To what extent does the design of statistical experiments, in particular sequential trials, affect their interpretation? Should postexperimental decisions depend on the observed data alone, or should they account for the used stopping rule? Bayesians and frequentists are apparently deadlocked in their controversy over these questions. To resolve the deadlock, I suggest a three‐part strategy that combines conceptual, methodological, and decision‐theoretic arguments. This approach maintains the pre‐experimental relevance of experimental design and stopping rules but vindicates their evidential, postexperimental irrelevance. †To (...) contact the author, please write to: Tilburg Center for Logic and Philosophy of Science, Tilburg University, P.O. Box 90153, 5000 LE Tilburg, The Netherlands; e‐mail: [email protected]. (shrink)

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)

I will open the first part of this paper by trying to elucidate the frequentist foundations of RCTs. I will then present a number of methodological objections against the viability of these inferential principles in the conduct of actual clinical trials. In the following section, I will explore the main ethical issues in frequentist trials, namely those related to randomisation and the use of stopping rules. In the final section of the first part, I will analyse why RCTs were accepted (...) for regulatory purposes. I contend that their main virtue, from a regulatory viewpoint, is their impartiality, which is grounded in randomisation and fixed rules for the interpretation of the experiment. Thus the question will be whether Bayesian trials can match or exceed the achievements of frequentist RCTs in all these respects. In the second part of the paper, I will first present a quick glimpse of the introduction of Bayesianism in the field of medical experiments, followed by a summary presentation of the basic tenets of a Bayesian trial. The point here is to show that there is no such thing as “a” Bayesian trial. Bayesianism can ground many different approaches to medical experiments and we should assess their respective virtues separately. Thus I present two actual trials, planned with different goals in mind, and assess their respective epistemic, ethical and regulatory merits. In a tentative conclusion, I contend that, given the constraints imposed by our current regulatory framework, impartiality should preside over the design of clinical trials, even at the expense of many of their inferential and ethical virtues. (shrink)