Randomised clinical trials provide the most valid means of establishing the efficacy of clinical therapeutics. Ethical standards dictate that patients and clinicians should not consent to randomisation unless there is uncertainty about whether any of the treatment options is superior to the others ("equipoise"). However, true equipoise is rarely present; most randomised trials, therefore, present challenging ethical dilemmas. Minimising the tension between science and ethics is an obligation of investigators and clinicians. This article briefly reviews several techniques for addressing this (...) issue and suggests that unbalanced randomisation, a technique rarely employed in current clinical trial practice, may be useful for enhancing the ethical design of human experimentation. (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)

For a few decades, patients with Parkinson's disease have been treated with intracerebral transplantations of fetal mesencephalic tissue. The results of open trials have been variable. Double blind, placebo-controlled studies have recently been started in order to further investigate the efficacy of this new medical technique. In this paper we challenge the need for sham surgery in neurotransplantation research on PD patients. Considerations regarding the research subjects' informed consent, therapeutic misconception, the integrity of the human body, and the assessment of (...) risks and benefits argue against sham surgery for patients with PD. Moreover, there is an alternative, less harmful mode of research that can provide the same or comparable scientific evidence. A plea is made for intrapatient research based on quantitative measurements of the patient's pre- and post-operative condition combined with similar research on a reference group of patients who have received the standard treatment. (shrink)

(2002). Clinical Research Should Not Be Permitted to Escape the Ethical Orbit of Clinical Care. The American Journal of Bioethics: Vol. 2, No. 2, pp. 27-28.

Sham surgery is a controversial and rarely used component of randomised clinical trials evaluating surgical interventions. The recent use of sham surgery in trials evaluating efficacy of intracerebral fetal tissue grafts in Parkinson’s disease has highlighted the ethical concerns associated with sham surgery controls. Macklin, and Dekkers and Boer argue vigorously against use of sham surgery controls. Macklin presents a broad argument against sham surgery controls while Dekkers and Boer present a narrower argument that sham surgery is unnecessary in the (...) specific setting of fetal tissue engraftment for Parkinson’s disease. I defend sham surgery controls against both these criticisms. Appropriate clinical trial design, sometimes including sham surgery, is needed to ensure that false positive trial results do not occur and endanger public safety. Results of a completed trial of fetal tissue grafting for Parkinson’s disease are used to illustrate the potential benefits of, and problems associated with, sham surgery controls. Sham surgery controls, however, should be employed only when absolutely necessary. I suggest criteria for appropriate use of sham surgery controls. (shrink)

Surgical clinical trials have seldom used a "sham" or placebo surgical procedure as a control, owing to ethical concerns. Recently, several ethical commentators have argued that sham surgery is either inherently or presumptively unethical. In this article I contend that these arguments are mistaken and that there are no sound ethical reasons for an absolute prohibition of sham surgery in clinical trials. Reflecting on three cases of sham surgery, especially on the recently reported results of a sham-controlled trial of arthroscopic (...) surgery for arthritis of the knee, I present an ethical analysis that focuses on the methodological rationale for use of sham surgery, risk-benefit assessment, and informed consent. (shrink)

Surgical clinical trials have seldom used a “sham” or placebo surgical procedure as a control, owing to ethical concerns. Recently, several ethical commentators have argued that sham surgery is either inherently or presumptively unethical. In this article I contend that these arguments are mistaken, and that there are no sound ethical reasons for an absolute prohibition of sham surgery in clinical trials. Reflecting on three cases of sham surgery, especially on the recently reported results of a sham-controlled trial of arthroscopic (...) surgery for arthritis of the knee, I present an ethical analysis that focuses on the methodological rationale for use of sham surgery, risk-benefit assessment, and informed consent. (shrink)

Franklin G. Miller and colleagues have stimulated renewed interest in research ethics through their work criticizing clinical equipoise. Over three years and some twenty articles, they have also worked to articulate a positive alternative view on norms governing the conduct of clinical research. Shared presuppositions underlie the positive and critical dimensions of Miller and colleagues' work. However, recognizing that constructive contributions to the field ought to enjoy priority, we presently scrutinize the constructive dimension of their work. We argue that it (...) is wanting in several respects. (shrink)

(2002). Avoiding a Jekyll-And-Hyde Approach to the Ethics of Clinical Research and Practice. The American Journal of Bioethics: Vol. 2, No. 2, pp. 14-17.

Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)

ABSTRACT In this paper, I support the claim that placing certain restrictions on public access to possible new treatments is morally problematic under some exceptional circumstances. Very ill patients may find that all available standard treatments are unacceptable, either because they are ineffective or have serious adverse effects, and these patients may understandably be desperate to try something new even if this means stepping into the unknown. Faced with certain death, it is rational to want to try something new and (...) to chance a dire outcome. Restricting possible new treatments to research trials may put these treatments scientifically, geographically or economically out of reach of these patients. For those who can get access, research restrictions could weaken, though not necessarily eliminate, the value of consent participants of such trials are able to give. Some participants may therefore be exploited for scientific purposes in the name of public interest. There are nonetheless compelling reasons for keeping some restrictive regulation in this area. (shrink)

Collected here in a single volume for the first time, On Liberty, Utilitarianism, Considerations on Representative Government, and The Subjection of Women show Mill applying his liberal utilitarian philosophy to a range of issues that remain vital today - issues of the nature of ethics, the scope and limits of individual liberty, the merits of and costs of democratic government, and the place of women in society. In his Introduction John Gray describes these essays as applications of Mill's doctrine of (...) the Art of Life, as set out in A System of Logic. Using the resources of recent revisionist scholarship, he shows Mill's work to be far richer and subtler than traditional interpretations allow. (shrink)