The Views of Participants in DNA Biobanks Kelly E. Ormond,I Maureen E. Smith,II & Wendy A. WolfIII Abstract Biobanks are generally created with the long-term goal of establishing genotype-phenotype correlations. These resources collect and link DNA with health information for use in future genetic research studies. The biobanking process can vary with regard to specific characteristics in study design. Biobanks may extract DNA by using DNA from leftover samples or obtaining new DNA samples specifically for the biobank. Biobanks also vary in whether they use an opt- in or opt-out informed consent process. Some biobanks collect health information at a single point in time, while others “re-access” such information at designated points in the future to categorize subjects accurately into affected/unaffected status. These study design differences can influence the perception of participants and affect their willingness to participate. This paper will address the following three key issues: (1) why people decide to participate in DNA biobanks, (2) what enrollees understand about their participation in DNA biobanks, and (3) how participants feel about the possibility that biobanks will re-contact them, either to obtain new information for future studies or to share potential study results. Finally, we will suggest how information related to these three key issues ought to inform future study design for biobanks. I. INTRODUCTION.................................................................................................................81 II. WHY DO PEOPLE DECIDE TO PARTICIPATE IN DNA BIOBANKS?...........................82 III. WHAT DO ENROLLEES UNDERSTAND ABOUT THEIR PARTICIPATION IN A DNA BIOBANK? ..............................................................................................................................83 IV. HOW DO PARTICIPANTS FEEL ABOUT BIOBANK RE-CONTACT, AND HOW SHOULD THIS INFORMATION INFORM STUDY DESIGN?..............................................84 V. CONCLUSION....................................................................................................................87 I Stanford University, Department of Genetics, Stanford, CA. II Northwestern University, Center for Genetic Medicine, Chicago, IL. III Northwestern University, Center for Genetic Medicine, Chicago, IL. 81 STANFORD JOURNAL OF LAW, SCIENCE & POLICY Vol. 1 I. INTRODUCTION DNA biobanks are created with the long-term goal of establishing genotype-phenotype correlations through collecting and linking DNA with health information. Researchers can use these correlations in research studies that are typically not yet conceived when the biobanks are created. These biobanks may utilize the stored DNA for discovery research, which may include targeted genomic tests, genome-wide association studies,1 and potentially whole genome sequencing studies in the future. The ethical issues that surround DNA biobanks depend largely on the study design and methods utilized by each biobank, and it is therefore important to understand the variety of ways that biobanks can differ in study design and methods. First, biobanks may extract DNA from leftover clinical samples2 or obtain new samples specifically intended for usage in a specific biobank.3 Second, biobanks may use different subject recruitment processes; biobanks can be population-based, narrowly focused on specific medical conditions with a “control” population, or broadly focused on a range of disorders varying in frequency, treatability, severity and social stigma.4 The subject recruitment process may either request subjects to “opt in” (so that a potential subject makes an active decision to participate subsequent to an informed consent process), or to “opt out” (so that a potential subject is assumed to enroll unless the subject actively declines). The “opt out” option is characteristic of a “presumed consent” model, where participants are presumed to enroll in biobanks after obtaining healthcare in certain settings.5 Finally, the last study method where biobanks differ is in their timing for collecting health information; they may collect health information at a single point in time or may “re-access” such information at designated points in the future to categorize subjects accurately as affected or unaffected. Some biobanks choose to have re-contact options so that they can follow up with participants with results from past studies or with requests to obtain consent for future specific studies.6 The health informatics required for these options may require varying levels of de- identification. Coded samples typically involve the efforts of biobank investigators to link the sample with a code rather than with personally identifiable information, such as a name or social security number. (However, investigators may maintain some links to participants in order to re- deposit genomic information and to re-contact participants in the future). Researchers who 1 These studies may include, for example, the assessment of assessing low penetrance genes for common diseases or the search for modifier genes that impact phenotype. 2 See Dan Roden et al., Development of a Large-Scale De-Identified DNA Biobank to Enable Personalized Medicine, 84 CLINICAL PHARMACOLOGY AND THERAPEUTICS 362, 364, 367 (2008) (discussing how a majority of the samples was collected from leftover blood samples). 3 See Catherine A. McCarty et al., Marshfield Clinic Personalized Medicine Research Project (PMRP): Design, Methods and Recruitment for a Large Population-Based Biobank, 2 PERSONALIZED MED. 49, 52 (2005) (discussing how DNA was extracted from each patient). 4 See Lyle J. Palmer, UK Biobank: Bank on It, 369 THE LANCET 1980 (2007); Greta Lee Splansky et al., The Third Generation Cohort of the National Heart, Lung, and Blood Institute’s Framingham Heart Study: Design, Recruitment, and Initial Examination, 165 AM. J. EPIDEMIOLOGY 1328 (2007). 5 See Melissa A. Austin et al., Genebanks: A Comparison of Eight Proposed International Genetic Databases, 6 COMMUNITY GENETICS 37, 39 (2003) (describing presumed consent and the opt-out option in Icelandic Health Center Database); Roden et al., supra note 2, at 365–66 (describing the advantages and limits of opt-out study design). 6 Kelly E. Ormond et al., Assessing the Understanding of Biobank Participants, 149 AM. J. MED. GENETICS 188, 189–90 (2009). 2010 THE VIEW OF PARTICIPANTS IN DNA BIOBANKS 82 utilize the samples typically receive only the coded samples and do not have access to the identification links. De-identified data sets include none of the eighteen HIPAA protected data points, while limited data sets may include either dates, geographic data, or both. Samples that have no link to identifiable information preclude biobanks from updating participants with results or re-contacting again to discover further health information. All of these different study methods influence the ethical issues related to biobank participation. This paper will focus on three key issues relevant to biobanks and their related ethical considerations: (1) why people decide to participate in DNA biobanks, (2) what enrollees understand about their participation in a DNA biobank, and (3) how participants feel about biobank re-contact, whether to give new information for future studies or to receive aggregate or individual study results. After addressing these concerns, we will conclude by proposing how information about these issues should inform study design for DNA biobanks. II. WHY DO PEOPLE DECIDE TO PARTICIPATE IN DNA BIOBANKS? Several studies have addressed the reasons why enrollees do or would participate in DNA biobanks7 or other genetic research studies.8 One important stated reason is altruism;9 participants report that they feel good “helping mankind” or want to give back after facing illness in themselves or family members. Less frequently, participants express that they want to contribute to the general knowledge for science, medicine, and genetics, or that they want to assist researchers with building a database that will aid the discovery of specific disease genes or genotype/phenotype correlations and subsequent research on treatments or cures. Other factors that appear to influence participation in DNA biobanks include general interest in science, genetics, or research participation, trust in the sponsoring institution,10 ease of participation (especially if no additional blood sample or time is required), and the perceived low risk of having a blood test. Finally, as will be discussed later in the paper, some participants report that they chose to participate because of the potential to gain personal or family benefits, such as improved testing or treatment.11 Several studies suggest that a majority of potential enrollees are comfortable with the study concepts and purposes12 and would consider participation in a DNA biobank.13 With that said, actual enrollment in biobanks varies significantly based on each biobank’s study design and 7 See Laura M. Beskow & Elizabeth Dean, Informed Consent for Biorepositories: Assessing Prospective Participants’ Understanding and Opinions, 17 CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION 1440 (2008); Catherine A. McCarty et al., Informed Consent and Subject Motivation to Participate in a Large, Population-Based Genomics Study: The Marshfield Clinic Personalized Medicine Research Project, 10 COMMUNITY GENETICS 2 (2007); Ormond et al., supra note 6, at 191. 8 See Donald J. Willison et al., Patient Consent Preferences for Research Uses of Information