Many challenging ethical questions come with the scientific efforts to understand the nature and treatment of schizophrenia. The empirical study of ethical aspects of schizophrenia research has sought to clarify and resolve many of these questions. In this article we provide an overview of the existing data-based literature on schizophrenia research ethics and outline directions for future inquiry. We examine 5 broad categories of inquiry into the ethics of schizophrenia research: (1) Scientific designs (eg, placebo-controlled studies and medication-free intervals, prodromal and high-risk research, and genetics research); (2) informed consent and decision-making capacity, including assessment of decisional abilities, as well as intervention studies; (3) understanding and perceptions of risk and benefit (including the therapeutic misconception); (4) influences on research participation (including voluntarism, altruism, and other motivations); and (5) key participant safeguards, such as protocol review and participant advocates. We discuss how empirical work in each of these areas answers certain questions and raises new ones. Finally, we highlight important gaps in our understanding of ethically relevant aspects of schizophrenia research and offer a specific research agenda for empirical ethics.

To characterize predictors of impairment in research decision-making capacity, we undertook a direct comparison of schizophrenia/schizoaffective (n=52), medically ill (diabetic; n=51), and non-ill (n=57) subjects. Scores on the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) were correlated with demographic variables and scores on the Positive and Negative Syndrome Scale (PANSS), Mini-Mental State Examination (MMSE), and Short-Form-36 (SF-36). Across diagnoses, cognitive capacity, physical functioning, and a diagnosis of mental illness had the greatest impact on decision-making capacity, with level of education also having an impact. 69-89% of schizophrenia/schizoaffective subjects attained MacCAT-CR subscale scores achieved by almost all comparison (98-100%) and medically ill (94-100%) subjects. Positive, negative, and general psychotic symptoms correlated with poorer scores. Prior research experience, number of queries used during interview, and emotional functioning also predicted MacCAT-CR scores. These data suggest that investigators and IRBs should consider a number of variables, many of which reach across diagnoses, as they decide which populations and individual subjects may require more intensive screening for decisional impairment or educational interventions to improve their abilities to make capable decisions about research participation.

In this study we assessed the quality of life of patients with panic disorder, with particular attention to the influence of anxiety and depression comorbidity on quality of life. Findings were compared with established general population norms as well as norms for patients with chronic medical conditions and major depression. The Medical Outcomes Study Short-Form Health Survey (SF-36) was administered to panic disorder patients entering clinical trials or treatment in an outpatient anxiety disorders program. Subjects were 73 consecutive patients with a primary diagnosis of panic disorder without current substance abuse or contributory medical illness. Their quality of life scores were compared with population mean estimates using single-sample t-tests, and the influence of comorbidity was examined with between-group comparisons. All SF-36 mental and physical health subscale scores were worse in patients with panic disorder than in the general population. This was true regardless of the presence of comorbid anxiety or mood disorders, although the presence of the comorbid conditions worsened select areas of functioning according to subscale analyses. SF-36 scores in panic patients were at approximately the same level as patients with major depression and tended to be worse in specific areas than patients with select medical conditions. This study provides evidence of the pervasive negative effects of panic disorder on both mental and physical health.

Greater attention is being focused on the willingness and motivations of potential subjects who are recruited for research protocols. Given the importance of subjects' abilities to choose freely and reason through their decisions about entering psychiatric research, empirical researchers have been developing assessment and education tools that address the potential vulnerabilities of research subjects. In this study subjects' responses and reasons for or against participation were elicited as part of an assessment of their research decision making. Fifty-two persons diagnosed with a thought disorder were asked to consider a hypothetical research study using the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Their responses were documented, coded for content, and correlated with demographic characteristics and scores on scales rating psychosis, cognition, and health-related quality of life. Subjects expressed common considerations that have been identified by other psychiatric investigators, as well as by those studying nonpsychiatric protocols. In general, reasons were both appropriate to the study being considered and appropriately linked to common considerations that flowed logically from the study. However, elements of the therapeutic misconception were evident as well. Willingness to participate was correlated with higher MacCAT-CR scores on certain scales, better education, and lower levels of psychosis and cognitive impairment. These findings highlight both the strengths and weaknesses of the decision making of research subjects with thought disorder. Research protections and assessments may consequently be appropriately targeted to specific vulnerabilities. Because of differences in severity of illness, cognition, and reasoning among subjects who decline to participate in research, greater attention to this population appears warranted.

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Purpose To determine how closely institutional review board (IRB) discussions reflect the ethical criteria specified in the Common Rule federal regulations Method Between November 2006 and July 2009, the authors observed, audio-recorded, transcribed, and coded protocol reviews from 20 IRB meetings at 10 leading academic medical centers. They also reviewed each of the applications discussed to identify the Common Rule criteria--(1) risk minimization, (2) risk/benefit comparison, (3) equitable subject selection, (4) informed consent, (5) data monitoring to ensure safety, (6) privacy protection and confidentiality, and (7) protection of vulnerable subjects--that were both relevant to the study and not adequately addressed in the application. They then determined if the IRB addressed each of the relevant and not discussed Common Rule criteria in their discussions. Results IRBs made no mention of many of the Common Rule criteria that required their discussion--in 17/82 (21%) reviews, they failed to address risk minimization; in 52/91 (57%), risk/benefit comparison; in 31/52 (60%), equitable subject selection; in 32/59 (54%), data monitoring; in 13/52 (25%), privacy and confidentiality; and in 7/55 (13%), protection of vulnerable populations. However, they discussed informed consent in 102/104 (98%) reviews and raised questions about, or requested changes about, informed consent for 92/104 (88%) protocols. Conclusions These findings suggest that essential elements of human subjects protection are not implemented uniformly across IRBs. While not directly addressing this issue, the current proposed changes to the Common Rule offer an opportunity to improve, in general, the effectiveness of IRBs to protect human subjects.

End-of-life care is often influenced by the stereotyping of patients by age, diagnosis, or cultural identity. Two common stereotypes arise from the presumed incompetence of many patients to contribute to end-of-life decisions, and the fear that the discussions themselves will be de-stabilizing. We present a model for end-of-life discussions that combines competence assessment with healthcare preferences in a psychiatric population that faces identical stereotypes. The model, which draws on clinical research in competence and suicide risk assessment, has important implications for all patients in the community who are marginalized or stereotyped during discussions of end-of-life treatment.

The goal of this study was to describe the contributions of community members (unaffiliated members) who serve on institutional review boards (IRBs) at large medical research centers and to compare their contributions to those of other IRB members. We observed and audiotaped 17 panel meetings attended by community members and interviewed 15 community members, as well as 152 other members and staff. The authors coded transcripts of the panel meetings and reviewed the interviews of the community members. Community members played a lesser role as designated reviewers than other members. They were infrequently primary reviewers and expressed hesitation about the role. As secondary or tertiary reviewers, they were less active participants than other members in those roles. Community members were more likely to focus on issues related to confidentiality when reviewing an application than other reviewers. When they were not designated reviewers, however, they played a markedly greater role and their discussion focused more on consent disclosures than other reviewers. They did not appear to represent the community so much as to provide a nonscientific view of the protocol and the consent form.