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Dying Children and Medical Research: Access to Clinical Trials as Benefit and Burden

Published online by Cambridge University Press:  06 January 2021

Michelle Oberman
Children’s Memorial Hopsital Institutional Review Board, Chicago, IL
Joel Frader
Feinberg School of Medicine, Northwestern University and the Children's Memorial Hospital, Chicago, Illinois; Division of General Academic Pediatrics at Children's Memorial


There is perhaps no greater tragedy in a parent's life than learning that one's child is terminally ill. Today, more than at any time in the past, when conventional treatment fails, dying children are given access to experimental treatment. To a surprising extent, society takes for granted the participation of dying children in medical experiments. In part, this is because we have come to view participation in clinical trials as a potential benefit. This view contrasts sharply with the dominant perception of the mid to late 20th century, which viewed medical research as a potential threat to vulnerable populations. Upon closer scrutiny, both of these perspectives carry with them some important truths. This Article seeks to build upon those truths by undertaking a critical analysis of contemporary ethical and legal policies governing the inclusion of terminally ill children in clinical research.

Research Article
Copyright © American Society of Law, Medicine and Ethics and Boston University 2003

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Both authors are profoundly grateful to Amy Young, DePaul Law, Class of 2004, for her spectacular assistance in preparing this Article for publication.

Dr. Frader’s clinical interests focus on palliative and hospice care for children.


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3 Michael D. Lemonick & Andrew Goldstein, At Your Own Risk, TIME MAGAZINE, Apr. 22, 2002, at 46, available at 2002 WL 8386181.

The revelation of these and other scandals led to the National Research Act of 1974, which required institutional review boards to approve and monitor all federally funded research. The Department of Health and Human Services followed up by creating what is now called the Office for Human Research Protection, whose job was supposed to be to oversee the IRBs.


4 However, an oddity in the definition of “childhood” used by the NIH permits an end-run around this objective. The NIH defines children as “individuals under the age of 21.” NAT’L INST. OF HEALTH, NIH Policy and Guidelines on the Inclusion of Children as Participants in Research Involving Human Subjects (1998), at Therefore, by allowing eighteen to twenty-one-year-old adults to count as children, one can meet the NIH requirement of inclusion without performing physiologically meaningful studies to assess children's vulnerability to medication at various stages prior to full adulthood.

5 Congress passed the Food and Drug Administration Modernization Act (FDAMA) in November 1997, reforming the Food, Drug, and Cosmetic Act of 1938. 21 U.S.C. § 301 (2000). Section 111 of the FDAMA contains the pediatric incentive provision. 21 U.S.C. § 355a (2000). Then, in December of 1998, the FDA codified the Final Rule: Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological Products on Pediatric Populations. 63 Fed. Reg. 66,632 (Dec. 2, 1998) (codified in 21 C.F.R. pts. 201, 312, 314 & 601). But see Ass’n of Am. Physicians & Surgeons, Inc. v. FDA, 226 F. Supp. 2d 204, 222 (2002) (holding that the FDA exceeded its authority in adopting a rule requiring drug manufacturers to conduct tests on the pediatric population and to suggest pediatric doses for all drugs, even those intended exclusively for adult use).

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8 See, e.g., Richard McCormick, Proxy Consent in Experimental Situations, 18 PERSPECTIVES BIOLOGY & MED. 2 (1974).

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12 To be sure, there may be psychic benefits gained by one who elects to undergo medical experimentation for altruistic reasons. These benefits are hard to measure, even when evaluating adult volunteers. The extent of their relevance in pediatric studies, particularly in those involving the youngest participants, is questionable. See infra Part IV for a discussion of evidence indicating that the desire for personal benefit, rather than altruism, is the central motivation behind adult participation in clinical studies.

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26 Many Gene Research Consent Forms Misleading: Study, at (Nov. 1, 2002) [hereinafter Consent Forms]; Henderson, Gail E. & King, Nancy M.P., Perceived Benefits of Participation in Gene Transfer Research, 7 HemAware 73 (2002)Google Scholar.

27 Consent Forms, supra note 26.

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32 See Daugherty, supra note 28.

33 Rodwin, Marc A., Strains in the Fiduciary Metaphor: Divided Physician Loyalties and Obligations in a Changing Health Care System, 21 AM. J.L. & MED. 241, 241-42 (1995)Google Scholar (noting that “[t]he idea that physicians are or should be fiduciaries for their patients … is a dominant metaphor in medical ethics and law today”).

34 Id. at 245-46.

35 See Oberman, Michelle, Mothers and Doctors’ Orders: Unmasking the Doctor's Fiduciary Role in Maternal-Fetal Conflicts, 94 NW. U. L. REV. 451 (2000)Google Scholar (demonstrating the manner in which what are commonly-termed “maternal-fetal conflicts” are in fact cases of breach of the obstetrician's fiduciary duty); see also Marshall, Mary Faith, Commentary: Mal-intentioned Illiteracy, Willful Ignorance, and Fetal Protection Laws: Is There a Lexicologist in the House?, 27 J. L. MED. & ETHICS 343 (1999)Google Scholar; L.J. Nelson & Mary Faith Marshall, Ethical and Legal Analysis of Three Coercive Policies Aimed at Substance Abuse by Pregnant Women, in ROBERT WOOD JOHNSON FOUNDATION, SUBSTANCE ABUSE POLICY RESEARCH PROGRAM (1997).

36 Letter from Steven Masiello, Director, Office of Compliance and Biologics Quality Center for Biologics Evaluation and Research, FDA, to James M. Wilson, Institute for Human Gene Therapy (Nov. 30, 2000), at Gelsinger suffered from a mild form of a rare metabolic disorder, manageable through diet and drug regimens, but enrolled in a clinical trial of a gene therapy study through the University of Pennsylvania; within three days, Gelsinger suffered respiratory disease, liver and kidney failure, then died. Baram, Michael, Making Clinical Trials Safer for Human Subjects, 27 AM. J.L. & MED. 253, 256 (2001)Google Scholar; Sheryl Gay Stohlberg, The Biotech Death of Jesse Gelsinger, N.Y. TIMES, Nov. 28, 1999, § 6, at 137; A. Caplan et al., With the Best of Intentions: Ethical Lessons from Adverse Events in Human Experimentation, Am. Soc’y for Bioethics & Humanities Annual Meeting Plenary Session, Nashville, Tenn. (Oct. 26, 2001).

37 As Professor Annas notes, “When physician and researcher are merged into one person, it is unlikely that patients can ever draw the distinction between these two conflicting roles because most patients simply do not believe that their physician would knowingly harm them or would knowingly use them as a means for their own end.” Annas, supra note 9, at 311-12.

38 Id. at 322.

39 Oberman, supra note 35, at 458-59 (citing Rodwin, supra note 33, at 247-48).

40 For example, the California Supreme Court held that a plaintiff's complaint stated a cause of action for breach of fiduciary duty where a surgeon failed to disclose his research and financial interests when obtaining the patient's informed consent for the procedures. Moore v. Regents of Univ. of Cal., 739 P.2d 479, 485 (Cal. 1990). Applying Minnesota law, the Eighth Circuit went further and commented that even when not recommending courses of treatment, physicians have fiduciary duties to disclose conflicting loyalties. Shea v. Esensten, 208 F.3d 712, 717 (8th Cir. 2000). The court recognized a financial interest in an HMO contract designed to minimize referrals as a conflicting loyalty. See id. at 717. But see Neade v. Portes, 739 N.E.2d 496, 498 (Ill. 2000) (refusing to impose a duty on physicians to disclose HMO financial incentives for reducing referrals for outside testing and specialists).

41 Rodwin, supra note 33, at 247.

42 In addition, the state plays a role in medical decision-making for minors, limiting parental authority over children through the doctrine of parens patriae. This doctrine provides that the state limits parental authority to the power to act in a child's best interest. To the extent that the state perceives a parent's action as inconsistent with a child's best interest, the state will intervene to order proper medical care. Although there is a line of cases where the state has ordered medical treatment that was refused by a parent, none of these cases involve experimental care. This may be because courts acknowledge that while states “may not permit a parent to deny a child all treatment for a condition which threatens his life,” it is not for them to determine the most “effective” treatment “when the parents have chosen between reasonable alternatives.” Crouse Irving Mem. Hosp. v. Paddock, 485 N.Y.S.2d 443, 444-45 (1985) (upholding order for blood transfusions, despite religious objections, for both mother and baby during a Cesarean section delivery, citing In re Matter of Hofbauer, 419 N.Y.S.2d 936 (1979)).

43 See Mark G.|Kuczewski, Commentary: Narrative Views of Personal Identity and Substituted Judgment in Surrogate Decision Making, 27 J.L. MED. & ETHICS 32 (1999)Google Scholar.

44 NAT’L COMMISSION FOR THE PROTECTION OF HUMAN SUBJECTS OF RESEARCH, U.S. DEP't OF HEALTH, EDUCATION, & WELFARE, THE BELMONT REPORT (1979), available at; see also Bartholome, W.G., Parents, Children, and the Moral Benefits of Research, 6 HASTINGS CTR. REPORT 44, 4445 (1976)Google Scholar; Comm. on Bioethics, Am. Acad. of Pediatrics, Informed Consent, Parental Permission, and Assent in Pediatric Practice, 95 PEDIATRICS 314, 314-17 (1995)Google Scholar.

45 See Rosato, Jennifer, The Ethics of Clinical Trials: A Child's View, 28 J. L. MED. & ETHICS 362, 367-70 (2000)Google Scholar.

46 This presumption is not without its shortcomings. See generally JOSEPH GOLDSTEIN ET AL., BEYOND THE BEST INTERESTS OF THE CHILD (2d ed. 1979) (focusing on the area of child placement and the impact of parental decision-making on the child's psychological development). For a fascinating critique of the legal system's failure to recognize children's rights, see Rutherford, Jane, One Child, One Vote: Proxies for Parents, 82 MINN. L. REV. 1463, 1525 (1998)Google Scholar (suggesting a model in which parents can represent their children's political views).

47 Ackerman, supra note 14, at 4.

48 Ackerman, supra note 14, at 4 (citing Harth, S.C. et al., The Psychological Profile of Parents Who Volunteer Their Children for Clinical Research: A Controlled Study, 18 J. MED. ETHICS 86 (1992)Google Scholar).

49 For a discussion of this debate, see Ackerman, Terrence F., Fooling Ourselves with Child Autonomy and Assent in Nontherapeutic Clinical Research, 27 CLINICAL RESEARCH 345, 345-48 (1979)Google Scholar.

50 See Ross, Lainie F., Children as Research Subjects: A Proposal to Revise the Current Federal Regulations Using a Moral Framework, 8 STAN. L. & POL’Y REV. 159, 169 (1997)Google Scholar; Ross, Lainie F., Health Care Decision Making by Children: Is It in Their Best Interest?, 27 HASTINGS CTR. REPORT Nov.-Dec. 1997, at 44CrossRefGoogle Scholar.