In this essay, we defend the design of the Salk polio vaccine trial and try to put some limits on the role schemata should play in designing clinical research studies. Our presentation is structured as a response to de Freitas and Pietrobon who identified the CONSORT statement as a schema that would have, had it existed at the time, ruled out the design of the Salk polio vaccine trial of 1954 in favor of a completely randomized controlled clinical trial. We (...) argue that large-scale public health interventions often require evidence beyond simple efficacy, the limit of what an RCT can provide, and that the design actually adopted for the Salk trial represented a reasonable—albeit imperfect—compromise. This is of more than historical interest in that many contemporary studies are of the scale and scope to require a more pragmatic, rather than explanatory, approach to study design. (shrink)

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 Belmont Report’s distinction between research and the practice of accepted therapy has led various authors to suggest that these purportedly distinct activities should be governed by different ethical principles. We consider some of the ethical consequences of attempts to separate the two and conclude that separation fails along ontological, ethical, and epistemological dimensions. Clinical practice and clinical research, as with yin and yang, can be thought of as complementary forces interacting to form a dynamic system in which the whole (...) exceeds the sum of its parts. Just as effective clinical practice cannot exist without clinical research, meaningful clinical research requires the context of clinical practice. We defend this thesis by triangulation, that is, by outlining how multiple investigators have reached this conclusion on the basis of varied theoretical and applied approaches. More confidence can be placed in a result if different methods/viewpoints have led to that result. (shrink)

Increasingly, clinical research is evaluated on the quality of its statistical analysis. Traditionally, statistical analyses in clinical research have been carried out from a ‘frequentist’ perspective. The presence of an alternative paradigm – the Bayesian paradigm – has been relatively unknown in clinical research until recently. There is currently a growing interest in the use of Bayesian statistics in health care research. This is due both to a growing realization of the limitations of frequentist methods and to the ability of (...) Bayesian methods explicitly to incorporate prior expert knowledge and belief into the analyses. This is in contrast to frequentist methods, where prior experience and beliefs tend to be incorporated into the analyses in an ad hoc fashion. This paper outlines the frequentist and Bayesian paradigms. Acute myocardial infarction mortality data are then analysed from both a Bayesian and a frequentist perspective. In some analyses, the two methods are seen to produce comparable results; in others, they produce different results. It is noted that in this example, there are clinically relevant questions that are more easily addressed from a Bayesian perspective. Finally, areas in clinical research where Bayesian ideas are increasingly common are highlighted. (shrink)

A patient's informed consent is required by the Nuremberg code, and its successors, before she can be entered into a clinical trial. However, concern has been expressed by both patients and professionals about the beneficial or detrimental effect on the patient of asking for her consent. We examine advantages and drawbacks of popular variations on consent, which might reduce the stress on patients at the point of illness. Both informed and uninformed responses to particular trials, and trials in general, are (...) discussed. The selection by doctors of patients, to whom entry to trials will be offered, is explored. (shrink)