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 selfassessments 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 myographybased 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 AE 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.

Free-Living Motor Activity Monitoring in Ataxia-Telangiectasia

“…Such tools have the potential to capture more ecologically valid information about the patient’s state and produce measures that better reflect how the disease impacts everyday function. Furthermore, more frequent or continuous sampling could reduce variance of disease assessments and enable more sensitive detection of changes in motor and cognitive behavior[ 4 – 7 ]. Detection of longitudinal, disease-related changes is important in initial diagnosis/determination of disease onset, monitoring for events that may require clinical intervention, and for determining efficacy in interventional trials.…”

Reply to: Frequent self‐assessments in ALS clinical trials: Worthwhile or an unnecessary burden?

“…However, with a smaller sample, a noisy measure with respect to within‐subject variance can also impact between‐subject variance and, consequently, the mean slope as well. Our study 2 clearly shows these effects, where ALSFRS‐R slope standard deviation drops from 0.041 to just 0.018 points/month, with an accompanying increase in the mean slope. Perhaps no measure demonstrates this better than right hand grip dynamometry, on which we had the most data.…”

Frequent self‐assessments in ALS Clinical Trials: worthwhile or an unnecessary burden for patients?

“…With interest I have read the article published by Rutkove and colleagues on frequent at-home self-assessment for clinical trials in amyotrophic lateral sclerosis (ALS). 1 An important consideration is to determine the optimal monitoring frequency (e.g., daily, weekly, or monthly) in order to balance the gain in information with the increase in patient-burden. The authors address this question by performing sample size calculations to detect a 30% reduction in the progression rate for a 9-month randomized clinical trial.…”