1. almost all trials had a good phase1 result - spheramine (retinal cadaver cells), **a gene, gdnf, etc. pd'ers who volunteer for these risky trials have a large placebo affect, they are bungee jumpers. phase2 trials have all failed or had minor success due to blinding of the treatments and a control group not receiving the treatment to measure the placebo affect.
2.there are no biomarkers for pd that can give you a quantitative measure of progression, no blood test so evaluation is all based on a clinician measuring patient movements/cognition/patient diaries and no machine is used, it's all a judgement call by the clinician. AND THERE'S no way to know if the patient took parkinson's medication before being evaluated except to search them for drugs and then lock them in a room the night before. with a such a small number of people in this trial, it only takes 1 patient to screw up the results by taking less meds when the baseline measurements are taken to give an artificially high UPDRS (the higher the number, the worse the pd) which would make the treatment seem more effective than it really is. OR, the patient just fakes being worse to produce a higher baseline score. my point here is that because measuring pd is somewhat imperfect it requires very careful clinicians and very careful patient management. i was diagnosed 15 years ago and some days i feel like crap, my meds don't work and my UPDRS score can be much higher, other days i feel great and you wouldn't guess i had pd. and, i can just try harder when taking the tests and get a better score, or try less hard and produce a worse score. without a biomarker, you are taking measurements via a method that itself has some variability. just eating a meal high in protein will negate the affect of meds for at least 2 hours. constipation can make my pd much worse. if i was an investor i'd like to know what rules they set forth with patients so they would be in the same physical condition each time they came in for measurement. did they have rules on how much sleep you needed, what you could eat before being scored?
3. every pd'er is different so your're starting with a fair amount of variability. only 40% of pd'ers have tremor and it is more difficult to treat than the other symptoms of pd such as rigidity. did by chance more pd'ers with tremor show up in a particular group? that's been the greatest barrier to finding a treatment that can slow down progression or reverse it, the fact that the underlying cause of pd varies quite a bit. they tried to get a homogeneous group of patients by only selecting those that qualified for DBS so they were similar in cognition and how well they respond to l-dopa. If i go to a pd exercise class or support group, everyone is different. so without a biomarker(s) to measure, you're treating something called pd. a good example of this is the DAT scan, which is supposed to show you indirectly how much dopamine producing cells you have. people with PD can have a perfectly normal DAT scan. so this ain't like diabetes where you can just measure insulin.
4. how many times did they measure UPDRS / patient at each measuring point, did they get an ANOVA on just measuring UPDRS? I.E., how much variablity did each patient show with UPDRS if they measured it everyday for a week?
5. gender differences?
6. did they evaluate the results by age and/or gender?
7. did they show in phase2 whether more dopamine was being produced, they did in phase1 and couldn't find an increase in dopamine.
the gdnf trials had great phase1 results and phase2 bombed yet many of the patients felt better, spouses and friends would attest to this. here's a trial which had a much larger sample and they decided to watch the patients longer because a few seemed to do much better
https://www.michaeljfox.org/foundation/news-detail.php?news-in-context-second-phase-trial-of-cere-120-yields-disappointing-resultsbottom line they were hoping for a large affect with such a small sample and inherent variability of advanced pd'ers from day to day. did they measure UPDRS variability in each patient and exclude people with excessive variability?
enuf said.
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