Google Research

A Machine-Learning Based Objective Measure for ALS disease progression

npj Digital Medicine (2022)


Amyotrophic Lateral Sclerosis (ALS) disease progression is usually measured using the subjective, questionnaire-based revised ALS Functional Rating Scale (ALSFRS-R). A purely objective measure for tracking disease progression would be a powerful tool for evaluating real-world drug effectiveness, efficacy in clinical trials, as well as identifying participants for cohort studies. Here we develop a machine learning based objective measure for ALS disease progression, based on voice samples and accelerometer measurements. The ALS Therapy Development Institute (ALS-TDI) collected a unique dataset of voice and accelerometer samples from consented individuals - 584 people living with ALS over four years. Participants carried out prescribed speaking and limb-based tasks. 542 participants contributed 5814 voice recordings, and 350 contributed 13009 accelerometer samples, while simultaneously measuring ALSFRS-R. Using the data from 475 participants, we trained machine learning (ML) models, correlating voice with bulbar-related FRS scores and accelerometer with limb related scores. On the test set (n=109 participants) the voice models achieved an AUC of 0.86 (95% CI, 0.847-0.884) , whereas the accelerometer models achieved a median AUC of 0.73 . We used the models and self-reported ALSFRS-R scores to evaluate the real-world effects of edaravone, a drug recently approved for use in ALS, on 54 test participants. In the test cohort, the digital data input into the ML models produced objective measures of progression rates over the duration of the study that were consistent with self-reported scores. This demonstrates the value of these tools for assessing both disease progression and potentially drug effects. In this instance, outcomes from edaravone treatment, both self-reported and digital-ML, resulted in highly variable outcomes from person to person.

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