Assessing the attitudes and understanding of participants in Nugene: Impacts on informed consent for a large-scale DNA research and banking project

Abstract

Genetic databases are generally created with the long-term goal of establishing genotype-phenotype correlations, and are explicitly NOT intended for participant benefit through the personal receipt of genetic information. In fact, most well-known genetic databases are set up to preclude the recontact of participants, both to protect confidentiality and because any genetic discoveries will likely have unclear implications in the near future. Issues of recontact and sample use raise significant issues around the informed consent process for such genetic databases. The NUgene study is a longitudinal genetic database at Northwestern University created to assess the genetic components of common diseases. In summer 2001, prior to the start of NUgene recruitment, a planning committee met for over one year to discuss the project's format, including ethical aspects. The project's advisory committee felt strongly that recontact of study participants was not warranted. However, because of the broad and longitudinal nature of the project, the IRB requested a modified consent process for recontacting subjects. This consent allowed participants to opt for recontact under either of the following circumstances: (1) if more information was required for a future study or to participate in future research and (2) if ''clinically significant results'' were discovered through researchmore » examination. During the first year of the study, 808 participants were enrolled in NUgene. 92% opted for recontact regarding more information or future research and 96% opted for recontact for ''medically significant'' findings. The current DOE funded study of NUgene participants examined informed consent, including recontact options. In November 2002, the NUgene project began recruiting for a large, longitudinal genetic database; concurrent with NUgene enrollment, we solicited 200 participants for interviews to address attitudes about participation in NUgene in both a quantitative and qualitative manner. Demographic data on these subjects was representative of the participants in the overall NUgene project. 200 subjects underwent the quantitative measure QuIC to measure the knowledge and understanding of participants using a previously validated measure. The summary knowledge score was 69.3 (on a scale of 0-100, being the highest possible score) and the summary self-assessment score was 89.6. The best understood domains included: the nature of the study (100), benefit to future patients (99.8), and the voluntary nature of participation (93.2). Domains with the lowest knowledge scores included: potential risks and discomforts (17.5), experimental nature of the research (24.0), procedures in the event of study-related injury (35.7), and confidentiality issues (42.9).In addition to this quantitative data, 109 semi-structured interviews were transcribed and analyzed. Themes focused on reasons for participation, beliefs regarding the risks and benefits of the study, expectations regarding results and ways in which participants would prefer to be recontacted if future studies or results become available. Most enrolled in NUgene in order to help mankind or the ''general population'' in some manner (>75%), to help find disease genes, treatments or cures, and/or to contribute to the overall medical knowledge. Many participants ({approx}30%) clearly expressed a hope for personal benefit and often named specific disorders or family members. Confidentiality protections of the study were described as good by most (>50%), and almost half specifically described one or more of the privacy protections. While many were able to articulate the general privacy concerns, and several cited concerns with employer (12%) or insurance discrimination (25%), most considered the risks to privacy low (25%) or none ({approx}60%). Only 10% of participants explicitly stated they had no expectation for personal benefit, and when asked whether they expected to be contacted with study results, respondents were split between having no expectation (39%), being hopeful for results (37%) and expecting to be contacted with results (12%). Over 75% of study participants felt that if a genetic test became available for their family they would wish to undertake it, and few caveats were mentioned. Overall, our study demonstrated that participants had a good understanding of the purposes of the study and that the benefit was for future patients; however, participants had difficulty understanding the potential risks and discomforts and confidentiality issues. The data show that participants in population-based studies may be less likely to harbor the ''therapeutic misconception'', often reported in clinical studies, but further study is needed to assess whether patients perceive personal benefits not revealed by this measure. These findings are informative to those providing informed consent and to the IRBs reviewing such studies.« less