Arlene M. Davis

Clinical Trials and Medical Care: Defining the Therapeutic Misconception

A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment.

Ethical, Legal, and Social Concerns About Expanded Newborn Screening: Fragile X Syndrome as a Prototype for Emerging Issues

Technology will make it possible to screen for fragile X syndrome and other conditions that do not meet current guidelines for routine newborn screening. This possibility evokes at least 8 broad ethical, legal, and social concerns: (1) early identification of fragile X syndrome, an “untreatable” condition, could lead to heightened anxiety about parenting, oversensitivity to development, alterations in parenting, or disrupted bonding; (2) because fragile X syndrome screening should be voluntary, informed consent could overwhelm parents with information, significantly burden hospitals, and reduce participation in the core screening program; (3) screening will identify some children who are or appear to be phenotypically normal; (4) screening might identify children with other conditions not originally targeted for screening; (5) screening could overwhelm an already limited capacity for genetic counseling and comprehensive care; (6) screening for fragile X syndrome, especially if carrier status is disclosed, increases the likelihood of negative self-concept, societal stigmatization, and insurance or employment discrimination; (7) screening will suggest risk in extended family members, raising ethical and legal issues (because they never consented to screening) and creating a communication burden for parents or expanding the scope of physician responsibility; and (8) screening for fragile X syndrome could heighten discrepancies in how men and women experience genetic risk or decide about testing. To address these concerns we recommend a national newborn screening research network; the development of models for informed decision-making; materials and approaches for helping families understand genetic information and communicating it to others; a national forum to address carrier testing and the disclosure of secondary or incidental findings; and public engagement of scientists, policy makers, ethicists, practitioners, and other citizens to discuss the desired aims of newborn screening and the characteristics of a system needed to achieve those aims.

Looking for Trouble: Preventive Genomic Sequencing in the General Population and the Role of Patient Choice

Advances in genomics have led to calls for developing population-based preventive genomic sequencing (PGS) programs with the goal of identifying genetic health risks in adults without known risk factors. One critical issue for minimizing the harms and maximizing the benefits of PGS is determining the kind and degree of control individuals should have over the generation, use, and handling of their genomic information. In this article we examine whether PGS programs should offer individuals the opportunity to selectively opt out of the sequencing or analysis of specific genomic conditions (the menu approach) or whether PGS should be implemented using an all-or-nothing panel approach. We conclude that any responsible scale-up of PGS will require a menu approach that may seem impractical to some, but that draws its justification from a rich mix of normative, legal, and practical considerations.

Stewardship Practices of U.S. Biobanks

Most U.S. biobanks do not create ongoing relationships with contributors but do practice stewardship over storing and sharing of specimens. Biobanks require new governance models that address their ethical and regulatory challenges. One model relies on stewardship of specimens throughout their life course. Here, we discuss findings from our survey of 456 U.S. biobank managers that addressed whether and how biobanks steward their specimens. The findings reveal that most biobanks do not create ongoing relationships with contributors but do practice stewardship over storing and sharing of specimens. Biobanks now need guidance to fully articulate stewardship practices that ensure respect for contributors while facilitating research.

Recommendations for ethical approaches to genotype-driven research recruitment

Recruiting research participants based on genetic information generated about them in a prior study is a potentially powerful way to study the functional significance of human genetic variation. However, it also presents significant ethical challenges that, to date, have received only minimal consideration. We convened a multi-disciplinary workshop to discuss key issues relevant to the conduct and oversight of genotype-driven recruitment and to translate those considerations into practical policy recommendations. Workshop participants were invited from around the US, and included genomic researchers and study coordinators, research participants, clinicians, bioethics scholars, experts in human research protections, and government representatives. Discussion was directed by experienced facilitators and informed by empirical data collected in a national survey of IRB chairs and in-depth interviews with research participants in studies where genotype-driven recontact occurred. A high degree of consensus was attained on the resulting seven recommendations, which cover informed consent disclosures and choices, the process for how and by whom participants are recontacted, the disclosure of individual genetic research results, and the importance of tailoring approaches based on specific contextual factors. These recommendations are intended to represent a balanced approach—protecting research participants, yet avoiding overly restrictive policies that hinder advancement on important scientific questions.

Genomics, Biobanks, and the Trade-Secret Model

An alternative to traditional informed-consent approaches to human subjects could provide flexibility and increased participation. Genomic biobanks—repositories of human DNA and/or associated data, collected and maintained for biomedical research—present ethical challenges different from those traditionally associated with medical research. Historically, when researchers obtained and used tissue samples, it was for defined purposes and the nature of the research was disclosed to contributors, who were asked to consent to the specific research project. With genomic biobanks, in contrast, the entity holding the samples may not be involved in the research, and future uses of the samples may be unknown. Although traditional research promised confidentiality and/or anonymity to participants, advances in DNA technology may render these safeguards meaningless (1–3). As a consequence, many ethicists argue that traditional informed consent may be illusory if not impossible (1, 4) and that different approaches to the ethics of genetic sample collections are needed (5, 6).

Underutilization of specimens in biobanks: an ethical as well as a practical concern?

“It’s totally false . . . that “if you build it they will come.” I thought if we build this [biobank] we’ll have people knocking on our door to use it” (Interview with a biobank director, 2011).Biobanks, organizations that acquire and store human speci-mens and associated data for future research use, may be essen-tial to realizing the promise of translational research—but not if researchers fail to come knocking on their doors. Indeed, lack of use of specimens and data by researchers may lead to biobank closure. Recent interviews and a national survey with US biobankers,

A Trade Secret Model for Genomic Biobanking

Genomic biobanks present ethical challenges that are qualitatively unique and quantitatively unprecedented. Many critics have questioned whether the current system of informed consent can be meaningfully applied to genomic biobanking. Proposals for reform have come from many directions, but have tended to involve incremental change in current informed consent practice. This paper reports on our efforts to seek new ideas and approaches from those whom informed consent is designed to protect: research subjects. Our model emerged from semi-structured interviews with healthy volunteers who had been recruited to join either of two biobanks (some joined, some did not), and whom we encouraged to explain their concerns and how they understood the relationship between specimen contributors and biobanks. These subjects spoke about their DNA and the information it contains in ways that were strikingly evocative of the legal concept of the trade secret. They then described the terms and conditions under which they might let others study their DNA, and there was a compelling analogy to the commonplace practice of trade secret licensing. We propose a novel biobanking model based on this trade secret concept, and argue that it would be a practical, legal, and ethical improvement on the status quo.

Genomic Research with the Newly Dead: A Crossroads for Ethics and Policy

Recent advances in next generation sequencing along with high hopes for genomic medicine have inspired interest in genomic research with the newly dead. However, applicable law does not adequately determine ethical or policy responses to such research. In this paper we propose that such research stands at a crossroads between other more established biomedical clinical and research practices. In addressing the ethical and policy issues raised by a particular research project within our institution comparatively with these other practices, we illustrate the moral significance of paying careful heed to where one looks for guidance in responding to ethical questions raised by a novel endeavor.

Transitions in Care for Infants with Trisomy 13 or 18

Background and Objectives The scope of interventions offered to infants with trisomy 13 (T13) or trisomy 18 (T18) is increasing. We describe the spectrum of care provided, highlighting transitions in care for individual patients. Patients and Methods This is a single‐center, retrospective cohort of infants with T13 or T18 born between 2004 and 2015. Initial care was classified as comfort care or intervention using prenatal counseling notes. Transitions in care were identified in the medical record. Results In this study, 25 infants were divided into two groups based on their care: neonates who experienced no transition in care and neonates who experienced at least one transition. Eleven neonates experienced no transition in care with 10 receiving comfort care. Fourteen neonates experienced at least one transition: three transitioned from comfort care to intervention and 11 from intervention to comfort care. The three initially provided comfort care were discharged home with hospice and readmitted. Among the 11 cases who transitioned from intervention to comfort care, 9 transitioned during the birth hospitalization, 6 had no prenatal suspicion for T13 or T18, and 5 experienced elective withdrawal of intensive care. Conclusion The spectrum of care for infants with T13 or T18 illustrates the need for individualized counseling that is on‐going, goal directed, collaborative, and responsive.