Ann: Appendix 3Y-Dr Geoffrey Brooke, page-3

If mesenchymal stem cells don't implant but do cause a change (like a reset of immune system) then it is quite likely that a single treatment of mscs plus standard of care would show a bigger difference than standard of care and nothing. Why should two treatments versus one treatment of the active (or hoped to be active agent) be a better test than the active agent alone (plus standard of care) versus null?

It shouldn't - but its easier to sell a trial with that design probably and in patients in countries now demand to be given something - they don't want to take a chance on getting the raw end of the trial lottery and getting treatment or control alone.

To recruit you need to offer a little something to everyone. Or your GvHD trial may recruit slow or your lung immunity trial might recruit slow - so offer a less effective trial but with a better chance of recruiting - is that really the thinking and to hang with the science of actually showing that there is a real cause behind a real change by doing a real test that is not confounded?