Capacity to consent to research: The evolution and current concepts

The ethical problem of the need to conduct research on the very conditions that impair the ability to consent to such research is widely acknowledged. People with cognitive impairment and mental illness have an equitable right to research being conducted in areas relevant to their treatment and care, and should be given an equitable opportunity to participate in such research, even if they lack capacity. They also have a right to adequate safeguards to protect their interests and respect their wishes in regards to research participation. Provisions for involvement in research of those who are unable to give consent have only developed over the last 50 years. Over this period we have witnessed a proliferation of policies, regulations and laws that govern research involving subjects unable to give consent. There has been a parallel increase in our understanding of the concepts of consent and capacity, specifically as it relates to the research context, with development of standards for research consent and instruments to guide capacity evaluation. We review the evolution of research governance and the underlying ethical principles that underpin such regulations, approaches to capacity evaluation and the use of proxies and advance research directives to facilitate research participation in adults who lack capacity.     

Impaired decision-making ability in subjects with Alzheimer's disease and willingness to participate in research

OBJECTIVE: Ethical concerns persist over research participation of decisionally impaired persons, such as those suffering from Alzheimer's disease. Such persons may be poor judges of the burdens and risks of specific research protocols. Since even decisionally incapacitated persons cannot be enrolled in studies against their objection, their preferences convey important ethical information. The authors examined the effects of cognitive and decisional impairment on willingness to participate in research among persons with Alzheimer's disease. METHOD: Cognitive status, decision-making ability, and willingness to participate in four hypothetical research protocols of varying risk/benefit profiles were measured in 34 subjects with mild to mild/moderate Alzheimer's disease and 14 healthy elderly comparison subjects. Univariate and multivariate methods were used to analyze the effects of impairment in cognitive and decision-making abilities on willingness to participate in research. RESULTS: There were no differences in willingness to participate found between the Alzheimer's and the healthy comparison subjects for three of the four hypothetical protocols. In both groups, willingness declined as risk increased. Within the Alzheimer's disease group, the presence of greater decisional impairment tended to predict less willingness to participate in research, even after adjusting for cognitive impairment, gender, and education. CONCLUSIONS: Persons with decisional impairment due to Alzheimer's disease are as a group able to distinguish between research protocols of varying risk/benefit profiles. Because declining decision-making abilities may predict declining willingness to participate in research, informed consent procedures for Alzheimer's disease research should be sensitive to this possibility.     

Assessing the competence of persons with Alzheimer's disease in providing informed consent for participation in research

OBJECTIVE: The capacity of persons with Alzheimer's disease or other neuropsychiatric disorders for giving consent to participate in research has come under increasing scrutiny. While instruments for measuring abilities related to capacity have been developed, how they should be used to categorize subjects as capable or incapable is not clear. A criterion validation study was carried out to help address this question. METHOD: The authors measured the ability of 37 subjects with mild-to-moderate Alzheimer's disease and 15 elderly comparison subjects to provide consent for participation in a hypothetical clinical trial. Using the judgment of three experts as the criterion standard, the authors performed a receiver operator characteristic analysis for the capacity ability measures from the MacArthur Competence Assessment Tool-Clinical Research VERSION: The results were compared with categorizations of capacity status that were based on normative values. RESULTS: While most comparison subjects scored perfectly on all measures of the competence assessment tool, the majority of the group with Alzheimer's disease showed significant decision-making impairment. Thresholds based on normative values resulted in 84% (N=31) of the Alzheimer's disease subjects being rated as incapable on at least one ability; thresholds based on expert judgment resulted in 62% (N=23) failing to meet cutoff scores on at least one ability. CONCLUSIONS: Even relatively mild Alzheimer's disease significantly impairs consent-giving capacity. But differentiating capable from incapable subjects remains an issue despite the aid of standardized tools. More research is needed to understand the relationship between subject factors (performance on ability measures) and categorical judgments about their capacity.     

Appreciation of research information in patients with bipolar disorder

Objective:  Ethicists have debated whether patients with serious mental illness can appreciate the risks of research participation and make autonomous decisions. We compared the abilities of euthymic and manic bipolar patients to appreciate and make voluntary decisions regarding research participation.
Methods:  Twenty-six subjects with mania and 25 euthymic subjects reviewed hypothetical consent forms for three research studies of varying risk. We assessed subjects' appreciation of: their diagnosis and need for treatment; the researcher's role; the risks of participation; and the degree of influence of family, the treating clinician, and payment on decisions to participate.
Results:  Most subjects (92%) agreed they had bipolar disorder requiring medication treatment. Subjects were less likely to participate in riskier studies. About half of subjects erroneously believed that researchers would make decisions based solely on what would be the best care for them (therapeutic misconception); and in randomized medication trials, they mistakenly believed they had improved chances of receiving one treatment over another. There were no differences between mood groups on these measures. Over half of subjects (59%) indicated that their mental health provider might influence them to participate in a study even when they did not want to, but most rejected a role for family in decision making. Payment was rated as having little impact on decisions to participate in research.
Conclusion:  Mania does not substantially influence appreciation of research participation. Subjects with bipolar disorder, regardless of mood state, are at risk for therapeutic misconception and optimistic bias. Special protections may be needed when mental health professionals approach their own patients to participate in research.     

Health care decision-making by adults with mental retardation

Abilities of adults with mild, moderate, or no mental retardation to understand hypothetical treatments was investigated using the Assessment of Consent Capacity-Treatment developed for this study based on Appelbaum and Roth's psycholegal consent standards. Performance in all groups decreased with increasing psycholegal complexity of consent decision-making. Most adults with mild and no mental retardation and almost half of adults with moderate mental retardation were able to make and justify treatment choices and fully or partially understand treatment information. Most adults without mental retardation, 50% with mild, and 18% with moderate mental retardation were able to partially appreciate relevance of treatment choice to patient's situation and weigh treatment risks against benefit. Implications of findings for patient rights are discussed.     

Ethical challenges in the conduct of research involving persons with mental retardation

Researchers face challenges in balancing the demands of sound research methods and ethical standards in studies involving persons with mental retardation. While the autonomy of individuals must be respected, researchers also have an ethical responsibility to protect vulnerable individuals from social, psychological, or physical risks of research participation. Some individuals may face significant barriers in the research decision-making process due to cognitive limitations, lack of information and support, and limited experience and opportunities for exercising choice. The historical context of biomedical and behavioral research involving persons with mental retardation and current ethical issues related to informed consent and surrogate decision-making are examined. Implications for researchers and professionals are discussed, including ways to support individuals with mental retardation and their families in research decision-making.     

Capacity to provide informed consent for participation in schizophrenia and HIV research

OBJECTIVE: The degree to which people with psychiatric symptoms and cognitive dysfunction can provide informed consent to participate in research is a controversial issue. This study was designed to examine the capacity of subjects with schizophrenia and subjects with HIV to provide informed consent for research participation and to determine the relationships among cognitive dysfunction, psychiatric symptoms, and decisional capacity. METHOD: Twenty-five men and women with a DSM-IV diagnosis of schizophrenia and 25 men and women with HIV were recruited. The groups were compared in terms of neuropsychological functioning, psychiatric symptoms, and ability to provide informed consent to a hypothetical drug trial. RESULTS: Eighty percent of the subjects with schizophrenia and 96% of the HIV-positive subjects demonstrated adequate capacity to consent to the hypothetical drug trial, but subjects in the schizophrenia group had significantly lower scores on two of the four aspects of decisional capacity. For the subjects with schizophrenia, neuropsychological functioning and psychiatric symptoms (e.g., apathy and avolition), but not psychotic symptoms (e.g., hallucinations and delusions), were significantly associated with decisional capacity. CONCLUSIONS: The majority of subjects who are recruited and willing to participate in schizophrenia or HIV research will have adequate capacity to provide consent. Cognitive dysfunction and the symptoms shown to be associated with impaired decisional capacity are not unique to schizophrenia and may occur with many other forms of illness. These findings underscore the importance of considering how decisional capacity will be assessed in all types of research, regardless of the specific condition being studied.     

Multimedia consent for research in people with schizophrenia and normal subjects: a randomized controlled trial

Limitations of printed, text-based, consent forms have long been documented and may be particularly problematic for persons at risk for impaired decision-making capacity, such as those with schizophrenia. We conducted a randomized controlled comparison of the effectiveness of a multimedia vs routine consent procedure (augmented with a 10-minute control video presentation) as a means of enhancing comprehension among 128 middle-aged and older persons with schizophrenia and 60 healthy comparison subjects. The primary outcome measure was manifest decisional capacity (understanding, appreciation, reasoning, and expression of choice) for participation in a (hypothetical) clinical drug trial, as measured with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California San Diego (UCSD) Brief Assessment for Capacity to Consent (UBACC). The MacCAT-CR and UBACC were administered by research assistants kept blind to consent condition. Additional assessments included standardized measures of psychopathology and cognitive functioning. Relative to patients in the routine consent condition, schizophrenia patients receiving multimedia consent had significantly better scores on the UBACC and on the MacCAT-CR understanding and expression of choice subscales and were significantly more likely to be categorized as being capable to consent than those in the routine consent condition (as categorized with several previously established criteria). Among the healthy subjects, there were few significant effects of consent condition. These findings suggest that multimedia consent procedures may be a valuable consent aid that should be considered for use when enrolling participants at risk for impaired decisional capacity, particularly for complex and/or high-risk research protocols.     

The history and current status of competence and informed consent in psychiatric research

Informed consent to research has recently become a focus of public attention as questions have been raised about the adequacy of information disclosed to potential research subjects and about the competence of psychiatric research subjects to provide valid informed consent to participate in potentially high risk studies. Around the world, policies and position statements have been written to address these concerns and to offer suggestions to protect potentially vulnerable research subjects, such as persons with neuropsychiatric disorders. Relevant literature has demonstrated that a subset of persons with such disorders have significant competence-related deficits, and thus may require specific means of protection with regard to informed consent to research. Recent guidelines offered to improve the informed consent process include review of potential studies for scientific merit and potential risk, assessment of subject competence to consent to research, and the use of proxy decision-makers when subjects are deemed incompetent.     

Decisional capacity for informed consent in schizophrenia research

BACKGROUND: The adequacy of subjects' informed consent to research is the focus of an important public and professional debate. The potential impairment of decisional capacity in persons with schizophrenia is central to the discussions. This study ascertains the decisional capacity for informed consent in schizophrenic research subjects, to determine if reduced capacity relates to specific aspects of psychopathologic features and to test the hypothesis that reduced capacity can be remediated with an educational informed consent process. METHODS: Decisional capacity was assessed for 30 research subjects with schizophrenia and 24 nonill (normal) comparison subjects. Measures of psychopathologic features and cognition were obtained for the subjects with schizophrenia. Subjects who performed poorly on the decisional capacity measure received an educational intervention designed to improve their ability to provide informed consent and were then retested. RESULTS: The patient group did not perform as well as the controls on initial decisional capacity assessment. Poor performance was modestly related to the extent of symptoms but robustly related to cognitive impairments. Following the educational intervention, the performance of subjects with schizophrenia was equal to that of the nonill comparison group. CONCLUSIONS: Many persons with schizophrenia may be challenged by the cognitive demands of an informed consent process for research participation. In many cases, their reduced capacity can be compensated by a more intensive educational intervention as part of the informed consent process.     

Recognition of facial expressions of emotion by persons with mental retardation. A matched comparison study.

Children and adults with mental retardation were tested on their ability to recognize facial expressions of emotion. The sample consisted of 80 children and adults with mental retardation and a control group of 80 nonhandicapped children matched on mental age and gender. Ekman and Friesen's normed photographs of the six basic emotions (anger, disgust, fear, happiness, sadness, and surprise) were used in a recognition task of facial expressions. Subjects were individually read two-sentence stories identifying a specific emotion, presented with a randomized array of the six photographs of the basic facial expressions of emotion, and then asked to select the photograph that depicted the emotion identified in the story. This procedure was repeated with 24 different stories, with each of the six basic emotions being represented four times. Results showed that, as a group, individuals with mental retardation were not as proficient as their mental-age-matched nonhandicapped control subjects at recognizing facial expressions of emotion. Although adults with mild mental retardation were more proficient at this task than those with moderate mental retardation, this finding was not true for children. There was a modest difference between the children with moderate mental retardation and their nonhandicapped matched controls in their ability to recognize facial expression of disgust.     

Competence to consent to research among long-stay inpatients with chronic schizophrenia

OBJECTIVE: Questions have been posed about the competence of persons with serious mental illness to consent to participate in clinical research. This study compared competence-related abilities of hospitalized persons with schizophrenia with those of a comparison sample of persons from the community who had never had a psychiatric hospitalization. METHODS: The study participants were administered the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), a structured instrument designed to aid in the assessment of competence to consent to clinical research. The scores of 27 persons who met DSM-IV criteria for schizophrenia who were long-stay patients on a state hospital research ward were compared with those of 24 individuals from the community who were of similar age, gender, race, and socioeconomic status. RESULTS: Significant differences were found between the patients and the community sample on three measures of competence-related abilities: understanding, reasoning, and appreciation. Degree of psychopathology and cognitive functioning were significantly negatively correlated with understanding and appreciation among the patients with schizophrenia. Length of hospitalization was significantly negatively correlated with all measures of decision-making capacities. CONCLUSIONS: The generally poor performance of the long-stay patients with chronic schizophrenia highlights the difficulties this group is likely to encounter in providing consent to research. However, variation across the sample points to the need for individualized assessment and for validated techniques for facilitating decision making in the face of decisional impairments.     

Worth the Risk? Relationship of Incentives to Risk and Benefit Perceptions and Willingness to Participate in Schizophrenia Research

Objective: Providing incentives for research participation is widely practiced but minimally studied. In schizophrenia research, questions about capacity to consent and potential vulnerability may raise concerns when offering incentives for participation. Despite empirical attention focused on consent and decision-making capacity in schizophrenia, the issue of incentives has been essentially ignored. We examined willingness to participate in research, in relation to perceived risks and benefits, among people with schizophrenia and schizoaffective disorder. Method: Forty-six people with schizophrenia or schizoaffective disorder rated perceived risks and benefits of 5 hypothetical research vignettes. They also indicated whether they would be willing to participate at each of 5 incentive levels (including no compensation). Cognition was assessed with Mattis Dementia Rating Scale. Results: Ratings of risk and potential personal benefit were inversely correlated. For all scenarios, significant correlations were found between perceived risk and willingness to participate for greater compensation. Conversely, lower perceived likelihood of benefit was associated with a higher compensation threshold for participation in each scenario. Even at the highest proffered payment level for each scenario, however, a substantial proportion of respondents were not willing to participate. Risk assessment and willingness to participate (at all levels of compensation) were not associated with demographic variables or cognitive status. Conclusions: Determining whether incentives impede voluntarism remains an important task for empirical ethics research. Assessing potential research participants’ understanding and perceptions of risks, benefits, and alternatives to participation will help ensure that informed consent fulfills its mission—embodying the ethical principle of respect for persons.     

Adverse reactions associated with studying persons recently exposed to mass urban disaster

This study assesses the psychological consequences of participation in a mental health study among people recently exposed to the September 11 attacks. Using cross-sectional telephone surveys, we interviewed random samples of English-speaking or Spanish-speaking adults living in New York City during the attacks 1 year after this event. Altogether, 2,368 people completed the surveys, including a random sample of 1,173 respondents who received mental health services after the attacks. Results indicated that 15% of New Yorkers found some of the survey questions stressful, whereas 28% of those who sought treatment found this to be the case. However, less than 2% reported being upset at survey completion, and among these persons, only four people consented to speak to the study's mental health consultant. Although the majority of those expressing adverse reactions had sought postdisaster treatment, even among these subjects, only 3% were still upset at survey completion, and 2% wanted more information about counseling services. In addition, more than 70% of participants expressed positive sentiments about survey participation. Predictive models indicated that respondents who met study criteria for posttraumatic stress disorder, depression, or anxiety were more likely to find questions stressful, with people having posttraumatic stress disorder or depression the most likely to be upset and to consent to psychiatric consultation at completion. We suggest that, with the proper safeguards, research with persons exposed to a resent mass urban disaster generally can be conducted safely and effectively.     

Continuum of intellectual disability: demographic evidence for the "forgotten generation"

Demographic features of Americans with mild intellectual disabilities were estimated in an analysis of the National Health Interview Survey. The cohort was compared to the population of the United States, persons with specific learning disabilities, and persons with mental retardation. Comparison on basic indices of adaptive functioning and SES suggest a large cohort of Americans who share many support needs and social and economic vulnerabilities with those labeled "mentally retarded." The combined prevalence of intellectual disability/mental retardation was estimated to be 1.27%. Implications are discussed in terms of the "forgotten generation" report of the 1999 President's Committee on Mental Retardation and evolving conceptions of mental retardation.     

Subjective evaluations of research participation by persons with mental illness

The present study focuses on the subjective experience of psychiatric patients who participate in psychobiological research, based on patients' self-reported evaluations of the experience. We studied 313 persons with mental illness admitted to an inpatient research unit. Each participant was administered the Patient Satisfaction Questionnaire, a structured self-report questionnaire designed to assess satisfaction with research participation and clinical care. Individuals who completed the research protocol were significantly more satisfied globally and more likely to express that treatment had been effective. Factors contributing to willingness to participate in future research included favorable perceptions of: (a) psychoeducation, (b) safety, and (c) comfort level with research procedures. Research participants were willing to participate in future research regardless of their perception of medication efficacy. This study emphasizes the importance of understanding the opinions of persons with mental illness who participate in research. Overall, the data suggest that persons with mental illness find psychiatric research to be beneficial. Although therapeutic misconception cannot be ruled out given the methodology used, at the very least the data indicate no sign that subjects found research participation to be harmful. Further studies should explore the source of this perception and attempt to separate the effect of "therapeutic misconception" from possible real benefit of protocol-driven assessment and treatment in a reputable clinical environment.     

Factor structure of maladaptive behavior across the lifespan of persons with mental retardation

Data obtained on a sample of persons with mild to profound degrees of mental retardation (N = 8255) and ranging from birth to 98 years of age were factor analyzed to provide information on the structure of maladaptive behavior relative to age and degree of mental retardation. Using the Problem Behavior scales of the Inventory for Client and Agency Planning, two principal factors emerged for children with mild to profound degrees of retardation: Internalized Maladaptive and Externalized Maladaptive. For adolescents and young adults, a three-factor solution which varied by degree of retardation was most appropriate. For middle and older adults, three- and four-factor solutions were identified across all ages and degrees of retardation. Across all samples as many as six different types of dimensions were identified, indicating that the structure of maladaptive behavior may well be influenced by age and level of mental retardation.     

Nonambulatory persons with profound mental retardation: Physical, developmental, and behavioral characteristics

Although profound mental retardation is generally associated with various organic etiologies that result in substantial cognitive and behavioral deficits, little is known about specific subgroups of persons with profound mental retardation. This study presents data on the physical, developmental, and behavioral characteristics of a group of 203 nonambulatory persons with profound mental retardation residing within a specialized service setting. The results indicate that nonambulatory persons with profound mental retardation have a high prevalence of physical and medical problems along with high rates of self-injurious, stereotypic, and aggressive behavior. Assessment results from the Stanford-Binet (L-M), Bayley Scales of Infant Development-Mental Scale, and Vineland Adaptive Behavior Scale reveal a high degree of variability in cognitive and adaptive functioning. However, developmental age-equivalent scores of cognitive ability, communication, daily living, socialization, and motor skills for the group fell below the 1-year level. The data illustrate the complexity of needs in providing habilitative services to nonambulatory persons with profound mental retardation.     

Costs and benefits of alternative rehabilitation models

Adaptive behavior skills of 2,144 adults with Down syndrome aged 20–69 years were compared to those of a matched group of 4,172 developmentally disabled people without Down syndrome. Adaptive competence in eight skill domains was examined as a function of etiology, age-group and level of mental retardation. In all behavioural domains, and at all levels of mental retardation, individuals with Down syndrome displayed significantly more age-related deficits than did age-matched controls. In individuals with Down syndrome, substantial age-related deficits in adaptive competence were observed after 49 years of age and were most pronounced after 59 years of age. Our findings support previous suggestions of increased risk for Alzheimer disease among adults with Down syndrome. However, Alzheimer neuropathology is found in people with Down syndrome by 40 years of age; signs of regression in adaptive behavior occur 10–15 years after the presumed onset of pathological processes. These results may suggest that the processes underlying dementia in individuals with Down syndrome can have an extremely prolonged course.     

Ethical issues in psychiatric research on children and adolescents

Psychiatric research on children and adolescents is ethically justified by the need to reduce the burden that mental illnesses place on young people, their families, and society. Such research must be conducted with careful attention to the ethical principles of beneficence, justice, and respect for persons. Child and adolescent psychiatrists who collaborate on research trials or advise patients and families about research participation should consider nine domains when evaluating the ethical acceptability of particular protocols. These domains include scientific merit and design; expertise, commitment, and integrity; risks and benefits; confidentiality; participant selection and recruitment; informed consent and decisional capacity; incentives; institution and peer/professional review; and data presentation. Special ethical issues in child and adolescent psychiatry research concern the use of randomized, controlled treatment trials; the informed consent process for research involving adolescents; the therapeutic misconception; and conflicts of interest in physician referrals.