Advertisement

Ethical issues in research and innovative therapy in children with mood disorders

  • Norman Fost
    Correspondence
    Address reprint requests to Norman Fost, Professor, Department of Pediatrics, Director, Program in Bioethics, University of Wisconsin Medical School, 600 Highland Avenue, Room H4/452, Madison, Wisconsin 53792
    Affiliations
    Professor, Department of Pediatrics, Director, Program in Bioethics, University of Wisconsin Medical School, Madison, Wisconsin, USA
    Search for articles by this author

      Abstract

      Research involving children with mood disorders should generally offer a reasonable prospect of benefit to those involved, unless the risks are minimal. While federal regulations require a prospect of direct benefit, from an ethical perspective indirect benefits, such as the advantages of being in a clinical trial, are relevant. Standard care should not be presumed to be preferable to treatment in the context of a clinical trial, particularly if it has not been evaluated in well designed studies involving groups comparable to the patient. Similarly, active treatments in a controlled trial should not be presumed to be preferable to placebos, particularly in studies involving mood disorders where the placebo effect is more likely to be substantial. Innovative therapy—using approved drugs for unapproved purposes—may be more problematic than research, on theoretical and empirical grounds. Studies with no prospect of direct benefit and more than minimal risk are problematic when the patient is incompetent to provide meaningful consent. Whether or not a controlled trial involving children with mood disorders can be ethically justified depends on several factors, including the validity of standard treatment, the seriousness of the disorder, the likelihood of adverse consequences if treatment is delayed, the burden of the proposed intervention, and value judgments by parents, working collaboratively with a caring physician.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Angell M.
        The ethics of clinical research in the Third World.
        N Engl J Med. 1997; 337: 847-849
        • Aranda J.V.
        • Hales B.F.
        • Rieder M.J.
        Developmental pharmacology.
        in: Fanaroff A.A. Martin R.J. Neonatal-Perinatal Medicine Diseases of the Fetus and Infant. Mosby, St. Louis1997
      1. Botstein P. Why FDA Is Encouraging Drug Testing in Children. FDA Consumer Special Report, Jan (1995). http://www.fda.gov/fdac/special/newdrug/kidmed.html (Accessed Apr 24, 2001).

        • Charney D.S.
        The use of placebos in randomized clinical trials of mood disorders.
        Biol Psychiatry. 2000; 47: 687-761
      2. Cooper JD, Research in the Service of Man – Hearings on Biomedical Development, Evaluation of Existing Federal Institutions before the Subcommittee on Government Research of the Senate Committee on Government Operations, 90th Congress, 1st Session 46–61 (1967), quoted in Katz J (1972): Experimentation With Human Beings, Russell Sage Foundation, New York, pp 986–992.

        • Daugherty C.
        • Ratain M.J.
        • Grochowski E.
        • Stocking C.
        • Kodish E.
        • Mick R.
        • Siegler M.
        Perceptions of cancer patients and their physicians involved in phase I trials.
        J Clin Oncol. 1995; 13: 1062-1072
      3. Edwards R.B. Psychiatry and Ethics. Prometheus Books, Buffalo, NY1982
        • Estlin E.J.
        • Cotterill S.
        • Pratt C.B.
        • et al.
        Phase I trials in pediatric oncology.
        J Clin Oncol. 2000; 18: 1900-1905
      4. Emanuel EJ, Wendler D, Grady C. What makes clinical research ethical? JAMA 283:2701–2711.

      5. FDA. http://www.fda.gov/cder/handbook/index.htm

        • Fost N.
        Ethical implications of screening asymptomatic individuals.
        FASEB J. 1992; 6: 2813-2817
        • Fost N.
        Ethical dilemmas in medical innovation and research.
        Semin Perinatol. 1998; 22: 223-232
      6. Gaylin W. Macklin R. Who Speaks for the Child The Problems of Proxy Consent. Plenum Press, New York1982
        • Glantz L.H.
        Conducting research with children.
        J Am Acad Child Adolesc Psychiatry. 1996; 35: 1283-1291
        • Glantz L.H.
        Research with children.
        Am J Law Med. 1998; 24: 213-244
      7. Grodin M.A. Glantz L.H. Children as Research Subjects Science, Ethics, and Law. Oxford University Press, New York1994
        • Hirschfeld R.M.A.
        Suicide and antidepressant treatment.
        Arch Gen Psychiatry. 2000; 57: 325-326
        • Hyman S.E.
        An NIMH perspective on the use of placebos.
        Biol Psychiatry. 2000; 47: 689-691
        • Janofsky J.
        • Starfield B.
        Assessment of risk in research on children.
        J Pediatr. 1988; 98: 842-846
        • Khan A.
        • Warner H.A.
        • Brown W.A.
        Symptom reduction and suicide risk in patients treated with placebo in antidepressant clinical trials.
        Arch Gen Psychiatry. 2000; 57: 311-317
        • Kinsey V.E.
        • et al.
        Retrolental fibroplasia.
        Arch Ophthalmol. 1956; 56: 481
      8. Kraemer HC (2000): Statistical analysis to settle ethical issues? Arch Gen Psychiatry 57:327–328, 2000.

        • Leber P.
        Placebo Controls.
        Arch Gen Psychiatry. 2000; 57: 319-320
        • Leber P.
        The use of placebo control groups in the assessment of psychiatric drugs.
        Biol Psychiatry. 2000; 47: 699-706
        • Leon A.C.
        Placebo protects subjects from nonresponse.
        Arch Gen Psychiatry. 2000; 57: 329-330
      9. Lietman PS (1973): personal communication.

        • Lurie P.
        • Wolfe S.M.
        Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries.
        N Engl J Med. 1997; 337: 853-856
        • McCormick R.A.
        Proxy consent in the experimentation situation.
        Perspect Biol Med. 1974; 18: 2-20
        • Meisel A.
        • McCormick R.A.
        Experimental subjects.
        JAMA. 1976; 236: 1844
        • McCormick Richard A.
        Experimentation in children.
        Hastings Cent Rep. 1976; 6: 41-46
        • Michels K.B.
        The placebo problem remains.
        Arch Gen Psychiatry. 2000; 57: 321-322
        • Ostrea E.M.
        • Odell G.B.
        The influence of bicarbonate administration on blood pH in a “closed system.”.
        J Pediatr. 1972; 80: 671-680
      10. Quitkin FM (1999): Placebos, drug effects and study design: A clinician’s guide. Am J Psychiatry 156(6): 829–638.

        • Quitkin F.M.
        • Klein D.F.
        What conditions are necessary to assess antidepressant efficacy?.
        Arch Gen Psychiatry. 2000; 57: 323-324
        • Ramsey P.
        The enforcement of morals.
        Hastings Cent Rep. 1976; 6: 21-30
        • Ramsey P.
        Children as research subjects.
        Hastings Cent Rep. 1977; 7: 40-42
        • Ramsey P.
        Ethical dimensions of experimental research on children.
        in: Van Eys J. Research on Children Medical Imperatives, Ethical Quandaries, and Legal Constraints. University Park Press, Baltimore1978: 57-68
        • Simmons M.A.
        • Adcock E.W.
        • Bard H.
        • Battaglia F.C.
        Hypernatremia and intracranial hemorrhage in neonates.
        N Engl J Med. 1974; 291: 6-10
        • Smithells R.
        Iatrogenic hazards and their effects.
        Postgrad Med J. 1975; 51: 39
        • Varmus H.
        • Satcher D.
        Ethical complexities of conducting research in developing countries.
        N Engl J Med. 1997; 337: 1003-1005
      11. Weiss R: Washington Post, Nov 7, (2000), p A25.

      12. World Medical Association (1996, October): Declaration of Helsinki: Recommendations Guiding Medical Doctors in Biomedical Research Involving Human Subjects. Adopted by the 18th World Medical Assembly, Helsinki, Finland, June 1964, amended by the 48th General Assembly, Somerset West, Republic of South Africa.

        • Zimmerman H.J.
        Hepatotoxicity. 2nd ed. Lippincott-Williams-Wilkins, Philadelphia1999