@AllanHU Great post. I already asked myself about most of the questions you pose... because many clinical trials with small patient groups produce anomalies... but then I went out and got answers for most of them. The reason I did this exercise is that many of these arguments were already brought up by a shorter, who published his arguments in a Seeking Alpha paid subscription article over a year ago. The thrust of his argument was that the Company selectively data mined the results for p values which supported its cause . This is of course nonsense. Have you ever asked yourself , what is the significance of the improved remodelling of the left ventricle achieved by the 150m dosage? You cannot explain that incredible achievement , or the logical improvement relative to the other dosing arms, unless the treatment is effective can you ?
Even for such a small phase 2 study there were quite significant differences in patients profiles between the dosing groups in terms of ischemic patients, smokers, diabetics etc., If I can get time over the weekend , I will try and dig out research which shows the patient profiles . I should point out that even with this patient information, you still do not know which of the dosing arms was allocated which patient, but you can draw conclusions against all three dosing groups relative to the control. Also you may wish to consider how improvements in ejection fraction ( which hitherto was considered almost impossible in late stage heart disease therapy) are correlated to very significant reduction in mortality rates.
I think you should be applauded for raising the bar in terms of the quality of the debate. You are obviously a very knowledgeable and well educated person and have taken considerable time to elucidate your point of view. Even the mighty Professor Arnold Kaplan who first discovered Mesenchymal cells only recently realised that their potency lies in their signalling capability and paracrine properties. Mesoblast is probably the most complex company I have ever had to analyse. When, I ever question the conclusions from my research, I take great comfort , knowing the company has successfully passed its interim futility analysis in April 2017 based on actual data from the phase 3 trial processed on an unblinded basis ...not to mention the 10 other DMC interim analyses. When in doubt it is worth reminding yourself of the words of the DMC (the only unblinded party at that date to the results) who examined the primary and some of the important secondary endpoints at the END of the clinical trial and said the trial should continue without alteration. It is important not to be too hung up about individual patient data and look at a whole body of evidence . The results from the LVAD trial showing a substantial reduction in bleeding events from ischemic patients is a further illustration that something pretty profound is happening.
Maybe once the Company has formally announced it has put a data lock on the trial results , it could persuade the FDA to allow publication of the futility hurdles set by Mesoblast with the DMC before the start of the trial. Now that would be interesting ! Of course they could have spent hundreds of millions on a heart trial that stood no chance of success ... but I don’t think so !
As you can probably gather I am spending an inordinate amount of time posting on this thread . The Mrs, is not impressed . Reluctantly I will have to reduce the number of contributions I make, or reduce the length and detail I go into with my replies.This is in the interests of self preservation !
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