What Conditions Justify Risky Nontherapeutic or “No Benefit” Pediatric Studies: A Sliding Scale Analysis

Janofsky J. and Starfield B. , “Assessment of Risk and Research on Children,” Journal of Pediatrics 98, no. 5 (1981): 842–46; Shah S. Whittle A. Wilfond B. Gensler G. , and Wendler D. , “How do Institutional Review Boards Apply the Federal Risk and Benefit Standards for Pediatric Research?” JAMA 291 (2004): 4; Lascari A.D. , “Risks of Research on Children,” Journal of Pediatrics 98, no. 5 (1981): 759–60; National Bioethics Advisory Commission (NBAC), Ethical and Policy Issues in Research Involving Human Participants, vol. I: Report and Recommendations, Bethesda, MD, August 2001; Kopelman L.M. , “Minimal Risk as an International Ethical Standard in Research,” The Journal of Medicine and Philosophy 29, no. 3 (2004): 351–78.

Efforts are underway to define and give examples of some of these locutions. For example, NBAC (2000) and NHRPAC (2001) understand a “minor increase over minimal risk” to be just a little more risk beyond what is allowed for healthy children. NHRPAC includes as examples, with suitable pain relief, a onetime skin punch biopsy, bone marrow aspirate, or lumbar puncture. NBAC, supra note 1.

“Nuremberg Code,” Dials of War Criminals Before the Nuremberg Tribunals Under Control Law no. 10, vol. 2 (Washington D.C.: U.S. Government Printing Office, 1949): 181–83.

Kopelman L.M. , “Children as Research Subjects: A Dilemma,” The Journal of Medicine and Philosophy 25, no.6 (2000): 745–64. This paper contains a fuller discussion of U.S. Regulations, including studies that are not otherwise approvable by local I.R.B.S. For a discussion of these studies, see Kopelman L.M. and Murphy T. , “Ethical Concerns about Risky Research,” Pediatrics 2004, Vol 113 (6), pp 1783–9.

World Medical Association (WMA), Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects, rev. ed. (Edinburgh: 52nd World Medical Association General Assembly, October 2000), available at <http://www.wma.net/e/policy/b3.htm>.

Royal College of Paediatrics and Child Health: Ethical Advisory Board, “Guidelines for the Ethical Conduct of Medical Research Involving Children,” Archives of Disease in Children, 82 (2000): 177–82.

Canada, Ethical Guidelines for Research in Canada, “Ethics Review” (1999), available at: <http://www.nserc.ca/programs/ethics/english/sec01.htm> and <http://www.nserc.ca/programs/ethics/english/index.htm>.

Grimes v. Kennedy Krieger Institute, Inc., 782 A.2d 807 (Md. 2001); T.D. vs. N.Y. State of Mental Health, 228 A.D.2d 95 (court 1996).

Grimes, 782 A.2d 807.

Id. at 814, n.5.

Id. at 814; 45 C.F.R. § 46:101–24 (“Federal policy for the protection of human subjects (The Common Rule)”).

Portions of this section were prepared by me as a committee member of the Institute of Medicine in 2004, see The Ethical Conduct of Clinical Research Involving Children, National Academy of Sciences, Washington, DC (2004). One of the most permissive interpretations of 45 C.F.R. § 46.406 may be found in the minutes of the Human Subjects Research Advisory Committee from Friday, January 12, 2001, which state: “Dr. Alexander explained to the Committee, with Dr. Robert Levine's confirmation, that the National Commission intended a child's “condition” to mean the condition of being a child, not a medical disease or disorder.” For a DHHS rejection of this, see U.S. Department of Health and Human Services, Office for Human Research Protection, Human Subjects Research Advisory Committee, Minutes from Friday, January 12, 2001; U.S. DHHS Office of Human Research Protections, Protection for Children in Research, A Report to Congress in Accord with Section 1003 of P.L. 106–310, “Children's Health Act of 2000,” (May 2001), available at <http://ohrp.osophs.dhhs.gov/reports/ohrp5–02.pdf>. Office for Human Research Protection (OHRP), Department of Health and Human Services (DHHS), Letter to Gottesman M. , “Re: Human Research Subject Protection Under Multiple Assurance (MPA) M-100 Research Project Population Differences in the Insulin Sensitivity, Resting Energy Expenditure, and Body Composition of Overweight Children and Children of Overweight Parents: Protocol Number 96-CH 0101,” (November 3, 2000): 1–9, available from <http://ohrp.osophs.dhhs.gov/detrm_letrs/lindex.htm>; National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Report and Recommendations: Research Involving Children, Washington, DC: Department of Health Education and Welfare, DHEW Publication No.(OS) (77–0004) (1977).

National Human Research Protections Advisory Committee (NHRPAC), Children's Workgroup Report (Draft) (2004), available at <http://ohrp.osophs.dhhs.gov/nhrpac/mtg04-01/child-workgroup4-5-01.pdf>.

National Commission for the Protection of Human Subjects, The Belmont Report, The Report to the Secretary of the Department of Health, Education and Welfare (1979), available from <http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm>.

The goal of using scientific method contrasts with many alternative forms of healing. A key value in evidence-based medicine is the commitment to a scientific grounding for diagnoses, treatments and prevention of diseases. Naturally, there are regional and theoretical disagreements. However, it is assumed that more information and better theories can in principle solve them. In what follows, I will assume agreement about the values of the commitment to use evidence-based medicine and scientific methods to justify ascription of something as diseases, disorders or conditions. Kopelman L.M. , “The Role of Science in Assessing Conventional, Complementary and Alternative Medicines,” in The Role of Complementary & Alternative Medicine: Accommodating Pluralism, Callahan Daniel , ed. (Washington, D.C.: Georgetown University Press, 2002): 36–53.

Values are things we regard as important. All value judgments express the view that someone or something has (or has not) worth, importance, significance, ability or merit to us in some way. Insofar as they are not responsible for their illness or sickness, the badness is not moral. See Kopelman L.M. , “If HIV/AIDS is Punishment, Who is Bad?” The Journal of Medicine and Philosophy 27, no. 2 (2002): 231–43, for a fuller discussion of this as well as of moral and nonmoral values. For further discussion of the evaluative basis of diagnosing and duties of those given the social authority to say someone has a disease, malady, disability, disorder or condition see Kopelman L.M. , “On the Evaluative Nature of Competency and Capacity Judgments,” International Journal of Law and Psychiatry 13, no. 4 (1990): 309–29. These overlapping and potentially conflicting duties include being accurate in making observations and descriptions, to benefit the person by signaling that he or she has important or unique needs, and to benefit society.

Kopelman L.M. , “Moral Problems in Psychiatry: The Role of Value Judgments in Psychiatric Practice,” in Medical Ethics, 2d. ed., Veatch Robert , ed. (Boston, Massachusetts: Jones and Bartlett Publishing Co., 1997): 275–320.

Viewing disease as punishment for sin has long been rejected in evidence-based medicine, and I have assumed that we are working within this framework. See Kopelman L.M. , “The Punishment Concept of Disease,” AIDS: Ethics and Public Policy, eds. Pierce C. and Van De Veer D. , (Belmont, California: Wadsworth Publishing Co., 1988): 49–55; Kopelman , supra note 15.

See Kopelman , supra note 18.

At least three important purposes exist for justifying diagnoses, whether of expressed diseases or being at risk for them: to benefit the person (such as to gain treatment or prevent suffering); to benefit society (such as to prevent an epidemic, stop a dangerous driver, or gain knowledge through research) and to prevent harm to the person. These purposes can conflict. See Kopelman L.M. , “On the Evaluative Nature of Competency and Capacity Judgments,” supra note 16.

See Kopelman , supra note 17.

In some cases, older adolescents can give consent for themselves.

Because of the anticipated benefits, the child's refusal may not play the same decisive role as it does in “no benefit” studies. A child participating in a clinical trial for cancer may insist that he does not want the therapy because he hates needles; but he should get the therapy over his objections if it is in his best interest.

I have argued elsewhere that “minimal risk” should be understood as the sort of risks encountered in routine examinations. See Kopelman , “Minimal Risk as an International Ethical Standard in Research,” supra note 1.

Some read the Grimes decision as forbidding research with any risk; although the court later clarified that it should not be understood in this way. For a fuller discussion of this, see Kopelman L.M. , “Pediatric Research Regulations Under Legal Scrutiny: Grimes Narrows Their Interpretation,” Journal of Law, Medicine & Ethics 30 (2002): 38–49.

Kopelman L.M. , “The Best-Interests Standard as Threshold, Ideal, and Standard of Reasonableness,” The Journal of Medicine and Philosophy 22, no. 3 (1997): 271–89.

See Kopelman , supra note 4.

Ross L. F. , “Do Healthy Children Deserve Greater Protection in Medical Research?” Journal of Pediatrics 142, no. 2 (2003): 102–107.

For example, see Brief of Amici Curiae Association of American Medical Colleges, Association of American Universities, Johns Hopkins University, and University of Maryland Medical System Corporation in Support of Appellee's Motion for Reconsideration of Grimes v. Kennedy Krieger, September 17, 2001. The AAMC and others were critical of the Grimes decision.

T.D. vs. N.Y. is more general, applying to persons lacking legal authority to make decisions for themselves.

See Kopelman supra note 25.

It is also true that what is minimal risk for sick children (e.g., discussing death, loss, or grief) may be high risk for healthy children.

Kopelman , supra note 21.

See 45 C.F.R. § 46:101–24; 45 CFR § 46:401–409 (“Additional protections for children involved as subjects in research (Subpart D)”); U.S. Department of Health and Human Services (DHHS), “Final Regulations Amending Basic HHS Policy for the Protection of Human Research Subjects,” Federal Register 46 (1981): 8366–91.

South Africa, Medical Research Council (MRC), “Guidelines on Ethics for Medical Research: General Principles including Research on Children, Vulnerable Groups, International Collaboration and Epidemiology,” available at <http://www.mrcac.za/ethics/values.htm>.

Council for International Organizations of Medical Science (CIOMS), “International Ethical Guidelines for Biomedical Research Involving Human Subjects,” (2002) available at <http://www.cioms.ch/frame_guidelines_nov_2002.htm>.

See Canada , supra note 7.

See Grimes v. Kennedy Krieger Institute, Inc., 782 A.2d 807 (Md. 2001).

See T.D. vs. N.Y. State of Mental Health, 228 A.D.2d 95 (court 1996).

See World Medical Association, supra note 5.

See Royal College of Paediatrics, supra note 6.

See Nuremberg Code, supra note 3.