The Cost-Effectiveness of Seizure Dogs for Persons Living With Severe Refractory Epilepsy: Results From the EPISODE Study.

OBJECTIVES: The Epilepsy Support Dog Evaluation study was commissioned by the Dutch Ministry of Health, Welfare and Sports to inform a reimbursement decision on seizure dogs. The randomized trial found that seizure dogs reduce seizure frequency and improve health-related quality of life of persons with severe refractory epilepsy (PSREs). This article examined the cost-effectiveness (CE) of adding seizure dogs to usual care for PSREs in The Netherlands. METHODS: A microsimulation model was developed, informed by generalized linear mixed models using patient-level trial data from the Epilepsy Support Dog Evaluation study. The model adopted a 10-year time horizon and took a societal perspective. Seizure frequency was predicted as a function of time with the seizure dog. Patient utilities, caregiver utilities, and costs were predicted as a function of seizure frequency and time with the seizure dog. RESULTS: Quality-adjusted life-years (QALYs) of PSREs with a seizure dog and usual care alone were estimated at 6.28 and 5.65, respectively (Δ 0.63). For caregivers, estimated QALYs were 6.94 and 6.52, respectively (Δ 0.42). Total costs were respectively €228 691 and €226 261 (Δ €2430). Intervention costs were largely offset by savings in informal care and healthcare. The incremental CE ratio was €2314/QALY. Probabilistic sensitivity analysis indicated a 91% probability of seizure dogs being cost-effective at the €50 000/QALY threshold. The incremental CE ratio fell well below this threshold in scenario analyses. CONCLUSIONS: Seizure dogs are likely to be a cost-effective addition to usual care for PSREs in The Netherlands.

Caregiver Burden and Quality of Life Across Alzheimer's Disease Severity Stages.

INTRODUCTION: The objective is to estimate the caregiver burden in terms of informal care time, health-related quality of life (HRQoL), and societal costs by disease severity (mild, moderate, or severe) and living situation (community-dwelling or institutionalized) of persons with AD (PwAD); and PwAD HRQoL. METHODS: Caregivers were recruited through an online panel provider in the Netherlands. The survey used validated instruments, including iMTA Valuation of Informal Care Questionnaire, CarerQoL, and EQ-5D-5L. RESULTS: One hundred two caregivers participated. PwADs received, on average, 26 hours of informal care per week. Informal care costs were higher for community-dwelling PwADs compared with institutionalized PwADs (€480 and €278, respectively). On the EQ-5D-5L, caregivers scored on average 0.797, reflecting a utility decrement of 0.065 compared with an age-matched population. Proxy-rated utility scores for PwADs decreased with increasing disease severity (0.455, 0.314, and 0.212 for mild, moderate, and severe AD, respectively). Institutionalised PwADs had lower utility scores than community-dwelling PwADs (0.590 vs. 0.421). There was no difference in informal care time, societal costs, CarerQol scores, and caregiver EQ-5D-5L scores between disease severities. CONCLUSION: The burden of AD extends to caregivers in terms of HRQoL and time investment, regardless of the disease severity of the target population. These impacts should be incorporated into the evaluation of new AD interventions.

Cost Effectiveness of Splenic Artery Embolization versus Splenectomy after Trauma in the Netherlands.

PURPOSE: To demonstrate that splenic artery embolization (SAE) is more cost-effective than splenectomy from a societal perspective in the Netherlands. MATERIALS AND METHODS: Patient-level data obtained from the SPLENIQ study were used to populate a health economic model and were supplemented with expert opinion when necessary. Propensity score matching was used to correct for baseline differences in injury severity scores. The health economic model consisted of 3 health states (complications after intervention, SAE failure, and recovery) and a dead state. Model outcomes were incremental quality-adjusted life years (QALYs) and incremental costs of SAE over splenectomy. The Dutch health economic guidelines were followed. The model used a lifetime time horizon. Uncertainty was assessed using probabilistic sensitivity analysis and scenario analyses. RESULTS: Patients undergoing SAE had a higher life expectancy than patients undergoing splenectomy. Incremental QALYs were 3.1 (mostly explained by difference in life expectancy), and incremental costs were €34,135 (explained by costs related to medical consumption and lost productivity in additional life years), leading to an incremental cost-effectiveness ratio of €11,010 per QALY. SAE was considered cost-effective in >95% of iterations using a threshold of €20,000 per QALY. CONCLUSIONS: SAE results in more QALYs than splenectomy. Intervention costs for SAE are lower than that for splenectomy, but medical consumption and productivity costs in later years are higher for SAE due to better survival. SAE was found to be cost-effective compared with splenectomy under appropriate Dutch cost-effectiveness thresholds.

Burden of Providing Informal Care for Patients with Atrial Fibrillation.

OBJECTIVES: Patients with atrial fibrillation (AF) have rapid and irregular heart rates, increasing the risk of comorbidities and mortality. Next to formal medical care, many patients receive informal care from their social environment. The objective of this study was to examine the well-being and economic burden of providing informal care to patients with AF in the UK, Italy, and Germany. METHODS: Caregivers of patients with AF completed an online survey based on the iMTA Valuation of Informal Care Questionnaire, with questions about their caregiving situation, perceived burden of caregiving, and absence from work due to health problems resulting from caregiving. Care-related quality-of-life utilities were calculated using the Care-related Quality of Life instrument and associated tariffs. Societal costs of caregiving were calculated based on the proxy good method. RESULTS: A total of 585 caregivers participated in this study. On average, caregivers provided 33 hours of informal care per week to patients (SD 29 hours). On a scale from 0 to 10, their self-rated burden was 5.4. The average Care-related Quality of Life utility was 72. Caregivers primarily indicated problems with daily activities, mental health, and physical health. Still, the vast majority of caregivers (87%) derived fulfillment from providing care. Weekly societal costs of caregiving were on average €636. Comorbidities contributed substantially to the caregiver time and burden. CONCLUSIONS: Caring for a patient with AF is associated with substantial objective and subjective burden, but also provides fulfillment from being able to care for a loved one.

Good Days and Bad Days: Measuring Health-Related Quality of Life in People With Epilepsy.

OBJECTIVES: Cost-effectiveness analyses typically require measurement of health-related quality of life (HRQoL) to estimate quality-adjusted life-years. Challenges with measuring HRQoL arise in the context of episodic conditions if patients are less likely-or even unable-to complete surveys when having disease symptoms. This article explored whether HRQoL measured at regular time intervals adequately reflects the HRQoL of people with epilepsy (PWE). METHODS: Follow-up data from the Epilepsy Support Dog Evaluation study on the (cost-)effectiveness of seizure dogs were used in which HRQoL is measured in 25 PWE with the EQ-5D at baseline and every 3 months thereafter. Seizure count is recorded daily using a seizure diary. Regression models were employed to explore whether PWE were more likely to complete the HRQoL survey on a good day (ie, when seizures are absent or low in frequency compared with other days) and to provide an estimate of the impact of reporting HRQoL on a good day on EQ-5D utility scores. RESULTS: A total of 111 HRQoL measurements were included in the analyses. Regression analyses indicated that the day of reporting HRQoL was associated with a lower seizure count (P<.05) and that a lower seizure count was associated with a higher EQ-5D utility score (P<.05). CONCLUSIONS: When HRQoL is measured at regular time intervals, PWE seem more likely to complete these surveys on good days. Consequently, HRQoL might be overestimated in this population. This could lead to underestimation of the effectiveness of treatment and to biased estimates of cost-effectiveness.

Assessing Costs Using the Treatment Inventory Cost in Psychiatric Patients (TIC-P), TIC-P Mini and TIC-P Midi.

BACKGROUND: The Treatment Inventory Cost in Psychiatric patients (TIC-P) instrument is designed to measure societal costs in patients with psychiatric disorders and to be applied in economic evaluations. Efforts have been made to minimize respondents' burden by reducing the number of questions and meanwhile retaining the comprehensiveness of the instrument. Previously, a TIC-P Mini version and a TIC-P Midi version were developed and tested in a predominantly inpatient patient population. AIMS OF THE STUDY: The aims of this study are to examine the comprehensiveness of the abridged questionnaires in estimating the societal costs for patients with anxiety or depressive disorders and to assess the impact of productivity costs on the total costs. METHODS: The comprehensiveness of the abridged versions of the TIC-P was assessed in four populations: a group of primary care patients with anxiety disorders (n=175) and three groups of patients with major depressive disorders in various outpatient settings (n=140; n=125; and n=79). Comprehensiveness was measured using the proportion of total health care costs and productivity costs covered by the abridged versions compared to the full-length TIC-P. Costs were calculated according to the guidelines for costing studies using the Dutch costing manual. RESULTS: Our results showed that the TIC-P Mini covered 26%-64% of health care costs and the TIC-P Midi captured 54%-79% of health care costs. Health care costs in these populations were predominantly dispersed over primary care, outpatient hospital care, outpatient specialist care and inpatient hospital care. The TIC-P Midi and TIC-P Mini captured 22% and 0% of primary care costs respectively. In contrast, inpatient hospital care costs and outpatient specialist mental health care costs were almost fully included in the abridged versions. Costs due to lost productivity as measured by the full-length TIC-P were substantial, representing 38% to 92% of total costs. DISCUSSION: A reduction of the number of items resulted in a substantial loss in the ability to measure health care costs compared to the full-length TIC-P, because these outpatient populations consumed health care from a variety of health care providers. Two limitations of the study need to be stressed. Firstly, the number of patients in each of the four studies was relatively small. However, results were consistent over the four studies despite the small number of patients. Secondly, we did not take costs of medication into account. IMPLICATIONS FOR HEALTH POLICIES: In developing mental health policy, it is important to include considerations on cost-effectiveness. Increasing the evidence on instruments to measure costs from a societal perspective may support policymakers to adopt a broader perspective. IMPLICATIONS FOR FURTHER RESEARCH: The TIC-P Mini is not suitable to capture health care costs in outpatients with anxiety or depressive disorders. The comprehensiveness of TIC-P Midi compared to the full-length TIC-P varied. The TIC-P Midi should therefore be revised in order to better capture costs in all patient groups.

Potential cost savings owing to the route of administration of oncology drugs: a microcosting study of intravenous and subcutaneous administration of trastuzumab and rituximab in the Netherlands.

There is little evidence on the costs associated with the route of administration of oncology drugs. We investigated time and resource use for hospitals and patients and compared healthcare and societal costs for intravenous (IV) and subcutaneous (SC) administration of trastuzumab and rituximab. Data for the preparation and administration of both drugs were collected at the hospital pharmacy and at the oncology day care unit. Patients completed a questionnaire for obtaining information on societal costs (productivity losses, informal care and traveling expenses). A total of 126 patients were recruited in six hospitals; 82 received trastuzumab (37 IV and 45 SC) and 44 received rituximab (23 IV and 21 SC). The costs per administration (including societal cost but excluding drug costs) were &OV0556;167 and &OV0556;264 for IV and &OV0556;76 and &OV0556;146 for SC trastuzumab and rituximab, respectively. The costs for SC administration were lower in all categories. The largest cost component was related to time spent at the day care unit (overhead costs). This resulted in savings of &OV0556;47 for SC trastuzumab and &OV0556;69 for SC rituximab. The costs related to time of healthcare professionals was &OV0556;9 lower for both drugs. The costs for consumables resulted in another &OV0556;12 savings. Societal costs were &OV0556;22 lower for SC trastuzumab and &OV0556;28 lower for SC rituximab. Although administration costs are relatively a small part of the total costs, important savings can be generated by switching to an SC route of administration especially because a large number of patients receive oncology drugs and patients receive more than one administration.

Quality of life and participation in daily life of adults with Pompe disease receiving enzyme replacement therapy: 10 years of international follow-up.

BACKGROUND: Pompe disease is an inheritable metabolic disorder for which enzyme replacement therapy (ERT) has been available since 2006. Effects of ERT have been shown on distance walked, pulmonary function and survival. We investigated whether it also improves quality of life and participation in daily life in adult patients with the disease. METHODS: In an international survey, we assessed quality of life (Short Form 36, SF-36) and participation (Rotterdam Handicap Scale, RHS) annually between 2002 and 2012. Repeated measurements mixed effects models were used to describe the data over time. RESULTS: Responses were available for 174 adult patients. In the periods before and after start of ERT, the median follow-up times were 4 years each (range 0.5-8). The SF-36 Physical Component Summary measure (PCS) deteriorated before ERT (-0.73 score points per year (sp/y); CI 95 % -1.07 to -0.39), while it improved in the first 2 years of ERT (1.49 sp/y; CI 0.76 to 2.21), and remained stable thereafter. The Mental Component Summary measure (MCS) remained stable before and during ERT. After declining beforehand (-0.49 sp/year; CI -0.64 to-0.34), the RHS stabilized under ERT. CONCLUSION: In adult patients with Pompe disease, ERT positively affects quality of life and participation in daily life. Our results reinforce previous findings regarding the effect of ERT on muscle strength, pulmonary function and survival.

Cost comparison of two implantable cardiac monitors in two different settings: Reveal XT in a catheterization laboratory vs. Reveal LINQ in a procedure room.

AIMS: Implantable cardiac monitors (ICMs) are used for long-term heart rhythm monitoring, e.g. to diagnose unexplained syncope or for detection of suspected atrial and ventricular arrhythmias. The newest ICM, Reveal LINQ™ (Medtronic Inc.), is miniaturized and inserted with a specific insertion tool kit. The procedure is therefore minimally invasive and can be moved from catheterization laboratory (cath lab) to a less resource intensive setting. This study aims to assess the change in procedure costs when performed outside the cath lab. METHODS AND RESULTS: A bottom-up costing methodology was used. Data were collected from interviews with physicians, cath lab managers, and financial controllers. Hospitals in the Netherlands, France, and the UK were included in this study. The cost comparison of a Reveal XT implantation in a cath lab setting vs. a Reveal LINQ insertion outside a cath lab resulted in an estimated reduction of €662 for the UK, €682 for the Netherlands, and €781 for France. These cost savings were primarily realized through fewer staff, less equipment, and overhead costs. The net effect on savings depends on the price differential between these two technologies. The patient care pathway can be improved due to the possibility to move the procedure out of the cath lab. CONCLUSION: Inserting the miniaturized version of the ICM is simpler and faster, and the procedure can take place outside the cath lab in a less resource intensive environment. Hospitals save resources when the higher price of the Reveal LINQ does not outweigh these savings.

Benefits of a digital health technology for older nursing home residents. A de-novo cost-effectiveness model for digital health technologies to aid in the assessment of toileting and containment care needs.

The aim of this study was first, to introduce a comprehensive, de-novo health economic (HE) model incorporating the full range of activities involved in toileting and containment care (T&CC) for people with incontinence, capturing all the potential benefits and costs of existing and future Digital Health Technologies (DHT) aimed at improving continence care, for both residential care and home care. Second, to use this novel model to evaluate the cost-effectiveness of the DHT TENA SmartCare Identifi in the implementation of person-centred continence care (PCCC), compared with conventional continence care for Canadian nursing home residents. The de-novo HE model was designed to evaluate technologies across different care settings from the perspective of several stakeholders. Health states were based on six care need profiles with increasing need for toileting assistance, three care stages with varying degrees of toileting success, and five levels of skin health. The main outcomes were incremental costs and quality-adjusted life years. The effectiveness of the TENA SmartCare Identifi was based primarily on trial data combined with literature and expert opinion where necessary. Costs were reported in CAD 2020. After 2 years, 21% of residents in the DHT group received mainly toileting as their continence care strategy compared with 12% in the conventional care group. Conversely, with the DHT 15% of residents rely mainly on absorbent products for incontinence care, compared with 40% with conventional care. On average, residents lived for 2.34 years, during which the DHT resulted in a small gain in quality-adjusted life years of 0.015 and overall cost-savings of $1,467 per resident compared with conventional care. Most cost-savings were achieved through reduced costs for absorbent products. Since most, if not all, stakeholders gain from use of the DHT-assisted PCCC, widespread use in Canadian residential care facilities should be considered, and similar assessments for other countries encouraged.

Including carer health-related quality of life in NICE health technology assessments in the United Kingdom.

The impact of health technologies may extend beyond the patient and affect the health of people in their network, like their informal carers. The National Institute for Health and Care Excellence (NICE) methods guide explicitly allows the inclusion of health-related quality of life (HRQoL) effects on carers in economic evaluations when these effects are substantial, but the proportion of NICE appraisals that includes carer HRQoL remains small. This paper discusses when inclusion of carer HRQoL is justified, how inclusion can be substantiated, and how carer HRQoL can be measured and included in health economic models. Inclusion of HRQoL in economic evaluations can best be substantiated by data collected in (carers for) patients eligible for receiving the intervention. To facilitate combining patient and carer utilities on the benefit side of economic evaluations, using EQ-5D to measure impacts on carers seems the most successful strategy in the UK context. Alternatives to primary data collection of EQ-5D include vignette studies, using existing values, and mapping algorithms. Carer HRQoL was most often incorporated in economic models in NICE appraisals by employing (dis)utilities as a function of the patient's health state or disease severity. For consistency and comparability, economic evaluations including carer HRQoL should present analyses with and without carer HRQoL.

Effectiveness of Seizure Dogs for People With Severe Refractory Epilepsy: Results From the EPISODE Study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate whether people living with severe medically refractory epilepsy (PSRE) benefit from a seizure dog. METHODS: An individual-level stepped-wedge randomized controlled trial was conducted. The study was conducted in the Netherlands among adults with daily to weekly seizures. All participants were included simultaneously (on June 1, 2019) while receiving usual care. Then, during the 36-month follow-up, they received a seizure dog in a randomized sequence. Participants kept a seizure diary and completed 3-monthly surveys. Seizure frequency was the primary outcome. Secondary outcomes included seizure-free days, seizure severity, health-related quality of life (HRQoL), and well-being. Data were analyzed using generalized linear mixed modeling (GLMM). The models assumed a delayed intervention effect, starting when the seizure dog reached an advanced stage of training. Effects were calculated as changes per 28-day period with the intervention. RESULTS: Data were collected from 25 participants, of whom 20 crossed over to the intervention condition. The median follow-up was 19 months with usual care and 12 months with the intervention. On average, participants experienced 115 (SD 164) seizures per 28-day period in the usual care condition and 73 (SD 131) seizures in the intervention condition. Seven participants achieved a reduction of 50% or more at the end of follow-up. GLMM indicated a 3.1% decrease in seizure frequency for each consecutive 28-day period with the intervention (0.969, 95% CI 0.960-0.977). Furthermore, an increase in the number of seizure-free days was observed (1.012, 95% CI 1.009, 1.015), but no effect on seizure severity measured with the NHS3. Generic HRQoL scores improved, as reflected in the decrease in EQ-5D-5L utility decrement (0.975, 95% CI 0.954-0.997). Smaller improvements were observed on overall self-rated HRQoL, epilepsy-specific HRQoL, and well-being, measured with the EQ VAS, QOLIE-31-P, and ICECAP-A, respectively. DISCUSSION: Seizure dogs reduce seizure frequency, increase the number of seizure-free days, and improve the quality of life of PSRE. The magnitude of the effect on generic HRQoL indicates that seizure dogs benefit PSRE beyond the impact on seizure frequency alone. Early discontinuation of seizure dog partnerships suggests that this intervention is not suitable for all PSRE and requires further study. TRIAL REGISTRATION INFORMATION: This study was registered in the Dutch Trial Register (NL6682) on November 28, 2017. Participants were enrolled on June 1, 2019. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that seizure dogs are associated with a decrease in seizure frequency in adult patients with medically refractory epilepsy.

The impact of informal care for patients with Pompe disease: an application of the CarerQol instrument.

BACKGROUND: Patients with Pompe disease, a rare progressive neuromuscular disorder, receive a considerable amount of informal care. In this study, we examined the impact of providing informal care to patients with Pompe disease. METHODS: Caregivers were administered various instruments, which measured the (impact of) informal care in the context of Pompe disease. Patients' quality of life and use of a wheelchair and respiratory support were used to investigate the impact of disease severity on the burden and well-being of caregivers. RESULTS: Of all Dutch patients with Pompe disease, 88 indicated to receive informal care, of which 67 (76%; 67 caregivers) participated in this study. On average, caregivers provided 17.7 hours of informal care per week. Higher disease burden was associated with more hours of informal care. Caregivers experienced burden due to caregiving. Half of the informal caregivers reported mental health problems and problems with daily activities due to providing informal care. Physical health problems occurred in 40% of informal caregivers. Caregiver burden was higher for patients with a lower quality of life and for wheelchair dependent patients. Burden was not associated with respiratory support. Caregivers reported deriving personal fulfillment from caregiving and, on average, would become unhappier if someone else were to take over their care activities. CONCLUSIONS: The provision of informal care causes burden to caregivers. However, caregivers also value caring for their loved ones themselves. The study may help physicians and policy makers to design measures to support informal caregivers.

The Disease Burden and Societal Costs of Hereditary Angioedema.

BACKGROUND: According to the current treatment guidelines, the goals of treatment of patients with hereditary angioedema (HAE) are to achieve total control of the disease and to normalize patients' lives. OBJECTIVE: This study aims to establish the entire burden of HAE comprising disease control, treatment satisfaction, reductions in quality of life, and societal costs. METHODS: Adult patients with HAE under treatment at the Dutch national center of reference completed a cross-sectional survey in 2021. The survey consisted of different questionnaires: angioedema-specific questionnaires (4-week Angioedema Activity Score and Angioedema Control Test), quality of life questionnaires (Angioedema Quality of Life [AE-QoL] questionnaire and EQ-5D-5L), the Treatment Satisfaction Questionnaire for Medication (TSQM), and societal costs questionnaires (iMTA Medical Consumption Questionnaire and iMTA Productivity Cost Questionnaire). RESULTS: The response rate was 78% (69 of 88). The entire sample had a mean Angioedema Activity Score of 16.61, and 36% of participants had poorly controlled disease as expressed by the Angioedema Control Test. The mean quality of life in the entire sample was 30.99 as expressed by the AE-QoL and 0.873 as expressed by the EQ-5D-5L utility value. Utilities dropped by 0.320 points during an angioedema attack. TSQM scores ranged from 66.67 to 75.00 across its 4 domains. On average, total costs per year incurred €22,764, predominantly existing of HAE-medication costs. Total costs showed substantial variation between patients. CONCLUSIONS: This study describes the entire burden of HAE among Dutch patients comprising disease control, quality of life, treatment satisfaction, and societal costs. These results can inform cost-effectiveness analyses that can aid reimbursement decisions for HAE treatments.

Costs of Persons with Dementia Living in Nursing Homes in The Netherlands.

BACKGROUND: Disease modifying treatments (DMTs) currently under development for Alzheimer's disease, have the potential to prevent or postpone institutionalization and more expensive care and might delay institutionalization of persons with dementia. OBJECTIVE: The current study estimates costs of living in a nursing home for persons with dementia in the Netherlands to help inform economic evaluations of future DMTs. METHODS: Data were collected during semi-structured interviews with healthcare professionals and from the financial administration of a healthcare organization with several nursing homes. Personnel costs were calculated using a bottom-up approach by valuing the time estimates. Non-personnel costs were calculated using information from the financial administration of the healthcare organization. RESULTS: Total costs of a person with dementia per 24 hours, including both care staff and other healthcare providers, were € 151 for small-scale living wards and € 147 for independent living wards. Non-personnel costs were € 37 per day. CONCLUSION: This study provides Dutch estimates for total healthcare costs per day for institutionalized persons with dementia. These cost estimates can be used in cost-effectiveness analyses for future DMTs in dementia.

Burden of illness in people with medically refractory epilepsy who suffer from daily to weekly seizures: 12-month follow-up of participants in the EPISODE study.

Background: A small group of people with epilepsy suffers from frequent seizures despite the available pharmacological and non-pharmacological interventions. The impact of epilepsy on these people extends beyond health-related quality of life (HRQoL), impacting a person's broader well-being and ability to participate in society. This study describes the burden of medically refractory epilepsy in people who suffer from daily to weekly seizures, in terms of HRQoL, well-being, and societal costs. Methods: Data from the EPISODE study on (cost-) effectiveness of seizure dogs for adults with severe medically refractory epilepsy were used, collected in 25 patients during the first 12 months before they were partnered with a certified seizure dog. Data comprised seizure diaries covering 365 days and five three-monthly surveys, including the EQ-5D-5L, QOLIE-31-P, and ICECAP-A to measure HRQoL and well-being. A societal perspective was applied to estimate costs using the iMCQ and iPCQ questionnaires about healthcare use, informal care, and productivity losses. Results: Daily seizure frequency and survey data were collected in 25 patients. A minimum of 114 observations was available for each instrument included in the survey. A total of 80% of participants experienced seizures on three or more days per week, with a median ranging from 1 to 17 seizures per seizure day. The mean EQ-5D-5L utility score was 0.682 (SD 0.235), which is considerably lower than the age-adjusted general population average. The mean QOLIE-31-P and ICECAP-A scores were 55.8 (SD 14.0) and 0.746 (SD 0.172), respectively. The average annual total cost amounted to €39,956 (range €3,804-€132,64). Informal care accounted for the largest share of costs (50%); those who received informal care reported, on average, 26 h per week (SD 30). Conclusions: Severe medically refractory epilepsy is associated with a considerable burden of illness at the patient and societal level. People with this condition have significantly reduced HRQoL and well-being and are limited in their ability to work while having substantial medical costs and a strong dependency on informal care.

Productivity of Working at Home and Time Allocation Between Paid Work, Unpaid Work and Leisure Activities During a Pandemic.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic and the measures taken by governments to contain it have affected many aspects of the daily lives of citizens. This study aimed to describe changes in the productivity of paid work and time allocation to paid and unpaid work and leisure resulting from working at home during the pandemic. METHODS: A sample of 851 people from the Netherlands who had paid work (≥ 24 h/week) and worked at least 4 hours per week extra at home because of lockdown measures completed a questionnaire during the first COVID-19 lockdown (April 2020). Respondents reported time spent on paid and unpaid work and leisure before and during the lockdown. Productivity was measured in terms of quantity and quality of paid work. RESULTS: On average, respondents spent less time (14%) on paid work and productivity decreased 5.5%. Changes in productivity were associated with the age of children, net income and having a separate home office. Respondents spent more time on unpaid work (27%) and leisure (11%). Women spent more time on unpaid work in absolute but not in relative terms. People with a partner and with children spent more time on unpaid work and less time on leisure. CONCLUSIONS: Productivity of paid work decreased, and people reallocated time between paid and unpaid work and leisure during the first COVID-19 lockdown. Changes in time allocation and productivity differed across subgroups. If working at home becomes more common, future research should focus on the long-term impact on productivity and mental and physical health.

Burden of illness of Pompe disease in patients only receiving supportive care.

BACKGROUND: Pompe disease is an orphan disease for which enzyme replacement therapy (ERT) recently became available. This study aims to estimate all relevant aspects of burden of illness--societal costs, use of home care and informal care, productivity losses, and losses in health-related quality of life (HRQoL)--for adult Pompe patients only receiving supportive care. METHODS: We collected data on all relevant aspects of burden of illness via a questionnaire. We applied a societal perspective in calculating costs. The EQ-5D was used to estimate HRQoL. RESULTS: Eighty adult patients (87% of the total Dutch adult Pompe population) completed a questionnaire. Disease severity ranged from mild to severe. Total annual costs were estimated at 22,475 (range 0-169,539) per adult Pompe patient. Patients on average received 8 h of home care and 19 h of informal care per week. Eighty-five percent of the patients received informal care from one or more caregivers; 40% had stopped working due to their disease; another 20% had reduced their working hours. HRQoL for Pompe patients who only received supportive care was estimated at 0.72, 17% lower than the Dutch population at large. CONCLUSIONS: Adult Pompe disease is associated with a considerable burden of illness at both the societal and patient levels. The disease leads to substantial costs and dependency on medical devices, home care, and informal care, and has a high impact on the patient's social network. In addition, patients are limited in their ability to work and have significantly reduced HRQoL.

Methodological Challenges in the Economic Evaluation of a Gene Therapy for RPE65-Mediated Inherited Retinal Disease: The Value of Vision.

The emergence of gene therapies challenge health economists to evaluate interventions that are often provided to a small patient population with a specific gene mutation in a single dose with high upfront costs and uncertain long-term benefits. The objective of this study was to illustrate the methodological challenges of evaluating gene therapies and their implications by discussing four economic evaluations of voretigene neparvovec (VN) for the treatment of RPE65-mediated inherited retinal disease. The checklist for economic evaluations of gene therapies of Drummond et al. was applied to the economic evaluations of VN performed by US Institute for Clinical and Economic Review, two country adaptations of the company model in the UK and the Netherlands, and another US publication. The main differences in methodological choices and their impact on cost-effectiveness results were assessed and further explored with sensitivity analyses using the Dutch model. To enable comparison between the economic evaluations, costs were converted to US dollars. Different methodological choices were made in the economic evaluations of VN resulting in large differences in the incremental cost-effectiveness ratio varying from US$79,618 to US$643,813 per QALY. The chosen duration of treatment effect, source of utility values, discount rate and model structure had the largest impact on the cost-effectiveness. This study underlines the findings from Drummond et al. that standard methods can be used to evaluate gene therapies. However, given uncertainty about (particularly long-term) outcomes of gene therapies, guidance is required on the acceptable extrapolation of treatment effect of gene therapies and on how to handle the uncertainty around this extrapolation in scenario and sensitivity analyses to aid health technology assessment research and align submissions of future gene therapies.

Hospital-based or home-based administration of oncology drugs? A micro-costing study comparing healthcare and societal costs of hospital-based and home-based subcutaneous administration of trastuzumab.

OBJECTIVE: To investigate resource use and time investments of healthcare professionals, patients and their family and to compare healthcare and societal costs of one single hospital-based and one single home-based subcutaneous administration of trastuzumab in The Netherlands. METHOD: We conducted a bottom-up micro-costing study. Patients diagnosed with HER2+ early or metastatic breast cancer were recruited in four Dutch hospitals. For healthcare costs, data were collected on drug use, consumables, use of healthcare facilities, time of healthcare professionals, and travelling distance of the nurse. For societal costs, data were collected on patient and family costs (including travelling expenses and time of informal caregivers) and productivity losses of paid and unpaid work. RESULTS: Societal costs of one single administration of SC trastuzumab were €1753 within the home-based and €1724 within the hospital-based setting. Drug costs of trastuzumab were identical in both settings (€1651). Healthcare costs were higher for home-based administration (€91 versus €47) mainly because of more time of healthcare professionals (110 versus 38 minutes). Costs for patient and family were, however, lower for home-based administration due to travelling expenses (€7 versus €0) and time of informal caregivers (€14 versus €4). Costs for productivity losses were similar for both settings. CONCLUSIONS: Home-based subcutaneous administration of trastuzumab is more time consuming for healthcare professionals and therefore more costly than hospital-based administration. The total budget impact can be large considering that a large number of patients receive a large number of cycles of oncology treatments. If home-based administration is the way forward, novel approaches are crucial for ensuring efficiency of home-based care.