Boann,

Yes - and the variability is a huge problem for us. Because trial after trial will "not meet their end points" for the majority of the trial participants, but SOME of the participants will do well, and endpoints WILL be met for certain individuals.

Carolyn got neurturin in the CERE-120 phase II trial, and it DID work for her. It just didn't work for the majority of the participants.

Spheremine is another such example. It worked for Peg.

So what to do? What to do? I see promising treatments not meeting endpoints. And for some of us is a real loss because it appears that these treatments would have helped at lease SOME of us.

But how do we prove that? How are we tested to know who will be helped by what treatments?

This is a huge problem.

and have one quick comment or question for something GregW said in the MJFF disappointment thread, i.e., that CERE 120 had failed to meet its endpoint.

The press release I read from Ceregene didn't say the trial failed to meet endpoints, it said:

"The trial did not demonstrate an appreciable difference between patients treated with CERE-120 versus those in the control group."

it also said:

"Both groups showed an approximate 7 point improvement in the protocol-defined primary endpoint (Unified Parkinson's Disease Rating Scale- motor off score at 12 months), relative to a mean at baseline of approximately 39 points. "

That's an 18% improvement, on average.

The rotigotine transdermal patch trial published in 2007 had as its primary end point:

"minimum of 20% decrease in the combined Unified Parkinson's Disease Rating Scale Part II and Part III scores."

So a 20% improvement is not unheard of as an endpoint.

So, the fact that the CERE-120 group and the placebo group improved by the same amount in and of itself, in my opinion, does not necessarily indicate that CERE 120 is not effective. – degree of improvement should also be considered - what if both groups had improved by 50%?

At what point do we consider the possibility that the placebo effect might be as effective as the actual treatment as opposed to the view that the actual treatment is no better than the placebo effect? The former acknowledges both as potentially beneficial, while the latter dismisses both as useless.

Rosie:

"At what point do we consider the possibility that the placebo effect might be as effective as the actual treatment as opposed to the view that the actual treatment is no better than the placebo effect? The former acknowledges both as potentially beneficial, while the latter dismisses both as useless. "

ABSOLUTELY!!!!

The fact that the placebo effect appears to be HUGE in PD patients is something that should be pursued. I think it is a factor in our lives beyond its appearance in drug trials. How many of us use denial to our great benefit? I find it very beneficial in my life - denial - the biggest placebo of them all!

he had seen the placebo effect cause improvements in Dat scan results which should be totally objective.

He takes the placebo effect seriously and told me he is always at pains to appear totally self confident, his thinking, if the PWP sees a confident Neuro then they will share that confidence/placebo and hence improve.

Neil.

<PD, its all in your head>.

Good points Rosie and welcome. The placebo effect could be keeping people from getting treated. I'll just point out here that DBS had no placebo control and it is wreaking havoc on many a pwp. But it also helps many so there it is...a treatment available if you want it.

paula

A very insightful post Rosie!!! I was a participant in the Ceregene clinical trial. I had a thrilling year. Here is a list of my improvements:

Energy level improved - able to eat meals and watch movies/tv without falling asleep (despite poor sleep patterns caused by PD meds).

Eye fluttering improved.

Foot drag almost completely resolved - still occurs during off times which have improved since Day 2. Gait and arm swing greatly improved. In fact, arm swings normally frequently throughout the day for first time in 8 years.

On times are improved Used to be off predictably during last 1-2 hours before each PD meds dose - sometimes off periods do not occur between doses

Levadopa more effective - virtually symptom free at various times - has not occurred in 8 years

Handwriting - Able to write faster and clearer

Keyboard typing - now able to use right hand

Food - Able to butter bread and cut food unassisted.

Able to hold phone to ear with right hand comfortably without fatigue

Able to shave and brush teeth with right hand without assistance from left hand

Able to get change out of right pants pocket

Feel better balance especially on stairs

Able to get in and out of car much faster

Able to give wife foot massage with right hand for first time in 2 years

Drooling less and swallowing better.

Mental outlook improved - happier, excited about the future for the first time in 8 years

Facial expressions have improved according to my family

Treadmill - Able to walk normally for 45 minutes with no foot drag!!! Before surgery, I could manage a few minutes before I would have to rest for a minute.

By the way, at my facility, only one person got the sham (placebo) surgery. That one person was ME!!!!!!!!!!!!!!!!
I imagined it was real and I improved my condition.

In my opinion, researchers are going to have to come up with a way to evaluate patients without human intervention. UPDRS scores are based on the judgements of a human being. I was such a cheerleader for myself I can't imagine I didn't influence the scores that were recorded.

I asked one of the scientists at Ceregene if the placebo group showed no improvement would the study be deemed a success - he said YES!!! On the other hand, how much of the improvement demonstrated by the treatment group was the placebo effect?

In my opinion, the treatment group and placebo group should be watched for an additional 12 months where a clear difference should reveal itself. The problem is that the study was unblinded very quickly. You can imagine the range of emotions I have felt since I heard the news. I am trying to remain positive by spreading the word about the power of placebo thinking but I also know there are 20 people with advanced PD walking around with two holes in their skull and visible scars on their skin who may never see the real treatment.

Researchers at Ceregene and MJFF have told me that an in-depth analysis of the stats would be performed over the coming weeks. One question I have which has not been answered is: How many folks from the treatment group have eliminated their meds? I know of at least two and I imagine there is more. I doubt anyone from the placebo group can make that claim.

Bottom line: this may turn out to be an effective treatment for some which most likely means back to the drawing board while we wait. For my fellow sham participants, this is a tough pill to swallow although I had a thrilling year and would do it all over again if I could!!!

Hey thank you for the thank you - I left you a private message.

Hey guys & gals!
I have been preaching this placebo effect for years. It could be the key as to why some PWP's react differently to the same treatments. I remember speaking to a group about my positive experience with Spheramine (surgical implanting of dopamine-producing cells into my brain). I made the coomment that one would probably never know if my progression course would have been the same with or without the surgical intervention. I also remember the group chuckling when I added, "And if it proves to be a placebo effect, you should bottle it and sell it!" Now I am thinking all the more how this could be for real.

Phase I Spheramine trials (only 6 people) maintained a 40+% improvement after 4 years. Phase II participants (78 people) did not meet their endpoints. This means that of the people who received sham or fake surgery, those who got the real stuff faired no better. Everyone, including the researchers were left with their jaws dropped, having reported only days earlier at international professional meetings about the anticipated potential of Spheramine.

My point - if "thinking" you are better can do that kind of thing to test results, there are 2-3 possible answers that might hold the answer to why PD hasn't found better therapy in 40 years:
1) we need to review the testing protocol presently used by research (those used to measure improvement - such as the UPDRS, Hohen & Yahr, etc.) or are we using unrealistic statistical formulas to analyze data?
2) we need to look at the way patients are recruited (are we allowing "unqualified" participants to enter trials which skews results - such as depressed patients who would naturally get "better" by default of feeling better about their treatment), and
3) if the placebo effect IS truly that powerful for Parkinsoon's, why aren't we seeing more treatments designed toward this? (Examples: biofeedback, anti-depressant therapies, etc)

Comments?

Peg