Concordance between patient- and physician-reported Myasthenia Gravis Activities of Daily Living (MG-ADL) scores.

INTRODUCTION/AIMS: Myasthenia gravis (MG) is a neuromuscular disease characterized by abnormal skeletal muscle fatiguability. The MG Activities of Daily Living (MG-ADL) scale assesses eight symptoms and is often used as primary endpoint in MG clinical trials where it is completed by neurologists. However, in observational studies, patients frequently complete the MG-ADL scale independently of their neurologist. In this study we aimed to assess the concordance between self- and physician-reported MG-ADL scores. METHODS: An international observational study was conducted among adult patients with MG scheduled for a routine visit or who entered the hospital via emergency services. Consenting patients and physicians completed the MG-ADL. Concordance between assessments was calculated using Gwet's agreement coefficient (Gwet's AC) for the MG-ADL individual items and the intraclass correlation coefficient (ICC) for the MG-ADL total score. RESULTS: Data were collected from 137 patients (63% female; mean age, 57.7 years). Physicians assessed the patient's symptoms as slightly more severe (8.1 vs 7.5 MG-ADL total score, respectively), corresponding to a difference of 0.6 on a range from 0 to 24. The ICC for the MG-ADL total score between the patient and the physician assessment was 0.94 (95% confidence interval, 0.89 to 0.95), showing excellent concordance. Gwet's AC showed substantial to almost perfect agreement for all items, except eyelid droop, for which the agreement was moderate. DISCUSSION: Our results demonstrate that patients and neurologists have a concordant assessment of the patient's MG symptoms when using the MG-ADL scale. This evidence supports patient self-administration of the MG-ADL in clinical practice and research.

Association Between Myasthenia Gravis-Activities of Daily Living (MG-ADL) and EQ-5D-5L Utility Values: The Additional Effect of Efgartigimod on Utilities.

INTRODUCTION: For patients with generalized myasthenia gravis (gMG), the association between symptom severity, often measured with the Myasthenia Gravis Activities of Daily Living (MG-ADL) instrument, and utility values is unknown. METHODS: Data was analyzed from the phase 3 ADAPT trial, which included adult patients with gMG randomly assigned to treatment with efgartigimod + conventional therapy (EFG + CT) or placebo + CT (PBO + CT). MG-ADL total symptom scores and the EQ-5D-5L, a measure of health-related quality of life (HRQoL), were collected biweekly up to 26 weeks. Utility values were derived from the EQ-5D-5L data with the United Kingdom value set. Descriptive statistics were reported for MG-ADL and EQ-5D-5L at baseline and follow-up. A normal identity-link regression model estimated the association between utility and the eight MG-ADL items. A generalized estimating equations (GEE) model was estimated to predict utility based on the patient's MG-ADL score and treatment received. RESULTS: A total of 167 patients (84 EFG + CT, 83 PBO + CT) contributed 167 baseline and 2867 follow-up measurements of MG-ADL and EQ-5D-5L. EFG + CT-treated patients experienced more improvements than PBO + CT-treated patients in most MG-ADL items and EQ-5D-5L dimensions, with the largest improvements observed in chewing, brushing teeth/combing hair, eyelid droop (MG-ADL); self-care, usual activities, mobility (EQ-5D-5L). The regression model indicated that individual MG-ADL items contributed differently to utility values, with the largest impact from brushing teeth/combing hair, rising from a chair, chewing, and breathing. The GEE model showed that each unit improvement in MG-ADL led to a statistically significant utility increase of 0.0233 (p < 0.001). In addition, a statistically significant improvement of 0.0598 (p = 0.0079) in utility was found for patients in the EFG + CT group compared to the PBO + CT group. CONCLUSION: Among patients with gMG, improvements in MG-ADL were significantly associated with higher utility values. MG-ADL scores alone were not sufficient to capture the utility gained from efgartigimod therapy.

Patient-reported burden of myasthenia gravis: baseline results of the international prospective, observational, longitudinal real-world digital study MyRealWorld-MG.

OBJECTIVES: Myasthenia gravis (MG) is a rare, chronic, autoimmune neuromuscular disease which can affect functional and mental aspects of health and health-related quality of life (HRQoL). This study aims to obtain detailed knowledge of the impact of MG on HRQoL in a broad population from the perspective of the patient. DESIGN: Prospective, observational, digital, longitudinal real-world study. SETTING: Adult patients with MG from seven countries (USA, Japan, Germany, UK, Italy, Spain and Canada) downloaded a mobile application onto their phones and entered data about themselves and their MG. OUTCOME MEASURES: Data was collected using the following general and disease-specific patient-reported outcome measurements: EuroQol 5 Domains Health-Related Quality of Life Questionnaire (EQ-5D-5L), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r), Hospital Anxiety and Depression Scale (HADS) and Health Utilities Index III (HUI3). Patients were categorised by their self-assessed Myasthenia Gravis Foundation of America (MGFA) class (I-V). RESULTS: Baseline results of 841 participants (mean age 47 years, 70% women) are reported . The distribution across the MGFA classes was: 13.9%, 31.0%, 38.1%, 15.5% and 1.6% for classes I-V. The MGFA class was a strong predictor of all aspects of HRQoL, measured with disease-specific and with generic instruments. The domains in which patients with MG most frequently mentioned problems were usual activities, anxiety and depression, tiredness, breathing and vision. The mean total MG-ADL Score was positively associated with increasing MGFA classes: 2.7, 4.4, 6.3 and 8.4 for MGFA classes I-IV. Mean baseline EQ-5D-5L utility was also associated with MGFA classes and was 0.817, 0.766, 0.648 and 0.530 for MGFA class I-IV. CONCLUSIONS: MG has a large impact on key aspects of health and HRQoL. The impact of this disease increases substantially with increasing disease severity.

An EQ-5D-Y-3L Value Set for Belgium.

BACKGROUND: In Belgium, a value set for children and adolescents for a generic health-related quality-of-life measure is not available. To inform drug pricing and make resource allocation decisions for children and adolescents, national tax-payers' preferences for youth health states should be known. OBJECTIVE: We aimed to obtain a value set for EQ-5D-Y-3L in Belgium, following the international youth valuation protocol for data collection. METHODS: Composite Time Trade-Off interviews were conducted in a sample of 200 adults, either face to face or via video conferencing. Another sample of 1000 adults completed an online discrete choice experiment survey. All adults were asked to take the perspective of a 10-year-old child for both methods. Both samples were representative for Belgium in terms of age, sex and region. A latent class analysis was selected to obtain the relative importance of the five dimensions and their levels based on the discrete choice experiment data, which were anchored with the composite Time Trade-Off censored value for the worst health state (33333). RESULTS: Preferences from Belgian adults revealed a mean censored value for 33333 for children and adolescents of - 0.475. All the estimated coefficients of the model with 4 latent classes were statistically significant and showed higher disutility as severity levels increase. The most important health dimension was pain/discomfort, followed by feeling sad/worried/unhappy. CONCLUSIONS: This study presents the Belgian EQ-5D-Y-3L value set, which will be included in the Belgian pharmacoeconomic guidelines. The value set enables the calculation of quality-adjusted life-years in children and adolescents, allowing a cost-effectiveness evaluation of health technologies and their youth-specific price setting.

Exploration of the Reasons Why Health State Valuation Differs for Children Compared With Adults: A Mixed Methods Approach.

OBJECTIVES: Evidence comparing utilities for adults and children consistently report higher utility values for child health states. This study investigates the reasons why child health states are valued differently. METHODS: A total of 80 respondents (United Kingdom, Belgium, The Netherlands) participated in 1.5-hour face-to-face interviews. Respondents valued 4 health states from 2 perspectives (8-year-old child, 40-year-old adult) using visual analog scale and time trade-off. A total of 32 respondents participated in think-aloud interviews. Audio recordings were analyzed by 2 independent coders using NVIVO software. Statements, nodes, and themes were reviewed cyclically until consensus was reached. RESULTS: Qualitative results: a total of 5 themes were identified in the data regarding child and adult valuation-intergenerational responsibility and dependency (childhood is crucial for forming life skills based on new experiences; adulthood is an important time to take care of the family), staying alive is important (life is worth living even with impaired health-related quality of life (HRQoL), for children and adults), awareness of poor HRQoL and ability to make decisions (children have difficulties comprehending poor HRQoL and their parents make their healthcare decision; adults can assess their own HRQoL and decide for themselves), coping ability (children are flexible and resilient; adults have experience with dealing with difficulties), and practical organization of care (children are cared for by their parents; adults are able to organize and pay for care). Mixed methods: comparing qualitative statements with respondents' higher utilities for child health states confirmed concordance between results. CONCLUSIONS: Quality-adjusted life-years are interpreted differently for children and adults. Child-specific value sets are needed to reflect society's preferences and to adequately conduct health technology assessment of pediatric treatments.

Exploring the Comparability of Face-to-Face Versus Video Conference-Based Composite Time Trade-Off Interviews: Insights from EQ-5D-Y-3L Valuation Studies in Belgium and Spain.

BACKGROUND: Face-to-face interviews are recommended for the collection of composite time trade-off (cTTO) data. The coronavirus disease 2019 (COVID-19) social distancing measures made researchers consider videoconferencing interviews as an alternative mode of administration, but little evidence about the implementation of videoconferencing in valuation studies is available. This study provides insights into the effect of videoconferencing on the quality of data, evaluating interviewers' and respondents' engagement level in videoconferences compared with face-to-face interviews. METHODS: We used cTTO data collected in Belgium and Spain following the EQ-5D-Y-3L valuation protocol. Due to the COVID-19 pandemic, both projects interrupted the face-to-face data collection before reaching the target sample. The remaining interviews were conducted by videoconference. We compared both modes of administration in terms of interviewers' engagement (task duration and number of moves in each example) and respondents' engagement (task duration and proportions of specific response values, in half-year units). To minimise interviewers' learning effects, we split our sample into three groups: (1) first 20 interviews conducted face-to-face; (2) subsequent interviews conducted face-to-face; and (3) videoconferencing interviews. RESULTS: The comparison between videoconferencing and subsequent face-to-face interviews showed the interviewer's engagement was not affected by the mode of administration as almost no significant results were found either in the task duration or the numbers of moves shown in the examples. Similarly, none of the respondents' task duration or proportion of specific responses or half-year units were affected by the mode of administration in either of the two countries. CONCLUSIONS: No evidence suggested that the quality of cTTO data is reduced when using videoconferencing compared with face-to-face interviews.

Thrombectomy is a cost-saving procedure up to 24 h after onset.

INTRODUCTION AND AIM: The treatment of ischemic stroke due to large-vessel occlusion has been revolutionized by mechanical thrombectomy (MT), as multiple trials have consistently shown improved functional outcomes compared to standard medical management both in the early and late time windows after symptom onset. However, MT is an interventional procedure that is more costly than best supportive care (BSC). METHODS: We set out to study the cost-utility and budget impact of MT + BSC versus BSC alone for large-vessel occlusion using a combined decision tree and Markov model. The analysis was conducted from a Belgian payer perspective over a lifetime horizon, and health states were defined by the modified Rankin Scale (mRS). The treatment effect of MT + BSC combined clinical outcomes from all published early and late treatment window studies showing improved mRS after 90 days. Resource use and utilities were informed by an observational Belgian study of 569 stroke patients. Long-term mRS transitions were sourced from the Oxford Vascular study. RESULTS: MT + BSC generated 1.31 additional quality-adjusted life years and resulted in cost savings of €10,216 per patient over lifetime. Deterministic sensitivity analyses demonstrated dominance of MT over a wide range of parameter inputs. In a Belgian setting, adding MT to BSC within an early time window for 1575 eligible stroke patients every year produced cost savings between €6.3 million (year 1) and €14.6 million (year 5), or a total cost saving of €56.2 million over 5 years. CONCLUSION: Mechanical thrombectomy is a highly cost-effective treatment for ischemic stroke patients, providing quality-adjusted survival at lower health care cost, both when given in an early time window, as well as in a late time window.

Patient-reportedimpact of myasthenia gravis in the real world: protocol for a digital observational study (MyRealWorld MG).

INTRODUCTION: Myasthenia gravis (MG) is a rare, chronic, autoimmune disease, mediated by immunoglobulin G antibodies, which causes debilitating muscle weakness. As with most rare diseases, there is little patient-reported data with which to understand and address patient needs. This study explores the impact of MG in the real world from the patient perspective. METHODS AND ANALYSIS: This is a 2-year prospective, observational, digital, longitudinal study of adults with MG, resident in the following countries: the USA, Japan, Germany, France, the UK, Italy, Spain, Canada and Belgium. The planned sample size is 2000. Recruitment will be community based, via patient advocacy groups, social media and word of mouth. Participants will use a smartphone application (app) to check eligibility, provide consent and contribute data. Planned data entry is as follows: (1) personal profile on enrollment-covering demographics, MG characteristics and previous care; (2) monthly event tracker-current treatments, healthcare visits, treatment-related adverse events, productivity losses; (3) monthly selection of validated generic and disease-specific patient-reported outcomes instruments: EQ-5D-5L, Myasthenia Gravis Activities of Daily Living, Myasthenia Gravis Quality of Life 15-item revised scale, Hospital Anxiety and Depression Scale and Health Utilities Index III. Analyses are planned for when the study has been running in most countries for approximately 6, 12, 18 and 24 months. ETHICS AND DISSEMINATION: The study protocol has been reviewed and granted ethics approval by Salus IRB for participants resident in the following countries: Germany, the UK and the US. Local ethics approval is being sought for the following study countries: Belgium, Canada, France, Italy, Japan and Spain. Study results will be communicated to the public and participants via conference presentations and journal publications, as well as regular email, social media and in-application communication. TRIAL REGISTRATION NUMBER: NCT04176211.

Estimating health state utilities in hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocyti.c lymphohistiocytosis (HLH) is a rare and severe disorder characterized by abnormal activation of the immune system. Primary HLH causes prolonged fever, spleen and liver enlargement, and organ dysfunction, usually in infancy and early childhood and is fatal if left untreated. As effective treatment options emerge, such as emapalumab-lzsg, Health Technology Assessment bodies around the world will assess them in terms of cost-effectiveness. This study was designed to estimate quality of life weights (utilities) for such analyses. METHODS: Vignettes were developed describing HLH treatment related health states. Health states included active HLH, HLH plus neurological symptoms, receiving chemotherapy, undergoing stem cell transplant (SCT), graft versus host disease (GVHD), cure and end of life care. The vignettes were based on information from in depth interviews with clinical specialists; and qualitative research with four parents of children with primary HLH aged between 1 and 18 years old. The vignettes were then assessed in time trade off (TTO) interviews with members of the UK general public in one on one face to face interviews with trained, experienced interviewers. Preference data were analysed using the generalised estimating equations framework. RESULTS: Detailed qualitative data captured the substantial burden of this disease for young children. One hundred participants completed the TTO interviews. The utility score for Active HLH was estimated as 0.32 (95% CI, 0.24 to 0.39). Values for other states were HLH plus neurological symptoms (0.27, 95%CI 0.18-0.35), receiving chemotherapy (0.26, 95%CI 0.17-0.34), undergoing SCT (0.18, 95%CI 0.07-0.28), GVHD (0.07, 95%CI -0.04-0.17), cure (0.72, 95%CI 0.67-0.77) and end of life care (- 0.17, 95%CI -0.27- -0.07). CONCLUSIONS: This study has estimated utility weights for seven different HLH related states which are based on detailed input from carers and physicians and have good face validity. There are few other options for collecting these data in an ultra-rare setting.

Evaluation of the cost-effectiveness of dexrazoxane for the prevention of anthracycline-related cardiotoxicity in children with sarcoma and haematologic malignancies: a European perspective.

BACKGROUND: Anthracycline-treated childhood cancer survivors are at higher risk of cardiotoxicity, especially with cumulative doses received above 250 mg/m2. Dexrazoxane is the only option recommended for cardiotoxicity prevention in high-risk patients supported by randomised trials but its cost-effectiveness in paediatric cancer patients has not been established. METHODS: A cost-effectiveness model applicable to different national healthcare system perspectives, which simulates 10,000 patients with either sarcoma or haematologic malignancies, based upon baseline characteristics including gender, age at diagnosis, cumulative anthracycline dose and exposure to chest irradiation. Risk equations for developing congestive heart failure and death from recurrence of the original cancer, secondary malignant neoplasms, cardiac death, pulmonary death, and death from other causes were derived from published literature. These are applied to the individual simulated patients and time until development of these events was determined. The treatment effect of dexrazoxane on the risk of CHF or death was based upon a meta-analysis of randomised and non-randomised dexrazoxane studies in each tumour type. The model includes country specific data for drug and administration costs, all aspects of heart failure diagnosis and management, and death due to different causes for each of the five countries considered; France, Germany, the UK, Italy, and Spain. RESULTS: Dexrazoxane treatment resulted in a mean QALY benefit across the five countries ranging from 0.530 to 0.683 per dexrazoxane-treated patient. Dexrazoxane was cost-effective for paediatric patients receiving anthracycline treatment for sarcoma and for haematologic malignancies, irrespective of the cumulative anthracycline dose received. The Incremental Cost Effectiveness Ratio (ICER) was favourable in all countries irrespective of anthracycline dose for both sarcoma and haematological malignancies (range: dominant to €2196). Individual ICER varied considerably according to country with dominance demonstrated for dexrazoxane in Spain and Italy and ratios approximately double the European average in the UK and Germany. CONCLUSIONS: Dexrazoxane is a highly cost-effective therapy for the prevention of anthracycline cardiotoxicity in paediatric patients with sarcoma or haematological malignancies in Europe, irrespective of the healthcare system in which they receive treatment. These benefits persist when patients who receive doses of anthracycline > 250 mg/m2 are included in the model.

The relationship between Home-time, quality of life and costs after ischemic stroke: the impact of the need for mobility aids, home and car modifications on Home-time.

Purpose: Home-time (the number of days spent at home during the first 3 months after stroke) shows a strong association with the modified Rankin scale (mRS). We studied whether Home-time was also a determinant of quality-of-life and medical care costs after ischemic stroke, and assessed factors delaying discharge home.Materials and methods: Five hundred and sixty nine patients participated in a retrospective study when returning for an in-person visit after an ischemic stroke. Home-time, mRS, EQ-5D-3L, inpatient and outpatient resource utilization, use of mobility aids, changes to home and car, comorbidities were recorded.Results: Each additional Home-time day was significantly associated with an increase in utility of 0.0056 (p < 0.0001) and an in- and outpatient cost saving of $99 (p = 0.0158). Requiring extra material support significantly decreased Home-time by 76 days (including: requiring home changes: -68 days, car alterations: -49 days, needing a wheelchair: -80 days or walker: -71 days, needing bed or bath rails: -79 days). This univariable effect was confirmed in multivariable analysis when comparing with patients having the same disability level without requiring material support.Conclusions: Home-time is a stroke outcome associated with disease severity, healthcare costs and patient wellbeing. Streamlining the discharge process for those requiring extra material support may lead to cost savings and higher quality-of-life.Implications for rehabilitationDelays in discharge from the acute hospital or rehabilitation facility are incurred when patients need extra material support in order to return home.Staff from the discharging facility should assist families by giving timely information on the availability and the cost of wheel chairs and walkers; and explaining and planning the need of a stair lift, bed and bath rails as well as car modifications.Planning the discharge process with the families will lead to a more rapid return home and will result in reduced overall health care costs and higher quality of life for the patients.

The combined impact of dependency on caregivers, disability, and coping strategy on quality of life after ischemic stroke.

BACKGROUND: To estimate the additional impact of coping and of being dependent on caregivers, over and above the large effects of disability on utility after ischemic stroke. METHODS: A total of 539 patients were recruited into an observational, retrospective study when returning for a check-up between 3 and 36 months after an ischemic stroke. Patients' modified Rankin Scale (mRS), dependency on caregivers, the Brandtstädter and Renner Coping questionnaire (with summary scores: Tenacity of Goal Pursuit (TGP) and Flexible Goal Adjustment (FGA) coping styles), EQ-5D-3 L and co-morbidities were evaluated. RESULTS: In multivariable regression, greater disability (mRS) resulted in large utility losses, between 0.06 for mRS 1 to 0.65 for mRS 5 (p < 0.0001). Dependency on caregivers caused an additional dis-utility of 0.104 (p = 0.0006) which varied by mRS (0.044, 0.060, 0.083, 0.115, 0.150 and 0.173 for mRS 0-5). The effect of coping on utility varied by coping style, by the disability level of the patient and by his or her dependency on caregivers. FGA coping was associated with additional increases in utility (p < 0.0001) over and above the effect of disability and dependency, whereas TGA had no significant impact. FGA coping was associated with larger utility changes among more disabled patients (0.018 to 0.105 additional utility, for mRS 0 to mRS 5 respectively). Dependent patients had more to gain from FGA coping than patients who function independently of caregivers: utility gains were between 0.049 and 0.072 for moderate to high levels of FGA coping. In contrast, the same positive evolution in FGA coping resulted in 0.039 and 0.057 utility gain among independent patients. Finally, we found that important stroke risk factors and co-morbidities, such as diabetes and atrial fibrillation, were not predictors of EQ-5D utility in a multivariable setting. CONCLUSIONS: This study suggests that treatment strategies targeting flexible coping styles and decreasing dependency on caregivers may lead to significant gains in quality of life above and beyond treatment strategies that solely target disability.

Hospital financing of ischaemic stroke: determinants of funding and usefulness of DRG subcategories based on severity of illness.

BACKGROUND: Several Western and Arab countries, as well as over 30 States in the US are using the "All-Patient Refined Diagnosis-Related Groups" (APR-DRGs) with four severity-of-illness (SOI) subcategories as a model for hospital funding. The aim of this study is to verify whether this is an adequate model for funding stroke hospital admissions, and to explore which risk factors and complications may influence the amount of funding. METHODS: A bottom-up analysis of 2496 ischaemic stroke admissions in Belgium compares detailed in-hospital resource use (including length of stay, imaging, lab tests, visits and drugs) per SOI category and calculates total hospitalisation costs. A second analysis examines the relationship between the type and location of the index stroke, medical risk factors, patient characteristics, comorbidities and in-hospital complications on the one hand, and the funding level received by the hospital on the other hand. This dataset included 2513 hospitalisations reporting on 35,195 secondary diagnosis codes, all medically coded with the International Classification of Disease (ICD-9). RESULTS: Total costs per admission increased by SOI (€3710-€16,735), with severe patients costing proportionally more in bed days (86%), and milder patients costing more in medical imaging (24%). In all resource categories (bed days, medications, visits and imaging and laboratory tests), the absolute utilisation rate was higher among severe patients, but also showed more variability. SOI 1-2 was associated with vague, non-specific stroke-related ICD-9 codes as primary diagnosis (71-81% of hospitalisations). 24% hospitalisations had, in addition to the primary diagnosis, other stroke-related codes as secondary diagnoses. Presence of lung infections, intracranial bleeding, severe kidney disease, and do-not-resuscitate status were each associated with extreme SOI (p < 0.0001). CONCLUSIONS: APR-DRG with SOI subclassification is a useful funding model as it clusters stroke patients in homogenous groups in terms of resource use. The data on medical care utilisation can be used with unit costs from other countries with similar healthcare set-ups to 1) assess stroke-related hospital funding versus actual costs; 2) inform economic models on stroke prevention and treatment. The data on diagnosis codes can be used to 3) understand which factors influence hospital funding; 4) raise awareness about medical coding practices.

What Impact Does Venous Thromboembolism and Bleeding Have on Cancer Patients' Quality of Life?

BACKGROUND: Venous thromboembolism (VTE) is common in cancer patients and its treatment is associated with a high risk of recurrent VTE (rVTE) and bleeding. OBJECTIVES: To analyze data from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) trial to describe the impact of rVTE and bleeding events on health-related quality of life. METHODS: The three-level EuroQol five-dimensional questionnaire (EQ-5D) data were collected monthly for up to 7 months in patients starting anticoagulation for newly diagnosed VTE. Analyses were designed to describe the impact of rVTE and bleeding on EQ-5D scores while controlling for effects of covariates such as background and clinical variables and longitudinal changes. A repeated-measures model with specification of the variance-covariance matrix to characterize the intrapatient correlation was used to estimate the utility values. The impact of an rVTE or a bleeding event was assumed to be reflected in the utility value when it occurred within 2 weeks from a planned data collection point. RESULTS: Data were available from 883 patients. A total of 76 rVTE and 159 bleeding events occurred during follow-up. rVTE had a significant impact on EQ-5D scores, with a decrement of -0.075 on the basis of our reference case (male, no metastasis, Eastern Cooperative Oncology Group score = 1, Western European), but different patients might have different decrements. Bleeding events had a smaller (nonstatistically significant) impact on EQ-5D scores. CONCLUSIONS: This data set study has quantified the decline in EQ-5D scores associated with experiencing rVTE or bleeding events in cancer patients. These results indicate the net gain in quality of life and impact on cost-effectiveness of secondary VTE prevention.

Modified Rankin scale as a determinant of direct medical costs after stroke.

Background Resource use in the acute and subacute phases after stroke depends on the degree of disability. Aims To determine if direct costs after stroke also vary by level of disability as measured using the modified Rankin scale at the chronic stage after stroke. Methods In a multicentre study, we collected acute and chronic in- and outpatient resource use in survivors of ischemic stroke stratified by levels of disability according to the modified Rankin Scale. Statistical inference on costs at each level of the modified Rankin Scale was estimated using a general linear model for the first three months, the first year, and any subsequent year after ischemic stroke. Results A total of 569 survivors of ischemic stroke with a mean age of 71.7 years were enrolled (41% female) from 10 academic and nonacademic centers. Costs varied substantially over time and with each modified Rankin Scale level. The total average costs in the first year were estimated $33,147 per patient, ranging from $9,114 for modified Rankin Scale 0 to $83,236 for modified Rankin Scale 5. In the second year, medical costs were on average $14,039, varying from $2,921 to $39,723 for patients with modified Rankin Scale 0-5. The level of disability based on the modified Rankin Scale was a major determinant of resource use, irrespective of age, gender, atrial fibrillation, and vascular risk factors. Conclusion Long-term resource use after stroke is high and is mainly driven by degree of disability as measured by the modified Rankin scale.

Health state utilities in non-small cell lung cancer: An international study.

AIM: Quality of life weights (utilities) are an important input in economic evaluation and evidence suggests that there can be important differences between countries. This study was designed to capture utilities for metastatic non-small cell lung cancer and common grade III/IV toxicities associated with treatment from local populations in the United Kingdom, Australia, France, China, Taiwan, and Korea. Toxicities included neutropenia, febrile neutropenia, fatigue, diarrhea, nausea and vomiting, rash, bleeding, hypertension, and hair loss. METHODS: Existing health state descriptions of non-small cell lung cancer were adapted to represent descriptions of patients on first-line treatment. Twenty-three states were translated and assessed in cognitive debrief content validation interviews with oncologists in each country. Seventy-five respondents per country completed a time trade-off interview to evaluate the states. Variation between countries for all states was explored with a Generalized Estimating Equations model. RESULTS: The mean utility for "stable disease and no side effects" (base state) varied between 0.84 (United Kingdom) and 0.54 (Taiwan). The largest utility decrements were found for febrile neutropenia (0.47) and neutropenia (0.35) across all countries. Asian countries regarded bleeds as a severe toxicity whereas non-Asian countries did not and valued diarrhea and fatigue as more severe. Significant differences in utilities between countries emerged with the Taiwanese population in particular rating states as significantly worse than other countries. CONCLUSION: This study improves our understanding of how utilities for the same states can vary across countries. The study shows the importance of capturing utilities that reflect the preferences of the local population.

Bendamustine-rituximab: a cost-utility analysis in first-line treatment of indolent non-Hodgkin's lymphoma in England and Wales.

OBJECTIVE: To evaluate the cost-effectiveness of bendamustine-rituximab (B-R) compared with CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and CVP-R (cyclophosphamide, vincristine, prednisone, rituximab) as first-line treatment for patients with advanced indolent non-Hodgkin's lymphoma (NHL). METHODS: A patient-level simulation was adapted from the model used by the University of Sheffield School of Health and Related Research (ScHARR) in a health technology appraisal of rituximab for first-line treatment of follicular lymphoma. This approach allowed modelling of the complex treatment pathways in indolent NHL. Data from a Phase 3 randomized, open-label trial were used to compare B-R with CHOP-R. The relative efficacy of CHOP-R and CVP-R was estimated using an indirect treatment comparison similar to the original ScHARR approach. The analysis was conducted from the perspective of the National Health Service in England and Wales, using a lifetime time horizon. A number of one-way sensitivity and scenario analyses were conducted, including one using recently published data comparing CVP-R with CHOP-R. RESULTS: The deterministic incremental cost-effectiveness ratio (ICER) was £5249 per quality adjusted life year (QALY) for B-R vs CHOP-R, and £8092 per QALY for B-R vs CVP-R. The alternative scenario using direct data comparing CVP-R with CHOP-R approximately halved the ICER for B-R vs CVP-R to £4733. Owing to its better toxicity profile, B-R reduced the cost of treating adverse events by over £1000 per patient vs CHOP-R. LIMITATIONS: The main limitations were: immaturity of overall survival data from the Phase 3 trial; reliance on quality-of-life data from previous health technology appraisals (as this was not collected in the trial); and a lack of direct evidence or a network of connected evidence comparing B-R with CVP-R. CONCLUSIONS: The ICERs for B-R vs CHOP-R and CVP-R were considerably below the thresholds normally regarded as cost-effective in England and Wales (£20,000-30,000 per QALY).

Investigating incoherence gives insight: clopidogrel is equivalent to extended-release dipyridamole plus aspirin in secondary stroke prevention.

OBJECTIVE: To identify confounding factors that may explain the incoherence between direct and indirect evidence in a published analysis comparing extended-release dipyridamole (ERDP) plus aspirin to clopidogrel for the reduction of stroke. STUDY DESIGN AND SETTING: An existing analysis was updated with new studies from a systematic literature review. Clinicians reviewed the studies for potential confounders. Network meta-analyses were conducted including or excluding potential confounders, and were estimated based on direct, indirect, or a combination of direct and indirect evidence. Model fit was compared using the residual deviance and the deviance information criterion (DIC); node splitting was used to test for incoherence between the networks. RESULTS: Six trials and one meta-analysis were identified; aspirin dosage was identified as a potential confounder. The odds ratio (OR) for stroke of aspirin plus ERDP vs. clopidogrel based on indirect evidence without aspirin dosage adjustment is 0.85 (0.68-1.05); when accounting for the aspirin dose-response relationship it is 0.96 (0.73-1.25); and the direct evidence based on PRoFESS resulted in an OR of 1.02 (0.93-1.12). CONCLUSION: When analyzing networks of evidence, attention should be paid to identifying and adjusting for potentially confounding factors. Investigating rather than ignoring inconsistency in the data set leads to clearer insight into relative efficacy.

Cost-effectiveness of adjunctive eptifibatide in patients undergoing coronary stenting in Germany.

OBJECTIVE: To determine the cost-effectiveness of adding eptifibatide to the standard treatment for selected high-risk patients undergoing coronary stenting in Germany. Furthermore, to investigate the impact of several extrapolation methods on the results. METHODS: A Markov model was developed to reflect the clinical events in this specific patient population, including target vessel revascularization, myocardial infarction, and death. To extrapolate clinical data beyond 1 year, a linear, an exponential, and a Weibull survival curves were estimated. Patient characteristics and transition probabilities were derived from a high-risk subgroup of the ESPRIT trial; patient-level utility data came from a published Dutch study. Costs were calculated from a hospital and from a third-party payer perspective. RESULTS: For both perspectives, the additional treatment with eptifibatide is the considered dominant alternative. The incremental net benefit of its use exceeds €10,000 for both perspectives. Results proved stable in probabilistic sensitivity analysis as well as under the different extrapolation scenarios. CONCLUSIONS: Eptifibatide is likely to be dominant strategy with 77.7 and 96.7% of the simulations leading to QALYs gained and generating cost savings from both the hospital and the third-party payer perspective. Eptifibatide offsets its additional treatment costs by avoiding costly repeat procedures and leads to positive QALY gains by preventing cardiovascular events lending themselves to transient or permanent lower quality of life. The method used to extrapolate the short-term risks did not impact on results, mainly due to similar clinical risk profiles between the two treatment groups in the long term.

Patient preferences for first-line oral treatment for mild-to-moderate ulcerative colitis: a discrete-choice experiment.

BACKGROUND: Patients with ulcerative colitis (UC) frequently require long-term therapy to prevent relapse. Treatments such as 5-aminosalicylic acid (5-ASA [mesalazine]) are efficacious and well tolerated, but adherence to treatment is often poor. OBJECTIVE: This discrete-choice experiment (DCE) was conducted to estimate differences in patient preferences for 5-ASA treatment in mild-to-moderate UC based on levels of self-reported adherence. Inclusion of patients residing in the US, UK, Germany, and Canada allowed for assessment of possible cultural differences in patient preferences. METHODS: DCE attributes were determined through literature review, clinician consultation, and patient interviews. Six treatment attributes were identified: ease of swallowing, time of day, quantity, extent of flare resolution, likelihood of flare occurrence, and cost. A total of 400 patients in four countries completed the DCE and adherence (Modified Morisky Scale) surveys. Data were analyzed using generalized estimating equations to estimate patient preference and willingness to pay (WTP) by levels of self-reported adherence and country of residence. RESULTS: All attributes had expected polarity and were significant predictors of patient preference. Self-reported 'good' versus 'poor' adherers significantly preferred symptom control (p = 0.0108) and mucosal healing (p = 0.0190) attributes. All patients stated preference for symptom control/mucosal healing and flare risk attributes; the latter attribute was significantly preferred across all countries. Country differences in patient preference for convenience versus clinical attributes were found. Overall, patients were willing to pay £29.24 ($US46.27) per month for symptom control and mucosal healing, and an additional £78.81 ($US124.70) per month for reduction in flare risk to 10% per year (WTP costs were equalized between each country using the published 2008 purchasing power parity). Those with flares in the past year significantly preferred avoiding future flares (p < 0.0001) versus other attributes, as well as lower risk of flares (10%, likelihood ratio: 0.64-0.70). CONCLUSIONS: Findings indicate that self-reported adherers to UC therapy have a stronger preference for clinical benefits over other treatment attributes, suggesting that positive patient assessment of effectiveness may influence adherence. Ongoing clinician assessment of patient preferences for treatment attributes, as well as education on the importance of adherence, may help improve treatment outcomes in UC.