The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency.

The National Institutes of Health Genetic Testing Registry (GTR; available online at http://www.ncbi.nlm.nih.gov/gtr/) maintains comprehensive information about testing offered worldwide for disorders with a genetic basis. Information is voluntarily submitted by test providers. The database provides details of each test (e.g. its purpose, target populations, methods, what it measures, analytical validity, clinical validity, clinical utility, ordering information) and laboratory (e.g. location, contact information, certifications and licenses). Each test is assigned a stable identifier of the format GTR000000000, which is versioned when the submitter updates information. Data submitted by test providers are integrated with basic information maintained in National Center for Biotechnology Information's databases and presented on the web and through FTP (ftp.ncbi.nih.gov/pub/GTR/_README.html).

New models for large prospective studies: is there a better way?

Large prospective cohort studies are critical for identifying etiologic factors for disease, but they require substantial long-term research investment. Such studies can be conducted as multisite consortia of academic medical centers, combinations of smaller ongoing studies, or a single large site such as a dominant regional health-care provider. Still another strategy relies upon centralized conduct of most or all aspects, recruiting through multiple temporary assessment centers. This is the approach used by a large-scale national resource in the United Kingdom known as the "UK Biobank," which completed recruitment/examination of 503,000 participants between 2007 and 2010 within budget and ahead of schedule. A key lesson from UK Biobank and similar studies is that large studies are not simply small studies made large but, rather, require fundamentally different approaches in which "process" expertise is as important as scientific rigor. Embedding recruitment in a structure that facilitates outcome determination, utilizing comprehensive and flexible information technology, automating biospecimen processing, ensuring broad consent, and establishing essentially autonomous leadership with appropriate oversight are all critical to success. Whether and how these approaches may be transportable to the United States remain to be explored, but their success in studies such as UK Biobank makes a compelling case for such explorations to begin.

Public opinion about the importance of privacy in biobank research.

Concerns about privacy may deter people from participating in genetic research. Recruitment and retention of biobank participants requires understanding the nature and magnitude of these concerns. Potential participants in a proposed biobank were asked about their willingness to participate, their privacy concerns, informed consent, and data sharing. A representative survey of 4659 U.S. adults was conducted. Ninety percent of respondents would be concerned about privacy, 56% would be concerned about researchers having their information, and 37% would worry that study data could be used against them. However, 60% would participate in the biobank if asked. Nearly half (48%) would prefer to provide consent once for all research approved by an oversight panel, whereas 42% would prefer to provide consent for each project separately. Although 92% would allow academic researchers to use study data, 80% and 75%, respectively, would grant access to government and industry researchers. Concern about privacy was related to lower willingness to participate only when respondents were told that they would receive $50 for participation and would not receive individual research results back. Among respondents who were told that they would receive $200 or individual research results, privacy concerns were not related to willingness. Survey respondents valued both privacy and participation in biomedical research. Despite pervasive privacy concerns, 60% would participate in a biobank. Assuring research participants that their privacy will be protected to the best of researchers' abilities may increase participants' acceptance of consent for broad research uses of biobank data by a wide range of researchers.

Civilian and military genetics: nondiscrimination policy in a post-GINA world.

Evidence is emerging of a growing societal consensus about appropriate and inappropriate uses of genetic information. The Genetic Information Nondiscrimination Act of 2008 provides new legal protections to Americans by prohibiting the discriminatory use of genetic information by health insurers and employers. Additionally, the United States military recently created new policies for fair use of genetic information in the determination of benefits for servicemen and servicewomen leaving military service. Although critical issues remain, such as the potential for genetic information to be used to deny people other forms of insurance, and how the military will use genetic medicine overall, significant progress has been made.

Veterans' attitudes regarding a database for genomic research.

PURPOSE: Large cohort studies to investigate interactions between genes, environment, and lifestyle require large representative samples of the population. The Department of Veterans Affairs health care system is uniquely positioned to carry out such research, with a large patient population and a sophisticated system of electronic medical records. As Veterans Affairs considers establishing a large database of genetic information and medical records for research purposes, a survey of 931 Veterans Affairs patients was carried out to measure their willingness to participate, what their concerns would be, and their preferences about some aspects of study design. METHODS: A sample of veterans who receive Veterans Affairs health care was surveyed online in April and May of 2008. The proposed genomic study was described to respondents, who then were asked about their support for the study and willingness to participate, and their opinions about the study and some of its components. A descriptive analysis examined differences in attitudes among demographic groups, and whether general beliefs were associated with support or willingness to participate. RESULTS: Most respondents (83%) said the database should definitely or probably be created, and overall, 71% said they would definitely or probably participate. CONCLUSION: Majorities of Veterans Affairs health patients in a broad range of demographic groups supported the establishment of a genomic database and showed willingness to participate. Although the desire to learn about one's own health from the study was high, altruistic characteristics were strongly related to whether or not veterans would participate.

The Scientific Foundation for personal genomics: recommendations from a National Institutes of Health-Centers for Disease Control and Prevention multidisciplinary workshop.

The increasing availability of personal genomic tests has led to discussions about the validity and utility of such tests and the balance of benefits and harms. A multidisciplinary workshop was convened by the National Institutes of Health and the Centers for Disease Control and Prevention to review the scientific foundation for using personal genomics in risk assessment and disease prevention and to develop recommendations for targeted research. The clinical validity and utility of personal genomics is a moving target with rapidly developing discoveries but little translation research to close the gap between discoveries and health impact. Workshop participants made recommendations in five domains: (1) developing and applying scientific standards for assessing personal genomic tests; (2) developing and applying a multidisciplinary research agenda, including observational studies and clinical trials to fill knowledge gaps in clinical validity and utility; (3) enhancing credible knowledge synthesis and information dissemination to clinicians and consumers; (4) linking scientific findings to evidence-based recommendations for use of personal genomics; and (5) assessing how the concept of personal utility can affect health benefits, costs, and risks by developing appropriate metrics for evaluation. To fulfill the promise of personal genomics, a rigorous multidisciplinary research agenda is needed.

Public perspectives on informed consent for biobanking.

The National Institutes of Health and other federal health agencies are considering establishing a national biobank to study the roles of genes and environment in health. We assessed the public's attitudes toward the proposed biobank, including preferences for providing informed consent. Sixteen focus groups were conducted, and themes arising from the focus groups were tested in a large, representative survey (n=4659) of the general population. Our research demonstrates that when considering participating in a genomic biobank, individuals want ongoing choices and control over access to their samples and information.

Ethical implications of including children in a large biobank for genetic-epidemiologic research: a qualitative study of public opinion.

The National Institutes of Health and other federal agencies are considering initiating a cohort study of 500,000 people, including 120,000 children, to measure genetic and environmental influences on common diseases. A community engagement pilot study was conducted to identify public attitudes and concerns about the proposed cohort study, including the ethics of involving children. The pilot included 15 focus groups where the inclusion of children in the proposed cohort study was discussed. Focus groups, conducted in six cities, included 141 adults of different ages, incomes, genders, ethnicities, and races. Many of the concerns expressed by participants mirrored those addressed in pediatric research guidelines. These concerns included minimizing children's fear, pain, and burdens; whether to include young children; and how to obtain children's assent. There was little agreement about which children can assent. Some voiced concern about children's privacy, but most expected that parents would have access to children's study results. Some believed children would not benefit from participating, while others identified personal and societal benefits that might accrue. A few people believed that children's participation would not advance the study's goals. To successfully include children, proposed cohort study would need to address children's changing capabilities and rights as they grow and reach the age of consent.

Subjects matter: a survey of public opinions about a large genetic cohort study.

PURPOSE: Cohort studies investigating genes, environment, and lifestyle require large study populations. To recruit and retain participants, it is important to understand the relative significance of influences on people's motivation to participate. To this end, 4659 Americans were surveyed about support for and willingness to participate in a proposed large cohort study. METHODS: An online survey of US adults was conducted between December 2007 and January 2008. To measure the influence of study burden, compensation and receipt of individual research results on willingness to participate, respondents were randomized to one of eight different study scenarios. RESULTS: Most respondents (84%) supported the study, and 60% would participate. Returning research results (odds ratio = 1.6, 95% confidence interval 1.3-1.8) and increasing compensation from $50 to $200 (odds ratio = 1.5, 95% confidence interval 1.2-1.7) were associated with increased willingness to participate. Decreasing study burden was less important (odds ratio = 1.2, 95% confidence interval 1.0-1.4). Three in four respondents would be less likely to participate without the return of research results. Support and willingness varied little among demographic groups; variation in influences of the three factors on willingness was observed. CONCLUSION: Widespread support exists in the general public for a large national cohort study. Providing individual research results is a strong motivation to participate; compensating participants $200 may increase participation a similar amount. Incentives, recruitment, and return of results could be tailored to demographics groups' interests.

Preimplantation genetic screening: a survey of in vitro fertilization clinics.

PURPOSE: The purpose of this study was to determine which US in vitro fertilization clinics provide preimplantation genetic screening for aneuploidy in treating infertility, and to explore clinic directors' attitudes toward this technique. METHODS: Online survey included 415 US assisted reproductive technology clinics. The survey had a valid response rate of 45% or 186 clinics. RESULTS: Nearly 68% of US in vitro fertilization clinics responding to the survey provided preimplantation genetic screening in an effort to increase success rates of fertility treatment. More than half of these in vitro fertilization clinics (56%) provided preimplantation genetic screening for advanced maternal age and the same percentage provided preimplantation genetic screening to treat repeated in vitro fertilization failure, whereas 66% provided preimplantation genetic screening to treat women with repeated miscarriage. Opinions of the effectiveness of preimplantation genetic screening for these indications varied widely, even among those providing it. Most directors (85%) of clinics providing preimplantation genetic screening believed that more data are needed to determine whether and to whom it should be offered. CONCLUSIONS: Despite the lack of data supporting the use of preimplantation genetic screening for recurrent pregnancy loss, in vitro fertilization failure, and advanced maternal age, a majority of in vitro fertilization clinics in the United States offer preimplantation genetic screening for these purposes. There is significant support among clinic directors for more research into the effectiveness of preimplantation genetic screening and for professional guidelines in this area.

Confidentiality, privacy, and security of genetic and genomic test information in electronic health records: points to consider.

As clinical genetics evolves, and we embark down the path toward more personalized and effective health care, the amount, detail, and complexity of genetic/genomic test information within the electronic health record will increase. This information should be appropriately protected to secure the trust of patients and to support interoperable electronic health information exchange. This article discusses characteristics of genetic/genomic test information, including predictive capability, immutability, and uniqueness, which should be considered when developing policies about information protection. Issues related to "genetic exceptionalism"; i.e., whether genetic/genomic test information should be treated differently from other medical information for purposes of data access and permissible use, are also considered. These discussions can help guide policy that will facilitate the biological and clinical resource development to support the introduction of this information into health care.