Thoughts on ALSFRS-r scores

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EricInLA

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PALS
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I am participating in a research study (through EverythingALS) where they do the ALSFRS survey every week and tell you your score. This has me thinking about this scoring model and I'm curious on opinions as to whether this thing is really useful, and how to tell, for instance, whether my handwriting has progressed from a '3' to a '2'. It's definitely become more challenging to write, as is keyboarding. I need a bigger pen, and my ability to write doesn't last long. And yet, in the beginning at least, with my gorilla grip, all the words are still legible, so I guess I'm still at 3 for that category? It's so strange knowing I'm progressing but staying on the same score. For dressing and hygiene, I'm self-sufficient except for cuff buttons and the very top button, so if I avoid dress shirts, I still get a 3!?! I guess this points out the silliness of the self-scoring nature of this thing. I think I'm obsessing on this in part because my still-high score gives me hope that I remain a slow progressor, even though certain things - like holding a glass of water and putting in my contact lenses - are undeniably becoming more challenging.
 
I am getting to hate the frs more and more. Not only for the reasons you mention though it is certainly true that when you are slow progressing you can have a lot of changes without anything showing up

even more I hate that it is the primary clinical endpoint that the fda accepts for trials. We need better and that is why I keep harping on study participation so we have better biomarkers for trials and for diagnosis

I haven’t found the roads scale much better even though it is longer. It probably works better in later stages or with respiratory involvement. I also have to guess at a couple. Can I blow out a candle? I don’t know -last time was precovid on my birthday- I don’t have candles at home
 
When our PALS was first diagnosed, and I became aware of the frs, I was astonished that such a seemingly unsophisticated, subjective and blunt tool had such profile in ALS management.
 
I like the measures but also see limitations. I regularly do ALSFRS and ALSFRS-R and track monthly noticeable changes on a spreadsheet. Between them all, I can kind of project and plan ahead. Every type of equipment (wheelchair, lift, etc.) were obtained prior to needing them. The value is the month-to-month look and being consistent and honest with how we answer. No need to sugar coat progression. We are not competing for the best score, rather the right score to make future plans.
 
Hi Eric. always good to hear from you, and I agree it is very frustrating. I, too, have a very slow progression to this point, and Nikki is so right on when she says we can have changes that aren’t captured on the scale. For my own evaluation and in conversations with my neurologist, I use a half point for the questions.

For example, I get slightly more fatigued on our brisk morning walks and other extended activities than my previous “normal,” but not to the point of shortness of breath. To me that’s at most a 1/2 point decline. Also, because my shoulders and upper chest have some atrophy, if I quickly pull on a sweatshirt with both arms fully overhead, my right collarbone sometimes gets out of place for lack of a better description. It causes intense pain that I can usually alleviate by rotating my arm in different directions until the ligaments and tendons realign. As a result I keep my right arm slightly lower when pulling something on or taking it off. Does that mean I have difficulty dressing? No, not at all, but it isn’t normal.

For what you are doing with the survey, I doubt there is the ability to score a 1/2 point. Truly an outdated and ludicrous basis for assessing progression, especially for critical drug trials.
 
I have to speak up for the ALS-FRS scale.

When I was first diagnosed I kept track of mine monthly, starting at 46, and I felt very satisfied when there was no decline. Fast forward 4 years, and I'm at 22. There are some things I can still do and others not at all.

All the items on the scale won't decline at the same rate for everyone. Someone may die from ALS complications but still be able to swallow and eat normally. Someone else may be doing mostly ok but be unable to write or dress themselves.

But for a large group, over time, it will correlate with decline. Key being a large enough group for statistical relevance. It may be that sometimes ALS-FRS results are used to justify a conclusion when there is an insufficiently large group, but that does not mean it can't be helpful with a larger population.
 
That’s a very good point, Bill, and I certainly don’t disagree with it being used as a broad based tool that does correlate with declining function, whether we use it for self evaluation or as part of our reporting with our neurologist or clinic. For those purposes, I think it’s fine to assign a 1/2 point for minor decline. On this issue my neurologist agrees.

My main concern, and that of many others in the ALS community is the use of the FRS as a primary measurement tool in clinical trials, or the study that Eric described. A good example is the case of Phil G., who was in the NurOwn EAP for a year after the Ph. 3 trial ended. His progression halted and he regained some fine and gross motor skills, incredibly important to him but not to the point of changing his FRS score. I trust Phil’s assessment of his gain in function (he even posted a video showing him performing activities he could not do prior to the EAP treatments), but the FRS data did not capture that.

Bottom line is we desperately need biomarkers, which could differentiate between a possible plateau and temporary improvement of function that some pALS exhibit apart from any trial therapy. From my reading of the recent NurOwn peer reviewed data analysis, it showed a strong potential to do so, at least for the hypothesized markers tested. The many contributing authors of the analysis were some of the most prominent ALS specialists in the world, including Dr. Cudkowicz, so I definitely think this treatment should not have been written off as a failure. Their analysis of the data is worth the read.
 
Your point is also good, Kevin. It's hard to measure trial results without some standard of measurement, which requires a large enough group and a long enough time to be meaningful. Even with a new measurement tool it would take a lot of time and patients (no pun intended) to validate the results.

I don't understand the reference to "being written off as a failure". Did someone say that about this trial? I get that, given there's a limited pool of researchers and money, someone has to decide whether to pursue a given treatment or not, but that doesn't mean the work was a failure. I can believe that someone said the treatment was a failure, or something like that, but it sounds a little over-heated to me. ;)
 
Bill, when NurOwn Phase 3 data failed to mean its primary and secondary endpoints, there were several articles, one in ALS News Today, that put the “failed” label on it. As a result, the company did not seek approval from the FDA and the drug is still in limbo, though they have teamed with another company to potentially ramp up production.

Once the data was parsed into subgroups the data was much more compelling, and thus there is still life (pun intended) for the therapy yet.
 
I think we all know that the plural of anecdote is not data but I think the case of Nurown and probably even more that of the sod1 Valor trial for tofersen illustrate that the frs is not the great primary endpoint and we need better. Certainly there are anecdotes aplenty to support hope for these interventions but there were also postive biomarker signals. The problem is that when a primary endpoint isn’t reached it is a much heavier lift at the FDA I believe Brainstorm is talking to the FDA about what is next. I know biogen is for tofersen

a really good biomarker would speed things greatly. I was in a pet mri imaging study that was looking at inflammation. I was told it looks promising and if they can validate it it could be used for an endpoint for drugs targeting inflammation and it could tell whether a drug was hitting target in about 3 months with far fewer participants. If it doesn’t then they would be able to turn resources elsewhere We need more things like that
 
Yes, yes, and again yes, Nikki.
 
I have no idea what my ALSFRS score is. When I saw it several years ago, I was shocked at how low it was. I can't speak other than one or two word responses, and trying to talk is exhausting and makes me short of breath. Yet, my standard response when asked if I am short of breath is, "I don't know. I can't go fast enough to find out." I can do 20 modified squats without breathing hard. I use an oximeter to check my oxygen level morning and night. At night it is 96% most of the time, but in the morning may be as low as 93% when I check it while still laying down and before moving much.

I can't blow out a candle, but this seems to be more of a facial muscle problem than a breathing difficulty. I can eat and swallow normally but have to have someone cut my food and must be careful to avoid too big of bites.

It seems that in my case, the FRS is contradictory. In my opinion, we need something more accurate.
 
My view is that the FRS is just a tool in the toolbox. For some functions, it is perfectly adequate. For other functions, it is a blunt instrument. We need to make sure it is fit for purpose. The problem is less with FRS than it is that our toolbox is largely empty -- we need other metrics and biomarkers, as others have pointed out.
 
My FRS score is remaining steady at 35, but my overall abilities are weakening. Hands are weaker along with knees. Somethings are just not measured by FRS.
 
I feel like just like MrEDS - my score is holding steady at somewhere between 43 and 45, but my abilities are definitely weakening. Hand and arm are weaker, and there's nothing in my score that captures the pain in my left leg and my favoring of my right leg when standing around.

Interesting points re biomarkers. That's one of those concepts that I look up every time I see it because it seems important, and then I think I comprehend it, but that comprehension dissipates 10 minutes later. Kind of like the prompt return of Homer Simpson's 5 o'clock shadow after he shaves :LOL:. But I think what y'all are saying is that we need precise measures of what characteristics in certain folks make them likely to respond better to a particular drug. And since we don't have much of that data, the industry is using the ALSFRS scale as a poor substitute. Maybe the new ACT for ALS law will help in some way.
 
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