The StarNet Case Control Study Investigating the Effects of Genes and Environment on Smoking Behavior

Overview of Research Study Phase 1: Designing the StarNet Case Control Study Phase 2: Recruiting subjects; collecting DNA and questionnaire data from them; genotyping subjects’ DNA; entering data into a database Phase 3: Analyzing data

The StarNet Study Phase 1: Designing the Study Study design includes: Research question Outcome and exposures Study population Research questionnaire

Research Question: What genetic and environmental exposures are associated with people moving from smoking initiation to maintenance? Cases are people who initiated smoking and became smokers. Controls are people who initiated smoking but never became smokers. Cases Controls Non-smokers never smoked, or tried smoking but did not continue 1. Initiation 2. Maintenance 3. Cessation 4. Relapse Former smokers successful quitters Stages of Smoking Experimental smokers Regular smokers

Outcome and Exposures Outcome: Moving from smoking initiation to maintenance Exposures: Several environmental factors and a few genes involved in the reward pathway or nicotine metabolism Subjects will be genotyped for a few candidate genes Subjects will complete a questionnaire that asks about environmental factors

Our Study Population subjects Both men and women Different ethnicities Age 25 to 54

Questionnaire Design What do we want to know? Demographic questions Smoking habit Environmental exposures

Progress on Phase 1 Study design was completed in 2007 Study has been approved by UW IRB What is the UW IRB? Why do we need approval?

Protection of Human Subjects The Belmont Report: Ethical principles and guidelines for research on human subjects The Common Rule: Federal regulations for human subjects research (based on the Belmont Report)

The Belmont Report Autonomy (respect for persons) Beneficence/non-maleficence (Do good; maximize benefits and minimize harms) Justice (Be fair)

Autonomy Research subjects have the right to decide whether to participate in a study Minors or people with limited capacity represented by a responsible guardian informed consent/assent People should not be coerced into participating and should not receive undue influence

Beneficence/Non-maleficence For each study, researchers need to minimize risks to research subjects while maximizing benefits of the study As a community, researchers needs to consider the long term benefits and risks from a field of study or from the development of a medical procedure

Justice Benefits and burdens of the study are fairly distributed Vulnerable populations do not bear an unfair burden of research

How Does the StarNet Study Meet the Ethical Guidelines of the Belmont Report? Autonomy Competent adults Give informed consent Small cash compensation Beneficence/Non-maleficence Potential risks: discomfort with some questions, blood draw, or revealing genetic information Benefits: improving education and our understanding of factors affecting smoking behavior Justice Diverse subject population Competent adult subjects who volunteer

The StarNet Study Phase 2: Recruitment and Genotyping Subjects are being recruited from around Puget Sound Subjects call the study coordinator, who screens each caller to determine whether they are eligible for the study as a case or a control

Meeting a Subject Eligible subjects: meet the study coordinator in a private office read consent form, have opportunity to ask questions sign consent form if interested in participating in study Fill out questionnaire, give blood sample

DNA Preparation and Genotyping Lab purifies DNA from the subjects’ blood samples StarNet lab uses PCR to amplify regions of subjects’ DNA StarNet team sends equipment, reagents, and PCR- amplified DNA to classrooms for genotyping High school students genotype the subjects’ DNA and send results back to StarNet The StarNet team enter genotyping data and environmental data from questionnaire into a queriable database.

The StarNet Study Phase 3: Data Analysis The database is a source of data for original research Students propose hypotheses about smoking behavior, and use the database to test them Students will share their discoveries with the StarNet team and with other classrooms

Case Studies Read one of the four case studies. Decide whether a human subjects violation has occurred. If so, recommend what should be done to improve the study or decide whether the study should be terminated.