Improved ALS clinical trials through frequent at-home self-assessment: a proof of concept study

Abstract

Objective: To determine the potential for improving amyotrophic lateral sclerosis (ALS) clinical trials by having patients or caregivers perform frequent self-assessments at home.

Methods and participants: We enrolled ALS patients into a nonblinded, longitudinal 9-month study in which patients and caregivers obtained daily data using several different instruments, including a slow-vital capacity device, a hand grip dynamometer, an electrical impedance myography-based fitness device, an activity tracker, a speech app, and the ALS functional rating scale-revised. Questions as to acceptability were asked at two time points.

Results: A total of 113 individuals enrolled, with 61 (43 men, 18 women, mean age 60.1 ± 9.9 years) collecting a minimum of 7 days data and being included in the analysis. Daily measurements resulted in more accurate assessments of the slope of progression of the disease, resulting in smaller sample size estimates for a hypothetical clinical trial. For example, by performing daily slow-vital capacity measurements, calculated sample size was reduced to 182 subjects/study arm from 882/arm for monthly measurements. Similarly, performing the ALS functional rating scale weekly rather than monthly led to a calculated sample size of 73/arm as compared to 274/arm. Participants generally found the procedures acceptable and, for many, improved their sense of control of their disease.

Interpretation: Frequent at-home measurements using standard tools holds the prospect of tracking progression and reducing sample size requirements for clinical trials in ALS while also being acceptable to the patients. Future studies in this and other neurological disorders should consider adopting this approach to data collection.

Conflict of interest statement

Dr. Rutkove holds equity in Myolex, Inc, (the company that produces the Skulpt® Scanner), has served on the board of directors, has received consulting income from the company, and is named as an inventor on patents owned or licensed to Myolex, Inc.

© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.

Figures

Figure 1

CONSORT diagram showing recruitment and attrition information.

Figure 2

Examples of how frequency of sampling impacts the uncertainty in the slope approximation for individual patients over the first 3 months of the study. Data are provided for the individual ALS patient who had the most data collected for that measure, so as to most clearly show the impact of down‐sampling on the confidence intervals. The line represents the least‐squares regression. As frequency decreases, the uncertainty in the slope of the line (gray regions) expand markedly for all measures. N refers to the number of measurements included in the calculation. Note that ALSFRS‐R data were collected on a weekly rather than a daily basis.

Figure 3

Examples of increasing sample sizes estimations as frequency of measures decreases (A) Left handgrip strength (B) SVC (C) EIM left biceps (D) ALSFRS‐R. Note: ALSFRS‐R data were only acquired weekly rather than daily.

Figure 4

PREMS data. The questions were as follows: (A) Overall, the online training provided the information I needed to conduct the self‐assessments (B) Since the start of the study or the time point of last survey, how easy or difficult was it to conduct self‐assessments with the equipment provided for this research study? (C) How confident were you in conducting self‐assessments with the equipment provided? (D) How easy or difficult was it to enter the data into the study portal? (E) How often did you have sadness, anxiety, regret, or feeling upset about the results of my data? (F) How often did you have thoughts on how the measurement results were affecting work or family life (G) Taking my measurements has made me more in control of my disease (H) Taking my own measurements has made it easier (or harder) to cope with my disease (I) Approximate time taken for measurements on Day 8 and Day 92.