Pfeifer wrote:https://pubmed.ncbi.nlm.nih.gov/15494428/Regarding...

Pfeifer wrote:

https://pubmed.ncbi.nlm.nih.gov/15494428/
Regarding confounding factors - sure, but MSB is trying to demonstrate that the product works independent of the donor that provided the bone marrow aspirate. How can you do that if a patient gets MSCs from potentially 2 (or more) different donors, especially since MSB have shown different levels that could have affect clinical outcome (INFgamma - see Aggarwal & Pittenger:)."

Bazsa responded:

It's not hard given the amount of data that would have been collected over the years. Let's say the first dose has been shown to be the dominant contributor of day 28 results, perhaps 50% the second 20% down to the last which may have very little influence on the day 28 result. The rest is mathematical . It would actually be considered a study failure not to include the data. given the amount of data that would have been collected over the years. Let's say the first dose has been shown to be the dominant contributor of day 28 results, perhaps 50% the second 20% down to the last which may have very little influence on the day 28 result. The rest is mathematical . It would actually be considered a study failure not to include the data.

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Ah but that is exactly the problem you are left having to guess just about everything about the potency of the first dose. Oh MSB can say they know how much TNFR1 is in that dose in terms of picograms per mililitre at p5 batch release time and MSB can also probably say how much IL2Ralpha inhibition occurred when a sample of cells from the same batch were co-cultured with activated T cells in an in vitro test. MSB can know those things about the dose - but they don't know how effective or potency it is if it only knows those things because it doesn't know that other things in the batch from donor weren't as or more important in determining the overall potency of the dose.

... because you haven't got an established validated potency assay you are entirely guessing about the potency of the first dose and always will be until you have a potency assay that has had alternate confounding factors in it eliminated.

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I think I've worked out a way to demonstrate that 11 data points on a x versus y linear correlation plot represent singles not multiples of 11 different sized groups - you simply imagine the line of best fit to be a straight rod looked down from above with strings attached at ninety degrees to that straight rod and to each data point. Then imagine each data point is a bucket. With a single unit weight (say a kilogram in it but the bucket has room for several more of the same unit weight) - all the 11 data points in buckets can pull on the rod half from the positive side and half from the negative side. The rod finds a natural balance point between the total weight of the buckets pulling on it from the positive and negative sides. With 11 unit weights in the bucket the rod would be in a place that exactly averages the positive and negative sides. Then if you add more weights one at a time to any of the buckets on the positive or negative sides you change the weights on that side which pulls on the string at ninety degrees to the rod and pulls the rod (the line of best fit) closer to the buckets (the buckets you have to imagine being suspended by string going that passes through a loop such that its a straight line to above the bucket then a ninty degree turn from horizontal to vertical. The horizontal distance of the lines or strings to the buckets measure the pull on the rod or line of best fit. Any change in any of the buckets weights moves the rod or line of best fit towards the side the extra weight is placed.