[Debi Brooks]

http://www.wired.com/print/medtech/d...placebo_effect

Fascinating article on placebo...

Debi Brooks

[paula_w]

Thanks Debi,

Benedetti has done extensive research in Italy on pain, which is truly mind blowing but this is the first I've seen on depression. What futuristic experiments that could come out of this phenomenon! Do we have illness because it is labeled? Does medicine helps us to live longer now or not? If we weren't told our kidneys or liver would fail from too much medicine would they still fail?

But it also could be dangerous. Like, "oh you're fine" as you send little Tommy to school with swine flu. which raises a very interesting question about how long placebo can last - do they work for life as vaccines? i can't get polio - i'm vaccinated.

we know so little!

let's all pretend to be perfectly happy and healthy and see what happens.


paula

[ZucchiniFlower]

From the article:

"Benedetti has helped design a protocol for minimizing volunteers' expectations that he calls "open/hidden." In standard trials, the act of taking a pill or receiving an injection activates the placebo response. In open/hidden trials, drugs and placebos are given to some test subjects in the usual way and to others at random intervals through an IV line controlled by a concealed computer. Drugs that work only when the patient knows they're being administered are placebos themselves."

Please explain this sentence to me. I understand it...

"Drugs that work only when the patient knows they're being administered are placebos themselves."

let's all pretend to be perfectly happy and healthy and see what happens.

Paula, I've often said that I wish we could harness the powerful placebo effect that exists in PD trials.

You may know about my theory of completing feedback loops with visual, auditory, and sensory cues. That also includes cues that we just think about, for example, an inner metronome to give us rhythm. These feedback loops allow us to move better, etc. because the automatic loops that healthy people have are broken for us, or work only occasionally.

Well, perhaps anticipating reward forms new connections in the brain that effect the same behavior as the drugs.

We read that electro stimulation of the spine affects neurons that are connected to tactile sensations which make connections in our brain. I would say it completes a loop necessary for our brain to react and allow us to move better.

We don't need to electro stimulator if our mind can supply the same connection by employing external cues!

Same with the drugs. We may be able to imagine our way to the same result.

We need to come up with a way to anticipate reward in a meaningful, efficient, effective way. Let's think about it, please. We need to get cracking!

[ZucchiniFlower]

People with PD who are depressed should not be lumped in with non PD depressed people.

Here's a study that confirms post-mortem findings:

Monoamine transporter availability in Parkinson’s disease patients with or without depression

"Conclusion Our data indicate that depression in PD is associated with a more pronounced loss of striatal dopamine transporter availability that is most likely secondary to increased dopaminergic degeneration. In addition, depressed PD patients have a lower availability of midbrain/brainstem monoamine transporters than nondepressed PD patients.

These findings provide in vivo evidence in support of the known post-mortem data demonstrating more extensive nerve cell loss in PD with depression and indicate that SPECT imaging can help to identify pathophysiological changes underlying nonmotor symptoms in this common movement disorder."

http://www.springerlink.com/content/v441tk2167663450/

[Conductor71]

Originally Posted by paula_w

we know so little!

let's all pretend to be perfectly happy and healthy and see what happens.


paula

I ran across some interesting reading this afternoon. Apologies to our senior members for any redundancies...

Interesting anecdotes about the failed efficacy of Levodopa in clinical trials. Apparently, the clinical trials did not meet outcomes due to placebo effect (much like Ceregene) back in the 60's when the drug was first introduced. Yet, today it is our gold standard. An interesting history on clinical trials of levodopa and the problems of motor fluctuations...Clinical Trials in Neurology. Roberto J. Guiloff. 2001.

The Power of Mind and the Promise of Placebo. World Research Foundation

Why Parkinson's drug trials should abandon Placebo...

Brain Mechanisms Underlying the Placebo Effect in Neurological Disorders.
Functional Neurology. Cavenna, et al. 2007

Expectation and Dopamine Release: Mechanism of the Placebo Effect in Parkinson's Disease. Science. Fuente-Fernandez, et al. 2001

Researchers found that the placebo provided benefits comparable to a therapeutic dose of levodopa. PET scans substantiated the results.

[LindaH]

Last March the Parkinson Pipeline Project presented a poster at the 2009 American Society for Experimental Neurotherapeutics (ASENT) Conference that raised similar questions about the impact of the placebo effect on growing numbwr of failed Phase II trials and the need to re-examine the use of sham surgery in PD clinical trials.
The text of the poster is at http://pdpipeline.org/advocacy/2009%20poster.htm

We agree with Andy Grove's statement on PD OnlineResearch. Writing about infusion trial designh that “, we should avoid institutionalizing the practice of drilling sham holes just because it has been the practice in the past. Such a reexamination would also allow us to focus early on the question, which of the competing infused substances is most effective – an issue we have to deal with urgently, “.
http://www.pdonlineresearch.org/resp...n-trial-design

We share Mr. Grove’s sense of urgency == “failed” trials may mean that potentially effective treatments are sitting on the shelf.
as more PWP are being asked to undergo the risks of possuble sham surgeries in gene therapy trials, it is crucial that we fully understand the placebo effecct in PD researcch and make necessary changes in trial design. Past trial “failures” should be reanalyzed and questions be answered, and perhaps more effective and ethical cllinical trial designs will be discovered.

[Perryc]

Linda,
Thank you for reporting on our ASENT presentation. I want to add to what you have said, by pointing out that the presentation may turn out to have a real impact on design of clinical trials involving brain surgery in the future. After seeing our poster and discussing it with us at the ASENT meeting, Dr. Howard Federoff, Chair of the RAC (Recombinant DnA Advisory commitee) which reviews all gene therapy trials, agreed to initiate a workshop by the RAC to address the concerns raised in our paper. The meeting now starting to be planned by NIH plan will include PWP as well as Scientists. The FDA generally accepts the RAC's recommendations.

Perry

Below is the entire text of an updated version of the paper which adds discussion of the real consequences of of 'failed' clinical trials. (I am sorry that the charts do not format well for posting here). I hope this is not overkill of too much information.

Parkinson's Disease Clinical Trials: Square Pegs in Round Holes?

Perry D. Cohen, Wilson H. DeCamp, Linda Herman, Arnold M. Kuzmack, Stan Planton, Carolyn Stephenson, Peggy Willocks and Paula Wittekind
Parkinson Pipeline Project, Washington, DC
ASENT Annual meeting
March 10, 2009

OBJECTIVE

This paper examines three failed clinical trials for promising new Parkinson’s therapies. All have similar designs that require surgical intervention to deliver the treatment and utilize sham brain surgery as a placebo control. It relates common reasons for their failure and gives close scrutiny to evidence on the benefits vs. risks of placebo brain surgery.

Phase II of all three trials were multicenter, randomized, double blind, sham surgery controlled studies All three showed favorable results in the open label Phase I trials, but did not meet their endpoints in Phase II.

All three trials were conducted using the dopamine replacement theory as treatment by either viability of available dopamine (GDNF), production of dopamine from transplanted cells (Spheramine), or genetic alteration for the production of dopamine (CERE 120).

Table 1. Summary of Design Characteristics of Failed Clinical trials

Therapy Name GDNF Spheramine NTN
Sponsor Amgen Titan Ceregene
Other Backer Medtronics Bayer/Schering Genzyme
Description
Phase 1 Design Open label, 2 sites Open label, unilateral for worst side Open label
# pts./duration 14/4 years 6/6+ years 12/36+ months
Results UPDRS 39% to 57% up 48% up after 1 year; 44% up after 4 years 40% up
Other evidence Autopsy Autopsy
Phase 2 design All therapies: multicenter, randomized, double blind, placebo surgery control
Sample 34 pts. (50% control) 78 pts. (50% control) 51 pts. (33% control)
Blind for placebo Install equipment w/saline solution Sham, but did not pierce dura Did not pierce dura
Duration 6 months 12 months 12 months
Increase in UPDRS Ave. 10% Not yet published Ave. 18%
Placebo Ave. 4.5% Not yet published Ave. 18%





GDNF (Neurotrophic factor) – recombinant GDNf by pump infusion method

Amgen sponsored two open label phase I safety trials of GDNF in 15 patients. The studies were initially for six months, with some patients treated for up to 3 1/2 years. Based on the clinical endpoint of reduction in the UPDRS motor "off" score, the efficacy ranged from 39 to 57%.

Randomized, double blind, placebo controlled, parallel group phase II trials were initiated in 34 patients. The clinical endpoint was the Change in UPDRS motor score in the practically defined off condition at 6 months.

The sponsor (Amgen, Inc.) terminated the phase II trials in September 2004. The rationale given was that, “Six months of treatment with GDNF delivered to the putamen failed to improve UPDRS scores compared to placebo." There was "evidence of alteration of brain function," a likely reference to changes on neuroimaging, but improvement on UPDRS scores did not meet the primary endpoint of the trial. However, a participant from the Bristol (UK) study died of an unrelated cause, and, upon examination of his brain via autopsy, neural sprouting was noted (the first report of its kind).

Open label extension studies were begun to resolve differing trial results. But in Sept. 2004, Amgen sent letters to clinical investigators halting further clinical studies, due to safety concerns – development of lesions in the cerebellum of 4 test monkeys and "anti-r-metHuGDNF neutralizing antibodies found in two of the study participants to date."

Spheramine [Retinal Pigmented Epithelial (RPE) Cells]

In 2000, Titan Pharmaceuticals in a Phase I open label trial consisting of six participants with advanced disease (3 3.5 or greater on the Hoehn & Yahr scale) received unilateral treatment (for their “worst” side) transplanting RPE cells (without the use of immunosuppression), using a donor eye from a cadaver. (One eye can be used to treat hundreds or patients.) At 12 months, an average improvement of 48% in the UPDRS M (off) outcome measure was realized, along with improvements seen in other measures of motor function and quality of life. One participant dropped out because of a later diagnosis of Parkinson’s Plus. Participants continued to be followed through 48 months, maintaining a 44% average improvement and continue to be followed. It was reported, "The data also demonstrate a very good preliminary safety profile for Spheramine. There has been no evidence to date of any significant side effects in any of the patients . . . a reduction in dyskinesias for most patients and . . . no ‘off state’ dyskinesias . . . observed."
(Titan handout, April 2002)

In 2003, a phase II study was initiated with a randomized, double blind, placebo controlled (sham surgery) trial of 71 patients (78 were actually recruited) receiving treatment bilaterally, and received fast track approval by the FDA. Titan was joined with the U.S. Berlex sponsor, which is also Schering AG (Germany), and was later acquired by Bayer (Bayer Schering/Titan). In July 2008, Titan announced that Phase II did not meet its primary or secondary endpoints and Bayer Schering AG withdrew as a sponsor. The sponsors (Bayer Schering / Titan) announced that they had discontinued development of Spheramine in July 2008.

Titan stated that its "potential cell based treatment for Parkinson's Disease failed to meet its primary and secondary endpoints in a Phase IIb study, and likely won't be continued by partner Bayer Schering Pharma... Initial analysis of results from the 71 patient study of Spheramine designed to test the safety, tolerability and efficacy of the treatment found that it had no significant differences from sham surgery arms after 12 months of follow up." (Company press release dated 7/2/08)

CERE 120 (neurturin) – Gene therapy

CERE 120, a gene therapy product in development for the treatment of Parkinson’s disease, was administered to the putamen with adeno associated virus carrying the gene for neurturin (NTN), a growth factor related to GDNF and shown in experimental models to protect dopaminergic neurons from degeneration. Six patients received a low dose and six a high dose (1.4 x 10^11 vs. 5.7 vector genomes). Neurturin was well tolerated and appeared to reduce symptoms by approximately 40% (p<0.001), as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS) motor “off” score, in an open label Phase 1 study in 12 patients with advanced disease. (Company press release dated 10/10/2006)

The sponsor (Ceregene) announced the phase II trial failure in Nov. 2008. Analysis of the phase II trial data did not demonstrate an appreciable difference between patients treated with CERE 120 versus those in the control group. 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. Both groups had a substantial number of patients who demonstrated a meaningful clinical improvement from baseline. CERE 120 appeared to be safe and well tolerated."

A company spokesman stated "...we are stunned by the results of this trial and will continue to analyze the data in order to gain greater insight into the factors that may have contributed to this negative outcome, not only to build upon this insight for our Parkinson’s program, but also to help assure continued successful development of our product candidates for other diseases.” (Company press release dated 11/28/08)

In an in depth interview with the Michael J. Fox Foundation, Raymond T. Bartus, PhD, executive vice president and chief scientific officer of Ceregene, reported that they are attempting to redesign the Cere 120 trial to expand the delivery target area and increase dosage. Two trial participants died from unrelated causes, providing the opportunity to view the progress of the neurturin through autopsies. Discoveries were made that may enable research to continue in the near future. (http://www.michaeljfox.org/research_...icle.cfm?ID=11)

RESEARCH FINDINGS ON PLACEBO BRAIN SURGERY

The Placebo Response is based on conditioned expectations from the social context of the intervention for a reward. It is a well known concept in social science including the Hawthorn effect from industrial engineering in studies of worker motivation showing the power of an experiment, and the Pygmalion effect in education documenting the subtle bias from the expectations of teachers (authority figures). The greater the saliency from the risk and other stimulation the more powerful the effect. No wonder experimental brain surgery produces such a dramatic effect.

The mechanism of the placebo effect is release of endogenous dopamine in the brain using the same channels that are used by humans for movement. This makes the placebo effect indistinguishable from and directly confounded with the most prominent features of PD.

• Dilution of placebo effects in randomized experiments. In the treatment group confounding placebo effects may diluted by the less than 100% likelihood that the patient is on the “real” treatment, and in the control group the chance that the patient is on the “real” thing elevates expectations. Also, unlike real medical practice where both doctors and patients want patients to improve, the experimental situation tendency to dampen hope for fear of biasing results also may dampen treatment effects. Attempts to mitigate the hopes and expectations of patients whose primary if not only reason for taking the significant risks of experimental brain surgery are those very hopes and expectations, will not succeed and may further bias results due to placebo effects.

• False negative (Type 2 errors) bias. Our observation is that in placebo brain surgery controlled trials that placebo effects are so strong that they overwhelm the power of the study and introduce type 2 errors. The assumption that blinding neutralizes this bias to allow measured improvements to be attributed to the treatment does not fit the findings that both treatment and control groups improve. Instead by randomizing the very strong placebo effect you dilute treatment group effects which may be masked by placebo response, and increase placebo response in the control group. For Ceregene both treatment and control improved (!!) for 70% of subjects; in other studies treatment groups did better than control groups but both IMPROVED so differences were not statistically significant.

• Triggering effects in pain control. Experiments with pain control show the necessity of letting the patient know s/he is getting pain medicine, and placeboes work well if the patient expects that s/he is receiving the medicine.

DISCUSSION

Based on the design of the three studies described above, we suggest two possible reasons for the unanticipated failures in phase II.

1. Selection bias resulted in different types of PD patients being enrolled.

Examples of such bias are:
• tremor dominant vs. rigidity dominant symptoms
• responders vs. non responders to standard therapy
• responders vs. non responders to placebo
• optimized on medications vs. non optimized

2. Sham brain surgery as placebo may be so powerful that it overwhelms treatment effects for a time (maybe up to 2 or more years, but usually not more than 1 year).

Such an effect could force type 2 errors when the interim study results are analyzed after a short time

CONSEQUENCES OF “Failed Pivotal Trials.”

Development of new therapies by industry sponsors is extraordinarily high risk and high cost. It not only requires great understanding and knowledge to identify targets for intervention, but it also requires flawless execution of complex protocols to get it right.

Dr. Stanley Fahn of the Columbia University Medical Center has stated:
“A negative trial result does not necessarily mean that the compound in question is of no therapeutic value – especially when that compound has demonstrated promise in animal studies and earlier, smaller, human trials. There could have been a problem with the study design or lack of optimum dosage of the experimental compound. A variation in the study design (e.g., different duration, different dosage, different patient selection criteria, a change in method of drug delivery) may yield different results, and should be explored before any particular approach is abandoned."

Business Decisions. The science, however, is only part of the decision to continue development of a new treatment. The economy, patent life, and competitive factors as well as the capital reserves and cash flow of the company weigh in heavily on what is primarily a business decision. Even when money was readily available enormous capital investments (close to $1B ) to carry the development more that 15 years for neurology before receiving any return, and even then many treatments fail in late stages of development, after most of the money is spent. To make matters worse, most of the innovative therapies are sponsored by small entrepreneurial firms with little revenue and investment capital that are betting the whole company on the outcome of the study. These entrepreneurs are usually committed to their idea, so want to give it every chance to succeed, but once a pivotal trial fails. Decisions about further development pass to the responsibility of a dispassionate large company executive or other investors who are not likely to be very familiar with the promise of the science or with patients that have done well on the treatment. Thus the real consequence of a failed study is most often a termination of the program, and often the closing of the business, such as Titan Pharmaceutical described earlier. Table 2 lists 7 more PD therapies that have terminated in late stages

KEY QUESTIONS

Our analysis of the three recent failed trials points to questions that need to be addressed in order to justify what many consider to be unjustified risk to ask patients to take in a blinded, placebo brain surgery controlled clinical trial, even given expectations that even if they do not benefit personally science will advance.

1. What adjustments in the design of statistical controls are necessary to account for the impact of the context of an experimental protocol that alters expectations of participants by blinded randomization into treatment and control groups?

2. What scientific criteria are used to determine efficacy or the lack of efficacy of a treatment?

3. What assumptions are made about the interaction effects between a treatment response and a placebo response?

4. What factors should be considered when selecting samples from a heterogeneous populations as the evidence grows that some endpoints may be achievable only for patients (responders) with certain genetic variants or clinical sub types of the disease or are influenced by other factors including the method of delivery?

This presentation adds urgency to the need for these discussions, because trials are failing, and promising therapies are being shelved in what has been called the “tyranny of the type 2 error". (M. Hutchinson, S. Gurney and R. Newson. GDNF in Parkinson disease: An object lesson in the tyranny of type II. Journal of Neuroscience Methods. 163, 2, July 2007, 190 92)

Table 2. Other Therapies recently terminated in late phases

Therapy Sponsor Clinical Endpoint FDA Action: NA = not approvable Company Action
CEP 1347 Cephalon disability requiring dopaminergic therapy phase 2/3 trial discontinued, 5/2005
Tesofensine (NS 2330) Neurosearch phase 3 canceled, 1/2006
GPI 1485 Symphony brain uptake of [123I}Beta CIT phase 3 terminated, 3/2006
Perampanel Eisai reduction in "off" time phase 3 trials terminated, 10/2007 and 4/2008
Sarizotan Merck phase 3 terminated, 6/2006
Vadova IMPAX alternate tapping of keys NA, 3/2006 & 1/2008 terminated development, 4/2008
Istradefylline Kyowa reduction in "off" time NA 2/2008 suspended phase 3 in North America, 6/2008


CONCLUSION

The above failed phase II studies were for therapies that were known to work for some people over extended periods. The members of the Parkinson Pipeline Project have analyzed possible explanations for this poor record of accomplishment. We have suggested hypotheses that fit the pattern of results seen in these studies. Our goal is to present a clear and convincing argument that these are plausible hypotheses that merit further study and such a study is a very high priority.

There is considerable research on pain, depression and the mechanism of the placebo effect. These studies suggest that an experimental protocol that views placebo surgery as a "bias" to be minimized may in fact undermine the validity of the study. Key questions are raised that researchers and regulators need to answer in order to prevent type 2 (false negative) errors. Based on the research literature, alternative design features and more rigorous methods are needed to reduce error. Particularly valuable would be acceptance of un-blinding patients (not raters) in comparison to best medical practice as was for DBS (a surgical intervention and the most important new therapy for PD in the 40 years since Levodopa was introduced 40 years ago).

Given the number of new, promising, surgically delivered, treatments in the PD pipeline, policy discussions among FDA officials, scientists and knowledgeable patient advocates (including patients that volunteer for experimental treatments) on both the scientific and ethical issues about what constitutes adequate control in the study design must be a high priority to provide guidance to sponsors. The topic needs to be addressed fully before other promising therapies are shelved based on faulty assumptions about human behavior and the response to medicines.

The authors wish to acknowledge the support of the Parkinson's Disease Foundation to the work of the Parkinson Pipeline Project.


QUOTE=LindaH;560638]Last March the Parkinson Pipeline Project presented a poster at the 2009 American Society for Experimental Neurotherapeutics (ASENT) Conference that raised similar questions about the impact of the placebo effect on growing numbwr of failed Phase II trials and the need to re-examine the use of sham surgery in PD clinical trials.
The text of the poster is at http://pdpipeline.org/advocacy/2009%20poster.htm

We agree with Andy Grove's statement on PD OnlineResearch. Writing about infusion trial designh that “, we should avoid institutionalizing the practice of drilling sham holes just because it has been the practice in the past. Such a reexamination would also allow us to focus early on the question, which of the competing infused substances is most effective – an issue we have to deal with urgently, “.
http://www.pdonlineresearch.org/resp...n-trial-design

We share Mr. Grove’s sense of urgency == “failed” trials may mean that potentially effective treatments are sitting on the shelf.
as more PWP are being asked to undergo the risks of possuble sham surgeries in gene therapy trials, it is crucial that we fully understand the placebo effecct in PD researcch and make necessary changes in trial design. Past trial “failures” should be reanalyzed and questions be answered, and perhaps more effective and ethical cllinical trial designs will be discovered.[/QUOTE]

[ZucchiniFlower]

Conductor, here is the PDF full article for
Brain Mechanisms Underlying the Placebo Effect in Neurological Disorders....

http://www.functionalneurology.it/ma...in/article.pdf

I haven't read it yet.

A later article on the subject: Biological Psychiatry

Volume 56, Issue 2, Pages 67-71 (15 July 2004)

Placebo mechanisms and reward circuitry: clues from Parkinson's disease

Raúl de la Fuente-Fernández, etc

"Recent evidence indicates that the placebo effect in Parkinson's disease is mediated by the release of dopamine in the dorsal striatum. Interestingly, there is also placebo-induced dopamine release in the ventral striatum, which establishes a connection between the placebo effect and reward mechanisms.

Specifically, we propose that placebo responses are related to the activation of the reward circuitry. Here, the clinical benefit induced by placebos represents the reward. The magnitude of the placebo effect likely depends on the a priori probability of clinical benefit. This notion has profound implications in the design of clinical trials and placebo investigations."

http://www.journals.elsevierhealth.c...240-X/abstract

It's pretty clear that the use of placebos in PD trials is self-defeating, since inherent in the trial is anticipation of reward. It's illogical to use placebos when it is KNOWN that anticipation of reward increases dopamine production. There must be a way around placebos. Heck, if a nurse during the war didn't inject a soldier with salt water instead of pain killer, we might not even use placebos in clinical trials. ~Zucchini

[pegleg]

As many of you are aware, I was one of the original six in the first phase of the Spheramine trial (later called the STEPS trial). Phase I was open-label (meaning we knew we were getting the treatment); in the larger Phase II (72 participants), half received the treatment (the injection of donor retinal pigmented epithelial cells) and the other half underwent “sham” surgery (the implanting of the cells was faked without participants’ knowledge until it was revealed 12 months later).

Phase I participants were followed after receiving the cells for almost 9 years. The effects were astounding – official peer-reviewed results indicated that phase I participants maintained approximately 47% improvement over their own baseline results.

It’s very difficult for me to reply to this because at the moment my PD symptoms are “full-blown,” due to recent foot surgery. Debi, you may recall Paula and I visiting Fox Foundation 2 maybe 3 years ago. At that time I was nursing this broken foot wearing a moon boot. I must have a high pain threshold, because we walked all over New York City ! I procrastinated on a metatarsal fixation until 2 weeks ago knowing how the pain and anesthesia really messes me up, having had the same procedure in my other foot years earlier.

I say all this to say that I do not see how my improvement after Spheramine could have been placebo effect. And that claim may well not be made. I’m no statistician, but how can you truly compare the two phases of the trial since the protocol was so different. Phase I was transplanting dopamine-producing cells unilaterally (one side of brain); Phase II was done bilaterally (both sides)? And how do you “think” improvement of such symptoms as balance?

And while on this topic, how ethical is it to deceive trial participants, especially with sham brain surgery? If the word “deceive” seems strong, read this excerpt from the article Debi gave:

After decades in the jungles of fringe science, the placebo effect has become the elephant in the boardroom.
The roots of the placebo problem can be traced to a lie told by an Army nurse during World War II as Allied forces stormed the beaches of southern Italy. The nurse was assisting an anesthetist named Henry Beecher, who was tending to US troops under heavy German bombardment. When the morphine supply ran low, the nurse assured a wounded soldier that he was getting a shot of potent painkiller, though her syringe contained only salt water. Amazingly, the bogus injection relieved the soldier's agony and prevented the onset of shock.
Source: http://www.wired.com/print/medtech/d...placebo_effect

Perry and the Parkinson Pipeline Project (I am a member as well as paula) are investigating whether sham surgery in Parkinson’s research is necessary, or is it even ethical? Watch for more on this.
Peggy

[paula_w]

....since that's all that counts.....paula

Reuters
Tue Sep 1, 2009 11:34am EDT
* Drug misses antipsychotic efficacy goal
* Acadia co-developing the drug with Biovail
* Acadia shares sink 68 pct; Biovail down 2 pct (Adds analyst comment, bylines; updates shares)
By Lewis Krauskopf and Ransdell Pierson
NEW YORK, Sept 1 (Reuters) - Acadia Pharmaceuticals Inc (ACAD.O: Quote, Profile, Research, Stock Buzz) said on Tuesday its experimental drug for psychosis related to Parkinson's disease failed to meet its primary goal in a late-stage trial, sending its shares down 68 percent.

From article:
Patients in the 298-patient trial who were taking pimavanserin showed improvement in psychosis measures, but the difference was not statistically significant. Acadia said the lack of a significant difference was primarily due to the larger-than-expected improvement in patients taking the placebo.


http://www.reuters.com/article/rbssPharmaceuticals%20-%20Diversified/idUSBNG48310420090901?sp=true