Most phase III clinical trials today are explanatory. Because explanatory, or efficacy, trials test hypotheses under “ideal” conditions, they are not well suited to providing guidance on decisions made in most clinical care contexts. Pragmatic trials, which test hypotheses under “usual” conditions, are often better suited to this task. Yet, pragmatic, or effectiveness, trials are infrequently carried out. This mismatch between the design of clinical trials and the needs of health care professionals is frustrating for everyone involved, and explains some (...) of the challenges inherent in attempts to enhance knowledge translation and encourage evidence-based practice. The situation is more than simply frustrating, however; it is potentially unethical. Clinical trials must be socially valuable in order to (1) warrant the risks they impose on human research subjects and (2) fairly and efficiently assess new clinical interventions. Most bioethicists would agree that trials that have no social value, for instance, because their results do not have the potential to advance clinical care, should not be performed. What is less widely appreciated is that given limited research resources, trials that are more socially valuable should be preferred to trials that are less socially valuable when all else is equal. With respect to clinical trial design, I argue that while explanatory trials often have some social value, many have less social value than their pragmatic counterparts. On the basis of this general ethical assessment, I provide a preliminary defense of the position that clinical researchers should aim to conduct pragmatic trials, that is, that researchers face a burden of justification related to any idealizing elements added to trial designs. (shrink)

The volume of clinical research is increasing exponentially—far beyond our ability to process and absorb the results. Given this situation, it may be beneficial to consider reducing the flow at its source. In what follows, I will motivate and critically evaluate the following proposal: researchers should conduct fewer clinical trials. More specifically, I c onsider whether researchers should be permitted to conduct only clinical research of very high quality and, in turn, whether research ethics committees should prohibit all other, lower-quality (...) research, even when it might appear to meet some minimal ethical standard. Following a close analysis of the social-value requirement of ethical clinical research, I argue that this proposal is defensible. The problem identified in this paper has two parts, quantity and quality, and some clarification is needed about the latter because “quality” is a highly contested term in the medical literature. When some scholars advocate for high-quality trials, they mean large-scale, simple, explanatory randomized controlled trials. Others, including myself, have defended a different characterization of high-quality research that tends more toward pragmatic trial design and the use of methods other than RCTs. Pragmatic trials aim to provide evidence that directly supports clinical decision-making in “usual” care settings. Unlike explanatory trials, which aim to abstract away from particular settings and patients, in the hopes of creating ideal conditions for the success of an intervention, pragmatic trials deliberately pursue knowledge of high applicability, through the use of representative subjects, clinically important questions, flexible treatment protocols, patient-oriented outcome measures, and so on. I see applicability as a marker of high-quality research. The context in which research is meant to be applied should be the context in which new interventions are evaluated. (shrink)

Deep brain stimulation as investigational intervention for symptomatic relief from Alzheimer disease has generated big expectations. Our aim is to discuss the ethical justification of this research agenda by examining the underlying research rationale as well as potential methodological pitfalls. The shortcomings we address are of high ethical importance because only scientifically valid research has the potential to be ethical. We performed a systematic search on MEDLINE and EMBASE. We included 166 publications about DBS for AD into the analysis of (...) research rationale, risks and ethical aspects. Fifty-eight patients were reported in peer-reviewed journals with very mixed results. A grey literature search revealed hints for 75 yet to be published, potentially enrolled patients. The results of our systematic review indicate methodological shortcomings in the literature that are both scientific and ethical in nature. According to our analysis, research with human subjects was performed before decisive preclinical research was published examining the specific research question at stake. We also raise the concern that conclusions on the potential safety and efficacy have been reported in the literature that seem premature given the design of the feasibility studies from which they were drawn. In addition, some publications report that DBS for AD was performed without written informed consent from some patients, but from surrogates only. Furthermore, registered ongoing trials plan to enroll severely demented patients. We provide reasons that this would violate Art. 28 of the Declaration of Helsinki, because DBS for AD involves more than minimal risks and burdens, and because its efficacy and safety are not yet empirically established to be likely. Based on our empirical analysis, we argue that clinical research on interventions of risk class III should not be exploratory but grounded on sound, preclinically tested, and disease-specific a posteriori hypotheses. This also applies to DBS for dementia as long as therapeutic benefits are uncertain, and especially when research subjects with cognitive deficits are involved, who may foreseeably progress to full incapacity to provide informed consent during the required follow-up period. (shrink)

The institutional review board is the social-oversight mechanism charged with protecting research subjects. Performing this task competently requires that the IRB scrutinize informed-consent procedures, the balance of risks and potential benefits, and subject-selection procedures in research protocols. Unfortunately, it may be said that IRBs are spending too much time editing informed-consent forms and too little time analyzing the risks and potential benefits posed by research. This time mismanagement is clearly reflected in the research ethics literature. A review of articles published (...) between 1979 and 1990 in IRB: A Review of Human Subjects Research, for example, reveals a large number of articles on informed consent and confidentiality and considerably fewer on the assessment of risks and potential harms, study design, and subject-selection procedures. (shrink)

The institutional review board is the social-oversight mechanism charged with protecting research subjects. Performing this task competently requires that the IRB scrutinize informed-consent procedures, the balance of risks and potential benefits, and subject-selection procedures in research protocols. Unfortunately, it may be said that IRBs are spending too much time editing informed-consent forms and too little time analyzing the risks and potential benefits posed by research. This time mismanagement is clearly reflected in the research ethics literature. A review of articles published (...) between 1979 and 1990 in IRB: A Review of Human Subjects Research, for example, reveals a large number of articles on informed consent and confidentiality and considerably fewer on the assessment of risks and potential harms, study design, and subject-selection procedures. (shrink)

Drawing on a conception of scientists and community members as partners in the construction of ethically responsible research practices, this article urges investigators to seek the perspectives of teenagers and parents in evaluating the personal and political costs and benefits of research on adolescent risk behaviors. Content analysis of focus group discussions involving over 100 parents and teenagers from diverse ethnic and socioeconomic backgrounds revealed community opinions regarding the scientific merit, social value, racial bias, and participant and group harms and (...) benefits associated with surveys, informant reports, intervention studies, blood sampling, and genetic research on youth problems. Participant comments highlight new directions for socially responsible research. (shrink)

Equipoise is an essential condition to justify a clinical trial. The term, describes a state of uncertainty: the data suggest but do not prove a drug's safety and efficacy The only way to resolve this uncertainty is further study In many cases, a clinical trial seems to be the most efficient way to prove safety and efficacy Equipoise is therefore not an esoteric philosophic construct applied to research ethics. Rather, since it is vital for the justification of clinical trials, it (...) is part of how society regulates medical progress. Where there is equipoise, drug design and development proceeds according to Food and Drug Administration and Health and Human Services regulations. When that equipoise ends, a drug is either not approved or becomes standard care. (shrink)

International documents on ethical conduct in clinical research have in common the principle that potential harms to research participants must be proportional to anticipated benefits. The anticipated benefits that can justify human research consist of direct benefits to the research participant, and societal benefits, also called social value. In first-in-human research, no direct benefits are expected and the benefit component of the risks-benefit assessment thus merely exists in social value. The concept social value is ambiguous by nature and is used (...) in numerous ways in the research ethics literature. Because social value justifies involving human participants, especially in early human trials, this is problematic. (shrink)

Institutional review boards, tasked with facilitating ethical research, are often pulled in competing directions. In what we call the protection-inclusion dilemma, we acknowledge the tensions IRBs face in aiming to both protect potential research participants from harm and include under-represented populations in research. In this manuscript, we examine the history of protectionism that has dominated research ethics oversight in the United States, as well as two responses to such protectionism: inclusion initiatives and critiques of the term vulnerability. We look at (...) what we know about IRB decision-making in relation to protecting and including “vulnerable” groups in research and examine the lack of regulatory guidance related to this dilemma, which encourages protection over inclusion within IRB practice. Finally, we offer recommendations related to how IRBs might strike a better balance between inclusion and protection in research ethics oversight. (shrink)

This commentary draws on the thoughtful contemplation and innovative procedures described in the special section articles as well as current professional codes and federal regulations to highlight ethical practices and paradoxes of deception research involving children. The discussion is organized around 4 key decision points for the conduct of responsible deception research involving children: (a) evaluating the scientific validity and social value of deception research within the context of alternative methodologies, (b) avoiding and minimizing experimental risk, (c) the use of (...) child assent procedures as questionable ethical safeguards, and (d) debriefing as both remedy and risk. (shrink)

Complementary and alternative medicine has become an important section of healthcare. Its high level of acceptance among the general population represents a challenge to healthcare professionals of all disciplines and raises a host of ethical issues. This article is an attempt to explore some of the more obvious or practical ethical aspects of complementary and alternative medicine.

The popularity of empirical methods in software engineering research is on the rise. Surveys, experiments, metrics, case studies, and field studies are examples of empirical methods used to investigate both software engineering processes and products. The increased application of such methods has also brought about an increase in discussions about adapting these methods to the particularities of software engineering. In contrast, the ethical issues raised by empirical methods have received little attention in the software engineering literature. In this chapter, we (...) introduce four ethics principles of primary importance for conducting ethical research. We additionally discuss and provide examples of applying these principles in the context of ethics review. (shrink)

Ethics in research are norms for conduct based on local regulations and universal recommendations such as the Nuremberg Code or the Declaration of Helsinki. However, these documents have a number of shortcomings that thwart the construction of a comprehensive ethical framework to guide research on humans in an effort to make better use of research results and to provide for ethical construction of knowledge. A broader ethical framework is suggested in this article, consistent with Ezekiel J. Emanuel's proposal, specifically one (...) that allows for evaluation, reflection and debate about scientific research on humans, based on eight fundamental principles. (shrink)

This paper addresses what should be an important question for many institutional ethics committees: How might they justifiably trust external peer review of the scientific merit of research proposals under their consideration, since these committees are typically not constituted to review the science themselves?