A number of drugs that have been successfully tested on animals (with chemically induced PD) have shown disappointing results on humans. And, some PD drug trials have been ended, because the results are not statistically significant, even though some participants have reported considerable benefit.

To add to this, we can all see PwP with different symptoms and different rates of progression.

Taking all this together must raise the possibility that there is more than one type of PD, and following from this the possibility that a therapy that helps one group of PwP might have no benefit for another or, even, make them worse.

This makes things difficult for traditionally run clinical trials: the results of one group being watered down by another, leading to statistical significance being lost and, therefore, a good drug for some being abandoned.

Fortunately, there are other testing techniques which overcome these problems. They focus on the individual, rather than the group.

As the simplest example, you could have a trial with one person. First, to get control figures they would be measured without the drug. They would then take the drug and be measured again. (For PD even this is non-trivial: given the fluctuation of symptoms, to get statistical significance each phase needs to be quite long.) Of course, taken alone it would be dangerous to assume that this result could be generalized to all PwP.

Another technique is to use cross-overs where there are a number of placebo/drug phases. These can be blinded.

As a final example, you can have variable length trials in which a participant stays in the trial until, based on a mixture of their data and that of the group, it becomes unlikely that he or she will benefit. In this form of testing the cohort size is gradually reduced, but people who are showing a good response stay in.

See
"Translational medicine in Parkinson’s Disease: Novel clinical trial designs have been proposed for evaluating novel anti-dyskinetic medications. Strengths and limits of the N-of-1 design."

http://www.pdonlineresearch.org/resp...signs-have-bee

Does anyone know the extent to which this form of clinical trial design is used in PD?

John

doctors could do the clinical trial on individuals, communicating with the head researchers. its' brilliant in its' simplicity.

seems like a few posters here are doing their own "clinical trials" and sharing. isn't that one of the major reasons many eyes are on this board, you don't need this board to keep up to date on clinical trials or pd news.

I'm trying to be good here and not say that we've been saying this for more than a decade. That could be why some try things on their own.

PUBLIC ENGAGEMENT AND CLINICAL TRIALS:
NEW MODELS AND DISRUPTIVE TECHNOLOGIES
June 27-28, 2011
Conduits and Department of Health Evidence and Policy
Mount Sinai School of Medicine, New York, NY



http://www.mssm.edu/static_files/MSS...g%20Agenda.pdf

23andme participating

Interesting reading. I believe that there is far too much emphasis on media engagement, and not enough on patient involvement. The last ten years has seen a constant stream of news about PD that gives the impression that there are new treatments that people will be able to access next week, not next decade. Disheartening for concerned family and friends who need something to hope for, and aggravating for us when we know the score.

Roll on the day when more participatory models of everything appear, from visiting your physician, to trial design. It is getting harder to ignore the world patient voice, now the cat has been let out of the bag.....

Lindy

See the Maths Unlocks ... thread:

http://neurotalk.psychcentral.com/sh...839#post780839

Mathematical analysis shows that there are different groups of PwP.

John

Great reading, John, very interesting....... seems like every day there is something new to consider....

Lindy

Two years later.

We still have people writing that successful mouse/rat trials are not passing human trials.

Perhaps some therapies that do work on rodents do work on humans, perhaps we just haven't noticed!

With rodents, it is common to induce PD using, for example, MPTP. To make it even simpler, the rats often have similar genetics.

http://www.ndineuroscience.com/userf...9;s%20info.pdf

With human trials, things are more complicated. Genetics differ. Environments differ. And, since most of us stay in the same or similar environment as the one that we were in when we got PD in the first place, we are faced with a continuing environmental assault.

In my opinion, looking for one cure for all is a mistake. We need to focus on what works for the individual.

We should consider making trials open ended in the following sense: a person would continue on the trial as long as his/her performance continues to be better than some function of his/her baseline performance.

As an example, we could set the bar as continuing to equal at least 105% of baseline performance at least once in the last 3 days.

A person who derives no benefit from the therapy under investigation would fail to reach the bar and drop out from the trial. The people who are left are either deriving a benefit frim the treatment directly, the placebo effect for them is real, or some confounding effect has taken over.

How would we judge a treatment that at the end of a year had 25% of the cohort left, each of whom were performing at least 5% better than at the start?

John

johnt,
basically statistics try to show that the difference between groups is greater than the natural variability within groups. every open label phase 1 trial does exactly what you are suggesting, there is no control, you are comparing the patient's status at the beginning of the trial against their status at the end. and unfortunately, the placebo affect has proven so large in pd'ers who volunteer for these trials requiring some risk that it caused phase2 trials to be conducted. so it wasn't phase2 trials failing that is frustrating as much as the failure to somehow account for placebo affect in phase1, basically the phase1 trials GAVE A FALSE POSITIVE, researchers ignored the well known placebo affect.

i'm not a researcher but i hope biomarker/gene research will find biomarkers/genetic changes so the a treatment can be measured other than thru observation which unfortunately includes the placebo affect and requires a control. once that is done, you truly can have small/individual trials that will also hopefully be much quicker, you might be able to tell in a few months if there are any significant changes.

just my opinion.

QUOTE=johnt;999817]Two years later.

In my opinion, looking for one cure for all is a mistake. We need to focus on what works for the individual.

John[/QUOTE]

I apologize for repeating something that was posted several years ago (it is hard to go back and reread years of posts prior to posting a new one).

I happen to agree with you 100%. Targeted therapies are likely to be the ultimate solutions in PD, as they appear to be in cancer (where there are now several dozen approved targeted cancer drugs). There was some very interesting research out of Stanford several years ago that reviewed the results of follow-up studies of successful drug trials. At least a one third of the follow-up studies with larger sample sizes showed less positive test results due to the sample dilution.

We need clinical trials with sub-samples that are more homogenous in their genetic traits and environmental factors. This also means we actually will need more total volunteers to get the actual sub-sample groups large enough to reasonably test. As soccertese said, open trials don't work all that well and will not allow for ultimate drug approvals.

It's up to us, the patients, to participate more actively in drug research. We need to get more control of the overall process, instead of just being the guinea pigs (or larger versions of the fruit fly and mouse).

Thanks for all of your ideas.