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The genetic testing and genetic screening of children are commonplace. Decisions about whether to offer genetic testing and screening should be driven by the best interest of the child. The growing literature on the psychosocial and clinical effects of such testing and screening can help inform best practices. This technical report provides ethical justification and empirical data in support of the proposed policy recommendations regarding such practices in a myriad of settings. Genet Med 2013:15(3):234–245

Biobanks and archived data sets collecting samples and data have become crucial engines of genetic and genomic research. Unresolved, however, is what responsibilities biobanks should shoulder to manage incidental findings and individual research results of potential health, reproductive, or personal importance to individual contributors (using “biobank” here to refer both to collections of samples and collections of data). This article reports recommendations from a 2-year project funded by the National Institutes of Health. We analyze the responsibilities involved in managing the return of incidental findings and individual research results in a biobank research system (primary research or collection sites, the biobank itself, and secondary research sites). We suggest that biobanks shoulder significant responsibility for seeing that the biobank research system addresses the return question explicitly. When reidentification of individual contributors is possible, the biobank should work to enable the biobank research system to discharge four core responsibilities to (1) clarify the criteria for evaluating findings and the roster of returnable findings, (2) analyze a particular finding in relation to this, (3) reidentify the individual contributor, and (4) recontact the contributor to offer the finding. We suggest that findings that are analytically valid, reveal an established and substantial risk of a serious health condition, and are clinically actionable should generally be offered to consenting contributors. This article specifies 10 concrete recommendations, addressing new biobanks as well as those already in existence. Genet Med 2012:14(4):361–384

Decompressive craniectomy (DC)—a surgical procedure that involves removal of part of the skull—has been used for many years in the management of patients with brain oedema and/or intracranial hypertension; however, the risk of post-surgery disability has raised important ethical issues. Here, Kolias et al . outline the history of DC, and review current considerations and evidence with regard to the use of this procedure in stroke, traumatic brain injury and other indications. The direction of future studies of DC is also discussed. Decompressive craniectomy (DC)—a surgical procedure that involves removal of part of the skull to accommodate brain swelling—has been used for many years in the management of patients with brain oedema and/or intracranial hypertension, but its place in contemporary practice remains controversial. Results from a recent trial showed that early (neuroprotective) DC was not superior to medical management in patients with diffuse traumatic brain injury. An ongoing trial is investigating the clinical and cost effectiveness of secondary DC as a last-tier therapy for post-traumatic refractory intracranial hypertension. With regard to ischaemic stroke (malignant middle cerebral artery infarction), a recent Cochrane review concluded that DC improves survival compared with medical management, but that a higher proportion of DC survivors experience moderately severe or severe disability. Although many patients have a good outcome, the issue of DC-related disability raises important ethical issues. As DC and subsequent cranioplasty are associated with a number of complications, indiscriminate use of this surgery is not appropriate. Here, we review the evidence and present considerations regarding surgical technique, ethics and cost-effectiveness of DC. Prospective clinical trials and cohort studies are essential to enable optimization of patient care and outcomes. Key Points Decompressive craniectomy is a useful operation for management of brain oedema and intracranial hypertension Early (neuroprotective) decompressive craniectomy is not superior to medical management in patients with diffuse traumatic brain injury The role of decompressive craniectomy as a last-tier therapy for post-traumatic refractory intracranial hypertension is under investigation in an ongoing multicentre trial Decompressive craniectomy improves survival rates in patients with malignant middle cerebral artery stroke, but some survivors have moderately severe or severe disability Although associated with good outcome in many patients, the fact that some individuals survive with severe disability raises important ethical issues

Purpose: Despite important recent work, US public attitudes toward specific biobank consent models are not well understood. Public opinion data can help shape efforts to develop ethically sound and publicly trusted mechanisms for informing and consenting prospective biobank donors. The purpose of this study was to explore public perspectives toward a range of consent models currently being used or considered for use among comprehensive US biobanks. Methods: The study used an exploratory mixed-methods design, using focus groups and telephone surveys. Eligible participants were English-speaking residents in the catchment area of a comprehensive biobank being developed at the University of Iowa. Results: Forty-eight participants in seven focus groups and 751 survey participants were recruited. Biobanks were unfamiliar to almost all study participants but were seen as valuable resources. Most focus group (63%) and survey (67%) participants preferred a prospective opt-in over an opt-out consent approach. Broad, research-unspecific consent was preferred over categorical and study-specific consent models for purposes of approving future research use. Conclusion: Many individuals may want to make an active and informed choice at the point of being approached for biobank participation but are prepared to consent broadly to future research use and to forego additional choices as a result.

Published guidelines suggest that research results and incidental findings should be offered to study participants under some circumstances. Although some have argued against the return of results in research, many cite an emerging consensus that there is an ethical obligation to return at least some results; the debate quickly turns to issues of mechanics (e.g., which results? who discloses? for how long does the obligation exist?). Although commentators are careful to distinguish this as an ethical rather than legal obligation, we worry that return of results may unjustifiably become standard of care based on this growing “consensus,” which could quickly lead to a legal (negligence-based) duty to offer and return individualized genetic research results. We caution against this and argue in this essay that the debate to date has failed to give adequate weight to a number of fundamental ethical and policy issues that should undergird policy on return of research results in the first instance, many of which go to the fundamental differences between research and clinical care. We confine our comments to research using data from large biobanks, the topic of the guidelines proposed in this symposium issue. Genet Med 2012:14(4):473–477

Clinical whole-exome and whole-genome sequencing will result in a broad range of incidental findings, but clinicians’ obligations to identify and disclose such findings are a matter of debate. We sought legal cases that could offer insights into clinicians’ legal liability. We searched for cases in which incidental findings were related to the cause of action, using the search engines WestLaw, WestLaw Next, Lexis, and Lexis Advance. We found no case law related to incidental findings from genetic testing but identified eight cases involving incidental findings in medical imaging. These cases suggest that clinicians may face liability for failing to disclose incidental findings that would have offered an opportunity for interventions to improve health outcome, if under the applicable standard of care, they fail to identify or appreciate the significance of the incidental finding or they negligently fail to notify other clinicians and/or the patient of the identified incidental finding. Other cases support liability for failure to refer appropriately to a clinician with greater expertise. Clinicians may face liability if they fail to disclose incidental information that could inform interventions to improve health outcome; information lacking clinical actionability is likely to have less import. Genet Med 2013:15(8):624–629

Genetic engineering has emerged as a powerful mechanism for understanding biological systems and a potential approach for redressing congenital disease. Alongside, the emergence of these technologies in recent decades has risen the complementary analysis of the ethical implications of genetic engineering techniques and applications. Although viral-mediated approaches have dominated initial efforts in gene transfer (GT) methods, an emerging technology involving engineered restriction enzymes known as zinc finger nucleases (ZFNs) has become a powerful new methodology for gene editing. Given the advantages provided by ZFNs for more specific and diverse approaches in gene editing for basic science and clinical applications, we discuss how ZFN research can address some of the ethical and scientific questions that have been posed for other GT techniques. This is of particular importance, given the momentum currently behind ZFNs in moving into phase I clinical trials. This study provides a historical account of the origins of ZFN technology, an analysis of current techniques and applications, and an examination of the ethical issues applicable to translational ZFN genetic engineering in early phase clinical trials.

Individual risk prediction and stratification based on polygenic profiling may be useful in disease prevention. Risk-stratified population screening based on multiple factors including a polygenic risk profile has the potential to be more efficient than age-stratified screening. In this article, we summarize the implications of personalized screening for breast and prostate cancers. We report the opinions of multidisciplinary international experts who have explored the scientific, ethical, and logistical aspects of stratified screening. We have identified (i) the need to recognize the benefits and harms of personalized screening as compared with existing screening methods, (ii) that the use of genetic data highlights complex ethical issues including discrimination against high-risk individuals by insurers and employers and patient autonomy in relation to genetic testing of minors, (iii) the need for transparency and clear communication about risk scores, about harms and benefits, and about reasons for inclusion and exclusion from the risk-based screening process, and (iv) the need to develop new professional competences and to assess cost-effectiveness and acceptability of stratified screening programs before implementation. We conclude that health professionals and stakeholders need to consider the implications of incorporating genetic information in intervention strategies for health-care planning in the future. Genet Med 2013:15(6):423–432

Researchers and clinicians face the practical and ethical challenge of if and how to offer for return the wide and varied scope of results available from individual exome sequencing and whole-genome sequencing. We argue that rather than viewing individual exome sequencing and whole-genome sequencing as a test for which results need to be “returned,” that the technology should instead be framed as a dynamic resource of information from which results should be “managed” over the lifetime of an individual. We further suggest that individual exome sequencing and whole-genome sequencing results management is optimized using a self-guided approach that enables individuals to self-select among results offered for return in a convenient, confidential, personalized context that is responsive to their value system. This approach respects autonomy, allows individuals to maximize potential benefits of genomic information (beneficence) and minimize potential harms (nonmaleficence), and also preserves their right to an open future to the extent they desire or think is appropriate. We describe key challenges and advantages of such a self-guided management system and offer guidance on implementation using an information systems approach. Genet Med15 9, 684–690.

Purpose: Prior research suggests that parents undervalue long-term risks associated with their children’s participation in research studies. The primary aim of this study was to evaluate parental understanding of informed consent for a pediatric biobanking study. Methods: The study population included parents who provided consent for their child to participate in a study examining the genetic etiology of congenital cardiovascular malformations. Informed consent understanding was measured by adapting the Quality of Informed Consent assessment to our study. We evaluated possible predictors of individual Quality of Informed Consent items using generalized estimating equations. Results: A total of 252 individuals representing 188 families completed the study. The Quality of Informed Consent items best understood by parents included consent to participate in research, the main purpose of the study, and the possibility of no direct benefit. The items least understood by parents were those involving the indefinite storage of DNA, the possible risks of participation, and the fact that the study was not intended to treat their child’s heart defect. Parent age and medical decision making by one versus both parents were frequent predictors of individual Quality of Informed Consent items. Conclusion: Parents overestimate personal benefit and underestimate the risks associated with their child’s participation in a biobanking study. Genet Med 16 2, 141–148.