Recommendations for returning genomic incidental findings? We need to talk!

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines

Public Attitudes toward Consent and Data Sharing in Biobank Research: A Large Multi-site Experimental Survey in the US

Individuals participating in biobanks and other large research projects are increasingly asked to provide broad consent for open-ended research use and widespread sharing of their biosamples and data. We assessed willingness to participate in a biobank using different consent and data sharing models, hypothesizing that willingness would be higher under more restrictive scenarios. Perceived benefits, concerns, and information needs were also assessed. In this experimental survey, individuals from 11 US healthcare systems in the Electronic Medical Records and Genomics (eMERGE) Network were randomly allocated to one of three hypothetical scenarios: tiered consent and controlled data sharing; broad consent and controlled data sharing; or broad consent and open data sharing. Of 82,328 eligible individuals, exactly 13,000 (15.8%) completed the survey. Overall, 66% (95% CI: 63%–69%) of population-weighted respondents stated they would be willing to participate in a biobank; willingness and attitudes did not differ between respondents in the three scenarios. Willingness to participate was associated with self-identified white race, higher educational attainment, lower religiosity, perceiving more research benefits, fewer concerns, and fewer information needs. Most (86%, CI: 84%–87%) participants would want to know what would happen if a researcher misused their health information; fewer (51%, CI: 47%–55%) would worry about their privacy. The concern that the use of broad consent and open data sharing could adversely affect participant recruitment is not supported by these findings. Addressing potential participants’ concerns and information needs and building trust and relationships with communities may increase acceptance of broad consent and wide data sharing in biobank research

When clinicians and a parent disagree on the extent of medical care

TG is a 32-month-old girl with a rare lysosomal storage disease. The diagnosis was confirmed at 8 months of age; she underwent bone marrow transplant at 14 months. TG's father remained at home with her siblings whereas her mother lived at the transplant hospital with TG for 1 year. Significant respiratory infections led to dependency on a tracheotomy and ventilator. She was transferred to the current hospital 10 months ago for respiratory rehabilitation, which has been complicated by pulmonary hemorrhages. On examination, TG was in a wheelchair with truncal support and leg splints. She is a small child with coarse facial features, generalized hypotonia, and significant joint restriction. She exhibited intermittent repetitive arm movements. A tracheotomy was in place, and she did not vocalize. Variable levels of alertness were observed although she rarely signaled to others for social engagement or to express her needs. Eye contact was limited and she responded inconsistently to her name. TG's mother states that her daughter interacts well with her and uses a number of signs for communication. The rehabilitation staff reported limited progress and recommends withdrawal of services. TG's mother expressed frustration with her daughter's poor developmental improvement and believes she needs more intensive therapy, not less. Staff members are now frustrated with TG's mother's level of involvement with her daughter's care. Although TG's mother spends full weekdays at her daughter's bedside, she is often working on her computer managing her business. TG's father works full time and visits on the weekends, when her mother returns home. TG's mother has expressed frustration with her daughter's level of improvement; she believes TG needs more intensive therapy that the hospital is not providing. She informed the staff that other children with this type of storage disease may have delays, but are often higher functioning. TG's mother made the point to the staff that the family's reason for pursuing a bone marrow transplant was to attempt to correct the enzyme deficiency and improve her daughter's outcome

Conducting a large, multi-site survey about patients’ views on broad consent: challenges and solutions

Abstract Background As biobanks play an increasing role in the genomic research that will lead to precision medicine, input from diverse and large populations of patients in a variety of health care settings will be important in order to successfully carry out such studies. One important topic is participants’ views towards consent and data sharing, especially since the 2011 Advanced Notice of Proposed Rulemaking (ANPRM), and subsequently the 2015 Notice of Proposed Rulemaking (NPRM) were issued by the Department of Health and Human Services (HHS) and Office of Science and Technology Policy (OSTP). These notices required that participants consent to research uses of their de-identified tissue samples and most clinical data, and allowing such consent be obtained in a one-time, open-ended or “broad” fashion. Conducting a survey across multiple sites provides clear advantages to either a single site survey or using a large online database, and is a potentially powerful way of understanding the views of diverse populations on this topic. Methods A workgroup of the Electronic Medical Records and Genomics (eMERGE) Network, a national consortium of 9 sites (13 separate institutions, 11 clinical centers) supported by the National Human Genome Research Institute (NHGRI) that combines DNA biorepositories with electronic medical record (EMR) systems for large-scale genetic research, conducted a survey to understand patients’ views on consent, sample and data sharing for future research, biobank governance, data protection, and return of research results. Results Working across 9 sites to design and conduct a national survey presented challenges in organization, meeting human subjects guidelines at each institution, and survey development and implementation. The challenges were met through a committee structure to address each aspect of the project with representatives from all sites. Each committee’s output was integrated into the overall survey plan. A number of site-specific issues were successfully managed allowing the survey to be developed and implemented uniformly across 11 clinical centers. Conclusions Conducting a survey across a number of institutions with different cultures and practices is a methodological and logistical challenge. With a clear infrastructure, collaborative attitudes, excellent lines of communication, and the right expertise, this can be accomplished successfully