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The Revised Common Rule and Mental Illness: Enduring Gaps in Protections

Published online by Cambridge University Press:  27 January 2021

Lisa E. Smilan
Lisa E. Smilan*
Affiliation:
Institute of Law, Psychiatry, and Public Policy, University of Virginia, Charlottesville, VA; George Washington University Law School, Washington, D.C.; University of Maryland Francis King Carey School of Law, Baltimore, MD; National Institutes of Health Intramural Institutional Review Board, Bethesda, MD
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American Journal of Law & Medicine , Volume 46 , Issue 4 , November 2020 , pp. 413 - 444
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Copyright © American Society of Law, Medicine & Ethics and Boston University 2020

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References

1 New research in the field of psychiatric genetics and neuroscience may yield valuable discoveries that potentially could lead to better treatments or cures. There is substantial interest in controversial experimentation, such as gene editing and deep brain stimulation, to explore possible treatments and/or cures for mental illness. See, e.g., Foulkes, Alexandra L. et al., Legal and Ethical Implications of CRISPR Applications in Psychiatry, 97 N.C. L. Rev. 1359, 1376 (2019)Google Scholar; Lawrence, Ryan E. et al., Patients’ Beliefs About Deep Brain Stimulation for Treatment-Resistant Depression, 9 Am. J. Bioethics Neuroscience 210, 210 (2018)Google Scholar. The Author’s future work will explore the need for additional human subjects research protections for mentally ill subjects (and their broader community) in genetics and genomics research, and the off-label use of gene-editing biotechnology in the practice of medicine. This Article focuses on current problems in the interpretation and application of revised federal regulations in the context of mentally ill participants in biomedical research. The words “subject” and “participant” are used interchangeably.

2 Decisively defining “mental illness” is no easy task. “Identifying what counts as a mental illness seems to require some understanding of what counts as mental health, and this may in turn depend on some conception of normal or acceptable behavior, moods, and thought patterns. Thus, an understanding of mental illness is not merely descriptive of actual behavior; it is also prescriptive of what healthy behavior actually is.” Gary E. Jones & Joseph P. Demarco, Bioethics in Context 416 (2016); see also Patient Care & Health Information: Diseases & Conditions: Mental Illness: Symptoms & Causes, Mayo Clinic, https://www.mayoclinic.org/diseases-conditions/mental-illness/symptoms-causes/syc-20374968 [https://perma.cc/7NAQ-AVM3] (The Mayo Clinic describes mental illness as “a wide range of mental health conditions—disorders that affect your mood, thinking and behavior. Examples of mental illness include depression, anxiety disorders, schizophrenia, eating disorders and addictive behaviors.”). Note, too, that there is now a small sector of the community moving to embrace “mental illness” as a part of one’s identity, critical of the extent to which psychiatry has pathologized “madness” and challenging “the tendency to adopt, too readily, the (medical) view that madness is inherently disabling.” See., e.g., Rashed, Mohammed Abouelleil, In Defense of Madness: The Problem of Disability, 44 J. Med. & Phil. 150, 152, 165 (2019).Google ScholarPubMed

3 For example, see Buck v. Bell, 274 U.S. 200, 207 (1927), an antiquated U.S. Supreme Court decision (never overturned and still “good law” in the United States) that wholeheartedly embraced systemic disregard of the human rights and dignity of people allegedly afflicted with mental illness. The Court gave its stamp of approval to the medical establishment’s abuse of “imbeciles” or “mental defectives.” Id. Specifically, in this case Justice Holmes upheld a Virginia eugenic sterilization statute and stated that “three generations of imbeciles” are enough, allowing sterilization of an allegedly mentally ill woman whose mother and daughter also had been designated mentally defective. Id. For a detailed overview and analysis of the case, the widely accepted historical abuse of persons with mental illness, and the machinations of the eugenics movement, see Paul A. Lombardo, Three Generations, No Imbeciles: Eugenics, the Supreme Court, and Buck V. Bell (2008).

4 For a critical report and overview of this research study, see State of Minn. Off. of the Legis. Auditor, A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case Special Review 5-7 (2015).

5 Id. at 7.

6 Id. at 9-10, 17, 19.

7 As early as 1997, Carl Elliott sounded the alarm that we must consider that “depression often leaves a patient’s cognitive abilities intact,” but frequently changes their values, thoughts and behaviors, and also may make them less concerned about potential risks of harm to themselves from research. Elliott, Carl, Caring About Risks: Are Severely Depressed Patients Competent to Consent to Research?, 54 Archives Gen. Psychiatry 113, 113 (1997)CrossRefGoogle Scholar. Elliott noted that if his hypothesis is correct, institutional review boards must be charged with taking “special precautions in allowing researchers to enroll depressed patients in research protocols.” Id. at 114.

8 DuBois, James et al., Restoring Balance: A Consensus Statement on the Protection of Vulnerable Research Participants, 102 Am. J. Pub. Health 2220, 2224 (2012).CrossRefGoogle ScholarPubMed

9 See Revised Common Rule, 45 C.F.R. § 46 (2019).

10 See Lajoie, Corinne et al., The Concept of Vulnerability in Mental Health Research: A Mixed Methods Study on Researcher Perspectives, 15 J. Empirical Res. on Hum. Res. Ethics 128, 138 (2020)CrossRefGoogle Scholar [hereinafter Lajoie et al., Concept of Vulnerability].

11 Paul S. Appelbaum & Thomas Grisso, Macarthur Competence Assessment Tool for Clinical Research (MACCAT-CR) iii (2001). The MacCAT-CR is a tool used for assessing a potential participant’s capacity to consent to clinical research participation, and focuses on the concepts of understanding, appreciation, reasoning, and ability to express a choice. Id. at 1. Notably, in one study severely depressed patients were shown to do remarkably well on the MacCAT-CR, most receiving “perfect or near-perfect scores.” Fisher, Carl Erik et al., The Ethics of Research on Deep Brain Stimulation for Depression: Decisional Capacity and Therapeutic Misconception, 1265 Annals of N.Y. Acad. Sci. 69, 74 (2012)CrossRefGoogle ScholarPubMed. The study authors argued that “[g]iven the consistency of these findings, the research community should consider whether most individuals with psychiatric disorders are actually as vulnerable to decisional impairments as they are commonly portrayed, or if such concerns might instead be a reflection of the widespread stigma and prejudice against psychiatric disorders.” Id. The fact that severely depressed patients consistently do well on a test for capacity to consent to research could also indicate that this type of capacity assessment is not the best means for detecting potential vulnerabilities in this population.

12 Link, Bruce G. et al., Stigma as a Barrier to Recovery: The Consequences of Stigma for the Self-Esteem of People with Mental Illnesses, 52 Psychiatric Servs. 1621, 1623 (2001).CrossRefGoogle ScholarPubMed

13 Phelan, Jo C. & Link, Bruce G., Fear of People with Mental Illnesses: The Role of Personal and Impersonal Contact and Exposure to Threat or Harm, 45 J. Health Soc. Behav. 68, 79 (2004).CrossRefGoogle ScholarPubMed

14 Brouwers, Evelien P. M., Social Stigma Is an Underestimated Contributing Factor to Unemployment in People with Mental Illness or Mental Health Issues: Position Paper and Future Directions, 8 BMC Psychol., no. 38, 2020CrossRefGoogle ScholarPubMed, at 1, 4.

15 Fortuna, Karen L. et al., Unmet Needs of People with Serious Mental Illness: Perspectives from Certified Peer Specialists, 90 Psychiatric Q. 579, 582-83 (2019CrossRefGoogle ScholarPubMed); see also, Wright, Eric R. et al., Stigma and the Sexual Isolation of People with Serious Mental Illness, 54 Soc. Probs. 78, 79 (2007).CrossRefGoogle Scholar

16 Lerner, Debra et al., Unemployment, Job Retention, and Productivity Loss Among Employees with Depression, 55 Psychiatric Servs. 1371, 1371 (2004)CrossRefGoogle ScholarPubMed; see also, Brouwers, supra note 14, at 4.

17 Sylvestre, John et al., Poverty and Serious Mental Illness: Toward Action on a Seemingly Intractable Problem, 61 Am. J. Community Psychol. 153, 156 (2018).CrossRefGoogle ScholarPubMed

18 Nugent, Allison C. et al., The Ethics of Clinical Trials Research in Severe Mood Disorders, 31 Bioethics 443, 451 (2017).CrossRefGoogle ScholarPubMed

19 See Elliot, supra note 7, at 115; Smilan, Lisa E., The Off-Label Loophole in the Psychopharmacologic Setting: Prescription of Antipsychotic Drugs in the Nonpsychotic Patient Population, 30 Health Matrix: J. L. Med. 233, 273, 302 (2020).Google Scholar On this point, however, it is important to recognize the heterogeneity among mental illnesses, how they affect those who live with them, and the effects of medications on specific illnesses. Jeste, Dilip V. & Saks, Elyn, Decisional Capacity in Mental Illness and Substance Use Disorders: Empirical Database and Policy Implications, 24 Behav. Sci. L. 607, 607 (2006).CrossRefGoogle ScholarPubMed For example, one could argue that a person who suffers from schizophrenia will have their authentic self restored with the aid of antipsychotic medication, whereas, a person without psychotic symptoms but taking an antipsychotic may lose their authentic self to the medication. See Thompson, Jemima et al., Experiences of Taking Neuroleptic Medication and Impacts on Symptoms, Sense of Self and Agency: A Systematic Review and Thematic Synthesis of Qualitative Data, 55 Soc. Psychiatry & Psychiatric Epidemiology 151, 161 (2020).CrossRefGoogle ScholarPubMed

20 Wendler, David, A Pragmatic Analysis of Vulnerability in Clinical Research, 31 Bioethics 515, 517 (2017).CrossRefGoogle ScholarPubMed

21 See Boulicault, Marion & Brown, Timothy Emmanuel, How Relationships Matter: The Need for Closer Attention to Relationality in Neuroethical Studies, 9 AM. J. Bioethics Neuroscience 235, 235 (2018)Google Scholar. The authors of this article used the term “power-relational vulnerability” to describe “the vulnerability a research participant experiences as a result of asymmetrical power relations existing between investigators and participants.” Id. Laura Weiss Roberts also warned about how “[t]he relationship with the caregiver or researcher … may have carefully hidden coercive influences that may be present, for example, when multiple roles or overlapping relationships exist.” Roberts, Laura Weiss, Informed Consent and the Capacity for Voluntarism, 159 Am. J. Psychiatry 705, 709 (2002).CrossRefGoogle ScholarPubMed This is especially an issue today where clinical trials are sometimes carried out through individual healthcare providers in their offices, in addition to treatment. See, e.g., Fisher, Jill A. & Kalbaugh, Corey A., United States Private-Sector Physicians and Pharmaceutical Contract Research: A Qualitative Study, 9 PLos Med., no. 7, 2012CrossRefGoogle ScholarPubMed, at 2, https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1001271 [https://perma.cc/PW9N-AQ52] (discussing clinical research conducted in physicians’ offices).

22 See, e.g., Robinson, Patrick et al., Measuring Attitudes Towards Mental Health Using Social Media: Investigating Stigma and Trivialisation, 54 SOC. PSYCHIATRY & PSYCHIATRIC EPIDEMIOLOGY 51, 51 (2019)CrossRefGoogle ScholarPubMed (finding stigma in regards to mental health is a significant barrier for early diagnosis and treatment); Yokoya, Shoji et al., A Brief Survey of Public Knowledge and Stigma Towards Depression, 10 J. CLINICAL MED. RES. 202, 202 (2018)CrossRefGoogle ScholarPubMed (finding that thirty percent of participants in the survey had the stigmatizing belief that a weak personality causes depression).

23 See, e.g., Noble, John H. Jr. & Sharav, Vera Hassner, Protecting People with Decisional Impairments and Legal Incapacity Against Biomedical Research Abuse, 18 J. Disability Pol’y Stud. 230, 230 (2008)CrossRefGoogle Scholar; see also, State of Minn. Off. of the Legis. Auditor, supra note 4, at 2.

24 Many scholars and researchers alike seem to find it repugnant to even consider saying that all mentally ill people are likely to be vulnerable to coercion or undue influence due to their mental illness. See Nugent et al., supra note 18, at 447 (“Indeed, we would argue that formally classifying those with mood disorders as a vulnerable population could potentially contribute to stigma and devalue the societal contributions made by these individuals.”); see also, Lajoie et al., Concept of Vulnerability, supra note 10, at 140. Why this is so offensive to these professionals, most of whom presumably are not members of this community, is unclear. While some in this patient population may argue that their mental differences are not an illness, it is fair to say that people who are mentally ill generally are considered to be ill, and mental illnesses specifically target the mind—where emotion, thought and information processing are regulated (or not). (Interestingly, for decades few in biomedical ethics, health policy or law balked at the notion that all pregnant women are vulnerable in research. See Mastroianni, Anna C. et al., The Pathway Forward: Insights on Factors that Facilitate Research with Pregnant Women, 42 Ethics & Hum. Res. 2, 2-3 (2020).CrossRefGoogle ScholarPubMed). A recent study explored perspectives of individuals living with mental illness on the word “vulnerable.” Lajoie, Corinne et al., Enriching Our Understanding of Vulnerability Through the Experiences and Perspectives of Individuals Living with Mental Illness, 26 Accountability in Res. 439, 439 (2019)CrossRefGoogle ScholarPubMed [hereinafter Lajoie et al., Enriching our Understanding]. While some participants had some objections to the word “vulnerable” as a label for all individuals living with mental illness, id. at 449, some interesting revelations included that “being called vulnerable can be upsetting, but it ultimately holds some truth and is ‘something that’s really not inaccurate,’” id. at 451, and “I find [the term ‘vulnerability’] absolutely correct and accurate. It says what it says.” Id. at 447. Another participant “thought that the use of the term ‘vulnerable’ to designate individuals living with mental illness was ‘sensitive’ and … seemed like ‘an appropriate term’ …. [S]he [did not] think that using the term in research contexts is stigmatizing given that it’s not ‘a public label’ or something that others outside this context might find out about.” Id. at 449. She viewed the term “vulnerable” as neither insulting nor stigmatizing. Id.

25 As applied in practice, “decision-making-capacity” as the catch-all category for vulnerability to coercion or undue influence in the context of mental illness precludes a broader understanding of mental illness vulnerabilities (even if this was not the intent of those who drafted the Revised Common Rule).

26 People with severe intellectual disabilities are also excluded here, as the assumption is that these individuals at no point possessed decision-making capacity required to consent to research. If abided by, the Common Rule and rCR should provide adequate protections for these individuals, as well as those who are experiencing active psychosis. See Common Rule, 45 C.F.R. § 46 (1991); Revised Common Rule, 45 C.F.R. § 46 (2019). Involuntarily institutionalized people also should be protected under the existing rules, because of the inherently coercive nature of that environment and the relationship between institutionalized patient and mental health provider. Extant literature addresses involuntarily institutionalized individuals in clinical research. See, e.g., Nat’l Comm’n for the Prot. of Hum. Subjects of Biomedical and Behav. Rsch., Research Involving those Institutionalized as Mentally Infirm (1978).

27 For a detailed overview of concerns and debates, see Bonnie, Richard J., Research with Cognitively Impaired Subjects: Unfinished Business in the Regulation of Human Research, 54 Arch. Gen. Psychiatry 105 (1997).CrossRefGoogle ScholarPubMed

28 45 C.F.R. § 46 (1991).

29 Common notions of “mental disability” bring to mind persons with lower IQs, congenital brain abnormalities or traumatic brain injuries. However, there could be near-genius individuals who suffer from bipolar disorder or major depressive disorder, for example, who may be vulnerable at certain times and under certain circumstances, not due to an inability to think but due to effects the mental illness (and, perhaps, medications used to treat the illness) has on their brains and true selves.

30 Elisa Eiseman, Nat’l Bioethics Advisory Comm’n, Contributing to Public Policy 43 (2003). “NBAC’s first task was to determine whether there were any important gaps in laws, regulations, guidelines, and practices and then to determine how to plug them.” Childress, James F., An Introduction to NBAC’s Report on Research Involving Persons with Mental Disorders that May Affect Decisionmaking Capacity, 7 Accountability Res. 101, 104 (1999)CrossRefGoogle ScholarPubMed.

31 Nat’l Bioethics Advisory Comm’n, Research Involving Persons with Mental Disorders that may Affect Decisionmaking Capacity (1998).

32 See id. at 5.

33 Id. at iii, 53.

34 Id. (emphasis added). Where the IRB ordinarily does not address protocols involving potential subjects who suffer from a “mental disorder,” NBAC recommended that the IRB’s discussion should include “two ad hoc consultants who are familiar with the nature of these disorders and with the concerns of the population being studied; at least one of these consultants should be a member of the population being studied, a family member of such a person, or a representative of an advocacy organization for this population.” Id. (emphasis added).

35 David B. Resnik, The Ethics of Research with Human Subjects 218, 227 (2018).Google Scholar

36 Resnik points to the diversity within populations living with mental disability or mental illness that makes it not necessarily appropriate to put them in categories: “[S]ome mentally ill or disabled adults may have good decision-making abilities, while others may not. Also, some may be able to make decisions under certain conditions … but not [under] others.” Id. at 227.

37 Revised Common Rule, 45 C.F.R. § 46 (2019).

38 Id. §§ 46.107, 46.111.

39 See infra Part IV.

40 See Protection of Human Subjects, 38 Fed. Reg. 31,738, 31,738 (proposed Nov. 16, 1973). For a full discussion, see Hoffmann, Diane E. et al., Regulating Research with Decisionally Impaired Individuals: Are We Making Progress?, 3 DePaul J. Health Care L. 547, 551-556 (2000).Google ScholarPubMed

41 Common Rule, 45 C.F.R. §§ 46.107, 46.111 (1991).

42 See 45 C.F.R. § 46 (1991).

43 Americans with Disabilities Act, Pub. L. 101-336, § 3, 104 Stat. 327, 330 (1990) (codified as amended at 42 U.S.C. § 12102(1)(A) (2012)).

44 See, e.g., Petrila, John & Brink, Thomas, Mental Illness and Changing Definitions of Disability Under the Americans with Disabilities Act, 52 Psychiatric Servs. 626, 626 (2005)CrossRefGoogle Scholar (discussing the relationship between the definition of disability and mental impairment, including organic brain syndrome and learning disabilities); Research and Training Ctr. on Indep. Living, Guidelines for Writing and Reporting About People with Disabilities (6th ed. 2001) (listing cognitive impairment, learning disability, and more as categories of mental disability).

45 Revised Common Rule, 45 CFR §§ 46.107(a), 46.107(e) (2018), WL 45 CFR § 46.107 (showing Westlaw comparison of version effective until July 18, 2018 and current version effective July 19, 2018). Other relevant changes in the Revised Common Rule, regarding criteria for IRB approval of research with potentially vulnerable subjects are:

§ 46.111 Criteria for IRB approval of research.

  • (a) In order to approve research covered by this policy the IRB shall determine that all of the following requirements are satisfied:

    ….

    (3) Selection of subjects is equitable. In making this assessment the IRB should take into account the purposes of the research and the setting in which the research will be conducted and. The IRB should be particularly cognizant of the special problems of research involving that involves a category of subjects who are vulnerable populations to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled personsindividuals with impaired decision-making capacity, or economically or educationally disadvantaged persons.

    ….

  • (b) When some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled personsindividuals with impaired decision-making capacity, or economically or educationally disadvantaged persons, additional safeguards have been included in the study to protect the rights and welfare of these subjects.

45 C.F.R. §§ 46.111(a)(3), 46.111(b) (2018), WL 45 CFR § 46.111 (italics added) (showing Westlaw comparison of version effective until July 18, 2018 and current version effective July 19, 2018).

46 Compare 45 C.F.R. §§ 46.107, 46.111 (1991) (omitting those with “impaired decision-making capacity” as an example of individuals vulnerable to coercion or undue influence), with 45 C.F.R. §§ 46.107, 46.111 (2019) (including those with “impaired decision-making capacity as an example of individuals vulnerable to coercion or undue influence).

47 See 45 C.F.R. § 46 (2019).

48 In the Preamble to the final revised rule, HHS stated that it was using “‘individuals with impaired decisionmaking ability’ to replace the term ‘mentally disabled persons.’” Federal Policy for the Protection of Human Subjects, 82 Fed. Reg. 7,149, 7,204 (Jan. 19, 2017) (to be codified at 45 C.F.R. pt. 46). HHS stated that some public comments had argued that the term “mentally disabled” was “potentially patronizing.” Id. One comment had suggested the use of the term “populations with impaired decision making ability” to replace the term “mentally disabled,” and HHS adopted this new language and incorporated it in the revised rule. Id. Note, too, that HHS stated that the Secretary’s Advisory Committee on Human Research Protections (SACHRP) suggested in 2009 the use of the phrase “impaired decisionmaking capacity,” but it is not stated what it was to replace or what categories of subjects it should include. See id. (citing SACHRP, Recommendations Regarding Research Involving Individuals with Impaired Decision-Making, U.S. Department of Health and Human Services (July 15, 2009), https://www.hhs.gov/ohrp/sachrp-committee/recommendations/2009-july-15-letter-attachment/index.html [https://perma.cc/MGZ7-WGUJ]); see also Elisa A. Hurley, From the Director: “Vulnerability” in the Revised Common Rule, Amp&rsand: The PRIM&R Blog (Sept. 12, 2017), https://blog.primr.org/vulnerability-revised-common-rule/ [https://perma.cc/Q2ZR-FX3J]. IRBs are tasked with delineating the concept of “impaired decisionmaking capacity” on a protocol-by-protocol basis.

49 45 C.F.R. § 46.111(b) (2019).

50 See, e.g., Appelbaum, Paul S. et al., Competence of Depressed Patients for Consent to Research, 156 Am. J. Psychiatry 1380, 1381 (1999)Google Scholar; Fields, Lindy Marie & Calvert, James Douglas, Informed Consent Procedures with Cognitively Impaired Patients: A Review of Ethics and Best Practices, 69 Psychiatry & Clinical Neurosciences 462, 469 (2015)CrossRefGoogle ScholarPubMed; MacFarlane, Gordon et al., Proposed Guidelines for the Protection of Vulnerable Subjects in Clinical Trials: Protections for Decisionally Impaired Subjects, 10 Clinical Ethics 59, 60 (2015)CrossRefGoogle Scholar; Morian-Sanchez, Ines et al., Assessment of Capacity to Consent to Research Among Psychiatric Outpatients: Prevalence and Associated Factors, 87 Psychiatric Q. 89, 90 (2016)CrossRefGoogle Scholar; Spike, Jeffrey P., Informed Consent is the Essence of Capacity Assessment, 45 J.L. Med. & Ethics 95, 95 (2017)CrossRefGoogle ScholarPubMed; Yanos, Phillip et al., Research Risk for Persons with Psychiatric Disorders: A Decisional Framework to Meet the Ethical Challenge, 60 Psychiatric Servs. 374, 376 (2009).CrossRefGoogle ScholarPubMed

51 45 C.F.R. §§ 46.107(a), 46.111 (1991); 45 C.F.R. §§ 46.107(a), 46.111 (2019).

52 Yes, some people with mental illness have impaired decision-making capacity. Many more, especially those with major depressive disorder, may score well in capacity assessments, see Fisher, supra note 11, at 74, but be vulnerable to coercion or undue influence for other reasons related to their mental illnesses and treatments. While many scholars and researchers argue that it is harmful to put all people with mental illness in one bucket (assuming that they all are vulnerable to coercion or undue influence), surely it is just as harmful to exclude many mentally ill people from the bucket because they happen to be able to provide reasonable and rational answers to questions, even if those answers do not reflect their true values, opinions and judgments.

53 See RESNIK, supra note 35, at 219-220; Yanos et al., supra note 50, at 377.

54 45 C.F.R. §§ 46.107(a), 46.111 (2019).

55 Id.; RESNICK, supra note 35, at 217-20.

56 45 C.F.R. §§ 46.107(a), 46.111 (2019).

57 See, e.g., Yanos et al., supra note 50, at 376 (recognizing the concept of vulnerability as broad despite focusing on only two interpretations during research).

58 See, e.g., Fisher et al., supra note 11, at 74.

59 Elliott, supra note 7, at 115.

60 Roberts, supra note 21, at 706.

61 Nugent et al., supra note 18, at 443.

62 Lawrence et al., supra note 1, at 215-16 (citing Am. Psychiatric Ass’n, Diagnostic and Statistical Manual of Mental Disorders (5th ed. 2013)); see also Bell, Emily et al., Beyond Consent in Research: Revisiting Vulnerability in Deep Brain Stimulation for Psychiatric Disorders, 23 Cambridge Q. Healthcare Ethics 361, 362-63 (2014)CrossRefGoogle ScholarPubMed (examining vulnerability and consent of patients diagnosed with major depression in deep brain stimulation trials).

63 Elliott, supra note 7, at 115.

64 Lawrence et al., supra note 1, at 216. Clouded judgment should qualify as impaired decision-making, but as the regulation is applied, most likely it would not because such nuances would not be picked up in the traditional capacity assessment. As long as the subject was agreeing to participate in the research, this likely would be assumed by the researcher to be a reasonable and rational decision, even if it differed from the subject’s prior beliefs (unknown to the researcher), e.g., that participating in research is a very bad idea. Some scholars have advocated in the clinical care setting that current assessments of capacity miss many aspects of how mental illness potentially changes one’s choices. See Goldberg, Aryeh L., How Bioethics and Case Law Diverge in Assessments of Mental Capacity: An Argument for a Narrative Coherence Standard, 11 Am. J. Bioethics Neuroscience 7, 8-9 (2020)Google ScholarPubMed; see also Smilan, Lisa E. & Conklin, David S., With NCS, the Clinician May Get Stuck in the Past or Lost in the Present, 11 Am. J. Bioethics Neuroscience 33, 34 (2020)Google ScholarPubMed. Additionally, some might argue that participation in potentially risky biomedical research is a “major life choice.” Lawrence et al., supra note 1, at 216.

65 See Smilan, The Off-Label Loophole, supra note 19, at 267 n.181, 268. The Author recognizes that there is great variability in mental illnesses and their treatment. While one medication, e.g., an antipsychotic, might alter the true self of the non-psychotic patient, that same medication may restore the true self of someone experiencing a “psychotic break” associated with bipolar disorder. See id. at 294.

66 See Fortuna, supra note 15, at 579.

67 See Corinne Lajoie et al., Lived Experiences of Participation in Mental Health Research in Canada: Breaking the Glass Wall, Disability & Society, Oct. 14, 2020, at 13, 18 [hereinafter Lajoie et al., Lived Experiences], https://www.tandfonline.com/doi/abs/10.1080/09687599.2020.1833313 [https://perma.cc/5JNK-Z9H7] (describing how mental health research participants expressed that their participation fostered a sense of involvement and belonging in society, making them feel “important, valued, and listened to,” believed, recognized, and helpful). Such recognition and validation “is especially meaningful for individuals who have historically been ignored and silenced.” Id. at 14.

68 Roberts, supra note 21, at 709.

69 RESNIK, supra note 35, at 228 (citing Nat’l Bioethics Advisory Comm’n, supra note 31, at iv; Council for Int’l Org. of Med. Scis., International Guidelines for Biomedical Research Involving Human Subjects (3d ed. 2002); Council for Int’l Org. of Med. Scis., International Guidelines for Biomedical Research Involving Human Subjects (4th ed. 2016)). Symptoms associated with mental illnesses can give rise to an ethical quandary for the psychiatrist who “wants to support the patient’s ability to make an authentic autonomous choice [but questions] the stability of that choice.” Lawrence et al., supra note 1, at 216.

70 Biros, Michelle, Capacity, Vulnerability, and Informed Consent for Research, 46 J.L. Med. & Ethics 72, 73 (2018).CrossRefGoogle ScholarPubMed

71 See, e.g., McCradden, Melissa D. & Cusimano, Michael D., Questioning Assumptions About Vulnerability in Psychiatric Patients, 9 Am. J. Bioethics Neuroscience 221, 222 (2018)Google Scholar (“Highlighting the vulnerability of patients with psychiatric disorders should not result in limiting their ability to participate in research.”); Tekin, Şerife, Listening to Patients: A Pillar for the Epistemology of Neurointerventions, 9 Am. J. Bioethics Neuroscience 239, 239 (2018)Google Scholar (there is a “gross and paternalistic overgeneralization that individuals with depression or other mental illnesses lack the capacity to make rational decisions.”). But, arguing that those suffering from mental illness should have autonomy to make their own decisions “may [be] unintentionally undermin[ing], rather than protect[ing], the rights of seriously mentally ill patients” who lack autonomy because they cannot safely make treatment decisions “yet are often required, allowed, or left to do so.” Williams, Arthur R., Opportunities in Reform: Bioethics and Mental Health Ethics, 30 Bioethics 221, 223 (2016)CrossRefGoogle ScholarPubMed. Williams states that “[a] philosopher’s conception of an autonomous patient is predicated upon his or her own experience of reality. The absence of such perspectives within the field of bioethics undermines its ability to fully engage related content.” Id. at 224. We are not doing psychiatric patients any favors by respecting their autonomy in situations where mental illness is stripping them of the ability to truly act autonomously. Fields & Calvert, supra note 50, at 469 (“[T]he boundary between autonomy and patient protection becomes blurred when patients do not have the capacity to make informed decisions.”). This concern for patients translates to the clinical research setting as well. However, another argument weighing in favor of including potentially “vulnerable” subjects is that “[p]olicies that exclude individuals from research to protect them from harm, exploitation, or coercion/undue influence may adversely impact the health of the group to which they belong.” Resnik, supra note 35, at 233 (citing Mastroianni, Anna & Kahn, Jeffrey, Swinging on the Pendulum: Shifting Views of Justice on Human Subjects Research, 31 Hastings Ctr. Rep. 21, 25 (2001)CrossRefGoogle ScholarPubMed; David Resnik, The Price of Truth: How Money Affects the Norms of Science (2007)). Noteworthy is how in one qualitative study examining patient-participant perspectives on deep brain stimulation (DBS), where no pressure was placed to accept the intervention, patients were cautious despite their depressive symptoms and frustration with existing treatments. Lawrence et al., supra note 1, at 216. Chronically depressed subjects in this qualitative study were aware of their impaired decisionmaking abilities and would have elected to defer any decisions regarding undergoing DBS until they were feeling more stable. Id. Roberts posits, however, that “[s]uffering and pain due to … mental health problems may cause one to move toward a decision out of desperation rather than deliberateness and adherence to personal values and previous life choices.” Roberts, supra note 21, at 706.

72 See Roberts, Laura Weiss et al., Perspectives of Patients with Schizophrenia and Psychiatrists Regarding Ethically Important Aspects of Research Participation, 157 Am. J. Psychiatry 67, 68 (2000).CrossRefGoogle ScholarPubMed “[T]he nature and quality of the investigator-participant relationship may greatly influence informed consent decisions of individuals with mental illness.” Id. Roberts et al. noted that psychiatric patients were more accepting than psychiatrists of “the influence of physician investigators, personal physicians, and family members” on a patient’s decision to participate in research. Id. at 71. Yet, “psychiatrists showed much stronger support than did our participants with schizophrenia regarding the inclusion of what have been defined historically as potentially vulnerable groups.” Id. at 72. See also, Lajoie et al., Lived Experiences, supra note 67, at 13 (alteration in original) (quoting a mental health research participant’s concerns about coercion and abuse in mental health research, stating that “the first time that [someone that has never been offered acceptation, tools, and support is recognized] as a human being, they’re willing to buy into everything [the person listening to them] says or does.”).

73 See, e.g., Appelbaum & Grisso, supra note 11, at 1-2.

74 See supra notes 45-47 and accompanying text.

75 See, e.g., Fisher, supra note 11, at 74; supra note 52 and accompanying text.

76 See Nat’l Bioethics Advisory Comm’n, supra note 31, at 53 (making recommendations related to review bodies, research design, informed consent and capacity, categories of research, surrogate decision-making, and education, research, and support).

77 See Coercion, Black’s Law Dictionary (11th ed. 2019) (“Compulsion of a free agent by physical, moral, or economic force or threat of physical force.”); Undue Influence, BLACK’S LAW DICTIONARY (11th ed. 2019) (“The improper use of power or trust in a way that deprives a person of free will and substitutes another’s objective; the exercise of enough control over another person that a questioned act by this person would not have otherwise been performed, the person’s free agency having been overmastered.”).

78 The words “vulnerable” and “vulnerability” are not found in the widely accepted authority on legal definitions, Black’s Law Dictionary. See Black’s Law Dictionary (11th ed. 2019) (failing to include “vulnerable” or “vulnerability”).

79 See Common Rule, 45 C.F.R. § 46.102 (1991); Revised Common Rule, 45 C.F.R., § 46.102 (2019).

80 Klitzman, Robert, How IRBs View and Make Decisions About Coercion and Undue Influence, 39 J. Med. Ethics 224, 226 (2013)CrossRefGoogle ScholarPubMed; see also, Fisher, Jill A., Expanding the Frame of “Voluntariness” in Informed Consent: Structural Coercion and the Power of Social and Economic Context, 23 Kennedy Inst. Ethics J. 355, 370 n.4 (2013).CrossRefGoogle ScholarPubMed

81 Fisher, supra note 80, at 369.

82 See Informed Consent FAQs, Off. for Hum. Res. Protections, U.S. Dep’t Health & Hum. Servs., https://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/informed-consent/index.html [https://perma.cc/QKG2-T43X].

83 Id. This is consistent with the legal definition: Coercion “may be actual, direct, or positive, as where physical force is used to compel act against one’s will, or implied, legal or constructive, as where one party is constrained by subjugation to other to do what his free will would refuse” and in the context of criminal law, coercion “can be mental as well as physical.” Coercion, Black’s Law Dictionary (5th ed. 1979). Note that the Belmont Report, the 1979 report by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, describes that coercion is present in instances where “an overt threat of harm is intentionally presented by one person to another in order to obtain compliance” and does not discuss implicit threats. Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 44 Fed. Reg. 23, 192, 23,195 (Apr. 18, 1979).

84 See Fisher, supra note 80, at 363-64.

85 Id. at 360.

86 Id. at 359.

87 Id. at 360.

88 Id. at 363-64.

89 See id. at 365 (noting how Phase I investigational drug studies often pay thousands of dollars to participants, who view the money as a way to support themselves and their families)..

90 See Fisher, supra note 80, at 364 (“What is often characterized by researchers and ethics scholars as participants’ ‘desperation’ can influence people’s perspectives that a clinical study is their only chance for an effective therapy or needed income.”); see also Lajoie et al., Lived Experiences, supra note 67, at 6, 8 (describing testimony of one mental health research participant who explained that “participating in research studies helped her financially and made her feel helpful to society,” and another who expressed that the financial compensation contributed to her decision to participate in research, along with the belief that participation would help her by getting her “mind off other things,” in addition to making her feel valued and important).

91 This brings to mind the friendship and sense of community at Miss Rivers’ Lodge, where the nurse who played a central role in the Tuskegee syphilis study continued friendships with study subjects for decades. See Reverby, Susan M., Rethinking the Tuskegee Syphilis Study: Nurse Rivers, Silence and the Meaning of Treatment, 7 Nursing Hist. Rev. 3, 18 (1999).CrossRefGoogle ScholarPubMed

92 Off. for Hum. Res. Protections, U.S. Dep’t Health & Hum. Servs., supra note 82. The Belmont Report describes “undue influence” as such: undue influence “occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture in order to obtain compliance. Also, inducements that would ordinarily be acceptable may become undue influences if the subject is especially vulnerable. … [I]t is impossible to state precisely where justifiable persuasion ends and undue influence begins. But undue influence would include actions such as manipulating a person’s choice through the controlling influence of a close relative and threating to withdraw health services to which an individual would otherwise be entitled.” Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 44 Fed. Reg. 23,192, 23,195 (Apr. 18, 1979). It logically would follow that manipulating a person’s choice through the controlling influence of the psychiatrist-researcher on the patient-subject would likewise be an undue influence. This should be an expected possibility in the context of research with psychiatric patients.

93 Off. for Hum. Res. Protections, U.S. Dep’t Health & Hum. Servs., supra note 82. “Undue influence” has been defined as: “Any improper or wrongful constraint, machination, or urgency of persuasion whereby the will of a person is overpowered and he is induced to do or forbear an act which he would not do or would do if left to act freely. Influence which deprives person influenced of free agency or destroys freedom of his will and renders it more the will of another than his own. Misuse of position of confidence or taking advantage of a person’s weakness, infirmity, or distress to change improperly that person’s actions or decisions.” Undue Influence, Black’s Law Dictionary (5th ed. 1979).

94 See Fisher, supra note 80, at 357.

95 Bracken-Roche, Dearbhail et al., The Concept of ‘Vulnerability’ in Research Ethics: An In-Depth Analysis of Policies and Guidelines, 15 Health Res. Pol’y & Sys., no. 8, 2017CrossRefGoogle ScholarPubMed, at 16; see also, Nugent et al., supra note 18, at 444 (“We would hypothesize that mood disorders may make potential research participants perceive non-coercive external forces (for instance, a doctor’s non-threatening recommendation) as influential in a way that is difficult to resist (due to, for example, loss of confidence in one’s own opinions if they differ from those of a trusted authority figure’s).”).

96 See Nugent et al., supra note 18, at 444.

97 Lawrence et al., supra note 1, at 214.

98 See supra note 71 and accompanying text (discussing voluntarism); infra note 157 and accompanying text (discussing “autonomous consent”); see also Roberts, supra note 21, at 706.

99 Martens, Hannah Skye & Brown, Timothy Emmanuel, Trusting Oneself and Others: Relational Vulnerability and DBS for Depression, 9 Am. J. Bioethics Neuroscience 226, 227 (2018)Google Scholar (noting that in order to be complete, scholars’ analyses of relationship vulnerability should consider one’s relationship to oneself).

100 Id. (quoting Carolyn McLeod & Susan Sherwin, Relational Autonomy, Self-Trust, and Health Care for Patients Who are Oppressed, in Relational Autonomy: Feminist Perspectives on Autonomy, Agency, and the Social Self 259, 262 (Catriona MacKenzie & Natalie Stoljar eds., 2000) (citation omitted)).

101 Id.

102 See Smilan, supra note 19, at 303-04 (noting that psychotropic medications sedate and control patient behaviors, often with “life-altering chronic and irreversible side effects”). Nugent et al. note that “[i]nformed consent requires that decisional autonomy not be compromised by either external and potentially coercive forces, or by internal forces resulting from the illness or impairment.” Nugent et al., supra note 18, at 444 (emphasis added).

103 See Elliott, supra note 7, at 114 (noting that an actor’s emotional state may impair his decision-making and render him incompetent to consent to treatment).

104 Revised Common Rule, 45 C.F.R. § 46.107 (2019) (recommending inclusion of persons who are knowledgeable about and experienced in working with vulnerable subjects); Common Rule, 45 C.F.R. § 46.107 (1991).

105 45 C.F.R. § 46.111(a)(3) (2019) (advising researchers to account for the purpose and setting of the research when selecting subjects); 45 C.F.R. § 46.111(a)(3) (1991).

106 45 C.F.R. § 46.111(b) (2019) (requiring additional safeguards for vulnerable subjects); 45 C.F.R. § 46.111(b); see Hurley, supra note 48 (noting that beyond the circumstances of enrollment, also important is how subjects are treated throughout the research process).

107 Bracken-Roche et al., supra note 95, at 15.

108 See Hurley, supra note 48 (noting that exploitation, excessive risks, and exclusion are types of vulnerability in research beyond coercion and undue influence). If anything, language in the rCR seems to yield even more discretion to IRB members than did the original rule by requiring judgments on the scope and parameters of “impaired decision-making capacity,” with no direction on implementation. See 45 C.F.R. § 46 (2019) (requiring special protections for persons with “impaired decision-making capacity” without defining this term).

109 See, e.g., Racine, Eric & Bracken-Roche, Dearbhail, Enriching the Concept of Vulnerability in Research Ethics: An Integrative and Functional Account, 33 BIOETHICS 19, 20 (2018)CrossRefGoogle ScholarPubMed (noting that scholars struggle to agree on consistent use and understanding of vulnerability in research ethics); Wendler, supra note 20, at 520 (defining “vulnerable” according to Merriam Webster’s Dictionary, research literature, and standard English).

110 Wendler, supra note 20, at 520 (citing Kenneth Kipnis, The Limitations of “Limitations”, 4 AM. J. BIOETHICS 70, 70 (2004)); see also Racine & Bracken-Roche, supra note 109, at 20 (“[S]cholars have been advancing competing accounts of vulnerability and struggling to reach consensus about the conceptualization and operationalization of vulnerability in research ethics.”).

111 Vulnerable, MERRIAM WEBSTER DICTIONARY, https://www.merriam-webster.com/dictionary/vulnerable [https://perma.cc/Q3UB-VARA]. The words “vulnerable” and “vulnerability” do not appear in Black’s Law Dictionary. BLACK’S LAW DICTIONARY (11th ed. 2019) (defining only “vulnerable adult,” “vulnerable-adult abuse,” and “vulnerable zone”).

112 Bracken-Roche et al., supra note 95, at 16.

113 Lawrence et al., supra note 1, at 216 (citing Coulter, Andrew, Deep Brain Stimulation Research Protocols and Depressive Patients with Previous Suicidality: We Can’t Afford to Lose Focus, 4 AM. J. BIOETHICS NEUROSCIENCE 41, 41 (2013)Google Scholar).

114 See Lajoie et al., Concept of Vulnerability, supra note 10, at 140 (citing the need for further qualitative research on mental health research participants’ perspectives regarding vulnerability in mental health and views relating to possible overuse and stigmatization).

115 Bracken-Roche et al., supra note 95, at 1; see also Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 44 Fed. Reg. 23,192, 23,195 (Apr. 18, 1979).

116 Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 44 Fed. Reg. at 23,195.

117 Id. at 23,196 (“Injustice may appear in the selection of subjects, [because] even if individual subjects are selected fairly … unjust social patterns may nevertheless appear in the overall distribution of the burdens and benefits of research.”).

118 Id. at 23,197 (emphasis added).

119 Wendler, supra note 20, at 517; see also Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research, 44 Fed. Reg. at 23,196.

120 Wendler, supra note 20, at 517 (citations omitted); see also Proposed Regulations on Research Involving Those Institutionalized as Mentally Disabled, 43 Fed. Reg. 53,950, 53,950 (proposed Nov. 17, 1978) (to be codified at 45 C.F.R. pt. 46) (“[Institutionalized mentally infirm] persons by the very nature of their disabilities may not be competent to provide informed consent …. At the same time, the nature of their disabilities requires extensive research efforts to study the etiology, pathogenesis, prevention, therapy, and management of their conditions.”). This “justification” for excluding mentally ill people from heightened protections while imposing unnecessary restrictions on pregnant women is illogical if it was done in good faith, and makes perfect sense if done to perpetuate stereotypes and inequitable gender roles in the case of pregnant women and make research with mentally ill patients who lacked the wherewithal to protect themselves that much easier for researchers.

121 Wendler, supra note 20, at 517. Similarly, FDA regulations regarding criteria for IRB approval of research in the context of clinical research, state: “When some or all of the subjects, such as children, prisoners, pregnant women, handicapped, or mentally disabled persons, or economically or educationally disadvantaged persons, are likely to be vulnerable to coercion or undue influence additional safeguards have been included in the study to protect the rights and welfare of these subjects.” 21 C.F.R. § 56.111(b) (2001); see also 21 C.F.R. § 56.111(a)(3) (2001) (stating that the IRB should be cognizant of the special research problems encountered by vulnerable populations); 21 C.F.R. § 56.107(a) (1991) (requiring at least one IRB member be “primarily concerned” with the welfare of vulnerable subjects if the IRB regularly reviews research involving these populations). FDA’s regulations have not been modified by the rCR.

122 Left to the interpretations of IRB members, “mentally disabled” persons could be those suffering from brain damage, or those with congenital brain abnormalities, or those with physical ailments that affect brain functioning. See Hoffman et al., supra note 40, at 550 (“Federal regulations merely call on [IRBs] to be attentive to the need for ‘additional safeguards’ ….”). Likewise, the term could be interpreted to include those with medically diagnosed mood disorders. See Nat’l Bioethics Advisory Comm’n, supra note 31, at 1-2, 5 (finding that “mental disorders,” including mood disorders such as depression, cannot be precisely defined, yet the condition may still affect the person’s ability to give informed consent and should thus qualify persons with mental disorders for special IRB protections as vulnerable populations during moments of impairment). Outcomes of IRB determinations could thus be driven entirely by who was sitting at the IRB table that particular day at that particular research institution. See Justin T. Clapp et al., Justification and Authority in Institutional Review Board Decision Letters, Soc. Sci. & Med., Dec. 2017, at 25, 28 (finding “substantial qualitative variation in … thoroughness and apparent clarity” when examining IRB rationales for stipulating changes to proposed studies).

123 Bracken-Roche et al., supra note 95, at 1.

124 Biros, supra note 70, at 75 (citing Aldridge, Jo, Working with Vulnerable Groups in Social Research: Dilemmas by Default and Design, 14 Qualitative Res. 112, 113 (2014)CrossRefGoogle Scholar); see also, Bracken-Roche et al., supra note 95, at 2 (citing Hurst, Samia A., Vulnerability in Research and Health Care; Describing the Elephant in the Room?, 22 Bioethics 191, 195 (2008)CrossRefGoogle ScholarPubMed).

125 Bracken-Roche et al., supra note 95, at 2 (citing Luna, Florence & Vanderpoel, Sheryl, Not the Usual Suspects: Addressing Layers of Vulnerability, 27 BIOETHICS 325, 326 (2013)CrossRefGoogle ScholarPubMed).

126 Wendler, supra note 20, at 517.

127 Carl H. Coleman et al., The Ethics and Regulation of Research with Human Subjects 141-43 (2d ed. 2015) (citing 1 Nat’l Bioethics Advisory Comm’n, Ethical & Policy Issues in Research Involving Human Participants 88-89 (2001)).

128 Fields & Calvert, supra note 50, at 463-64; see also MacFarlane et al., supra note 50, at 64 (explaining temporary impairments and listing examples of such transient impairments).

129 Wendler, supra note 20, at 517. Interestingly, in a recent qualitative study, one participant living with mental illness stated that “you lose your capacity to make decisions in a sense. No, not your capacity, but it makes it harder […]. [You’re] quite vulnerable to whatever doctors will tell you you should do or your parents or your family or husband, whatever.” Lajoie et al., Enriching our Understanding, supra note 24, at 451.

130 See Bracken-Roche et al., supra note 95, at 16 (noting the capability of research environments to disempower research participants and subjects).

131 Id. at 16.

132 Wendler, supra note 20, at 519 (citing Grinnell, Frederick, Subject Vulnerability: The Precautionary Principle of Human Research, 4 Am. J. Bioethics 72, 73 (2004)CrossRefGoogle ScholarPubMed) (recognizing that all humans are vulnerable before challenging the claim and concluding that vulnerability in clinical research is comparative and context dependent).

133 Id. at 519, 522.

134 Id. at 519.

135 Id. at 524.

136 Id. at 516.

137 Id.; see also Morian-Sanchez, Luna & Perez-Carceles, supra note 50, at 102.

138 Bracken-Roche et al., supra note 95, at 10 (quoting Can. Inst. of Health Research, Nat. Scis. and Eng’g Research Council of Can., & Soc. Scis. and Humanities Research Council of Can., Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans 54 (2014) (Can.)). Here one can see the merit of arguments against naming all people with mental illness as vulnerable to coercion or undue influence.

139 DuBois et al., supra note 8, at 2222, 2224. “Labeling particular groups as at risk for lacking decisional capacity or as incapable of making a voluntary choice reinforces stigma or stereotypes, when in fact members of such groups are frequently diverse and function as well as so-called healthy volunteers.” Id. at 2222 (citations omitted).

140 Leaving some discretion to ethics oversight committees or IRBs is often a good thing; however, inconsistent practices among various research institutions receiving federal funding is indeed problematic.

141 MacFarlane et al., supra note 50, at 64; see also Racine & Bracken-Roche, supra note 109, at 20 (discussing research ethics boards in Canada, a similar challenge there “of assessing and appropriately responding to vulnerability,” and implications for potentially vulnerable research subjects that may flow from boards’ actions or inaction); Yanos et al., supra note 50, at 374 (recognizing the lack of consensus among IRBs “on how to evaluate studies in which considerations of both degree of risk and vulnerability need to be made”).

142 Though, some scholars complain that “IRB members overestimate the risk of incapacity” present in the psychiatric patient population while underestimating levels of risk for patients with medical diagnoses that are unrelated to mental illness but nonetheless may impair decisional capacity. DuBois et al., supra note 8, at 2222 (citing Luebbert, et al., IRB Member Judgments of Decisional Capacity, Coercion, and Risk in Medical and Psychiatric Studies, 3 J. Empirical Res. on Hum. Res. Ethics 15, 15 (2008))CrossRefGoogle ScholarPubMed.

143 Wendler, supra note 20, at 516.

144 Id. at 522.

145 Id. at 524 (recognizing how a contextual analysis may determine “that only some subjects are vulnerable” and “whether there are individuals for whom the general protections are not sufficient”).

146 Biros, supra note 70, at 75.

147 There are many instances that might give rise to impaired decision-making capacity: One might include a person in a comatose state after an automobile accident, another a person experiencing catatonia due to disease or infection. The category “impaired decision-making capacity” includes many potential research subjects, diluting the specific needs of and attention given those who are suffering from mental illness. See, e.g., Resnick, supra note 35, at 217-20.

148 See generally id. at 217-19 (summarizing different bioethicist’s definitions of vulnerable populations).

149 See supra Section II.C.

150 See Resnick, supra note 35, at 217-19 (recognizing the vagueness of the Common Rule and the term “vulnerability” in summarizing a non-exhaustive list of vulnerable populations).

151 See supra Section II.D.

152 Fisher, supra note 80, at 360.

153 See Elliott, supra note 7, at 114.

154 See Roberts, supra note 21, at 705.

155 Id.

156 Id. at 707.

157 See Smilan & Conklin, supra note 64, at 33-34 (using the term “autonomous consent” to highlight how true autonomy may be lacking in consent where the effects and implications of mental illness make voluntarism—a necessary component of autonomous consent—unlikely or impossible).

158 See Elliot, supra note 7, at 114-15.

159 Earlier scholarship discussed the authenticity of a mentally ill person’s actions and behaviors: “The authenticity argument supposes a person with a stable character and entrenched dispositions, who, while depressed, makes decisions so uncharacteristic that we feel bound to question whether those decisions were truly hers.” Id. at 115. The Author acknowledges that for certain severe mental illnesses, e.g., schizophrenia, it is the psychotropic medication that may elicit the true self of the psychiatric patient. See Smilan, supra note 19, at 302; Thompson et al., supra note 19, at 161.

160 Wendler, supra note 20, at 524.

161 Id.

162 Id. (emphasis added).

163 Dresser, Rebecca, Experimentation Without Representation, 40 IRB. 3, 5 (2018)CrossRefGoogle Scholar. Bracken-Roche and colleagues similarly suggest that research participants, who “seem to have been largely left out of the development of research ethics guidelines” might also be important to the process of framing vulnerability. Bracken-Roche et al., supra note 95, at 17.

164 Dresser, supra note 163, at 5. Dresser acknowledges the inherent challenges in tasking research institutions and organizations with locating and recruiting research subjects as advisors or board members who also have “the necessary contacts and background to represent” the diversity and diverse experiences of other research participants. Id. at 6. In arguing for her proposed initiative, Dresser notes that “the complex perspectives of researchers, ethicists, and members of the public are weighed and balanced in research ethics and policy deliberations. Subjects’ complex perspectives could simply be added to the mix.” Id.

165 Id. at 5.

166 Id.

167 See Cargill, Stephanie Solomon, Moving from the “Why” to the “How”: Two Approaches to Including Research Participants’ Voices, 40 IRB 8, 9 (2018).CrossRefGoogle Scholar

168 See, e.g., Yokoya et al., supra note 22, at 203.

169 Cargill, supra note 167, at 9. Cargill concedes that the indirect approach of research subject input via empirical research may be compromised by “the current dearth of empirical research on research ethics, and research with research participants in particular.” Id. at 10. Also problematic is the difficulty in locating ethics research studies and translating mixed-methods or qualitative work into generalizable information. Id.

170 Id.

171 Id. Cargill states that this could result in strategic use of participant perspectives only “where it would promote the efficacy or expediency of research, and its dismissal in realms where it may hinder or challenge it.” Id.

172 See id.

173 Lippman, Abby, Led (Astray) by Genetic Maps: The Cartography of the Human Genome and Health Care, 35 Soc. Sci. & Med. 1469, 1472 (1992)CrossRefGoogle ScholarPubMed (quoting Stuart F. Spicker & H. Tristram Englehardt, Jr., Causes, Effects, and Side Effects: Choosing Between the Better and the Best, in 16 Philosophy of Med., Health, Disease, and Causal Explanations in Medicine 225, 225 (Lennart Nordenfelt & B. Ingemar B. Lindahl eds., 1984)).

174 Lawrence et al., supra note 1, at 210. “Deep brain stimulation is a neurosurgical procedure in which electrodes are placed inside the brain and an electrical current is delivered to specific brain regions.” Id. While conducted with 24 adult psychiatric in-patients, excluded were patients “experiencing psychosis, delirium, dementia, intoxication, or catatonia, or [those with an] intellectual disability (mental retardation), … under court-ordered treatment, or [who] were non-English speaking.” Id. at 212.

175 Id. at 210.

176 Id. at 211.

177 Id. The cohort was not drawn from patients who had self-selected DBS as a potential treatment, but instead patients who were not necessarily seeking this treatment. Id.

178 Id. at 217.

179 See Busetto, Loraine et al., How to Use and Assess Qualitative Research Methods, 2 Neurological Res. & Prac., no 14, 2020CrossRefGoogle ScholarPubMed, at 1, 2, 6 (explaining the researcher’s ability to make educated decisions regarding methods and the importance of reflexivity).

180 Boulicault & Brown, supra note 21, at 235 (citing Bell et al., supra note 62, at 364) (describing “power-relational vulnerability” as “the vulnerability a research participant experiences as a result of asymmetrical power relations existing between investigators and participants”).

181 Id. at 236 (describing “identity-relational vulnerability” as “vulnerability that arises from how a person’s (evolving) self-identity both shapes and is shaped by their relationships with others”).

182 Id.

183 Şerife Tekin, supra note 71, at 240.

184 Revised Common Rule, 45 C.F.R. § 46.107 (2019).

185 Id.

186 See Klitzman, Robert, Institutional Review Board Community Members: Who Are They, What Do They Do, and Whom Do They Represent?, 87 ACAD. MED. 975, 978-79 (2012)CrossRefGoogle ScholarPubMed (finding that IRBs vary widely in the roles and functions assigned to community members).

187 The “working with” requirement may exclude perspectives of community members who are disabled or not members of the traditional workforce. See 45 C.F.R. § 46.107 (2019).

188 Id. (emphasis added). This proposition is discussed more fully in Part IV. See supra Part IV.

189 Jeste & Saks, supra note 19, at 623.

190 Id. at 609.

191 See Nugent et al., supra note 18, at 447; Lajoie et al., Concept of Vulnerability, supra note 10, at 129.

192 See supra Sections II.C, II.D.

193 See supra text accompanying note 52 and Section II.D.

194 Nugent et al. state that it is potentially harmful to declare all adults with mood disorders to be a vulnerable population, potentially contributing to stigma and devaluing of the societal contributions made by people with mood disorders. Nugent et al., supra note 18, at 447. These scholars draw comparisons between the dying cancer patient who consents to risky research and the patient suffering from depression because “severely ill patients rate the state of severe depression as equivalent to or worse than death.” Id. It is understandable why those who conduct research with mentally ill people want to show how their work is justifiable and should not be interfered with, however, there is no comparison between a dying cancer patient who literally has no alternative treatment and elects—with mental functioning fully intact—to take a huge risk to possibly avoid death and the severely depressed patient whose mental functioning is likely greatly compromised to take a huge risk in agreeing to take investigational psychotropic drugs or undergo other experimental psychiatric interventions. See Smilan, supra note 19, at 296-97.

195 Nugent et al. argue that our current system of informed consent is adequate, and that characteristics such as “extreme hopelessness and/or willingness to assume risk inappropriately should be relatively obvious in any properly conducted informed consent discussion, and could be deemed to invalidate consent.” Nugent et al., supra note 18, at 446. Underlying studies, such as those examined by Nugent et al. (to support their conclusions), that consider the benefits of research with mentally ill people are problematic in that research that asks mentally ill people about their experiences with research must be eyed with some skepticism: Structural coercion (or regular coercion) and undue influence may have been factors affecting their choices and preferences for the original research in which they participated, and then similarly in the research about that research. See, e.g., id. at 445-47; Edlinger, Monika et al., Attitudes of Patients with Schizophrenia and Depression Towards Psychiatric Research, 177 Psychiatry Res. 172 (2010)CrossRefGoogle ScholarPubMed; Misra, Sashana et al., Appreciation of Research Information in Patients with Bipolar Disorder, 10 Bipolar Disorders 635 (2008)CrossRefGoogle ScholarPubMed; Roberts, Laura Weiss & Kim, Jane Paik, Giving Voice to Study Volunteers: Comparing Views of Mentally Ill, Physically Ill, and Healthy Protocol Participants on Ethical Aspects of Clinical Research, 56 J. Psychiatry Res. 90 (2014)CrossRefGoogle ScholarPubMed; Tallon, Deborah et al., Involving Patients with Depression in Research: Survey of Patients’ Attitudes to Participation, 61 Brit. J. Gen. Prac. 134 (2011)CrossRefGoogle ScholarPubMed; Widom, Cathy Spatz & Czaja, Sally J., Reactions to Research Participation in Vulnerable Subgroups, 12 Accountability in Res. 115 (2005)CrossRefGoogle ScholarPubMed; see also Fisher, supra note 80, at 360 (introducing the concept of structural coercion). Nugent et al. use as an example one study of participants experiencing active mental distress associated with adult and childhood trauma, stating that these participants “were even more likely to state that they would participate in research again than those without such vulnerability, potentially indicating that open and detailed questioning of [intrusive and] sensitive topics is not harmful and may even be beneficial.” Nugent et al., supra note 18, at 446 (emphasis added) (discussing Widom & Czaia, supra, at 134). This is an unfounded inference and consequential conclusion (especially given the fact that Widom & Czaja explicitly stated that their research was limited and not generalizable to other kinds of research), not only about the benefit received by participants from being provided an opportunity to talk about trauma (one of the most important therapeutic tools for PTSD—but research is not therapy), but also in failing to address potential latent harms to patients from “detailed questioning of sensitive topics” without appropriate therapeutic guidance to work through the sensitive information they had shared. Id. (discussing Widom & Czaia, supra, at 136).

196 Given the changes to one’s mind in many mental illnesses, reconsent would provide an opportunity for participants to express a change of choice if they changed their mind about participation.

197 Martha Rosenberg, Pharma Funding Advocacy Groups, U. Southern Cal. Annenberg: Ctr. for Health Journalism (Oct. 15, 2014), https://www.centerforhealthjournalism.org/2014/10/15/discredited-patient-group-fights-mental-illness#:~:text=The%20patient%20front%20groups%20include,to%20the%20Wall%20Street%20Journal [https://perma.cc/XM4A-HBQQ]. Large pharmaceuticals corporations have had their share of representation and influence already.

198 Suggestions have been offered in the context of consent in clinical care and in the treatment of mentally ill patients, where the traditional MacArthur criteria for decision-making capacity have been perceived as insufficient. See Goldberg, supra note 64, at 11 (“The ability to govern along one’s own self-narrative can, and therefore should, be clinically assessed and qualified. Although palpably absent from the current MacArthuer criteria, it is crucial to an assessment of self-governing capacity.”).

199 One participant in a recent study interviewing people who live with mental illness conveyed that “mental illness never completely disappears from one’s life and can always potentially reemerge.” Lajoie et al., Enriching our Understanding, supra note 24, at 448. Another participant in this same study offered that “[s]he has ‘accepted herself as a vulnerable person’ and knows that she needs to be vigilant and develop strategies to protect herself.” Id. at 447.

200 A current movement in the United States involves the use of Mental Health Peer Specialists in the treatment and recovery process of people with severe mental illness. See Chinman, Matthew et al., Establishing a Research Agenda for Understanding the Role and Impact of Mental Health Peer Specialists, 68 Psychiatric Servs. 955, 955 (2017).CrossRefGoogle ScholarPubMed These peer specialists are people who themselves live with mental illness. Id. The position of “peer specialist” has been professionalized through training and certification, and services are covered by Medicaid in over 30 states. Id. There is, however, a call for further research on the benefits of using peer specialists. Id.; see also Fortuna, supra note 15, at 580 (“Initial insights from this study can be used to guide researchers’ efforts to incorporate certified peer specialists perspectives in developing programs to meet the needs of people with SMI.”).

201 See Sapfo Lignou et al., Ethical Challenges in Research, Industry and People Partnerships in Mental Health 1-2 (OSF Preprints, 2020) (quoting Make a Strong Application, Nat’l Inst. for Health Res., https://www.nihr.ac.uk/researchers/apply-for-funding/how-to-apply-for-project-funding/make-a-strong-application.htm [https://perma.cc/8NGM-JLGF]), https://osf.io/uwstp [https://perma.cc/2BK9-SAZU].

202 However, the Author advocates elsewhere that for genetics and genomics research relating to vulnerable or historically stigmatized populations (which would include people with mental illness) new governance approaches that include affected community members in decisions about research topics, design, recruitment, implementation, translation and dissemination are needed, especially when research results may lead to downstream harms to that community domestically and/or abroad. See Smilan, Lisa E., Balancing Benefits and Harms of Sexual Orientation and Gender Identity Genomics Research: Legal and Life Implications, 50 U. Balt. L. Rev. (forthcoming Dec. 2020).Google Scholar

203 Gottesman, Michael & Wyatt, Richard, IRBs at NIH Revisited: Serving the Interests of Patients and Clinical Investigators, 25 NIH Catalyst 2, 2 (2017)Google Scholar.

204 Id.

205 Id.

206 Baylis, Françoise, IRBs: Protecting the Well-Being of Subject-Participants with Mental Disorders That May Affect Decisionmaking Capacity, 7 Accountability in Res. 183, 186 (1999)CrossRefGoogle ScholarPubMed. Note that in the United Kingdom, people with mental illness are involved in the planning process at the earliest stages for research affecting their community. See Dep’t of Health, A Framework for Mental Health Research 6 (2017) (U.K.) (“Recommendation 2: Patient and public involvement (PPI)”); id. pt. 4, at 19 (“[This initiative] includes involving members of the public in all stages of the research process, in activities such as priority setting, defining research outcomes, selecting research methodology, recruiting participants, interpretation of research findings and dissemination of results.”).

207 There is no need to “reinvent the wheel.” The work of NBAC, leading to the 1998 Research Involving Persons with Mental Disorders That May Affect Decision-making Capacity report, is still quite relevant and could be built upon in any current efforts to better protect in the biomedical research arena those subjects who suffer from mental illness. Nat’l Bioethics Advisory Comm’n, supra note 31.

208 The Subcommittee on Inclusion of Individuals with Impaired Decision-making in Research (SIIIDR) was convened to develop recommendations regarding whether guidance and/or additional regulations were needed for research involving individuals with impaired decision-making capacity. SACHRP, supra note 48.

209 Id.

210 Lawrence et al., supra note 1, at 214.

211 See Harriet A Washington, Medical Apartheid 401 (2006) (proposing “that each IRB be composed of equal numbers of scientists and of peers of the group who will be asked to participate as subjects.”)

212 See Gottesman & Wyatt, supra note 203.

213 This is not to say that all people who live with mental illness would find participation burdensome.

214 The Author’s current work-in-progress focuses on this prospective concern. See Lisa Smilan, Rethinking Regulation in the Context of New Biologic Drugs: Psychiatric Polygenic Risk Scores, Somatic Genome Editing & Legal Off-Label Uses (forthcoming).

215 Nat’l Bioethics Advisory Comm’n, supra note 31, at 1-2.

216 Williams, supra note 71, at 222.

217 Berkman, Benjamin E. et al., A Proposed Process for Reliably Updating the Common Rule, 17 Am. J. Bioethics 8, 12 (2017)CrossRefGoogle ScholarPubMed. For example, the rCR instructs “agencies that implement the Common Rule to collaborate on a process of redefining the definitions of ‘identifiable private information’ and ‘identifiable biospecimen’ at least every 4 years.” Id. (quoting Federal Policy for the Protection of Human Subjects, 82 Fed. Reg. 7,149, 7,169 (Jan. 19, 2017) (to be codified at 45 C.F.R. pt. 46)).

218 The National Institute of Mental Health (NIMH) has created the Human Subjects Protection Unit with Clinical Research Advocates (CRAs). Nat’l Inst. of Mental Health, Human Subjects Research Protections Toolkit 1.2 (2019). CRAs support individual subjects and provide education and advice to researchers. Id. NIMH has created a Toolkit, available for use and/or modification by outside organizations, based on “NIMH’s experience conducting research with potentially vulnerable subjects [with the aim] to help research organizations assess, implement, and refine appropriate levels of human subjects protections during all phases of research.” Id. Note, however, that the Toolkit is not to be construed as official interpretation of federal policy. While the Toolkit and CRAs are positive steps for built-in protections in the clinical research endeavor for subjects who suffer from mental illness, CRAs work with both subjects and researchers: for this reason (at least from a distance without intimate knowledge of the innerworkings of this office) CRAs may more closely resemble mediators than advocates and, thus, cannot substitute for federal regulations or binding guidance specifically designed to protect those who are vulnerable to coercion or undue influence in relation to their mental illness.

219 “Journals have devolved into information laundering operations for the pharmaceutical industry.” Smith, Richard, Medical Journals Are an Extension of the Marketing Arm of Pharmaceutical Companies, 2 PLoS Med. 364, 364 (2005)CrossRefGoogle ScholarPubMed (quoting Richard Horton, The Dawn of McScience, N.Y. Rev., Mar. 11, 2004 (reviewing Sheldon Krimsky, Science in the Private Interest: Has the Lure of Profits Corrupted Biomedical Research? (2003))).

220 See Rosenberg, supra note 197.