THANK YOU! This is why I joined Beehaw.

Exactly. Some things just can't be studied as part of a double blind RCT. For example, see: Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials

The perception that parachutes are a successful intervention is based largely on anecdotal evidence. Observational data have shown that their use is associated with morbidity and mortality, due to both failure of the intervention and iatrogenic complications...

The paper is funny, but the authors are making a serious point. RCTs are great when they're possible, but just because they're not possible doesn't mean we can't gather strong evidence anyway.

Thanks for that.

Lack of blinding is a serious issue for subjective outcomes but blinding when treatment effects are obvious to both intervention and control groups is dishonest (Pharma does it all the time to make their trials look more credible than they are).

Open label is the norm for cancer trials for exactly this reason. It is important to consider the biases that may arise, in subjective endpoints especially. But it is ludicrous to dismiss research on this basis alone. We can't randomise 12 year olds to become lifetime smokers or not, let alone use placebo controls, but we do know that smoking kills. It's just a bit more complicated to prove it when perfectly designed RCTs are not possible.