Addressing risks to advance mental health research.

IMPORTANCE: Risk communication and management are essential to the ethical conduct of research, yet addressing risks may be time consuming for investigators and institutional review boards may reject study designs that seem too risky. This can discourage needed research, particularly in higher-risk protocols or those enrolling potentially vulnerable individuals, such as those with some level of suicidality. Improved mechanisms for addressing research risks may facilitate much needed psychiatric research. OBJECTIVE: To provide mental health researchers with practical approaches to (1) identify and define various intrinsic research risks, (2) communicate these risks to others (eg, potential participants, regulatory bodies, and society), (3) manage these risks during the course of a study, and (4) justify the risks. EVIDENCE REVIEW: As part of a National Institute of Mental Health-funded scientific meeting series, a public conference and a closed-session expert panel meeting were held on managing and disclosing risks in mental health clinical trials. The expert panel reviewed the literature with a focus on empirical studies and developed recommendations for best practices and further research on managing and disclosing risks in mental health clinical trials. No institutional review board-review was required because there were no human subjects. FINDINGS: Challenges, current data, practical strategies, and topics for future research are addressed for each of 4 key areas pertaining to management and disclosure of risks in clinical trials: identifying and defining risks, communicating risks, managing risks during studies, and justifying research risks. CONCLUSIONS AND RELEVANCE: Empirical data on risk communication, managing risks, and the benefits of research can support the ethical conduct of mental health research and may help investigators better conceptualize and confront risks and to gain institutional review board-approval.

Medical student views on interactions with pharmaceutical representatives.

OBJECTIVE: In 2006, the Housestaff Association presented the Dean at Oregon Health and Science University (OHSU) with a proposal to effectively end the influence of the pharmaceutical industry on campus. The Dean convened a workgroup to examine the issue, and faculty, residents, and medical students were surveyed on their views and interactions. Authors present here the responses from medical students. METHODS: A web-based, anonymous survey was sent to all OHSU medical students in 2007; 59% completed it. The survey included items measuring attitudes about the pharmaceutical industry and interactions with pharmaceutical representatives (PRs). RESULTS: Only 5% of clinical and 7% of preclinical students agreed that PRs have an important teaching role, and fewer than 1 in 6 believed that PRs provided useful and accurate information on either new or established drugs; 54% of clinical students indicated that PRs should be restricted from making presentations on campus, versus 32% of preclinical students, and only 30% of clinical students agreed that accepting gifts had no impact on their own prescribing, versus 50% of preclinical students. Students who acknowledged the influence of PRs and perceived less educational benefit were less likely to accept gifts such as textbooks; however, 84% of clinical students had attended an on-campus event sponsored by a pharmaceutical company in the previous year. CONCLUSIONS: Only a small proportion of OHSU medical students value interactions with PRs, but many still attend events sponsored by pharmaceutical companies.

"A feeling that you're helping": proxy decision making for Alzheimer's research.

Surrogate (proxy) decision makers must make research decisions for people with dementia who lack decision-making capacity. Proxies' decision-making processes are minimally understood. We randomly assigned 82 proxies of AD patients to informed consent for one of three hypothetical protocols with differing levels of risk and benefit. Proxies answered questions about potential benefits of the described research to the patient and society, as well as about whether they would enroll their relative and why or why not. Proxies interested in enrolling their relative cited the potential for direct benefit to their relative, altruism, and trust in researchers. Those declining cited risks, inconvenience, and stage of illness. Proxies weighed numerous factors, incorporating both substituted judgment and best interests standards in their decision-making processes. Although further empirical work is needed to understand the influences on and adequacy of proxies' decision making regarding research, these findings can help inform policy regarding surrogate consent.

Psychiatric resident and faculty views on and interactions with the pharmaceutical industry.

OBJECTIVE: Sales visits, or detailing, by pharmaceutical industry representatives at academic institutions has been increasingly criticized. The authors surveyed psychiatric residents and faculty members on their views and interactions with representatives of the pharmaceutical industry. METHODS: In 2007, a 46-item online survey measuring attitudes toward and interactions with pharmaceutical industry representatives was sent to 49 faculty psychiatrists and 40 psychiatric trainees (residents and fellows) at a Northwest academic medical center. RESULTS: Sixty-five percent (N=58) of surveys were completed. Two-thirds of respondents did not agree that pharmaceutical representatives have an important teaching role. Only 24% of faculty and 18% of trainees agreed that pharmaceutical representatives provide useful and accurate information on new drugs. Forty-one percent of faculty and 53% of trainees agreed that pharmaceutical representatives should be restricted from making presentations on campus. Trainees were less likely than faculty to agree that they would maintain contact with representatives if no gifts or food were distributed. Nevertheless, most respondents endorsed that pharmaceutical companies supported important conferences, and more than 90% had attended an industry-sponsored event in the previous year. In open-ended questioning, respondents revealed worries that bans would undermine the ability to secure national speakers and to support other activities that residents valued. CONCLUSION: Faculty and psychiatric residents and fellows do not view pharmaceutical representatives as having an important teaching role and mistrust the information they offer but believe that loss of industry financial support does adversely affect educational and other highly valued activities. They favor greater policy restrictions but do not support an outright ban on pharmaceutical support.

Research ethics issues in geriatric psychiatry.

Progress in geriatric psychiatric research may be impeded by lack of attention to collecting evidence relevant to ethical issues. As has been noted for some time, unless proactive work is done to identify, clarify, and remediate ethical challenges (see Table 2 for research directions), deleterious effects on research can result, including research bans, unduly overprotective stances, or inaccurate weighing of risks and benefits of research by review boards. With regard to proxy consent, a number of issues require further study. These include: how state laws address (or fail to address) research involving cognitively impaired individuals and what effects this has on research conduct; how IRBs define and weigh risks and benefits in considering research involving proxy consent; how various stakeholders, including the general public, people with disorders that may impair decision-making capacity, and proxies themselves view proxy consent for research; and to what degree proxies' research decisions reflect what patients themselves would decide. The use of advanced directives as a stand alone method for future consent is fraught with difficulties around adequate informed consent for a particular study; however, future study may clarify if such directives provide surrogates with improved understanding of their relative's overall views of the research enterprise and possibly the types of studies they would be willing to participate in even if they are no longer able to provide their own consent. In depression and suicide research, further work is needed to develop standard procedures for meeting the ethical demands of research while conducting rigorous, crucial research.

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.

Influence of mood state on capacity to consent to research in patients with bipolar disorder.

OBJECTIVES: Experts have debated the ability of patients with bipolar illness to consent to research participation when manic. We compared 25 euthymic bipolar and 26 manic bipolar patients in their understanding of three hypothetical studies of varying complexity. METHODS: Hypothetical studies were presented as written informed consent forms, which were reread up to three times. Questions included assessment of hypothetical study purposes, procedures, risks and benefits, and voluntariness of participation. RESULTS: After adjusting for educational level, subjects with mania had lower mean understanding scores for all three hypothetical studies compared to euthymic subjects on initial assessment. By the end of Trial 3 of each hypothetical study, there were no significant differences between groups. The proportion of subjects with mania who met predetermined pass criteria for sufficient understanding was lower than the proportion of euthymic subjects on initial assessment of the first hypothetical study, but not the other hypothetical studies (odds ratio = 0.24; 95% confidence interval = 0.07-0.8; p = 0.02). Both groups exhibited an increase in the pass proportion by the end of the third trial for each hypothetical study with no significant differences between groups. CONCLUSIONS: We conclude that subjects with mania exhibited significantly poorer levels of understanding of relevant information in hypothetical research consent forms compared to euthymic subjects when initially presented with research information. The improvement in manic patients' understanding scores with the iterative review of consent forms suggests that many manic patients may be able to consent to research protocols containing an educational intervention as a part of the informed consent process.

Capacity to consent to research among patients with bipolar disorder.

Experts have debated the influence of mental illness on decision-making capacity. This paper reviews concepts of decision-making capacity and existing research on the influence of mental illness on capacity to consent to research. We propose how bipolar disorder, especially mania, may have an effect on consent capacity. The current conceptualization of capacity utilizes legal standards of 'choice', 'understanding', 'appreciation' and 'rational reasoning', as well as voluntarism, or the assurance that the patient is free to agree or to decline to participate in research. Studies of patients with schizophrenia suggest impaired cognition influences 'understanding' and is more important than severity of psychosis in affecting decision-making abilities. There are no studies of sources and extent of impairment to consent to research among manic patients. Mania may influence a patient's understanding of the research protocol, but also alter the patient's views, values and level of insight, thus impairing decision-making abilities at the 'appreciation' standard even when the patient understands the relevant information. Mania may impact freedom to decide, yet paradoxically, manic patients may be less influenced by others and less vulnerable to coercion, undue influence and undue incentives compared to patients without mental illness. We suggest that in patients with mood disorders, the legal standard of appreciation be thoroughly probed during the consent procedure. Studies of the effect of mania and depression on consent capacity and voluntarism are needed in order to develop processes that increase safeguards in the informed consent process.

Delirium, depression, and anxiety.

Patients who are critically ill often develop a variety of psychiatric symptoms, which require assessment and treatment. The most common psychiatric disorder in the intensive care unit is delirium. Depressed mood and anxiety also occur, at times as discrete disorders, but more often secondary to delirium. Patients with severe mental illnesses, such as schizophrenia and bipolar affective disorder, also may become critically ill--assessment and management of these patients often requires specialized psychiatric care and is not addressed here.

Referral paths, patient profiles and treatment adherence of older alcoholic men.

We sought factors affecting completion by older men of 1-year outpatient treatment for alcohol dependence. We retrospectively studied clinical datasets of 110 men, age > or =55 years, consecutively admitted over 4 years, examining the association of 18 referral, treatment and patient variables with completion of treatment. We found that referral source was the most significant correlate of completion. Legal and self/family referrals were far more likely to complete treatment than patients referred by health or social services. Referral groups had distinctive profiles. Legal referrals were the healthiest. Self/family referrals were most likely to be married, to have had prior alcoholism treatment (a factor also associated with treatment completion), and to suffer currently from depression. Health/social services referrals showed the highest levels of psychosocial and physical dysfunction. Referral pathways deserve special consideration by programs treating older alcoholics. Special strategies for engaging dysfunctional older patients in alcoholism treatment are discussed.