research v. Phase II exam

Mulling over the results of LCT's failed Phase II test, I repeatedly come back to this worry. Could such small samples ever expect to meet the targets of the strict Phase II rules for success?

At present we are handicapped by the lack of raw data, but I think it is worth considering the results from the point of view of research rather than as merely a failed Phase II exam.

Let's consider this. I wonder whether a major problem for LCT's Phase II test is inter-rater and intra-rater reliability over time.

https://www.ncbi.nlm.nih.gov/pubmed/16116612

I don't know how the rating took place, but on the face of it quite small deviations from consistency of rating reliability over time could explain the strong tendency for improvement in the sample that received the placebo.

In fact rating reliability could explain all the improvements over time, and the tendency for all samples to trend downwards.

Now this possibility is significant, because all that is required for experimental success is that the lines follow the horizontal baseline of no worsening. It would be nice if the lines (other than the placebo line) sloped downwards with time, but mere lack of any worsening in symptoms over time is surely a success.

This consideration raises another question. Are there studies that show the expected worsening of symptoms (i.e. increase in the UPDRS score) over a period of 26 weeks?

I am thinking of the attached model, which shows a hypothetical line of worsening as an upwards, red slope.

https://app.box.com/shared/static/z79yaaj2syf67qmi9je3r5zh0801vbad.jpg

If such statistics of expected worsening are available, then surely this is the line that should be the basis of a null hypothesis for statistical testing of LCT's results - not the placebo line? The placebo effect creates too much noise in patients to be suitable as the sole basis for comparison, but of course it had to be used in the failed Phase II test.

Just to repeat, I realise that LCT had to pass a Phase II examination, but its failure in the exam does not mean failure of the treatment.

Let's hope, for the sake of PD sufferers, that somebody with deep pockets (eg. the Bill Gates Foundation) picks up the porcine ball and runs. Such developments may not do shareholders any good, but they sure could benefit sufferers of PD and other neurological conditions.