Ethics and Feasibility of Placebo-Controlled Interventional Acute Stroke Trials

To the Editor:The ethics of performing a randomized controlled trial (RCT) of thrombolytic therapy in the 3- to 6-hour window with a placebo arm were recently debated in Stroke and during the recent International Stroke Conference. The key ethical principle involved is equipoise.Grotta and Barreto,1 both vascular neurologists, address equipoise as follows: “So, is it “ethical” to have placebo-controlled trials given the data? This can best be answered by posing the following question. Would I be willing to be randomized into such a trial at a center capable of expert intravenous or endovascular therapy if I myself had an M1 middle cerebral artery occlusion and NIHSS score of 15 at 4 hours after the onset of symptoms? The answer would be a hesitant “yes,” but I surely hope that we hurry and obtain an answer before I have to make such a decision.”This tepid response represents only individual equipoise. However, because individuals rarely agree, the most widely used definition of equipoise is “collective” equipoise. Johnson et al2 conducted an ethometric study to find out how much collective equipoise can be disturbed before the potential subjects in a trial think that it is unethical. “Half of our subjects perceived …