I just finished Nick Nelson's fine book about the GDNF trials by Amgen called "Monkeys in the Middle". As a medical researcher, I can tell you that whoever designed the Amgen trials didn't know some of the basic scientific aspects of organizing and running such a study. I worry that the same may have been true for the Spheramine trial and hope that the Ceregene and Neurologix trials have better research design consultation.

For the Amgen GDNF trials it appears that the various treatment sites had a great deal of latitude in the tubing that they used to pump the GDNF into the brain and the way in which this was accomplished. Some of the pumping strategies were better than others and there were site specific differences in outcomes. The other very distressing issue is that in many of these studies the major outcome measure is the Unified Parkinson's Disease Rating Scale (UPDRS). The truth of the matter is that the UPDRS is a lousy measure with poor inter-rater reliability. It is highly subjective with poor guidelines for raters to use in measuring what they are seeing.

According to Nelson there is 25% or more variance between raters in scoring the scale. If the endpoint you are looking for to deem a treatment as effective is 30% improvement from time 1 to time 2, a finding or a lack of finding may be due totally to a lack of rater reliability from one time to the next.

I have been doing research on substance abuse and pain for about 20 years and although that area has some similar problems, they are not as bad as the ones that I have seen in the Parkinson's area.

Nelson's very strong conclusion is that for many people from some of the GDNF sites the outcomes were outstanding and irrefutable some sites did not get such great results. There also looked to be some systematic differences between sites that could account for these differences.

On a hopeful note it appears that within Amgen there came to be a growing feeling that the pump was not a good long term solution to the delivery of GDNF to the brain and that the way to go was gene therapy. All of us hope that this will be borne out when Ceregene reports their Phase II results in Q4. Just pray that they ran the study carefully and in a way that will show differences between treatment and control if they exist.