Measuring Quality of Life in Huntington’s Disease Using a Proxy Approach: Validation of the HD-mQoL-prx Measure
Author(s)
Mariusz T. Grzeda, Msc1, Jeanette Thorpe, BA, MSc2, Ellie Johnstone, BSc2, Isobel Spray, BSc2, Wiebke Hannemann, PhD3, Ferdinando Squitieri, PhD4, Giulia Giancaterino, PhD4, Jiri Klempir, PhD5, Olga Ulmanova, MD5, Pearl van Lonkhuizen, PhD6, Anne Wil Heemskerk, PhD6, Jennifer Hoblyn, PhD7, Emer OMalley, PhD8, Ramona Moldovan, PhD9, Alzbeta Muehlbaeck, PhD10, Stephen Mckenna, PhD11, Georg Bernhard Landwehrmeyer, PhD12.
1Head of quantitative science, Galen Research, Manchester, United Kingdom, 2Galen Research Ltd, Manchester, United Kingdom, 3Department of Neurology University Hospital, Ulm, Germany, Germany, 4Huntington and Rare Diseases Unit, Fondazione IRCCS Casa Sollievo della Sofferenza Research Hospital, San Giovanni Rotondo, Italy., Rome, Italy, 5Department of Neurology and Centre of Clinical Neuroscience, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic., Prague, Czech Republic, 6Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands., Leiden, Netherlands, 7Trinity College Dublin, Ireland, Dublin, Ireland, 8Trinity College Dublin, Ireland., Dublin, Ireland, 9University of Manchester, UK, Manchester, United Kingdom, 10Huntington Center South, Isar-Amper-Klinikum, Taufkirchen, Germany, Taufkirchen, Germany, 11Galen Research, Manchester, United Kingdom, 12Department of Neurology University Hospital Ulm, Germany., Ulm, Germany.
1Head of quantitative science, Galen Research, Manchester, United Kingdom, 2Galen Research Ltd, Manchester, United Kingdom, 3Department of Neurology University Hospital, Ulm, Germany, Germany, 4Huntington and Rare Diseases Unit, Fondazione IRCCS Casa Sollievo della Sofferenza Research Hospital, San Giovanni Rotondo, Italy., Rome, Italy, 5Department of Neurology and Centre of Clinical Neuroscience, General University Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic., Prague, Czech Republic, 6Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands., Leiden, Netherlands, 7Trinity College Dublin, Ireland, Dublin, Ireland, 8Trinity College Dublin, Ireland., Dublin, Ireland, 9University of Manchester, UK, Manchester, United Kingdom, 10Huntington Center South, Isar-Amper-Klinikum, Taufkirchen, Germany, Taufkirchen, Germany, 11Galen Research, Manchester, United Kingdom, 12Department of Neurology University Hospital Ulm, Germany., Ulm, Germany.
OBJECTIVES: Assessing quality of life (QoL) in Huntington’s disease (HD) is challenging due to progressive cognitive decline, which often impairs patients’ ability to self-report. This limits longitudinal QoL monitoring. Proxy-reported measures, completed by caregivers or close family members, offer a valuable alternative by ensuring the patient’s perspective remains represented throughout disease progression. This study presents the development and validation of the HD-mQoL-prx, a proxy-reported version of the HD-mQoL instrument. Rasch Measurement Theory (RMT) and Classical Test Theory (CTT) were used to evaluate the psychometric properties. The study emphasizes the importance of proxy measures in supporting patient-centred care.
METHODS: Caregivers of individuals with HD were recruited across Germany, UK, and Italy to complete a 49-item proxy questionnaire developed in parallel with the patient-reported HD-mQoL. Both instruments were based on the same conceptual model and items were derived from qualitative interviews and refined through translation, lay panel input, and cognitive debriefing. The HD-mQoL-prx was adapted for assessment by carers, ensuring alignment with the patient perspective.
RESULTS: Data from 150 caregivers (Germany: 65; UK: 61; Italy: 24) were analysed in two stages using RMT. Stage 1 involved independent analysis of proxy responses, during which misfitting items were removed through a series of diagnostic tests. This resulted in a refined 23-item scale, including 16 items shared with the patient-reported HD-mQoL. Stage 2 combined data from both patient (HD-mQoL) and proxy (HD-mQoL-prx) questionnaires, analysed on a shared Rasch continuum. Model estimates were anchored by HD-mQoL responses to the common items, confirming measurement equivalence and supporting the development of a crosswalk table for score conversion.
CONCLUSIONS: The HD-mQoL-prx is a psychometrically robust, unidimensional proxy-reported QoL measure for HD. By aligning proxy and patient responses on a shared scale, it enables accurate, continuous, and comparable QoL assessment across disease stages, supporting more informed and patient-centred care.
METHODS: Caregivers of individuals with HD were recruited across Germany, UK, and Italy to complete a 49-item proxy questionnaire developed in parallel with the patient-reported HD-mQoL. Both instruments were based on the same conceptual model and items were derived from qualitative interviews and refined through translation, lay panel input, and cognitive debriefing. The HD-mQoL-prx was adapted for assessment by carers, ensuring alignment with the patient perspective.
RESULTS: Data from 150 caregivers (Germany: 65; UK: 61; Italy: 24) were analysed in two stages using RMT. Stage 1 involved independent analysis of proxy responses, during which misfitting items were removed through a series of diagnostic tests. This resulted in a refined 23-item scale, including 16 items shared with the patient-reported HD-mQoL. Stage 2 combined data from both patient (HD-mQoL) and proxy (HD-mQoL-prx) questionnaires, analysed on a shared Rasch continuum. Model estimates were anchored by HD-mQoL responses to the common items, confirming measurement equivalence and supporting the development of a crosswalk table for score conversion.
CONCLUSIONS: The HD-mQoL-prx is a psychometrically robust, unidimensional proxy-reported QoL measure for HD. By aligning proxy and patient responses on a shared scale, it enables accurate, continuous, and comparable QoL assessment across disease stages, supporting more informed and patient-centred care.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
PCR155
Topic
Health Technology Assessment, Methodological & Statistical Research, Patient-Centered Research
Topic Subcategory
Instrument Development, Validation, & Translation
Disease
Mental Health (including addition), Musculoskeletal Disorders (Arthritis, Bone Disorders, Osteoporosis, Other Musculoskeletal), Neurological Disorders, Rare & Orphan Diseases