Robert M. Nelson

Child assent and parental permission in pediatric research.

Since children are considered incapable ofgiving informed consent to participate inresearch, regulations require that bothparental permission and the assent of thepotential child subject be obtained. Assent andpermission are uniquely bound together, eachserving a different purpose. Parentalpermission protects the child from assumingunreasonable risks. Assent demonstrates respectfor the child and his developing autonomy. Inorder to give meaningful assent, the child mustunderstand that procedures will be performed,voluntarily choose to undergo the procedures,and communicate this choice. Understanding theelements of informed consent has been theparadigm for assessing capacity to give assent.This method leaves the youngest, leastcognitively mature children vulnerable towaiver of assent and forced researchparticipation. Voluntariness can also becompromised by the influence of authorityfigures who can exert undue influence andcoerce children to participate in research. This paper discusses factors that may influencethe decision to give assent/permission,potential parent-child conflict in theassent/permission process and how it isresolved, and potential parental undueinfluence on research participation. Theseissues are illustrated with quotations drawnfrom a larger qualitative study of parentalpermission and child assent (data notpresented). We suggest a developmentalapproach, viewing assent as a continuum rangingfrom mere affirmation in the youngest childrento the equivalent of the informed consentprocess in the mature adolescent.

The European Union Directive and the protection of incapacitated subjects in research: an ethical analysis

ObjectiveWe perform an ethical analysis of European Union Directive 2001/20/EC on the simplification and harmonization of guidelines regarding good clinical practice in the conduct of clinical trials involving drugs.BackgroundThe Directive provides guidance on protecting incapacitated subjects who participate in drug clinical trials. Such guidance promotes society’s obligations of beneficence because the participation of incapacitated subjects in research is crucial in advancing the understanding and treatment of serious diseases. The Directive requires proxy consent for incapacitated subjects which adheres to the principle of respect for persons. The Directive also recommends additional safeguards to further protect subjects against exploitation and harm. These include respect for the assent and dissent of incapacitated subjects and the “necessity” and “subject-condition” requirements.ResultsWhile these essential protection mechanisms are commendable, the Directive fails to endorse other safeguards that have been recommended by other research ethics guidelines, especially for riskier research. The Directive’s silence regarding research in the emergency setting frustrates the principle of beneficence because the lack of guidance might prove to be a barrier for the conduct of such potentially beneficial research.ConclusionsWe conclude that the European Directive fails in many respects to promote several important ethical principles in research involving incapacitated subjects.

Challenges in the Conduct of Emergency Research in Children: A Workshop Report

A workshop on “Emergency Research in Children: Ethical, Regulatory, and Clinical Challenges” was sponsored by the National Institute of Child Health and Human Development, National Institutes of Health, and held on January 12 to 13, 2006, in Bethesda, MD. The purpose of the workshop was to identify issues and concerns with the conduct of research involving children under the emergency exception from informed consent (EFIC) allowed under United States Food and Drug Adiminstration (FDA) and Department of Health and Human Services (DHHS) regulations. Invited participants included investigators, ethicists, and local institutional review board (IRB) members. The workshop was not designed to achieve nor reach consensus among the workshop participants, nor was it intended to provide advice to any branch of the federal government. Federal officials were present at the meeting as observers and provided information on policies or regulations as needed. This report was prepared from the minutes of the meeting; however, it represents only the views of this author. The meeting was arranged as a focused discussion around five general topics: 1) subject eligibility; 2) study design; 3) consent; 4) communication; and 5) implementation. Following an introductory “Review of the Ethical and Regulatory History of the Current EFIC Regulation,” each topic (and related questions) was afforded up to 2 hours of group discussion. Each topic included one or more questions to stimulate discussion. The following sections are arranged according to the five general topics, starting with the initial question(s), a summary of the discussion, and one or two concluding remarks by this author.

Issues in the Institutional Review Board Review of PET Scan Protocols

The lack of reliable information on the use of medications for children has been addressed in the United States through two legislative initiatives: the Best Pharmaceuticals for Children Act (BPCA) of 2002 (1) and the Pediatric Research Equity Act (PREA) of 2003 (2). These two initiatives have stimulated pediatric pharmaceutical research, resulting in valuable information to guide the appropriate use of many medications (3). In addition, the National Institutes of Health now requires (as of 1998) that children be included in research unless there are scientific and ethical reasons not to include them (4). The resulting increase in pediatric research has led to concerns that the regulations governing pediatric research provide insufficient protection. This chapter refers to only the Food and Drug Administration (FDA) regulations governing research with children (21 CFR 50 and 56), as the use of radiopharmaceuticals in PET scanning is regulated by the FDA. Comparable regulations are found in 45 CFR 46, subparts A and D.

Ethics in the Pediatric Intensive Care Unit

death within minutes to years. In fact, most children who die in the PICU do so after a decision has been made to either limit or withdraw (i.e., forgo) some form of LSMT [1]. The use of LSMT assumes that the burden of treatment is justifi ed by the anticipated outcome of an acceptable quality of life. As the anticipated quality of life deteriorates or becomes increasingly unlikely, or as the burden of treatment becomes intolerable, continued LSMT may not make sense. Decisions to limit LSMT may include not attempting resuscitation, not escalating inotropic or ventilator support, or not starting new treatments (such as endotracheal intubation or new modes of ventilation). Decisions to withdraw LSMT may include stopping inotropic support, decreasing or stopping ventilator support, stopping endotracheal intubation, or stopping artifi cially provided hydration and nutrition. The reasons for forgoing LSMT can be grouped into two broad categories: the intervention either (1) does not or will not work (i.e., futility) or (2) is not worth doing as the burden of treatment outweighs any expected or actual benefi t (i.e., disproportionate burden) [2]. For example, performing a tracheotomy and instituting long-term ventilation for a child in a persistent vegetative state who aspirates and develops respiratory failure may be disproportionately burdensome, but it is not futile. The majority of decisions to forgo LSMT in the PICU are based on the judgment of disproportionate burden rather than on the more limited concept of futility. The judgment that continued LSMT presents a disproportionate burden involves a complex and value-laden balancing between the burden of intervention and the benefi t of the anticipated outcome for the child. In striking this balance, the focus should be on the quality of the child’s experience and not on the worth of that child’s life to others. Although pain and agitation can be minimized through medication, caregivers and parents may perceive differently the degree to which a child is suffering and to what purpose. The loss of interaction with a child who is on extracorporeal membrane oxygenation (ECMO) or nonconventional forms of mechanical ventilation because of the need for sedating medication may be especially diffi cult for parents. In conversation, clinicians should seek to understand the parents’ perspective and the role of factors such as tolerance for disability, hope for recovery, religious faith, views of other family members, and so forth. Clinicians often use the term futility broadly and thus obscure the fact that the assessment of disproportionate burden rests on a value judgment about the anticipated outcome that the family may not share. As futility may be used to justify a decision to forgo Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Setting Limits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 The Process of Delivering Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38 Declaring Death and Organ Transplantation. . . . . . . . . . . . . . . . . 39 Research with Critically Ill Children in the Pediatric Intensive Care Unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40