[pegleg]

Since the Hoehn & Yahr Scale is often used as part of the protocol to "screen" patients for participation in clinical trials, I thought you might like to see it.
http://www.parkinson.org/Page.aspx?pid=367
(from the NPF site)

Also, keep scrolling down when you access the above link to see the lengthy and often subjective UPDRS (United Parkinson's Disease Rating Scale.

In another thread, we were discussing the validity of these evaluation tools. I would like to see or hear your comments. I think we should be making more demands of statiscians and other research professionals since we've not had a really big therapy (not counting DBS) for over 40 years.
Peg

[Conductor71]

Originally Posted by pegleg

Since the Hoehn & Yahr Scale is often used as part of the protocol to "screen" patients for participation in clinical trials, I thought you might like to see it.
http://www.parkinson.org/Page.aspx?pid=367
(from the NPF site)

Also, keep scrolling down when you access the above link to see the lengthy and often subjective UPDRS (United Parkinson's Disease Rating Scale.

In another thread, we were discussing the validity of these evaluation tools. I would like to see or hear your comments. I think we should be making more demands of statiscians and other research professionals since we've not had a really big therapy (not counting DBS) for over 40 years.
Peg

Peg,

I was one of those discussers expressing surprise and concern over the validity of our 'scientific' trials. Of course, I have more to say on the matter

We let neurosurgeons delicately manipulate and play in our brains delivering what promises to be a progressive treatment or breakthrough in treatment, yet we measure the results with a paper and pencil test based on observation at a given moment in time? Do raters learn to cut us some slack in rating, credit us +1, when the stress of examination makes our tremor worse, or do they rate us a -1 when a placebo effect is in play? Does this not seem entirely incongruous and almost at odds? It's as if they are saying, we hope to deliver the state of the art research and treatment to you, but we don't know how else to measure the results other than through watching you and figuring out where you fit on a scale from 0-4. While the new UPDRS (revised fairly recently) incorporates H&Y scale and more importantly now includes non-motor symptoms, it serves to highlight how woefully outmoded our treatment is.

**See this good article on the recent revision of the scale and its history, reliability, etc. through the Movement Disorder Society - I can't link to this since it invokes a PDF file, but Google in this:
"http://www.movementdisorders.org/UserFiles/MDS_UPDRS.pdf" and link from there.

I don't want to discredit the training and experience of neurologists; they receive specific guidance in how to rate us using this scale and it is accepted as a standard measurement tool. Since it is used to both stage us in disease onset and progression by practitioners who treat us it makes sense to use it as a measurement tool in clinical trials where the primary goal is to only improve masking of our symptoms. This is key though - the problem is that they are mired in thinking only in terms of symptomatic control. If the scale is good enough to track our symptom control at visits, then it is good enough, period. Is it? Never mind the problems in diagnosing (25 % error rate) or the huge issue that the placebo effect is creating in our trials. Instead, the widespread dependence on the UPDRS only serves to highlight how better measure needs to be developed for us over all from initial diagnosis to progression (think SPECT technology or biochemical tests of some sort) and management. At this point, it seems unrealistic to have the measurement tools in clinical trials surpass the diagnostic, everyday tools, limited as they are, used by clinicians, right? Does this make sense? We need to push for newer, better tools over all before we can expect them to be used as a standard in clinical trials.

In the end, the rating scale is extremely limiting to us as patients - imagine using a paper/pencil tool based on observation in staging and treating cancer?!?! Insane! Yet we are subjected to being misdiagnosed, mistreated, misled, you get the idea because those that have the power to make change happen do not see the need; compared to other diseases and disorders, we're small potatoes- much more money to be made elsewhere. Remember, PD is a life sentence- the current approach is to merely manage it, never mind how uncomfortable or miserable we are, it is not life threatening, nor is time of the essence (says who?) like it is in diagnosing and treating cancer. It sucks really when compared to that- it's like they're telling us- "it's progressive, you can live with it, and we can't stop it..." so "why bother" developing better tools for all of you who should just suck it up and get on with living? It's worked for 20 some years, so it's good enough. The problem is that it isn't good enough- not only should we be thinking of advocacy at the clinical trial stage; we should be vocal in our need for better scientific measures from diagnosis on. Only when we have a reliable way of measuring dopa levels through tomography will we have much more accurate diagnosis, staging, and both reliable and valid trials that do may actually get past the placebo problem. Is it any wonder our new drug trials go nowhere? They are centered on cash cows in offering no more than another teat. I expect this of the pop a pill for the rest of your life pharma, but I expect so much more of newer treatments like neurotrophic delivery - where do our more prominent representatives (think MJFF and Intel) stand on this?

[pegleg]

I appreciate the info on changing the UPDRS. I knew a group had worked on it, but had forgotten what was changed.

The UPDRS is still left with ambiguous questions which are too subjective. Here's an excerpt from the article mentioned by conductor1:

The Unified Parkinson’s Disease Rating Scale (UPDRS)
was originally developed in the 1980s1 and has
become the most widely used clinical rating scale for
Parkinson’s disease (PD).2 In 2001, the Movement Disorder
Society (MDS) sponsored a critique of the UPDRS,
and this document lauded the strengths of the scale but
identified a number of ambiguities, weaknesses, and areas
in need of inclusion to reflect current scientific developments.
3 *The summary conclusions recommended
the development of a new version of the UPDRS that
would retain the core four-part structure of the original
scale, but resolve identified problems and especially incorporate
a number of clinically pertinent PD-related
problems poorly captured in the original version.

* * * *
* The summary conclusions recommended
the development of a new version of the UPDRS that
would retain the core four-part structure of the original
scale, but resolve identified problems and especially incorporate
a number of clinically pertinent PD-related
problems poorly captured in the original version

source: http://www.movementdisorders.org/Use.../MDS_UPDRS.pdf

So why hasn't Parkinson's advanced more? I am certain it is the ambiguity of working with the weak research evaluation tools used to measure results and the lack of definitive diagnostic tools.

As patients (and for many potential trial participants), we should be fighting for better evaluation tools for Parkinson's research. Likewise, we should be strongly supportive of companies or groups who endorse or are working on better ways to both diagnose PD and obtain baseline information. One such area would be diagnostic imaging (examples would be scanning the brain.) The most often-used assessment tool is the MRI (magnetic reasonance imaging), which is basically done to rule out other disorders (e.g. muliple sclerosis, brain tumor, etc.) And with the recent association of cancer with CT scans, I'm sure this diagnostic tool will soon be questioned as to whether benefits outweight the risks.

If anyone reading this knows of some promising work being done in these areas, please share with us through this thread.
Thanks
Peggy

[Ronhutton]

Hi Peg,
Mounting my Blood-brain barrier (BBB) horse again, the BBB permeabilty can be measured in a non invasive technique on living patients.
I would like to see the permeabilities of groups of PWP measured, with a spectrum from just diagnosed to 20 or more years with the disease.
Have a control number of healthy people as standards. If you can show a broard straight line graph of permeability (P) against number of years with PD, then you can simply measure the permeability at regular intervals to see if the PWP is following the average progression or a faster or slower progression. Then there would be all sorts of correlation tests you could do, study the effect on permeability of new treatments, assign a H & Y figure to a permeability, See if there is a threshold value of P, above which the symptoms of PD are evident. You could see whether a non PWP is getting close to the threshold level.
I can't imagine it would be an expensive project, but we will have to win the lottery to do it ourselves!!
Ron

[indigogo]

I wanted to be sure before I wrote anything, so I emailed Debi Brooks at MJFF with the following question:

Debi - wondering if the PPMI (the MJFF biomarkers study)would address some of the concerns voiced in this Neurotalk thread, Evaluation Tools in Clinical Trials - would the establishment of known biomarkers take some of the subjectivity out of PD station and progression?

Debi replied: "Yes, the PPMI study will collect clinical and biological samples from patients and controls with the express goal of validating markers (or more likely a set of markers) that correlate with disease progression…some lead biomarkers (that have been discovered through MJFF biomarker initiatives over the past 7 years) will be tested to see if they verify in the larger population. Not only would verified markers help with diagnosis but most critically we seek tools for clinical trial sponsors…this is in complete recognition of the fact that we don’t have objective clinical end points for trials…UPDRS (despite its shortcomings) is all we have and is tolerated since it can be adequate/useful for trials symptomatic treatments but there is a broad appreciation for the fact that testing disease modifying therapies is essentially a non-starter without validated, objective markers of progression.

Hence the real need and real excitement in the research community about taking this on through PPMI. Feel free to share if you’d like and I can weigh-in if questions arise. "

Hope this is useful for this conversation!

[Conductor71]

Originally Posted by Ronhutton

Hi Peg,
Mounting my Blood-brain barrier (BBB) horse again, the BBB permeabilty can be measured in a non invasive technique on living patients.
I would like to see the permeabilities of groups of PWP measured, with a spectrum from just diagnosed to 20 or more years with the disease.
Have a control number of healthy people as standards. If you can show a broard straight line graph of permeability (P) against number of years with PD, then you can simply measure the permeability at regular intervals to see if the PWP is following the average progression or a faster or slower progression. Then there would be all sorts of correlation tests you could do, study the effect on permeability of new treatments, assign a H & Y figure to a permeability, See if there is a threshold value of P, above which the symptoms of PD are evident. You could see whether a non PWP is getting close to the threshold level.
I can't imagine it would be an expensive project, but we will have to win the lottery to do it ourselves!!
Ron

Ron,

It is good to know that there are other more objective, scientific methods to pursue. My knowledge and reading is limited, so I get hung up on developing SPECT technology. I like the idea of the spectrum approach- sounds expensive but I'm sure someone could get a grant for it!

Laura

[pegleg]

You guys have some very interesting suggestions! It's just that right now I am operating on about 2 of a 4-cylinder engine (most people WITHOUT PD would feel the same). I popped an extra Sinemet to get home from a church Christmas party - so now I'm up all night. But I will "sleep" on this. Please keep the scholarly stuff coming.
g-nite
Peg