title: The ethics and science of placebo-controlled trials: assay sensitivity and the Duhem-Quine thesis.
abstract: The principle of clinical equipoise requires that, aside from certain exceptional cases, second generation treatments ought to be tested against standard therapy. In violation of this principle, placebo-controlled trials (PCTs) continue to be used extensively in the development and licensure of second-generation treatments. This practice is typically justified by appeal to methodological arguments that purport to demonstrate that active-controlled trials (ACTs) are methodologically flawed. Foremost among these arguments is the so called assay sensitivity argument. In this paper, I take a closer look at this argument. Following Duhem, I argue that all trials, placebo-controlled or not, rely on external information for their meaningful interpretation. Pending non-circular empirical evidence that we can trust the findings of PCTs to a greater degree than the findings of ACTs, I conclude that the assay sensitivity argument fails to demonstrate that placebo-controlled trials are preferable, methodologically or otherwise, to active-controlled trials. Contrary to the intentions of its authors, the fundamental lesson taught by the assay sensitivity argument is Duhemian: the validity of all clinical trials depends on external information.
authors.affiliation: Department of Philosophy, Dalhousie University, Halifax, Nova Scotia, Canada. jaanders@dal.ca
authors.forename: James A
authors.initials: JA
authors.lastname: Anderson
mesh_terms: D003627:Data Interpretation, Statistical; D004341:Drug Evaluation / Q000941:ethics / Q000379:methods; D026690:Ethics, Clinical; D032984:Ethics, Research; D006801:Humans; D010919:Placebos; D017410:Practice Guidelines as Topic; D016032:Randomized Controlled Trials as Topic / Q000941:ethics* / Q000379:methods; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D010919:Placebos