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ALS/MND phenotype

General
#1

Hello everyone,

I am leading a team of ALS/MND patient advocates (plus one clinician) in a “Phenotype Phebruary” type of exercise to create a phenotype for ALS/MND. Hopefully, they will learn a lot about OHDSI along the way so that they can advocate for it! Incidentally, they are totally into it, and I recently heard them discussing common data models with a government official. Also note that I work at Johns Hopkins and co-taught the JHU OHDSI course during February, so I have a good template to follow for the phenotype submission. But all of that experience did not prepare me for this project!

Some background:
In the US, amyotrophic lateral sclerosis is typically differentiated from other forms of MND. In part, this is due to the motor neurons involved (upper vs lower vs both) and, importantly to our patient advocates, the speed of progression (with ALS being more rapidly progressing than some other forms like PLS). However, in other parts of the world, MND is used more broadly and interchangeably with ALS. Further, evidence is growing that ALS is more heterogeneous than once believed.

More information on types of MND is here:

MND is here: Athena

The advocates have the following question:
We feel strongly about having the option of singling out ALS specifically if researchers desire. Should we cast a wide net with MND in the cohort definition? If so, would researchers use that phenotype but then use exclusion criteria to restrict it to ALS-only, if desired? Or should we create separate phenotypes for MND broadly vs. ALS-only?

Thank you for any advice!

Danielle

#2

I think (I think!) @mattspotnitz did some research with ALS, so tagging him along.

1 Like
#3

@DanielleBoyce:

Welcome to the family. Your question: This is exactly what you need to define from your use case or scientific question. Do you want to contrast ALS with MND? Then you need to have criteria which make a sharp distinction. Or do you want to study the effects of treatments? Then it probably doesn’t matter that much, particularly if the treatments are indication-specific. A clinical characterization should state how you want to use the phenotype.

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#4

This sometimes parallels the work we have worked on for Parkinson’s disease:

Still work in progress (and we just setup a new local Atlas instance to characterize phenotypes for PD before we elevate back to OHDSI at large for publishing our phenotypes and collaborating)

Parkinson’s disease, like ALS, is a distinct (though increasingly heterogenous by basic science/precision medicine work) clinical entity of great interest for researchers (interventional trials and quality outcomes research) that is relatively straightforward to recognize once established. Parkinson’s disease is a specific type of “parkinsonism” just as ALS is a form of MND. The challenge in both conditions is that

  1. there is a long subtle early phase where there is debate as to when “PD” is considered prodromal vs early – and when one wants to count it for a given use case (recruitment for early studies vs epidemiology of incidence)
  2. there is a late phase where the neurodegenerative process becomes clearly an atypical Parkinsonism (i.e. atypical MND when early presentation is ALS). In the case of atypical Parkinsonism, there are clear syndromes that are not Parkinson’s disease. Not sure how often this occurs in the MND space.

The way we have approached this is two fold:

  1. there is a clear epidemiological incidence/prevalence assessment indication. This is where the current work with CDC and state PD registries is going - for this we advocate for a broad definition that allows for poorer specificity but higher sensitivity. This is “easier” to do as we don’t need to worry as much for all the criteria to assure specificity, but will require some strategies for determining just what that tradeoff is.
  2. Within the broad registry of #1, we want to establish the cohort of specific probable PD (in between the too early and confounded late types) - maybe like your ALS cohort – presumably for ensuring they are seeing neurologists, assessing quality of care, enrolling in interventional trials. This is where our P8 work has been and are still selecting the various phenotypes to the satisfaction of most OMOP-CDM datasets and tradeoffs.

Happy to chat about how to configure your use cases and clinical characterization as a neurologist who has become very interested in OMOP-CDM tools.

2 Likes
#5

Thank you so much for this response. Yes, what you describe is very similar to ALS. I read your response just as I was hopping on a Zoom with my patient advocates (we call ourselves the Phenomenal Phenotypers of ALS). They were very excited and touched that experts weighed in on their phenotype. I will definitely reach out to you after I read through your documentation again and update our description. Thanks again!
Danielle

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