Quality of Life with Late-Onset Pompe Disease: Qualitative Interviews and General Public Utility Estimation in the United Kingdom.

Background: Late-onset Pompe disease (LOPD) is a rare, progressive neuromuscular condition typically characterized by weakness of skeletal muscles, including those involved in respiration and diaphragmatic dysfunction. Individuals with LOPD typically eventually require mobility and/or ventilatory support. Objectives: This study aimed to develop health state vignettes and estimate health state utility values for LOPD in the United Kingdom. Methods: Vignettes were developed for 7 health states of LOPD with states defined in terms of mobility and/or ventilatory support. Vignettes were drafted based on patient-reported outcome data from the Phase 3 PROPEL trial (NCT03729362) and supplemented by a literature review. Qualitative interviews with individuals living with LOPD and clinical experts were conducted to explore the health-related quality-of-life (HRQoL) impact of LOPD and to review the draft vignettes. Vignettes were finalized following a second round of interviews with individuals living with LOPD and used in health state valuation exercises with people of the UK population. Participants rated the health states using the EQ-5D-5L, visual analogue scale, and time trade-off interviews. Results: Twelve individuals living with LOPD and 2 clinical experts were interviewed. Following the interviews, 4 new statements were added regarding dependence on others, bladder control problems, balance issues/fear of falling, and frustration. One hundred interviews with a representative UK population sample were completed. Mean time trade-off utilities ranged from 0.754 (SD = 0.31) (no support) to 0.132 (SD = 0.50) (invasive ventilatory and mobility support-dependent). Similarly, EQ-5D-5L utilities ranged from 0.608 (SD = 0.12) to -0.078 (SD = 0.22). Discussion: The utilities obtained in the study are consistent with utilities reported in the literature (0.670-0.853 for nonsupport state). The vignette content was based on robust quantitative and qualitative evidence and captured the main HRQoL impacts of LOPD. The general public rated the health states consistently lower with increasing disease progression. There was greater uncertainty around utility estimates for the severe states, suggesting that participants found it harder to rate them. Conclusion: This study provides utility estimates for LOPD that can be used in economic modeling of treatments for LOPD. Our findings highlight the high disease burden of LOPD and reinforce the societal value of slowing disease progression.

Burden associated with Fabry disease and its treatment in 12-15 year olds: results from a European survey.

BACKGROUND: Fabry Disease (FD) is a rare X-linked metabolic lysosomal disorder. FD has a broad range of symptoms which vary markedly between patients. The heterogenous nature of the disease makes diagnosis difficult for health care professionals (HCPs), which in turn has a significant effect on the patient's quality of life (QoL). As few adolescent patients are eligible for treatment, to date there has been little published data on the burden of disease and impact of treatment on these patients and their caregivers. This study was developed to provide some insight into these groups. METHODS: An online-based survey was performed to gather further insights on the burden of FD in 14 adolescents aged 12-15 years old across three European countries, from the perspective of the patients, caregivers and HCPs. RESULTS: Symptom burden was found to be high in the adolescent population, with 'pain' and 'intolerance to heat or cold' commonly reported symptoms, both by patients and to HCPs. Eleven of the 14 patients surveyed were receiving enzyme replacement therapy (ERT), with their post-ERT symptomology showing improvement when compared to symptoms before receiving ERT. The majority of caregivers believe their child's overall health has improved since starting ERT. While there was a positive outlook towards ERT noted by the patients and caregivers, 4/5 HCPs believed there is 'a need for more efficacious treatment options' and all HCPs noted that there is 'a need for more manageable treatment options'. FD was shown to place a burden on caregivers, who reported feelings of guilt and absences from work. CONCLUSIONS: Data show there is a significant symptom burden for the adolescent, which affects their QoL and mental health, as well as placing a burden on the wider family. While ERT is an effective treatment and provides symptom relief for many of the respondents in the survey, they still reported symptom burden. Additionally, there was reporting of reluctance to engage in treatment or difficulties associated with the treatment. Heterogeneity in symptom presentation suggests that the treatment regimen needs to be tailored to the individual. Physicians therefore need to have a choice of treatment options available to help them manage symptoms and disease where the benefit to risk ratio is in favour of undergoing treatment.

The impact of home parenteral nutrition on the burden of disease including morbidity, mortality and rate of hospitalisations.

INTRODUCTION: Home parenteral nutrition (HPN) provides fluid and nutrition essential for the survival of patients with type 3 intestinal failure (IF). However, it is associated with complications and re-admission to hospital. This study aims to investigate the effect of HPN on mortality, morbidity and hospital re-admissions. METHOD: This is a retrospective cohort study. All patients newly dependent on HPN discharged over a 4-year period between 2011 and 2015 were included. Patients' characteristics, nutritional status and diagnosis were recorded, along with frequency and duration of HPN administration. Outcomes collected included hospital re-admissions, morbidity, catheter related blood stream infections (CRBSIs) and mortality. Regression analyses were performed to estimate the rate of different outcomes adjusted for prognostic factors. RESULTS: There were 210 patients included, 561 separate HPN prescriptions equating to 110,537 catheter days. Total number of deaths was 44 (0.398 deaths per 1000 catheter days). There were 196 re-admissions to hospital recorded for a total of 5594 days, 69 (33%) of these re-admissions were unplanned (2484 days in hospital). Principle reasons for unplanned re-admissions included: CRBSIs (n = 31, 45%); other sepsis (n = 10, 14.5%) and abdominal symptoms (n = 9, 13%). CRBSIs were recorded in 22 (10%) patients, equating to a rate of 0.199 per 1000 catheter days. Days per week on HPN increased the relative rate (RR) of time in hospital due to any reason or for unplanned readmissions, RR 1.50 (95% CI: 1.26, 1,78 p < 0.001) and RR 1.39 (95% CI: 1.10, 1.75 p = 0.006) respectively. However, there was no association between days per week on HPN and CRBSI occurrence. CONCLUSION: Unplanned re-admissions for patients with IF accounted for a third of all hospitalisations in those on HPN and the majority were due to CRBSI. The number of HPN dependent days per week was related to all-cause unplanned re-admissions, although not to CRBSI rate.

Social preference weights for treatments in Fabry disease in the UK: a discrete choice experiment.

OBJECTIVE: Fabry disease is a rare inherited lysosomal storage disorder caused by deficiency of α-galactosidase A. Effective enzyme replacement therapies are available that are administered intravenously. However, a new oral treatment is being developed as an alternative option for patients with amenable mutations. This study was designed to understand the value that people place on the different features of treatments for Fabry disease. RESEARCH DESIGN AND METHODS: A discrete choice experiment (DCE) was designed to assess the importance of different aspects of treatments for Fabry disease. The attributes included overall survival, mode of administration, treatment related reactions, treatment related headaches and risk of antibody formation. Attributes were combined using a published orthogonal array into choice sets. A research panel was used to survey the UK general public. The mixed logit model was used to estimate strength of preference for the attributes and marginal rates of substitution (MRSs). Disutilities were estimated from the DCE data for changes in each attribute. RESULTS: The sample (n = 506) was broadly representative of UK demographics. The logit model revealed that all attributes were significant predictors of choice. Participants were significantly more likely to choose a treatment which meant an increase in their life expectancy by 1 year (odds ratio = 1.574; 95% CI = 1.504-1.647) and significantly less likely to choose self-administered intravenous (IV) treatment compared to an every other day tablet (OR = 0.426 95% CI = 0.384-0.474). Estimated disutilities were -0.0543 (self-administered infusion), treatment related headaches 12 times a year (-0.0361) and infusion reactions six times a year (-0.0202). CONCLUSIONS: The survey revealed a significant preference for oral treatment compared with IV even in the context of a treatment that can extend overall survival. MRSs were used as a basis for estimating disutilities associated with changes in attribute levels which could be used to weight QALYs. It is possible that other important treatment attributes are missing from this research which may have provided further insights. It would also be useful to extend this research to include Fabry disease patients so their preferences can be assessed against the societal perspective.