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Restrict the Recruitment of Involuntarily Committed Patients for Psychiatric Research

Restrict the Recruitment of Involuntarily Committed Patients for Psychiatric Research Can an involuntarily committed psychiatric patient give truly voluntary consent for medical research? This question has been fiercely debated in Minnesota since 2008, when the St Paul Pioneer Press reported the death of Dan Markingson, a mentally ill young man who had been recruited into an antipsychotic study at the University of Minnesota while under a civil commitment order. Along with many others, we have argued that the circumstances of Markingson’s commitment order compromised the voluntariness of his consent to the study. Although federal guidelines are silent on the issue, we believe the Markingson case serves as a powerful argument for serious restrictions on the recruitment of involuntarily committed patients into psychiatric research studies. Concerns about recruiting involuntary patients have ample precedent. The Nuremberg Code states that every research participant “must be so situated as to be able to exercise free power of choice.”1 The Declaration of Helsinki urges particular caution when a person “is in a dependent relationship with the physician or may consent under duress.” Yet the very nature of some institutional settings places significant constraints on the voluntariness of consent. The 1976 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research recognized this when it recommended severe restrictions on research in prisons. Pointing to “the closed nature of prisons, with the resulting potential for abuse of authority,” the commission concluded that the principle of “respect for persons” in prison settings means “protection from exploitation.”2 These concerns apply with even greater force to patients who are involuntarily confined to state institutions because of serious mental impairments. Many of these patients are so impaired that they do not have sufficient decision-making capacity to give proper informed consent.3 Some have been committed because they are suicidal, raising questions about the quality of their judgments about their own health and welfare. Some patients are estranged from family members and other potential surrogate decision-makers who could act as advocates for the patients. Most importantly, however, involuntary patients are profoundly dependent on the authorities who have confined them and who will decide when they are released. This problem is conceptually separate from that of the involuntary patients’ decision-making capacity. In a well-known 1973 case, Kaimowitz v Department of Mental Health for the State of Michigan, a Michigan court cited the Nuremberg Code in ruling that an involuntarily committed psychiatric patient, while competent, was nonetheless incapable of giving legally adequate consent to experimental psychosurgery. The court concluded that true consent under such conditions was impossible, citing the pervasive atmosphere of constraint and coercion in psychiatric institutions.4 The Department of Health and Human Services Office for Human Research Protections has echoed this concern, noting that “[t]he eagerness for release may induce an institutionalized person, especially one who is involuntarily confined, to participate in research out of a desire to appear ‘rational’ and ‘cooperative’ to those who will make decisions about his or her release.”5 Dan Markingson’s case starkly illustrates the potential for coercion inherent in recruiting involuntarily committed patients into research. When Markingson was committed to a locked ward at the University of Minnesota Medical Center, Fairview Health Services hospital, he was acutely psychotic and threatening mass murder. After a week of hospitalization, Markingson’s treating psychiatrist persuaded a court to grant a “stay of commitment,” meaning Markingson remained under a civil commitment order but could avoid confinement if he obeyed the psychiatrist’s recommendations. One day later, the treating psychiatrist asked Markingson to enroll in a year-long antipsychotic trial sponsored by AstraZeneca (the so-called CAFÉ study), for which the treating psychiatrist was a principal investigator. Given a choice between participating in the CAFÉ study and being confined to an institution, Markingson enrolled in the study. He later committed suicide. Although University of Minnesota officials insisted Markingson’s consent to the CAFÉ study was valid, 2 independent reviews strongly disagreed. Although it declined to assign a causal connection between the CAFÉ study and Markingson’s death, a state watchdog agency found that Markingson was “extraordinarily vulnerable” when he was recruited: acutely psychotic, medicated, confined to a locked unit, and dependent on the principal investigator of the CAFÉ study “not only for care but also in deciding whether he would live independently again.”6 Another review of research policies and procedures, overseen by the Association for the Accreditation of Human Research Protection Programs and conducted by independent experts, including 2 psychiatrists, concluded: “… the fear of being subjected to an involuntary legal process for perceived noncooperation, even if there is no direct threat of such legal compulsion, is an overwhelming barrier to voluntariness.”7 In the absence of formal recruitment restrictions, institutional review board (IRB) review is insufficient to protect involuntarily committed patients. In T. D. v New York State Office of Mental Health, a group of involuntarily committed patients successfully challenged state regulations that allowed them to be deemed incompetent and enrolled in clinical research over their objections, without notice, and without an opportunity to challenge these decisions. In invalidating the regulations a state court dismissed the notion that patients were adequately protected by IRBs, determining that “in practice, the IRBs do not conduct in-depth evaluations” and did not “review the work of the researchers on a day-to-day or even monthly basis.”8 Exactly how formal protections should be instituted—through state legislation, new US Food and Drug Administration guidance, or changes to the Common Rule or to the Declaration of Helsinki—is a matter for further discussion. Minnesota’s state legislature has offered a way forward by enacting Dan’s Law—legislation that, with a few exceptions, prohibits patients under civil commitment orders from participating in psychiatric drug studies. If a court were to grant an exception, the patient’s treating psychiatrist would still be banned from serving as an investigator for the study.6 The question of whether some limited research should be permitted also merits further examination. Dan’s Law, for example, specifically restricts psychiatric drug studies, not all psychiatric research. It might be argued that some psychiatric research should be permitted as long as it involves no more than minimal risk, aims at studying the conditions of involuntary commitment or institutionalization, and has strong potential to benefit the population in question. Some might also argue that there are important, potentially beneficial interventions that cannot be soundly tested except with involuntary patients. On the other hand, it is widely accepted that medical research should not be conducted on vulnerable populations if it could be conducted on persons who are less vulnerable, especially if the research involves significant risks. It will rarely, if ever, be the case that investigational psychiatric drugs or other interventions must be tested on patients who are involuntarily committed, rather than, for instance, voluntary patients or outpatients. If investigators feel strongly that an important question can be answered only by conducting research on involuntarily committed patients, they should be required to apply formally for an exception. The history of medical research is replete with abuses enabled by the use of individuals who lacked either the ability to perceive their mistreatment or the power to combat it. Because involuntarily committed patients often meet both these criteria, they are extraordinarily vulnerable to exploitation. For this reason, we believe IRBs can best protect such patients by ending their recruitment into psychiatric drug studies until more detailed modifications to current guidelines and ethical codes are put into place. Back to top Article Information Corresponding Author: Carl Elliott, MD, PhD, Center for Bioethics, University of Minnesota, 410 Church St SE, Minneapolis, MN 55455-0346 (ellio023@tc.umn.edu). Published Online: February 10, 2016. doi:10.1001/jamapsychiatry.2015.3117. Conflict of Interest Disclosures: None reported. Dr Elliott is a faculty member of the University of Minnesota, where the Markingson controversy took place, and Mr Lamkin holds a graduate degree from the university. Both have been outspoken critics of the way the university handled the case. References 1. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law, No. 10.Vol 2. Washington, DC: US Government Printing Office; 1949:181-182. https://www.loc.gov/rr/frd/Military_Law/pdf/NT_war-criminals_Vol-II.pdf. Accessed January 11, 2016. 2. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (NCPHS). Research Involving Prisoners. Washington, DC: NCPHS; 1976. 3. Kovnick JA, Appelbaum PS, Hoge SK, Leadbetter RA. Competence to consent to research among long-stay inpatients with chronic schizophrenia. Psychiatr Serv. 2003;54(9):1247-1252.PubMedGoogle ScholarCrossref 4. Kaimowitz v. Department of Mental Health for the State of Michigan. 73-19434-AW (Mich 1973). 5. US Department of Health and Human Services, Office for Human Research Protections. Institutional review board guidebook: cognitively impaired persons.http://www.hhs.gov/ohrp/archive/irb/irb_chapter6.htm. Accessed August 13, 2015. 6. Office of the Legislative Auditor. A clinical drug study at the University of Minnesota department of psychiatry: the Dan Markingson case.http://www.auditor.leg.state.mn.us/sreview/markingson.pdf. Accessed August 14, 2015. 7. Association for the Accreditation of Human Research Protection Programs. An external review of the protection of human research participants at the University of Minnesota with special attention to research with adults who may lack decision-making capacity. http://research.umn.edu/advancehrp/documents/final_report.pdf. Accessed August 13, 2015. 8. T.D. v. New York State Office of Mental Health. 2d 650, 173. (N.Y. 1996). http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Psychiatry American Medical Association

Restrict the Recruitment of Involuntarily Committed Patients for Psychiatric Research

JAMA Psychiatry , Volume 73 (4) – Apr 1, 2016

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Publisher
American Medical Association
Copyright
Copyright © 2016 American Medical Association. All Rights Reserved.
ISSN
2168-622X
eISSN
2168-6238
DOI
10.1001/jamapsychiatry.2015.3117
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Abstract

Can an involuntarily committed psychiatric patient give truly voluntary consent for medical research? This question has been fiercely debated in Minnesota since 2008, when the St Paul Pioneer Press reported the death of Dan Markingson, a mentally ill young man who had been recruited into an antipsychotic study at the University of Minnesota while under a civil commitment order. Along with many others, we have argued that the circumstances of Markingson’s commitment order compromised the voluntariness of his consent to the study. Although federal guidelines are silent on the issue, we believe the Markingson case serves as a powerful argument for serious restrictions on the recruitment of involuntarily committed patients into psychiatric research studies. Concerns about recruiting involuntary patients have ample precedent. The Nuremberg Code states that every research participant “must be so situated as to be able to exercise free power of choice.”1 The Declaration of Helsinki urges particular caution when a person “is in a dependent relationship with the physician or may consent under duress.” Yet the very nature of some institutional settings places significant constraints on the voluntariness of consent. The 1976 National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research recognized this when it recommended severe restrictions on research in prisons. Pointing to “the closed nature of prisons, with the resulting potential for abuse of authority,” the commission concluded that the principle of “respect for persons” in prison settings means “protection from exploitation.”2 These concerns apply with even greater force to patients who are involuntarily confined to state institutions because of serious mental impairments. Many of these patients are so impaired that they do not have sufficient decision-making capacity to give proper informed consent.3 Some have been committed because they are suicidal, raising questions about the quality of their judgments about their own health and welfare. Some patients are estranged from family members and other potential surrogate decision-makers who could act as advocates for the patients. Most importantly, however, involuntary patients are profoundly dependent on the authorities who have confined them and who will decide when they are released. This problem is conceptually separate from that of the involuntary patients’ decision-making capacity. In a well-known 1973 case, Kaimowitz v Department of Mental Health for the State of Michigan, a Michigan court cited the Nuremberg Code in ruling that an involuntarily committed psychiatric patient, while competent, was nonetheless incapable of giving legally adequate consent to experimental psychosurgery. The court concluded that true consent under such conditions was impossible, citing the pervasive atmosphere of constraint and coercion in psychiatric institutions.4 The Department of Health and Human Services Office for Human Research Protections has echoed this concern, noting that “[t]he eagerness for release may induce an institutionalized person, especially one who is involuntarily confined, to participate in research out of a desire to appear ‘rational’ and ‘cooperative’ to those who will make decisions about his or her release.”5 Dan Markingson’s case starkly illustrates the potential for coercion inherent in recruiting involuntarily committed patients into research. When Markingson was committed to a locked ward at the University of Minnesota Medical Center, Fairview Health Services hospital, he was acutely psychotic and threatening mass murder. After a week of hospitalization, Markingson’s treating psychiatrist persuaded a court to grant a “stay of commitment,” meaning Markingson remained under a civil commitment order but could avoid confinement if he obeyed the psychiatrist’s recommendations. One day later, the treating psychiatrist asked Markingson to enroll in a year-long antipsychotic trial sponsored by AstraZeneca (the so-called CAFÉ study), for which the treating psychiatrist was a principal investigator. Given a choice between participating in the CAFÉ study and being confined to an institution, Markingson enrolled in the study. He later committed suicide. Although University of Minnesota officials insisted Markingson’s consent to the CAFÉ study was valid, 2 independent reviews strongly disagreed. Although it declined to assign a causal connection between the CAFÉ study and Markingson’s death, a state watchdog agency found that Markingson was “extraordinarily vulnerable” when he was recruited: acutely psychotic, medicated, confined to a locked unit, and dependent on the principal investigator of the CAFÉ study “not only for care but also in deciding whether he would live independently again.”6 Another review of research policies and procedures, overseen by the Association for the Accreditation of Human Research Protection Programs and conducted by independent experts, including 2 psychiatrists, concluded: “… the fear of being subjected to an involuntary legal process for perceived noncooperation, even if there is no direct threat of such legal compulsion, is an overwhelming barrier to voluntariness.”7 In the absence of formal recruitment restrictions, institutional review board (IRB) review is insufficient to protect involuntarily committed patients. In T. D. v New York State Office of Mental Health, a group of involuntarily committed patients successfully challenged state regulations that allowed them to be deemed incompetent and enrolled in clinical research over their objections, without notice, and without an opportunity to challenge these decisions. In invalidating the regulations a state court dismissed the notion that patients were adequately protected by IRBs, determining that “in practice, the IRBs do not conduct in-depth evaluations” and did not “review the work of the researchers on a day-to-day or even monthly basis.”8 Exactly how formal protections should be instituted—through state legislation, new US Food and Drug Administration guidance, or changes to the Common Rule or to the Declaration of Helsinki—is a matter for further discussion. Minnesota’s state legislature has offered a way forward by enacting Dan’s Law—legislation that, with a few exceptions, prohibits patients under civil commitment orders from participating in psychiatric drug studies. If a court were to grant an exception, the patient’s treating psychiatrist would still be banned from serving as an investigator for the study.6 The question of whether some limited research should be permitted also merits further examination. Dan’s Law, for example, specifically restricts psychiatric drug studies, not all psychiatric research. It might be argued that some psychiatric research should be permitted as long as it involves no more than minimal risk, aims at studying the conditions of involuntary commitment or institutionalization, and has strong potential to benefit the population in question. Some might also argue that there are important, potentially beneficial interventions that cannot be soundly tested except with involuntary patients. On the other hand, it is widely accepted that medical research should not be conducted on vulnerable populations if it could be conducted on persons who are less vulnerable, especially if the research involves significant risks. It will rarely, if ever, be the case that investigational psychiatric drugs or other interventions must be tested on patients who are involuntarily committed, rather than, for instance, voluntary patients or outpatients. If investigators feel strongly that an important question can be answered only by conducting research on involuntarily committed patients, they should be required to apply formally for an exception. The history of medical research is replete with abuses enabled by the use of individuals who lacked either the ability to perceive their mistreatment or the power to combat it. Because involuntarily committed patients often meet both these criteria, they are extraordinarily vulnerable to exploitation. For this reason, we believe IRBs can best protect such patients by ending their recruitment into psychiatric drug studies until more detailed modifications to current guidelines and ethical codes are put into place. Back to top Article Information Corresponding Author: Carl Elliott, MD, PhD, Center for Bioethics, University of Minnesota, 410 Church St SE, Minneapolis, MN 55455-0346 (ellio023@tc.umn.edu). Published Online: February 10, 2016. doi:10.1001/jamapsychiatry.2015.3117. Conflict of Interest Disclosures: None reported. Dr Elliott is a faculty member of the University of Minnesota, where the Markingson controversy took place, and Mr Lamkin holds a graduate degree from the university. Both have been outspoken critics of the way the university handled the case. References 1. Trials of War Criminals before the Nuremberg Military Tribunals under Control Council Law, No. 10.Vol 2. Washington, DC: US Government Printing Office; 1949:181-182. https://www.loc.gov/rr/frd/Military_Law/pdf/NT_war-criminals_Vol-II.pdf. Accessed January 11, 2016. 2. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (NCPHS). Research Involving Prisoners. Washington, DC: NCPHS; 1976. 3. Kovnick JA, Appelbaum PS, Hoge SK, Leadbetter RA. Competence to consent to research among long-stay inpatients with chronic schizophrenia. Psychiatr Serv. 2003;54(9):1247-1252.PubMedGoogle ScholarCrossref 4. Kaimowitz v. Department of Mental Health for the State of Michigan. 73-19434-AW (Mich 1973). 5. US Department of Health and Human Services, Office for Human Research Protections. Institutional review board guidebook: cognitively impaired persons.http://www.hhs.gov/ohrp/archive/irb/irb_chapter6.htm. Accessed August 13, 2015. 6. Office of the Legislative Auditor. A clinical drug study at the University of Minnesota department of psychiatry: the Dan Markingson case.http://www.auditor.leg.state.mn.us/sreview/markingson.pdf. Accessed August 14, 2015. 7. Association for the Accreditation of Human Research Protection Programs. An external review of the protection of human research participants at the University of Minnesota with special attention to research with adults who may lack decision-making capacity. http://research.umn.edu/advancehrp/documents/final_report.pdf. Accessed August 13, 2015. 8. T.D. v. New York State Office of Mental Health. 2d 650, 173. (N.Y. 1996).

Journal

JAMA PsychiatryAmerican Medical Association

Published: Apr 1, 2016

Keywords: psychotropic drugs,informed consent,institutional review board,ethics, medical,institutionalization,mental disorders,mentally ill persons,patients,psychiatry,involuntary commitment,hospitalization, involuntary,incompetence,consent,clinical trials, controlled,patient recruitment,research subjects,nuremberg code,minnesota

References