Regulatory and ethical issues in the conduct of clinical research involving children

Hirtz, Deborah; Fitzsimmons, Lorraine

doi:10.1097/00008480-200212000-00003

Cited by 22 publications

(7 citation statements)

References 2 publications

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“…Neuropsychological AED data in children are limited 22 and adult AED findings are not readily generalizable to children. 23 For example, the primary behavioral phenobarbital side effect is hyperactivity in children, depression in young adults, and sundowning in the elderly. Although neuropsychological impairment may be present at the time of initial diagnosis, 24 AED exposure during neurodevelopment can produce impairments that may continue into adulthood even after AED discontinuation.…”

Section: Fetal Aed Risks For Autism and Autisticmentioning

confidence: 99%

Developmental effects of antiepileptic drugs and the need for improved regulations

2016

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Antiepileptic drugs (AEDs) are among the most common teratogenic drugs prescribed to women of childbearing age. AEDs can induce both anatomical (malformations) and behavioral (cognitive/behavioral deficits) teratogenicity. Only in the last decade have we begun to truly discriminate differential AED developmental effects. Fetal valproate exposure carries a special risk for both anatomical and behavioral teratogenic abnormalities, but the mechanisms and reasons for individual variability are unknown. Intermediate anatomical risks exist for phenobarbital and topiramate. Several AEDs (e.g., lamotrigine and levetiracetam) appear to possess low risks for both anatomical and behavioral teratogenesis. Despite advances in the past decade, our knowledge of the teratogenic risks for most AEDs and the underlying mechanisms remain inadequate. Further, the long-term effects of AEDs in neonates and older children remain uncertain. The pace of progress is slow given the lifelong consequences of diminished developmental outcomes, exposing children unnecessarily to potential adverse effects. It is imperative that new approaches be employed to determine risks more expediently. Our recommendations include a national reporting system for congenital malformations, federal funding of the North American AED Pregnancy Registry, routine meta-analyses of cohort studies to detect teratogenic signals, monitoring of AED prescription practices for women, routine preclinical testing of all new AEDs for neurodevelopmental effects, more specific Food and Drug Administration requirements to establish differential AED cognitive effects in children, and improved funding of basic and clinical research to fully delineate risks and underlying mechanisms for AED-induced anatomical and behavioral teratogenesis.

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Section: Fetal Aed Risks For Autism and Autisticmentioning

confidence: 99%

Developmental effects of antiepileptic drugs and the need for improved regulations

2016

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“…Although Moser et al [ 30 ] demonstrated a correlation between salsolinol levels in urine and CSF and a time course study of N-methyl-norsalsolinol in CSF indicated a parallel decline of TIQ derivatives on both sides of the blood-brain barrier [ 17 , 31 ] the evidence for a reliable correlation between TIQ levels in urine and the central nervous system remains limited. However, analyses of urine levels seem to be methodologically and ethically justified as the first step to investigate TIQ in children with ADHD, because in studies analyzing other dopamine metabolites in the CSF, the lack of a control group [ 9 ] due to ethical considerations [ 32 ] limited the significance of the findings and they were not superior to the results of plasma or urine analyses. Nevertheless, increased central dopamine concentrations might cause increased concentrations of salsolinol and norsalsolinol in urine resulting also in increased urine concentrations of N-methyl-salsolinol and N-methyl-norsalsolinol.…”

Section: Discussionmentioning

confidence: 99%

Tetrahydroisoquinoline derivatives: a new perspective on monoaminergic dysfunction in children with ADHD?

et al. 2007

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BackgroundThe dopamine-derived tetrahydroisoquinolines (TIQ) synthesized endogeneously from aldehydes and catecholamines have shown to modulate neurotransmission, central metabolism and motor activity. Converging evidence has implicated abnormalities of the dopamine metabolism to the pathophysiology of Attention-Deficit/Hyperactivity Disorder (ADHD). Therefore, four TIQ derivatives involved in central dopamine metabolism (salsolinol, N-methyl-salsolinol, norsalsolinol, N-methyl-norsalsolinol) have been analyzed for the first time in children and adolescents with ADHD and healthy controls.Methods42 children and adolescents with ADHD and 24 controls from three sites participated in this pilot study. Free and bound amounts of salsolinol, N-methyl-salsolinol, norsalsolinol, N-methyl-norsalsolinol have been analyzed in urine.ResultsIn the ADHD group, free and total amounts of the four TIQ derivatives in urine were significantly higher compared to urine levels of healthy controls. For N-methyl-salsolinolfree, most of the ADHD patients were identified correctly with a sensitivity of 92.5% (specificity 94.4%).ConclusionUrine levels of salsolinol, N-methyl-salsolinol, norsalsolinol and N-methyl-norsalsolinol are elevated in children and adolescents with ADHD and point to a new perspective on catecholaminergic dysfunction in ADHD. However, replication and extension of this pilot study would progress this innovative and promising field.

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“…5 It can be argued that fertility preservation aimed at children is ethical because it prevents morbidity (reproductive and psychosocial) and it safeguards their reproductive autonomy. 6 Therefore, the main ethical question concerns the process involved in achieving fertility preservation and the techniques that are required.…”

Section: Ethics Of Fertility Preservation In Cancer Patients 719mentioning

confidence: 99%

“…As a result, they require special protection against potential violation of their rights that may occur during research investigations. 4,5 Until very recently, institutional attitudes impeded significant participation by children in medical research for fear of exploitation.…”

Section: Ethics Of Fertility Preservation In Cancer Patients 719mentioning

confidence: 99%

“…With respect to childhood fertility preservation, proper attainment of informed consent from a legally authorized representative (ie, parent or guardian) of childhood assent must be ensured. 4,5 Assent-the active affirmation by the research participant-can be obtained from incompetent minors and it should be obtained from children whenever possible. Although the benefits of gamete cryopreservation are promising, they are largely unquantifiable because human data on the survival of gametes after the freeze-thaw-transplant process are limited.…”

Section: Ethics Of Fertility Preservation In Cancer Patients 719mentioning

confidence: 99%

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Ethical Issues Surrounding Fertility Preservation in Cancer Patients

Patrizio

Caplan

2010

Clinical Obstetrics &Amp; Gynecology

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Fertility preservation is a newly developed branch of reproductive medicine aimed at preserving the potential for genetic parenthood in adults of reproductive age or children, who are at risk of sterility before undergoing anticancer treatments. Except for embryo and semen freezing, all the available options to preserve fertility are considered experimental and thus, they raise ethical issues. In this study, we reviewed the informed consent and the risk-benefit analysis of offering experimental procedures for both adults and children when they are in vulnerable situations. In particular, children represent a special category of patients and their assent to treatment to be sought at anytime should be possible. Overall, there should be no ethical objections to offer these services as they are offered with the scope of preserving future fertility.

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Regulatory and ethical issues in the conduct of clinical research involving children

Cited by 22 publications

References 2 publications

Developmental effects of antiepileptic drugs and the need for improved regulations

Developmental effects of antiepileptic drugs and the need for improved regulations

Tetrahydroisoquinoline derivatives: a new perspective on monoaminergic dysfunction in children with ADHD?

Ethical Issues Surrounding Fertility Preservation in Cancer Patients

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