Abstract
Objective: To determine the reliability and convergent validity of a novel digital biomarker smartphone application for objective, daily assessment of cognition and motor symptoms in Huntington’s disease (HD).
Background: Objective, more precise, longitudinal tracking of HD signs and symptoms through frequent, ecologically valid, at-home testing promises to augment standard clinical testing methods. Standard methods may fail to capture natural symptom fluctuations and be influenced by inter-rater variability, and the clinical visit itself.
Design/Methods: A smartphone application composed of seven active tests (Symbol Digit Modalities Test, Stroop Word Reading, Speeded Tapping, Chorea, Balance, U-turn, and 2-Minute-Walk) and continuous passive monitoring is deployed in an ongoing, open-label extension study of huntingtin antisense oligonucleotide RG6042 in early manifest HD (ClinicalTrials.gov. NCT03342053). Forty-one of 46 participants were enrolled and available for the reported baseline analysis. Sensor features were extracted from each active test and aggregated over 2-week periods and compared with standard clinical measures at baseline. Intra-class correlation coefficients and Spearman correlations quantified test-retest reliability and convergent validity of novel digital measures compared with equivalent standard in-clinic tests.
Results: Average adherence was high, with 80% of all active tests performed each week in the first 20 weeks. The test-retest reliability of active tests ranged from 0.74–0.97, median 0.95. Digital versions of standard in-clinic tests showed strong correlations ranging from r=0.69 (P <0.001, Stroop Word Reading) to r=0.86 (P <0.001, Speeded Tapping). Active tests showed good correlations with established clinical motor measures, ranging from r=0.34 (P=0.03, U-Turn) to r=0.64 (P <0.001, Chorea, non-dominant hand). Updated results from ongoing data collection will be presented.
Conclusions: The results suggest that frequent remote patient monitoring yields reliable and valid measures of cognition and motor symptoms in HD when compared with standard clinical measures. The digital biomarker smartphone application has potential to improve measurement of disease progression in HD.
Disclosure: Dr. Lipsmeier has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Lipsmeier has received royalty, license fees, or contractual rights payments from F. Hoffmann-La Roche Ltd. Dr. Lipsmeier has received research support from F. Hoffmann-La Roche Ltd. . Dr. Simillion has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd.. Dr. Bamdadian has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Inovigate GmbH, and F.Hoffmann La-Roche. Dr. Smith has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals Inc. Dr. Schobel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Schobel holds stock and/or stock options in F. Hoffmann-La Roche Ltd. Dr. Czech has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann–LaRoche. Dr. Gossens has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman-La Roche, Ltd. Dr. Gossens holds stock and/or stock options in F. Hoffmann-La Roche Ltd. Dr. Weydt has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche and Biogen. Dr. Wild has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann La Roche Ltd., Mitoconix Bio Ltd., and PTC Therapeutics. All payments were made to UCL Consultants, a wholly owned subsidiary of University College London. Dr. Wild has received research support from Yes, a research grant to University College London by F. Hoffmann-La Roche. Dr. Lindemann has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of F. Hoffman-La Roche, Ltd.
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