Abstract
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.
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References
McIntyre J, Conroy S, Avery A et al (2000) Unlicensed and off label prescribing of drugs in general practice. Arch Dis Child 83:498–501
Conroy S, McIntyre J, Choonara I (1999) Unlicensed and off label drug use in neonates. Arch Dis Child Fetal Neonatal Ed 80:F142–F145
Spielberg SP (2000) Paediatric therapeutics in the USA and internationally: an unparallel opportunity. Paed Perinatal Drug Ther 4:71–74
Food and Drug Administration Modernization Act (FDAMA) of 1997, Pub. L. No. 105-15, 105th Congress (Nov 21, 1997)
Best Pharmaceuticals for Children Act, Pub. L. No. 107-9, 107th Congress (Jan 4, 2002)
Saint-Raymond A, Seigneuret N (2005) Medicines for children: time for Europe to act. Paed Perinatal Drug Ther 6(3):142–146
Koren G, Kearns GL, Reed M et al (2003) Use of healthy children as volunteers in drug studies: the ethical debate. Clin Pharmacol Ther 73(3):147–152
Koren G (2003) Healthy children as subjects in pharmaceutical research. Theor Med 24:149–159
Jonsen A (2006) Nontherapeutic research with children: the Ramsey versus Mccormick debate. J Pediatr 149:S12–S14
Edwards SD, McNamee MJ (2005) Ethical concerns regarding guidelines for the conduct of clinical research on children. J Med Ethics 31:351–354
Ross L (2006) Phase 1 research and the meaning of direct benefit. J Pediatrics 149:S20–S24
Miller, Franklin G, Shorr AF (2002) Unnecessary use of placebo controls: the case of asthma clinical trials. Arch Int Med 162(15):1673–1677
McIntyre J, Robertson S, Norris E et al (2005) Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 366:205–210
Acknowledgements
Thank you to everyone who completed the questionnaires. Thank you to Apostolos Fakis (Derbyshire Acute Hospital Trust) for his statistical help and advice.
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No competing interests are declared.
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Appendix 1: scenarios of clinical trials used within the questionnaire
Appendix 1: scenarios of clinical trials used within the questionnaire
Scenario 1
A new antibiotic is developed and could be used for treating children with antibiotic resistance in cystic fibrosis. It has had clinical trials carried out in the adult population that have shown good treatment and safety profiles. The pharmaceutical company would like to obtain a license in children and would like to carry out a pharmacokinetic dose-finding study. They propose a study on ten healthy 6- to 12-year-old children who will receive a 14-day course of the antibiotic with a blood sample taken on days 7 and 14 by venipuncture to check the antibiotic levels in the blood. A 2-ml sample will be needed at each sample for analysis.
Scenario 2
A trial is proposed to study the emergency treatment of seizures in children comparing the treatments of rectal diazepam and buccal midazolam. Both treatments are currently in use and are accepted practice within paediatrics in the United Kingdom. Two hundred children admitted to the emergency department having a generalised tonic/clonic seizure will be pre-randomised for treatment with one of the two treatments by a pre-arranged sequence of weeks. Following the treatment of the child, the parents will be approached for consent for their child’s data to be used in the trial comparing the two treatments. Outcome will be time for seizure to stop following treatment.
Scenario 3
Studies in adults suggest that a new analgesic agent may be of use in mild to moderate pain in children. It has a good safety profile and no major side effects have been noted. A trial is proposed to assess this medication in a double-blind randomised controlled trial in 120 children aged 6–12 years who have undergone tonsillectomy. The new analgesic will be compared to acetaminophen and placebo. In the immediate post-operative period, pain will be assessed by a nurse and in the 7-day post-discharge period by parental pain diaries.
Scenario 4
A new anticonvulsant has been shown in studies to be useful as an add-on therapy in difficult-to-control epilepsy. Pharmacokinetic studies in adults have shown a good safety profile with a slow elimination half-life (28 h). A dose-finding study is proposed in 20 children with uncontrolled epilepsy who will receive the additional anticonvulsant along with their existing therapy. A liquid formulation has been devised. Many of these children will have severe learning difficulties but this will not exclude their participation in the study. The study period will be 6 weeks with weekly blood samples (2 ml) being taken.
Scenario 5
A new treatment has been developed that may help babies suffering from bronchiolitis. This is an oral liquid medication to decrease the incidence of wheeze and cough by decreasing inflammation within the lungs. It has been tested in the adult healthy population with few side effects. A pharmacokinetic study is proposed in healthy children (aged 6 months to 2 years). This will involve 40 children taking a 3-day course of medicine four times a day with one 2-ml sample of blood being taken from each patient. Population-based approaches will then be used to analyse the data and establish a proposed dose and safety profile for the drug.
Scenario 6
A new antibiotic has been developed and tested in adult studies with a good safety profile. It would be suitable for the treatment of otitis media in children. A liquid formulation has been developed for children. It is proposed to use 120 children aged 6–12 years with otitis media as the study group for a randomised placebo-controlled trial. Outcome will be recorded as resolution of symptoms with children being assessed at 3 and 7 days into the treatment courses.
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Sammons, H.M., Malhotra, J., Choonara, I. et al. British and Canadian views on the ethics of paediatric clinical trials. Eur J Clin Pharmacol 63, 431–436 (2007). https://doi.org/10.1007/s00228-007-0281-9
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DOI: https://doi.org/10.1007/s00228-007-0281-9