Estimating the minimum important difference in the ALSFRS-R-instrument in people living with MND

Abstract

Objective: The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) is a commonly used outcome measure in clinical trials for motor neuron disease (MND) therapies. As such, understanding how differences in scores relate to patient perception of their disease status is important when interpreting ALSFRS-R data. Our study sought to estimate the minimal important difference (MID) for the ALSFRS-R, the smallest difference in scores at which patients perceive a change in their quality of life. Methods: Data were collected as part of a longitudinal, observational saliva management study, ProSec3. These included both the ALSFRS-R and a global rating of change question (GRoC), which asked participants to rate how their disease had progressed since the previous visit. Anchor-based and distribution-based methods have been used to estimate the MID of the ALSFRS-R. The MID was estimated using two methods of calculating the total ALSFRS-R score, the original summation scale method and the recently proposed interval scale method. Results: A total of 145 people with MND had longitudinal ALSFRS-R and GRoC data. Different methods estimated the ALSFRS-R MID to be in the range of 2.02-5.43 for the summation scale and 1.23-3.31 for the interval scale method over a 3-month period, the time between study visits. Using anchor-based methods our MID estimates for the ALSFRS-R are 3.8 points and 2 points, respectively. Conclusions: The results of this study can guide clinicians and researchers in the interpretation of ALSFRS-R data. However, further studies are required to more precisely estimate the ALSFRS-R MID.

Keywords: ALS; ALSFRS-R; MID; MND; Motor neuron disease; amyotrophic lateral sclerosis; functional rating scale; minimal important difference.

Figure 1.

Natural progression of the ALSFRS-R scores across the five study visits. The continuous lines include all data (regardless of the number of visits individual participants completed), the broken lines only include participants who completed 5 study visits (though ALSFRS-R data may not be complete for all visits). Black and blue lines refer to transformed (interval) scores, green and orange lines are based on standard summation of question scores. Mean values are heavily influenced at the different visits by people with slow disease progression as people with fast-progressing MND were less likely to complete later visits. Mean ALSFRS-R score over time split by all data and those with complete cases. Random effects linear regression: monthly rate of decline in ALSFRS-R score estimated as −0.58 (95% CI: −0.69, −0.48) on the summation scale and −0.33 (95% CI: −0.39, −0.27) on the interval scale.

Figure 2.

Estimates for the MID at group level (circles) and individual level (triangles) for the ALSFRS-R summation scale (a) and transformed interval scale (b). The y-axis labels are the same for both graphs.