Inclusion body myositis-health-related quality of life and care situation during phases of the "patience journey" in Germany: results from a qualitative study.

BACKGROUND: To understand the health-related quality of life (HRQoL) in inclusion body myositis (IBM) from a holistic perspective on the background of a complex care situation. The focus was on how the patient journey may be structured over the course of this rare disease. METHODS: An exploratory qualitative study was performed via in-depth semi-structured interviews. Seven patients (males n = 5) with 2011 European Neuromuscular Centre (ENMC) IBM criteria from the German IBM patient registry were interviewed for this study. The dynamic network approach of resilience and the throughput-model of health services research were used to structure the qualitative analysis. RESULTS: Our results suggest that IBM patients experience the holistic HRQoL and care situation typically in four phases: (1) uncertainty about physical vulnerability until diagnosis, (2) promising treatment approaches, (3) self-management and dyadic coping, (4) weak body, busy mind and caregiver burden. The homophonous in-vivo code "patience journey" describes the frequently reported emotional perspective of the patient journey. Although the overarching theme of perceived social support varied throughout these phases, a reliable patient-partner-dyad may lead to improved HRQoL in the long-term. CONCLUSIONS: New hypotheses for future quantitative research were generated to better understand the IBM patients' burden in the long term. The identified relevance of social support emphasizes the patients' need to handle IBM as manageable in medical settings. During exhausting phases of IBM progression, more effective care elements for patients and their partners could disclose varying needs. Strengthening multi-professional healthcare services via individualised informational, practical, or emotional support could improve HRQoL, especially since there is no curative treatment available so far.

Intradialytic neuromuscular electrical stimulation with optional virtual reality distraction improves not only muscle strength and functional capacity but also serum albumin level in haemodialysis patients: a pilot randomized clinical trial.

BACKGROUND: Sarcopenia is highly prevalent in haemodialysis (HD) patients and linked to a poor prognosis regarding comorbidities and premature mortality. Previous studies assessed the effects of neuromuscular electrical stimulation in haemodialysis patients. This study adds to the relevance of neuromuscular electrical stimulation (NMES) applications combined with a virtual reality (VR) distraction to increase intensity, dosage, and efficiency of NMES and slow sarcopenia progression in HD patients. METHODS: We conducted a 12-week multicenter prospective randomised controlled trial. The patients were randomly assigned to one of the three groups: neuromuscular electrical stimulation with or without combined virtual reality distraction or control group. RESULTS: The final analysis included 32 haemodialysis patients (mean age of 68 ± 10 years, 26 men). Interaction effects between groups and time (12 weeks) were significant regarding serum albumin levels (p = 0.008) and left quadriceps femoris muscle (QFM) force (p = 0.026). Both endpoints were increased in the NMES compared to the CO group at the end of the intervention. The NMES group increased serum albumin levels significantly after 12 weeks. The main effect of time was an increase in mean right QFM force between beginning and end of the intervention (p = 0.021). Functional capacity improved after 12 weeks in the NMES and NMES + VR but not in the control group, with a significant difference between the three groups (p = 0.022). Weight and body mass index increased in the NMES and NMES + VR groups, albeit not significantly. The effects of VR distraction on NMES efficiency were inconclusive. CONCLUSION: Intradialytic NMES increases serum albumin level, functional capacity, muscle strength in lower limb and in tendency weight and body mass index of HD patients. Effects on VR distraction are inconclusive. Large-scaled follow-up studies on integrated sports programs with NMES and active training in combination with VR as distraction and motivation accelerator are needed. TRIAL REGISTRATION: German Clinical Trial Register: DRKS00029276 (Retrospectively registered: 30/06/2022).

The First Year of Noninvasive Remote Telemonitoring in Chronic Heart Failure Is not Cost Saving but Improves Quality of Life: The Randomized Controlled CardioBBEAT Trial.

Introduction: Remote telemonitoring (RTM) for patients with chronic heart failure (HF) holds promise to improve prognosis and well-being beyond the standard of care (SoC). The CardioBBEAT trial assessed the health economic and clinical impact of an interactive bidirectional RTM system (Motiva®) versus SoC for patients with HF and a reduced ejection fraction (HFrEF), in Germany. Methods: This multicenter, randomized controlled trial enrolled 621 patients with HFrEF (mean age 63.0 ± 11.5 years, 88% men). The primary endpoint was the integrated effect of the intervention on total costs and nonhospitalized days alive after 12 months, reported as incremental cost-effectiveness ratio (ICER). Costs (in k€) were based on actual charges of patients' statutory health insurance. Among secondary outcome measures were mortality and disease-specific quality of life. Results: We found a neutral effect on nonhospitalized days alive (RTM mean 341 ± 59 days, SoC 346 ± 45 days; p = 0.298) associated with increased total costs (RTM 18.5 ± 39.5 k€, SoC 12.8 ± 22.0 k€; p = 0.046). This yielded an ICER of -1.15 k€/day. RTM did not impact mortality risk. All quality of life scales were consistently and meaningfully improved in the RTM group at 12 months compared to SoC (all p < 0.01). Conclusions: The first 12 months of RTM were not cost-effective compared to SoC in patients with HFrEF, but associated with a relevant improvement in disease-specific quality of life. The balanced assessment of the potential benefit of RTM requires integration of both the societal and patient perspective. ClinTrials.gov (NCT02293252).

Clinical benefit and cost-effectiveness analysis of liquid biopsy application in patients with advanced non-small cell lung cancer (NSCLC): a modelling approach.

PURPOSE: Targeted therapies are effective therapeutic approaches in advanced stages of NSCLC and require precise molecular profiling to identify oncogenic drivers. Differential diagnosis on a molecular level contributes to clinical decision making. Liquid biopsy (LB) use has demonstrated its potential to serve as an alternative to tissue biopsy (TB) particularly in cases where tissue sampling is not feasible or insufficient. We aimed at evaluating the cost-effectiveness of ctDNA-based LB use (molecular multigene testing) according to German care guidelines for metastatic NSCLC. METHODS: A Markov model was developed to compare the costs and clinical benefits associated with the use of LB as an add-on to TB according to the guidelines for NSCLC patients. Usual care TB served as comparator. A microsimulation model was used to simulate a cohort of non-squamous NSCLC patients stage IV. The parameters used for modelling were obtained from the literature and from the prospective German CRISP registry ("Clinical Research platform Into molecular testing, treatment, and outcome of non-Small cell lung carcinoma Patients"). For each pathway, average direct medical costs, and QALYs gained per patient were used for calculating incremental cost-effectiveness ratios (ICER). RESULTS: The use of LB as an add-on was costlier (€144,981 vs. €144,587) but more effective measured in QALYs (1.20 vs. 1.19) for the care pathway of NSCLC patients (ICER €53,909/QALY). Cost-effectiveness was shown for EGFR-mutated patients (ICER €-13,247/QALY). CONCLUSION: Including LB as an add-on into the care pathway of advanced NSCLC has positive clinical effects in terms of QALYs accompanied by a moderate cost-effectiveness.

Patient-Reported Health-Related Quality of Life, Anxiety and Depression in Patients with Inclusion Body Myositis: A Register-Based Cross-Sectional Study in Germany.

Inclusion body myositis (IBM) is a rare neuromuscular disease and the most prevalent idiopathic inflammatory myopathy (IIM) in patients aged older than 50 years. A systematic review has shown that no clear-cut conclusions can be drawn about the health-related quality of life (HRQoL) and mental health in IBM. We aimed to assess the HRQoL and mental health, to explore associated disease-related and socioeconomic factors as well as the utilization of psychological support in German IBM patients. This cross-sectional study included 82 patients registered in the German IBM patient registry. Patients had completed a survey battery including the EQ-5D-5L, the Individualized Neuromuscular Quality of Life (INQoL) and the Hospital Anxiety and Depression Scale German version (HADS-D). The physical HRQoL dimension was suggested to be most relevant. Most impaired life domains of HRQoL were mobility, independence, and activities. We identified significant differences in the total INQoL score for the degree of disability and care level as well as in depression for the degree of disability (p < 0.05), respectively. Most patients indicated no symptoms of anxiety (64.6%) and depression (62.2%). A more need-oriented psychological support in German IBM patients, reporting doubtful or definite anxiety or depression, could be suggested.

Cost of illness in inclusion body myositis: results from a cross-sectional study in Germany.

BACKGROUND: Inclusion body myositis (IBM) is the most frequent type of myositis in elder patients with a slow chronic progression and refractory to treatment. Previous cost of illness (COI) studies in IBM used claims data to estimate direct costs in the US. No evidence exists globally on both direct and indirect costs in IBM from a societal perspective. We conducted a survey in patients registered in the German IBM patient registry. Self-developed items were used to assess the utilized healthcare resources and estimate the cost. The German Self-Administered Comorbidity Questionnaire (SCQ-D), the sIBM Physical Functioning Assessment (sIFA) and patient-reported measures for satisfaction and improvements in healthcare were applied for an explorative analysis. RESULTS: In total, 82 patients completed the survey. We estimated the mean total annual per capita COI of US$102,682 (95% CI US$82,763-US$123,090) in 2021. 92.7% of the total COI were direct costs. Medical costs were similar to nonmedical costs, with substantial costs for pharmacotherapy and informal care. Depending on the prevalence estimate, the total national COI per year were US$42.7 million-US$213.7 million. Significant differences in total COI were identified for the degree of disability, marital and employment status (p < 0.05). CONCLUSIONS: We identified remarkable and heterogenous cost in IBM. As informal care costs represented the most relevant cost driver, caregiver burden is a major factor in the patient journey. For the first time, comprehensive economic potentials were identified as a basis to improve the actual care situations and prioritizing future activities for research, pharmaceutical and digital product development as well as health politics.

The health-related quality of life, mental health and mental illnesses of patients with inclusion body myositis (IBM): results of a mixed methods systematic review.

BACKGROUND: Inclusion body myositis (IBM) is a rare neuromuscular disease (NMD) and effective therapies are not available. Thus, it is relevant to determine the health-related quality of life (HRQoL) in IBM patients including aspects of mental health and illnesses. OBJECTIVES: To identify and summarize the assessment of HRQoL, mental health and illnesses in IBM, the major factors that determine and influence them as well as the respective influence of IBM in general and compared to other NMD as a systematic review. METHODS: We performed a mixed methods systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was conducted within the databases PubMed, PsycINFO, LIVIVO and the Cochrane Database. Data were narratively summarized and categorized in the physical, psychological and social HRQoL dimensions. RESULTS: The systematic screening totalled 896 articles. Six studies were finally identified, comprising of 586 IBM patients. The applied patient reported outcome measures (PROMs) varied. Quantitatively, the main physical impairments (e.g. weakness, functioning, role perception) were assessed using the general population or other NMD as comparators. Results on social and psychological HRQoL were frequently inconsistent. Qualitatively, psychological and social limitations accompanied IBM related physical deteriorations. CONCLUSIONS: A research gap exists regarding rigour determinants of HRQoL and mental illness in IBM. In-depth qualitative studies could help to prepare the ground for the assessment of long-term HRQoL data combined with appropriately focussed psychological PROMs advancing the understanding of the HRQoL in IBM throughout the course of the disease from a patient perspective.

Health-related Quality of Life and Satisfaction with German Health Care Services in Patients with Charcot-Marie-Tooth Neuropathy.

BackgroundCharcot-Marie-Tooth (CMT) neuropathies entail a large group of diseases with different gene mutation patterns, which produce heterogeneous phenotypes. Although health-related quality of life (HRQOL) is significantly impaired, a comprehensive assessment of HRQOL in CMT patients in Germany considering phenotypical heterogeneity represented a research gap.ObjectiveThe aim was to assess HRQOL and the satisfaction with health care in CMT patients in Germany.MethodsCMT patients > 15 years with a genetically confirmed CMT subtype were recruited through a national CMT patient registry. HRQOL was assessed using the EQ-5D-5L questionnaire. Furthermore, subjective impairments in daily or work activities and satisfaction with health care were assessed using 4-point scales.ResultsHRQOL in CMT patients (n = 385) was impaired compared to the German population. Most patients reported problems in the dimension mobility (89.6%), pain/discomfort (89.4%) and usual activities (81.0%). Except for patients with hereditary neuropathy with liability to pressure palsy (HNPP), we found no differences in HRQOL between the CMT subtypes. 72.0%of CMT patients were satisfied with available health care services. However, patients reported to expect more CMT-specific knowledge and support as well as easier prescription and cost coverage procedures from health professionals and insurances.ConclusionsThe patient-reported outcomes in the assessed CMT cohort elucidate the need for more specific health care services that also address the heterogeneous phenotypes. Although the assessment has been limited to the German health services setting, insights may be applicable to CMT-specific care in other national settings.

Cost-Effectiveness Analysis of Direct-Acting Antiviral Agents for Occupational Hepatitis C Infections in Germany.

Around 1% of the world's population is infected with hepatitis C. The introduction of new direct-acting antiviral agents (DAAs) in 2014 has substantially improved hepatitis C treatment outcomes. Our objective was to evaluate the long-term cost effectiveness of DAAs in health care personnel (HP) with confirmed occupational diseases in Germany. A standardised database from a German statutory accident insurance was used to analyse the cost-effectiveness ratio for the DAA regimen in comparison with interferon-based triple therapies. Taking account of the clinical progression of the disease, a Markov model was applied to perform a base case analysis for a period of 20 years. The robustness of the results was determined using a univariate deterministic sensitivity analysis. The results show that treatment with DAAs is more expensive, but also more effective than triple therapies. The model also revealed that the loss of 3.23 life years can be averted per patient over the 20 years. Compared to triple therapies, DAA treatment leads to a higher sustained virologic response (SVR). Although this results in a decrease of costs in the long term, e.g., pension payments, DAA therapy will cause greater expense in the future due to the high costs of the drugs.

Cost of illness in Charcot-Marie-Tooth neuropathy: Results from Germany.

OBJECTIVE: To assess cost associated with the disease-specific need of patients diagnosed with Charcot-Marie-Tooth neuropathies (CMT) in Germany. METHODS: Patients with CMT were identified through the national patient registry and invited to complete a standardized questionnaire. The data collected include information about health care use, informal care, and other disease-related expenses as well as the working situation. Based on this information, we estimated the annual cost of CMT from the perspective of society. RESULTS: This study included 397 patients with a genetically confirmed CMT diagnosis. We estimated total annual cost of illness (COI) of $22,362 (95% CI $19,464-$25,723) per patient, of which 67.3% were direct costs. The highest single cost factor was informal care cost. For Germany, we extrapolated total cost of CMT of $735.0 million ($639.8 million-$845.5 million). Multivariate regression analysis showed that total annual cost increased with disease severity (Charcot-Marie-Tooth Neuropathy Score). Age, CMT subtype, comorbidities, body mass index, and employment status were also predictors of a change in cost (p < 0.05). Moreover, we found differences in total cost depending on marital status, subjectively evaluated impairments, dependence on other persons, care level, educational level, and disease duration. CONCLUSIONS: CMT is associated with a substantial economic burden. For the first time, the COI of CMT has been assessed and will serve as important input to decision-making in health policy, especially regarding research and development of therapies. Moreover, our results indicate the importance of the patient-reported perception of disease severity related to the consumption of resources.

Economic data for particle therapy: Dealing with different needs in a heterogeneous landscape.

BACKGROUND: In the light of scarce resources to be allocated for cancer care and a steady stream of costly innovations in all modalities applied to treat cancer, particle therapy needs to demonstrate its cost-utility balance to allow its positioning in the context of competing modalities. In the continuous evolving particle therapy landscape, the timely availability of appropriate economic data is crucial. METHODS: Economic data collection and compilation for particle therapy needs to follow health economic standards. Costing related analyses particularly need attention as clinical outcome data follow international standards to provide comparability. Among others, perspective, time horizons and cost categories are critical. RESULTS: In this report from the "Health Economics Work Package" of the European Particle Therapy Network, the approaches commonly applied in health economic assessments are described and tailored to the specific needs of particle therapy. Data collection for cost calculation, economic evaluation and budget impact analysis are discussed. CONCLUSION: The presented data are intended to serve as a guidance for economic data collection, bearing in mind that in each specific case, the heterogeneous requirements of national health systems will need to be considered and assessments adapted accordingly.

Disease burden of spinal muscular atrophy in Germany.

BACKGROUND: This study aimed at analyzing the economic burden and disease-specific health-related quality of life (HRQOL) of patients with spinal muscular atrophy (SMA) in Germany. SMA is a so far non-curable neuromuscular disease of the anterior nerve cells that causes high rates of morbidity and mortality. METHODS: In a cross-sectional study we analyzed the cost of illness (COI) and factors that influence the direct, indirect and informal care costs of affected patients and their families by using standardized, self-developed questionnaires. We used the PedsQL™(©) Measurement Model to analyze the disease-specific HRQOL of patients. RESULTS: One hundred eighty nine patients with SMA types I to III aged <1 to 73 years were enrolled. The average annual COI was estimated at €70,566 per patient in 2013. The highest cost resulted in SMA I with significant lower costs for the milder phenotypes. Inversely, the self-estimated HRQOL increased from SMA I to SMA III. Major cost drivers were informal care cost and indirect cost incurred by patients and their caregivers. CONCLUSIONS: Although SMA requires high standards of care, there has been a distinct lack of health services research on SMA. Accordingly, our results significantly contribute to a more comprehensive insight into the current burden of SMA and quality of life status as related to SMA health services in Germany. In the light of innovative therapeutic interventions, our results suggest a notable potential for a reduction in overall COI and improvement of HRQOL if the therapeutic intervention leads to a less severe course of the disease.

First outline and baseline data of a randomized, controlled multicenter trial to evaluate the health economic impact of home telemonitoring in chronic heart failure - CardioBBEAT.

BACKGROUND: Evidence that home telemonitoring for patients with chronic heart failure (CHF) offers clinical benefit over usual care is controversial as is evidence of a health economic advantage. METHODS: Between January 2010 and June 2013, patients with a confirmed diagnosis of CHF were enrolled and randomly assigned to 2 study groups comprising usual care with and without an interactive bi-directional remote monitoring system (Motiva®). The primary endpoint in CardioBBEAT is the Incremental Cost-Effectiveness Ratio (ICER) established by the groups' difference in total cost and in the combined clinical endpoint "days alive and not in hospital nor inpatient care per potential days in study" within the follow-up of 12 months. RESULTS: A total of 621 predominantly male patients were enrolled, whereof 302 patients were assigned to the intervention group and 319 to the control group. Ischemic cardiomyopathy was the leading cause of heart failure. Despite randomization, subjects of the control group were more often in NYHA functional class III-IV, and exhibited peripheral edema and renal dysfunction more often. Additionally, the control and intervention groups differed in heart rhythm disorders. No differences existed regarding risk factor profile, comorbidities, echocardiographic parameters, especially left ventricular and diastolic diameter and ejection fraction, as well as functional test results, medication and quality of life. While the observed baseline differences may well be a play of chance, they are of clinical relevance. Therefore, the statistical analysis plan was extended to include adjusted analyses with respect to the baseline imbalances. CONCLUSIONS: CardioBBEAT provides prospective outcome data on both, clinical and health economic impact of home telemonitoring in CHF. The study differs by the use of a high evidence level randomized controlled trial (RCT) design along with actual cost data obtained from health insurance companies. Its results are conducive to informed political and economic decision-making with regard to home telemonitoring solutions as an option for health care. Overall, it contributes to developing advanced health economic evaluation instruments to be deployed within the specific context of the German Health Care System. TRIAL REGISTRATION: ClinicalTrials.gov NCT02293252 ; date of registration: 10 November 2014.

Comparative cost of illness analysis and assessment of health care burden of Duchenne and Becker muscular dystrophies in Germany.

BACKGROUND: Our study aimed to determine the burden of illness in dystrophinopathy type Duchenne (DMD) and Becker (BMD), both leading to progressive disability, reduced working capacity and high health care utilization. METHODS: A micro-costing method was used to examine the direct, indirect and informal care costs measuring the economic burden of DMD in comparison to BMD on patients, relatives, payers and society in Germany and to determine the health care burden of these diseases. Standardized questionnaires were developed based on predefined structured interview guidelines to obtain data directly from patients and caregivers using the German dystrophinopathy patient registry. The health-related quality of life (HRQOL) was analyzed using PedsQL™ Measurement Model. RESULTS: In total, 363 patients with genetically confirmed dystrophinopathies were enrolled. Estimated annual disease burden including direct medical/non-medical, indirect and informal care costs of DMD added up to € 78,913 while total costs in BMD were € 39,060. Informal care costs, indirect costs caused by loss of productivity and absenteeism of patients and caregivers as well as medical costs of rehabilitation services and medical aids were identified as the most important cost drivers. Total costs notably increased with disease progression and were consistent with the clinical severity; however, patients' HRQOL declined with disease progression. CONCLUSION: In conclusion, early assessments of economic aspects and the disease burden are essential to gain extensive knowledge of a distinct disease and above all play an important role in funding drug development programs for rare diseases. Therefore, our results may help to accelerate payer negotiations such as the pricing and reimbursement of new therapies, and will hopefully contribute to facilitating the efficient translation of innovations from clinical research over marketing authorization to patient access to a causative treatment.