BACKGROUND: Enrolling children in clinical trials typically requires parental or guardian permission and, when appropriate, child assent. Aligning requirements across jurisdictions would facilitate multisite pediatric trials. Guidance from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is the best candidate for a global standard but would benefit from additional specification.

METHODS: Ethical analysis of ICH guidance for permission and assent for pediatric trials, with recommendations for clarification.

RESULTS: ICH guidance regarding permission and assent would be enhanced by additional detail in the following areas: (1) what information should be provided to parents, guardians, and children considering a trial, and how that information should be provided; (2) the definition of "assent," the criteria for when assent should be required, and the need to include children in discussions even when assent is not mandated; (3) criteria for requiring children's signatures indicating agreement; (4) greater specificity regarding children's right to decline or withdraw; and (5) clarification of when children's wish to decline or withdraw from participation may be overridden and of what the overriding process should entail.

CONCLUSION: ICH guidance provides a global standard for decision making regarding children's participation in trials. Several clarifications would facilitate the conduct of multinational pediatric research.

IMPACT: Enrolling children in clinical trials requires the permission of a parent/guardian ± the assent of the minor. Differing global regulatory requirements for enrolling children complicate the conduct of multicenter and multinational trials. The authors identify points of ambiguity and/or contradiction in the International Council for Harmonization guidelines and offer recommendations for a common ethical platform for conducting global pediatric research.

<p><strong>BACKGROUND AND OBJECTIVES: </strong>Genetic testing is expanding among ill neonates, yet the influence of genetic results on medical decision-making is not clear. With this study, we sought to determine how different types of genetic information with uncertain implications for prognosis influence clinicians' decisions to recommend intensive versus palliative care.</p>

<p><strong>METHODS: </strong>We conducted a national study of neonatologists using a split sample experimental design. The questionnaire contained 4 clinical vignettes. Participants were randomly assigned to see one of 2 versions that varied only regarding whether they included the following genetic findings: (1) a variant of uncertain significance; (2) a genetic diagnosis that affects neurodevelopment but not acute survival; (3) a genetic versus nongenetic etiology of equally severe pathology; (4) a pending genetic testing result. Physicians answered questions about recommendations they would make for the patient described in each vignette.</p>

<p><strong>RESULTS: </strong>Vignette versions that included a variant of uncertain significance, a diagnosis foreshadowing neurodevelopmental impairment, or a genetic etiology of disease were all associated with an increased likelihood of recommending palliative rather than intensive care. A pending genetic test result did not have a significant effect on care recommendations.</p>

<p><strong>CONCLUSIONS: </strong>Findings from this study of hypothetical cases suggest neonatologists apply uncertain genetic findings or those that herald neurodevelopmental disability in problematic ways. As genetic testing expands, understanding how it is used in decision-making and educating clinicians regarding appropriate use are paramount.</p>