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. 2025 Nov;14(4):369-381.
doi: 10.1177/18796397251358375. Epub 2025 Jul 22.

Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease

Jennifer Petrillo  1 , Ruta Sawant  1 , Rebecca Rogers  2 , Sophie Cleanthous  2 , Stefan Cano  2 , Rajeev Kumar  3 , Jennifer Klapper  4 , Luis A Sierra  5 , Jee Bang  6 , Karen Elta Anderson  7 , Deborah A Hall  8 , Susan Perlman  9 , Henry Moore  10 , Danny Bega  11 , Jason Johannesen  1 , Emma Elliott  2
Affiliations

Reliability and validity of the Huntington's Disease Everyday Functioning (Hi-DEF): A patient-reported measure of cognitive capacity on daily functioning in Huntington's disease

Jennifer Petrillo et al. J Huntingtons Dis. 2025 Nov.

Abstract

BackgroundThe Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a novel patient-reported outcome (PRO) scale developed to assess the impact of cognitive impairment on daily functioning in early HD patients.ObjectiveTo examine the psychometric properties, including reliability and validity, of the Hi-DEF. Findings from psychometric analyses using classical test theory (CTT) approach are presented here.MethodsA non-interventional validation study was conducted across nine HD Centers of Excellence across the US.ResultsPatients with HD (n = 151) were recruited: 59% were female, mean (SD) age was 47 (12) years, and mean (range) Total Functional Capacity (TFC) score was 11.4 (8-13). Excellent internal consistency reliability was observed for the Hi-DEF scale total score (Cronbach's alpha: 0.98) and across subscales (alpha range 0.87-0.96). Most targeting and scaling assumptions were met, although there were ceiling effects for three subscales. Construct validity was demonstrated by moderate to high Spearman's rank-order correlations with TFC scores (range r = -0.38 to -0.62) and known and validated measures such as the HD-PRO-TRIADTM (range r = 0.75-0.90), and ability to discriminate between levels of functional impairment (TFC 13, 12-11, and 10-8; p < 0.001). Correlations with Cambridge Neuropsychological Test Automated Battery (CANTAB) cognitive performance measures were low to moderate and ranged from 0.06 to 0.38.ConclusionsThe Hi-DEF is a reliable and valid PRO scale measuring the impact of cognitive impairment on daily functioning, assessing facets of cognitive functioning in context of activities of daily living impacted in early stages of HD.

Keywords: Huntington's disease; activities of daily living; executive function; psychometrics; reliability; validity.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RS is an employee of Sage Therapeutics and may have stock and/or stock options. JP and JJ were employees of Sage Therapeutics at the time the study was conducted and may have stock.RR, SC, and SC are employees of Modus Outcomes, a division of THREAD, which received payment from Sage Therapeutics to conduct this research. EE was an employee of Modus Outcomes at the time this study was conducted.Medical writing support was provided by Modus Outcomes, a division of THREAD (funded by Sage Therapeutics, Inc.). Medical writing and logistical support were provided by Boston Strategic Partners, Inc. (funded by Sage Therapeutics, Inc.).KEA has served as a consultant for Teva, AskBio, Roche, Biogen, Neurocrine, Sage Pharmaceuticals and Novartis. She has served as a scientific advisor for Neurocrine, Medscape, atheneum, GLG and CHDI. She is also an Editorial Board member of this journal but was not involved in the peer-review process nor had access to any information regarding its peer review. DB is on the speaker's bureau for Teva Pharmaceuticals (Teva), Neurocrine Biosciences, Supernus Pharmaceuticals, Acorda Therapeutics, Abbvie and Kyowa Kirin, and has served as a consultant for Teva, Deerfield Institute, Alexion Pharmaceuticals, Orphalan, Medscape and GLG. He has received grants from the Huntington Disease Society of America and the Parkinson Foundation. HM has served on the advisory board for Ipsen Pharma, served as a consultant for Abbvie Neuroscience, and received grants from MODUS Outcomes, Teva, Sage, Bukwang Pharmaceutical, Neurocrine Biosciences, CHDI Foundation, American Parkinson's Disease Association and Huntington's Disease Society of America. DH has served as an editor for AAN, Elsevier - Parkinsonism and Related Disorders, and Annals of Neurology. She has received research grants from CHDI, Neurocrine, Uniqure and Sage. LS and JK have nothing to disclose. JB serves on the scientific advisory board for Wave Life Sciences. RK has served as a consultant for Supernus, Abbvie, Teva, Annexon, Roche, Acorda Therapeutics, and Cerevel Therapeutics. He has served as a scientific advisor for Impel Pharma. He is on the speaker's bureau for Teva, Supernus, Acorda Therapeutics and Kyowa Kirin. He has served as an officer or member of the board of directors Research Catalyst, LLC (and holds stock) and CenExel RMCR. He has received research grants from Supernus, Sage, Prilenia Therapeutics, Roche, Triplet Therapeutics, CHDI Foundation, Neurocrine Biosciences, Biovie, Neuroderm, Sanofi, Addex Pharma, Integrative Research Laboratories, Takeda, Neuraly, Abbvie, Cerevel Therapeutics,Transposon Therapeutics, Lundbeck, Biohaven, Revance Therapeutics, Impax Laboratories, Pharma Two B, Enterin, CND Life Sciences, Neuron23, Annexon Biosciences, Annovis, PTC Therapeutics, Uniqure, Alexza, SparkNeuro, Praxis, Scion Neurostim, Cognition Therapeutics and Eli Lilly.

Figures

Figure 1.
Figure 1.
Convergent validity results: Correlations between Hi-DEF and HD PRO TRIAD and CANTAB tests.
Figure 2.
Figure 2.
Known-groups validity results: Hi-DEF total score and subscales by TFC score groups. Leftmost bars for each scale/subscale represent the group of patients with a TFC score of 13. Middle bars represent patients with a TFC score of 12–11; rightmost bars represent patients with a TFC score of 10–8.
See this image and copyright information in PMC

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