Research with decisionally incapacitated human subjects: An argument for a systemic approach to risk-benefit assessment

Indiana Law Journal

Volumn 83, Issue 3, 2008, Pages 743-789

  Coleman, Carl H ^a,b  

^a GEORGETOWN UNIVERSITY   (United States)

^b HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

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EID: 49149107558     PISSN: 00196665     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (232)

1. See infra text accompanying notes 29-30.
2. See Carol B. Stocking, Gavin W. Hougham, Aliza R. Baron, & Greg A. Sachs, Are the Rules for Research with Subjects with Dementia Changing? 61 NEUROLOGY 1649, 1651 (2003) ("[T]he process [of surrogate selection] appears to be unsystematic in most settings.").
3. See infra Part II.B.
4. See infra note 85.
5. See infra text accompanying note 117.
6. See infra text accompanying note 118.
7. See Jeannie Baumann, OHRP Asks for Comments on Protections for Decisionally Impaired Research Subjects, 6 MED. RES. L. & POL'Y REP., Sept. 19, 2007, at 482.
8. Jeannie Baumann, Panel Leans Toward Guidance, Not Rules to Protect Decisionally Impaired Subjects, 5 MED. RES. L. & POL'Y REP., Nov. 15, 2006, at 733.
9. Jeannie Baumann, House Measure Would Apply Common Rule Consistently to All Human Subject Research, 5 MED. RES. L. & POL'Y REP., Jun. 21, 2006, at 422.
10. See AMERICAN PSYCHIATRIC ASSOCIATION, DIAGNOSTIC AND STATISTICAL MANUAL OF MENTAL DISORDERS 39-40 (4th ed. 1994).
11. See Eija Jumisko, Jan Lexell & Siv Söderberg, The Meaning of Living with Traumatic Brain Injury in People with Moderate or Severe Traumatic Brain Injury, J. NEUROSCIENCE NURSING, Feb. 2005 at 42.
12. See ALZHEIMER'S DISEASE EDUCATION AND REFERRAL (ADEAR) CENTER, ALZHEIMER'S DISEASE FACT SHEET (July 2006), available at http://www.nia.nih.gov (follow "Alzheimer's Disease Information" hyperlink; then follow "general information" hyperlink; then follow "AD Fact Sheet" hyperlink).
13. See AMERICAN ACADEMY OF NEUROLOGY, POSITION OF THE AMERICAN ACADEMY OF NEUROLOGY ON CERTAIN ASPECTS OF THE CARE AND MANAGEMENT OF THE PERSISTENT VEGETATIVE STATE PATIENT (1989).
14. See THOMAS GRISSO & PAUL S. APPELBAUM, ASSESSING COMPETENCE TO CONSENT TO TREATMENT: A GUIDE FOR PHYSICIANS AND OTHER HEALTH PROFESSIONALS 1637 (1998).
15. See Lawrence A. Frolik, Plenary Guardianship: An Analysis, a Critique and a Proposal for Reform, 23 ARIZ. L. REV. 599, 601 (1981).
16. JESSICA W. BERG, PAUL S. APPELBAUM, LISA S. PARKER & CHARLES W. LIDZ, INFORMED CONSENT: LEGAL THEORY AND CLINICAL PRACTICE 96 (2d ed. 2001).
17. See, e.g., In re Farrell, 529 A.2d 404, 413 n.7 (N.J. 1987) ("A competent patient has a clear understanding of the nature of his or her illness and prognosis, and of the risks and benefits of the proposed treatment, and has the capacity to reason and make judgments about that information.").
18. See Paul S. Appelbaum & Loren H. Roth, Clinical Issues in the Assessment of Competency, 138 AM. J. PSYCHIATRY 1462, 1465 (1981).
19. See Joan Stephenson, Probing Informed Consent in Schizophrenia Research, 281 J. AM. MED. ASS'N 2273 (1999).
20. For example, it also arises when juries are asked to determine whether a witness is credible.
21. As Allen Buchanan and Dan Brock explain: In the conflict between the values of self-determination and patient well-being, a tradeoff between avoiding two kinds of errors should be sought. The first error is that of failing to protect a person from the harmful consequences of his or her decision when the decision is the result of serious defects in the capacity to decide. The second error is failing to permit someone to make a decision and turning the decision over to another, when the patient is able to make the decision him- or herself. With a stricter or higher standard for competence, more people will be found incompetent, and the first error will be minimized at the cost of increasing the second sort of error. With a looser or more minimal standard for competence, fewer persons will be found incompetent, and the second sort of error is more likely to be minimized at the cost of increasing the first. Allen Buchanan & Dan W. Brock, Deciding for Others, 64 MILBANK Q. 17, 30-31 (1986).
22. Carl Elliott, Caring About Risks: Are Severely Depressed Patients Competent to Consent to Research?, 54 ARCHIVES GEN. PSYCHIATRY 113, 115 (1997);
23. see also Marsha Garrison, The Empire of Illness: Competence and Coercion in Health-Care Decision Making, 49 WM. & MARY L. REV. 781, 829 (2007) ("[I]t seems likely that depression acts as a coercive influence that interferes with the patient's capacity to recognize her genuine treatment preferences.").
24. Bernard Lo, Assessing Decision-Making Capacity, 18 L. MED. & HEALTH CARE 193, 195 (1990);
25. see also 1 PRESIDENT'S COMMISSION FOR THE STUDY OF ETHICAL PROBLEMS IN MEDICINE AND BIOMEDICAL AND BEHAVIORAL RESEARCH, MAKING HEALTH CARE DECISIONS: THE ETHICAL AND LEGAL IMPLICATIONS OF INFORMED CONSENT IN THE PATIENT-PRACTITIONER RELATIONSHIP 171 (1982) (emphasizing the importance of "consistency between the person's choice and that individual's underlying values").
26. Elliott, supra note 22.
27. See Buchanan & Brock, supra note 21, at 30-31.
28. Indeed, the surrogate may be legally required to do this. See infra text accompanying notes 141-146.
29. Buchanan & Brock, supra note 21, at 40.
30. This Article focuses on studies involving drugs, medical devices, and other medical procedures, because those are the studies where the potential for harm is the greatest. Examples of other types of research that might involve incapacitated subjects include observational studies in which no interventions are provided, and studies in which the sole interventions consist of interviews or questionnaires.
31. ALZHEIMER'S ASSOCIATION, 2006: THE YEAR IN ALZHEIMER SCIENCE, http://www.alz.org/ alzheimers_disease_research_ad.asp.
32. Erica Goode, Leading Drugs for Psychosis Come Under New Scrutiny, N.Y. TIMES, May 20, 2003, at A1.
33. Barry Reisberg, Rachelle Doody, Albrecht Stöffler, Frederick Schmitt, Steven Ferris & Hans Jörg Möbius, Memantine in Moderate-to-Severe Alzheimer's Disease, 348 NEW ENG. J. MED. 1333 (2003).
34. See id.
35. 45 C.F.R. § 46.102(d) (2008) (defining "research" as a "systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalized knowledge").
36. See generally Carl H. Coleman, Duties to Subjects in Clinical Research, 58 VAND. L. REV. 387, 396-402 (2005).
37. E. Haavi Morreim, Litigation in Clinical Research: Malpractice Doctrine Versus Research Realities, 32 J.L. MED. & ETHICS 474, 475 (2004).
38. A. Strachan & J. Train, Letter to the Editor, Lumbar Puncture and Headache: Aspirating Cerebrospinal Fluid Speeds Up Procedure, 316 BRIT. MED. J. 1015, 1018 (1998).
39. See generally CARL H. COLEMAN, JERRY A. MENIKOFF, JESSE A. GOLDNER & NANCY NEVELOFF DUBLER, THE ETHICS AND REGULATION OF RESEARCH WITH HUMAN SUBJECTS 271 (2005). Not all medication washouts are nontherapeutic. In one study conducted at UCLA, researchers sought to identify factors that could help doctors determine which schizophrenic patients could safely be taken off their medications without experiencing relapses. Subjects were given medications for one year, following which they were either continued on their medications or given a placebo. The study generated controversy when one subject in the placebo group relapsed and committed suicide. Yet, while there were problems with the way in which the study was conducted, it would not be accurate to characterize the study as nontherapeutic. Subjects who were able to go off their medications without negative consequences were freed of an unnecessary medication that can have intolerable side effects - a clear benefit in the view of both schizophrenic patients and physicians. Indeed, the point of the study was to determine whether medication washouts could be offered to some categories of patients as a standard treatment. The study was therefore different from those in which taking subjects off their medications is not expected to have any therapeutic benefit. Id. at 271-78.
40. Sometimes, however, studies are designed so that subjects who initially receive the placebo will receive the experimental intervention later in the trial. See, e.g., Sarah A. Eagger, R. Levy & Barbara J. Sahakian, Tacrine in Alzheimer's Disease, 337 LANCET 989 (1991). In other cases, subjects in the placebo group are given the option of receiving the experimental intervention after the study is over, assuming the experimental intervention is shown to be effective.
41. See, e.g., Martin R. Farlow, NMDA Receptor Antagonists: A New Therapeutic Approach for Alzheimer's Disease, GERIATRICS, June 2004, at 22.
42. Benjamin Freedman, Equipoise and the Ethics of Clinical Research, 317 NEW ENG. J. MED. 141, 144 (1987). The principle of clinical equipoise, if applied strictly, means that "placebo-controlled trials are appropriate only when no effective treatment exists for a particular condition, or when the treatments that exist are inadequate for a particular subset of patients." COLEMAN ET AL., supra note 37, at 262. However, the World Medical Association has determined that placebo-controlled trials can be acceptable "even if proven therapy is available," if there are "compelling and scientifically sound methodological reasons its use is necessary to determine the efficacy or safety of a proposed prophylactic, diagnostic or therapeutic method," or if the study involves "a minor condition and the patients who receive placebo will not be subject to any additional risk of serious or irreversible harm."
43. WORLD MEDICAL ASSOCIATION, NOTE OF CLARIFICATION ON PARAGRAPH 29 OF THE WORLD MEDICAL ASSOCIATION DECLARATION OF HELSINKI (2002).
44. See Coleman, supra note 34, at 397-98.
45. See Lester M. Crawford, Acting Commissioner of the FDA, Speech before the Mayo Alliance for Clinical Trials Conference (August 26, 2004), available at http://www.fda.gov/oc/speeches/2004/mayo0826.html ("We're currently seeing a 50 percent failure rate among products in late-stage Phase 3 trials. 50 percent!").
46. Jacobo Mintzer, Andrew Greenspan, Ivo Caers, Ilse Van Hove, Stuart Kushner, Myron Weiner, Georges Gharabawi & Lon S. Schneider, Risperidone in the Treatment of Psychosis of Alzheimer Disease: Results from a Prospective Clinical Trial, 14 AM. J. GERIATRIC PSYCHIATRY 280, 280 (2006).
47. Jonas Bergh, Commentary, Where Next with Stem-Cell-Supported High-Dose Therapy for Breast Cancer?, 355 LANCET 944 (2000).
48. See J. Bruce Moseley, Kimberly O'Malley, Nancy J. Petersen, Terri J. Menke, Baruch A. Brody, David H. Kuykendall, John C. Hollingsworth, Carol M. Ashton & Nelda P. Wray, A Controlled Trial of Arthroscopic Surgery for Osteoarthritis of the Knee, 347 NEW ENG. J. MED. 81 (2002).
49. See Gina Kolata, Parkinson's Research Is Set Back by Failure of Fetal Cell Implants, N.Y. TIMES, March 8, 2001, at A1.
50. See Jerry Menikoff, The Hidden Alternative: Getting Investigational Treatments Off-Study, 361 LANCET 63, 63 (2003).
51. See generally Patricia C. Kuszler, Financing Clinical Research and Experimental Therapies: Payment Due, but from Whom!, 3 DEPAUL J. HEALTH CARE L. 441, 446-53 (2000) (describing the FDA approval process).
52. See Menikoff, supra note 46, at 63.
53. COLEMAN ET AL., supra note 37, at 147. In Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach, 445 F.3d 470 (D.C. Cir. 2006), a D.C. Circuit panel held that terminally ill individuals had a constitutional right to access to unapproved drugs that had passed early-phase safety testing, thereby calling into question the validity of the FDA's compassionate use regulations. However, the decision was reversed en banc, 495 F.3d 695 (D.C. Cir. 2007) (en banc), and the Supreme Court denied certiorari, 128 S. Ct. 1069 (2008). Prompted in part by the panel's decision, the FDA has undertaken efforts to clarify its compassionate use rules. See Mark Barnes, Clinton D. Hermes, Katherine Jaral & Ellen Moskowitz, Looking Back at 2006, Looking Ahead to 2007: 'Expanded Access,' Research Billing, International Research, Grants Accounting, Catalona, Gene Therapy, and Central IRBs, 6 MED. RES. L. & POL'Y REP., Jan. 3, 2007, at 14.
54. Menikoff, supra note 46, at 63.
55. Shawn L. Cassady, Helene Adami, Marianne Moran, Rick Kunkel, & Gunvant K. Thaker, Spontaneous Dyskinesia in Subjects with Schizophrenic Spectrum Personality, 155 AM. J. PSYCHIATRY 70 (1998).
56. Jack M. Gorman, Justine Kent, Jose Martinez, Susan Browne, Jeremy Coplan, & Laszlo A. Papp, Physiological Changes During Carbon Dioxide Inhalation in Patients with Panic Disorder, Major Depression, and Premenstrual Dysphoric Disorder: Evidence for a Central Fear Mechanism, 58 ARCHIVES OF GEN. PSYCHIATRY 125, 125 (2005). In another example of a challenge study, subjects with major depression who had recently attempted suicide were given the drug fenfluramine in order to identify differences in brain activity between "high-lethality" and "low-lethality" suicide attempters.
57. See Maria A. Oquendo, Giovanni P. A. Placidi, Kevin M. Malone, Carl Campbell, John Keilp, Beth Brodsky, Lawrence S. Kegeles, Thomas B. Cooper, Ramin V. Parsey, Ronald L. Van Heertum, & J. John Mann, Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge and Lethality of Suicide Attempts in Major Depression, 60 ARCHIVES OF GEN. PSYCHIATRY 14 (2003).
58. Peter M. Thompson, Mary Kelley, Jeffrey Yao, Guochuan Tsai, & Daniel P. van Kammen, Elevated Cerebrospinal Fluid SNAP-25 in Schizophrenia, 53 BIOLOGICAL PSYCHIATRY 1132, 1133 (2003).
59. See Dolores Kong, Study Harmed Mentally Ill, Agency Reports, BOSTON GLOBE, Feb. 9, 1999, at A8 (reporting the National Institute of Health's Office for Protection from Research Risks' criticism of the Mount Sinai study).
60. John R. Atack & Mark B. Schapiro, Inositol Monophosphatase Activity in Normal, Down Syndrome and Dementia of the Alzheimer Type CSF, 23 NEUROBIOLOGY OF AGING 389 (2002).
61. Alan J. Lerner, Robert C. Elston, Chien Hsiun Chen, & Robert P. Friedland, Response of the Hypothalamic-Pituitary-Adrenal Axis to Lumbar Puncture-Induced Stress, 2 J. ALZHEIMER'S DISEASE 193 (2000).
62. 1 NATIONAL BIOETHICS ADVISORY COMMISSION, RESEARCH INVOLVING PERSONS WITH MENTAL DISORDERS THAT MAY AFFECT DECISION-MAKING CAPACITY 13 (1998) [hereinafter NBAC REPORT].
63. Id. at 4.
64. Id. (quoting Nancy C. Andreasen, Daniel S. O'Leary & Stephan Arndt, Neuroimaging and Clinical Neuroscience: Basic Issues and Principles, in 12 AMERICAN PSYCHIATRIC PRESS REVIEW OF PSYCHIATRY, (John M. Oldham, Michelle B. Riba & Allan Tasman eds., 1993)).
65. See Rebecca Dresser, Research Involving Persons with Mental Disabilities: A Review of Policy Issues and Proposals, 2 NATIONAL BIOETHICS ADVISORY COMMISSION, RESEARCH INVOLVING PERSONS WITH MENTAL DISORDERS THAT MAY AFFECT DECISIONMAKING CAPACITY 23 (1999).
66. See Nancy M. P. King, Defining and Describing Benefit Appropriately in Clinical Trials, 28 J.L. MED. & ETHICS 332, 333 (2000).
67. See REBECCA DRESSER, WHEN SCIENCE OFFERS SALVATION: PATIENT ADVOCACY AND RESEARCH ETHICS 65 (2001) ("If opportunities to enroll in clinical trials increase, and the number of people with adequate health coverage decreases, research will become a more enticing means for low-income people to obtain a modicum of clinical attention.").
68. See Nancy E. Kass, Jeremy Sugarman, Ruth Faden & Monica Schoch-Spana, Trust: The Fragile Foundation of Contemporary Biomedical Research, 26 HASTINGS CENTER REP. 25, 27 (1996).
69. 45 C.F.R. pt. 46. The Common Rule applies to all research conducted or supported by the federal agencies that have adopted the rule. 45 C.F.R. § 46.101(a) (2008). In addition, many institutions that conduct federally-funded research have contractually agreed to comply with the Common Rule in all their human subject research, regardless of the source of funding. See COLEMAN ET AL., supra note 37, at 107.
70. 21 C.F.R. § 56.102 (2008). The FDA regulations apply to all "clinical investigations" related to drugs, biologic products, or medical devices that are intended for "human use." 21 C.F.R. § 56.102(c), (1) (2008). Some research, such as federally-funded drug studies, are covered by both the Common Rule and the FDA regulations. Other studies escape all federal regulation, because they (1) are not conducted or supported by federal agencies; (2) are not conducted in institutions that have agreed to apply the Common Rule to all their human subject research; and (3) do not involve an FDA-regulated product.
71. 45 C.F.R. § 46.111(a)(2) (2008); 21 C.F.R. § 56.111(a)(2) (2008).
72. See infra text accompanying notes 77-80.
73. 45 C.F.R. § 46.111(a)(4) (2008); 21 C.F.R. § 56.111(a)(4) (2008). IRBs also must determine that risks to subjects are minimized, that the selection of subjects are equitable, and that appropriate measures are in place to monitor the research and to protect subjects' confidentiality. See 45 C.F.R. § 46.111 (2008); 21 C.F.R. § 56.111 (2008).
74. See generally ROBERT JAY LIFTON, THE NAZI DOCTORS: MEDICAL KILLING AND THE PSYCHOLOGY OF GENOCIDE (1986).
75. THE NUREMBERG CODE ∥ 1, reprinted in COLEMAN ET AL. ET AL., supra note 37, at 27.
76. Pub. L. No. 93-348, 88 Stat. 342 (1974).
77. See ALBERT R. JONSEN, THE BIRTH OF BIOETHICS 142-48 (1998).
78. The Tuskegee study was designed to "document the natural history" of untreated syphilis. The subjects in the study were poor African-American sharecroppers, and "government officials went to extreme lengths to ensure that they received no therapy from any source." TUSKEGEE SYPHILIS STUDY LEGACY COMMITTEE, FINAL REPORT OF THE TUSKEGEE SYPHILIS STUDY LEGACY COMMITTEE (1996), available at http://www.healthsystem.virginia.edu/internet/library/ historical/medical_history/bad_blood/report.cfm.
79. See Henry K. Beecher, Ethics and Clinical Research, 274 NEW ENG. J. MED. 1354 (1966). In one of the studies Beecher described, researchers injected live cancer cells into indigent, elderly patients at the Brooklyn Jewish Chronic Disease Hospital. Id. at 1358. In another study, children at a state facility for "mentally defective persons" were deliberately infected with hepatitis. COLEMAN ET AL., supra note 37, at 39-40.
80. See TOM L. BEAUCHAMP & JAMES F. CHILDRESS, PRINCIPLES OF BIOMEDICAL ETHICS 350-51 (5th ed. 2001).
81. Hans Jonas, Philosophical Reflections on Experimenting with Human Subjects, 98 DAEDALUS 219 (1969), reprinted in JAY KATZ, EXPERIMENTATION WITH HUMAN BEINGS: THE AUTHORITY OF THE INVESTIGATOR, SUBJECT, PROFESSIONS AND STATE IN THE HUMAN EXPERIMENTATION PROCESS 668 (1972).
82. See id.
83. In addition to the two categories described in the text, waivers of informed consent are also available in certain studies of public benefit programs. See 45 C.F.R. § 46.116(c) (2008).
84. Id. at § 46.116(d).
85. Another way to conduct such a study would be for the researchers to record only non-identifying information from the medical records, which would make the study exempt from the Common Rule. Id. at § 101(b)(4) (exempting studies involving the review of existing records "if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects").
86. 21 C.F.R. § 50.24 (2008).
87. 45 C.F.R. § 46.116 (2008); 21 C.F.R. § 50.20 (2008). In addition to the provisions on legally authorized representatives, the regulations contain three other references to mentally disabled subjects. First, they provide that, if an IRB regularly reviews research involving vulnerable populations, including mentally disabled subjects, "consideration shall be given to the inclusion [on the IRB] of one or more individuals who are knowledgeable about and experienced in working with these subjects." 45 C.F.R. § 46.107(a) (2008). Second, in determining whether the "selection of subjects is equitable," the IRB "should be particularly cognizant of the special problems of research involving vulnerable populations," including mentally disabled subjects. 45 C.F.R. § 46.111(a)(3) (2008). Third, IRBs should ensure that, "[w]hen some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as . . . mentally disabled persons . . . additional safeguards have been included in the study to protect the rights and welfare of these subjects." 45 C.F.R. § 46.111 (b) (2008).
88. 45 C.F.R. § 46.102(c) (2008); 21 C.F.R. § 50.3(1) (2008).
89. See Gonzalez v. Oregon, 546 U.S. 243, 270-72 (2006).
90. In at least one situation, however, federal law provides additional substantive restrictions. See 10 U.S.C. § 980(a)(2) (2000) (providing that funds appropriated by the Department of Defense may not be used for research with incapacitated subjects unless the research is "intended to be beneficial to the subject" and "the informed consent of the subject or a legal representative of the subject is obtained in advance").
91. See CAL. HEALTH & SAFETY CODE § 24178 (2007); KAN. STAT. ANN. § 65-4974 (2006); N.J. STAT. § 26:14-1 (2008); VA. CODE ANN. § 32.1-162.18(B) (2008), 12 VA. ADMIN. CODE § 5-20-40 (2007); OKLA. STAT. ANN. tit. 63, § 3102A (2007); WYO. STAT. ANN. § 25-5-132(d)(iii) (2007). Some states have statutes authorizing surrogate consent to "experimental treatment" for certain incapacitated patients. See, e.g., FLA. STAT. ANN. § 393.13(4)(c)(6) (2007). However, these statutes would probably exclude studies that do not offer a prospect of direct medical benefit, as such studies could not plausibly be considered a form of treatment.
92. CAL. HEALTH & SAFETY CODE § 24178; see also COLEMAN ET AL., supra note 37, at 608-09 (discussing the history behind the California statute).
93. CAL. HEALTH & SAFETY CODE § 24178(c).
94. See ALASKA STAT. § 47.30.830 (2008) (stating that "experimental treatments involving any significant risk of physical or psychological harm may not be administered to a patient" in a state mental health facility); DEL. CODE ANN. tit. 16, § 5175(f) (2008) ("No [resident of a state mental hospital] shall be approached to participate in pharmaceutical research if patient is incapable of understanding the nature and consequences of patient's consent."); MO. ANN. STAT. § 630.192 (West 2007) (prohibiting research in state-funded or licensed mental health facilities "unless such research is intended to alleviate or prevent the disabling conditions or is reasonably expected to be of direct therapeutic benefit to the participants," and further providing that no research may be performed on involuntarily committed persons without a court order).
95. See ARK. CODE ANN. § 28-65-302 (2008); N.H. REV. STAT. ANN. § 464-A:25(I)(c) (2008); 405 ILL. COMP. STAT. ANN. 5/2-110 (West 2008); CONN. GEN. STAT. § 45a-677(e)(6) (2007) (requiring that research be approved by an IRB and the patient's primary physician and endorsed by the state Department of Mental Retardation).
96. See, e.g., 405 ILL. COMP. STAT. ANN. 5/2-110 (West 2008).
97. See generally Joan L. O'Sullivan, Role of the Attorney for the Alleged Incapacitated Person, 31 STETSON L. REV. 687, 689-94 (2002) (discussing the history and powers of guardianship).
98. See CHARLES P. SABATINO, ABA COMMISSION ON LAW AND AGING, 10 LEGAL MYTHS ABOUT ADVANCE MEDICAL DIRECTIVES 5, available at http://www.abanet.org/aging/publications/docs/ 10legalmythsarticle.pdf.
99. See generally ALAN MEISEL, THE RIGHT TO DIE §§ 5.17-.21 (2d ed. 1995). For a summary of state statutes, see ABA COMMISSION ON LAW AND AGING, SURROGATE CONSENT IN THE ABSENCE OF AN ADVANCE DIRECTIVE, available at http://www.abanet.org/aging/legislativeupdates/docs/Famcon_05-07.pdf [hereinafter ABA COMMISSION, SURROGATE CONSENT].
100. See MEISEL, supra note 94, at § 7.3 (describing a continuum of standards, ranging from a "subjective standard" based on "knowledge of the patient's actual ('subjective') wishes," to a "substituted judgment" standard, in which the patient's wishes are "inferred from the patient's statements and conduct," to a pure "best interests" standard, which "reflects and seeks to implement the value of welfare or well-being, rather than self-determination or autonomy") (emphases omitted).
101. 45 C.F.R. § 46.102(c) (2008).
102. Michele Russell-Einhorn & Thomas Puglisi, Three Exceptions to the Requirement to Obtain Informed Consent in Research, 1 MED. RES. L. & POL'Y REP., Nov. 6, 2002, at 514.
103. See Letter from Leslie K. Ball, Compliance Oversight Coordinator, OHRP, to Ralph Snyderman, President, Duke University Health System (Feb. 1, 2002), available at http://www.hhs.gov/ohrp/detrm_letrs/YR02/feb02a.pdf.
104. See United States v. Mead Corp., 533 U.S. 218, 228 (2001) ("The weight [accorded to an administrative] judgment in a particular case will depend upon the thoroughness evident in its consideration, the validity of its reasoning, its consistency with earlier and later pronouncements, and all those factors which give it power to persuade, if lacking power to control.") (alteration in original) (quoting Skidmore v. Swift, 323 U.S. 134, 140 (1944)).
105. 650 N.Y.S.2d 173 (App. Div. 1996), appeal dismissed, 690 N.E.2d 1259 (N. Y. 1997).
106. Id. at 176. The New York Court of Appeals ultimately concluded that it was unnecessary to reach the constitutional and common law questions, and it therefore vacated those portions of the intermediate appellate court's decision. See T.D., 690 N.E.2d at 1260.
107. Grimes v. Kennedy Krieger Inst., 782 A.2d 807, 862 (Md. 2001); see also id. at 814 ("[P]arents . . . have no more right to intentionally and unnecessarily place children in potentially hazardous nontherapeutic research surroundings . . . than do researchers. In such cases, parental consent, no matter how informed, is insufficient."). The Grimes decision placed greater restrictions on research with children than the federal regulations, which permit no-direct-benefit research involving more than minimal risks in limited circumstances. 45 C.F.R. §§ 46.406-.407 (2008).
108. See infra text accompanying notes 175-81.
109. Diane E. Hoffmann, Jack Schwartz & Evan G. DeRenzo, Regulating Research with Decisionally Impaired Individuals: Are We Making Progress?, 3 DEPAUL J. HEALTH CARE L. 547, 551-52 (2000).
110. Id. at 551-55.
111. Id. at 565. Existing regulations on research with children contain a similar requirement. See 45 C.F.R. § 46.407 (2008).
112. Hoffmann et al., supra note 104, at 563-64.
113. See id. at 568.
114. Id. at 569.
115. See supra text accompanying notes 100-101.
116. ADVISORY WORK GROUP ON HUMAN SUBJECT RESEARCH INVOLVING THE PROTECTED CLASSES, N.Y. STATE DEPARTMENT OF HEALTH, RECOMMENDATIONS ON THE OVERSIGHT OF HUMAN SUBJECT RESEARCH INVOLVING THE PROTECTED CLASSES 26 (1998) [hereinafter NYSAWG REPORT]. The author of this Article served as a staff member to the NYSAWG.
117. NBAC REPORT, supra note 57.
118. See Diane E. Hoffmann & Jack Schwartz, Proxy Consent to Participation of the Decisionally Impaired on Medical Research - Maryland's Policy Initiative, 1 J. HEALTH CARE L. & POL'Y 123, 140-46 (1998).
119. See NYSAWG REPORT, supra note 111, at 26; NBAC REPORT, supra note 57, at 60-62; Hoffmann & Schwartz, supra note 113, at 140-46.
120. NBAC recommended that surrogate consent to such research be permitted only if the study receives approval from a national ethics panel. See NBAC REPORT, supra note 57, at 58-60. The NYSAWG, by contrast, concluded that surrogates should be permitted to consent to no-direct-benefit research involving a "minor increase over minimal risk" without special national approval. However, the NYSAWG recommendations limited no-direct-benefit studies involving more than a minor increase over minimal risk to persons who had expressly authorized such research before losing capacity. NYSAWG REPORT, supra note 111, at 25, 32-33. The Maryland commission fell somewhere between these two approaches: It concluded that decision-makers appointed by the prospective subject through a health care proxy (i.e., "health care agents") should be permitted to consent to no-direct-benefit research involving a minor increase over minimal risk, but that surrogates not appointed by the prospective subject should not have this authority. Like the NYSAWG, the Maryland commission would have limited no-direct-benefit research involving more than a minor increase over minimal risk to persons who had expressly authorized such research while competent. See Hoffmann & Schwartz, supra note 113, at 141-46.
121. Hoffmann et al., supra note 104, at 592.
122. Naomi Toy & Gregg Birnbaum, O'Connor: No-Consent Testing Recalls Nazis, N.Y. POST, Jan. 18, 1999, at 5.
123. Hoffmann et al., supra note 104, at 592.
124. See supra note 86.
125. See supra text accompanying notes 92-93.
126. See supra note 95 and accompanying text.
127. NBAC REPORT, supra note 57, at 62.
128. NYSAWG REPORT, supra note 111, at 32-33; Hoffmann & Schwartz, supra note 113, at 140.
129. See CAL. HEALTH & SAFETY CODE § 24178(g) (West 2006) (requiring surrogates to make decisions "in accordance with the person's individual health care instructions, if any, and other wishes, to the extent known to the surrogate decisionmaker," or if those wishes are not known, "in accordance with the person's best interests"). By contrast, the New Jersey statute provides that, if the incapacitated person's wishes are not known, the surrogate "shall make a decision in accordance with the subject's personal values and his best estimation of what the subject would have chosen if he were capable of making a decision." N.J. STAT. § 26:14-5.d. The statute does not incorporate the best interests standard. Other research consent statutes state only that the surrogate may not make decisions that contravene what is known about the patient's wishes or values. See KAN. STAT. ANN. § 65-4974 (2006); OKLA. STAT. ANN. tit. 63 § 3102A (West 2004); VA. CODE ANN. § 32.1-162.18(B) (2004). Under these statutes, if the patient's prior wishes cannot be determined, the surrogate would appear to have unlimited authority to consent to any IRB-approved study.
130. See infra text accompanying note 152.
131. See, e.g., In re Gardner, 534 A.2d 947, 953 (Me. 1987) (noting that the patient "had specifically observed friends and neighbors in desperate medical straits and had declared that he did not want to be kept alive artificially if he ever came into that condition"); In re Eichner, 420 N.E.2d 64, 68, 72 (N.Y. 1981) (finding clear and convincing evidence of the patient's prior decision to refuse a respirator, in part based on the patient's comments about the Karen Ann Quinlan case).
132. See supra text accompanying notes 34-40.
133. See supra text accompanying note 50.
134. See supra text accompanying notes 51-52.
135. See supra text accompanying notes 34-40.
136. See supra text accompanying notes 41-45.
137. See supra text accompanying notes 46-50.
138. NORMAN L. CANTOR, MAKING MEDICAL DECISIONS FOR THE PROFOUNDLY MENTALLY DISABLED 127 (2005).
139. Id. at 127-28.
140. See id.
141. See infra text accompanying notes 176-79.
142. As the Supreme Court has observed, the best interests of the child is not the legal standard that governs parents' or guardians' exercise of their custody: So long as certain minimum requirements of child care are met, the interests of the child may be subordinated to the interests of other children, or indeed even to the interests of the parents or guardians themselves. Reno v. Flores, 507 U.S. 292, 304 (1993).
143. The use of best interests rhetoric to justify decisions that are actually based on other factors is not limited to decisions about medical research. In family law, for example, scholars have recognized that appeals to the "best interests of the child" mask the fact that decisions about children's welfare are often made on an arbitrary basis. Robert Mnookin has suggested that instead of claiming that custody decisions are based on the child's best interests, "[w]e would more frankly acknowledge both our ignorance and the presumed equality of the natural parents were we to flip a coin." Robert H. Mnookin, Child-Custody Adjudication: Judicial Functions in the Face of Indeterminacy, 39 LAW & CONTEMP. PROBS. 226, 289 (1975). However, there is a difference between using best interests language when all of the options are equally acceptable, as in the custody example, and using it when a surrogate is making decisions that are inconsistent with the incapacitated person's welfare.
144. See Steven I. Friedland, The Health Care Proxy and the Narrative of Death, 10 J.L. & HEALTH 95, 135 (1995/1996).
145. In fact, both NYSAWG and the Maryland commission recommended that states enact legislation authorizing the appointment of "research agents." See NYSAWG REPORT, supra note 111, at 25; MARYLAND GENERAL ASSEMBLY S.B. BILL 307 (1999), at § 20.701(W). Similarly, NBAC proposed "an amendment to the Common Rule that would define the term 'legally authorized representative' to include those who, under the law of the state where the research is conducted, may serve as proxy decision makers for clinical care." NBAC REPORT, supra note 57, at 63. However, under all of these proposals, agents would have the authority to consent to high-risk, no-direct-benefit research only if the incapacitated person had expressly indicated her willingness to participate in such research while competent. See NYSAWG REPORT, supra note 111, at 25, 32-33; MARYLAND GENERAL ASSEMBLY S.B. BILL 307 (1999), at § 20.745(A)(1)(I); NBAC REPORT, supra note 57, at 63.
146. See Bernard Lo & Robert Steinbrook, Resuscitating Advance Directives, 164 ARCHIVES INTERNAL MED. 1501 (2004).
147. See ABA COMMISSION, SURROGATE CONSENT, supra note 94.
148. E.g., In re Conroy, 486 A.2d 1209, 1232 (1985).
149. E.g., D.C. CODE § 21-2211 (2001).
150. Norman L. Cantor, Déjà Vu All Over Again: The False Dichotomy Between Sanctity of Life and Quality of Life, 35 STETSON L. REV. 81, 85 (2005) (noting that patients must rely on "personal values and preferences" to decide "whether the prospective preservable state would be so intolerably painful or degrading as to make treatment unwanted").
151. See In re Jobes, 529 A.2d 434, 444-45 (1987).
152. The most likely reason a surrogate would seek to do this would be for religious reasons. See, e.g., Kent Greenawalt, Objections in Conscience to Medical Procedures: Does Religion Make a Difference?, 2006 U. ILL. L. REV. 799, 803 (2006) (noting that Jehovah's Witnesses "believe that God's will is that they not accept transfers of blood").
153. See supra text accompanying notes 145-46.
154. E.g., Fosmire v. Nicoleau, 551 N.E.2d 77 (N.Y. 1990) (upholding the right of a Jehovah's Witness patient to refuse a life-saving blood transfusion).
155. See generally Rosamond Rhodes & Ian R. Holzman, The Not Unreasonable Standard for Assessment of Surrogates and Surrogate Decisions, 25 THEORETICAL MED. & BIOETHICS 367 (2004) (arguing that physicians should not accede to surrogates' unreasonable decisions).
156. LL. COMP. STAT. 40/15 (2007).
157. Indeed, it is often the case that policies ostensibly motivated by respect for individual autonomy are constrained by societal assumptions about what is objectively reasonable. For example, proponents of physician-assisted suicide frequently ground their arguments in claims about individuals' autonomous right to make life-and-death decisions, but at the same time, most of them emphasize that they would legalize assisted suicide only for terminally ill patients. See generally Charles H. Baron, Clyde Bergstresser, Dan W. Brock, Garrick F. Cole, Nancy S. Dorfman, Judith A. Johnson, Lowell E. Schnipper, James Vorenberg & Sidney H. Wanzer, A Model State Act to Authorize and Regulate Physician-Assisted Suicide, 33 HARV. J. ON LEGIS. 1 (1996). Thus, they are not prepared to recognize all autonomous decisions to commit suicide; their support is limited to decisions that fall within parameters they consider to be objectively reasonable.
158. Strunk v. Strunk, 445 S.W.2d 145, 146 (Ky. 1969) (finding that the donation would be beneficial to the incapacitated person because he "was greatly dependent upon [his brother], emotionally and psychologically, and that his well-being would be jeopardized more severely by the loss of his brother than by the removal of a kidney"). See generally CANTOR, supra note 133, at 75-78.
159. Similar constraints apply outside the area of medical decision making. For example, courts have held that guardians may not use the assets of their wards to make charitable contributions unless the ward "manifested [a] commitment to such charity" before losing capacity or the donation would be in the incapacitated person's best interests. In re: Erna Marx Probate Court, 18 QUINNIPIAC PROB. L.J. 35, 40-41 (2004).
160. See generally David I. Shalowitz, Elizabeth Garrett-Mayer & David Wendler, 166 ARCHIVES INTERNAL MED. 493 (2006).
161. CANTOR, supra note 133, at 37 (noting that some advocates for people with disabilities "fear substituted judgment as a cover for exploitation based on prejudice and stereotyped views of the quality of life experienced by the profoundly disabled").
162. One such effort is the federal Patient Self-Determination Act (PSDA), which requires health care facilities to ask patients upon admission if they have advance directives, to document the existence of any such directives in the patient's record, and to provide notice to patients without advance directives of their rights to create advance directives and the facility's policies with respect to such directives. See 42 U.S.C. §§ 1395cc, 1396a (2000 & Supp. IV 2004). The PSDA appears to have had little impact. Carl E. Schneider & Lee E. Teitelbaum, Life's Golden Tree: Empirical Scholarship and American Law, 2006 UTAH L. REV. 53, 95 (2006).
163. Will Lester, Poll: More Americans Have Living Wills, ASSOCIATED PRESS, Jan. 5, 2006 (reporting that twenty-nine percent of the population claims to have a living will).
164. See, e.g., JOSEPH J. FINS, A PALLIATIVE ETHIC OF CARE: CLINICAL WISDOM AT LIFE'S END 125 (2006) (arguing that "[l]iving wills have limited utility in the clinical context" because they may be "too vague," "ambiguous," or "too specific").
165. Rebecca Dresser, Precommitment: A Misguided Strategy for Securing Death with Dignity, 81 TEX. L. REV. 1823, 1823 (2003) (citing the difficulty of predicting future treatment preferences as a reason that advance directives are an "inferior strategy for making end-of-life decisions").
166. See generally Terri R. Fried, Amy L. Byers, Williams T. Gallo, Peter H. Van Ness, Virginia R. Towle, John R. O'Leary & Joel A. Dubin, Prospective Study of Health Status Preferences and Changes in Preferences Over Time in Older Adults, 166 ARCHIVES INTERNAL MED. 890 (2006);
167. Nina A. Kohn & Jeremy A. Blumenthal, Designating Health Care Decision-Makers for Patients Without Advance Directives: A Psychological Critique, http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1008494 (showing that individuals often do a poor job of predicting their future treatment preferences).
168. E.g., In re Westchester County Med. Qr., 531 N.E.2d 607 (N. Y. 1988) (holding that the hospital was authorized to insert a feeding tube into the incapacitated patient in the absence of clear and convincing evidence that the patient's wishes were otherwise).
169. Norman L. Cantor, Discarding Substituted Judgment and Best Interests: Toward a Constructive Preference Standard for Dying, Previously Competent Patients Without Advance Instructions, 48 RUTGERS L. REV. 1193, 1245 (1996) (arguing that requiring evidence of the patient's desire to refuse life-sustaining treatment ignores the fact that "the vast majority of competent people do not wish to be preserved in a demented, gravely debilitated, and helpless state"); see also Cruzan v. Dir., Mo. Dep't of Health, 497 U.S. 261, 316 (1990) (Brennan, J., dissenting) (arguing that requiring clear and convincing evidence of the patient's prior decision to refuse life-sustaining treatment imposes a "markedly asymmetrical evidentiary burden" that undermines the goal of promoting the patient's autonomy).
170. The commission reports discussed in Part II did not recognize this distinction. The NBAC report said nothing about the level of evidence of the incapacitated person's wishes that would be required in any type of study. The NYSAWG would have required heightened evidence of the incapacitated person's wishes only in no-direct-benefit studies involving more than a minor increase over minimal risk. For all other studies, surrogates could rely on "any relevant information" suggesting that "the research is in accordance with the individual's wishes." NYSAWG REPORT, supra note 111, at 26-27. The report's list of "relevant information" is quite broad, including, for example, "statements by the individual about the effect of research participation on the individual's family or on others who have the same condition." Id. at 27. Nothing in the report suggests that surrogates would have to produce specific evidence to support their claims about the incapacitated person's wishes. In contrast to the NYSAWG, the Maryland group would have applied a heightened evidentiary standard to all more-than-minimal-risk no-direct-benefit studies. See Hoffmann & Schwartz, supra note 113, at 144 (noting that the group's proposal would have required health care agents to have "direct and explicit evidence of the individual's wish to participate, as documented in accordance with standards and procedures set by the IRB"). However, the heightened evidentiary standard would not have applied to any studies involving a prospective of direct benefits, regardless of the risk level.
171. See supra text accompanying notes 125-29.
172. But cf. CANTOR, supra note 133, at 175 (pointing out that lifelong incapacitated persons are unable to develop personal values concerning altruism). See generally Michael T. Morley, Note, Proxy Consent to Organ Donation by Incompetents, 111 YALE L.J. 1215 (2002).
173. Morley, supra note 165, at 1242; see also In re Pescinski, 226 N.W.2d 180, 184 (Wis. 1975) (Day, J., dissenting) (arguing that preventing incapacitated persons from donating their kidneys "condemn[s] the incompetent to be always a receiver, a taker, but never a giver").
174. See, e.g., David Orentlicher, Making Research a Requirement of Treatment: Why We Should Sometimes Let Doctors Pressure Patients to Participate in Research, HASTINGS CTR. REP., Sept.-Oct. 2005, at 24.
175. See Research Notes - Clinical Trials: Efforts to Increase Participation Examined, AM. HEALTH LINE, June 22, 2006.
176. Gaia Bernstein, Accommodating Technological Innovation: Identity, Genetic Testing, and the Internet, 57 VAND. L. REV. 965, 977 (2004).
177. Michael J. Sandel, Introduction to LIBERALISM AND ITS CRITICS 1,6 (Michael J. Sandel ed., 1984).
178. See WILL KYMLICKA, MULTICULTURAL CITIZENSHIP: A LIBERAL THEORY OF MINORITY RIGHTS 91 (1995) (explaining that some communitarian theories call for the state to "reinforce people's allegiances" to ends that are "constitutive of people's identity").
179. See generally Kathleen Cranley Glass & Marc Speyer-Ofenberg, Incompetent Persons as Research Subjects and the Ethics of Minimal Risk, 5 CAMBRIDGE Q. HEALTHCARE ETHICS 362, 368-69 (1996).
180. Sandel, supra note 170 (emphasis added); see also Michael J. Sandel, Justice and the Good, in LIBERALISM AND ITS CRITICS 159, 167 (Michael J. Sandel ed., 1984) ("For a society to be a community in this strong sense, community must be constitutive of the shared self-understandings of the participants and embodied in their institutional arrangements, not simply an attribute of certain of the participants' plans of life.").
181. See KYMLICKA, supra note 171, at 152 ("Liberals are committed to supporting the right of individuals to decide for themselves which aspects of their cultural heritage are worth passing on.").
182. E.g., In re Hughes, 611 A.2d 1148 (N.J. Super. Ct. App. Div. 1992); In re Dorone, 534 A.2d 452 (Pa. 1987).
183. 406 U.S. 205, 234 (1972).
184. Id. at 210.
185. See id. at 242 (Douglas, J., dissenting in part) (criticizing the majority for "assum[ing] an identity of interest between parent and child").
186. See supra note 173 and accompanying text.
187. Yoder, 406 U.S. at 213-14.
188. 268 U.S. 510, 535 (1925).
189. Randall Baldwin Clark, Speed, Safety, and Dignity: Pediatric Pharmaceutical Development in an Age of Optimism, 9 U. CHI. L. SCH. ROUNDTABLE 1, 28 (2002) (arguing that enrolling children in no-direct-benefit research could be "yet another context in which children might develop the charitable instincts that parents want them to possess").
190. This distinction raises a difficult question: what standard should apply to parents making decisions about research for minor children with mental impairments who will never develop the capacity to make their own decisions? Such parents cannot justify exposing the child to risk by appealing to the educational aspects of research participation. In these cases it may be appropriate to require the parents' decisions to conform to whatever limitations apply to surrogate decision making for adult incapacitated subjects.
191. See, e.g., Troxel v. Granville, 530 U.S. 57, 66 (2000).
192. E.g., Elizabeth S. Scott & Robert E. Scott, Parents as Fiduciaries, 81 VA. L. REV. 2401, 2433-34 (1995).
193. Stefan Staicovici, Respite Care for All Family Caregivers: The Lifespan Respite Care Act, 20 J. CONTEMP. HEALTH L. & POL'Y 243, 251 (2003).
194. Id.
195. As Rebecca Dresser points out: Proxies and surrogates may see a dementia patient's research participation as a vehicle to secure services or other benefits that ease caregiving responsibilities. Biological relatives may seek to enroll a family member in studies that offer the promise of reducing their own risks of future disease affliction. In empirical studies, some representatives said they would be willing to enroll a decisionally incapable relative in research even if they thought the relative would refuse participation if capable. Some representatives also said they would enroll a relative in a study that the representatives would refuse for themselves. Rebecca Dresser, Dementia Research: Ethics and Policy for the Twenty-First Century, 35 GA. L. REV. 661, 675-76 (2001).
196. CANTOR, supra note 133, at 186.
197. Id. at 187.
198. Id.
199. Id.
200. Id. at 188.
201. Id. at 191.
202. Id. at 192-93.
203. Id. at 194.
204. Id. at 198.
205. See id. at 199.
206. Jesse A. Goldner, Dealing with Conflicts of Interest in Biomedical Research: IRB Oversight as the Next Best Solution to the Abolitionist Approach, 28 J.L. MED. & ETHICS 379, 380 (2000).
207. Carl H. Coleman, Rationalizing Risk Assessment in Human Subject Research, 46 ARIZ. L. REV. 1, 3 (2004).
208. The possibility that individuals may be better off being governed by a policy that leads to negative outcomes in specific situations, while seemingly paradoxical, is in fact widely recognized. For example, this is the premise underlying the widely accepted theory of "rule utilitarianism." See John Lawrence Hill, A Utilitarian Theory of Duress, 84 IOWA L. REV. 275, 317 (1999) (explaining that rule utilitarianism "holds that one should follow the rule that tends to maximize happiness in similar cases even if doing so does not maximize happiness in this particular case") (emphasis added).
209. A well-known example of this ex ante approach to risk-benefit assessment is John Rawls's social contract approach to political justification. See JOHN RAWLS, A THEORY OF JUSTICE 15-19 (rev. ed. 1999). Rawls states that a system of rules is legitimate if it would be accepted by individuals deliberating behind a "veil of ignorance" - that is, without knowing what particular social advantages or status they would have once the rules are implemented. Id. Rawls argues that behind this veil, persons would rationally choose a system that granted everyone as much liberty as possible, as long as everyone else had the same amount of liberty, and they would apportion benefits and burdens equally, unless an unequal distribution would make everyone, especially the less fortunate, better off. Id. The approach proposed in this Article is consistent with this Rawlsian analysis. From behind a veil of ignorance, it is likely that people would accept some risk of being enrolled in studies without their personal authorization, but only if there were no other way that they could reap the benefits of improved medical treatments, and only if those benefits would have greater value to them than the risk of being made an involuntary research subject. While such an approach would create a certain degree of inequality, insofar as the risk of being enrolled in research involuntarily would fall entirely on persons without decision-making capacity, the inequality is necessary to promote better medical treatments for those who would be disproportionately burdened.
210. CANTOR, supra note 133, at 187.
211. Although the argument presented here represents a departure from the way that risk-benefit assessment is usually carried out in health care, the idea of evaluating individuals' best interests from a systemic perspective has been advanced in other legal areas. For example, David Rosenberg relies on a similar analysis to explain why it is in everyone's best interest to adopt a rule requiring mass tort cases to be adjudicated by class actions, as opposed to individual litigation. See David Rosenberg, Mandatory-Litigation Class Action: The Only Option for Mass Tort Cases, 115 HARV. L. REV. 831 (2002). While such a rule would impose burdens on some people, by preventing them from bringing individual lawsuits that might offer them greater financial rewards than participating in a class action, those burdens would be outweighed by the fact that a mandatory system is more likely to "maximize individual welfare by securing optimal deterrence and insurance." Id. at 832. The structure of Rosenberg's argument is similar to the argument presented here. In both situations, the claim is that everyone is better off by accepting limits on individual autonomy, even if those limits impose burdens on certain people, if those limits are necessary to create a system that ultimately maximizes individual well-being.
212. Of course, this statement must be tempered by the fact that the ideals of informed consent are often not realized in practice. See, e.g., Nancy Neveloff Dubler, Remaining Faithful to the Promises Given: Maintaining Standards in Changing Times, 32 SETON HALL L. REV. 563, 567 (2002). Many research subjects agree to participate because of a "therapeutic misconception" - the mistaken belief that everything that happens to them in research is motivated by the researchers' commitment to their personal medical needs, rather than the researchers' pursuit of general knowledge.
213. Rebecca Dresser, The Ubiquity and Utility of the Therapeutic Misconception, 19 SOC. PHIL. & POL'Y 271, 271 (2002). These problems demonstrate the importance of continued efforts to improve the process of informed consent to research.
214. See supra text accompanying notes 125-29.
215. NBAC REPORT, supra note 57, at 55-56; NYSAWG REPORT, supra note 111, at 28.
216. COUNCIL FOR INT'L ORG. OF MED. SCI. & WORLD HEALTH ORG., INTERNATIONAL ETHICAL GUIDELINES FOR BIOMEDICAL RESEARCH INVOLVING HUMAN SUBJECTS Guidelines 51-53 (2002).
217. Participants in the 2001 Conference on Ethical Aspects of Research in Developing Countries, Fair Benefits for Research in Developing Countries, in ETHICAL AND REGULATORY ASPECTS OF CLINICAL RESEARCH 354, 354 (Ezekiel J. Emmanuel, Robert A. Crouch, John D. Arras, Jonathan D. Moreno & Christine Grady eds., 2003). It might be argued that offering incapacitated persons greater access to health care in exchange for enrolling in research would constitute an "undue inducement." A possible response to this argument is that concerns about undue inducement are unwarranted as long as the risks of a study are not excessive. As Ezekiel Emanuel argues, "[u]ndue inducement is when we offer people goods to assume clearly excessive and unreasonable risks."
218. Ezekiel J. Emanuel, Undue Inducement: Nonsense on Stilts? AM. J. BIOETHICS, Sept/Oct. 2005, at 9, 11 (emphasis in original).
219. In addition, to the extent that the concern with undue inducement is that it compromises the voluntariness of an individual's decision to enroll in research, see, e.g., Harold Y. Vanderpool, A Quartet of Criticisms, AM. J. BIOETHICS, Sept/Oct. 2005, at 16, 17, this concern is attenuated in studies in which consent is provided by a surrogate. In research with competent persons, establishing the voluntariness of the subject's decision is critical because the main justification for exposing competent persons to risks is that they have voluntarily agreed to assume them. See supra text accompanying notes 74-76. By contrast, under the proposed framework, the acceptability of research with incapacitated persons depends less on the surrogate's motivations for consenting and more on characteristics of the study itself - specifically, whether it fits within a policy that provides a net benefit to incapacitated people. Because the surrogate's reasons for consenting do not determine the ethical acceptability of the research, there is less reason to be concerned about the "purity" of the surrogate's choice.
220. "High risk" should be defined as "more than a minor increase over minimal risk," the standard used in the existing federal regulations on research with children. See 45 C.F.R. § 46.406 (2008). A "minor increase" is by definition "minor," and preventing this minor increase could exclude many important types of research, such as studies involving brain imaging. See supra text accompanying notes 58-59.
221. NYSAWG REPORT, supra note 111, at 32-33. By contrast, NBAC would allow surrogate consent to more-than-minimal-risk, no-direct-benefit research without the subject's advance authorization, provided that the study was approved by a special national panel and the subject's surrogate consents. NBAC, supra note 57, at 61.
222. See, e.g., In re Westchester County Med. Ctr., 531 N.E.2d 607, 613-14 (N.Y. 1988) (holding that clear and convincing evidence of an incapacitated person's decision to refuse life-sustaining treatment need not be in writing).
223. Ideally, the regulations would also address other issues that arise in research with incapacitated subjects, such as the process of determining incapacity.
224. See, e.g., 45 C.F.R. § 46.407 (2008) (requiring the approval of a national board for pediatric research that would otherwise not be approved under the regulatory standards).
225. Cf. Rosamond Rhodes, Rethinking Research Ethics, AM. J. BIOETHICS, Jan./Feb. 2005, at 7, 15 (aruging that all people should be required to perform "periodic service as research subjects," and suggesting that "[t]o withhold endorsement from such a policy would be taking advantage of the kindness of others - that is, being a free-rider on the system and failing to recognize the moral equality of others").
226. See Dresser, supra note 60, at 27.
227. NBAC REPORT, supra note 57, at 44.
228. See supra text accompanying notes 173-79.
229. See Nancy M.P. King, Defining and Describing Benefit Appropriately in Clinical Trials, 28 J.L. MED. & ETHICS 332, 334 (2000) ("When benefit cannot reasonably be expected, the consent form should say, '[Y]ou will not benefit.'").
230. See supra text accompanying notes 33-40.
231. See supra text accompanying notes 46-50.
232. See supra text accompanying notes 205-06.