According to Howick (2009a), the three main reasons for believing that placebo-controlled trials (PCTs) are methodologically superior to active-controlled trials (ACTs)—sensitivity, absolute effect...

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. (shrink)

A resilient issue in research ethics is whether and when a placebo-controlled trial is justified if it deprives research subjects of a recognized treatment. The clinicians' moral duty to provide the best available care seems to require the use of ‘active’ controlled trials that use an established treatment as a control whenever such a therapy is available. In another regard, ACTs are supposedly methodologically inferior to PCTs. Hence, the moral duty of the clinical researcher to use the best methods will (...) favor PCTs. In this target article, I analyze the three reasons for believing that ACTs are inferior to PCTs namely: 1) ACTs lack ‘assay sensitivity’; 2) ACTs do not measure absolute effect size; and 3) ACTs require more participants; and I contend that none are acceptable. Consequently the tension between clinical and research ethics dissolves: the moral duty of the clinician to avoid PCTs is unopposed by methodological considerations. (shrink)