Methodology for conducting clinical trials of new drugs and treatments on people need not be regarded as fixed. After reviewing the currently most popular method (randomization) and its ethical problems, this paper explores the possibilities of a new method for conducting such trials. It relies on new Bayesian technology for eliciting the opinions of medical experts. These opinions are conditioned on specific predictor variables, and are held in a computer. At any stage in a trial, these opinions can be updated (...) in the computer using the information collected in the trial up to that point. Consider as an admissible treatment for a patient having specific values of predictor variables only those treatments that at least one expert regards as best (in the computer model) for this patient. It is proposed that only admissible treatments, so defined, be allowed to be assigned to the patient. The ethical and statistical consequences of this principle are explored. Experience to date with a trial at Johns Hopkins designed on this principle is reported. Keywords: Bayesian statistics, information, clinical trial CiteULike Connotea Del.icio.us What's this? (shrink)

As more AIDS patients seek access to nonvalidated therapies, Authorized Investigational Units can preserve the integrity of clinical trials, protect patients' interests, and enhance clinicians' flexibility.

The purpose of this paper is to examine whether randomized clinical trial (RCT) methods are necessarily morally problematic. If they are intrinsically problematic, then there may be a dilemma such that tragic choices might have to be made between this socially very useful method for making medical progress on the one hand, and patients' rights and welfare, or physicans' duties on the other. It is argued that the dilemma may be avoided if RCTs can sometimes be viewed as an honorable (...) and cooperative venture between investigators and subjects. Another dilemma may take shape, however, if too few people are willing to cooperate to maintain the structural integrity of many important RCTs. Given their importance, does this method justify easing some of the consent requirements? It is argued that RCT methods are not so ideal that special consideration should be given to them regarding consent requirements. To examine the compatibility of current consent requirements and frequently used RCT schemas, seven RCT designs are discussed. It is found that some, but not all, RCTs, are intrinsically problematic but that sufficient reason has not been found to hold all RCT schemas as intrinsically morally troubling. Keywords: randomized clinical trials, informed consent, randomization CiteULike Connotea Del.icio.us What's this? (shrink)

It has often been argued that if a clinician cannot decide which of two treatments to offer, a trial may be ethical, but it is unethical if she/he has a preference. Since individual clinicians usually have a preference, most trials could be judged unethical according to this line of argument. A recent important article in the New England Journal of Medicine argued that individual preferences are not as important as the collective uncertainty of informed clinicians. If clinicians are equally divided, (...) there is a state of collective equipoise and a trial is ethical. However, clinicians will seldom be exactly equally divided. We conducted an ethometric study to find out how much collective equipoise can be disturbed before the potential subjects in a trial think that it is unethical. Half of our subjects perceived a trial as unethical when equipoise was disturbed beyond 70:30. In other words, when 70 per cent of experts favour one treatment, 50 per cent of subjects would prefer that treatment to be administered rather than subjected to critical assessment. When equipoise is disturbed beyond 80:20, less than 3 per cent of subjects would consider human trials morally justifiable. (shrink)

The central dilemma concerning randomized clinical trials (RCTs) arises out of some simple facts about causal methodology (RCTs are the best way to generate the reliable causal knowledge necessary for optimally-informed action) and a prima facie plausible principle concerning how physicians should treat their patients (always do what it is most reasonable to believe will be best for the patient). A number of arguments related to this in the literature are considered. Attempts to avoid the dilemma fail. Appeals to informed (...) consent and mechanisms for minimizing the resulting harm are important for policy, but informed consent is problematic and mechanisms for minimization of harm do not address the dilemma. Appeals to some sort of contract model of justification are promising and illuminating. Keywords: randomized clinical trials, ethics CiteULike Connotea Del.icio.us What's this? (shrink)