Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for pediatric diagnostic testing.

INTRODUCTION: Measuring effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents' perceived utility of pediatric diagnostic GS. METHODS: Informed by a five-domain conceptual model, the study comprised five steps: (1) item writing, (2) cognitive testing, (3) pilot testing and item reduction, (4) psychometric testing, and (5) evaluation of construct validity. Parents of pediatric patients who had received results of clinically indicated GS participated in structured cognitive interviews and two rounds of surveys. After eliminating items based on theory and quantitative performance, we conducted an exploratory factor analysis and calculated Pearson correlations with related instruments. RESULTS: We derived the 21-item Pediatric Diagnostic version of the GENEtic Utility (GENE-U) scale, which has a two-factor structure that includes an Informational Utility subscale (16 items, α = 0.91) and an Emotional Utility subscale (5 items, α = 0.71). Scores can be summed to calculate a Total scale score (α = 0.87). The Informational Utility subscale was strongly associated with empowerment and personal utility of GS, and the Emotional Utility subscale was moderately associated with psychosocial impact and depression and anxiety. DISCUSSION: The Pediatric Diagnostic GENE-U scale demonstrated good psychometric performance in this initial evaluation and could be a useful tool for translational genomics researchers, warranting additional validation.

Ethical considerations and decision making in opioid prescribing for chronic pain: A case study in rheumatology practice.

ABSTRACT: Dilemmas regarding opioid prescribing for chronic pain frequently occur within health care settings. The ethical principles of autonomy, beneficence, nonmaleficence, and justice, as well as the principles of care ethics, can assist in addressing these opioid-related dilemmas. The purpose of this clinical case study is to provide a case study highlighting an opioid prescribing dilemma and then identify opioid-related transition considerations; address ethical questions that nurse practitioners (NPs) may encounter in clinical practice when providing care for individuals living with chronic pain who may need or use a prescribed opioid medication; and draw on the ethical principles and care ethics to provide guidance for NPs who face these challenging issues.

Uninformed Origins: Should We Be Advising Parents on the Source of Medicines and Therapies?

Respecting patient autonomy through the process of soliciting informed consent is a cornerstone of clinical ethics. In pediatrics, until a child becomes an adult or legally emancipated, that ethical tenet takes the form of respect for parental decision-making authority. In instances of respecting religious beliefs, doing so is not always apparent and sometimes the challenge lies not only in the healthcare provider's familiarity of religious restrictions but also their knowledge of medical interventions themselves which might conflict with those restrictions. We examine a case of a newborn receiving animal-derived surfactant, a common scenario in neonatology, and present considerations for providers to weigh when confronting when such an intervention might conflict with parent's religious beliefs. We end with strategizing ways to address this issue as a medical community.

Views of Adolescents and Young Adults with Cancer and Their Oncologists Toward Patients' Participation in Genomic Research.

Purpose: With increased use of genomic testing in cancer research and clinical care, it is important to understand the perspectives and decision-making preferences of adolescents and young adults (AYAs) with cancer and their treating oncologists. Methods: We conducted an interview substudy of the BASIC3 Study, which enrolled newly diagnosed cancer patients <18 years of age with assent. Of 32 young adults (YAs) with cancer who reached the age of majority (AOM; 18 years) while on study, 12 were successfully approached and all consented to study continuation at AOM. Of those, seven completed an interview. Patients' oncologists, who enrolled and participated in return of clinical genomic results, were also interviewed (n = 12). Interviews were transcribed, deidentified, and analyzed using thematic analysis. Results: YAs cited the possibility of helping others and advancing science as major reasons for their assent to initial study enrollment and their willingness to consent at AOM. YAs thought obtaining informed consent from research participants for study continuation at AOM was a good idea in case they changed their minds or wanted to make their own decisions, and to keep them aware of study activities. There was diversity in what YAs understood and learned from genomic testing: some recalled specific findings, while some remembered minimal information about their results. Oncologists varied in their assessment of adolescents' engagement with the study and understanding of their results. Conclusion: Given the different ways AYAs engage with genomic information, careful assessment of AYAs' diverse communication and decision-making preferences is needed to tailor interactions accordingly.

From Bridge to Destination? Ethical Considerations Related to Withdrawal of ECMO Support over the Objections of Capacitated Patients.

Extracorporeal membrane oxygenation (ECMO) is typically viewed as a time-limited intervention-a bridge to recovery or transplant-not a destination therapy. However, some patients with decision-making capacity request continued ECMO support despite a poor prognosis for recovery and lack of viability as a transplant candidate. In response, critical care teams have asked for guidance regarding the ethical permissibility of unilateral withdrawal over the objections of a capacitated patient. In this article, we evaluate several ethical arguments that have been made in favor of withdrawal, including distributive justice, quality of life, patients' rights, professional integrity, and the Equivalence Thesis. We find that existing justifications for unilateral withdrawal of ECMO support in capacitated patients are problematic, which leads us to conclude that either: (1) additional ethical arguments are necessary to defend this approach or (2) the claim that it is not appropriate to use ECMO as a destination therapy should be questioned.

Building Effective Mentoring Relationships During Clinical Ethics Fellowships: Pedagogy, Programs, and People.

How should clinical ethicists be trained? Scholars have stated that clinical ethics fellowships create well-trained, competent ethicists. While this appears intuitive, few features of fellowship programs have been publicly discussed, let alone debated. In this paper, we examine how fellowships can foster effective mentoring relationships. These relationships provide the foundation for the fellow's transition from novice to competent professional. In this essay, we begin by discussing our pedagogical commitments. Next, we describe the structures our program has created to assist our fellows in becoming competent ethicists. We then outline the kinds of knowledge, skills, and professional attributes mentors should possess. Following this, we focus on the knowledge, skills, and professional attributes that fellows develop as they co-create effective mentoring relationships. We will not prescribe a single approach to fellowship training; instead, our perspective will, we hope, become a catalyst for further conversation on training and mentoring clinical ethics fellows.

Perceived Utility of Genomic Sequencing: Qualitative Analysis and Synthesis of a Conceptual Model to Inform Patient-Centered Instrument Development.

BACKGROUND AND OBJECTIVES: Successful clinical integration of genomic sequencing (GS) requires evidence of its utility. While GS potentially has benefits (utilities) or harms (disutilities) across multiple domains of life for both patients and their families, there is as yet no empirically informed conceptual model of these effects. Our objective was to develop an empirically informed conceptual model of perceived utility of GS that captures utilities and disutilities for patients and their families across diverse backgrounds. METHODS: We took a patient-centered approach, in which we began with a review of existing literature followed by collection of primary interview data. We conducted semi-structured interviews to explore types of utility in a clinically and sociopolitically diverse sample of 60 adults from seven Clinical Sequencing Evidence-Generating Research (CSER) consortium projects. Interviewees had either personally received, or were parents of a child who had received, GS results. Qualitative data were analyzed using thematic analysis. Findings from interviews were integrated with existing literature on clinical and personal utility to form the basis of an initial conceptual model that was refined based on expert review and feedback. RESULTS: Five key utility types that have been previously identified in qualitative literature held up as primary domains of utility and disutility in our diverse sample. Interview data were used to specify and organize subdomains of an initial conceptual model. After expert refinement, the five primary domains included in the final model are clinical, emotional, behavioral, cognitive, and social, and several subdomains are specified within each. CONCLUSION: We present an empirically informed conceptual model of perceived utility of GS. This model can be used to guide development of instruments for patient-centered outcome measurement that capture the range of relevant utilities and disutilities and inform clinical implementation of GS.

Beyond babies: Implications of human genome editing for women, children, and families.

Scholarship on human germline editing has centered on the risks to the genetically-modified child. However, far less emphasis is focused on women who will become pregnant with a genetically modified embryo as part of human subject research or the families that raise children whose genomes were modified as an embryo. The lack of attention on women and families places these key stakeholders in genomic technologies at significant medical, ethical, and personal harm as research rapidly moves forward to advance the science of genomic modification. Now is the time to address how the interests of women and families should be represented in the ethical and scientific frameworks of human genomic modification, with specific considerations for Institutional Review Boards who review protocols for rigorous human subject protections and scientists who develop scientific methodologies that dictate the potential risks conferred to research participants. In this paper, we examine the implications of genomic modification of human embryo for women, children, and families to explore how to review a first-in-human clinical protocol of human genomic officiation responsibly.

Conceptualization of utility in translational clinical genomics research.

Prior to integration into clinical care, a novel medical innovation is typically assessed in terms of its balance of benefits and risks, often referred to as utility. Members of multidisciplinary research teams may conceptualize and assess utility in different ways, which has implications within the translational genomics community and for the evidence base upon which clinical guidelines groups and healthcare payers make decisions. Ambiguity in the conceptualization of utility in translational genomics research can lead to communication challenges within research teams and to study designs that do not meet stakeholder needs. We seek to address the ambiguity challenge by describing the conceptual understanding of utility and use of the term by scholars in the fields of philosophy, medicine, and the social sciences of decision psychology and health economics. We illustrate applications of each field's orientation to translational genomics research by using examples from the Clinical Sequencing Evidence-Generating Research (CSER) consortium, and we provide recommendations for increasing clarity and cohesion in future research. Given that different understandings of utility will align to a greater or lesser degree with important stakeholders' views, more precise use of the term can help researchers to better integrate multidisciplinary investigations and communicate with stakeholders.

Pediatric Oncologists' Experiences Returning and Incorporating Genomic Sequencing Results into Cancer Care.

Pediatric oncologists' perspectives around returning and incorporating tumor and germline genomic sequencing (GS) results into cancer care are not well-described. To inform optimization of cancer genomics communication, we assessed oncologists' experiences with return of genomic results (ROR), including their preparation/readiness for ROR, collaboration with genetic counselors (GCs) during ROR, and perceived challenges. The BASIC3 study paired pediatric oncologists with GCs to return results to patients' families. We thematically analyzed 24 interviews with 12 oncologists at two post-ROR time points. Oncologists found pre-ROR meetings with GCs and geneticists essential to interpreting patients' reports and communicating results to families. Most oncologists took a collaborative ROR approach where they discussed tumor findings and GCs discussed germline findings. Oncologists perceived many roles for GCs during ROR, including answering families' questions and describing information in lay language. Challenges identified included conveying uncertain information in accessible language, limits of oncologists' genetics expertise, and navigating families' emotional responses. Oncologists emphasized how GCs' and geneticists' support was essential to ROR, especially for germline findings. GS can be successfully integrated into cancer care, but to account for the GC shortage, alternative ROR models and access to genetics resources will be needed to better support families and avoid burdening oncologists.

"You can't make me!" Managing adolescent dissent to anesthesia.

When adolescents require health care, the need to obtain consent from the parent/legal guardian and assent from the patient can create the potential for an ethical dilemma when these two parties are not in agreement. Here, we describe a representative and common case scenario in which both parent and adolescent patient gave consent and assent, respectively, with a full understanding of the risks and benefits of the procedure and anesthetic. At the time of anesthetic induction, however, the patient expresses that she no longer wishes to have the procedure. We identify a number of considerations that inform the ethical analysis of such cases and offer recommendations about the most appropriate path forward for a practitioner faced with a difficult decision about how to respond.

iPLEDGE Must Abstain from Abstinence.

Isotretinoin has unmatched efficacy in the treatment of acne. However, because isotretinoin is a teratogen that can cause profound birth defects, the iPLEDGE program regulates the drug's distribution in the United States. To minimize fetal exposure to isotretinoin, the program requires that female patients capable of becoming pregnant use two forms of contraception or commit to abstinence while using this therapy. This manuscript argues that iPLEDGE should be revised to remove abstinence as an acceptable contraceptive option in the face of evidence that disputes its efficacy. All patients, regardless of reported sexual activity, should be required to use data-proven contraception. Potential benefits of the proposed change (iPLEDGE-R) include reducing the number of isotretinoin pregnancies, increasing patient privacy protection, and standardizing patient care. Further investigation needs to guide additional strategies to achieve the program's public health goal; however, the ethical and pragmatic advantages of iPLEDGE-R merit consideration.

The Top 10 Questions Facing the Field of Clinical Ethics in 2020: Reflections on the Evolving Clinical Ethics UnConference.

Evolving Clinical Ethics: A Working UnConference, held 5 through 7 February 2020 in Houston, Texas, brought together 91 participants from a variety of institutions, many of whom are engaged in clinical ethics work. The event followed the success of the first Clinical Ethics UnConference hosted by the Cleveland Clinic Center for Bioethics in 2018, and offered an opportunity for ethicists to share both their challenges and their solutions to clinical ethics issues. In this article we explore the emerging themes of the second UnConference and identify the top 10 questions currently faced by the field. We address both unresolved issues and areas of agreement and highlight new collaborations that have been developed to work toward greater standardization in our field.

"Do we have to replace the balloon pump when it fails?"

Mrs. Duong had coronary artery disease, ischemic cardiomyopathy, and mildly altered mental status when her case was presented before an advanced heart therapy medical review board. She was accepted for left ventricular assist device placement pending additional insight into her cognitive state. Before the LVAD could be implanted, however, Mrs. Duong went into cardiogenic shock, and her heart failure team placed an intra-aortic balloon pump in her subclavian artery. Within two weeks, Mrs. Duong became IABP dependent and deconditioned. The attending deemed her as lacking capacity to make complex medical decisions, and the medical review board officially declined her for LVAD placement. The heart failure and CICU teams feel that Mrs. Duong is not being helped by the care they are giving her. They recommend terminal weaning of the IABP and initiation of comfort care. Her family disagrees, pointing to activities like continued eating and interacting with family. At an impasse after yet another family meeting, the attending for the heart failure team asks the clinical ethics consultant, "Do we have to replace the balloon pump when it fails?"