Community Concerns Regarding Genomic Research and Data Sharing: Adding Genome-wide Association to Population Studies

Community Concerns Regarding Genomic Research and Data Sharing:Adding Genome-wide Association to Population Studies Daniel Levy, MD Framingham Heart Study National Heart, Lung, & Blood Institute

A Fifty-Year Promise Under Attack • “They’re not selling my data.” Evelyn Langley was adamant. In the spring of 2000, she again became a study activist. She was dead set against the undertaking she read about in a letter to participants and a newspaper report….[A] university had formed a for-profit company called Framingham Genomic Medicine to distribute a half century of data and genetic information from Framingham Heart Study participants. Excerpted From: Levy, D and Brink, S. A Change of Heart. Published by Alfred A. Knopf. New York. 2005.

A Fifty-Year Promise Under Attack • After attending her twenty-six voluntary appointments over the course of more than half a century, Langley was livid. When she was young, she had walked the streets of Framingham, urging her neighbors to volunteer. And all those years ago, she gave them her word of honor that their privacy would be protected at the same time that the information gleaned from their volunteerism would be available free of charge to scientists. Langley believed that none of the original five thousand participants or their descendants had ever expected their efforts to enrich medical entrepreneurs. Now she was reading and hearing speculation that their personal medical information would be sold, and that a private, for-profit company stood to make money off her and her neighbors’ altruism. Excerpted From: Levy, D and Brink, S. A Change of Heart. Published by Alfred A. Knopf. New York. 2005.

Framingham Genome-wide Association Study

Framingham SHARe:Three Generations 2008 1948 Original Cohort: 28 Exams N = 5209 men and women (ages 28-62) 1644 spouse pairs, 596 extended families 2008 1971 Offspring Study: 8 Exams N = 5124 men & women (ages 5-70) 1576 spouse pairs, 3514 biological offspring 2005 2002 Third Generation Study N = 4095 men and women

Framingham SHARe • Genome-Wide Association Study • All consenting Framingham Heart Study participants with DNA from three generations (n=~9500) • Genotype 550,000 genetic variants (SNPs) in each participant • >5 billion genotypes

Community Questions About Genetic Research • How will participant privacy and confidentiality be ensured? • How will participants be involved in planning? • What ethical oversight will take place? • How will DNA be used in relation to consent? • How will this resource be shared with the scientific community?

1. Protection of Privacy and Confidentiality • Data and samples de-identified • Data shared only after: • Review and approval of application by Data Access Committee • IRB approval from user’s institution • Signed data distribution agreement

2. Involvement of Study Participants • December 2005 - January 2006: Communication with study participants • Focus group meeting (Dec. 14, 2005) • Newsletter (mid Jan. 2006) • Press release (mid Jan. 2006) • Town meeting (late Jan. 2006) • Notify scientific community (Spring 2006)

3. Ethics Oversight • April 2003: Ethics Advisory Panel Convened • The Panel recommended that a formal Ethics Advisory Board be established to make recommendations on such issues as they arise and that the Board include study participants as well as local clergy, physicians, genetic counselors and an ethicist.

Newsletter: Spring 2004 • “To help us with complex decision making and to advise us, at the recommendation of an Ethics Advisory Panel that met in April, 2003, we have established an Ethics Advisory Board.” • “To keep you informed about matters that may be of concern to you, we will publish summaries of the Ethics Advisory Board’s opinions in our newsletters.” • “Your participation in this process of posing questions to and reviewing opinions of the Ethics Board is something we value greatly. If you have a question for the Ethics Board, please send it in writing to Ms. Esta Shindler.”

3. Ethics Oversight • Ethics Advisory Board established and charged to: • Consider complex questions posed by Study participants and investigators • Provide viewpoint of Study participants and the community • Generate written responses to questions that will be summarized in newsletters and shared with all Study participants

3. Ethics Oversight: • On November 9, 2005 the Ethics Advisory Board met and reviewed a proposal for a Framingham genome wide study

Newsletter: Winter 2005 • A team of researchers…is using a new technique for identifying disease-causing genes. • Using the new technique, the researchers will scan about 100,000 different SNPs simultaneously to find those that could explain cardiovascular and other diseases and their associated risk factors.

4. Informed Consent • Purpose of Study • Description of clinic exam procedures • Rights • Benefits, risks, costs • Genetic aims of study • Participant preferences determined

4. Informed Consent • You may choose to withdraw your blood samples at a future date and your samples will be destroyed at that time. • The coded samples will be stored securely, separated from files which link your name to the code numbers. • You will be kept informed through periodic publications from the Framingham Heart Study of any new findings about genetics, cardiovascular disease or other health conditions generated from the DNA analysis.

4. Informed ConsentBlood, DNA, and Cell Lines 1). □YES □ NO I agree to participate in the Framingham Heart Study examinations described above to study the frequency of and factors contributing to heart and blood vessel diseases, lung and blood diseases, stroke, memory loss, and other diseases and health conditions.2) □YES □ NO I agree to provide a blood sample from which DNA and other components can be extracted. The DNA will be made available to researchers studying the diseases listed above.3) □YES □ NO If a cell line has not already been collected, I agree to allow a cell line to be made from a sample of my blood to provide a renewable supply of DNA.

4. Informed Consent:Traits That Can Be Studied 4) □YES □ NO I agree to participate in the genetic studies of factors contributing to heart and blood vessel diseases, lung and blood diseases, stroke, and memory loss.5) □YES □ NO I agree to participate in genetic studies of other diseases and health conditions including but not limited to joint disease, bone loss, and cancer. 6) □ YES □ NO I agree to participate in genetic studies of reproductive conditions and mental health conditions such as alcohol use and depressive symptoms.

4. Informed Consent:For-profit Access to Data 7) □ YES □ NO • I agree to allow researchers from private companies to have access to my DNA and genetic data which may be used to develop diagnostic lab tests or pharmaceutical therapies that could benefit many people.

4. Informed ConsentBlood, DNA, and Cell Lines

4. Informed Consent:Traits That Can Be Studied

4. Informed Consent:For-profit Access to Data

5. Data Sharing • Rapid sharing of the resource with the scientific community via NCBI • Aggregate data posted on dbGAP • Individual participant data available via application process • NIH Data Access Committee review and approval • IRB approval required • Data distribution agreement • Data distribution according to consent provisions • Launch date: October 1, 2007

Conclusions • Genetic research in prospective observational studies must include • Participant involvement • Multiple consent provisions • Ethical oversight • To be maximally beneficial, data sharing should be encouraged and planned in advance

Proposed Genome-Wide Association Study: Mission Statement • To create a non-profit scientific resource to study the connections between genetic variation and common diseases by using the wealth of data and specimens from the Framingham Heart Study in concert with a dense SNP map of the human genome and high throughput genotyping technologies. • To do so while meeting the highest ethical standards and protecting the confidentiality of participant data. • To provide free access to this resource for all qualified scientists in accordance with NIH/NHLBI guidelines.

Establishment of Framingham Ethics Advisory Board

Description of Existing Oversight • Framingham Heart Study • Executive Committee, Exam Committee • U.S. government • National Heart, Lung, & Blood Institute • Office of Management and Budget • Boston University Institutional Review Board • Informed Consent • Independent oversight • Observational Studies Monitoring Board

Ethics Advisory Board • Dr. Greg Koski, Chair • Dr. James Alderman • Michelle Feinberg • Deborah Fuller • Victor Galvani • Rev. J. Anthony Lloyd • Dr. Ralph Sherman • Maryann Whalen • David Whittemore

Comments from the Ethics Advisory Board • Participants needs to realize that their genetic data will be scattered all over the globe. • This is an extraordinary gift of the Framingham community to the world. • A plan needs to be developed to announce this to participants in a sensitive manner • Does the consent adequately provide for this research?

Informed Consent • Confidentiality • Any information we obtain about you during this study will be treated as strictly confidential • Notification • You will not be informed of the results of the research performed upon your genetic blood sample • You will be kept informed through periodic publications from the Framingham Heart Study of any new information or findings about genetics

4. Informed Consent • Your Rights • Taking part in this study is voluntary • You have the right to refuse to take part in any/all components • You have the right to stop participating at any time • You may withdraw your blood samples at any time and your samples will be destroyed

Framingham Heart Study Informed Consent: Genetics (1) • The purpose of this research study is to 1) investigate factors related to the development of heart and blood vessel diseases, lung and blood diseases, stroke, memory loss, cancer, and other diseases and health conditions; and 2) examine DNA and its relationship to the risks of developing these diseases and health conditions. • The blood samples will also be tested for genetic studies.

Framingham Heart Study Informed Consent: Genetics (2) • You will be asked if a sample of the blood you have donated may be used for the preparation of DNA and for the creation of a cell line. • Neither your name nor Framingham clinic number will appear on the sample. • You will not be routinely informed of the results of the research performed upon your genetic blood sample.

Framingham SHARe • NHLBI oversight of genotyping, database creation, data distribution • No commercial funding • Sharing genetic and clinical database with the scientific community

4. Informed Consent • Data and DNA will be distributed to Framingham researchers and other qualified researchers interested in the genetics of [various] diseases and health conditions. • The researchers will be given the DNA without any potentially identifying information. • Information gained from research on your DNA may be used for the development of diagnostic procedures or new treatments for major diseases. • Your DNA will not be sold to any person, institution, or company for financial gain or commercial profit.

Community Concerns Regarding Genomic Research and Data Sharing: Adding Genome-wide Association to Population Studies