here's mud in your eye. what if there was something screwy in the phase1 results? that they were not exactly "right"? The phase2b results turned out to be totally due to chance and not the treatment, the patient's basically said so in the daily diaries they kept where they described if their daily activities of living improved and they didn't. i'd love to see a before video of the woman who said she improved so much. as far as the placebo group doing better after 6 months, this article explains that, it's the excitement/anticipation of being in the trial. if there is no affect from the treatment there is an affect from just getting evaluated, it's exciting, causes an adrenaline rush - these people are supposed to be rated when OFF, no medication for 10hrs or something like that. they are still progressing but like i mentioned before, i took the UPRDS motor test in order to qualify for a DBS, was OFF for 12hrs, had to be driven because i can't drive whenOFF, yet when i got to the doctor's office adrenaline or something produced an unexpected low score. pd'ers continue to get worse but they can work out, do things to improve their score on the test, it's all just simple movements, finger tapping, wrist turning, standing up/sitting down, walking back and forth down the hall, resistance testing.
they didn't even pierce the skull with the placebo/sham surgery so you can't even attribute the improvement to cell repair from damaging neurons.
"Sham treatments help to tease out the placebo effect and biases. In Parkinson's disease, the placebo effect is especially strong. One reason is that patients' expectations that they will benefit from a treatment induce the release of dopamine
11, the neurotransmitter that is lacking in the disease. "The placebo effect is real, it's huge and it's got a physiological basis," says Jon Stoessl, a neurologist at the University of British Columbia in Vancouver, Canada, who studies Parkinson's and the placebo effect. In one double-blind study of fetal nerve-cell transplants, patient improvement correlated with whether they believed they had received the treatment, irrespective of whether they actually had
12. And the effect can last as long as two years, Stoessl says, citing an unpublished study by his colleagues."
"
Many regard bias as a more significant confounder. "Investigators have a tremendous vested interest in seeing that their treatment is effective," says Anthony Lang, a neurologist at the University of Toronto in Canada who has participated in several neurosurgical trials for experimental Parkinson's therapies. In any trial, bias can affect how researchers assess patient responses and may inflate the patients' expectations, further enhancing the placebo effect. Compounding the problem for Parkinsons' research is the fact that there are no objective measures for how well a patient is doing. "It's just a sort of perfect storm conspiring against our ability to see definitive changes in the underlying disease," says Steven Piantadosi, a clinical-trials methodologist at Cedars-Sinai Medical Center in Los Angeles, California. "Sham surgery, properly done, can control for that."
Barker counters that it is possible to control for investigator bias in an open-label trial by taking steps such as having blinded raters assess patients. His position is in some ways unsurprising; in Europe, sham surgery is deemed much less acceptable than it is in the United States. It has never been used in the United Kingdom. Barker is categorical about his belief that transplantation of fetal tissue works, at least for some people. "I don't need sham surgery to show that," he says, pointing instead to a paper
13 published last year describing two patients treated 13 and 16 years previously who were still benefiting from the treatment, and whose brains showed functional dopamine-producing neurons at the transplant site. He attributes the mixed results in past studies to variation in the patients selected for treatment, the characteristics of the tissue being implanted and the methods used to implant it. His trial will have to demonstrate efficacy without eliciting some of the side effects found in the two sham-controlled studies. That will require some type of control study, he says, but it might take the form of comparison to an approved therapy that is known to work, such as deep brain stimulation.
But time, says Barker, will best establish efficacy. In most trials the end point is no more than a year after the treatment. That may not be long enough: implanted cells or injected growth factors might take longer than this to become fully functional, and the placebo effect may not have had time to dissipate. "We want a 3–5-year endpoint," says Barker.
There are hints from some of the failed phase II trials that patients followed up beyond study endpoints might tell a more positive story
4. Some say, therefore, that sham controls are sinking the prospects of valuable drugs. Anders Björklund, a neuroscientist at Lund University in Sweden who is collaborating with Barker, says that sham surgery can lead researchers to throw out a strategy prematurely if the trial fails because of technical or methodological glitches rather than a true lack of efficacy."
keep in mind that they did a scan on the LCT phase1 patients and found no increase in dopamine production.
http://www.nature.com/news/2011/110810/full/476142a.html?s=news_rss
what stands out the most for me is that the phase2b NTCELL40 group got 2 implants so i would have expected as good or better results than phase1 and the phase2b results appeared to be a little worse. they had 12(14?) month data from the NTCELL40 group, why didn't they mention it? and they had results from the other endpoints, why didn't they show that. from the trial protocol:
Secondary Outcome Measures:
- Change in total Unified Parkinson's Disease Rating Scale (UPDRS in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
- Change in Unified Parkinson's Disease Rating Scale (UPDRS Part III in the 'on' state) over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
- Change in Quality of life as assessed by Parkinson's Disease Questionnaire (PDQ-39) over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
- Change in L-dopa dosage over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
- Change in scores measured by the Unified Dyskinesia Rating Scale (UDysRS Parts I, II, III, IV - Parts III and IV will be performed in the 'off' and 'on' state) over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
- Change in scores measured by the modified walking test in accordance with the CAPSIT-PD protocol (Defer et al. 1999) over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
- Change in Modified Hoehn and Yahr stage over 26 weeks post-intervention compared with baseline [ Time Frame: Baseline and 26 weeks ]
https://clinicaltrials.gov/ct2/show/study/NCT02683629?show_desc=Y#desc
i assuming they're reviewing everything right now, maybe even the phase1 data. having no biomarkers for pd that measure improvement allows patients to possibly cheat a little by taking meds when they are supposed to be measured in the OFF stage, you could measure l-dopa in the blood i guess but that doesn't really measure it in the brain, but that doesn't seem to be the case in phase2b, noone got statistically better.
almost done posting here.
