Improving the measurement properties of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): deriving a valid measurement total for the calculation of change

Abstract

Background

The Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) total score is a widely used measure of functional status in Amyotrophic Lateral Sclerosis/Motor Neuron Disease (ALS), but recent evidence has raised doubts about its validity. The objective was to examine the measurement properties of the ALSFRS-R, aiming to produce valid measurement from all 12 scale items.

Method

Longitudinal ALSFRS-R data were collected between 2013-2020 from 1120 people with ALS recruited from 35 centers, together with other scales in the Trajectories of Outcomes in Neurological Conditions-ALS (TONiC-ALS) study. The ALSFRS-R was analyzed by confirmatory factor analysis (CFA), Rasch Analysis (RA) and Mokken scaling.

Results

No definite factor structure of the ALSFRS-R was confirmed by CFA. RA revealed the raw score total to be invalid even at the ordinal level because of multidimensionality; valid interval level subscale measures could be found for the Bulbar, Fine-Motor and Gross-Motor domains but the Respiratory domain was only valid at an ordinal level. All four domains resolved into a single valid, interval level measure by using a bifactor RA. The smallest detectable difference was 10.4% of the range of the interval scale.

Conclusion

A total ALSFRS-R ordinal raw score can lead to inferential bias in clinical trial results due to its non-linear nature. On the interval level transformation, more than 5 points difference is required before a statistically significant detectable difference can be observed. Transformation to interval level data should be mandatory in clinical trials.

Keywords:

• Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, Trajectories of Outcome in Neurological Conditions-ALS, Rasch
• outcome measurement, disability

Acknowledgments

The authors thank the participants and their families for their invaluable contributions, the research and clinical staff for recruitment, and the TONiC team.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Data access

Data supporting this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Walton Center NHS Trust. Please contact [email protected].

Additional information

Funding

The authors thank Motor Neurone Disease Association UK under Grant: Young/Jan15/929-794, and Neurological Disability Fund 4530 for financial support for participant recruitment, data collection and processing. We thank Biogen Idec for financial support for data analysis. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors also thank the NIHR CLRN for research support. For the purpose of Open Access, the author has applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising.