Clinical significance in the change of decline in ALSFRS-R

Abstract

Our objective was to survey ALS clinicians and researchers regarding what percentage reduction in the ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised) slope they would consider clinically meaningful. A nine-question survey was provided to 65 members of the Northeast ALS Consortium (NEALS). They were asked to rate the clinical relevance of 10-50% changes in decline of the ALSFRS-R slope on a seven-point scale (1-7), where 1='not at all clinically meaningful', 4='somewhat clinically meaningful', and 7='very clinically meaningful'. Ninety per cent of participants rated a 20% change in the decline of the ALSFRS-R score as the percentage in which a somewhat clinically significant change starts to be noted (i.e. score of 4 or higher). All participants endorsed a 25% or higher change in the ALSFRS-R score as at least somewhat clinically meaningful (score of 4 or higher). Ninety-three per cent of the participants viewed a 50% change in decline as very clinically meaningful (score of 7). This survey demonstrated that the majority of clinicians and clinical researchers surveyed believe that a therapy that resulted in a change of 20% or greater in the slope of the ALSFRS-R would be clinically meaningful.

Influence of Resistance Training on Neuromuscular Function and Physical Capacity in ALS Patients

“…A previous study has reported ALSFRS-R to decline 0.92 ± 0.08 points per month [23], which is in line with our data (overall decline: 0.83 ± 0.64 points per month). The same study suggests a change of 20% or greater in the slope of the ALSFRS-R to be clinically meaningful [23], indicating that the resistance training in our study had no attenuating effect; rather it might have had a worsening effect. This observation differs from three previous studies, reporting positive effects on ALSFRS-R scores following resistance training using different regimes [9–11].…”

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial

“…No new safety concerns were identified for masitinib, findings being consistent with masitinib's known risk profile (12)(13)(14). Masitinib showed significant benefit in DALSFRS-R over placebo for the study's predefined primary efficacy population, exceeding the clinically meaningful target of slowing ALSFRS-R decline by !20% (27). Exploratory subgroup analyses indicated further improvement is possible when initiating treatment at a less severe stage of disease (e.g.…”

Heterogeneity in ALSFRS-R decline and survival: a population-based study in Italy

“…The efficiency of RCT in terms of time and costs may be improved using only one or few reliable outcome measures [15] and this should be a scale-like ALSFRS-R because of its simplicity, reliability, and ability to predict survival. Nevertheless, knowing what influences ALSFRS-R imposes to enrol patients accordingly, especially in consideration of the fact that a difference of 20 % in the decline of ALSFRS-R in subject treated with a new treatment compared with placebo has resulted to be significant for the majority of caring neurologists [20].…”