7.3.4 Research Involving Children
Thérèse St-Laurent-Gagnon MD, FRCP(C), PhD
- Reflect on the assessment of risks among children
- Reflect on the assessment of benefits among children
- Reflect on the involvement of children in research consent
This study was discussed in March 2004 during the Clinical Center Ethics Grand Rounds (http://www.bioethics.nih.gov/courses/ethgr/orourkemar04.pdf ).
The study examined children with attention deficit hyperactivity disorder (ADHD). ADHD is the most common behavioural disorder in children (5-10% of children overall). Symptoms include impulsiveness, inattention and inappropriate behaviours. The cause of ADHD is unknown, although a genetic component has been identified. Psychostimulants (for example, dextroamphetamine, or methylphenidate) are the standard medications for treatment.
Scientific objective of the research: verify whether children with ADHD experience a different response to stimulants in the central nervous system compared to children without ADHD.
Subjects: children ages 9 to 18, including: 14 children with ADHD and 14 healthy control subjects, as well as 24 monozygotic twins discordant for ADHD and 24 dizygotic twins discordant for ADHD.
Experimental procedures: all of the subjects will undergo data collection, a physical exam, and a neuropsychological assessment. They will all have blood drawn for genetic analyses and functional magnetic resonance imaging. Some children from both the control group and the ADHD group will receive either a single dose of dextroamphetamine (10 mg orally) or a placebo in a randomized, double-blind manner.
This study examined the relationship between the metabolism of serotonin in the central nervous system and aggressive behaviour in children with behavioural disorders associated with attention deficit and hyperactivity (ADHD). This study was adapted from a study published in The British Journal of Psychiatry 2007; 190: 410-414.
Subjects: children ages 7 to 11 presenting ADHD and aggressive or oppositional defiant behaviours.
Experimental procedures: clinical assessment, a low-monoamine diet for three days, an eight-hour fast (12:00 a.m. to 8:00 a.m.), and then a day at the experimental laboratory for a fenfluramine challenge.
Description of the fenfluramine challenge: An intravenous catheter was inserted. A baseline blood sample was taken between 9:00 a.m. and 10:00 a.m. A 1-mg/kg dose of fenfluramine was ingested orally. Blood samples to assess the levels of prolactin, fenfluramine and norfenfluramine in plasma were taken at 60, 120, 180, 240 and 300 minutes after the fenfluramine was ingested orally.
- AAP (1995). Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations (RE9503). Pediatrics, 95 (2),286-294
- AAP (1995). Informed Consent, Parental Permission, and Assent in Pediatric Practice (RE95190). Pediatrics, 95, 314-317
- CNBRH et SCP. (1993). Réflexions sur la recherche auprès des enfants, Ottawa IOM. (2004). Chapitre 4. Defining, interpreting, and applying concepts of risk and benefit in clinical research involving children. In The ethical conduct of clinical research involving children (pp. 113-145): Institute of Medicine.
- Trois conseils. (1998). énoncé de politique. éthique de la recherche avec des �tres humains.
- Baylis F, Downie J, Denny NP. (1999). Children and decision making in health research. Health Law Review, 8(2), 3-9
- Flory JD, Newcorn JH, Miller C, Harty S, Halperin JM, � Serotonergic function in children with attention-devicit hyperactivity disorder �m The British Journal of Psychiatry 2007; 190: 410-414.
- Freedman B, Fuks A, & Weijer C, (1993). In loco parentis, minimal risk as an ethical threshold for research upon children. Hastings Center Report, 23(2),13-19
- Weijer C.(2002) L'analyse des risques et des avantages éventuels dans la recherche. NCEHR Communiqué, 9(2)
- The standard of minimal risk is commonly defined as follows: if potential subjects can reasonably be expected to regard the probability and magnitude of possible harms implied by participation in the research to be no greater than those encountered by the subject in those aspects of his or her everyday life that relate to the research, then the research can be regarded as within the range of minimal risk.” (C.1, p.1.5, Tri-Council Policy Statement, 1998)
- Interpret minimal risk in relation to the normal experiences of average, healthy, normal children, see Recommendation 4.1 of The Ethical Conduct of Clinical Research Involving Children, p.126 (IOM, 2004).
- These research committees are "designated" by the Minister of Health and Social Services pursuant to Section 21 of the Civil Code of Quebec and their operating procedures are published in the Gazette officielle du Québec.
- The age of majority is 18 in Quebec, Saskatchewan, Prince Edward Island, Ontario, Alberta and Manitoba. It is 19 in other provinces, the Northwest Territories, Nunavut and the Yukon.
- Assent is the voluntary acceptance of the action or suggestion of another, but without a full understanding of it [translation] (NCBHR, 1993; vii)