Ethical considerations in psychopharmacological research involving children and adolescents
- First Online:
- 260 Downloads
Increased community utilization of psychotropic medications among children has brought attention to pediatric psychopharmacology research and associated ethical issues.
To discuss ethical aspects of child participation in psychopharmacology protocols.
Selective review of relevant scientific and regulatory literature.
Efficacy and safety of psychotropics in children cannot be entirely inferred from adult data and direct participation of children in research is necessary. Child research must follow special regulations that are in addition to those common to all human research. For research with prospect of direct benefit, a critical factor is whether the risk/benefit ratio is favorable to the participating child. For research without such a prospect, the concepts of minimal risk and minor increase over minimal risk apply. However, the interpretation and application of these principles to specific protocols vary across settings and among ethics committees. Thus far, little empirical investigation has been conducted on children and parents' motivation for research participation, effectiveness of the informed consent and assent procedures, possibility of persistent consequences of exposure to experimental treatments and placebo, and validation of the concepts of minimal risk and minor increase over minimal risk.
Research on human subject issues relevant to child participation is a promising approach to improving ethical methods and procedures of pediatric psychopharmacology.
KeywordsEthics Psychopharmacology Children Research
- Agency of Health Care Policy and Research (1999) Treatment of attention deficit/hyperactivity disorder. AHCPR Publication No. 99-E017, December 1999. Rockville, Maryland, http://www.ahrq.gov/clinic/epcsums/adhdsum.htmGoogle Scholar
- Charney DS, Nemeroff CB, Lewis L, Laden SK, Gorman JM, Laska EM, Borenstein M, Bowden CL, Caplan A, Emslie GJ, Evans DL, Geller B, Grabowski LE, Herson J, Kalin NH, Keck PE Jr, Kirsch I, Krishnan KR, Kupfer DJ, Makuch RW, Miller FG, Pardes H, Post R, Reynolds MM, Roberts L, Rosenbaum JF, Rosenstein DL, Rubinow DR, Rush AJ, Ryan ND, Sachs GS, Schatzberg AF, Solomon S (2002) National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders. Arch Gen Psychiatry 59:262–270CrossRefPubMedGoogle Scholar
- Department of Health and Human Services (1991a) Protection of human subjects. Basic HHS policy for protection of human research subjects. Code of Federal Regulations, Title 45, Public Welfare: Part 46, Subpart A: 46.101–46.124, Revised June 18, 1991, Effective August 19, 1991. Office of the Federal Register, National Archives and Records Administration, Washington, DC, October 1, 1994 (45 CFR Subtitle A), pp 116–127Google Scholar
- Department of Health and Human Services (1991b) Protection of human subjects. Subpart D: Additional protections for children involved as subjects in research. Code of Federal Regulations, Title 45, Public Welfare: Part 46, Subpart D: 46.401–46.409, Revised June 18, 1991, Effective August 19, 1991, Office of the Federal Register, National Archives and Records Administration, Washington, DC, October 1, 1994 (45 CFR Subtitle A), pp 132–135Google Scholar
- Emslie GJ, Rintelman J, Mayes T (2000) Are placebo-controlled trials detrimental to depressed children and adolescents? 47th annual meeting of the American Academy of Child and Adolescent Psychiatry, New York, NY, 24–29 October 2000Google Scholar
- Food and Drug Administration (2000) International Conference on Harmonization; E11: Clinical investigation of medicinal products in the pediatric population. Federal Register 65:19777–19781Google Scholar
- Food and Drug Administration (2001) 21CFR Parts 5- and 56. Additional safeguards for children in clinical investigations of FDA-regulated products. Federal Register 65:20589–20600, http://www.fda.gov/OHRMS/DOCKETS/98fr/042401a.pdfGoogle Scholar
- Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, Hagino OR, Koplewicz H, Carlson GA, Clarke GN, Emslie GJ, Feinberg D, Geller B, Kusumakar V, Papatheodorou G, Sack WH, Sweeney M, Wagner KD, Weller EB, Winters NC, Oakes R, McCafferty JP (2001) Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial. J Am Acad Child Adolesc Psychiatry 40:762–772PubMedGoogle Scholar
- March JS, Biederman J, Wolkow R, Safferman A, Marekian J, Cook EH, Cutler NR, Dominguez R, Ferguson J, Muller B, Riesenberg R, Rosenthal M, Sallee FR, Wagner KD (1998) Sertraline in children and adolescents with obsessive-compulsive disorder: a multicenter randomized controlled trial. JAMA 280:1752–1756CrossRefPubMedGoogle Scholar
- McCarthy AM, Richman LC, Hoffman RP, Rubenstein L (2001) Psychological screening of children for participation in nontherapeutic invasive research. Arch Pediatr Adolesc 155:1197–1203Google Scholar
- National Institutes of Health (2002) Research on ethical issues in human subjects. PA-02–103, NIH Guide, 1 May 2002, http://grants2.nih.gov/grants/guide/pa-files/PA-02–103.htmlGoogle Scholar
- Research Units on Pediatric Psychopharmacology Autism Network (2001) Risperidone protocol II: results. Presentation at the 48th annual meeting of the American Academy of Child and Adolescent Psychiatry, Honolulu, HI, October 25, 2001Google Scholar
- U.S. Congress (1997) Food and Drug Administration Modernization Act. Public Law 105–115Google Scholar
- U.S. Congress (2002) Best Pharmaceuticals for Children Act. Public Law 107–109Google Scholar