Abstract

BackgroundWe aimed to develop a Human Activity Recognition (HAR) model using a wrist-worn device to assess patient activity in relation to negative symptoms of schizophrenia.MethodsData were analyzed in a randomized, three-way cross-over, proof-of-mechanism study (ClinicalTrials.gov: NCT02824055) comparing two doses of RG7203 with placebo, given as adjunct to stable antipsychotic treatment in patients with chronic schizophrenia and moderate levels of negative symptoms. Baseline negative symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptom Scale (BNSS). Patients were given a GeneActiv™ wrist-worn actigraphy device to wear over a 15-week period. For this analysis, actigraphy data and behavioral and clinical assessments obtained during placebo treatment were used. Motivated behavior was evaluated with a computerized effort-choice task. A trained HAR model was used to classify activity and an activity–time ratio was derived. Gesture events and features were inferred from the HAR-detected activities and the acceleration signal.ResultsThirty-three patients were enrolled: mean (±SD) age 36.6 ± 7 years; mean (±SD) baseline PANSS negative symptom factor score 23.0 ± 3.5; and mean (±SD) baseline BNSS total score 36.0 ± 11.5. Activity data were collected for 31 patients with a median monitoring time of 1,859 h per patient, equating to ~11 weeks or 74% monitoring ratio. The trained HAR model demonstrated >95% accuracy in separating ambulatory and stationary activities. A positive correlation was seen between the activity–time ratio and the percent of high-effort choices (Spearman r = 0.58; P = 0.002) in the effort-choice task. Median daily gesture counts correlated negatively with the BNSS total score (Spearman r = −0.44; P = 0.03), specifically with the diminished expression sub-score (Spearman r = −0.42; P = 0.03). Gesture features also correlated negatively with the BNSS total score and diminished expression sub-scores. Activity measures showed similar correlations with PANSS negative symptom factor but did not reach significance.ConclusionOur findings support the use of wrist-worn devices to derive activity and gesture-based digital outcome measures for patients with schizophrenia with negative symptoms in a clinical trial setting.

Highlights

  • Negative symptoms are a key psychopathologic dimension and an important driver of functional disability in schizophrenia with up to 60–70% of patients exhibiting at least one such symptom [1, 2]

  • Known problems with rating scales include challenges in establishing interrater reliability in large multinational studies, reliance on patients’ reports for symptoms that are not directly observable in the interview, and expectation bias. These factors reduce the likelihood of signal detection in clinical trials of novel therapies for schizophrenia, increase the risk and cost of drug development, and diminish the chance of finding a treatment for this debilitating disease [5]

  • 33 patients with negative symptoms of schizophrenia were enrolled at three study centers in the United States

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Summary

Introduction

Negative symptoms are a key psychopathologic dimension and an important driver of functional disability in schizophrenia with up to 60–70% of patients exhibiting at least one such symptom [1, 2]. Known problems with rating scales include challenges in establishing interrater reliability in large multinational studies, reliance on patients’ reports for symptoms that are not directly observable in the interview, and expectation bias. These factors reduce the likelihood of signal detection in clinical trials of novel therapies for schizophrenia, increase the risk and cost of drug development, and diminish the chance of finding a treatment for this debilitating disease [5]. We aimed to develop a Human Activity Recognition (HAR) model using a wrist-worn device to assess patient activity in relation to negative symptoms of schizophrenia

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