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

300-400 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

The Common Rule Federal regulations for conducting research

with human subjects Adopted by 17 federal agencies in 1991

Research institutes must give assurance that they will enforce protection of human subjects in research done at their institution

Research institutes must have an Institutional Review Board (IRB) to review federally funded research studies with human subjects

Research with human subjects requires informed consent

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 will be a source of data for original research

Students will 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.