Patricia A. Marshall

Integrating common and rare genetic variation in diverse human populations.

Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called ‘HapMap 3’, includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of ≤5%, and demonstrated the feasibility of imputing newly discovered CNPs and SNPs. This expanded public resource of genome variants in global populations supports deeper interrogation of genomic variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

The difference that culture can make in end-of-life decisionmaking.

Cultural difference has been largely ignored within bioethics, particularly within the end-of-life discourses and practices that have developed over the past two decades in the U.S. healthcare system. Yet how should culture—specifically cultural differences as reflected among groups defined as ethnically or racially different—be taken into account?

Informed consent in international health research.

Informed consent is universally recognized as a central component of ethical conduct in scientific research. Investigators working with diverse populations throughout the world face myriad challenges. The application of standards for informed consent can be daunting for researchers when they face the pragmatic constraints of the field and the reality of cultural beliefs about consent that may be in direct conflict with regulatory requirements. This paper explores cultural and social factors underlying informed consent for health research with diverse populations in international settings. Sociocultural influences on comprehension of information, perceptions of risk, and beliefs regarding decisional authority are reviewed. The implications of power inequities between study sponsors, researchers and participants are also considered. Issues associated with the development and preparation of consent forms, including translation and documentation are highlighted. Recommendations for good practices are outlined and future directions for research are explored.

Ethical Challenges in Community-Based Research

&NA; Investigators in population‐based studies confront unique ethical challenges due to the community context of their research, their methods of inquiry, and the implications of their findings for social groups. Issues surrounding requirements for informed consent, the protection of privacy and confidentiality, and relationships between investigators and participants take on greater complexity and have significance beyond the individual research subject. In this paper, ethical challenges associated with community‐based epidemiological research are briefly examined. We argue that ethically responsible population‐based studies must seriously consider community needs and priorities and that researchers should work collaboratively with local populations to implement study goals. Strategies that promote respect for populations in community‐based studies are outlined. These include community participation in research development, implementation and interpretation; adequate provision of information about study objectives to community members; and systematic feedback of study results.

Accounting for Culture in a Globalized Bioethics

How might a global bioethics account for profound cultural difference in a world marked by porous borders? The authors endorse a critical, self-reflexive bioethics, suggesting that bioethics needs to change its fundamental orientation if it is going to remain relevant and intellectually vibrant throughout the twenty-first century. Bioethics must attend to issue of social justice and public health, while seriously considering the implications of social context for medical morality. Negotiating moral consensus across cultural boundaries will be difficult, but is is more likely to succeed if we critically engage with the cultural assumptions underlying bioethics itself.

Community Engagement and Informed Consent in the International HapMap Project

The International HapMap Consortium has developed the HapMap, a resource that describes the common patterns of human genetic variation (haplotypes). Processes of community/public consultation and individual informed consent were implemented in each locality where samples were collected to understand and attempt to address both individual and group concerns. Perceptions about the research varied, but we detected no critical opposition to the research. Incorporating community input and responding to concerns raised was challenging. However, the experience suggests that approaching genetic variation research in a spirit of openness can help investigators better appreciate the views of the communities whose samples they seek to study and help communities become more engaged in the science.

The decision dynamics of clinical research: the context and process of informed consent.

This article explores the neglected dimensions of informed consent. In such documents as the Code of Federal Regulations that govern clinical research, it is explicitly stated that informed consent is a process, not a form to be signed. However, virtually all research on informed consent has proceeded as if informed consent is an event similar to a Miranda warning. The authors review what is known about the process of informed consent and ask what questions must be explored if the dynamics of the clinical decision-making process are to be better understood. Their investigation takes place in two parts. First, the authors survey what is known or not known about the effect and influence of two major parties to the decision-making process (ie, support groups in which the subject participates and the subject’s primary care physician). Second, they focus on the cultural and demographic factors that contribute to the subject’s identity. Although they do not propose that informed consent must become a complicated and burdensome process, they stress that understanding the process in any meaningful way will mean that one must understand these various influences to get beyond the voluminous, but often facile, research that has characterized work on informed consent.

Cultural influences on perceived quality of life

Cross-cultural investigations of quality of life will provide a more well-rounded picture of the multidimensional aspects of life satisfaction and personal well-being. Careful attention must be given to the nuances of language and sociocultural context in the translation of questionnaires and the implementation of cross-national research. Future explorations of the concept of quality of life should incorporate qualitative and ethnographic data to insure an adequate representation of the social and emotional context surrounding perceptions of well-being and life satisfaction. A meaning-centered approach to the examination of quality of life will facilitate understanding of the nature of wellness and the impact of illness on individuals and families of every cultural background.

Marketing human organs: The autonomy paradox

The severe shortage of organs for transplantation and the continual reluctance of the public to voluntarily donate has prompted consideration of alternative strategies for organ procurement. This paper explores the development of market approaches for procuring human organs for transplantation and considers the social and moral implications of organ donation as both a “gift of life” and a “commodity exchange.” The problematic and paradoxical articulation of individual autonomy in relation to property rights and marketing human body parts is addressed. We argue that beliefs about proprietorship over human body parts and the capacity to provide consent for organ donation are culturally constructed. We contend that the political and economic framework of biomedicine, in western and non-western nations, influences access to transplantation technology and shapes the form and development of specific market approaches. Finally, we suggest that marketing approaches for organ procurement are and will be negotiated within cultural parameters constrained by several factors: beliefs about the physical body and personhood, religious traditions, economic conditions, and the availability of technological resources.

How patients view probiotics: Findings from a multicenter study of patients with inflammatory bowel disease and irritable bowel syndrome

Background Patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) have access to a growing number of probiotic products marketed to improve digestive health. It is unclear how patients make decisions about probiotics and what role they expect their gastroenterologists to play as they consider using probiotics. Understanding patients’ knowledge, attitudes and expectations of probiotics may help gastroenterologists engage patients in collaborative discussions about probiotics. Study Focus groups were conducted with patients with IBD and IBS at the Cleveland Clinic, Mayo Clinic, and Johns Hopkins University. Inductive analytic methods were used to identify common themes and draw interpretations from focus group narratives. Results One hundred thirty-six patients participated in 22 focus groups between March and August 2009. Patients viewed probiotics as an appealing alternative to pharmaceutical drugs and understood probiotics as a more “natural,” low-risk therapeutic option. Many patients were hesitant to use them without consulting their gastroenterologists. Patients would weigh the risks and benefits of probiotics, their disease severity and satisfaction with current treatments when considering probiotic use. Conclusions Patients are interested in probiotics but have many unanswered questions about their use. Our findings suggest that patients with IBD and IBS will look to gastroenterologists and other clinicians as trustworthy advisors regarding the utility of probiotics as an alternative or supplement to pharmaceutical drugs. Gastroenterologists and other clinicians who care for patients with these diseases should be prepared to discuss the potential benefits and risks of probiotics and assist patients in making informed decisions about their use.