Paula,

I love your logical way of thinking but my concern is the expense to do the right thing for the sham group. With my luck, they will decide to have us as a seperate group
(19 real 1 sham) and guess who will get the sham? Incidentally, at my facility, 4 got the real treatment and only 1 got the sham, me!!!

I pride myself on being very perceptive and felt that the folks who knew post-surgery were behaving in kind of an awkward fashion. In fact, the surgeon literally ran away from me after making sure I was OK. A year later, he laughed and said it was his only placebo. I had misinterpreted this behavior as confirmation that I received the real treatment. Guess I over-thunk it!!!

OK. I wrote so much last time that I was only going to say "thanks" to Tom's post. You put a face20on the trial participant - and that's the story we have to tell. That is why we have "human" trials - people who must cope with diseases like Parkinson's - who live its emotional ups and downs every day - otherwise we could just stop the trials at the primate (monkey) level.

There's a wonderful opportunity for us to ask an expert all of these questions first-hand on an upcoming webinar (the first I've heard of ever!) see announcement below:

Participating in Parkinson's Clinical Research: The Key to Becoming an Informed Study Volunteer

Wednesday, January 14, 2009, at 3:00 PM Eastern time

Featuring Kenneth Getz, M.B.A., author of The Gift of Participation: A Guide to Making Informed Decisions About Volunteering for a Clinical Trial

Click here to register:
http://event.netbriefings.com/event/.../register.html

I think this idea of testing of subtypes of Parkinson’s is brilliant. Greg Wasson came up with theidea (I believe) andwrote about it in an OpEd on the Pipeline site:
http://pdpipeline.org/advocacy/oped_..._july23008.htm

I'm not a statistician, and only took a couple of statistics courses at the Master's degree level, so if I am way off course, please correct me. We have small numbers of participants in phase I trials, because they are conducted to evaluate the safety of a treatment in humans. Any improvement of participants is a plus. Any unsafe results, and the trial is halted immediately.

The Phase II level is (or should be) carefully planned, with a requirement of "testing" enough participants to show that any improvement from the treatment didn't just happen per chance. Endpoints, or outcomes, must be hypothesized and projected. The IRB (Institutional Review Board) at each research institution decides what those expected results will be. There are statistical tests that must be done after all the data is gathered and a significance level at a minimum of 0.5 must be shown for the trial to be valid. Validity means the study tests what it said it was to test. Reliability is achieved when the study can be replicated with relatively the same results when repeated.

At present there is no test to “prove” that one has PD (with Multiple sclerosis, for instance, an MRI shows demyelinating or white patches visible on the brain). With Parkinson’s, we go by symptoms and the ruling out of other disorders.

So , I pose this question:
Is it ethical to “fake” the surgery a trial? Since PD is diagnosed via observation of symptoms, why doesn’t observing whether or not there is improvement of symptoms count?

I have been searching through some old books and online about this subtypes testing. There’s some really good stuff at this site: http://www.improvingmedicalstatistics.com/

If a study did test a treatment dividing them into subtypes of PD (e.g. tremor dominant vs rigidity or balance issues dyskinesia vs no dyskinesia), we would have to be very, very careful with how those groups were divided because itsays "the validity tends to be inversely proportional to the number of subgroups which are analyzed":

Inappropriate subgroup analysis can lead to ludicrous results.

Subgroup analysis, at times, can lead to findings that are incorrect. If a subgroup analysis results in an unexpected finding in outcome that is different from a highly significant and beneficial effect for the group as a whole, the subgroup analysis is often incorrect. In fact,it is more likely that the unexpected subgroup finding that runs counter to the group finding is simply not valid.
Source: Improving Medical Statistics

Read this very easy-to-comprehend article for a better explanation.:
http://www.improvingmedicalstatistic...s%20%20%20.pdf

This same article says, “A subgroup analysis which results in variance from the overall group outcome is more likely to be true if it involves a large subgroup and there are a very limited number of pre-specified analyses.” This means the Phase II recruiting of volunteers would be even greater in number. Recruitment would be even more difficult. It isn’t like people are knocking down doors to enter a trial where half of them will have sham surgery. But the results using subtype analysis would result in some real meat to chew on – a way of treating PD that’s never been done before. I sincerely believe this could turn the treatment of PD around.

Peg thanks so much for a really comprehensive and honest post. And to those pipeline members who contributed. Outstanding points and what do i know about statistics if someone doesn't write it down and explain it well?


i took out the reference i had here. it didn't seem specific enough for what we are focusing on.

paula

Expectations in clinical trials were investigated in 2005 resulting in a good paper by Fabrizio Benedetti et al. Altho a few years old, it talks about expectation pathways in our minds, that could be working in a way similar to the actual treatment. He also comments about "hidden treatments", where the person doesn't know he/she received a treatment, not working as well as when the person knows he is getting it. Here are two references about this.

Ray Bartus has not responded to emails asking for more information about ceregene, so based on his first comments to Perry Cohen about "lowering trial participant expectations to reduce placebo noise", I thought these may be interesting:

http://www.sfn.org/index.cfm?pagename=news_111505c

[from ppp email - planton]: actual Benedetti study

http://dcscience.net/placebo.pdf

excerpt:

Interesting, paula. One may not buy into the "heal thyself" theory, but cannot deny its positive effect on both physical and emotional wellness. I want to address a sensitive subject now, and I hope the monitors can see the science in what I am about to say, and not the "religion" so that others can read it.

Growing up with the philosophy of Norman Vincent Peale (especially in his book The Power of Positive Thinking), I have to say that I am convinced with all my heart that attitude plays the most powerful role in healing. This isn't about Christianity, but it is about the mindset of Christianity (and just like with any religion, there are good and bad apples). If we feel a power within us that we can overcome something, what could be unhealthy or even unscientific about that?

I found this tidbit about Peale that I want to share:

Peale applied Christianity to everyday problems and is the person who is most responsible for bringing psychology into the professing Church, blending its principles into a message of "positive thinking." Peale said, "through prayer you ... make use of the great factor within yourself, the deep subconscious mind ... [which Jesus called] the kingdom of God within you ... Positive thinking is just another term for faith." He also wrote, "Your unconscious mind ... [has a] power that turns wishes into realities when the wishes are strong enough."

This is a whole "nutter" topic, but I sincerely believe that scientists should not be so quick to poo-poo the theory of positive thinking and its impact on healing. If it improves the well-being of a person suffering with pain and disabling symptoms, I fail to see the bad in that - and I definitely fail to see "failure" in that.

And what - do tell - could possibly be wrong with that???
Peg

Nothing like a middle of the night post. We all used to be much braver. Anyway, Peg, your message is personal, which is not used by younger generations or various professionals, medical in particular, I've discovered...if I'm wrong, you know all someone has to do is explain it and set me straight.

I like to spend time learning the scriptures and get great comfort from them, and I am pretty sure i know what you mean about Norman VP. There isn't much Norman Vincent Peale around now. Currently, there is an attack mode that never seems to let up; balanced "positively" with the obsession to get wealthy and place accumulating wealth as the highest priority.

And here we are.....trying to stay positive using the only successful ways that work. Scriptures are so cool.

The entire world could use a good chill out with scripture quotes, just ignoring the source so as to avoid pcitis - and taking in the wisdom

Perhaps a thread could be started. It could be quite profound - just the verses - no preaching - particularlly as they might apply to this situation with the pd community. Competitive, fractured, don't really know the patients on the inside. It 's such an inside disease.

Ok I'll leave one here and if you want to start another thread go for it.

Hebrews 10:1

Now faith is the substance of things hoped for, the evidence of things not seen.

paula

I didnt intend to turn this very important thread around. There is a "Santuary for Spiritual Support" forum where we can share our spiritual life.
http://neurotalk.psychcentral.com/forum27.html

But I did want to show the connection between placebo/attitude/and positive thinking/spirituality. Guess we'll keep this thread "clinical."

Hope is what we all need and must have - and I believe the research people who don't see the connection are the real losers.

Peg

Ok this is going to sound different and it just might be a determiner [something that determines lol] who or what is real in this thread.

I 'm assuming some things just from writing this story; would anyone correct an error if they read one here? If not, I feel it's possible that some of the researchers, industry, orgs, etc., [and if reading] are still way behind in how they view patients studying current research, especially now that it is getting very sophisticated. You can't ignore how we feel about these things .....heres why:

• it's not going to stop the aggressive verbal ...ness. this is science/journalism; with forums and blogs having bad reputations. We are in a very unique postion to interact with 100% innovation. And do it right.
• Ok - there's a recent patent application - Dr. Gill et al for an infusion pump to be approved in the USA......includes mentioning of Amgen's gdnf. Dr, Gill stayed mostly out of the fray, always knew he could possibly need that gdnf. Dr. Clive Svendsen , I would love to hear from you about this.
• Teamwork - can you all have a phase III or phase II/III of pump infused GDNF and at the same time, let's have Ceregene Phase III , along with an accompanying smaller study of supplying the phase II placebo with the real treatment. Lots to watch and learn.
• Give us some choices, many of us are your next - what da?? patients, participants, consumers, patient consumers, clients, lab rats - who are we? [and what is the meaning of life...lol]

Repeating the previous one, many of us are at the point where clinical trial participation is where the hope lies. But as I said in the above post... Hebrews 10:1 says "Faith is the substance of what is hoped for...the evidence of what is unseen." Where do patients place their faith? How do the non-pwp gain the trust of the pwp and their loved ones?


One way is by interacting on an equal level with all. Doctors and medical personnel, I want to say here that I respect your position but do not always agree with what you say. I've caught doctors in mistakes, not deliberately looking for them, and usually don't correct them. The few times I have, a fancy song and dance conversation switch usually occurs, to avoid the correction.

• Progress has been made in many areas buy you are still a ways off on what we can do....It's like the movie ..darn can't think of name...Tim Allen was a washed up superpower; he gets kidnapped by the gov. to train new young kids with uncontrolled superpowers. They bonded and did great things.

ok for the 689th time....can someone in the research or industry of ceregene, mjff, UK, Gill, investigators. clinicians, grad assistants.......kindly give us an update of whether we could possibly have these 3 choices in place soon? Or comment on placebo; there's an abundance of issues....really....in this thread. It behooves someone to be respectful enough to enter into this peaceful thread and enlighten us. Allow us into the research agenda plannng .....Andy Grove.....we were nice to you!..lol

I do not know how to think on a more local scale. This is where I was taken from the beginning - all things are possible.

When we were little, we used to call each other "yellow bellied chicken livers." Note how I have not done that. I 'm here in peace and will squawk if anyone is mean.

I'll attempt to clean up or organize this thread, unless somebody else wants to? ...

I attempted to address subtypes in post #15 above. Are those of you who are speaking of subtypes thinking in this way about subtypes? If not, can you be more specific about what you would consider subtypes to be.

Subtypes would include:
1) slow progression with tremor,
2) rapid progression with tremor,
3) #1 without tremor,
4) #2 without tremor,
5) with dynkinesia,
6) with dystonia,
7) with both 3 and 4.

--------------------------------------------------------------------------------

On the topic of placebo I found this:

plac-, placi-, -plais
(Latin: to please, to satisfy; peace, peacefulness; calm, calmness)

http://www.wordinfo.info/words/index...age=8&letter=P

placate
placebo (antonym: "nocebo")

1. "I shall please".
2. In medicine, a prescription given to please a patient who, in the physician's opinion, needs no medication.
3. something of no inherent benefit that is done, or said, simply to placate or to reassure someone.
4. Something prescribed for a patient that contains no medicine, but is given for the positive psychological effect it may have because the patient believes that he or she is receiving treatment.
5. A "sugar pill" or any dummy medication or treatment; for example, in a controlled clinical trial, one group may be given a real medication while another group is given a placebo that looks just like it in order to learn if the differences observed are due to the medication or to the power of mental suggestion.
6. Etymology: from Latin placebo, "I shall please"; future indicative of placere, "to please".

The medical sense is first recorded in about 1785, "a medicine given more to please than to benefit the patient".


The placebo effect and the power of belief
"Michael Brooks, a writer of an article in New Scientist magazine, took part in a "placebo" experiment in which he was told that a computer screen would indicate whether electric shocks would be mild when a green light showed up or a red light would indicate when the shock would be "more severe".

"After about fifteen minutes, the experiment ended with what he thought were a series of "mild shocks" until he was told that the "last series of shocks" were all severe. He "felt the electric fence jolts as a series of gentle taps" on his arm until he was told that the "last series of shocks were all severe".

"He realized that he had experienced "the placebo effect" because his brain had been conditioned to anticipate low pain when he saw the green light on the computer screen for the series.

"The "placebo effect" for quite awhile has been considered to be nothing more than the "power of positive thinking" and so people believed that they were receiving good medical care even though it might have been nothing more than a sugar pill or an encouraging manner of the physician. In many cases, people started to feel better without any additional medical treatment.

"Some current research about the placebo effect indicates that it is more complicated than simply being a "positive thinking" result; however, depending on how it is done, the placebo effect can make some people feel better even when they are not really any better."


Editorial: "Patient, heal thyself"
"The placebo effect has been known since the beginnings of medicine.

"About the only medicine doctors from long ago could offer their patients was the reassurance that a medical treatment would work and it often was successful.

"It has become apparent that a patient's state of mind, awareness of his/her condition and expectations of the care she/he is about to receive can influence many outcomes of medicine from consultations with a doctor to clinical trials of a new drug.

"Apparently the usefulness of a drug, for example, depends on much more than the chemicals in a pill, and a deeper understanding of the placebo effect can turn it into a valuable tool for reducing suffering."

Yes I saw that stitcher and didn't reply because I don't know what kinds of sub-types are possible, altho your choices sounded very logical. This is an area of interest and one that needs to be put to use, which i'm sure they are. We may have something to contribute here.

paula