low HDL• Hypertensive heart disease• Glaucoma• Myocardial infarction• Coronary artery disease• Dyslipidemia in severely obese subjects

Other Activities

• Molecular finger printing and master plating of DNA samples

• Quality control for serum and plasma samples

• Twice-yearly newsletter to subjects

Infrastructure Funding Office of Rural Health Policy, Health

Resources and Services Administration1 D1A RH00025-01

Technology Development Fund Program, Department of Commerce, State of Wisconsin

Marshfield Clinic

• Approximately $150 per person to enroll in Phase 1

• Currently $250 per person to enroll with smaller staff

Summary

• Population-based biobank with nearly 20,000 adults enrolled

• DNA, plasma and serum samples• Diet and activity questionnaires• Access to electronic medical records• Ability to recontact subjects• Consent to share data and samples

www.mfldclin.edu/pmrp