Armand H. Matheny Antommaria

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.Genet Med 15 11, 854–859.Genetics in Medicine (2013); 15 11, 854–859. doi:10.1038/gim.2013.113

The OHRP and SUPPORT

A group of medical ethicists and pediatricians asks for reconsideration of the recent Office for Human Research Protections decision about informed consent in SUPPORT.

A systematic literature review of individuals’ perspectives on broad consent and data sharing in the United States

Purpose:In 2011, an Advanced Notice of Proposed Rulemaking proposed that de-identified human data and specimens be included in biobanks only if patients provide consent. The National Institutes of Health Genomic Data Sharing policy went into effect in 2015, requiring broad consent from almost all research participants.Methods:We conducted a systematic literature review of attitudes toward biobanking, broad consent, and data sharing. Bibliographic databases included MEDLINE, Web of Science, EthxWeb, and GenETHX. Study screening was conducted using DistillerSR.Results:The final 48 studies included surveys (n = 23), focus groups (n = 8), mixed methods (n = 14), interviews (n = 1), and consent form analyses (n = 2). Study quality was characterized as good (n = 19), fair (n = 27), and poor (n = 2). Although many participants objected, broad consent was often preferred over tiered or study-specific consent, particularly when broad consent was the only option, samples were de-identified, logistics of biobanks were communicated, and privacy was addressed. Willingness for data to be shared was high, but it was lower among individuals from under-represented minorities, individuals with privacy and confidentiality concerns, and when pharmaceutical companies had access to data.Conclusions:Additional research is needed to understand factors affecting willingness to give broad consent for biobank research and data sharing in order to address concerns to enhance acceptability.Genet Med 18 7, 663–671.

An Ethical Analysis of Mandatory Influenza Vaccination of Health Care Personnel: Implementing Fairly and Balancing Benefits and Burdens

Health care institutions have paid increasing attention to preventing nosocomial transmission of influenza through vaccination of health care personnel. While multifaceted voluntary interventions have increased vaccination rates, proponents of mandatory programs contend the rates remain unacceptably low. Conventional bioethical analyses of mandatory programs are inadequate; they fail to account for the obligations of nonprofessional personnel or to justify the weights assigned to different ethical principles. Using an ethics framework for public health permits a fuller analysis. The frameworks focus on fairness accentuates the potential differences between the risk of transmitting infection and employment status, and the need to equitably evaluate exemptions. The frameworks emphasis on balancing benefits and burdens highlights the need to justify a specific goal and questions the need to exclude all nonmedical exemptions. While mandatory vaccination programs are justifiable, greater attention should be paid to their implementation.Health care institutions have paid increasing attention to preventing nosocomial transmission of influenza through vaccination of health care personnel. While multifaceted voluntary interventions have increased vaccination rates, proponents of mandatory programs contend the rates remain unacceptably low. Conventional bioethical analyses of mandatory programs are inadequate; they fail to account for the obligations of nonprofessional personnel or to justify the weights assigned to different ethical principles. Using an ethics framework for public health permits a fuller analysis. The frameworks focus on fairness accentuates the potential differences between the risk of transmitting infection and employment status, and the need to equitably evaluate exemptions. The frameworks emphasis on balancing benefits and burdens highlights the need to justify a specific goal and questions the need to exclude all nonmedical exemptions. While mandatory vaccination programs are justifiable, greater attention should be paid to their implementation.

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 11xa0US 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.

Practical Guidance on Informed Consent for Pediatric Participants in a Biorepository

In the decade since the Human Genome Project was completed, the knowledge and technologies that this project enabled have led to a remarkable evolution in the way biorepositories are designed and operate. Early biobanks were often designed to facilitate the study of a single condition, while biobanks established in the last decade have more frequently been created with a broader research mission in mind.1 Accompanying this transition have come other changes in biobank practices, including the generation and storage of genome-scale sequencing data, frequent sharing of biosamples and data, pooling of resources among sample collections, and increased interest in returning genetic research results to sample donors. n nAs biorepository practices have become more complex, the task of developing appropriate informed consent practices has become more challenging. There are at least three reasons for this. First, the regulations that govern research with human subjects in the U.S., known collectively as the Common Rule, were written at a time when many of the recent innovations in biobank practices were not anticipated. Second, Institutional Review Boards (IRBs) are tasked with evaluating whether research studies meet both federal regulations and local standards for acceptable research, yet IRB members are often unfamiliar with the complexities of biobanks. Third, it can be quite challenging to explain these practices in informed consent documents in a way that is easy for potential research participants to read and understand. n nBecause of these challenges, several groups have developed practical guidance on informed consent. For example, the website of the National Human Genome Research Institute (NHGRI), Genome.gov, provides model informed consent language developed for genomic research studies, including biobanks.2 The NHGRI website also hosts a white paper developed by our group, the Electronic Medical Records and Genomics (eMERGE) Network.3 This document provides model language for informed consent documents that investigators may adapt for their own biorepository projects. n nOne limitation of these resources, however, is their focus on adult research participants. There are currently no similar resources that address the unique issues that arise for biorepositories that aim to collect samples from pediatric participants. This is an important gap in the literature, since the challenges associated with biobanking are magnified in the setting of pediatric research. The ability of children to engage in informed decision-making varies according to their developmental level, so parental permission is usually required for pediatric research participation. However, a parent’s permission for a child to participate in research is quite different from an adult’s consent for his or her own research participation. A parent’s decision must account for the best interests of the child, while at the same time balancing the future autonomy of the child and the needs of the family. n nTo be sure, there is a robust literature on these unique issues that arise in pediatric research,4,5 including a number of helpful papers that address pediatric biorepositories specifically.6,7 However, it can be difficult for investigators and IRB members to distill these empirical and analytical resources into concrete practices related to the informed consent process. This document is designed to address that need. Writing on behalf of the Consent, Education, Regulation, and Consultation (CERC) workgroup of the eMERGE Network, we provide pediatric-focused guidance for investigators and IRB members working in the U.S regulatory context on pediatric informed consent practices for biorepositories.

Adolescents' preferences regarding disclosure of incidental findings in genomic sequencing that are not medically actionable in childhood.

Next‐generation sequencing has challenged the consensus that predictive testing should not be performed on asymptomatic minors for conditions that are not medically actionable in childhood. While the available literature suggests that most parents want access to incidental findings discovered in genomic sequencing, there is little information regarding adolescents’ views. This studys goal is to determine adolescent views regarding the disclosure of incidental findings for adult onset conditions that are not medically actionable in childhood. We conducted a cross‐sectional survey of students enrolled in 7–12th grade science classes in three Cincinnati public schools. Most (235 of 282, 83%) students wanted access to non‐actionable incidental findings. These participants most frequently (38%) endorsed future planning as the reason for disclosure. Seventy‐two percent of students believed they should participate in the decision making process. Seventy‐three percent of students believed that parents of children less than 12 years old should have access to this information. Adolescents want to have access to and participate in decisions about incidental findings.

Laboratory policies on reporting secondary findings in clinical whole exome sequencing: initial uptake of the ACMG's recommendations.

Laboratory Policies on Reporting Secondary Findings in Clinical Whole Exome Sequencing: Initial Uptake of the ACMG’s Recommendations Sophia B. Hufnagel,* and Armand H. Antommaria Division of Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Division of Hospital Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio Ethics Center, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio

A qualitative study of adolescents’ understanding of biobanks and their attitudes toward participation, re-contact, and data sharing

While biobanks have become more prevalent, little is known about adolescents’ views of key governance issues. We conducted semi‐structured interviews with adolescents between 15 and 17 years old to solicit their views. All interviews were audiotaped and transcribed. Two investigators coded the transcripts and resolved any discrepancies through consensus. We conducted 18 interviews before reaching data saturation. Four participants (22%) had previously heard of a biobank. Many participants had misunderstandings about biobanks, some of which persisted after education. Participants believed that enrolling in a biobank would benefit others through scientific research. Many study participants were unable to identify risks of biobank participation. Thirteen participants (72%) were willing to enroll in a biobank and only one (6%) initially was not. Participants believed that if they were unable to provide assent when enrolled, then they should be re‐contacted at the age of majority and their data should not be shared until that time. Participants emphasized the importance of being aware of their enrollment and the possibility of disagreeing with their parents. Participants’ misunderstanding of biobanks suggests that assent may not be adequately informed without additional education. While adolescents had positive attitudes toward biobanks, they emphasized the importance of awareness of and involvement in the decision to enroll.

Two Infants, Same Prognosis, Different Parental Preferences

A central principle of justice is that similar cases should be decided in similar ways. In pediatrics, however, there are cases in which 2 infants have similar diagnoses and prognoses, but their parents request different treatments. In this Ethics Rounds, we present such a situation that occurred in a single NICU. Three physician-ethicists analyze the issues.