Skip to main content

Advertisement

SpringerLink
Log in

Ethical considerations in research involving children

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Ethical concerns and medical advances unique to children and adolescents make pediatric research an evolving endeavor. The child’s changing physiology from infancy to maturity requires understanding of the benefits and risks of medical therapies currently available, but often not tested in children, as well as the risks and benefits of inclusion of children in clinical research. Recent mandates from the US Food and Drug Administration (FDA) require that drugs be tested for safety and efficacy in children. Growing concern for the prevalence of chronic disorders and increasing understanding of distinct phenotypes of these disorders points to a likely need for unique interventions matched to specific phenotypes. All contribute to the increasing complexity of ethical considerations in pediatric research.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research: The Belmont Report: Ethical principles and guidelines for the protection of human subjects of research. US Department of Health: Pub. No (OS) 78-0012. Washington, DC: US Department of Health; 1978.

  2. Appelbaum P, Lidz C, Meisel A: Informed Consent: Legal Theory and Clinical Practice. New York: Oxford University Press; 1987.

    Google Scholar 

  3. Federal Policy for the Protection of Human Subjects: “The Common Rule.” Subpart D. Additional DHHS Protections for Children Involved as Subjects in Research, 45CFR46.401–409.

  4. OHRP, Office for Human Research Protections: HIV Replication and Thymopoiesis in Adolescents 45 CFR 46.407 Review. Washington, DC: Department of Health and Human Services; 2004:March 5.

  5. Purdy L: In Their Best Interest: Against Equal Rights for Children. Ithaca, NY: Cornell University Press; 1992.

    Google Scholar 

  6. Shirkey H: Clinical pharmacology in pediatrics. Clin Pharmacol Ther 1972, 13:827–830.

    PubMed  CAS  Google Scholar 

  7. Shirkey H: Therapeutic orphans. Pediatrics 1999, 104(3 pt 2):583–584.

    PubMed  CAS  Google Scholar 

  8. Ramsey P: Ethical dimensions of experimental research on children. In Research on Children: Medical Imperatives, Ethical Quandaries, and Legal Constraints. Edited by van Eys J. Baltimore, MD: University Press; 1978:57–68.

    Google Scholar 

  9. White Beck L (ed): Kant: Foundations of the Metaphysics of Morals, edn 2. New York: Macmillan/Library of Liberal Arts; 1990.

    Google Scholar 

  10. Mill J: Utilitarianism. New York: The Library of Liberal Arts, Bobbs-Merrill; 1957.

    Google Scholar 

  11. Redmon R: How children can be respected as “ends” yet still be used as subjects in non-therapeutic research. J Med Ethics 1986, 12:77–82.

    PubMed  CAS  Google Scholar 

  12. Leikin S: An ethical issue in biomedical research: the involvement of minors in informed and third party consent. Clin Res 1982:34–40.

  13. Federman D (ed): IOM: Ethical Conduct of Clinical Research Involving Children. Washington, DC: Institute of Medicine of the National Academies; 2004. The report is comprehensive and addresses contemporary and historical issues.

    Google Scholar 

  14. Hull D, Child Health: Equity Advisory Committee, Royal College of Paediatrics: Guidelines for the ethical conduct of medical research involving children. Arch Dis Child 2000, 82:177–182.

    Article  Google Scholar 

  15. Pediatric Research Equity Act of 2003. The Pediatric Research Equity Act is available online at http://www.fda.gov/opacom/ laws/prea.html.

  16. Best Pharmaceuticals for Children Act of 2002. The Best Pharmaceuticals for Children Act is available online at http://www.fda.gov/opacom/laws/pharmkids/contents.html.

  17. Food and Drug Administration (FDA): Special Ethical Protections for Pediatric Research Participants 2004, http://www.fda.gov/oc/ opt/presentations/PennandTemple.html

  18. Emanuel E, Crouch RA, Arras JD, et al. (eds): Ethical and Regulatory Aspects of Clinical Research: Readings and Commentary. Baltimore, MD: Johns Hopkins University Press; 2003. This text is exhaustively comprehensive, covering ethics and regulations in addition to all aspects of research that bear on ethics, such as trial design, recruitment, special populations, international research, and much more.

    Google Scholar 

  19. Tauer C: The NIH Trials of Growth Hormone for Short Stature. In Ethical and Regulatory Aspects of Clinical Research: Readings and Commentary. Edited by Emanuel E, et al. Baltimore, MD: Johns Hopkins University Press; 2003.

    Google Scholar 

  20. Freedman B, Fuks A, Weijer C: In loco parentis: minimal risk as an ethical threshold for research upon children.In Ethical and Regulatory Aspects of Clinical Research: Readings and Commentary. Edited by Emanuel E, et al. Baltimore, MD: Johns Hopkins University Press; 2003. This is a philosophic and conceptual analysis of the use of the term “minimal risk.”

    Google Scholar 

  21. Gidding S, Camp D, Flanagan MH, et al.: A policy regarding research in healthy children. J Pediatr 1993, 123:852–855.

    Article  PubMed  CAS  Google Scholar 

  22. Gaylin WM: The “competence” of children no longer all or none. J Am Acad Child Adolesc Psychiatry 1982, 21:153–162.

    Article  CAS  Google Scholar 

  23. Dworkin G: Consent, representation, and proxy consent. In Who Speaks for the Child? Edited by Gaylin W. New York: Plenum Press; 1982.

    Google Scholar 

  24. Leikin SL: Medical progress: minors’ assent or dissent to medical treatment. J Pediatr 1983, 102:169–176.

    Article  PubMed  CAS  Google Scholar 

  25. Koocher GP, DeMaso DR: Children’s competence to consent to medical procedures. Pediatrician 1990, 17:68–73.

    PubMed  CAS  Google Scholar 

  26. Hurley JC, Underwood MK: Children’s understanding of their research rights before and after debriefing: Informed assent, confidentiality, and stopping participation. Child Dev 2002, 73:132–143.

    Article  PubMed  Google Scholar 

  27. Susman EJ, Dorn LD, Fletcher JC: Participation in biomedical research: the consent process as viewed by children, adolescents, young adults, and physicians. J Pediatr 1992, 121:547–552.

    Article  PubMed  CAS  Google Scholar 

  28. Weithorn L: Children’s capacities to decide about participation in research. IRB 1983, 5:1–5.

    Article  PubMed  Google Scholar 

  29. Weithorn L: Competency to Render Informed Treatment Decisions: A Comparison of Certain Minors and Adults, in Graduate Faculty of Arts and Sciences in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy. Pittsburgh, PA: University of Pittsburgh; 1980:1–237.

  30. Weithorn L, Campbell S: The competency of children and adolescents to make informed treatment decisions. Child Dev 1982, 53:1589–1598.

    Article  PubMed  CAS  Google Scholar 

  31. Zinner SE: The elusive goal of informed consent by adolescents. Theor Med Bioeth 1995, 16:323–331.

    Article  CAS  Google Scholar 

  32. Koren G, Carmeli DB, Carmeli YS, Haslam R: Maturity of children to consent to medical research: the babysitter test. J Med Ethics 1993, 19:142–147.

    Article  PubMed  CAS  Google Scholar 

  33. Lindeke L, Hauck M, Tanner M: Practical issues in obtaining child assent for research. J Pediatric Nurs 2000, 15:99–103.

    Article  CAS  Google Scholar 

  34. Erb TO, Schulman SR, Sugarman J: Permission and assent for clinical research in pediatric anesthesia. Anesth Analg 2002, 94:1155–1160.

    Article  PubMed  Google Scholar 

  35. Sigman G, O’Connor C: Exploration for physicians of the mature minor doctrine. J Pediatr 1991, 119:520–525.

    Article  PubMed  CAS  Google Scholar 

  36. Thompson RA: Vulnerability in research: a developmental perspective on research risk. Child Dev 1990, 61:1–16.

    Article  PubMed  CAS  Google Scholar 

  37. Nelson RM: Children as research subjects. In Beyond Consent: Seeking Justice in Research. Edited by Kahn JP, Mastroianni AC, Sugarman J. New York: Oxford University Press; 1998:47–66.

    Google Scholar 

  38. Meaux J, Bell P: Balancing recruitment and protection: children as research subjects. Issues Compr Pediatr Nurs 2001, 24:241–251.

    Article  PubMed  CAS  Google Scholar 

  39. Arnold EL, Stoff DM, Cook E Jr, et al.: Ethical issues in biological psychiatric research with children and adolescents. Acad Child Adolesc Psychiatry 1995, 34:929–939.

    Article  CAS  Google Scholar 

  40. Federman D (ed): IOM: Responsible Research: A Systems Approach to Protecting Research Participants. Washington, DC: Institute of Medicine of the National Academies; 2002.

    Google Scholar 

  41. Committee on Drugs: Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations. Washington, DC: American Academy of Pediatrics; 1995:286–294.

  42. Stang A, Hense HW, Joekel KH, et al.: Is it always unethical to use a placebo in a clinical trial? PLoS Med 2005, 2:0177–0180.

    Article  Google Scholar 

  43. Onder R: The ethics of placebo-controlled trials: the case of asthma. J Allergy Clin Immunol 2005, 155:1228–1234. The author asserts that absence of equipoise, “genuine uncertainty on the part of the clinical investigator regarding the comparative therapeutic merits” of the therapies under investigation, does not necessarily make the use of placebo-controlled trials unethical.

    Article  Google Scholar 

  44. Miller F, Shorr A: Ethical assessment of industry-sponsored clinical trials. Chest 2002, 121:1337–1342.

    Article  PubMed  Google Scholar 

  45. WMA: Declaration of Helsinki, 1964: revised in 1975, 1982, 1989, 1996, 2000. Ferney-Voltaire, France: World Medical Association; 1964. For a subsequent modification of paragraph 29 (addressing the use of placebo in clinical trials) see the clarification of paragraph 29 issued in 2002. It is available on line at http://www.wma.net/e/ policy/b3.htm.

  46. Saunders J, Wainwright P: Risk, Helsinki 2000 and the use of placebo in medical research. J R Coll Physicians 2003, 3:435–439.

    Google Scholar 

  47. Flynn J: Ethics of placebo use in pediatric clinical trials: the case of antihypertensive drug studies. Hypertension 2003, 42:865–869. The author offers practical advice on study design for trials that could be modified across multiple disciplines.

    Article  PubMed  CAS  Google Scholar 

  48. Coffey M, Wilfond B, Friedman R: Ethical assessment of clinical asthma trial including children subjects. Pediatrics 2004, 113:87–94. This article criticizes trial design that allows children with asthma to not be treated to NHLBI standards.

    Article  PubMed  Google Scholar 

  49. Newburger P, Elfenbein D, Boxer L: Adolescents with cancer: access to clinical trials and age-appropriate care. Curr Opin Pediatr 2002, 14:1–4.

    Article  PubMed  Google Scholar 

  50. Olechnowicz J, Eder M, Simon C, et al.: Assent observed: children’s involvement in leukemia treatment and research discussions. Pediatrics 2002, 109:806–814.

    Article  PubMed  Google Scholar 

  51. Glantz L: Conducting research with children: legal and ethical issues. Acad Child Adolesc Psychiatry 1996, 34:1283–1291.

    Article  Google Scholar 

  52. Vitiello B: Ethical considerations in psychopharmacological research involving children and adolescents. Psychopharmacology 2003, 17:186–191.

    Google Scholar 

  53. Charlton B: Public health medicine: a different kind of ethics. J R Soc Med 1993, 86:194–195.

    PubMed  CAS  Google Scholar 

  54. Last L: Epidemiology and ethics. Law, Medicine, and Health Care 1991, 19:166–174.

    CAS  Google Scholar 

  55. Waters W: Ethics in epidemiological research. Int J Epidemiol 1985, 14:48–51.

    Article  PubMed  CAS  Google Scholar 

  56. Coughlin S, Beauchamp T: Ethics, scientific validity and the design of epidemiologic studies. Epidemiology 1992, 3:343–347.

    PubMed  CAS  Google Scholar 

  57. Gold E: Confidentiality and privacy protection in epidemiological research. In Ethics and Epidemiology. Edited by Coughlin S, Beauchamp T. Oxford: Oxford University Press; 1996:128–141.

    Google Scholar 

  58. Gordis L: Ethical and professional issues in the changing practice of epidemiology. J Clin Epidemiol 1991, 44:9S-13S.

    Article  PubMed  Google Scholar 

  59. Gostin L: Ethical principles for the conduct of human subject research: population-based research and ethics. Law Med Health Care 1991, 19:191–201.

    PubMed  CAS  Google Scholar 

  60. Nakajima H: The responsibilities of epidemiologists. Law Med Health Care 1991, 19:164–165.

    PubMed  CAS  Google Scholar 

  61. Juengst E: FACE Facts: why human genetics will always provoke bioethics. J Law Med Ethics 2004, 32:267–275. Juengst dismisses the hyperbole surrounding the use of genetic testing and lays out the social nature of the genuine concerns.

    Article  PubMed  Google Scholar 

  62. Kodish E: Testing children for cancer genes: the rule of earliest onset. J Pediatr 1999, 135:390–395. The author examines a common rule for genetic testing as applied to oncology trials and recommends that the rule not be applied because of our limited and growing understanding of the role genetics plays in oncology and because its application would impede progress toward improving our understanding.

    Article  PubMed  CAS  Google Scholar 

  63. Leeder J, Kearns G: The challenges of delivering pharmacogenomics into clinical pediatrics. Pharmacogenomics 2002, 2:141–143.

    Article  CAS  Google Scholar 

  64. Ross LF, Moon MR: Ethical issues in genetic testing of children. Arch Pediatr Adolesc Med 2000, 154:873–879.

    PubMed  CAS  Google Scholar 

  65. American Academy of Pediatrics: Ethical issues with genetic testing in pediatrics. Committee on Bioethics. Pediatrics 2001, 107:1451–1455.

    Article  Google Scholar 

  66. Silverman M, Pedersen S, Martinez F: Early intervention in childhood asthma. Eur Respir J 1998, 12(Suppl):65s-68s.

    Article  Google Scholar 

  67. Milgrom H: Is there a role for treatment of asthma with omalizumab? Arch Dis Child 2003, 88:71–74.

    Article  PubMed  CAS  Google Scholar 

  68. Holt P, Sly P: Prevention of adult asthma by early intervention during childhood: potential value of new generation immunomodulatory drugs. Thorax 2000, 55:700–703.

    Article  PubMed  CAS  Google Scholar 

  69. Davies J, Payne D: Research applications of bronchoscopy. Paediatr Respir Rev 2003, 4:230–236.

    Article  PubMed  Google Scholar 

  70. Salva P, Theroux C, Schwartz D: Safety of endobronchial biopsy in 170 children with chronic respiratory symptoms. Thorax 2003, 58:1058–1060.

    Article  PubMed  CAS  Google Scholar 

  71. Roberts R, Rodriguez W, Murphy D, Crescenzi T: Pediatric drug labeling: improving the safety and efficacy of pediatric therapies. JAMA 2003, 290:905–911. This interesting paper reports on new drug labeling information resulting from pediatric studies submitted to the FDA after Congress passed the Food and Drug Administration Modernization Act (FDAMA) in 1997. Significant new dosing and/or safety information was identified for 36% of the studied drugs.

    Article  PubMed  Google Scholar 

  72. Hampton T: Pediatric drug studies required by law. JAMA 2004, 291:412–413.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric General Clinical Research Center, University of Colorado at Denver Health Sciences Center, 1056 E. 19th Avenue, B218, 80218, Denver, CO, USA

    Theresa A. O’Lonergan MA & Henry Milgrom MD

Authors
  1. Theresa A. O’Lonergan MA
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry Milgrom MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

O’Lonergan, T.A., Milgrom, H. Ethical considerations in research involving children. Curr Allergy Asthma Rep 5, 451–458 (2005). https://doi.org/10.1007/s11882-005-0025-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-005-0025-9

Keywords

Search

Navigation