Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jan 21;20(1):12.
doi: 10.1186/s12955-022-01919-9.

Qualitative measures that assess functional disability and quality of life in ALS

Susan L Hartmaier  1 , Thomas Rhodes  2 , Suzanne F Cook  2 , Courtney Schlusser  2   3 , Chao Chen  4 , Steve Han  4 , Neta Zach  4 , Venkatesha Murthy  4 , Shreya Davé  4
Affiliations
Review

Qualitative measures that assess functional disability and quality of life in ALS

Susan L Hartmaier et al. Health Qual Life Outcomes. .

Abstract

Background: Selection of appropriate trial endpoints and outcome measures is particularly important in rare disease and rapidly progressing disease such as amyotrophic lateral sclerosis (ALS) where the challenges to conducting clinical trials, are substantial: patient and disease heterogeneity, limited understanding of exact disease pathophysiology, and lack of robust and available biomarkers. To address these challenges in ALS, the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised version (ALSFRS-R) was developed and has become a key primary endpoint in ALS clinical trials to assess functional disability and disease progression, often replacing survival as a primary outcome. However, increased understanding of the ALS disease journey and improvements in assistive technology for ALS patients have exposed issues with the ALSFRS-R, including non-linearity, multidimensionality and floor and ceiling effects that could challenge its continued utility as a primary outcome measure in ALS clinical trials. Recently, other qualitative scale measures of functioning disability have been developed to help address these issues. With this in mind, we conducted a literature search aimed at identifying both established and promising new measures for potential use in clinical trials.

Methods: We searched PubMed, Google, Google Scholar, and the reference sections of key studies to identify papers that discussed qualitative measures of functional status for potential use in ALS studies. We also searched clinicaltrials.gov to identify functional status and health-related quality of life (HRQoL) measures that have been used in ALS interventional studies.

Results: In addition to the ALSFRS-R, we identified several newer qualitative scales including ALSFRS-EX, ALS-MITOS, CNS-BFS, DALS-15, MND-DS, and ROADS. Strengths and limitations of each measure were identified and discussed, along with their potential to act as a primary or secondary outcome to assess patient functional status in ALS clinical trials.

Conclusion: This paper serves as a reference guide for researchers deciding which qualitative measures to use as endpoints in their ALS clinical trials to assess functional status. This paper also discusses the importance of including ALS HRQoL and ALS cognitive screens in future clinical trials to assess the value of a new ALS therapy more comprehensively.

Keywords: ALS; ALS cognitive screens; ALSFRS-R; Clinical trials; HRQoL; Qualitative outcome measures.

PubMed Disclaimer

Conflict of interest statement

Takeda Pharmaceuticals contracted with CERobs Consulting, LLC, a consulting firm with focus on real-world evidence, outcomes research, epidemiology and clinical outcome assessments, including patient reported outcomes; S. Hartmaier, T. Rhodes, S. Cook, and C. Schlusser consulted on this project through CERobs Consulting, LLC. C. Chao, S. Han, N Zach, V. Murthy, and S. Dave are/were salaried employees of Takeda Pharmaceuticals at the time the publication was written.

References

    1. Quereshi M, Schoenfeld DA, Paliwal Y, Shui A, Cudkowicz ME. The natural history of ALS is changing: improved survival. Amyotroph Lateral Scler. 2009;10(5–6):324–331. - PubMed
    1. Norris FH, Calanchini PR, Fallat RJ, Panchari S, Jewett B. The administration of guanidine in amyotrophic lateral sclerosis. Neurology. 1974;24(8):721–728. - PubMed
    1. Appel V, Stewart S, Smith G, Appel SH. A rating scale for amyotrophic lateral sclerosis: description and preliminary experience. Ann Neurol. 1987;22(3):328–333. - PubMed
    1. Cedarbaum JM, Stambler N. Performance of the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) in multicenter clinical trials. J Neurol Sci. 1997;152(Suppl 1):S1–9. - PubMed
    1. Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, et al. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III) J Neurol Sci. 1999;169(1–2):13–21. - PubMed