Ethics in Pediatric Trials

Acta Facultatis Pharmaceuticae Universitatis Comenianae, 2012

Ethical issues in clinical trials in children Clinical trials (CTs) in children involve much methodological specificity that are reflected in the ethical issues related to them, as well as in the evaluation of ethical acceptability of the given protocol by an ethics committee. A child in comparison to an adult exhibits numerous patho/physiological differences that are in addition characterized by the quick changes during the child's growth and development. Nowadays, there are no doubts about the necessity of conducting specific CTs in children that are not possible to perform in adults. Despite children are not able to give legally valid informed consent and it is necessary to obtain consent from the child's parents, or from the legal representative, it is also necessary, before including the child into the trial, to obtain his/her appropriate agreement (assent) with participation. It is a must always to fully respect the requirements of minimization of pain, discomfort, fea...

International Journal of Basic & Clinical Pharmacology

Children were acknowledged as ‘therapeutic or pharmaceutical orphans’ in 1960s, since then there has been a worldwide recognition of the need to conduct clinical trials in children, to improve their health. Prescribing in children is often based on extrapolation of trial results from adults, due to the lack of paediatric data. Children have different pharmacokinetic and pharmacodynamics responses as compared to adults. Hence extrapolating the adult safety and efficacy data and using it for prescribing in children can have disastrous effects. Relevant literature on clinical trials in paediatrics was gathered and scrutinized with emphasis on legal and ethical perspectives. This research is an exploratory attempt which surveys and summarizes previously published studies simultaneously trying to answer few research questions which addresses the current debates and scenario. Common problems encountered during pediatric clinical trials are unnecessary scrutiny of even minimal risk studies,...

European Journal of Clinical Pharmacology, 2007

Background Ethical problems are quoted as a reason not to perform clinical trials in children. Little is known about the views of researchers regarding ethics. Objectives A pilot study was conducted to assess the applicability of a questionnaire design containing trial scenarios to examine views regarding the use of children in drug trials and to elicit possible international differences. Setting Paediatricians and researchers in the United Kingdom and Canada. Methods Responders were presented with a questionnaire containing direct questions and six trial scenarios, each containing an ethical dilemma. Responders were asked regarding their own approval and their perceived opinion of whether an ethical review board (ERB) would approve. Results One hundred questionnaires (50 each country) were received. Few responders had research ethics training (14% United Kingdom and 8% Canada). Most (80 and 88%) felt children could be harmed by participation in trials and half (47 and 59%) felt children should only participate if they receive direct benefit. Many (58 and 61%) disagreed with payments beyond travel expenses. In the trial scenarios, 34% of responders were willing to enter healthy children in a pharmacokinetics study of an antibiotic for cystic fibrosis and 22% considered their ERBs would approve. Only a third (33%) would enter children in an analgesia trial that was placebo-controlled. Conclusion Using healthy children and placebos in trials caused concern. Similar views were found between the two countries. The majority had no training in research ethics. The study highlights the usefulness of a questionnaire with clinical trial scenarios to try to elicit views on the ethics of conducting research in children.

Controlled Clinical Trials, 1996

During a clinical trial of recombinant growth hormone in a population of short stature but otherwise healthy children the following ethical problems were confronted: What are the prospective benefits compared with the foreseeable risks associated with this therapy? Can the doctor really inform the parent and/or the child about the outcomes of the treatment? Who must make the decision about participation in the trial? From which age can the child himself decide about continuing or dropping out? Since the treatment requires frequent check-ups for years, to what extent does the child become psychologically dependent upon the medical profession? Given this possibility, is the child really free to withdraw from the treatment? Is there a conflict between the doctor's autonomy to propose the treatment and the patient's autonomy to decide about participation? Is there a clear threshold between life-threatening problems and minor, cosmetic problems? These dilemmas are discussed in a cross-cultural context.

Pediatric Drugs, 2014

The assessment of safety and efficacy of therapeutics for children and adolescents requires the use of multi-centered designs. However, the need to obtain ethical approval from multiple independent research ethics boards (REBs) presents as a challenge to investigators and sponsors who must consider local requirements while ensuring that the protection of human subjects is consistent across sites. In pediatrics, this requirement is complicated by pediatric-specific ethical concerns such as the acquisition of assent and consent and the need for pediatric expertise to assess the scholarly merit of the proposed research. Efforts to tackle these challenges have focused on the process of ethics review, which will improve efficiency. In addition to improving process, we suggest further research to fill gaps in the evidence base for recommendations and decisions made by REBs, specifically their effectiveness to protect human subjects. Evidence gathered will contribute to the successful development, adoption and implementation of harmonized guidance to apply ethics principles in order to protect children through research rather than from research.

Pediatric Clinics of North America, 2012

Children have been identified as uniquely vulnerable clinical research subjects since the early 1970s. In this paper we review the historical underpinnings of this designation, the current regulatory framework for pediatric and neonatal research, and common problems in pediatric research oversight. We also present three areas of pediatric and neonatal research (genomic screening, healthy children donating stem cells, and therapeutic hypothermia for neonates with hypoxic-ischemic encephalopathy) that highlight contemporary challenges in pediatric research ethics, including balancing risk and benefit, informed consent and assent, and clinical equipoise.

European Journal of Cancer, 2002

Pan-European collaboration in studies of novel therapies and treatment strategies in childhood cancer is playing an increasing role in the attempt to improve cure rates. Differences in the systems of various countries with regard to drug control and ethical issues may lead to problems and delays. This applies in particular to phase I/II studies in children where the ethical considerations may be complex. In this review, the systems in three large countries-UK, France and Germany-are reviewed and current moves within the European Community towards a more standard approach are discussed.

Journal of clinical pharmacology, 2017

Reviews on Recent Clinical Trials, 2006

Randomized controlled clinical trials are felt by the medical community to provide the best evidence. Participation in trials involves the possibility of obtaining benefits but also of suffering some risks. Those risks are often considered unacceptable for children but if clinical trials are not conducted in children, clinicians are forced to extrapolate study data from adults. In 1968 H. Shirkey termed children "therapeutic orphans" because of the lack of adequately tested and labeled drugs available in appropriate formulations. Research involving children entails specific difficulties as the need to study children of different ages, the small number of children affected by certain diseases or ethical issues. This paper considers aspects of pediatric clinical pharmacology and children's responses to drugs. It also reviews some of the current situations in pediatric clinical trials, covering aspects such as: the benefits and risks of trial participation; the specificity of pediatric trial design; the ethical issues such as consent; the use of placebo or the participation of healthy children; and the current legal situation in Europe and in the USA.

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