Thank you for correcting your previous comment that you thought...

Thank you for correcting your previous comment that you thought there was a different level of evidence pyramid for surgical products vs medications. In all cases a RCT (or Meta-analysis of) in terms of the reliability of the evidence is Gold Standard and I am glad you found my reference helpful.

Now that you have clarified that you were instead referring to the specific situation where it may not be deemed appropriate to run a Gold Standard RCT I have no problem with your position upon clarification. I have read the first reference you provided previously and agree that when a proper RCT can not be conducted case studies are an appropriate alternative for surgical intervention.

To bring it back to mesoblast: like with the design of surgical/devices trials, there are also times in pharmaceuticals or biologics where a RCT may not be ideal/appropriate and a sponsor/regulator can make a case for a trial design further down the hierarchy in terms of reliability of evidence. Such instances include (a life threatening disease where SOC has failed/ or no approved therapies, extremely rare diseases may not practically warrant running a full RCT etc). These are not easy decisions I would imagine and involve the input of complex ethical issues. For that is really one of the primary reason that RCT may not be selected. At times there may be a case for the greater good that it is appropriate to trade off some reliability of evidence in terms of a non-RCT trial design to address some of the most human ethical issues. This will soon be before the FDA, so time will tell soon enough...

Just a bit rich that you heavily critisise Mesoblast on a continual basis as a non-holder for not conducting a RCT in children with SR-aGvHD with severe ethical issues at play; when you also post for surgical products you have a financial interest as to why case studies will unlock new indications. Agree, need to take posts with a grain of salt at times.

To end on a positive, what a great back presentation today! Happy to hear further details on how they are going to run the forthcoming RCT, why HA is not needed as a control as agreed with FDA, targeting patient with CLBP earlier in the disease process - like with CHF - whilst they are inflammed and before they become too fibrotic, additional imaging tools to firm up MOA in additional to biomarkers. Hope you find the recording insightful when you get a chance to watch if you decide to.