Whether to return individual research results from cancer genetics studies is widely debated, but little is known about how participants respond to results disclosure or about its time and cost burdens on investigators.
We recontacted participants at one site of a multicenter genetic epidemiologic study regarding their CDKN2A gene test results and implications for melanoma risk. Interested participants were disclosed their results by telephone and followed for 3 months.
Among 39 patients approached, 27 were successfully contacted, and 19 (70% uptake) sought results, including three with mutations. Prior to disclosure, participants endorsed numerous benefits of receiving results (mean = 7.7 of 9 posed), including gaining information relevant to their children’s disease risk. Mean psychological well-being scores did not change from baseline, and no decreases to melanoma prevention behaviors were noted. Fifty-nine percent of participants reported that disclosure made participation in future research more likely. Preparation for disclosure required 40 minutes and $611 per recontact attempt. An additional 78 minutes and $68 was needed to disclose results.
Cancer epidemiology research participants who received their individual genetic research results showed no evidence of psychological harm or false reassurance from disclosure and expressed strong trust in the accuracy of results. Burdens to our investigators were high, but protocols may differ in their demands and disclosure may increase participants’ willingness to enroll in future studies.
Providing individual study results to cancer genetics research participants poses potential challenges for investigators, but many participants desire and respond positively to this information.
To explore the neuropsychological correlates of the capacity to consent to research and to appoint a research proxy among persons with Alzheimer’s disease.
Design, Setting, and Participants
Interview study of 77 persons with Alzheimer’s disease recruited through an Alzheimer’s disease research center and a memory disorder clinic.
The capacity to consent to two research scenarios (a drug randomized clinical trial and a neurosurgical clinical trial) and the capacity to appoint a research proxy were determined by five experienced consultation psychiatrists who rendered categorical judgments based on videotaped interviews of the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and the Capacity to Appoint a Proxy Assessment (CAPA). Mattis Dementia Rating Scale-2 (DRS-2) was used to assess neuropsychological functioning.
The capacity to appoint a proxy and to consent to the drug randomized clinical trial, as determined by a majority or greater opinion of the 5-psychiatrist panel, were predicted by Conceptualization and Initiation/Perseveration subscales whereas the capacity to consent to a neurosurgical randomized clinical trial was predicted by the Memory subscale. Furthermore, the more lenient individual psychiatrists’ judgments were predicted by the Conceptualization subscale whereas the stricter psychiatrists’ judgments were predicted by the Memory subscale.
How experienced psychiatrists view Alzheimer’s patients’ capacity for consenting to research and for appointing a proxy may be related to the patients’ conceptualization and memory functioning. More explicit and standardized guidance on the role of short term memory in capacity determinations may be useful.
decision-making capacity; neuropsychology; Alzheimer’s disease
To describe how members of the older general public deliberate with one another in finding solutions to the dilemma of involving decisionally incapable persons in dementia research.
Design, Setting, and Participants
160 persons aged 50+ who participated in an all-day deliberative democracy (DD) session on the ethics of surrogate consent for dementia research. The DD day consisted of both extensive, interactive education with experts in clinical research and ethics, as well as small group deliberations.
Audiotaped small group deliberations were transcribed and analyzed, and the main thematic elements were coded.
During deliberation, participants acknowledged the limitations of advanced research directives and discussed ways to improve their use. Although there was consensus about the necessity of surrogate consent, the participants recognized potential pitfalls and looked for ways to safeguard the process. Participants supporting surrogate consent for research emphasized societal and individual benefit, the importance of assent, and trust in surrogates and the oversight system. Other participants felt that the high risk of some research scenarios was not sufficiently offset by benefits to patients or society.
Members of the older general public are able to make use of in-depth education and peer deliberation to provide reasoned and informed opinions on the ethical use of surrogate consent for dementia research. The public’s approach to surrogate consent is one of cautious pragmatism: an overall trust in science and future surrogates with awareness of the potential pitfalls, suggesting that their trust cannot be taken for granted.
surrogate consent; dementia; deliberative democracy
Sham surgery controls are increasingly used in neurosurgical clinical trials in Parkinson disease (PD), but remain controversial. We interviewed participants of such trials, specifically examining their understanding and attitudes regarding sham surgery.
We conducted semi-structured qualitative interviews with participants of three sham surgery controlled trials for PD, focusing on their understanding of sham design, their reactions to it, its impact on decision-making, and their understanding of post-trial availability of the experimental intervention and its impact on decisions to participate.
All subjects (N=90) understood the two-arm design; most (86%) described the procedural differences between the arms accurately. 92% referred to scientific or regulatory reasons as rationales for the sham control, with 62% specifically referring to the placebo effect. 91% said post-trial availability of the experimental intervention had a strong (48%) or some (43%) influence on their decision to participate but only 68% understood the conditions for post-trial availability.
Most subjects in sham surgery controlled PD trials comprehend the sham surgery design and its rationale. Although there is room for improvement, most subjects of sham surgery trials appear to be adequately informed.
sham surgery; gene therapy; Parkinson disease; bioethics
Concerns have been raised that persons with serious illnesses participating in high risk research, such as Parkinson disease (PD) patients in sham surgery trials, have unrealistic expectations and are vulnerable to exploitation. A comparison of enrollees and decliners of such research may provide insights about the adequacy of decision-making by potential subjects.
We compared 61 enrollees and 10 decliners of two phase 2 neurosurgical intervention (cellular and gene transfer) trials for PD regarding their: demographic and clinical status; perceptions and attitudes regarding research risks, potential direct benefit, and societal benefit; and perspectives on the various potential reasons for and against participation. In addition to bivariate analyses, a logistic regression model examined variables regarding risks and benefits as predictors of participation status.
Enrollees perceived lower risk of harm while tolerating higher risk of harm, were more action oriented, but did not have more advanced disease. Both groups rated hope for benefit as a strong reason to participate, while the fact that the study’s purpose was not solely to benefit them was rated as ‘not a reason’ against participation. Hope for benefit and altruism were rated higher than expectation of benefit as reasons in favor of participation for both groups.
Enrollees and decliners are different in their views and attitudes toward risk. Although both are attracted to research due to hopes of personal benefit, this hope is clearly distinguishable from an expectation of benefit and it does not imply a failure to understand the main purpose of research.
Parkinson disease; sham surgery; therapeutic misconception; decision making; gene transfer
There is a longstanding concern about the accuracy of surrogate consent in representing the health care and research preferences of those who lose their ability to decide for themselves. We sought informed, deliberative views of the older general public (≥50 years old) regarding their willingness to participate in dementia research and to grant leeway to future surrogates to choose an option contrary to their stated wishes.
503 persons aged 50+ recruited by random digit dialing were randomly assigned to one of three groups: deliberation, education, or control. The deliberation group attended an all-day education/peer deliberation session; the education group received written information only. Participants were surveyed at baseline, after the deliberation session (or equivalent time), and one month after the session, regarding their willingness to participate in dementia research and to give leeway to surrogates, regarding studies of varying risk-benefit profiles (a lumbar puncture study, a drug randomized controlled trial, a vaccine randomized controlled trial, and an early phase gene transfer trial). At baseline, 48% (gene transfer scenario) to 92% (drug RCT) were willing to participate in future dementia research. A majority of respondents (57–71% depending on scenario) were willing to give leeway to future surrogate decision-makers. Democratic deliberation increased willingness to participate in all scenarios, to grant leeway in 3 of 4 scenarios (lumbar puncture, vaccine, and gene transfer), and to enroll loved ones in research in all scenarios. On average, respondents were more willing to volunteer themselves for research than to enroll their loved ones.
Most people were willing to grant leeway to their surrogates, and this willingness was either sustained or increased after democratic deliberation, suggesting that the attitude toward leeway is a reliable opinion. Eliciting a person’s current preferences about future research participation should also involve eliciting his or her leeway preferences.
Clinical research on Alzheimer disease (AD) is much needed but requires the participation of patients with substantial cognitive impairment who have difficulty providing informed consent. Despite decades of debate, policies regulating such research are not well-defined. Although numerous studies have underscored the difficulties of obtaining informed consent for clinical research from patients compromised by AD, there is also increasing evidence that such individuals and their surrogates can make decisions about research participation that are consistent with the patients’ values. Policy discussions and future research should consider how the ethical reservations about enrolling incapacitated patients in research could be mitigated by developing ways to promote the congruence between surrogates’ decisions and patients’ values.
Assessment of decision-making capacity is a common and important function of psychiatric consultants. However, the sources of variability in evaluators’ judgments have not been well characterized.
To examine the degree and potential sources of variability in the categorical capacity judgments of experienced psychiatrists.
The setting was a study comparing the decision-making capacities of 188 persons with Alzheimer’s disease to appoint a research proxy and to consent to two hypothetical randomized controlled trials for dementia (a new drug RCT and a neurosurgical RCT). We compared 5 experienced consultation psychiatrists’ capacity judgments for 555 videotaped capacity interviews. Both quantitative and qualitative data were used.
Pairwise kappa statistics ranged from slight agreement (0.17) to substantial agreement (0.64) with group kappa statistics ranging from fair to moderate agreement (0.40 to 0.45) for the psychiatrists’ judgments regarding the three capacities. The sources of variability included varying “strictness” among judges, moderate test-retest reliability within judges, the relative novelty of assessing decision-making capacity for research participation decisions, as well as the limitations of the methods used to obtain capacity judgments in the study.
There is considerable variability in capacity judgments of experienced consultation psychiatrists regarding the capacities to appoint a research proxy and to consent to research. The potential sources of variability identified in this study may provide starting points for more effective training in capacity assessment.
Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception (TM). However, there is a continuing debate about the definition and measurement of TM, making assessments of TM controversial. In this qualitative pilot study of persons enrolled in a phase I test of gene transfer for Parkinson’s disease, we developed and tested an interview guide focusing on how the subjects made their decision to participate, with an emphasis on understanding the subject as the unit of interest, rather than focusing only on isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participation. Doing so reveals potential avenues for measuring and preventing TM.
informed consent; gene transfer; Parkinson’s disease; therapeutic misconception; qualitative research
Research involving persons with impaired decision-making capacity, such as persons with Alzheimer’s disease, remains ethically challenging, especially when the research involves significant risk. If subjects incapable of consenting to research studies were still able to appoint a research proxy, it would allow for an appointed surrogate, rather than a de facto surrogate, to represent the subject.
To assess the extent to which persons with Alzheimer’s disease retain their capacity to appoint a research proxy.
Design, Setting, and Participants
188 persons with Alzheimer’s disease were interviewed for their capacity to appoint a proxy (CAP) for research and to provide consent to two hypothetical research scenarios, a lower risk randomized clinical trial testing a new drug (drug RCT) and a higher risk randomized clinical trial testing neurosurgical cell implants using a sham control condition (neurosurgical RCT). Categorical capacity status for each subject was determined by independent videotape reviews of capacity interviews by five experienced psychiatrists.
Main Outcome Measures
Categorical capacity determinations for the capacity to appoint a research proxy, capacity to consent to a drug RCT, and capacity to consent to a neurosurgical RCT.
37.7% (40/106) of those deemed incapable of consenting to the drug RCT and 54.4% (86/157) of those deemed incapable of consenting to the neurosurgical RCT were still found capable of appointing a research proxy. Very few subjects (7/186, 3.8%) were deemed capable of consenting to the neurosurgical RCT by all five psychiatrists.
A substantial proportion of AD subjects thought incapable of consenting to lower or to higher risk studies have preserved capacity for appointing a research proxy. Since so few subjects are found to be unequivocally capable of providing independent consent to higher risk AD research, providing for an appointed surrogate even after the onset of AD, which might best be done in the very early stages of the illness, may help address key ethical challenges to AD research.
The goal of democratic deliberation (DD) bioethics research is to elicit informed and considered opinions on ethically controversial issues. But the trustworthiness of DD outcomes depends on the quality of deliberations. We provide a framework to evaluate the quality of deliberations and apply that framework to a DD project on surrogate consent for dementia research involving randomly selected samples of the older general public. Using a mixed method approach, we found that participants were very satisfied with the sessions, learned and used new information, were respectful and collaborative, and were able to “reason together” to arrive at societal policy recommendations. Implications and limitations of the paper are also discussed.
surrogate consent; dementia; deliberative democracy; quality of deliberation
With increasing numbers of studies on research ethics and a need to improve the recruitment of research subjects, the ability to measure attitudes toward biomedical research has become important. The Research Attitudes Questionnaire is a significant predictor of the public’s attitudes toward and willingness to participate in research, yet limited data are available on its psychometric properties. This study establishes the scale’s internal consistency and dimensionality using a large Internet-based sample from the United States. One item was removed due to a poor item-total correlation, and three additional items were removed which formed a reverse-wording measurement artifact factor. With improved internal consistency and dimensionality, the seven-item version has the advantages of shorter administration time and improved psychometric properties.
research participation; research attitudes; research ethics; exploratory factor analysis; confirmatory factor analysis; psychometrics
The obligations of researchers to disclose clinically and/or personally significant individual research results are highly debated, but few empirical studies have addressed this topic. We describe the development of a protocol for returning research results to participants at one site of a multicenter study of the genetic epidemiology of melanoma. Protocol development involved numerous challenges: (1) deciding whether genotype results merited disclosure; (2) achieving an appropriate format for communicating results; (3) developing education materials; (4) deciding whether to retest samples for additional laboratory validation; (5) identifying and notifying selected participants; and (6) assessing the impact of disclosure. Our experience suggests potential obstacles depending on researcher resources and the design of the parent study, but offers a process by which researchers can responsibly return individual study results and evaluate the impact of disclosure.
genetic testing; cancer; CDKN2A; risk communication; return of research results; protocol development
Research involving incapacitated persons with dementia involves complex scientific, legal, and ethical issues, making traditional surveys of layperson views regarding the ethics of such research challenging. We therefore assessed the impact of democratic deliberation (DD)—involving balanced, detailed education and peer deliberation—on the views of those responsible for persons with dementia.
178 community-recruited caregivers or primary decision-makers for persons with dementia were randomly assigned to either an all-day DD session group or a control group. Educational materials used for the DD session were vetted for balance and accuracy by an interdisciplinary advisory panel. We assessed the acceptability of family surrogate consent for dementia research (‘surrogate-based research’ or SBR) from a societal policy perspective as well as from the more personal perspectives of deciding for a loved one or for oneself (surrogate and self perspectives), assessed at baseline, immediately post-DD session, and a month after DD date, for 4 research scenarios of varying risk-benefit profiles.
At baseline, a majority in both DD and control groups supported a policy of family consent for dementia research for all research scenarios. The support for a policy of family consent for SBR increased for the DD group, but not for the control group; the change in the DD group was maintained one month later. In the DD group, there were transient changes in attitudes from surrogate or self perspectives; in the control group, there were no changes from baseline in attitude toward surrogate consent from any perspective.
Intensive, balanced, and accurate education along with peer deliberation provided by democratic deliberation leads to a sustained increase in support for a societal policy of family consent for dementia research among those responsible for dementia patients.
Alzheimer’s Disease; informed consent; deliberative democracy; bioethics; research ethics; surrogate-based research; impaired decision-making capacity
Little is known about research participants' understanding of consent information over the course of a clinical study and the relationship of this information with participant behavior.
We conducted a cross sectional patient completed questionnaire of comprehension and satisfaction administered at the end of a Parkinson's disease clinical trial.
Scores on 9 comprehension items in a 30 item questionnaire covering the key elements of informed consent.
78% of eligible trial participants completed this sub-study. Greater than 90% of respondents showed good comprehension of the study purpose, method of treatment assignment, experimental nature of drugs, voluntary participation, and expected effect of the trial on their PD. However, 42.3% of subjects incorrectly endorsed that participating in the study was part of the “usual treatment” for their PD. We found no relationship between comprehension, compliance, and satisfaction with whether or not one's own neurologist was also the study doctor. Years of education and cognitive function at baseline were correlated with comprehension of study information.
Overall comprehension of key study information presented in the consent was high after 12 months of trial participation, although there were inconsistencies in responses that need further study.
Parkinson's disease; comprehension; understanding; informed consent; clinical trial
Recent discussions about health care reform have raised questions regarding the value of advance directives.
We used data from survey proxies in the Health and Retirement Study involving adults 60 years of age or older who had died between 2000 and 2006 to determine the prevalence of the need for decision making and lost decision-making capacity and to test the association between preferences documented in advance directives and outcomes of surrogate decision making.
Of 3746 subjects, 42.5% required decision making, of whom 70.3% lacked decision-making capacity and 67.6% of those subjects, in turn, had advance directives. Subjects who had living wills were more likely to want limited care (92.7%) or comfort care (96.2%) than all care possible (1.9%); 83.2% of subjects who requested limited care and 97.1% of subjects who requested comfort care received care consistent with their preferences. Among the 10 subjects who requested all care possible, only 5 received it; however, subjects who requested all care possible were far more likely to receive aggressive care as compared with those who did not request it (adjusted odds ratio, 22.62; 95% confidence interval [CI], 4.45 to 115.00). Subjects with living wills were less likely to receive all care possible (adjusted odds ratio, 0.33; 95% CI, 0.19 to 0.56) than were subjects without living wills. Subjects who had assigned a durable power of attorney for health care were less likely to die in a hospital (adjusted odds ratio, 0.72; 95% CI, 0.55 to 0.93) or receive all care possible (adjusted odds ratio, 0.54; 95% CI, 0.34 to 0.86) than were subjects who had not assigned a durable power of attorney for health care.
Between 2000 and 2006, many elderly Americans needed decision making near the end of life at a time when most lacked the capacity to make decisions. Patients who had prepared advance directives received care that was strongly associated with their preferences. These findings support the continued use of advance directives.
In a Liberal Democracy, Policy Decisions regarding ethical controversies, including those in research ethics, should incorporate the opinions of its citizens. Eliciting informed and well-considered ethical opinions can be challenging. The issues may not be widely familiar and they may involve complex scientific, legal, historical, and ethical dimensions. Traditional surveys risk eliciting superficial and uninformed opinions that may be of dubious quality for policy formation. We argue that the theory and practice of deliberative democracy (DD) is especially useful in overcoming such inadequacies. We explain DD theory and practice, discuss the rationale for using DD methods in research ethics, and illustrate in depth the use of a DD method for a long-standing research ethics controversy involving research based on surrogate consent. The potential pitfalls of DD and the means of minimizing them as well as future research directions are also discussed.
deliberative democracy; public opinion; surveys; bioethical issues; dementia; surrogate consent
Although decisional incapacity can be caused by various medical conditions, incapacity due to mental illness is often singled out for scrutiny in research ethics policy debates. We assessed whether there is a general discriminatory perception of mental illness research and, if so, aimed to characterize the nature of that perception. We conducted an experimental, randomized Internet survey of the general public. We recruited 3140 adults through a web-research survey panel, with oversampling of racial and ethnic minorities and the elderly. Willingness to allow medical versus mental illness research was compared by randomly assigning the respondents to 1 of 7 web-based experimental scenarios depicting a subject being considered for research participation. Respondents were more willing to allow research with medically ill than the mentally ill subjects, even when ethically relevant factors were equal. This difference was mediated through the respondents' tendency to view mentally ill subjects as more decisionally incapable than medically ill subjects, even when they were told that the subjects portrayed were in fact competent. Discriminatory perception of mental illness research exists and is mediated by an outdated view of mental illness and decisional capacity. Policymakers and institutional review board members may need to guard against its influence in their deliberations.
ethics; stigma; mental illness; schizophrenia; research attitudes; decision-making capacity
Most decision-making capacity (DMC) research has focused on measuring the decision-making abilities of patients, rather than on how such persons may be categorized as competent or incompetent. However, research ethics policies and practices either assume that we can differentiate or attempt to guide the differentiation of the competent from the incompetent. Thus there is a need to build on the recent advances in capacity research by conceptualizing and studying DMC as a categorical concept. This review discusses why there is a need for such research and addresses challenges and obstacles, both practical and theoretical. After a discussion of the potential obstacles and suggesting ways to overcome them, it discusses why clinicians with expertise in capacity assessments may be the best source of a provisional “gold standard” for criterion validation of categorical capacity status. The review provides discussions of selected key methodological issues in conducting research that treats DMC as a categorical concept, such as the issue of the optimal number of expert judges needed to generate a criterion standard and the kinds of information presented to the experts in obtaining their judgments. Future research needs are outlined.
decision-making capacity; competence; research ethics; categorical determinations of capacity; expert judgment