Understanding the effects on HR-QoL of treatment for overactive bladder: a detailed analysis of EQ-5D clinical trial data for mirabegron

Abstract

Background:

Analysis of EQ-5D data often focuses on changes in utility, ignoring valuable information from other parts of the instrument. The objective was to explore how the utility index, EQ-5D profile, and EQ-VAS captured change in clinical trials of mirabegron, a new treatment for overactive bladder (OAB).

Data:

Data were pooled from three phase III clinical trials that investigated the efficacy and safety of mirabegron vs placebo. Tolterodine ER 4?mg was included as an active control in one study: (1) placebo, mirabegron 50?mg and 100?mg, and tolterodine 4?mg ER; (2) placebo, mirabegron 50?mg and 100?mg; (3) placebo, and mirabegron 25?mg and 50?mg. Data were collected at baseline, week 4, 8, and 12.

Methods:

Analyses were performed on full analysis and modified intention to treat (ITT) data sets using UK utilities. Analysis controlled for relevant patient characteristics. Analysis of Covariance identified changes from baseline at each time point in utilities and EQ-VAS. Areas Under the Curve were estimated to summarize inter-temporal differences in effect. EQ-5D profile data were analysed using the Paretian Classification of Health Change.

Results:

In modified ITT analyses, mirabegron 50?mg was superior to tolterodine 4?mg in changes from baseline utilities after 12 weeks (p?<?0.05); similarly, AUC results showed mirabegron 50?mg to be superior to tolterodine (p?<?0.05) and placebo (p?<?0.05) with the benefit already apparent at 4 weeks (p?<?0.05). EQ-VAS more consistently indicated superior outcomes: all three mirabegron doses showed statistically significant greater effectiveness compared to tolterodine at 12 weeks. Individual EQ-5D dimensions and the overall profile showed no significant differences between study arms.

Conclusion:

Mirabegron showed quicker and superior improvement in HR-QoL compared to tolterodine 4?mg ER. A limitation of the study is that EQ-5D was a secondary outcome in the pivotal trials, which were not powered to measure differences on EQ-5D.     

Mapping EORTC-QLQ-C30 to EQ-5D-3L in patients with colorectal cancer

Aims: The primary aim of this study was to perform a mapping of the EORTC-QLQ-C30 scores to EQ-5D-3L for the SIRFLOX study; a large dataset of patients with previously untreated liver-only or liver-dominant metastatic colorectal cancer (mCRC). A secondary aim was to compare the predictive validity of existing mappings from EORTC-QLQ-C30 to EQ-5D-3L conducted in other cancers.

Methods and materials: Questionnaires (completed within 529 patients) were used in a linear mixed regression to model EQ-5D-3L utility values (scored using the UK tariff) as a function of the five function scores, nine symptom scores, and the global score from the EORTC-QLQ-C30 questionnaire. A Tobit regression was also performed. The mean EQ-5D-3L values for the SIRFLOX trial were calculated and compared with predicted EQ-5D-3L values derived using published mapping algorithms.

Results: The linear mixed regression model provided a satisfactory mapping between the EORTC-QLQ-C30 and the EQ-5D-3L, whilst the Tobit model did not perform as well. When utilities from the SIRFLOX data were calculated with previously published mapping studies, three out of five studies performed well (< 10% mean difference).

Limitations: The main limitation of the study was the lack of meaningful observations post-progression (67 paired observations). For this reason, this study was unable to test whether the mapping holds by disease stage. Additionally, although the study adds to the literature of mappings to the EQ-5D-3L, it is not known how results would differ using the EQ-5D-5L.

Conclusion: This study is the first of its kind in liver-only or liver-dominant mCRC, and mCRC in general. The mapping constructed showed a good fit to the data and provides practitioners with an additional mapping between EORTC-QLQ-C30 to EQ-5D-3L using a large dataset (529 patients, 707 paired observations). The study also confirmed the generalizability of mappings published by Proskorovsky, Kontodimopoulos, and Longworth to liver-only or liver-dominant mCRC.     

EQ-5D health utilities: exploring ways to improve upon responsiveness in psoriasis

Aims: To determine if EuroQoL 5-Dimension Health Questionnaire (EQ-5D) health utility scores were able to discriminate among different levels of improvement in psoriasis severity following therapy.

Materials and methods: Data were from three placebo-controlled phase 3 ixekizumab studies (UNCOVER-1, UNCOVER-2, and UNCOVER-3) with patients who had baseline Dermatology Life Quality Index scores >10 (DLQI >10). Psoriasis severity (Psoriasis Area and Severity Index [PASI]), general health utility (EQ-5D), and psoriasis-specific utility (EQ-PSO, UNCOVER-3 only) were assessed. EQ-5D-5L utility scores were generated using the England EQ-5D-5L value set, a crosswalk applied to the EQ-5D-3L United States (US) and United Kingdom (UK) value sets, and a regression-based exploratory scoring function for the EQ-PSO (UK). Analysis of variance was used to estimate change in EQ-5D-5L from baseline to Week 12 per PASI improvement level: PASI <50, PASI 50 to <75, PASI 75 to <90, PASI 90 to <100, and PASI 100. Missing data were imputed using the last observation carried forward method. Value sets for the UK, England, and the US were applied.

Results: In total, 2085 patients across UNCOVER-1, UNCOVER-2, and UNCOVER-3 had baseline DLQI >10 and available utility scores. At Week 12, mean EQ-5D utility scores increased with increasing PASI improvement levels (p?n?=?645; PASI 90 to <100: 0.141, PASI 100: 0.200; adjusted p?=?0.043).

Limitations: EQ-5D-5L index-based scores have limited ability to differentiate among psoriasis patients at the highest PASI improvement levels.

ConclusionsL Adding psoriasis-specific EQ-PSO dimensions to the EQ-5D may enhance responsiveness to improvement in skin clarity at the highest PASI levels, and, therefore, generate utility scores that better reflect treatment benefit in cost-utility models.     

采用EQ-5D测量中国急性缺血性脑卒中患者生存质量的相关性实证研究

目的:通过EQ-5D量表中EQ-5D健康描述系统和EQ-VAS(直观相似尺度)评分对急性缺血性脑卒中患者健康相关生存质量测量的相关性进行研究.方法:采用前瞻性的随机对照试验设计,对220例急性缺血性脑卒中患者从就诊第0天、第8天、出院至第90天的生存质量和健康状况,运用EQ-5D健康描述系统和EQ-VAS进行研究.结果:以EQ-5D指数得分(健康描述系统评分)和EQ-VAs得分对患者四个阶段生存质量的表达进行线性回归模型拟合,发现两者对患者生存质量的表达趋势一致;进而进行的无控制变量和有控制变量(教育程度和从事职业)的相关性分析显示两者的相关系数均较高(>0.500;P=0.000),且相关性的稳定性也较好.结论:EQ-5D健康描述系统和EQ-VAS的相关性较好,两者的配合使用适用于我国急性缺血性脑卒中患者生存质量和健康状况测量,能够反映其变化情况,也适宜做进一步的成本-效用分析.     

采用EQ-5D评估2型糖尿病患者的生活质量及影响因素研究

目的：采用EuroQol五维调查问卷表（EQ-5D）对2型糖尿病患者健康相关的生活质量进行评价,并分析其主要影响因素,探讨健康状况发展与生活质量下降的关系。方法：采用EQ-5D问卷及访问,对南京大学附属南京鼓楼医院内分泌门诊256例2型糖尿病患者生活质量和健康状况进行研究。结果全体患者EQ-5D分值平均0．790±0．158。理想控制的患者组平均值0．836（0．810～0．861;95％CI）,良好控制和控制差的组的分值分别相当于理想患者的92．2％、84．8％。出现一种或多种并发症的患者分值0．692（0．667～0．717．95％CI）,未出现并发症的患者提高到0．863（0．842～0．883,95％CI）。各种并发症的发生发展与血糖控制情况对生活质量影响程度最强。结论：EQ-5D量表适用于中国2型糖尿病患者健康状况测量,适宜成本-效果分析研究。血糖控制不理想和各并发症的发生发展是患者生活质量下降的主要影响因素。     

Cost utility of allogeneic stem cell transplantation with matched unrelated donor versus treatment with imatinib for adult patients with newly diagnosed chronic myeloid leukaemia

Objective: To estimate, from the perspective of the German statutory health insurance, the cost utility of allogeneic stem cell transplantation with matched unrelated donor (MUD-SCT) in newly diagnosed, chronic-phase chronic myeloid leukaemia (CML) patients aged 40 years or younger, relative to the treatment with imatinib.

Methods: The incremental cost-effectiveness ratio (ICER) of the additional cost of imatinib versus MUD-SCT per quality-adjusted life year (QALY) gained was chosen as a target assessment. ICER was quantified using a Markov cohort modelling approach. The evaluation encompassed 5 years of treatment with either approach, and only direct medical costs (in €, year 2005) were considered.

Results: There were incremental costs of €77,410 for imatinib therapy per QALY gained versus MUD-SCT. No strategy was clearly dominant; on average, during 5 years, cost savings of €63,433 were obtained and 0.82 QALY lost by SCT compared to treatment with imatinib. QALYs gained in CML patients with either treatment resulted in considerable cost to the third-party payer in Germany. The results were particularly sensitive to the price of imatinib.

Conclusions: The analysis finds that imatinib is more costly but more effective (as measured in QALYs) over a 5-year time horizon. The resulting ICER of €77,410 per QALY is higher than commonly cited thresholds. The cost utility of MUD-SCT to treat CML in patients with a European Group for Blood and Marrow Transplantation score ≤ to 2 compares with that of the imatinib strategy.     

Factors associated with adherence to phosphodiesterase type 5 inhibitors for the treatment of pulmonary arterial hypertension

Abstract

Objectives:

To assess factors associated with adherence to phosphodiesterase type 5 inhibitors (PDE5Is) in the management of pulmonary arterial hypertension (PAH).     

The need for cost-effective choices to treat patients with bipolar 1 disorders including asenapine

Abstract

Background:

Bipolar 1 disorders (BPD) are a chronic disorder with prevalence rates of up to 2.6% of the adult population or higher and appreciable direct and indirect costs. As a result, these are a concern to health authorities especially given the low age of onset. Consequently, there is a need to treat BPD patients well and improve their quality-of-life. Pharmacotherapy includes mood stabilizers and atypical antipsychotics (AAPs). AAPs have different mechanisms of action and side-effects, so treatment needs to be tailored. Asenapine in clinical trials is as effective as olanzapine, with less metabolic side-effects.     

Economic evaluation of rituximab in addition to standard of care chemotherapy for adult patients with acute lymphoblastic leukemia

Aims: Acute lymphoblastic leukemia (ALL) is an aggressive form of leukemia with a poor prognosis in adult patients. The addition of the monoclonal antibody rituximab to standard chemotherapy has been shown to improve survival in adults with ALL. However, it is unknown whether the addition of rituximab is cost-effective. The objective was to determine the economic impact of rituximab in addition to standard of care (SOC) chemotherapy vs SOC alone in newly-diagnosed Philadelphia chromosome-negative, CD20-positive, B-cell precursor ALL.

Methods: A decision analytic model was constructed, based upon the Canadian healthcare system. It included the following health states over a lifetime horizon (max ≈60 years): event-free survival (EFS), relapsed/resistant disease, cure, and death. SOC was either hyper-CVAD or the Dana Farber Cancer Institute (DFCI) ALL consortium. EFS, overall survival, and serious adverse event (SAE) rates were derived from a large randomized controlled trial. Costs of the model included: first-line treatment and administration, disease management, second-line and third-line treatment and administration, palliative care, and SAE-related treatments. Inputs were sourced from provincial and national public data, the literature, and cancer agency input.

Results: Quality-adjusted life-years (QALYs) increased by 2.20 QALYs with rituximab in addition to SOC. The resulting mean Incremental Cost-Effectiveness Ratio (ICER) was C$21,828/QALY. At a willingness-to-pay threshold of C$100,000/QALY, the probability of being cost-effective was 98%. Decision outcomes were robust to the probabilistic and deterministic sensitivity analyses, including the SOC backbone as either hyper-CVAD or DFCI.

Limitations: The results of this analysis are limited by generalizability of the chemotherapy backbone to Canadian practice.

Conclusions: For adults with ALL, rituximab in addition to SOC was found to be a cost-effective intervention, compared to SOC alone. The addition of rituximab is associated with increased life years and increased QALYs at a reasonable incremental cost.     

Palonosetron versus other 5-HT3 receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States

Abstract

Objective:

This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting.

Methods:

Patients aged?≥?18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed.

Results:

Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p?=?0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p?=?0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p?=?0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p?=?0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship.

Conclusion:

In this retrospective hospital study, patients with hematologic malignancies treated with HEC or MEC and initiated on antiemetic prophylaxis with palonosetron in the hospital outpatient setting were more likely to experience significantly lower CINV event rates (in the hospital outpatient, inpatient, and emergency room settings) versus patients initiated on other 5-HT₃ RAs.     

Final development and validation of the BOMET-QoL questionnaire for assessing quality of life in patients with malignant bone disease due to neoplasia

SUMMARY

This paper describes the final development and validation of the BOMET-QoL questionnaire for assessing health-related quality of life (HRQoL) in patients with malignant bone disease due to neoplasia (MBDN).

An observational prospective study was conducted of 263 patients with MBDN. Sociodemographic and clinical variables, Eastern Cooperative Oncology Group (ECOG) Performance Scale Index and Pain Management Index (PMI) were gathered. Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and BOMET-QoL questionnaires and the perception of general health status. Both questionnaires were completed again 15 days after the baseline visit by 98 clinically stable patients (Group A), and 3 months and 6 months after the baseline visit by 165 clinically unstable patients (Group B). Prior to validation of the BOMETQoL questionnaire, a factor analysis and psychometric selection of the original items was developed by means of Rasch analysis.

The BOMET-QoL questionnaire consisting of 25 items was reduced to an integrated version of 10 items. Scores on the BOMET-QoL-10 questionnaire were shown to be related to the presence, number and duration of irruptive pain crises, the PMI and the ECOG index (p<0.001), and with changes in the perception of general health status and ECOG index (p<0.01). The internal consistency of the questionnaire and the intraclass correlation coefficient (ICC) were high (Cronbach's α=0.93; ICC =0.97). BOMET-QoL-10 is an easy to manage and valid questionnaire in clinical practice conditions.     

Cost-effectiveness of G5 Mobile continuous glucose monitoring device compared to self-monitoring of blood glucose alone for people with type 1 diabetes from the Canadian societal perspective

Aims: To evaluate the cost-effectiveness of real-time continuous glucose monitoring (CGM) compared to self-monitoring of blood glucose (SMBG) alone in people with type 1 diabetes (T1DM) using multiple daily injections (MDI) from the Canadian societal perspective.

Methods: The IMS CORE Diabetes Model (v.9.0) was used to assess the long-term (50 years) cost-effectiveness of real-time CGM (G5 Mobile CGM System; Dexcom, Inc., San Diego, CA) compared with SMBG alone for a cohort of adults with poorly-controlled T1DM. Treatment effects and baseline characteristics of patients were derived from the DIAMOND randomized controlled clinical trial; all other assumptions and costs were sourced from published research. The accuracy and clinical effectiveness of G5 Mobile CGM is the same as the G4 Platinum CGM used in the DIAMOND randomized clinical trial. Base case assumptions included (a) baseline HbA1c of 8.6%, (b) change in HbA1c of –1.0% for CGM users vs –0.4% for SMBG users, and (c) disutilities of –0.0142 for non-severe hypoglycemic events (NSHEs) and severe hypoglycemic events (SHEs) not requiring medical intervention, and –0.047 for SHEs requiring medical resources. Treatment costs and outcomes were discounted at 1.5% per year.

Results: The incremental cost-effectiveness ratio for the base case G5 Mobile CGM vs SMBG was $33,789 CAD/quality-adjusted life-year (QALY). Sensitivity analyses showed that base case results were most sensitive to changes in percentage reduction in hypoglycemic events and disutilities associated with hypoglycemic events. The base case results were minimally impacted by changes in baseline HbA1c level, incorporation of indirect costs, changes in the discount rate, and baseline utility of patients.

Conclusions: The results of this analysis demonstrate that G5 Mobile CGM is cost-effective within the population of adults with T1DM using MDI, assuming a Canadian willingness-to-pay threshold of $50,000 CAD per QALY.     

A PCT algorithm for discontinuation of antibiotic therapy is a cost-effective way to reduce antibiotic exposure in adult intensive care patients with sepsis

Abstract

Objective:

Procalcitonin (PCT) is a specific marker for differentiating bacterial from non-infective causes of inflammation. It can be used to guide initiation and duration of antibiotic therapy in intensive care unit (ICU) patients with suspected sepsis, and might reduce the duration of hospital stay. Limiting antibiotic treatment duration is highly important because antibiotic over-use may cause patient harm, prolonged hospital stay, and resistance development. Several systematic reviews show that a PCT algorithm for antibiotic discontinuation is safe, but upfront investment required for PCT remains an important barrier against implementation. The current study investigates to what extent this PCT algorithm is a cost-effective use of scarce healthcare resources in ICU patients with sepsis compared to current practice.     

Impact of increasing adherence to disease-modifying therapies on healthcare resource utilization and direct medical and indirect work loss costs for patients with multiple sclerosis

Abstract

Objectives:

To estimate the effect of adherence to disease-modifying therapies (DMTs) among patients with multiple sclerosis (MS) on healthcare resource utilization (HRU) and costs, and model the impact of a 10 percentage point increase in adherence on these outcomes.     

Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USA

Background and aims: IDegLira, a fixed ratio combination of insulin degludec and glucagon-like peptide-1 receptor agonist liraglutide, utilizes the complementary mechanisms of action of these two agents to improve glycemic control with low risk of hypoglycemia and avoidance of weight gain. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira vs liraglutide added to basal insulin, for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US setting.

Methods: Projections of lifetime costs and clinical outcomes were made using the IMS CORE Diabetes Model. Treatment effect data for patients receiving IDegLira and liraglutide added to basal insulin were modeled based on the outcomes of a published indirect comparison, as no head-to-head clinical trial data is currently available. Costs were accounted in 2015?US dollars ($) from a healthcare payer perspective.

Results: IDegLira was associated with small improvements in quality-adjusted life expectancy compared with liraglutide added to basal insulin (8.94 vs 8.91 discounted quality-adjusted life years [QALYs]). The key driver of improved clinical outcomes was the greater reduction in glycated hemoglobin associated with IDegLira. IDegLira was associated with mean costs savings of $17,687 over patient lifetimes vs liraglutide added to basal insulin, resulting from lower treatment costs and cost savings as a result of complications avoided.

Conclusions: The present long-term modeling analysis found that IDegLira was dominant vs liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the US, improving clinical outcomes and reducing direct costs.     

Cost-effectiveness of once daily GLP-1 receptor agonist lixisenatide compared to bolus insulin both in combination with basal insulin for the treatment of patients with type 2 diabetes in Norway

Abstract

Background:

Lixisenatide is a potent, selective and short-acting once daily prandial glucagon-like peptide-1 receptor agonist which lowers glycohemoglobin and body weight by clinically significant amounts in patients with type 2 diabetes treated with basal insulin, with limited risk of hypoglycemia.