I know much of this is old hat, but just wanted to revisit, with a particular thought in mind. Possibly in the wrong thread, in which case mods please feel free to relocate. As best I understand this, though others here far better qualified: Surely a "controlled" trial is where you control so that the only things you ultimately measure, are the effects of the intervention itself; nulling out any other unwanted but unavoidable effects within the trial. So, simplistically, if your intervention arm has influences Intervention, I, plus unwanted but unavoidable influences x, y and z, then you also run another trial arm identical but without I ... i.e. with just the unwanted influences x, y and z. And so to null out x, y and z from your results you take the differences between the two arms. So to be clear, the only influence you want to measure the effects of, is the intervention itself. What you absolutely do not want to be measuring is any effects from participants' awareness of the intervention being administered - that would be an unwanted influence that needs to be controlled for and nulled out, as per x, y and z in the above example. But in an open label trial you simply cannot separate out the intervention itself, from participants' awareness of the intervention; two distinctly separate influences. So, surely, you cannot control an open label trial simply by having a "control" arm that has: no intervention, an alternative intervention, or mix of interventions ... because that can only work if the participants have no awareness that that is being done to them. If the arms are not identical in all respects apart from what you want to measure, then you will not be able to know what the mix of effects is that you are measuring. People's awareness of their interventions would have to be identical across all arms, which they clearly can not be, not in the real world anyway. So I do not understand how any of these open label trials are able to claim that they are Randomised Controlled Trials? What are they controlling for? Surely it is only legitimate to claim to be controlling things that ensure you end up measuring only the intervention itself? But if intervention-awareness cannot be controlled for, then you surely cannot claim your trial to be controlled? And just because you cannot do it, is no excuse for then claiming it anyway. In the infamous FINE trial for example, it says "Our control condition is treatment as usual by the general practitioner (GP)." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1456982/. But this is like running a drug trial with the placebo tablet being labelled "DO NOT EXPECT ME TO WORK, I AM NOT WHAT THIS TRIAL IS ABOUT", and the intervention arms labelled the opposite; instead of being indistinguishable from each other. So are there any regulations on what controls a trial has to have in place, in order for it to claim itself as being a controlled trial? It feels to me there should be a standard check list that every trial protocol should have to fill out, listing all sources of biases that trials are known to be prone to, with each item being filled in with how the trial will control, or not control, for that particular bias. And of course the 2011 PACE paper ended up not claiming it to a be a controlled trial, though its protocol - which it inevitably referenced of course - did claim it would be. It just feels wrong that such revered terminology can be abused so easily.