Is the EDSS the best scale to measure progression?

Is it time to bin the EDSS in its current form? #MSBlog #MSResearch

"It is always nice to someone looking at data from a different perspective; i.e. without blinkers. What this data trawl shows that the EDSS is not all it is cracked-up to be when measuring disability progression. The EDSS is heavily weighted to three functional systems; pyramidal or motor, cerebellar or coordination, and the sensory system. The other four systems (vision, brainstem, sphincters and mental) don't contribute very much to our assessment of disability progression. We have known for a long time now that the EDSS is a very poor scale. When you judge it using various psychometric tests it fails miserably as an outcome measure; it is non-linear, it has ceiling and floor effects, has a high inter and intra-rater variability, is an impairment scale low down and a disability scale high-up. is dominated by walking and is not very responsive. My biggest gripe is that it requires someone to examine you and if you are mobile to walk you for up to 500m. It should take 20-30 minutes to do a EDSS score properly. Very few neurologists do the EDSS properly in routine clinical practice, which is why I am sceptical about the reliability of data collected outside of clinical trials. 

  1. Non-linear: this means that a change from 1.0 to 2.0 is not the equal to a change from 4.0 to 5.0. In fact MSers move from 3.0 to 5.0 very quickly and this creates the double hump with one group of MSers clustered low down and a second clustered higher up from 6.0-7.0. Statisticians prefer working with linear scales.
  2. Ceiling and floor effects; in other words the EDSS is not very good low down or high-up the scale. Simply put the scale moves very slowly at the extremes and does not capture biological change.
  3. High inter-rater variability: when two raters examine the same MSers they get different scores.
  4. High intra-rater variability: when the same rater examines the same MSer on different days they get different scores.
  5. Impairment scale: at low EDSS scores the MSer is unaware of problem; a neurologist has to examine you to detect subtle problems with your nervous system. 
  6. Disability scale: this is when neurological impairment is affecting your neurological functioning. 
  7. Dominated by walking: once you hit EDSS 4.0 it become a walking scale up until EDSS 7.0 (wheelchair) when upper limb function starts to be taken into account. Most trials don't allow MSers above 6.5 to participate. Is this fair? It excludes everyone who is already using a wheelchair. 
  8. Responsiveness: the EDSS often does not detect any change (response) when the MSers is fully aware that they have deteriorated or improved. 
I am reassured to see that based on my length-dependent axon theory that the systems that are driving disease progression involve long axons; motor, cerebellar and sensory. More on this theory later. This is what underpins my asynchronous progressive MS hypothesis. What we now need is to use these insights to improve on the EDSS as an outcome measure for progressive MS. I think one of the main reasons we don't have licensed therapies for progressive MS is because of the EDSS. I am hoping the International Progressive MS Alliance will change this."

"The following is the neurostatus that we use in clinical trials to do the EDSS score; it may help you understand the scale more. The summary of the EDSS score is at the end of the document."

Scott et al. Relationship between Sustained Disability Progression and Functional System Scores in Relapsing-Remitting Multiple Sclerosis: Analysis of Placebo Data from Four Randomized Clinical Trials. Neuroepidemiology. 2015;44(1):16-23.

BACKGROUND: The Expanded Disability Status Scale (EDSS), based on different functional system scores (FSS), remains the most frequently used disability assessment in relapsing-remitting multiple sclerosis (RRMS). In this analysis, we evaluated the relationship between sustained disability progression, measured by EDSS, and simultaneous changes in individual FSS domains.

METHODS: A post hoc analysis was performed on data from placebo-treated RRMSers from four large, randomized, multicenter, phase 3 clinical trials. Sustained disability progression was defined as a ≥1.0-point EDSS score increase over a ≥3- or ≥6-month period. Simultaneous sustained disability progression and worsening of individual FSS domains was analyzed.

RESULTS: The majority of MSers experienced sustained disability progression and simultaneous worsening of ≥1 FSS domain, with ≥1-point worsening in the pyramidal domain being most frequently associated with sustained disability progression (in 31-51% of patients), followed by ≥1-point worsening in the cerebellar (35-41% of patients) and sensory (31-45% of patients) domains.

CONCLUSION: The key FSS components correlating with sustained disability progression, measured by EDSS, appear to be pyramidal, cerebellar, and sensory. In this analysis, the simultaneous worsening of consistent FSS domains confirms the validity and reliability of the use of sustained EDSS progression as a measure of disability progression

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