thanks

[jeanb]

Most clinical trials fail - but scientists still learn from failed trials!

We still have too few people with PD who are willing to step up and join - fewer than 1% of all pwp in the US participate in clinical trials.

Thanks to all those who have participated in clinical trials in the past or who are in trials now.

[paula_w]

jean,

i know what you mean and agree that trials are sorely lacking people. Neither patients or doctors are involved enough. But I feel like we are at a crossroads right now. I'm going to list - faster and you already know them anyway:


placebo is an elephant in the living room
sham surgeries do not end up getting any treatment for reasons that aren't quite acceptable - psychology of that ignored.
do they learn more from autopsies than the trial results? Would ceregene have continued if they hadn't been provided autopsy opportunities when 2 patients died? Also an autopsy in the GDNF trials.
I think patients should be told exactly what is going on. They would be more inclined to take part in something that reflects a more modern, updated trial design. Subtypes would be attractive.
The low numbers are from [iMHO] a lack of trust. Changes are mandatory.
editing the last statment: there are other reasons, namely lack of affordability, transportation and just plain motivation and energy levels are very low.


paula

[jeanb]

Paula,

I do think that the clinical trial system is flawed – but I hope that doesn’t stop pwp from at least considering joining a trial. I hope pwp will at least visit pdtrials.org and see what is available in their community. If they need a ride, contact the trial coordinator and see if transportation can be provided. If they have other barriers but would otherwise like to participate, contact the trial coordinator and see if accommodations can be made so they will be able to participate.

Anyone considering any clinical trial should be fully informed. All pwp have a terrific resource on pdpipeline.org: the database of drugs in the pipeline. I encourage pwp to review the info in the database about treatments, companies, previous studies, etc etc in the database.

Jean

PS I hate sham surgery and will not participate in a trial that uses it.

[indigogo]

I would not volunteer as a participant in a clinical trial that involved invasive procedures under any circumstances (excepting, perhaps, being at the very end of other therapeutic methods and physically declining fast), at this point in time.

The points raised by Paula are critical to be addressed before the PD medical establishment can assume they will get the unwaivering support they have received in the past from the patient community.

We have become too sophisticated as consumers and human beings to any longer loan our bodies and pay with our health for experiments gone right or wrong without the appropriate compensation and without complete transparency, communication, and information.

All those we know here, Peg, Carolyn, Jean, Jingle belle, and others, who have willingly given themselves to advance the science without expectation of a good medical or financial return are true heroes, and we are grateful.

But their example is not one to be followed, and should not be expected by researchers until they take the responsibility to fix the problems (impossible end points, placebo effect, known deficiencies in the mouse to human model, subtypes, etc) that have come to light recently - and as Paula indicated, are ready to explain to patients what they have done to correct for them.

Clinical trials participants should be well-informed, knowledgeable heroes-as-research-partners, and not be asked to attain their hero status by being willing to jump into the abyss blindfolded with a mere "trust us" as their only lifeline.

[indigogo]

I would not volunteer as a participant in a clinical trial that involved invasive procedures under any circumstances (excepting, perhaps, being at the very end of other therapeutic methods and physically declining fast), at this point in time.

The points raised by Paula are critical to be addressed before the PD medical establishment can assume they will get the unwaivering support they have received in the past from the patient community.

We have become too sophisticated as consumers and human beings to any longer loan our bodies and pay with our health for experiments gone right or wrong without the appropriate compensation and without complete transparency, communication, and information.

All those we know here, Peg, Carolyn, Jean, Jingle belle, and others, who have willingly given themselves to advance the science without expectation of a good medical or financial return are true heroes, and we are grateful.

But their example is not one to be followed, and should not be expected by researchers until they take the responsibility to fix the problems (impossible end points, placebo effect, known deficiencies in the mouse to human model, subtypes, etc) that have come to light recently - and as Paula indicated, are ready to explain to patients what they have done to correct for them.

Clinical trials participants should be well-informed, knowledgeable heroes-as-research-partners, and not be asked to attain their hero status by being willing to jump into the abyss blindfolded with a mere "trust us" as their only lifeline.


Peg, Jean, Carolyn, Jingle Belle, et al - you entered your clinical trials based on the information you were given at the time; no one could have, or should have, expected more of you - you literally gave it all. Even though the trials "failed," you advanced the science greatly (as Jean noted) - helping to expose the problems with Parkinson's clinical trials that we have listed in this thread. That is how science is supposed to work. You are all trailblazers; your experiences changing the landscape for future trials.

What you have also helped bring to light is that now that we know these things, steps must be taken to correct for them before others can responsibly fill your shoes in new trials.

Just the fact that we know what kind of troubles are occurring is also remarkable - due to the increased transparency among all parties involved in research. I hope that pressure from the patient community was in part responsible for the better communication.

Now that we are privvy to more information than before means that patient participants have a greater need and reason for answers to their questions before signing on the dotted line. Caution advised when considering an invasive surgical, gene, or pharmacalogical trial - become fully educated!

[reverett123]

Why can't there be a bargain whereby Big Pharma sets up a fund to establish a series of residential sanctuaries around the world where PWP who took part in trials were entitled to live out their lives with the basics of existence and state of the art care. It would have the bonus of continued followup even after the trial was over.

They do it for primates.

[jeanb]

When I got my PD diagnosis, I searched the internet for something –anything that would help me fight back. I discovered clinical trials. And a few months later I joined my first trial. I’ve been in 5 now – with 2 on-going. And I’m signed up for #6 -- my brain donation for research (thanks to the funding from the Fox Foundation & Sun Health).

I have also worked long on the Declaration of Clinical Research Rights & Responsibilities for PWP. And I believe we are making a difference. We are being heard. I’m not ready to give up on the system.

And as I posted earlier, no one should consider joining a clinical trial without first doing thorough research. I stand by that. Just as I will continue to advocate for increased clinical trial participation by pwp.

Sometimes people of good conscience must disagree on important issues. This is one of those times.

[jeanb]

Why can't there be a bargain whereby Big Pharma sets up a fund to establish a series of residential sanctuaries around the world where PWP who took part in trials were entitled to live out their lives with the basics of existence and state of the art care. It would have the bonus of continued followup even after the trial was over.

They do it for primates.

I love that idea!! :p

[paula_w]

I think we're talking about the trials that involve surgery more aren't we? I was. That's where the "benefits are not worth the risk" comes in.

Rick, your suggestion does make one think twice.....lol.

paula

[jeanb]

Many trials involve risk - even if they don't involve surgery. CEP-1347 turned off the mechanism for cell death. When I considered joining the trial in the hopes it would slow PD's progression, I decided I'd take the cancer risk. So now am I at an increased for cancer one day - all because I participated in that clinical trial? I don't know. I hope not, but fully informed, it's a risk I took.

[reverett123]

...I started out being a little facetious as is my wont, but actually the idea has some merit. It would be great PR for Big Pharma and the cost would be low compared to marketing and a write-off as well. And while the ethics would have to be handled properly, I am sure that a good research team following PWP closely through the years could find something valuable. Maybe Pfizer or GKS should start buying up those old motel sites we once discussed.


I love that idea!! :p

[Debi Brooks]

Not that I want to defend all actions of all trial sponsors...can't and won't, but I did want to throw some additional thoughts into the mix in this thread.

If we want new and improved treatments for PD, we must recognize the truth that we are all best served by a constructive contract between the patient community and industry. I'm not talking about patient bill of rights kind of stuff (which, in general and theory I support) but rather more of a fuller appreciation for what it takes for industry to maintain, let along increase its investment in PD. Whether we like it or not, no company is obliged to develop new treatments for our indication. They will only do so if there is an opportunity for a sensible/competitive return on capital for equity holders. We didn't make these rules but they are the facts on the ground and, to my mind, it is imperative that this be front and center when we contemplate anything to do with trying to advance new things to the clinic.

Biology is hard. We don't understand enough about PD to make it a slam dunk for industry to develop new products. It's not clear that success in animal models is sufficiently predictive of success in patients. We don't have biomarkers. Trials must enroll large numbers of people and follow them over long periods of time to gather data needed to demonstrate the statistically significant improvement over current treatments. Patient recruitment for clinical studies and clinical trials is chronically low in PD--adding more costs of course. All these factors make it borderline for large companies to even get involved. Some of the world's largest pharmaceutical companies don't even have an interest or active PD program...we would all be well served to do what we can to change these circumstances. Many of these elements are out of our control. Again, biology is hard. But finding ways to increase patient participation / contribution of data is one thing we can do to improve at least part of the equation.

I wholeheartedly recommend and endorse the idea that each individual patient needs to pause and ascertain the appropriateness (in consultation with family and their healthcare team) for them to paticipate in any given clinical study. But please realize that when the patient community sees industry trial sponsors as the enemy or the establishment and assume we have competing goals leading us to systematically step back with a sense of what they owe us, it could/will lead to fewer opportunities for new, transformative treatments.

Again, I'm not a patsie for every sponsor and all their decisions but without a sensible/affordable plan/expectation for patient recruitment in any study, the study could be doomed from the start. And lots of non-starters add up to no new treatments. An anecdote: at MJFF we are working on a pretty big study (still in the planning stages) where we will need ~ 400 patients and ~ 200 age and gender matched controls to participate in an observational study for biomarkers. So, no intervention being tested, but rather trying to collect clinical and biological samples over a multi-year study to see if we can validate some biomarker candidates already in the works (ie, get to the next stage toward being able to use these markers of progression as endpoints in trials)...anyway, in planning meetings experts in top academic labs and companies think we are delirious to think we can complete this recruitment at 10 to 12 sites in 18 months...they have such low expectations of the PD community. I have to think that works against us. We happen to think at MJFF that we, as a community can do better.

Additionally, the learning that takes place in clinical trials is on both sides -- researchers and patients. For instance, the plea above for trials to better utilize subtypes in clinical trials...everyone would like to do this...interest and will is not what stops trial sponsors. It is that we have yet to validate subtypes (whether they exist and how they should be defined) sufficiently to appropriately use them in trials as inclusion/exclusion criteria. Or, if we wait for all the mysteries of placebo to be resolved before any more patients participate in trials, we will be shooting ourselves in the foot. And yes there are some interventional trials where sham surgery might still be our best trial design--maybe not ideal but the best we have. Patients need to trust that trial sponsors will do the best they can -- but trials are a web of complex trade-offs of knowns and unknowns; not just costs and benefits.

I guess my point here is that participation / involvement in clinical studies might be one of the most important things that every patient can consider and act on when it comes to contributing to finding new treatments. Participation is not for everyone and not all trials are created equally, but, even doubling our current efforts could make a difference not just in accelerating progress but in guaranteeing that studies in PD continue to make economic sense for industry. And, I believe that we want / benefit from as much industry commitment to PD that we can get. More shots on goal increase our chances.

Debi Brooks

[indigogo]

Debi –

Thanks for posting. It is becoming clear that MJFF is not part of the PD “establishment;” that to compliment your innovative approach to research, you have an ongoing, vigorous, good faith effort to increase communication with patients. This is exactly the kind of partnership that is needed, the kind of dialogue that can end our us vs. them mentality.

Transparency is tricky. Patients have never had so much information. The interview with Dr. Bartus (http://www.michaeljfox.org/research_viewpoints_newsInContext_article.cfm?ID=1 1) on the Ceregene 120 phase II trial failure recently posted on the Fox website is a good example. It was refreshing to have access to his remarkably frank answers to equally frank questions. One of the issues that reemerged was the annoying presence of the placebo effect. It’s great that this is being pursued by MJFF (I know that my own doctor is involved in the discussions), but should I worry that the conundrum of the placebo be solved before other trials go forward; should I participate in a trial that might be torpedoed by the placebo effect? Or do I have too much information?

Regarding your statement, “anyway, in planning meetings experts in top academic labs and companies think we are delirious to think we can complete this recruitment at 10 to 12 sites in 18 months...they have such low expectations of the PD community. I have to think that works against us. We happen to think at MJFF that we, as a community can do better.”

Apathy is a little understood but major impediment to clinical trial participation among PD patients. It is also a major impediment to us leading normal lives. If MJFF can decipher and solve the problem of PD apathy, then maybe they’ve solved PD. (see this recent thread on “do you have trouble making decisions? (http://neurotalk.psychcentral.com/thread79565.html)”) Not only is decision making difficult (a major executive functioning function), follow through can be down right impossible at times. I would do almost anything to solve this problem.

It seems we have more questions than answers right now; research is done to find answers; how do we protect the health of the patient as we move forward? What is acceptable risk?

Thank you for engaging in the conversation, Debi.

[olsen]

Just a thought--bet you could obtain participants for your observational study from this forum. I know my husband would willingly participate, and I would volunteer to be a control subject. Any way to tap the resources of this forum for the study? guess you would have to determine to which of the participating centers each of the members have access--listing the centers involved and providing contact information for each center may be a way to achieve more participation than is needed.
Noodling on a friday night....madelyn

[Jaye]

Thank you, Debbie, for providing this forum with a broader picture of research than we usually see. I think it's obvious that many of us trust you and MJFF to serve us honestly, unencumbered by expectations or rules based on the past performance of the medical and patient communities. I especially applaud yor observation that "the learning that takes place in clinical trials is on both sides -- researchers and patients."

Like others here (even the guy named Et Al) I try to report back what I can from the studies I am in, from "depression can be a part of PD and is nothing to be ashamed of and not something you can shake off with a day at the circus" to "Strattera has helped me with executive function, but it makes me more grouchy than I care to live with" (a study that has just been published).

I'm sure I'm as apathetic as the next person, but I've been in a dozen or so studies (not all for drugs), beginning in 1999, and I'm one of the reasons we know something about the psychological processes of PD over time. Proud? You darn betcha. I have a pin that says "outstanding research volunteer," and I earned it. Yes, I have wonderful doctors, but I work with them in full partnership, and the time they take to teach me is found because of and during my research participation.

I don't mean to brag. I do mean to let my peers here understand that there is a lot of reward in jumping in to an imperfect world and helping out, even taking some risks (there were no data on taking Strattera and istradefylline at the same time) and facing one's own deterioration (those cognitive tests get appreciably harder as the years go by), while discussing with advocates like the Pipeliners some of the things I've observed that could be better (like the ethical dilemma of doctors whose patients can lose a medicine that's benefitting them by the order of the manufacturer). I also hope that MJFF can see that we don't all scorn the professionals who are trying to save us.

I hope this ramble can be understood by more articulate advocates than I and by the professionals they are in touch with.

God help us all.

Jaye

[Jaye]

pdtrials.org
pdpipeline.org

J.

[SherylJ]

[QUOTE=Debi Brooks;476218] "If we want new and improved treatments for PD, we must recognize the truth that we are all best served by a constructive contract between the patient community and industry."

I agree with you 100%, but question whether this can ever be an equal relationship when industry has time, money, and power on its side, and patients have only their disease ravaged brains to offer.

The points you raised make is quite clear who has the upperhand in this relationship. You say patients need "a fuller appreciation for what it takes for industry to maintain, let along increase its investment in PD. No company is obliged to develop new treatments for our indication. They will only do so if there is an opportunity for a sensible/competitive return on capital for equity holders." Ok, I don't like this argument, but I know it's true. Do any of the national PD orgs tell industry they need to have any appreciation for what PWP go through? Not to mention why we might find the insistence on sham surgery more than a little troubling.

If we truly want to increase patient participation, industry is going to have to see and treat patients as human beings and not subjects. This must go beyond paying lip service to patient rights and actually incorporating them into clinical trials.

I do not see industry trial sponsors as the enemy, but I don't necessarily see them as the true partner I'd like them to be. Clinical trials are the only hope for increased profits for the drug companies and better treatments for PWP. At a minimum, we owe each other a commitment to make the system better for all stakeholders.

"We happen to think at MJFF that we, as a community can do better."

Yes we can with an equal and willing partner.

Carey asks "What is acceptable risk (to patients' health)?"

Like "fair," it is in the eye of the beholder.

sheryl

[SherylJ]

Ok, I obviously don't know how to add on to my original post, so I'll finish up here.

While I obviously have strong feelings about the clinical trial process and continue working towards improvements, I am pragmatic enough to know that it is the only game in town. Most importantly, it is also the only road to a cure. I have participated in several clinic trials and will continue to do so when appropriate. I urge everyone to seriously consider participating in the trials available to them.

Sheryl

[girija]

I just want to add my two cents worth here. I am not adding anything new to the ongoing discussion, but stating a personal experience. I just attended a day long symposium on PD tailored to PWP, for the first time as a patient. I was totally taken aback by the condescending attitude of some of the clinicians/scientists/pharma representatives when responding to patients questions. The speakers are highly intelligent, successful people and their answers were good and logical/ But they need to realize that its time to treat patients as equal partners/ Patients I think, need to be more forceful and not be intimidated by science. After all, its the patients head thats in the spot light!! I also feel once mutual trust is built, patient participation will go up

All these years I was on the other side of fence, wondered why patients complain, hesitate to take part in clinical trials and appear to be in a rush all the time. Now I know I tell you, it is a lot easier to be the researcher working in a lab than being a patient waiting for the research to benefit me>

Girija

[girija]

They do it for primates.[/UOTE]
[/I]
We are not that different from these guys! Its even easier for me, I am a vegetarian too!! Rick, where are these primate sanctuaries?????

:D

[reverett123]

http://www.google.com/search?q=research+primate+sanctuary&ie=utf-8&oe=utf-8&aq=t&rls=org.mozilla:en-US:official&client=firefox-a



They do it for primates.[/UOTE]
[/I]
We are not that different from these guys! Its even easier for me, I am a vegetarian too!! Rick, where are these primate sanctuaries?????

:D

[paula_w]

Debi,
I understand your post to be saying that it is possible to have constructive relations between industry and patients, something I have believed for some time. When we don't have any way to talk to them, we have to second guess and have focused mostly on our own needs. Understanding their needs is just as important, but prior to just recently, we may as well have been monkeys.

I think your communications could do much toward bridging this gap.

Secondly, the study you are planning sounds low [no] risk and high impact. No treatment, just collection. If provided with all the information in a statement, along with updates, which can be posted anywhere [many have other means of promoting it], allow us to post in full with no copyright, including updates, then you could meet that goal of high numbers in a short period of time.

Knowledge is power, and we'd be glad to use whatever power we can muster to help, if we have the knowledge. Doctors must become more involved and we could give them regular information and updates also.

Final thought: getting a pwp anywhere can be hard. Is there anyway you could go mobile with that study? Get closer to everyone instead of them coming to the centers? Maybe that is too impractical but if you could, it might work very well, depending on what you are collecting.

Thanks again for posting.
paula

[indigogo]

Sheryl and girija - great stuff!

Seems like there is a fundamental misunderstanding of the PD population; we have a great understanding of and knowledge about the need for trials, how they work, the research details, how the industry works, etc. Logical or informational arguments for more participation isn't the solution; they don't address the problem, which seems two fold:

1. Disease related
The problem is motivation; and "movement" initiation; asking people who have damaged dopaminergic systems to do things we can no longer do without incredible effort. To be overwhelmed by the details of any project. Wanting to be in a trial and even making the decision to do so is the easy part; following through is the hard part. Often it's those pesky executive functions. Multi-tasking; concentration; making decisions and following through. Other times it's not being able to walk. It's movement initiation of any kind that has been damaged by dopamine depletion; motor and non motor.

Researchers should know their patients (clients) better That's the point of this whole "listen to the patient" thing - up until recently the medical establishment has been researching and treating a disease very different than the one we are living. It's because they never bothered to look beyond the stiff and shaky body that came through their doors. Why did it take so long to get them to understand that there was something else going on?

2. Researcher/Industry - Patient relationship
Patients are more informed; we have moved into a different era where trial participation as "human subjects" sounds, if not medieval, then oh so 20th century. We need to develop a new contract, partnership, relationship that accurately reflects the current situation.

On both counts above, seems like the researchers are the ones who need to catch up with the patients. It's a new paradigm; get with the program!

[Stitcher]

So much to reply too...

This is probably a topic I should not bring up, but...here goes anyway. Dr. Bartus interview with MJFF. Since that interview, which does appear to be open and honest, I have wondered why the interview took place. I have first-hand knowledge that Dr. Bartus, and maybe others at Ceregene, had had conversation with PWPs about the end results of the trial. Knowing this and having read the interview, I have wondered about the reason for the interview. Was the interview Ceregene's way of silencing the PWPs who had been "stirring the pot?" If not, why have the interview. I find it hard to believe it was just a "why not!" idea.

It is very true that talking to PWPs who have never been involved in a trail about trials is like talking to a brick wall...they look at the one suggesting the idea with that "you want me to do what!" look. Then comes the it is too far away to travel. It is had to find a patients, and the family, who will participate in a trial of any kind.

I am attending the Philadelphia CISCRP AWARE for All at the end of March because I want to hear the presentation on Informed Consent (also to help PDF with their table, but this part was an after thought). They are having a pretend Informed Consent, which will be particularly interesting.

I hope MJFF can see their 18-month trial recruitment goals. Recruitment goals being the first challenge can be most difficult. I was shocked by the swiftness by which Ceregene recruited for Cere-120. Was it that patients were just desperate for something good to come of trials, and that Phase I had such a positive outcome? Was it the way in which the PIs recruited patients by having an open around-the-conference-table Q-A presentation of the trial to the prospective patients before Informed Consent was presented? I don't have the answers to these questions, but the questions continue to bug me to this day.

Cere-120 was recruited within a VERY short time. I remember it being an unheard of time-frame. Which does then indicate that the placebo effect will be big part of patient participation. I want to see the end result of Dr. Kim's interviews with Cere-120 participants. We were all interviewed, including the non-participating patients who had considered the trial, after surgery and again after the un-blinding. [Scott Kim, MD, PhD is an assistant professor in the Department of Psychiatry and a core faculty member of the Bioethics Program and an investigator at the Center for Behavioral and Decision Sciences in Medicine at the University of Michigan (http://www.med.umich.edu/bioethics/people/kim.html). The interviews were done by a staffer at Univ of Rochester.]

At one point I presented my PI with the Declaration that we had been developing. He said it was a good idea, and in somewhat of an appalled tone, said the he had always treated his trial patients as "part of the trial team." I know this was a sincere comment, but being on the other side of that table, as a trial participant, I never truly saw this as fact.

As to the argument about placebo. Well, I see myself as a major player in the Placebo-Effect. I sincerely and without a doubt see that I suffered the placebo effect from June 2007 until January 2009. And I still have the questions: Why is no one closely studying patients who obviously have had a placebo effect? Isn't it the patient who had the placebo effect that are important in the argument?

Dr. Robert Hauser, Univ of South Florida, is working with a trail regarding sub-groups (may not be the correct terminology). But I see this as a small and almost an unimportant trial...to researchers that is. Is research taking sub-grouping of patients seriously?

Carolyn

participant in five trials

[SherylJ]

[QUOTE=paula_w;476440]
Debi,
I understand your post to be saying that it is possible to have constructive relations between industry and patients, something I have believed for some time. When we don't have any way to talk to them, we have to second guess and have focused mostly on our own needs. Understanding their needs is just as important, but prior to just recently, we may as well have been monkeys."

I, too, believe there can be constructive relations between industry and patients, but only with a change in attitude by both sides. Much like a marriage, this relationship must be respectful, aware and attentive to the needs of all stakeholders, and constantly nurtured. So, how do we get to this point from where we are now?

MJFF and the other national PD orgs must serve as "marriage counselors," bringing patients and industry together for frank discussions. This is probably the most important thing they can do. No matter how many dollars are raised for research, there will be no trials unless patients feel they are a valued member of the team and willingly participate.

sheryl

[jeanb]

So much to reply too...

It is very true that talking to PWPs who have never been involved in a trail about trials is like talking to a brick wall...they look at the one suggesting the idea with that "you want me to do what!" look. Then comes the it is too far away to travel. It is hard to find a patients, and the family, who will participate in a trial of any kind.


Agree with Carolyn - we have a huge population of pwp who won't consider joining a trial for any reason. And it doesn't matter where they are in the disease - early - middle - late - the answer is and has been no thanks. (early in the disease it's easier to participate than when advanced - that's a given - but this population has steadfastly refused to participate at any stage).

So let's focus on those who DO want to be part of the process:


1. Disease related
The problem is motivation; and "movement" initiation; asking people who have damaged dopaminergic systems to do things we can no longer do without incredible effort. To be overwhelmed by the details of any project. Wanting to be in a trial and even making the decision to do so is the easy part; following through is the hard part. Often it's those pesky executive functions. Multi-tasking; concentration; making decisions and following through. Other times it's not being able to walk. It's movement initiation of any kind that has been damaged by dopamine depletion; motor and non motor.


So how can we help the pwp who are motivated and want to participate in the system? As Carey states, we increasingly have executive-disfunction and motor disfunction. We need science and industry to work with us when they are designing the trials to make it easier for those pwp who are motivated and interested to actually become partners in the process.

P.S My father, who has Alzheimer's, has participated in several clinical trials. They ALWAYS gave my folks rides to and from the study center. It was part of the contract, and a necessary part of the process. Frankly, not having transportation to and from a study center is a major barrier to many pwp. I know my day is coming - now I drive 100 miles round trip on freeways to see my MDS & Study Doctor. And the staff accommodate me by scheduling my appointments between 10:30 and 1:30 (avoiding the worst of the traffic) but I won't always be able to make that drive.

[indigogo]

Jean - I think the issue of motivation and movement is key to making everything better in our lives - from joining clinical trials, to exercising!

It's so hard to overcome - and so difficult to communicate to others!

[paula_w]

We would all agree, I think, with Debi about how hard; complicated biology is. We are suffering from so much biological misfiring. I think we need to have some real hard conversations with all the stakeholders. [not a new idea!] Lack of trust comes from lack of communication - in fact it is deliberate withholding in some cases and we know it's due in part to competition and also to obligations to stockholders. But how is that considered to be fair? When did this become fair play?

Now my "gut feeling", "instincts" "inner voice" is flashing a warning light about possible waste of time and money on ESCR, that could be spent on adult cells now that they seem to be able to do the same thing with them. Can someone please explain how far ahead they are in one or the other? Do they both have the same uses now? SCNT is illegal. Women dont' want to donate their eggs. They mentioned in one of the recent advances that skin cells can now be made into neurons. What is the difference between the two? I would very much appreciate that. Maybe someone could make my light stop flashing, even tho I won't see either one on the market.

I would be glad to promote a clinical trial that I was thoroughly familiar with and could easily explain on this forum in lay language, including the risks vs the benefits. i think this is possible and have said it a few thousand times. Honesty is the way to go....always. Trust will follow. Energy and motivation are even harder to non-existent - if you don't know what to believe - what the facts are, why this must be, etc. - in other words, we must know the rationale for the design. We are pretty with it considering the condition of our brains and psyche. But to be in a clinical trial takes a ton of energy and motivation. And it just can't be shrugged off when you do it for nothing [surgery]

Industry and medical community do need to know the illness much better than they do. Just switching a med is hard work and can cause us to lose something that may not come back. We feel much more and much worse than what you see.

oh forgot to address carolyn - i may be having feelings of grandeur carolyn but i kinda thought the Bartus interview was for us [and other inquiring patients]....no?

paula

[olsen]

I am wondering why the idea to recruit members on this forum for the biomarker study has not been commented upon? Jaye, I visited the web sites whose links you posted, and neither has this clinical trial listed. I really am interested in participating, as is my husband. Is this idea so far fetched? Just listing the centers participating would be enough....or could someone with the knowledge of where this info is available provide a link?.madelyn

[paula_w]

madelyn, i'm lost please help lol. what biomarker study do you mean so i can follow the thread...long day lol

paula

[Debi Brooks]

Regarding the mysterious biomarker study: planning is underway for a progressive marker study (sponsored by MJFF with industry partners hopefully sharing half the costs--its a big, expensive trial)...the trial hasn't been launched--probably not recruiting patients until early 2010...recruiting will be targeted to folks who can reliably get to the study sites and the sites have not yet been selected so can tell what part of the country will be sensible...more to come down the road and believe me we are counting on the community being of great help. The study population will be de novo patients, meaning recently diagnosed and not yet medicated. So, many pwp in this forum wouldn't likely be eligible but you will likely be connected to such candidates through various networks so everyone can be a resource.

Regarding the motive behind the interview with Dr. Bartus of Ceregene was done purely and simply because we knew there was great interest and hope tagged to the outcomes of the trial and that patients would have lots of questions. As a partial funder of both the phase I and II trials, we had worked with Ceregene and among other things suggested that it would be critical to share as much as possible as quickly as possible (this was our assessment having observed the responses following the Amgen-sponsored GDNF trial fail to meet its end points. So, no angle except transparency and urgency in the face of disappointment. By the way, I'm not suprised folks don't trust each other...don't know if that can be eliminated but, again, we are doing everything we can. Our view/goal is to be a pragmatic as possible.

Regarding the scientific robustness of various stem cell sources, I commented on this not too long ago in neurotalk. (Sorry, I don't know how to search for it--but I think in the thread that talked about Katie Hood's recent Huffington Post). Additionally, I believe we might have some additional information on our site in the coming days in the form of a Q & A on the heels of the Obama executive order. (Sorry, I don't know exactly is being worked on for that piece so may or may not get into those particular issues).

Debi

[olsen]

Thank you, Debi , for your response. I would be a willing "control" subject for this study, even though my husband would not qualify. Madelyn

[SherylJ]

[QUOTE=paula_w;476697] Women dont' want to donate their eggs.

Of the estimated 40,000 embryos left over from in vitro fertilization and languishing in cryogenic limbo, there must be more than a few women who would turn these loose for medical research.

I won't argue when human life begins, because that is a no-win situation. Surely though we can all agree that human life ends when tossed out with medical waste. Maybe no one has presented the issue in this basic a way before.

To those who disagree, I'd like to understand why it is ok to create so many excess embryos if your intent is to throw them in the garbage once you get the children you want, rather than see them used in potentially life-saving research. If there is a logical answer to this, I sincerely would like to know it. I'm not looking for a religious debate.

Respectfully,
sheryl

[paula_w]

I should have elaborated on the women. i'm talking about a harvard study that called for women to donate their eggs, It was a very respectable study and one of the researchers spoke wiith us on a pAN call, emphasizing the need for SCNT to create cells in a lab, give them illnesses and run molecules thru for potential treatment. here's the article that puts out the call.

http://www.bioedonline.org/news/news.cfm?art=2576

As i recall, and i'll go back and look, he got no volunteers at all. But i will confirm or change this.

Religion isn't the only reason people question ESCR. If they can do the same thing with skin, well it's available in abundance. It sounds like it would be cheaper and faster. This is about time, and sorry to say, once again, lack of trust. Without a gestalt of some kind to see where we are, I am just shooting in the dark with my thoughts...second guessing is not acceptable to one who is advanced. Thus i am asking the experts, who are invited to join us or speak thru Debi - and then i will have a truer picture. I'm sorry to say that i don't trust the close mix of business and medicine and with good reason. Are there people out there who could make a nice living on ESCR, keep renewing their grants, and produce nada. This I get from the media and from experience.

i'm picking debi's whole brain, she is letting us release our thoughts with objectivity and without judgement, and we are at a point where this is exactly what we need.....it's probably even good for us chemically.

i'll check for the article that says no one volunteered.

paula

found it:
http://www.boston.com/yourlife/health/diseases/articles/2007/06/07/reluctance_of_egg_donors_stymies_harvard_efforts/




[quote=paula_w;476697] Women dont' want to donate their eggs.

Of the estimated 40,000 embryos left over from in vitro fertilization and languishing in cryogenic limbo, there must be more than a few women who would turn these loose for medical research.

I won't argue when human life begins, because that is a no-win situation. Surely though we can all agree that human life ends when tossed out with medical waste. Maybe no one has presented the issue in this basic a way before.

To those who disagree, I'd like to understand why it is ok to create so many excess embryos if your intent is to throw them in the garbage once you get the children you want, rather than see them used in potentially life-saving research. If there is a logical answer to this, I sincerely would like to know it. I'm not looking for a religious debate.

Respectfully,
sheryl

[olsen]

Hi Paula, I am behind on the science info on adult cells , though when researching this a couple of yrs ago, remembered that they do not reliably divide and multiply--that their utility was in perhaps delivering genes to cells, but not in regeneration. Reprogramming was formerly done with 4 viruses and some of the viral DNA remained within the newly created cell, to be injected into the target area--newest way of reprogramming reported to be "electroportation" in which genes are inserted via pores, changes the cell to pluripotent, and then these genes are removed prior to inserting them without leaving behind the fragments of viral DNA
http://www.guardian.co.uk/science/2009/mar/01/stem-cells-breakthrough

The former studies done with reprogrammed adult stem cells resulted in fusion of the adult cell with cells of organs--not regeneration.

It has been repeated by scientists that ESCs will first be successful in Type 1 diabetes--that the neurodegenerative diseases are more difficult to treat. My simplistic understaning is if one is interested in regeneration, ESCs are needed; if insertion of genes into a cell, adult stem cells would work just fine..Thus BOTH sources of stem cells will be necessary.

[paula_w]

Thanks Madelyn! I have not heard it explained in those terms before.
We may not see a cure, but the whole thing is so interesting ......

paula

[bandido1]

[QUOTE=Debi Brooks;476735] The study population will be de novo patients, meaning recently diagnosed and not yet medicated. So, many pwp in this forum wouldn't likely be eligible but you will likely be connected to such candidates through various networks so everyone can be a resource.

Debi Can you elaborate on this quote? It seems to me "not yet medicated" would signficantly reduce the patient recruitment process not to mention the liability potential to referring physicianhs who have avoided an RX after a PD DX. Bob C

The study population will be de novo patients, meaning recently diagnosed and not yet medicated. So, many pwp in this forum wouldn't likely be eligible but you will likely be connected to such candidates through various networks so everyone can be a resource.

[SherylJ]

Sorry Paula, I turned down a different fork in the road of ESCR than you were discussing. I tried very hard not to be judgmental, but to seek facts that would help me understand the other side of the issue.

As it turned out, the link you provided illustrated the point that research of any kind can be set up to fail by virtue of the parameters. In this case, women in MA were receiving $5,000 to donate eggs for reproduction, and nothing to donate those same eggs for research. It doesn't surprise me that the donated eggs are going to fertility clinics.

"...thousands of women give eggs to fertility clinics every year in the United States, for fees averaging about $5,000 per person. But a 2005 Massachusetts law makes payment illegal when eggs are used for research purposes.

"We think that is why people aren't participating, particularly when they know they can do exactly the same thing for another woman's reproduction, which is an equally lofty pursuit, and be compensated well," Eggan said.

Prohibiting payment is meant to insulate scientists from charges that they are coercing women into controversial research.

But other ethicists see the law as unnecessary. When paying women for egg donation, "There does not seem to be any compelling reason for making a distinction between reproduction and research," said Bonnie Steinbock, a bioethicist at the University at Albany, State University of New York.

I have no idea which kind of stem cell research is most promising, but I do know that we must be able to put our trust in the scientific advisory boards, etc. who use their knowledge and experience to make funding decisions. Until we build this trust, we are back where this thread started... too few patients willing to participate in clinical trials.

sheryl

[lindylanka]

Am interested to know how 'de novo' works when recruiting for a PD trial, when PD is often diagnosed by response to sinemet, when many people complaining of PD symptoms spend time with a dx of 'possible' or 'probable' PD, sometimes stretching for months or even years, under the observation of their neuro - and even well experienced neuros sometimes have difficulties with dx. And then there is the issue of 'atypical' etc ....... If the symptoms are mild enough for the doctor to recommend a delay in drug intervention then maybe trial participation is not so appropriate for the truly de novo possible pwps? I understand the need for trial participants, and why it is better that they should not have had any medical intervention, with almost any other disease this would make total sense; so there are questions there like how many of those de novos actually do have ipd - if they do is this verified by dat? which is also not 100%........... and is this before recruitment or after? It seems that these factors would very much limit those eligible for trials, that there is a fair margin for error even before recruitment..... and that those in the de novo stage with a lesser knowledge of the implications of a pd dx may not have the same motivation to participate..... (for instance,there have been more than a few people on the forums who have described an initial 'denial' stage to their pd journey.)

Lindy


[QUOTE=Debi Brooks;476735] The study population will be de novo patients, meaning recently diagnosed and not yet medicated. So, many pwp in this forum wouldn't likely be eligible but you will likely be connected to such candidates through various networks so everyone can be a resource.

Debi Can you elaborate on this quote? It seems to me "not yet medicated" would signficantly reduce the patient recruitment process not to mention the liability potential to referring physicianhs who have avoided an RX after a PD DX. Bob C

[reverett123]

Am I the only one who feels that participating in a study that has no chance of preserving my existence due to time frames, subject matter, or similar restrictions is a losing proposition? And that the hallowed scientific method reduces my life to an academic exercise. There is an old joke in business describing a ham and eggs breakfast- the chicken took part but the pig was committed.

I think it has value to fill in the gaps in our knowledge as much as we can. But if you want people to take part in trials, go to them and say "This cured a rat and a monkey with no ill effects that we could find. You want to try it?" No controls. No sham surgery. Just a bunch of desperate people taking an educated risk with all the cards on the table. Bring Whitton's EX-4 trial within driving range and I'll sign up if I'm not a control. Why? Because it might cure me! Self interest is a very powerful recruiting tool.

Now, if you'll excuse me, I'll go back to the grumpy corner and leave nice people alone.:)

[Debi Brooks]

Without getting too far out in front of this (the trial is in the planning stages and its design is not final)...

Different trials have different objectives...this particular one is looking to identify and validate biomarkers of disease progression. It is not an interventional trial testing some particular therapeutic.

So, basically, you want to learn as much as you can about the natural history of the disease and see if there are biological features that correlate with the clinical features of the disease. In an ideal world, if we could identify people at risk for the disease (pre-diagnosis) we would follow large groups of them and collect all sorts of data. Well, we can't identify large groups of at-risk people (at least not yet but that's another goal). And, we can't afford the cost to follow them for long periods of time. So, is there an alternative strategy that can inform us and is cost-effective? Experts generally agree that the greatest rate of change in clinical features (and hopefully biological ones too--that's what were trying to capture) is taking place at the time when a patient goes from asymptomatic to symptomatic so, that's the window we are after.

So, the best we can do today is find people right at diagnosis and start to follow them for several years...it is still common for patients not to go on medication immediately but it is recognized that they will need to at some point. To the extent such a group of people can be followed in large enough numbers, they could provide extraordinary insights. The expectation, again for the purpose of this study, would be to recruit such newly diagnosed pwp and collect clinical, biological, and imaging data (some of which will be before meds and much after) as well as evaluate some of the emerging biomarker candidates using these biological samples, once collected.

My hope and expectation is that we will have much more to say on this anticipated study in the coming months. Please realize that I know that by sharing some of our intentions (in the discussion/ examples of challenges for patient recruitment into trials) I am generating further questions on a new tact. I am limited, however, it what I can share as I pointed out before that the study is still in the planning stages. We are working diligently to finalize the design and funding commitments for the trial and look forward to sharing more soon.

Debi

[jeanb]

After the precept/cep1347 trial ended, they started a new trial - postcept - to follow 500 of the original 800 trial participants.

When we entered the precept trial, one of the conditions was that we be "de novo." And the decision to follow us after the trial ended was made because scientists considered us a large 'control group' of pwp which they'd never had before. We've each had 3 SPECT scans, and I think maybe are on schedule for a 4th SPECT scan at Yale.

As a trial looking for biomarkers for PD-- which ran with postcept, my husband participated in PROBE. They'll compare him to me. (My husband consented to give many vials of blood for research -{around 7, I think...})

"PROBE will test three biomarkers in PD subjects and controls to determine their feasibility and potential utility as markers of risk and prognosis for PD. This is a case control study, in which PD subjects will be compared to neurologically healthy controls and disease controls (MSA and PSP). The blood biomarker samples will be drawn once to evaluate blood alpha-synuclein levels as well as collection of lymphocyte mass for array analysis. Olfaction will be measured using the UPSIT for all subjects. The UPSIT will be conducted as part of PostCEPT for PD subjects and will only be repeated in this study for PD subjects in not done within 6 months. Control subjects may also choose to submit a blood specimen for processing and storage at the Coriell Institute for Medical Research, a research resource supported by the NINDS Human Genetics Resource Center.

Follow-up of the PD population over a 3-year period will allow us to evaluate the prognosis for important motor aspects of PD that will occur frequently in this cohort. These complications of PD include motor complications, postural instability, and non-motor impairment such as cognitive decline."
(from clinicaltrials.gov - permission to post from this government site)

[LindaH]

Thanks Debi!
Debi wrote:
“My hope and expectation is that we will have much more to say on this anticipated study in the coming months. Please realize that I know that by sharing some of our intentions (in the discussion/ examples of challenges for patient recruitment into trials) I am generating further questions on a new tact. I am limited, however, it what I can share as I pointed out before that the study is still in the planning stages. We are working diligently to finalize the design and funding commitments for the trial and look forward to sharing more soon.”

This thread has been a remarkable example of the type of communication that should be taking place during the planning stages of every clinical trial. If sponsors are having recruitment problems – why don’t more of them talk to patients? Browsing back through this thread they would have learned about issues such as, lack of trust in pharma (just open a newspaper any day), need for communication and education, concerns about placebo controls and sham surgery, difficulty with transportation to trial centers, feelings of being used by academics, difficulty recruiiting early stage PWP, etc.

And most importantly as paula wrote – they need to better understand what PD does to people
“paula wrote “Industry and medical community do need to know the illness much better than they do. Just switching a med is hard work and can cause us to lose something that may not come back. We feel much more and much worse than what you see.”

Debi, we encourage you to share this information with those planning the study, and we look forward to getting more information about the study from you. Maybe it will help solve some potential recruitment problems before they begin.

What would be even better would be for all new studies to include some patients in the planning stages from the very beginning. We are only asking to be a part of the process that hopefully will bring us all to a cure --- soon.
linda

[olsen]

Rick, am curious--what is "whitton's Ex 4 trial? I must have missed reading something important. madelyn

[reverett123]

Madelyn-
It is a fast-moving trial that Tom Isaac's group is funding and is the most hopeful thing I have seen. Here is an earlier thread
http://neurotalk.psychcentral.com/showthread.php?t=57670&highlight=exendin


Rick, am curious--what is "whitton's Ex 4 trial? I must have missed reading something important. madelyn