The Belmont Report’s distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole (...) exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. (shrink)

In this essay, we defend the design of the Salk polio vaccine trial and try to put some limits on the role schemata should play in designing clinical research studies. Our presentation is structured as a response to de Freitas and Pietrobon who identified the CONSORT statement as a schema that would have, had it existed at the time, ruled out the design of the Salk polio vaccine trial of 1954 in favor of a completely randomized controlled clinical trial. We (...) argue that large-scale public health interventions often require evidence beyond simple efficacy, the limit of what an RCT can provide, and that the design actually adopted for the Salk trial represented a reasonable—albeit imperfect—compromise. This is of more than historical interest in that many contemporary studies are of the scale and scope to require a more pragmatic, rather than explanatory, approach to study design. (shrink)

Survival of the fittest in evolutionary biology has a counterpart in the evolution of research paradigms. It’s called survival of the funded, and there is a sense in which paradigms are even more adaptable than species. Whereas species may become extinct if their fitness declines below a critical threshold, paradigms can rise again, perhaps with a new name, following fiscal collapse, provided only that funding is once again made available.A current example is the born-again concept of comparative effectiveness research , (...) which achieved resurrection status with the passage of the Affordable Care Act of 2010. The ACA established a private, nonprofit entity to oversee publicly financed CER. According to .. (shrink)

David Sackett and Jack Wennberg have each introduced and developed ideas and methods that have had major impacts on how we think about and perform clinical research. Sackett is best known for his work in Evidence-Based Medicine (Sackett et al. 1997); Wennberg, upon noting wide geographic (and other) variations in best practices for the same conditions, stressed the importance of comparative effectiveness in clinical decision-making (Wennberg et al. 1993). When these two collaborated in an editorial about the current state of (...) the art and science of clinical research, it comes as no great surprise that they produced some truly memorable guidance. And, as is so often the case for inspired—and inspiring—advice, their .. (shrink)

That dichotomization is, at least under certain circumstances, a bad idea is not news. A well-known, early example is the biblical story of King Solomon, who used the absurdity of the procedure to help adjudicate a dispute between two women who each claimed to be the mother of a contested child. Solomon reasoned that his proposal to split the child into two, giving half to each woman, would be abhorrent to the real mother, and when one of the women objected (...) while the other thought the proposal was "only fair," the choice between the women was made obvious.Things, however, are not always so clear-cut, and it is not difficult to find arguments that point to the advantages that accrue to those that simplify matters.... (shrink)

In a recent paper in this journal, John Worrall (2008) used the example of a series of trials involving extracorporeal membrane oxygenation (ECMO), a technology for the treatment of respiratory failure in newborns, to illustrate the relationship between ethics and epistemology in medical research. One of the issues considered was whether or not it was ethical to perform a particular clinical trial at all, and he showed clearly that the answer was intimately related to epistemological judgments about the weight to (...) be given existing evidence concerning treatment effectiveness. In the case of ECMO, a trial was initiated at the University of Michigan (Bartlett et al. 1985), despite the fact that the researchers had .. (shrink)

It is perhaps most useful to approach the Doctor-Patient relationship (DPR) by admitting that it’s complicated. We review some of the strategies that have been employed to mitigate this complexity, zeroing in on one that promises to capture the main features of the DPR without eliminating some of its more important, existential components; pieces of the puzzle that must be retained if we are to avoid oversimplification and the errors that can arise by ignoring important foundational properties. We believe that (...) a useful way to look at the DPR and to capture essential features that must be balanced in the process is provided by Partnership Theory and its definition in terms of the so-called domination and partnership systems. We apply this theory to the DPR and investigate the implications of this application to health care. We see that in the absence of mitigating circumstances, adoption of the patient-as-partner model serves healthcare well and is flexible enough to accommodate circumstances that dictate modifications. (shrink)

Following Bernheim,1 we examine aspects of 'felicitometrics,'2 the measurement of the 'quality' term in Quality of Life (QOL). Bernheim argued that overall QOL is best captured as the Gestalt3 of a global self-assessment and suggested that the Anamnestic Comparative Self Assessment (ACSA) approach, in which subjects' memories of the best and worst times of their lives are used to anchor a Visual Analog Scale (VAS), provided a serious answer to the serious question, 'How have you been?' Bernheim compares and contrasts (...) the ACSA to multi-item questionnaire QOL instruments, such as the SF-36, concluding that the ACSA has a number of advantages. His discussion assumes that the use of QOL outcomes in clinical trials is both relevant and appropriate. In the present paper, we document the reasonableness of this latter assumption,4 contribute to the characterization of the similarities and differences between multi-item and individualized QOL instruments, and point to some other individualized instruments that may be used in clinical trial contexts. These 'other individualized instruments' differ from the ACSA in fundamental ways; but they are individualized in that the subject defines those areas in his/her life that are most important, and these may vary from subject-to-subject. (shrink)

The use of quality of life (QOL) outcomes in clinical trials is increasing as a number of practical, ethical, methodological, and regulatory reasons for their use have become apparent. It is important, then, that QOL measurements and differences between QOL scores be readily interpretable. We study interpretation in two contexts: when determining QOL and when basing decisions on QOL differences. We consider both clinical situations involving individual patients and research contexts, e.g., randomized clinical trials, involving groups of patients. We note (...) the ethical importance of such understanding: proper interpretation and communication facilitate health care decision making. Communication that facilitates interpretation is of moral significance since better communication can attenuate ethical problems and inform choices. Much of what is communication worthy about QOL assessments is determined by the particular QOL instrument used in the assessment and how it is administered. In practice, these choices will be driven by the purpose of the assessment, but, it is argued, to maximize understanding, we should combine the information garnered from traditional standardized QOL instruments, from individualized QOL assessments, and from a recently proposed dialogic paradigm, where QOL is determined by shared conversation regarding the interpretation of texts. And, while some studies can surely succeed using abbreviated methods of administration (e.g., postal surveys may suffice for certain purposes), we will focus on methods of administration involving interviewer–respondent interaction. We suggest that during the QOL elicitation process, interviewer and respondent should engage in a two-way conversation in order to achieve a shared understanding of the “answers” to QOL “questions” and, finally, to reach a shared interpretation of the individual’s QOL. (shrink)

Data Safety and Monitoring Boards have been referred to as a “growth industry,” and this trend continues to be fueled by recent FDA guidance and the NIH's requirement that DSMBs be employed in virtually all phase III clinical trials. The widening role of DSMBs has been sporadically questioned on ethical grounds, but growth has continued, despite the fact that many of the questions endure, unanswered, save for repeated references to safeguarding the scientific integrity of trials. This may be about to (...) change. The recently appointed director of the Office for Human Research Protections , Jerry Menikoff, is on record as regarding current practices — where consent forms often promise what the DSMB has been assembled to specifically not provide — as constituting fraudulent behavior. That is, a subject may inherently rely on, to their detriment, information that has been misrepresented in the consent document. In this paper, we assemble some of the enduring questions and top them off with Menikoff's tour de force to present what we hope will be a compelling argument to require that consent forms fairly represent what the DSMB will do — and not do — with trial data as they accumulate. We argue that DSMBs should be used only in rare circumstances, and question the practice of precluding principal investigators from DSMB membership, but our main thrust is to ensure that DSMBs, when used at all, are properly described in trial consent forms. (shrink)

Data Safety and Monitoring Boards were introduced in the 1960s to monitor data in clinical trials to ensure subject safety. It was thought important that DSMB members be experts in the field of interest, but not otherwise involved in the study in order to maximize objectivity. Since then, the use of DSMBs has increased dramatically, and their scope has expanded to include scientific issues — in particular, to avoid bias that can result when trials are stopped early because of evidence (...) that one treatment has greater efficacy or causes greater harm than another; or that no treatment is likely to do better than any other. (shrink)