Table 3 Strengths and limitations of ALSFRS-R and other qualitative scale measures that assess functional disability
From: Qualitative measures that assess functional disability and quality of life in ALS
Tool | Description | Strengths | Limitations | Recommendations for best use in a clinical trial |
|---|---|---|---|---|
ALSFRS-R [7] | 12-item self-reported function scale of bulbar, fine motor, gross motor, respiratory domains | Patient centered Fast, easy administration (clinician, self or proxy, in person or via telephone) Cost efficient Long history of reliability and validity Validated as a predictor of survival Frequently used Supported by EMA and FDA Translated into many languages with cultural adaptations | Little information on its development and patients Not responsive to progression of disease if non-linear Multidimensional; total score may not be meaningful if not stratified on type of ALS onset Floor and ceiling effects, unable to capture early or late-stage clinical changes Use of ordinal raw scores, 1-point changes can represent a small or large loss of functional ability depending on the domain Lack of discrimination between response categories can lead to response variability | If used as primary outcome, FDA and EMA require supplemental objective primary outcome of function Supplement with a newer function measure (e.g., ROADS) Consider domain subscores with total score Use Rasch or GRM methodology to account for non-linearity of ALS progression; stratify on tyle of onset Supplement with function or symptom specific measure to discriminate more severe and less severe patients Stratify on predictors of functional decline |
ALSFRS-EX [36] | Addition of 3 items to the 12-item ALSFRS-R (2 motor, 1 bulbar) | Based on an already validated measure New items based on PRO guidelines Sensitive to change in low-functioning patients | Limited validity data | Could be substituted for the ALSFRS-R for improved sensitivity in patients with advanced ALS, on assisted technology and lower levels of functioning |
ALS-MITOS [37] | Based on domains of the ALSFRS-R. Focuses on the rate of loss of each function within each domain | Based on already validated measure Considers lost functions within each domain Sensitive to smaller treatment effect Stages correlate with generic QoL (SF-36) and health service costs | Limited use data Further investigation of transitions through stages required to further assess the utility of this proposed staging system | Supplement to the ALSFRS-R, particularly when additional measures of QOL or health care costs are not feasible |
CNS-BFS [45] | A 21-item self-administered scale across bulbar functioning—speech, swallowing, salivation | Swallowing and salivation items appear more sensitive to treatment effect than in the ALSFRS-R Developed using FDA PRO guidelines | Bulbar specific – would need other measures to assess treatment impact on other functions | Supplement to the ALSFRS-R as a more sensitive measure of bulbar dysfunction Use as primary or key secondary outcome measure if treatment is aimed at reducing bulbar decline |
DALS-15 [47] | Self-reported 15 item Rasch modeled scale to assess dyspnea in ALS | Follows FDA PRO guidelines Satisfies Rasch model with good fit Optimal targeting Unidimensional, meaningful overall score | Dyspnea specific—needs other measures to assess treatment impact on other functions Limited validity data | Use to identify ALS patients with dyspnea Aid in the early assessment and monitoring of dyspnea for symptom management as an outcome measure supplementary to the ALSFRS-R respiratory domain |
MND-DS [49] | Self-reported 3 item measure of dyspnea in MND patients including ALS | Follows FDA PRO guidelines Better diagnostic performance for capturing reduced respiratory function than the ALSFRS-R respiratory domain | Limited validity data. No longitudinal validity data Supine vital capacity used to assess respiratory functioning instead of the gold standard (trans-diaphragmatic pressure) Assessments across MND centers not standardized | Consider use as secondary outcome or as a supplement to the ALSFRS-R respiratory domain if treatment is aimed at reducing respiratory decline Use to monitor respiratory functioning remotely, between site visits, between pulmonary function testing during a clinical trial or in patients unable to travel Use to identify/screen patients with reduced respiratory functioning |
ROADS [20] | Self-reported 28-item Rasch modeled ALS disability scale | Follows FDA PRO guidelines Satisfies Rasch model with good fit Linearly weighted Unidimensional, meaningful total score Targets broad range of disability levels May be more sensitive to smaller changes in functioning | New measure with limited validity data Longitudinal validity currently not available but is being assessed in ongoing clinical trial(s) No translations or cultural adaptations available | Potential replacement for the ALSFRS-R Supplement to the ALSFRS-R until longitudinal validity data is available |