Randomized Controlled Trials are currently the gold standard within evidence-based medicine. Usually, they are conducted as sequential trials allowing for monitoring for early signs of effectiveness or harm. However, evidence from early stopped trials is often charged with being biased towards implausibly large effects. To our mind, this skeptical attitude is unfounded and caused by the failure to perform appropriate conditioning in the statistical analysis of the evidence. We contend that a shift from unconditional hypothesis tests in the style of (...) Neyman and Pearson to conditional hypothesis tests gives a superior appreciation of the obtained evidence and significantly improves the practice of sequential medical trials, while staying firmly rooted in frequentist methodology. (shrink)

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)

(2013). What to Think of Canine Obesity? Emerging Challenges to Our Understanding of Human–Animal Health Relationships. Social Epistemology: Vol. 27, No. 1, pp. 90-104. doi: 10.1080/02691728.2012.760662.

Clinical equipoise has been proposed as an ethical principle relating uncertainty and moral leeway in clinical research. Although CE has traditionally been indicated as a necessary condition for a morally justified introduction of a new RCT, questions related to the interpretation of this principle remain woefully open. Recent proposals to rehabilitate CE have divided the bioethical community on its ethical merits. This paper presents a new argument that brings out the epistemological difficulties we encounter in justifying CE as a principle (...) to connect uncertainty and moral leeway in clinical ethics. The argument proposes, first, that the methodology of hypothetical retrospection is applicable to the RCT design and that it can accommodate uncertainty. As currently understood, however, HR should give up its reliance on the assumption of uncertainty transduction, because the latter assumes the principle of indifference, which does not accommodate uncertainty in the right way. The same principle is then seen to distort also the received interpretations of CE. (shrink)

Robert Truog describes the controversial randomized controlled trials (RCTs) of extracorporeal membrane oxygenation (ECMO) therapy in newborns. Because early results with ECMO indicated that it might be a great advance, saving many lives, Truog argues that ECMO should not have been tested using RCTs, but that a long-term, large-scale observational study of actual clinical practice should have been conducted instead. Central to Truog’s argument, however, is the idea that ECMO is an unusual case. Thus, it is an open question whether (...) Truog’s conclusions can be extended to other areas of medical research. In this paper, I look at epistemological and ethical issues arising in the care of patients with chronic diseases, using ECMO as a starting point. Both the similarities and the dissimilarities of these two cases highlight important issues in biomedical research and support a conclusion similar to Truog’s. Observational studies of clinical practice provide the best evidence to inform the treatment of patients with chronic disease. (shrink)