Clinical Innovations Near the Boundary of Viability—The Artificial Womb

Extreme prematurity is the leading cause of infant death and morbidity. And, despite advances in neonatal medicine and surgery, the rate of prematurity has risen. The urgent need for a better way to support the extremely premature infant led to the development of an extrauterine system to better bridge the transition from fetal to postnatal life. The goal of this “artificial womb” is to maintain prenatal physiology in the extremely premature neonate to support normal development and reduce the complications associated with prematurity. This chapter discusses the development and applications of the artificial womb, as well as the limitations of this technology. It explores three current ethical challenges: ectogenesis, the boundary of viability, and the difference between physiological and clinical success.

Payments for Participation of Children in Research

Providing payment to those who participate is common practice for research studies involving both children and adults. While there may be good reasons for providing payment for research participation, there are also reasons to be concerned about the practice, especially when the subjects are children and the payment has the potential to distort parental decision-making by tempting parents to consider issues other than the welfare of their child. This chapter examines the ethical implications of providing payment to children and their parents for participation in research. After a brief survey of current practices regarding payments to research participants, the chapter will examine the distinct kinds of payments offered to research participants and their parents (Those intended to reimburse expenses and those intended to induce participation), evaluate the ethical considerations relevant to each kind of payment, and make some final recommendations concerning the provision of payments for research involving children.

Social Media and Pediatric Research Recruitment

Social media use has increased exponentially across all demographics. With social media’s widespread popularity comes an increased potential for research sponsors and investigators to use it as an effective tool for recruiting individuals into clinical research. Despite this, there has been relatively little attention paid to the general ethical issues implicated in social media recruitment and even less attention paid to the distinct ethical issues raised by using social media to recruit pediatric populations more specifically. This chapter examines these issues, providing an overview of the use of social media in clinical practice, an assessment of the general ethical issues associated with social media recruitment, and analysis of the potential risks and benefits of using social media to target adolescents for recruitment into clinical research.

Ethical Issues in Genetic Research with Infants

There are a number of ethical issues raised when newborns participate in research. Two examples include genetic testing, and the storage and research use of biospecimens collected from newborns. This chapter highlights a range of ethical, legal, and social implications with these practices. Examples from retention of residual newborn screening bloodspots, use of biospecimens collected from infants in biomedical research, concerns with the use of whole genome sequencing, and challenges of consent during the newborn period are discussed. These issues are explored within the context of newborns who are healthy or newborns faced with an undiagnosed condition. At this time, more research is needed to understand the impact of genomics on newborn health care, the storage and use of data generated from biospecimens, and how genetic results from newborns impact families. Further challenges around consent and parental permission are also discussed.

Catastrophically Ill Children, Access to Unregistered Medical Interventions, and Trial Recruitment Needs

This chapter discusses the case of a young girl infected by the Ebola virus during the epidemic outbreak in West Africa. She arrives alone to a medical center run by a non-governmental organization and is relatively well, but she has a high viral load and will with all certainty die within a week. This chapter argues that, in the face of imminent and certain death, it is permissible for the doctors at the medical center to use unregistered medical interventions, if they deem it to be in the best interest of the child. It further argues that they are permitted to do so without enrolling the child in a clinical trial, if the unregistered intervention is not scarce and the trial has placebo control groups.

Ethics and Research with Children

This brief introductory chapter highlights the central tension between the need to protect children from research risk with the imperative to conduct pediatric research. After reviewing several policy shifts that help to provide historical context, the authors discuss the case-based method that is employed in the remainder of the book. The value and perils of using cases are explored. The chapter subsequently provides some suggestions for how the book might best be used inside and out of the classroom and concludes with a discussion of the ultimate aspiration for this second edition of Ethics and Research with Children: A Case-Based Approach.

Invasive Placebos, Patient Burdens, and Community Advocacy

The “Additional Safeguards for Children in FDA-Regulated Clinical Investigations,” 21 CFR 50 subpart D, places limits on the risk to which a child can be exposed in a study. Absent a prospect of direct clinical benefit, institutional review boards (IRBs) cannot approve an intervention or procedure that exceeds “a minor increase over minimal risk.” If there is an ethical justification for the study to proceed, the IRB may refer the protocol for review by a federal panel under 21 CFR 50.54. A study allowing use of a totally implantable central venous access device (TICVAD) to provide placebo was referred for federal panel review; the committee voted unanimously in favor of a TICVAD. A determination by the Food and Drug Administration commissioner was issued within 10 weeks of the initial referral, an unprecedented time line. The Duchenne Muscular Dystrophy community was instrumental in initiating the referral and informing the panel’s decision.

Ethical Issues in the Neonatal SUPPORT Trial

The controversy over the neonatal Surfactant, Positive Pressure, and Oximetry Randomized Trial (SUPPORT) study of oxygen saturation targets in extremely premature babies was intense and polarizing. The fundamental issue turned on whether or not there were reasonably foreseeable risks to the babies who were enrolled in the study and, if so, whether that should have either (a) been disclosed in the consent form or (b) led institutional review boards to never approve the study in the first place. The federal Office for Human Research Protections (OHRP) took the first view. The advocacy group Public Citizen (PC) took the second. This chapter suggests that both views were wrong. Being in the study was, in fact, safer than not being in the study. The mistakes made by both OHRP and PC have dangerous implications for research ethics and regulation. They could lead to mandates for consent forms that are inaccurate and misleading.

Ethics and Research with Children

This chapter explores the ethical tension between protecting vulnerable children from research risks and protecting children through access to appropriate research in support of safe and effective pediatric products. The history of the debate over pediatric research is reviewed briefly, along with central ethical themes within that debate. Each of the chapters in this volume are set within this context. Themes examined include the role of the clinician-investigator, the concept of the best interests of the child, appropriate risk assessment, the importance of component analysis to the assessment of pediatric research protocols, the choice of an appropriate control group, parental permission and child assent, compensating children for research participation, and the fetus as research subject.

The Welfare of Children, Research Ethics, and the Bucharest Early Intervention Project

Ethical principals demand that science foster human goodness and flourishing—serving as a tool to help, not harm, humanity. This chapter considers as a case study the Bucharest Early Intervention Project (BEIP), a randomized controlled trial comparing the effects of foster care as an alternative to institutional care for young children in Bucharest, Romania. The study results suggested that early institutionalization leads to profound deficits in many domains. The ethical issues triggered by these experiments span the domains of randomization to harm, clinical equipoise, standard of care, researcher ambivalence, duty to rescue, political cooptation and conflicts of interest, and logicality. The alleged methodological rigor of the randomized controlled BEIP has a seductive internal consistency, but careful analysis reveals that gloss distracted the scientific community from our fundamental ethical obligation to provide authentic witness to, and compassionate care for, the most vulnerable among us.