Informing patients of uncertainty in clinical trials.
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Ethics, Research↗
Biomedical subjects
J H Karlawish
Publications and source records attributed to J H Karlawish.
How do AD patients and their caregivers decide whether to enroll in a clinical trial?
To examine how patients and caregivers decide whether to enroll in a clinical trial, the authors conducted semi-structured interviews with 22 family caregivers of patients with mild to moderate AD who were recruited for a clinical trial. They found that a caregiver who enrolls a patient in research generally involves the patient in the decision-making process, reports that the patient shares in the decision, and regards the risks and benefits to the patient and to the caregiver as interdependent.
Alzheimer Disease↗
The relationship between caregivers' global ratings of Alzheimer's disease patients' quality of life, disease severity, and the caregiving experience.
OBJECTIVES: To compare caregivers' ratings of Alzheimer's disease (AD) patients' global quality of life (QOL) using direct assessments and substituted judgments, and to identify qualities of the patients and their caregivers that are associated with these QOL assessments. DESIGN: Cross-sectional interviews. SETTING: A university-based Memory Disorders Clinic. PARTICIPANTS: Forty primary caregivers of AD patients. MEASUREMENTS: Direct scaling of overall quality of life (poor, fair, good, very good, or excellent) and measures of dementia severity, the caregiving experience, and patient and caregiver demographics. RESULTS: The majority of patients had mild (n = 20) or moderate (n = 11) AD. Caregivers' direct assessments of patient QOL were poor (5%, n = 2), fair (28%, n = 11), good (40%, n = 16), very good (20%, n = 8), and excellent (8%, n = 3). Twenty-one (52.5%) of the caregivers rated the patient's QOL the same as they thought the patient would; 12 (30.0%) rated the patient's QOL worse; and seven (17.5%) rated the patient's QOL better. Agreement between the two ratings was fair to moderate. Bivariate analyses showed that lower ratings of caregivers' direct assessments of patient QOL were associated with decreasing ratings of patient mental health and increasing dementia severity, caregiver burden, and caregiver depression. Multivariate models showed burden to be the significant predictor of caregivers' rating of patient QOL and the subscale measuring the caregivers' distress at controlling patient behavior had the strongest association with QOL. Lower ratings of substituted judgment assessments of patient QOL were associated with lower caregiver ratings of the patient's mental health. CONCLUSIONS: Nearly one-half of the caregivers of patients with predominantly mild to moderate AD assess a patient's QOL differently than they believe the patient would. Dementia severity and the caregiver's experiences of depression and burden negatively affect caregivers' assessments of QOL. These results provide a compelling reason why clinicians should take the time to screen for and address caregiver depression and burden and problematic patient behaviors.
Adult↗
Predictors of withdrawal from hospice.
CONTEXT: Hospice is designed to provide end-of-life care to patients who are terminally ill. However, some patients withdraw from hospice even though they are medically eligible. Little is known about these patients, and the factors associated with their withdrawal have not been described. OBJECTIVES: To identify predictors of withdrawal from hospice in a diverse cohort of hospice patients who are eligible to receive service. DESIGN: Retrospective cohort study. PATIENTS AND SETTING: Between January 1997 and January 1999 1,691 patients enrolled in an urban, nonprofit hospice program were identified and data were gathered until discharge or death. MAIN OUTCOME MEASURES: Time to discharge of eligible patients from hospice. RESULTS: Over the study period, 15% of patients were discharged from hospice while they still met medical eligibility criteria. Patients were more likely to withdraw if they were male, unmarried, and younger than 65, if they did not have cancer, and if they lacked a do-not-resuscitate order, intravenous access, and symptoms requiring intervention. CONCLUSIONS: A substantial proportion of hospice patients who meet medical criteria for services choose to withdraw. Further research is needed to define more clearly the reasons for withdrawal and to investigate whether withdrawal is consistent with patient preferences.
Aged↗
Addressing the ethical problems of randomized and placebo-controlled trials of CPAP.
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Ethics, Medical↗
Addressing the ethical challenges of clinical trials that involve patients with dementia.
Research subjects face uncertainties, risks, burdens, and indignities, and research protocol requirements inhibit the physician's ability to make individualized treatment decisions. To address these problems, investigators and Institutional Review Boards (IRBs) should justify research risks using informed consent and the judgment that the risks of research are reasonable with respect to the potential benefits, if any, to subjects and to the expectation that the research will produce important knowledge. But clinical research in Alzheimer's disease (AD) presents investigators and IRBs with significant challenges to achieve these two requirements. Broadly, these challenges are the result of the impact of patients' cognitive impairment and the caregiving experience on decision making and the indeterminacy of defining clinically meaningful treatment benefits. In this article, we review the data that begin to answer whether and how patients' cognitive impairments and the caregiving experience impact on their decision making and what kinds of research results justify research risks. We will use these data to suggest changes to the design and conduct of clinical research in AD that can meet the challenge of justifying research risks.
Alzheimer Disease↗
Placebo-controlled trials are unethical in clinical hypertension research.
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Controlled Clinical Trials as Topic↗
Caregivers' preferences for the treatment of patients with Alzheimer's disease.
OBJECTIVES: To learn caregivers' preferences for the treatment of AD with a disease-slowing therapy, and to identify relationships between these preferences and the characteristics of caregivers and patients. METHODS: A structured interview with 40 caregivers of patients with AD. Preferences were measured for an AD-slowing medicine with the benefits of a gain in survival and a delay to nursing home placement (NHP), and risks of three degrees of severity of GI bleeding. RESULTS: Using a six-point scale ranging from "not at all important" to "extremely important," the median rating of the importance of survival as a treatment benefit was "very important" and of a delay to NHP was "extremely important." Fifty-five percent of the caregivers identified a benefit more important than these two benefits. Qualitative data showed that caregivers' reasons for these preferences featured the importance of patient quality of life, and the preservation of patient cognition and function. Bivariate analyses showed that increasing importance of the benefit of survival was related to higher assessments of the patient's health and quality of life, and lower ratings of the caregiver's experience of burden. In order to slow disease progression by 1 year, 25/38 (66%) of caregivers would accept some risk of death from gastrointestinal bleeding. Regression models showed that risk tolerance was higher among caregivers who were working, adult children caring for early stage patients or from families with an history of dementia. CONCLUSIONS: Caregivers generally are willing to tolerate notable amounts of risk to slow AD progression. Factors that describe the caregiver's experience and perception of the patient and the patient-caregiver relationship influence how they want to treat the disease. This information may be useful for decisions about how to study and prescribe AD treatments.
Adult↗
Determining when quality improvement initiatives should be considered research: proposed criteria and potential implications.
Quality improvement initiatives have become a major force in shaping health care. These initiatives are diverse but share a common goal of generating knowledge that will guide improvements in health care. Although quality improvement occupies an uncertain territory between clinical care and research, this difference is extremely important. If a quality improvement initiative is research, federal regulations require a variety of procedures that must be followed to protect the human subjects involved. Conversely, if the same initiative is not research, the regulations outlining these procedures are not applicable. This article proposes 2 criteria to determine whether a quality improvement initiative should be reviewed as research. Such an initiative should be reviewed and regulated as research if (1) the majority of patients involved are not expected to benefit directly from the knowledge to be gained or (2) if additional risks or burdens are imposed to make the results generalizable. Implementation of these criteria offers the possibility that the rights and interests of those who participate in quality improvement initiatives will be protected.
Ethical Review↗
Should assisted suicide be only physician assisted? University of Pennsylvania Center for Bioethics Assisted Suicide Consensus Panel.
Discussions in the media, courts, legislatures, and professional societies generally assume assistance with suicide to be a physician's task; in these venues it is commonly referred to as "physician-assisted suicide." This paper defines both the necessity and the limits of the physician's role in assisted suicide by asking the question: Should assisted suicide be only physician assisted? Although physician involvement is necessary, we argue that it is not sufficient to ensure that patients requesting assisted suicide receive the best care. Assisted suicide requires physician involvement, but physicians' limited competence in performing the full range of tasks, the competencies of other professions, and the possibility that other professions could expand their authority in this area suggest that physician-assisted suicide is a far too narrow construct of the task. The willingness of other professionals--including nurses, social workers, and clergy--to participate and even take the lead in assisting suicides is critical to meet society's interest that assisted suicide should be humane, effective, and confined to appropriate cases. As long as legislation and guidelines focus exclusively on the physician's role, our laws and regulations will fall short of meeting societal expectations.
Ethics, Medical↗
Are special ethical guidelines needed for palliative care research?
Recent studies have made it clear that there are substantial opportunities to improve end-of-life care. Doing so will require solid evidence on which to base clinical and policy decisions and this, in turn, will require a focused research effort. However, research that involves patients near the end of life creates numerous ethical challenges. Moreover, the inclusion of dying patients in research may make many providers uncomfortable. In short, there seems to be something ethically unique, and uniquely challenging, about palliative care research. This paper considers 4 arguments for this unique status: 1) dying patients are especially vulnerable; 2) adequate informed consent may be difficult to obtain; 3) balancing research and clinical roles is particularly difficult; and 4) the risks and benefits of palliative research are difficult to assess. We conclude that the first three of these arguments are weak, and that special guidelines are not needed. We suggest, however, that the fourth argument may have some merit, and should be the focus of discussion among investigators, providers, and patients.
Ethics, Medical↗
Why physicians need to become more proficient in assessing their patients' competency and how they can achieve this.
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Alzheimer Disease↗
Sildenafil for diabetic men with erectile dysfunction.
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Clinical Trials as Topic↗
A consensus-based approach to providing palliative care to patients who lack decision-making capacity. ACP-ASIM End-of-Life Care Consensus Panel. American College of Physicians-American Society of Internal Medicine.
Making palliative care decisions for a patient who lacks decision-making capacity presents several challenges. Other people, such as family and caregivers, must choose for the patient. The goals and values of these decision makers may conflict with those of each other and with those of the patient, who now lacks the capacity to participate in the decision. This paper presents a case study of a patient with severe Alzheimer disease who has two common clinical problems: neurogenic dysphagia and aspiration pneumonia. The case study describes a consensus-based decision-making strategy that keeps what is known about the patient's wishes and values in the foreground but also expects guidance from the physician and elicits input from family members and other people who care for and have knowledge about the patient. The steps of this process, including key clinical prompts and potential transition statements, are outlined and described. The overall goal of the case commentary is to demonstrate that physicians can guide a highly emotional and personal process in a structured manner that has meaning for the patient, family, physician, and other caregivers.
Advance Care Planning↗
What is the quality of the reporting of research ethics in publications of nursing home research?
OBJECTIVE: To assess the quality of reporting of research ethics in published clinical research that involves a particularly vulnerable population: nursing home residents. DESIGN: A structured review of publications researched from 1992 to 1996 that involve nursing home residents. The review instrument assessed each publication's compliance with four common standards for research that involves nursing home residents or the cognitively impaired: justification of the use of nursing home residents, Institutional Review Board (IRB) review, nursing home committee review, and informed consent. For each publication, these results were summed into a quality score. The research ethics requirements contained in the journals' instructions for authors that corresponded with each publication were categorized in order to compare whether an association exists between the average quality score for each category and the detail of its research ethics instructions. RESULTS: Forty-five publications were identified. The four quality measures of research ethics showed that (1) all 45 publications reported justification of use of nursing home residents, (2) 36 publications reported that informed consent was obtained or waived, (3) 18 publications reported IRB review, and (4) six publications reported nursing home committee review. Of the 35 publications reporting informed consent was obtained, 16 reported assessing subjects' decisional capacity, and 24 reported whether cognitively impaired subjects were included (19) or excluded (5). The research ethics requirements of each publication's instructions for authors ranked it in one of four categories: (A) None (9); (B) Less than "Uniform Requirements (UR) for Manuscripts Submitted to Biomedical Journals" (7); (C) UR (24); (D) UR plus Additional Instructions (5). A positive association exists between the detail of a research ethics instructions category and the average research ethics quality score for each category (Kruskal-Wallis chi2 = 11.2, P = .01). That is, the more detailed the instructions, the greater the quality score. CONCLUSION: In publications of research that involves nursing home residents, basic standards of research ethics are not typically reported. However, the positive association between research ethics instructions category and research ethics quality score suggests that a journal's instructions for authors or other features of peer review and editing can affect the quality of reporting research ethics.
Clinical Trials as Topic↗
Is the placebo control obsolete in a world after donepezil and vitamin E?
Recent clinical trials of donepezil and vitamin E have produced active therapeutic drugs for the treatment of patients with Alzheimer disease (AD). The AD research community is now in a gray zone between the absence of accepted therapies and the presence of completely effective therapies. How should these therapies guide the choice of the proper control for future AD clinical trials? The community equipoise principle can guide a process to answer this question. The principle is that a clinical trial should answer clinical questions that are valued by the community who will use the results of that trial. This means that the choice of the proper control for future AD clinical trials ought to be guided by the values of a community who will experience the results of those trials: physicians and patients or their representatives such as caregivers. The values of patients can be included by giving them a voice in the design and review of clinical trials. Community dialogue should be the norm for the design and review of AD clinical trials. We conclude with suggestions to foster this dialogue and issues that should be addressed.
Cognition Disorders↗
Community equipoise and the architecture of clinical research.
We have argued for a revision of Freedman's concept of clinical equipoise to a broader sense of community that includes physicians and patients. Community equipoise is an essential condition for physicians and patients to answer these questions: Should there be a trial? If so, what kind? We have argued that community equipoise exists because of changes in the knowledge gap between physicians and patients and in the moral justification of medical decision-making. Finally, we have briefly examined the social aspect of medical knowledge to argue that it necessarily includes patients and their values. In effect, community equipoise is not so much an effort to change things, as to explain the way they are. We suggest that patients can participate at a number of points in the process of drug study design and approval: (1) study design with attention to criteria for eligibility, endpoints, and choice of methodology, (2) research review and approval with attention to enhancing community participation in IRB activities, and (3) interim evaluation of ongoing studies with attention to including patient and clinician values in the decisionmaking. Clinical trials are a tool. Like a gun or a bomb or the very drugs they test, they are powerful tools to achieve their ends. The issue is how to properly use such tools as randomization, placebo controls, endpoints, and eligibility. To the extent that community equipoise exists prior to a trial, it means that clinical researchers and patients have collectively addressed the risk and benefit trade-offs that govern the decision to start and to end a clinical trial. In this way, trials can be both valid and valued.
Acquired Immunodeficiency Syndrome↗
Research on the cognitively impaired: lessons and warnings from the emergency research debate.
OBJECTIVES: To demonstrate that the recent events in emergency research have broad implications for the conduct of human subjects research with the cognitively impaired. This essay illustrates the similarities between the two kinds of research and suggests how understanding these similarities might help to resolve issues in human subjects research on the cognitively impaired. METHODS: A review of pertinent journal articles, books, regulations, and court cases. RESULTS: The emergency research controversy resulted in large part because of conflicting interpretations of arguably inadequate research regulations. The proposed Food and Drug Administration (FDA) regulations include advance informed consent, a broad role for family in approving a subject's participation, replacement of a threshold of permissible risk, called minimal risk, with a more sensible balancing of risks and benefits, and a role for the community in research approval. The current state of research on the cognitively impaired suggests that many of the same problems exist now that existed in emergency research before the FDA issued its proposed regulations. The ongoing case of T.D. et al. vs N.Y. State Office of Mental Health suggest that unless steps are taken similar to those taken in emergency research, much of clinical research on the cognitively impaired could cease. CONCLUSION: Representatives of the government, medicine, and the public must recognize the unresolved issues and inadequate regulations relating to research on the cognitively impaired. The proposed FDA regulations for emergency research may provide guidance for a settlement of these issues.
Cognition Disorders↗