At least since the seminal work of the (US) National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research in the 1970s, a fundamental distinction between research and practice has underwritten both conceptual work in research ethics and regulations governing research involving human subjects. Notwithstanding its undoubted historical importance, I believe the distinction is problematic because it misrepresents clinical inquiry. In this essay, I aim to clarify the character of clinical inquiry by identifying crucial contextual constraints on (...) justification constitutive of clinical science. This analysis shows that, from an epistemological point of view, clinical research and clinical practice are not sharply distinct but intimately intertwined. This result is important in its own right—an enriched understanding of the epistemology of clinical research is valuable in and of itself. But this result is also important because it has profound implications for the ethics of human subjects research. (shrink)

One of the most important questions in the ethics of human clinical research asks what obligations investigators owe the people who enroll in their studies. Research differs in many ways from standard care - the added uncertainties, for instance, and the nontherapeutic interventions such as diagnostic tests whose only purpose is to measure the effects of the research intervention. Hence arises the question whether a physician engaged in clinical research has the same obligations toward research subjects that he owes his (...) medical patients, or whether they differ in any fundamental way.Perhaps the most common answer is that the relationship is the same. Investigators, like physicians, are said to be fiduciaries of the volunteers who enroll in research trials. Each owes the best available medical care, which means that a physician can only justify enrolling his patient in research if the study meets the requirements of clinical equipoise, namely, that there is legitimate disagreement within the medical community as to whether the standard treatment or the investigational intervention is superior. (shrink)

When a patient could be offered one of multiple established treatments, doctors should be able to offer treatment only if the patient agrees to participate in research aimed at determining which of the treatments is most effective. Making treatment conditional on research participation will help researchers complete badly needed studies.

Bioethics is currently witnessing unprecedented debate over the moral and legal norms governing the conduct of clinical research. At the center of this debate is the duty of care in clinical research, and its most widely accepted specification, clinical equipoise. In recent work, we have argued that equipoise and cognate concepts central to the ethics of clinical research have been left unnecessarily vulnerable to criticism. We have suggested that the vulnerability lies in the conspicuous absence of an articulated foundation in (...) moral and legal theory of the physician-researcher's duty of care to the patient-subject. We have repeatedly suggested that the requisite foundation is in the ethics of trust and the law of fiduciaries.Curiously, despite the absence of a published thorough exposition of our position, some have preemptively criticized our suggestion that the relationship between physician-researcher and patient-subject is fiduciary. Others have offered their own accounts of the implications of fiduciary law for the relationship. (shrink)

Heated debate surrounds the question whether the relationship between physician-researcher and patient-subject is governed by a duty of care. Miller and Weijer argue that fiduciary law provides a strong legal foundation for this duty, and for articulating the terms of the relationship between physician-researcher and patient-subject.

One of the most important questions in the ethics of human clinical research asks what obligations investigators owe the people who enroll in their studies. Research differs in many ways from standard care - the added uncertainties, for instance, and the nontherapeutic interventions such as diagnostic tests whose only purpose is to measure the effects of the research intervention. Hence arises the question whether a physician engaged in clinical research has the same obligations toward research subjects that he owes his (...) medical patients, or whether they differ in any fundamental way.Perhaps the most common answer is that the relationship is the same. Investigators, like physicians, are said to be fiduciaries of the volunteers who enroll in research trials. Each owes the best available medical care, which means that a physician can only justify enrolling his patient in research if the study meets the requirements of clinical equipoise, namely, that there is legitimate disagreement within the medical community as to whether the standard treatment or the investigational intervention is superior. (shrink)

: When a patient could be offered one of multiple established treatments, doctors should be able to offer treatment only if the patient agrees to participate in research aimed at determining which of the treatments is most effective. Making treatment conditional on research participation will help researchers complete badly needed studies.

Worries about safety of approved drugs have pushed post registration research to become the fastest growing drug research phase. Until recently, phase IV studies were mainly conducted for marketing purposes and run much like a phase III trial—at institutions with experienced investigators and a list of inclusion and exclusion criteria. Innovative phase IV studies involve ordinary physicians in research naïve communities. This brings ethical issues familiar to medical research into clinical practice. As a consequence, individual physicians are challenged to protect (...) scientific integrity and to secure the ethical conduct of research. Several ethical issues need to be addressed in the process of developing a scientifically sound and ethically high principled practice of phase IV research.PHASE IVEssential to phase IV research is the focus on how drugs work in the real world. The research goal may be to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. They may also be designed to establish a new clinical indication for a drug.1 Subjects may or may not be randomised, and the studies typically involve large numbers of patient-subjects and physicians.Doubts concerning the scientific rigor and clinical value have put postmarketing research in a poor light. However, high quality phase IV research is badly needed to further pharmaceutical science. First, because it can provide reliable data on the effectiveness, safety and optimal use of a drug in treated populations.2 3 In pre-registration clinical trials , a pharmaceutical product is studied under unrealistic circumstances. Under-representation of women and elderly are common and the concomitant use of medicines is usually extremely restrictive in these trials.4 Second, phase IV can provide much needed data for evidence-based …. (shrink)