Key factors in children's competence to consent to clinical research

Background: Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. Methods: From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and socio-economic status (SES). We used logistic regression analysis and change in explained variance in competence judgments to quantify the contribution of a child variable to the total explained variance. Contextual factors included risk and complexity of the decision to participate, parental competence judgment and the child's or parents decision to participate. Results: Out of 209 eligible patients, 161 were included (mean age, 10.6 years, 47.2 % male). Age, SES, intelligence, ethnicity, complexity, parental competence judgment and trial participation were univariately associated with competence (P∈∈0.05). Conclusions: Age is the factor that explaines most of to the variance in children's competence to consent, followed by intelligence. Experience with disease did not affect competence in this study, nor did other variables. Clinical trial registration: Development and use of a standardized instrument for assessing children's competence to consent in drug trials: Are legally established age limits valid?, NTR3918

The Algebra of Physical Observables in Nonlinearly Realized Gauge Theories

We classify the physical observables in spontaneously broken nonlinearly realized gauge theories in the recently proposed loopwise expansion governed by the Weak Power-Counting (WPC) and the Local Functional Equation. The latter controls the non-trivial quantum deformation of the classical nonlinearly realized gauge symmetry, to all orders in the loop expansion. The Batalin-Vilkovisky (BV) formalism is used. We show that the dependence of the vertex functional on the Goldstone fields is obtained via a canonical transformation w.r.t. the BV bracket associated with the BRST symmetry of the model. We also compare the WPC with strict power-counting renormalizability in linearly realized gauge theories. In the case of the electroweak group we find that the tree-level Weinberg relation still holds if power-counting renormalizability is weakened to the WPC condition.Comment: 20 pages, 1 figur

The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology

Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Neuropsychological effects of risperidone in children with pervasive developmental disorders: a blinded discontinuation study.

Contains fulltext : 49615.pdf (publisher's version ) (Open Access)OBJECTIVE: Little is known about the neuropsychological effects of risperidone in children with pervasive developmental disorders. METHOD: Twenty-four children (aged 5-17 years) with pervasive developmental disorders and co-morbid disruptive behavior who responded favorably to open-label treatment with risperidone as part of a previously described controlled discontinuation study completed two different computerized attention tasks at baseline, weeks 4, 8, and 24 of open-label treatment, and, at 8 weeks after random assignment to either placebo or risperidone. The primary efficacy measures were response latencies to visually presented stimuli requiring two different types of attention-controlled processing, i.e., focused and divided attention. RESULTS: About half of the clinical responders did not produce valid performance measures. These could be shown to be of younger mental age and less adaptive as measured by the Vineland Behavior Scales. For the valid task performers divided attention (serial search in working memory) was shown to regress in the placebo group (n = 7), while in the risperidone group (n = 7) there was further improvement. No such group difference was found for focused attention. CONCLUSIONS: The study suggests a beneficial effect of risperidone after several months of treatment, enhancing divided attention in children with pervasive developmental disorders

Atomoxetine for attention-deficit/hyperactivity disorder symptoms in children with pervasive developmental disorders: a pilot study.

Contains fulltext : 50798.pdf (publisher's version ) (Open Access)OBJECTIVE: This pilot study examined the effects of atomoxetine on attention-deficit/hyperactivity disorder (ADHD) symptoms and autistic features in children with pervasive developmental disorders (PDD). METHOD: Twelve children (aged 6-14 years) with PDD accompanied by ADHD symptoms entered a 10-week open-label study with atomoxetine (1.19 +/- 0.41 mg/kg/day). Response was assessed by using parent and clinician rating scales with change in the ADHD-Rating Scale (ADHDRS) as primary outcome measure. RESULTS: Atomoxetine reduced ADHD-symptoms as measured by the ADHDRS (44% decrease vs. baseline, p < 0.003), the Conners' Parent Rating Scale-R:S (CPRS-R) (25% in the subscale "Cognitive Problems," p < 0.028; 32% in "Hyperactivity," p < 0.030; and 23% in "ADHD index," p < 0.023). We found a reduction of 21% (p = 0.071) for changes in the subscale "Hyperactivity" of the Aberrant Behavior Checklist (ABC). No change was found in any of the other ABC subscales, nor in the subscale "Oppositional" of the CPRS-R. Five patients (42%) discontinued because of side effects. Gastrointestinal symptoms, irritability, sleep problems, and fatigue were the most frequent side effects. CONCLUSIONS: These preliminary findings indicate that atomoxetine may be a promising new agent in the treatment of ADHD symptoms in children with PDD. However, children with PDD may have a higher vulnerability for some of the known side-effects of atomoxetine

Why is it hard to make progress in assessing children's decision-making competence?

Developmen

Informed consent instead of assent is appropriate in children from the age of twelve: Policy implications of new findings on children's competence to consent to clinical research

Background: For many decades, the debate on children's competence to give informed consent in medical settings concentrated on ethical and legal aspects, with little empirical underpinnings. Recently, data from empirical research became available to advance the discussion. It was shown that children's competence to consent to clinical research could be accurately assessed by the modified MacArthur Competence Assessment Tool for Clinical Research. Age limits for children to be deemed competent to decide on research participation have been studied: generally children of 11.2 years and above were decision-making competent, while children of 9.6 years and younger were not. Age was pointed out to be the key determining factor in children's competence. In this article we reflect on policy implications of these findings, considering legal, ethical, developmental and clinical perspectives. Discussion: Although assessment of children's competence has a normative character, ethics, law and clinical practice can benefit from research data. The findings may help to do justice to the capacities children possess and challenges they may face when deciding about treatment and research options. We discuss advantages and drawbacks of standardized competence assessment in children on a case-by-case basis compared to application of a fixed age limit, and conclude that a selective implementation of case-by-case competence assessment in specific populations is preferable. We recommend the implementation of age limits based on empirical evidence. Furthermore, we elaborate on a suitable model for informed consent involving children and parents that would do justice to developmental aspects of children and the specific characteristics of the parent-child dyad. Summary: Previous research outcomes showed that children's medical decision-making capacities could be operationalized into a standardized assessment instrument. Recommendations for policies include a dual consent procedure, including both child as well as parents, for children from the age of 12 until they reach majority. For children between 10 and 12 years of age, and in case of children older than 12 years in special research populations of mentally compromised patients, we suggest a case-by-case assessment of children's competence to consent. Since such a dual consent procedure is fundamentally different from a procedure of parental permission and child assent, and would imply a considerable shift regarding some current legislations, practical implications are elaborated

Key factors in children's competence to consent to clinical research

Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and socio-economic status (SES). We used logistic regression analysis and change in explained variance in competence judgments to quantify the contribution of a child variable to the total explained variance. Contextual factors included risk and complexity of the decision to participate, parental competence judgment and the child's or parents decision to participate. Out of 209 eligible patients, 161 were included (mean age, 10.6 years, 47.2 % male). Age, SES, intelligence, ethnicity, complexity, parental competence judgment and trial participation were univariately associated with competence (P 0.05). Age is the factor that explaines most of to the variance in children's competence to consent, followed by intelligence. Experience with disease did not affect competence in this study, nor did other variables. Development and use of a standardized instrument for assessing children's competence to consent in drug trials: Are legally established age limits valid?, NTR391

Feasibility of an Assessment Tool for Children's Competence to Consent to Predictive Genetic Testing: a Pilot Study

Knowledge on children's capacities to consent to medical treatment is limited. Also, age limits for asking children's consent vary considerably between countries. Decision-making on predictive genetic testing (PGT) is especially complicated, considering the ongoing ethical debate. In order to examine just age limits for alleged competence to consent in children, we evaluated feasibility of a standardized assessment tool, and investigated cutoff ages for children's competence to consent to PGT. We performed a pilot study, including 17 pediatric outpatients between 6 and 18 years at risk for an autosomal dominantly inherited cardiac disease, eligible for predictive genetic testing. The reference standard for competence was established by experts trained in the relevant criteria for competent decision-making. The MacArthur Competence Assessment Tool for Treatment (MacCAT-T) served as index test. Data analysis included raw agreement between competence classifications, difference in mean ages between children judged competent and judged incompetent, and estimation of cutoff ages for judgments of competence. Twelve (71 %) children were considered competent by the reference standard, and 16 (94 %) by the MacCAT-T, with an overall agreement of 76 %. The expert judgments disagreed in most cases, while the MacCAT-T judgments agreed in 65 %. Mean age of children judged incompetent was 9.3 years and of children judged competent 12.1 years (p = .035). With 90 % sensitivity, children younger than 10.0 years were judged incompetent, with 90 % specificity children older than 11.8 years were judged competent. Feasibility of the MacCAT-T in children is confirmed. Initial findings on age cutoffs are indicative for children between the age of 12 and 18 to be judged competent for involvement in the informed consent process. Future research on appropriate age-limits for children's alleged competence to consent is neede

Prolactin release in children treated with risperidone: impact and role of CYP2D6 metabolism.

Contains fulltext : 53270.pdf (publisher's version ) (Closed access)OBJECTIVE: Little is known about the role of CYP2D6 polymorphism in risperidone-induced prolactin release in children. METHOD: Twenty-five children (aged 5-15 years) with pervasive developmental disorders were genotyped for CYP2D6 polymorphisms. Serum prolactin, risperidone, and 9-hydroxyrisperidone were assessed at baseline and after 8 weeks of risperidone treatment (mean dosage, 0.06 +/- 0.03 mg/kg/d). After 24 weeks of treatment, prolactin was measured in a subsample of 15 children. Adverse effects were evaluated using a clinician-rated survey. RESULTS: Mean +/- SD prolactin levels increased from 7.8 +/- 8.0 ng/mL at baseline to 33.2 +/- 12.8 ng/mL at week 8 (P < 0.001), with a slight decrease to 28.8 +/- 13.6 ng/mL at week 24. At week 8, serum prolactin level was positively correlated with dose per kilogram (r = 0.648, P < 0.001), number of functional CYP2D6 genes (J = 2.117, P = 0.034), and serum 9-hydroxyrisperidone concentration (r = 0.664, P = 0.001) and was negatively correlated with the risperidone/9-hydroxyrisperidone ratio (r = -0.571, P = 0.004) but not with risperidone concentration (r = -0.243, P = 0.264) nor age (r = 0.072, P = 0.733). Prolactin elevation was not associated with adverse effects. CONCLUSIONS: Low-to-intermediate doses of risperidone induced a 4-fold prolactin increase in children without a clear development of tolerance up to 6 months. CYP2D6 ultrarapid metabolism may be a risk factor for more pronounced prolactin elevation