ok fair enough. I agree on the points of NZ, Canada, and also on...

ok fair enough. I agree on the points of NZ, Canada, and also on adults where it is not clear what is going to happen.

For CHF, I think it is hard to not use a control group even though these patients are also very sick. The biggest reasons for me is that the time taken before a conclusion can be made is very long, and there are lots of other interventions (of varying degrees of usefulness) that can possibly be tried which makes muddying the waters almost certain. That is little comfort to those who are very sick and end up getting the placebo, but unfortunately it is a different set of clinical parameters for CHF and GVHD. It is of course possible to conduct a trial without a placebo for these CHF patients, who are supposed to be the sickest ones. If the MACE annual rate is 25% in the baseline population, and in a trial the MACE rate is 5%, then it is compelling even without a placebo group. But I think the time frame to efficacy conclusion just introduces too much uncertainty about whether any effect is attributable to the intervention being studied or some other action taken by the patient over the course of the study period, so a control group really is necessary. Yes it can be an unpleasant debate, people's lives at stake...

Thanks for your response.