Potential bias in the bank: what distinguishes refusers, nonresponders and participants in a clinic-based biobank?

BACKGROUND: Biobanks are an important resource for genetic and epidemiologic research, but bias may be introduced if those who accept the recruitment invitation differ systematically from those who do not in terms of attributes important to health-related investigations. To understand potential bias in a clinic-based biobank of biological samples, including genetic data linked to electronic health record information, we compared patient characteristics and self-reported information among participants, nonresponders and refusers. We also compared reasons for nonparticipation between refusers and nonresponders to elucidate potential pathways to reduce nonparticipation and any uncovered bias. METHODS: We mailed recruitment packets to 1,600 adult patients with upcoming appointments at Mayo Clinic (Rochester, Minn., USA) and recorded their participation status. Administrative data were used to compare characteristics across groups. We used phone interviews with 26 nonresponders and 26 refusers to collect self-reported information, including reasons for nonparticipation. Participants were asked to complete a mailed questionnaire. RESULTS: We achieved 26.2% participation (n=419) with 12.1% refusing (n=193) and 61.8% nonresponse (n=988). In multivariate analyses, sex, age, region of residence, and race/ethnicity were significantly associated with participation. The groups differed in information-seeking behaviors and research experience. Refusers more often cited privacy concerns, while nonresponders more often identified time constraints as the reason for nonparticipation. CONCLUSION: For genomic medicine to advance, large, representative biobanks are required. Significant associations between patient characteristics and nonresponse, as well as systematic differences between refusers and nonresponders, could introduce bias. Oversampling or recruitment changes, including heightened attention to privacy protection and participation burden, may be necessary to increase participation among less-represented groups.

Integrating genetic studies of nicotine addiction into public health practice: stakeholder views on challenges, barriers and opportunities.

OBJECTIVE: Will emerging genetic research strengthen tobacco control programs? In this empirical study, we interview stakeholders in tobacco control to illuminate debates about the role of genomics in public health. METHODS: The authors performed open-ended interviews with 86 stakeholders from 5 areas of tobacco control: basic scientists, clinicians, tobacco prevention specialists, health payers, and pharmaceutical industry employees. Interviews were qualitatively analyzed using standard techniques. RESULTS: The central tension is between the hope that an expanding genomic knowledge base will improve prevention and smoking cessation therapies and the fear that genetic research might siphon resources away from traditional and proven public health programs. While showing strong support for traditional public health approaches to tobacco control, stakeholders recognize weaknesses, specifically the difficulty of countering the powerful voice of the tobacco industry when mounting public campaigns and the problem of individuals who are resistant to treatment and continue smoking. CONCLUSIONS: In order for genetic research to be effectively translated into efforts to minimize the harm of smoking-related disease, the views of key stakeholders must be voiced and disagreements reconciled. Effective translation requires honest evaluation of both the strengths and limitations of genetic approaches.

Ethical decision making and patient autonomy: a comparison of physicians and patients in Japan and the United States.

BACKGROUND: Patient-centered decision making, which in the United States is typically considered to be appropriate, may not be universally endorsed, thereby harboring the potential to complicate the care of patients from other cultural backgrounds in potentially unrecognized ways. This study compares the attitudes toward ethical decision making and autonomy issues among academic and community physicians and patients of medical center outpatient clinics in Japan and the United States. METHODS: A questionnaire requesting judgments about seven clinical vignettes was distributed (in English or Japanese) to sample groups of Japanese physicians (n = 400) and patients (n = 65) as well as US physicians (n = 120) and patients (n = 60) that were selected randomly from academic institutions and community settings in Japan (Tokyo and the surrounding area) and the United States (the Stanford/Palo Alto, CA, area). Responses were obtained from 273 Japanese physicians (68%), 58 Japanese patients (89%), 98 US physicians (82%), and 55 US patients (92%). Physician and patient sample groups were compared on individual items, and composite scores were derived from subsets of items relevant to patient autonomy, family authority, and physician authority. RESULTS: A majority of both US physicians and patients, but only a minority of Japanese physicians and patients, agreed that a patient should be informed of an incurable cancer diagnosis before their family is informed and that a terminally ill patient wishing to die immediately should not be ventilated, even if both the doctor and the patient's family want the patient ventilated (Japanese physicians and patients vs US physicians and patients, p < 0.001). A majority of respondents in both Japanese sample groups, but only a minority in both US sample groups, agreed that a patient's family should be informed of an incurable cancer diagnosis before the patient is informed and that the family of an HIV-positive patient should be informed of this disease status despite the patient's opposition to such disclosure (Japanese physicians and patients vs US physicians and patients, p < 0.001). Physicians in both Japan and the United States were less likely than patients in their respective countries to agree with physician assistance in the suicide of a terminally ill patient (Japanese physicians and patients vs US physicians and patients, p < 0.05). Across various clinical scenarios, all four respondent groups accorded greatest authority to the patient, less to the family, and still less to the physician when the views of these persons conflicted. Japanese physicians and patients, however, relied more on family and physician authority and placed less emphasis on patient autonomy than the US physicians and patients sampled. Younger respondents placed less emphasis on family and physician authority. CONCLUSIONS: Family and physician opinions are accorded a larger role in clinical decision making by the Japanese physicians and patients sampled than by those in the United States, although both cultures place a greater emphasis on patient preferences than on the preferences of the family or physician. Our results are consistent with the view that cultural context shapes the relationship of the patient, the physician, and the patient's family in medical decision making. The results emphasize the need for clinicians to be aware of these issues that may affect patient and family responses in different clinical situations, potentially affecting patient satisfaction and compliance with therapy.

Collective fear, individualized risk: the social and cultural context of genetic testing for breast cancer.

The purpose of this article is to provide a critical examination of two aspects of culture and biomedicine that have helped to shape the meaning and practice of genetic testing for breast cancer. These are: (1) the cultural construction of fear of breast cancer, which has been fuelled in part by (2) the predominance of a 'risk' paradigm in contemporary biomedicine. The increasing elaboration and delineation of risk factors and risk numbers are in part intended to help women to contend with their fear of breast cancer. However, because there is no known cure or foolproof prevention for breast cancer, risk designations bring with them recommendations for vigilant surveillance strategies and screening guidelines. We argue that these in effect exacerbate women's fears of breast cancer itself. The volatile combination of discourses of fear, risk and surveillance have significant ethical and social consequences for women's lives and well-being. Genetic testing decisions are made within this context; if nurses understand this context they can play an important role in helping women to cope with the anxiety and fear of breast cancer risk.

Genetic testing and Alzheimer disease: recommendations of the Stanford Program in Genomics, Ethics, and Society.

Several genes associated with Alzheimer disease (AD) have been localized and cloned; two genetic tests are already commercially available, and new tests are being developed. Genetic testing for AD--either for disease prediction or for diagnosis--raises critical ethical concerns. The multidisciplinary Alzheimer Disease Working Group of the Stanford Program in Genomics, Ethics, and Society (PGES) presents comprehensive recommendations on genetic testing for AD. The Group concludes that under current conditions, genetic testing for AD prediction or diagnosis is only rarely appropriate. Criteria for judging the readiness of a test for introduction into routine clinical practice typically rely heavily on evaluation of technical efficacy. PGES recommends a broader and more comprehensive approach, considering: 1) the unique social and historical meanings of AD; 2) the availability of procedures to promote good surrogate decision making for incompetent patients and to safeguard confidentiality; 3) access to sophisticated genetic counselors able to communicate complex risk information and effectively convey the social costs and psychological burdens of testing, such as unintentional disclosure of predictive genetic information to family members; 4) protection from inappropriate advertising and marketing of genetic tests; and 5) recognition of the need for public education about the meaning and usefulness of predictive and diagnostic tests for AD. In this special issue of Genetic Testing, the PGES recommendations are published along with comprehensive background papers authored by Working Group members.

Understanding probabilistic risk in predisposition genetic testing for Alzheimer disease.

The utility of genetic testing in preventing the onset of conditions such as Alzheimer disease (AD) depends upon categorizing individuals based on their "risk" of illness. Although no strategies to prevent the occurrence of AD have been proven effective, the promise of the new molecular medicine is based on the assumption that those "at risk" can be identified, counseled about their likelihood of developing a disease, and prescribed specific preventive interventions. We suggest that this paradigm of disease prevention through risk stratification has limitations that have not been fully explored. Within the fields of cognitive and health psychology, research has addressed how individuals understand the numeric presentation of uncertain future events; this research often focuses on the "perceptual pathology" of lay people. The uncertainty inherent in the risk estimates themselves is rarely considered, nor has research addressed how those risk estimates are created. There has been limited work to date focused on genetic risk assessment, and little is known about how individual might understand the meaning or consequences of being at genetic risk for AD. An emerging social science critique of concepts of risk in genetic medicine offers a broader perspective, examining the process of producing scientific risk estimates as well as the response of individual patients, such as the experience of embodied risk that is central to genetic testing. Making fully informed choices about genetic testing for AD may prove more difficult than our current model of ethical practice suggests.

Acute profound thrombocytopenia following C7E3 Fab (Abciximab) therapy: case reports, review of the literature and implications for therapy.

Platelets play a crucial role in the ischemic complications of percutaneous coronary procedures. The recent availability of C7E3 Fab (Abxiximab or ReoProtrade mark), a chimeric monoclonal antibody Fab fragment directed against the platelet glycoprotein IIb/IIIa receptor, has reduced abrupt closure and other adverse events and lessened the need for revascularization procedures. As the use for this drug has increased, rare cases of severe thrombocytopenia have been revealed. From August 1995 to June 1997, 452 patients at Charleston Area Medical Center who underwent percutaneous coronary revascularization procedures and were treated with abciximab were evaluated for the development of severe thrombocytopenia (i.e., platelet count less than 20,000 within 48 hr of treatment). A review of published reports of severe thrombocytopenia was also reviewed. A review of published reports of abciximab-induced severe thrombocytopenia, as well as our three cases, reveals that: 1) the incidence is less than 0.7%; 2) the nadir platelet count (range 1, 000-16,000) was noted within 2-31 hr after abciximab infusion; 3) the platelet count increases to greater than 100,000 within 12 days in all patients; 4) bleeding episodes were treated with platelet transfusion with an improvement in platelet count within 24 hr in all patients in whom they were given; and 5) in the one patient treated with gamma globulin alone, no significant rise in platelet count was noted. Acute severe thrombocytopenia can occur after ReoProtrade mark administration. Its development is not predictable and may occur within 2 hr of administration. Thrombocytopenia, therefore, requires consideration in every patient treated with this drug. It appears prudent to obtain a platelet count 2 hr after initiating ReoProtrade mark. If thrombocytopenia develops, then the drug can be stopped in a timely manner and platelet transfusion can be given.

Multicultural considerations in the use of advance directives.

PURPOSE/OBJECTIVES: To describe advance directives and the Patient Self-Determination Act (PSDA), to explore the European American sociocultural values underlying advance directives, and to describe the ethical and cultural issues that arise when attempting to encourage and use advance directives in culturally diverse populations. DATA SOURCES: Research articles, case studies, and theoretical articles from clinical and bioethical literature. DATA SYNTHESIS: An overview of advance directives and the PSDA is provided. The European American cultural values underlying advance directives are reviewed and contrasted with sociocultural values of culturally diverse groups to raise the question of cross-cultural applicability of advance directives and European-based bioethics. CONCLUSIONS: The sociocultural values of many culturally diverse groups conflict with the values on which the use of advance directives is based. Thus, working with end-of-life decisions and advance directives for people from culturally diverse groups may be problematic. IMPLICATIONS FOR NURSING PRACTICE: Nurses should be sensitive to sociocultural beliefs that influence decisions affecting end-of-life care, especially the use of advance directives. Practitioners must incorporate this knowledge to increase flexibility of institutional practices and standards of care in the application of advance directives.

Informed consent in a multicultural cancer patient population: implications for nursing practice.

Obtaining informed consent, an ethical obligation of nurses and other health care providers, occurs routinely when patients make health care decisions. The values underlying informed consent (promotion of patients' well-being and respect for their self-determination) are embedded in the dominant American culture. Nurses who apply the USA's cultural values of informed consent when caring for patients who come from other cultures encounter some ethical dilemmas. This descriptive study, conducted with Latino, Chinese and Anglo-American cancer patients in a large, public, west-coast clinic, describes constraints on the informed consent process in a multicultural setting, including language barriers, the clinical environment, control in decision making, and conflicting desired health outcomes for health care providers and patients, and suggests some implications for nursing practice.

Report of the Northern California Conference for Guidelines on Aid-in-Dying: definitions, differences, convergences, conclusions.

In September 1996, the Stanford University Center for Biomedical Ethics convened a conference entitled "Comprehensive Care of the Terminally Ill: The Northern California Consensus Development Conference for Guidelines on Aid-in-Dying." The regionally based, multidisciplinary conference gathered people from a variety of disciplines and diverse perspectives on physician aid-in-dying. This report documents important points of convergence, disagreement, and uncertainty that emerged from the conference and provides commentary on crucial issues: the definition of terminal illness, ensuring adequate palliative care, psychiatric challenges, coping with family pressures, the doctor-patient relationship, the managed care context, the role of ethics committees, and institutional challenges. Should physician aid-in-dying become a legal practice in California, the report will provide guidance to health care organizations, health professionals, and public policy officials engaged in local or state guideline or policy development.