The learning effect. To test patients for cognition over different points of the trial patients are retested with the same type of tests and like anything, practice makes you better. In mild Alzheimer's where brain damage is not yet severe, both the treatment arm and the placebo improve at the early testing before dropping below the base line later on in the trial. The PBT2 trial only went for 12 weeks, so PBT2 had to show improvement over patients in the placebo arm who had improved.
[The Journal of Alzheimer's Disease paper reports the results of a post-unblinding analysis of the cognitive data that was not included in the original paper. The objective
of the analysis was to see how individual patients who were receiving PBT2 responded compared to the individual patients who only received placebo. Importantly, even placebo patients showed some improvement in the tests because of a ‘learning effect’ of repeated testing. This new analysis has adjusted for this and demonstrated that:
• 81% of patients on the 250mg dose of PBT2 responded better on the Executive Factor NTB score than the best performing patient on placebo.
• 41% of patients on the 250mg dose of PBT2 responded better on the overall Composite NTB score than the best performing patient on placebo (of which
Executive Function is one of 2 parts). ]
http://www.pranabio.com/downloads/Media%20Releases/Media%20Release%202010/New%20Analysis%20JAD%2019%20April%202010.pdf
That learning effect has brought a few trials crashing down at the end, when pre unblinding, researchers thought they could see gains.
The first big ani plaque trial was done by Neurochem, and failed with a rising placebo, even out to 18 months, blamed.
[Dr. Bellini hesitated to describe the study as negative, pointing out that the statistical analysis was complicated by improvement in more than 30% of the control patients. "This complicated the analysis beyond expectation, so that our results are inconclusive," Dr. Bellini said.
Dr. Paul S. Aisen, principal investigator of the North American trial, noted the unexpected improvement of so many control patients is probably a result of the effect of concomitant medications, and will be a recurring problem in all long-term studies of disease-modifying agents for AD.]
http://www.thefreelibrary.com/Tramiprosate+falls+short+in+phase+III+Alzheimer's+trial%3A+unusually...-a0172316596
I find it comforting to know PBT2 has already demonstrated convincingly it can rise above that placebo effect.
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