[Nan Cyclist]

At the World Parkinson's Congress we're going to be asked what particular areas of research we think are important to pursue. Our answers will be given to young researchers who are seeking grants from the Parkinson's Disease Foundation. Here is your opportunity to speak up, because I will enter every single request that appears on this board. Please don't be shy. What research question is most important to you?

These questions will be given to young researchers who are encouraged to submit their proposals to the Parkinson's Disease Foundation. Several proposals will be selected and funded by PDF.

[Tupelo3]

Originally Posted by Nan Cyclist

At the World Parkinson's Congress we're going to be asked what particular areas of research we think are important to pursue. Our answers will be given to young researchers who are seeking grants from the Parkinson's Disease Foundation. Here is your opportunity to speak up, because I will enter every single request that appears on this board. Please don't be shy. What research question is most important to .

Nan, thanks so much for this opportunity to give some input to future research. I can probably come up with a dozen suggestions in just a few minutes. However, I trust that you'll receive many suggestions from members of this site as well as other PWP from your extensive network.

My main issue involves research on disease altering drugs, whether it be slowing progression or potentially curative. I believe it is important to begin adding early stage patients to some of the trials. I think it is very possible that some of the unsuccessful drug trials have failed because the patients samples were too advanced with the disease. It just seems logical if a drug were to slow PD progression, we would be more likely to see these results with people who still have the most functioning brain cells. I don't even see the early stage animal studies defining subsets of disease stages when testing for progression altering drugs.

Thank you for taking our input and thanks for everything you do for our cause.

Gary

[Nan Cyclist]

Gary, thanks for your input. Please add your other 11 suggestions as it may be that we will see patterns emerge around interest in research topics.

Do I understand your question correctly that you would like to see participants in clinical trials for disease altering drugs categorized according to their level of involvement with the disease. Your hypothesis is that people who are early on in the disease may very well react differently to drugs than those who are further along. By conflating the participants as they do now in most studies, they are not able to accurately discern how a potential treatment works on a particular segment of the population. Do I have that right? If not, please clarify.

[Tupelo3]

Originally Posted by Nan Cyclist

Gary, thanks for your input. Please add your other 11 suggestions as it may be that we will see patterns emerge around interest in research topics.

Do I understand your question correctly that you would like to see participants in clinical trials for disease altering drugs categorized according to their level of involvement with the disease. .... Do I have that right? If not, please clarify.

Perfect!

I'll send you some more suggestions tomorrow (it's getting late on the East coast...).

[soccertese]

Originally Posted by Tupelo3

Nan, thanks so much for this opportunity to give some input to future research. I can probably come up with a dozen suggestions in just a few minutes. However, I trust that you'll receive many suggestions from members of this site as well as other PWP from your extensive network.

My main issue involves research on disease altering drugs, whether it be slowing progression or potentially curative. I believe it is important to begin adding early stage patients to some of the trials. I think it is very possible that some of the unsuccessful drug trials have failed because the patients samples were too advanced with the disease. It just seems logical if a drug were to slow PD progression, we would be more likely to see these results with people who still have the most functioning brain cells. I don't even see the early stage animal studies defining subsets of disease stages when testing for progression altering drugs.

Thank you for taking our input and thanks for everything you do for our cause.

Gary

tupelo3,
i think 1 problem with including less advanced pd'ers is that the placebo affect is so great in pd that you need major symptoms to see a statistically significant affect. that's why biomarker research is so important, to cut thru the placebo affect. especially for measuring neuroprotection. so far as far as i can tell, a whole lot of azilect is being prescribed on the hope that it may be neuroprotective and until biomarkers for measuring pd progression before you can detect it visually are found and easily measured, neuroprotection research might just be a major crapshoot? just food for thought.

but thanks for coming up with some research ideas!
what i'd like to see is more money going towards pd research, this U.S. congress is terrible and i see funding as the biggest problem. so lets hope the new MJF sitcom is a big hit!!

[indigogo]

I think that trials have failed because we don't have a handle on who really has PD or even what PD is. I think science needs to clear up the mystery. Identifying biomarkers is a good start. Coming up with a way to objectively diagnose is another.

How can we cure/modify it if we don't know exactly what it is?

[girija]

Originally Posted by Nan Cyclist

At the World Parkinson's Congress we're going to be asked what particular areas of research we think are important to pursue. Our answers will be given to young researchers who are seeking grants from the Parkinson's Disease Foundation. Here is your opportunity to speak up, because I will enter every single request that appears on this board. Please don't be shy. What research question is most important to you?

These questions will be given to young researchers who are encouraged to submit their proposals to the Parkinson's Disease Foundation. Several proposals will be selected and funded by PDF.

Thanks for your post and it is a great opportunity to voice our ideas.

In the last couple of years, several promising therapeutics that worked well in open label Phase 1 trials "failed" or proved no better than placebo in phase 2 studies. I find it hard to believe a treatment that worked well in phase 1 is no longer good in phase 2. My question is it the treatment that failed or is it the design and analysis of clinical trial?

IMHO, it is time to invest time and money to resolve this issue before another promising treatment (eg GDNF gene therapy) is buried.

Here are a few ideas:
Clinical trial design and analyses need to be modified to take placebo effect into account while determining the efficacy of a treatment.
If placebo effect is due to the production of dopamine in our brains, it makes sense to take advantage of that feature rather than perceiving it as a problem.

I suggest that research projects to understand the biology of placebo effects, as well as new statistical and mathematical models that include placebo effect as a positive feature, are to be developed to analyze data.

Increase the # of parameters to be studied as each PWP is different. Programs that can analyze as many parameters as end points (motor, non motor, quality of life issues and electronic and video monitoring (self, care partner or physician-assisted) of trial participants in their homes on a regular basis and more emphasis on patient kept records rather than UPDRS scores recorded in a clinic.

more long term longitudinal studies and including PWP in early stages of PD in clinical trials.

PD is such a complex disease, there is no shortage for research ideas! We can come up with plenty of good hypotheses to be tested.

I will be at WPC too. Hope to meet you in Montreal.

[johnt]

Forgive me if I adopt a wide definition of research.

First, as I see it, there should be a balance between blue skies research, which may pay off in 20 years time, and practical research, which may pay off today, and everything in between. My bias, is very much to the short end.

1. Registration of all cases of PD.
(This would make epidemiological analysis much easier.)

2. Open access to all data sets.
(As above. It would allow more people to study the data, increasing the chance that something would be found.)

3. Open access to all medical journals.
(This would make the dissemination of knowledge faster.)

4. Categorization of PD subtypes.
(This would reduce the chance of clinical trials failing.)

5. Symptom measurement - common hardware platform.
(This would make measurement easier and more accurate.)

6. Symptom measurement - correlation with biomarkers.
(This would allow the tracking of progression to work from both ends.)

7. Determination of the symptoms which have the most impact on PwP.
(This would allow resources to be used more effectively.)

8. Measurement of the placebo effect.
(This confounds the data but, otherwise, it is our friend.)

9. Find ways to gain benefit from the placebo effect.
(I call this placebo distillation.)

10. Explore methods to make personal clinical trials easier.
(PwP need to know what works for them.)

11. Investigation in how to build citizen science ethics committees.
(If patients are going to run clinical trials, these are necessary.)

12. Investigation in how to get more out of our present drugs.
(Timing schedules; co-drugs, e.g. grapefruit juice; delivery mechanisms, e.g. nasal delivery.)

13. The ethics of drug regulation.
(Regulation reduces the chance that a harmful drug will go into the market, but raises costs and delays the entry of new drugs.)

14. Investigate the implications of moving from a clinical trial based on showing efficacy, to a clinical trial based on doing no harm.
(This would save time and money but at a cost of mistakes being more likely.)

15. The delivery of a "kitchen sink" method to measure levodopa content of foods.
(This would allow fava bean breeding.)

John

[Tupelo3]

Originally Posted by soccertese

tupelo3,
i think 1 problem with including less advanced pd'ers is that the placebo affect is so great in pd that you need major symptoms to see a statistically significant affect. that's why biomarker research is so important, to cut thru the placebo affect. especially for measuring neuroprotection.

Soccertese, I certainly agree that placebo effect is a problem in many of these studies. However, this is really an issue of design and analysis. Rather than foregoing important research, we should focus on moving forward with proper trial designs to account for miscellaneous variables, including placebo. I would rather try to do that than continue on the path of wasting funds on trials that are designed to fail (e.g. testing neuroprotective drugs only on later stage patients). Placebo control is fairly simple with pill based drugs, but gets more complicated with injectables and is clearly quite difficult with surgical interventions. One source of control is to have longer longitudinal trials where any placebo effect may wane over time when compared with the control group.

However, the best way to control for the problem is to put funds into developing more objective measures of PD, as indigogo stated. We need to move beyond the UPDRS as the standard measuring instrument as its subjective and raises all of the problems of trying to use a questionnaire to account for all of the varieties of PD symptoms which were likely caused by multiple factors. The development of DatScan was a great start to an objective analysis, but there has been little in the way of improvements over all these years (keeping in mind that although only recently approved for use in the US, DatScan was developed in the 90's and first approved in Europe in 2000). If we can get a better view of what's happening in the brain, the placebo issue will go away.

With regard to biomarkers, there already is a great ongoing, longitudinal study - PPMI. The problem, once again, is we are getting all of this historical personal information, as well as a variety of other physiological data from the subjects. What we aren't getting is any real objective data regarding their individual disease.

[Tupelo3]

Originally Posted by girija

Thanks for your post and it is a great opportunity to voice our ideas.

In the last couple of years, several promising therapeutics that worked well in open label Phase 1 trials "failed" or proved no better than placebo in phase 2 studies. I find it hard to believe a treatment that worked well in phase 1 is no longer good in phase 2. My question is it the treatment that failed or is it the design and analysis of clinical trial?

IMHO, it is time to invest time and money to resolve this issue before another promising treatment (eg GDNF gene therapy) is buried.

Here are a few ideas:
Clinical trial design and analyses need to be modified to take placebo effect into account while determining the efficacy of a treatment.
If placebo effect is due to the production of dopamine in our brains, it makes sense to take advantage of that feature rather than perceiving it as a problem.

I suggest that research projects to understand the biology of placebo effects, as well as new statistical and mathematical models that include placebo effect as a positive feature, are to be developed to analyze data.

Increase the # of parameters to be studied as each PWP is different. Programs that can analyze as many parameters as end points (motor, non motor, quality of life issues and electronic and video monitoring (self, care partner or physician-assisted) of trial participants in their homes on a regular basis and more emphasis on patient kept records rather than UPDRS scores recorded in a clinic.

more long term longitudinal studies and including PWP in early stages of PD in clinical trials.

.

I couldn't possibly agree more with all of your points!. Well said!

Gary