Investigating health-related quality of life in rare diseases: a case study in utility value determination for patients with CLN2 disease (neuronal ceroid lipofuscinosis type 2)

Orphanet Journal of Rare Diseases

Amanda Mortensen¹  Mohit Jain²  Thomas Butt²  Zlatko Sisic²  Charlotte Camp²  Andrew Olaye²  Eva Wibbeler³  Christoph Schwering³  Angela Schulz³  Annabel Griffiths⁴  Benjamin Ruban-Fell⁴  Wrik Ghosh⁵  Laura Lee⁶  Marina Trivisano⁷  Nicola Specchio⁷  Miriam Nickel⁸  Paul Gissen⁹ 

[1] Batten Disease Family Association, London, UK;BioMarin Europe Ltd, London, UK;Children’s Hospital, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;Costello Medical, Cambridge, UK;Costello Medical, Singapore, Singapore;Department of Metabolic Medicine, Great Ormond Street Hospital, London, UK;Department of Neuroscience, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;NIHR Biomedical Research Centre, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, WC1N 1EH, London, UK;

关键词: CLN2;    Utility values;    Vignettes;    Cerliponase alfa;   

DOI  :  10.1186/s13023-021-01829-x

来源: Springer

【 摘 要 】

BackgroundUtility studies enable preference-based quantification of a disease’s impact on patients’ health-related quality of life (HRQoL). It is often difficult to obtain utility values for rare, neurodegenerative conditions due to cognitive burden of direct elicitation methods, and the limited size of patient/caregiver populations. CLN2 disease (neuronal ceroid lipofuscinosis type 2) is an ultra-rare, progressive condition, for which there are no published utility data fully capturing all disease stages. This case study demonstrates how utility values can be estimated for ultra-rare paediatric diseases by asking clinicians to complete EQ-5D-5L questionnaires based on vignettes describing the stages of CLN2 disease.MethodsAn indirect elicitation method using proxy-reporting by clinical experts was adopted. Eighteen vignettes were developed, describing nine progressive disease stages as defined by motor and language domain scores of the CLN2 Clinical Rating Scale, in individuals treated with cerliponase alfa or standard care. Eight clinical experts with experience of treating CLN2 disease with cerliponase alfa and current standard care completed the proxy version 2 EQ-5D-5L online after reading these vignettes. Resulting scores were converted to EQ-5D-5L utility values for each disease stage, using UK, German and Spanish value sets.ResultsUtility values, which are typically anchored by 0 (equivalent to death) and 1 (full health), decreased with CLN2 disease progression (results spanned the maximum range of the utility scale). Assigned utility values were consistently higher for patients receiving cerliponase alfa than standard care; differences were statistically significant for the 6 most severe disease stages (p < 0.05). Analysis of the individual dimensions of the EQ-5D-5L showed that greatest differences between patients treated with cerliponase alfa and standard care occurred in the pain dimension (differences in mean scores ranged between no difference and 1.8), with notable differences also observed in the anxiety/depression dimension (differences in mean scores ranged between 0.1 and 1.0).ConclusionsThis study demonstrates a feasible methodology for eliciting utility values in CLN2 disease, indicating HRQoL declines with disease progression. Vignettes describing patients receiving cerliponase alfa were consistently assigned higher utility values for the same disease state, suggesting this treatment improves HRQoL compared with standard care.Trial registration NCT01907087, NCT02485899.

【 授权许可】

CC BY