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)

Abstract

Background Utility 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. Methods An 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. Results Utility 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). Conclusions This 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.

Evaluating the Health-Related Quality of Life of the Rare Disease Population in Hong Kong Using EQ-5D 3-Level

“…Given that children's perspective of the different dimensions is likely to differ from adults, pediatric utility scores proxied by adults may not be accurate. 60,61 Nevertheless, the proxy version of EQ-5D has been validated in HK and .60 other jurisdictions and is well recognized in international studies. 30…”

Neuronal Ceroid Lipofuscinosis: The Multifaceted Approach to the Clinical Issues, an Overview

“…percutaneous gastrostomy), respiratory support, as well as the improved quality of skin and general care (e.g. prevention of bed sores), the availability of new anti-epileptic drugs, and the overall improved awareness of caregivers to provide care in order to enhance the length and quality of life of those affected ( 120 , 121 ).…”

Development and validation of Gaucher disease type 1 (GD1)-specific patient-reported outcome measures (PROMs) for clinical monitoring and for clinical trials

“…9 PHMR, London, UK. 10 Takeda Pharmaceuticals Company Ltd, Cambridge, MA, USA. 11 Gaucher Unit, Shaare Zedek Medical Center, Jerusalem, Israel.…”

“…The importance of individualized patient-centric monitoring is now widely recognized, both with regard to individual patient management and for informing commissioning of healthcare services, and the US Food and Drug Administration (FDA) has issued guidance as to how these measures should be incorporated in clinical trial design [9]. Generic measures of health-related quality of life (HRQoL), including the 36-item Short Form Health Survey (SF-36), the EuroQoL-5 Dimension (EQ-5D) [10], and the Lansky play performance scale for children [11], have been used in rare disease clinical trials and in post-approval surveillance studies, including those for GD1 [12][13][14][15][16][17][18][19][20]. However, because of their generality, these HRQoL instruments may miss important nuances of the disease by failing to capture disease-specific patient-reported outcome measures (PROMs).…”