BackgroundLittle is known about volunteers from Northern research settings who participate in vaccine trials of highly infectious diseases with no approved treatments. This article explores the motivations of HIV immunocompromised study participants in Canada who volunteered in a Phase II clinical trial that evaluated the safety and immunogenicity of an Ebola vaccine candidate.MethodsObservation at the clinical study site and semi-structured interviews employing situational and discursive analysis were conducted with clinical trial participants and staff over one year. Interviews were recorded, transcribed (...) and analysed using critical qualitative interpretivist thematic analytical techniques. Patterns were identified, clustered and sorted to generate distinct and comprehensive themes. We then reassembled events and contexts from the study participants’ stories to develop two ideal portraits based on "composite characters" based on study participants features. These provide ethnographically rich details of participants’ meaningful social worlds while protecting individual identities.ResultsTen of the 14 clinical trial participants, and 3 study staff were interviewed. Participant demographics and socio-economic profiles expressed limited contextual diversity. Half were men who have sex with men, half were former injection drug users experiencing homelessness, one was female, none were racialized minorities and there were no people from HIV endemic countries. Fully 90% had previous involvement in other clinical studies. Their stories point to particular socio-economic situations that motivated their participation as clinical labor through trial participation.ConclusionsOur findings support Fisher’s argument of “structural coercion” in clinical trial recruitment of vulnerable individuals experiencing precarious living conditions. Clinical trials should provide more detail of the structural socio-economic conditions and healthcare needs which lie “under consent” of study participants. Going well beyond an overly convenient narrative of altruism, ethical deliberation frameworks need to sufficiently address the structural conditions of clinical trials. We offer concrete possibilities for this and acknowledge that further research and clinical data should be made available underlying study participant contexts with regards to recruitment and participation in resource poor settings, in both the South and the North. (shrink)

Gaining informed consent among marginalized groups that include decisionally incapacitated individuals and those outside of the researcher's own geo-social and ethnic background still challenges many researchers. We suggest that there is a need for consideration of a different approach to research ethics in international settings. Based on extensive field work in West Africa on medical knowledge transfers and patient–healer relationships, this paper will discuss the challenges posed in obtaining informed individual consent in international settings. It is argued that while being (...) on the whole convincing, the top-down approach of the proposed solutions, which clearly dominates the participative approach, fails in building sustainable capacity, decision-making competency, and empowerment in the communities in which the research is conducted. Using appropriate decision aids can help resolve these issues. (shrink)

The evolution of a relevant nosological concept reflects changes in the distinction between what is recognized and defined as normal and pathologic. Attention is directed to the rationale and value of detecting subclinical aging-related modifications in cognitive performance. The position that different kinds of dementias may have precedents in etiological-specific kinds of early or mild cognitive impairments (MCI) supports targeting people earlier for study of these subclinical symptoms. Because heterogeneous disorders can be expected to have multiple patterns of cognitive and (...) behavioral changes, useful conceptual nosologies should be flexible. Yet clinical research primarily restricts its focus to a single pathway where MCI leads to Alzheimer's disease (AD), and uses selective recruitment, washout screenings, repeated trialing of similar compounds, and other methods that bank the published evidence in favor of the existing therapies and their modest efficacy. This focus on AD recursively colors MCI, not as a flexible "human kind" in need of more careful research, but like AD, as an essential "natural kind." Early determination of MCI targets a potential pharmaceutical market of a quarter to a half of the population over sixty-five and the individual experiencing cognitive decline in its early stages is aware and sensitive to their surroundings, to a linked sociodegeneration with neurodegeneration. This paper examines how classifying people changes both the classifier and the subject of classification. The potential for conflict of interest is raised regarding what new causal knowledge and techniques for ascertainment are selected. Reading evidence from epidemiology, neurology, and clinical studies through science studies and bioethics lenses, we explore the possibility of a pluralistic model of cognitive impairment nosology where biological/pathologic processes respond and interrelate with a normal healthy state. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Reifying Relevance in Mild Cognitive Impairment:An Appeal for Care and CautionJanice E. Graham (bio) and Karen Ritchie (bio)KeywordsAlzheimer’s disease, construction, dementia, market forces, mild cognitive impairmentWe thank the reviewers for their thoughtful comments that probe shadowy areas in our argument, and we welcome this opportunity to elucidate our position. First, we are not repudiating the natural and social facts of pathologic brain degeneration and the physical and cognitive impairments (...) that manifest in people affected by dementia disorders. We are, however, questioning the epistemology, politics, and persistence by some to harden the construct of mild cognitive impairment (MCI) prematurely as a "natural" precursor to dementia. We suggested insufficiencies in viewing MCI as prodromal to Alzheimer's disease (AD; Graham and Ritchie 2006, 36), and pointed to evidence for the prognostic irrelevance of some MCI subcategories (35). The commentators have read our manuscript as suggesting that AD and MCI are different kinds, and that a diagnosis of AD is more "real" than that of MCI. But AD is also fraught with classification issues, as we describe in the section of our paper that deals with consensus committees, published practice guidelines, and the determination of treatment efficacy. Like MCI, AD is a heterogeneous condition, but unlike MCI, AD is a constructed practical kind that does some "work" beyond essentialist (neural degeneration, brain atrophy) claims. Its criteria identify people with well-defined dementia symptoms and multiple cognitive and functional impairments who are in need of, and benefit from, support. Even with these criteria, however, there have been great attempts to achieve definitional accuracy in dementia diagnoses. Practical refinements to the differential diagnosis of dementia based on solid research evidence have made way for more specific recognitions of vascular dementias, dementia of the Lewy body type, and other subtypes beyond AD. So AD too has been subject to more careful, more cautious operationalization in recent years, with research supporting multiple factors and the comorbidity of several types (kinds) of dementia in any one individual.Our paper takes up concerns that are not resolved for dementia and suggests that the nascent category of MCI is still so insufficiently defined as to be ambiguous, and as such, is in danger of identifying individuals with what will be, and has [End Page 57] already been, linked to a debilitating and deeply stigmatizing and fatal disorder (AD). We are not contesting the reality that some people begin to display early signs of cognitive loss, nor are we suggesting that symptoms be ignored; as researchers, we stand behind the careful tracking of symptoms and signs in patients and research participants as an essential clinical and research practice. In a era where the public has been made wary of the potentially fatal effects of new treatments whose more careful scrutiny in specific populations would have saved lives (e.g., Fontanarosa, Rennie, and DeAngelis 2004; Psaty and Furberg 2005), and made all the more popular by what Kramer coined "diagnostic bracket creep" (1993, 15), we are questioning the drivers and value of a premature diagnostic classification whose definitional accuracy is neither sufficient nor effective for specific identification of individuals.That matters of fact are constructed does not take away from their natural fact. Some people have subjective reports or show objective evidence of cognitive decline while having preserved activities of daily living—the construction of this evidence indicates they are not normal and they are not demented. Based on such evidence, where then does the balance of probability for MCI lie? A multidisciplinary international group of experts gathered in Stockholm in 2003 to discuss MCI concepts (Winblad et al. 2004). They acknowledged that the heterogeneous etiology of MCI contributes to "some confusion concerning the specific boundaries of the condition", stating that this "not normal, not demented" condition is nonetheless "useful both clinically and as a research entity" (p. 241). Importantly, they concluded that MCI needs "better definition" (p. 246). It was at this stage that we first wrote our manuscript, and in the subsequent two years we have eagerly awaited new studies, and the recognition of flexible, practical subtypes to evolve.We state "that MCI cannot be considered to be a separate clinical entity" (Graham and... (shrink)

An amendment to this paper has been published and can be accessed via the original article.