The ethics of sham surgery in Parkinson's disease: back to the future?

Despite intense academic debate in the recent past over the use of 'sham surgery' control groups in research, there has been a recent resurgence in their use in the field of neurodegenerative disease. Yet the primacy of ethical arguments in favour of sham surgery controls is not yet established. Preliminary empirical research shows an asymmetry between the views of neurosurgical researchers and patients on the subject, while different ethical guidelines and regulations support conflicting interpretations. Research ethics committees faced with a proposal involving sham surgery should be aware of its ethical complexities. An overview of recent and current placebo-controlled surgical trials in the field of Parkinson's Disease is provided here, followed by an analysis of the key ethical issues which such trials raise.

Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5.

Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists. The bile acid-induced cAMP production does not lead to an increase in contraction rate, and seems to be mediated by the RI isoform of adenylate cyclase, unlike adrenaline-dependent release which is mediated by the RII isoform. In contrast, bile acids elicited slowing of neonatal cardiomyocyte contraction indicating that other signalling pathways are involved. The conjugated bile acids were found to be partial agonists of the muscarinic M2, but not sphingosin-1-phosphate-2, receptors, and act partially through the Gi pathway. Furthermore, the contraction slowing effect of unconjugated bile acids may also relate to cytotoxicity at higher concentrations.

Using expert patients' narratives as an educational resource.

In this article, we examine the topic of patient participation in health care and report on how we have drawn on the concept of patient expertise to produce a new kind of information booklet for chronic arthritis patients. The booklet is patient-generated and contains the illness narratives of patients with three kinds of arthritis. The booklet draws upon the knowledge of patients who feel they are flourishing despite their condition. By communicating information through the powerful medium of narrative it is hoped the booklet will be a useful educational and supportive resource for other patients with a similar condition. We would encourage health professionals to acknowledge patient expertise and to consider the expertise of certain patients as a valuable educational resource both for themselves and for other patients.

Sham surgery trial controls: perspectives of patients and their relatives.

This study reports on qualitative research conducted in the UK with people with Parkinson's Disease and their relatives on the subject of "sham surgery." It explores attitudes toward sham surgery and reasoning about hypothetical participation in a sham-controlled trial. Results showed that attitudes toward sham surgery may not necessarily predict trial participation behavior. A small majority of interviewees deemed sham surgery ethically acceptable with certain provisos, but hypothetical participation was driven primarily by disease severity and a lack of standard treatment options, with a preference for receiving the real surgery over sham. Ethical implications for patient equipoise and the autonomy of patients' research participation decisions are discussed.

Differences between research ethics committees.

OBJECTIVES: To examine differences in the ethical judgments made by Research Ethics Committees (RECs) or Institutional Review Boards (IRBs). METHODS: We did a review of the literature and included any study that attempted to compare the ethical judgments made by different RECs or IRBs when reviewing one or more protocol. RESULTS: There were twenty-six articles reporting such discrepancies across Europe, within the United Kingdom, Spain, and United States. Of these studies, there were only five reports of some RECs approving while others rejecting the same protocol. All studies, however, reported differences in the clarifications and revisions asked of researchers regarding consent, recruitment, risks and benefits, compensation arrangements, and scientific issues. CONCLUSIONS: The studies were generally anecdotal reports of researchers trying to do research. New rules requiring a single ethical opinion for multi-site research at least in European Member States may simply conceal problematic issues in REC decision making. In the last analysis, we should expect a certain degree of variation and differences if we are to keep a committee system of review, although there is a pressing need to investigate the way in which RECs make these judgments. In particular, we need to identify the source of any aberrations, distortions, or confusions that could arbitrarily affect these judgments. Furthermore, local conditions remain important ethical considerations and should not be sidelined in pursuit of greater "consistency."

The ethics of placebo-controlled trials: a comparison of inert and active placebo controls.

Because of the recent and controversial example of sham surgery for the evaluation of fetal tissue transplants for Parkinson's disease, there is renewed interest in the ethics of using "active" placebos in surgical trials, where otherwise there are no inert procedures available, and in pharmacological trials, where there are inert substances, but where patients may guess to which arm they have been allocated. This paper seeks to clarify the ethical arguments surrounding the use of active placebos in trials, and to set up a notation for assessing the ethics of trials more generally. We first establish an framework by which ethics committees can analyze such trials. We examine (1) the scientific value of the research; (2) the expected risks and benefits to individual patients, and (3) the voluntary nature of consent. We then contrast the implications of this framework for inert and active placebo-controlled trials, respectively. In particular, we analyze their relative expected utility using three main utility factors, namely, treatment effects, placebo effects, and altruism. We conclude that, when the intervention is already widely available, active placebo trials rely more heavily on altruism than do inert placebo trials and, when the intervention is restricted, this excess reliance may not be needed. What our analysis provides is the explicit justification for the apparent caution of Institutional Review Boards or ethics committees when reviewing sham operations, especially when the expected harm is not trivial and the risk of exploitation is high.

Living well through chronic illness: the relevance of virtue theory to patients with chronic osteoarthritis.

OBJECTIVE: Virtues and vices possessed by patients may affect their quality of life and how well they cope with disease. The objective of this study is to assess the relevance of the concept of virtue and vice to patients with chronic arthritis. METHODS: Aristotle's theory of virtue and vice was used to construct a guide for in-depth interviews, carried out with 5 patients with chronic osteoarthritis. Interviews were tape recorded, transcribed, and analyzed (using Interpretative Phenomenological Analysis) for information on personal qualities or intellectual approaches that participants thought necessary to thrive in the face of chronic disease. RESULTS: Five main themes emerged: strength, prudence, gratitude, self-worth, and insight into flourishing. The data on each of these is compared with Aristotle's definitions of virtues and vices. CONCLUSIONS: Aristotle's virtue theory can be applied to the narratives of these patients with chronic osteoarthritis, and may help in understanding their coping strategies and quality of life.