Bronchodilator reliever use and its association with the economic and humanistic burden of COPD: a propensity-matched study

Background and aims: Short-acting bronchodilators are normally used as supplemental relief medication for breakthrough symptoms in COPD patients. The objective of this cross-sectional study was to assess if more frequent vs infrequent use of relief medication in maintenance-treated COPD patients, split by the severity dyspnea, was associated with an increase in the overall disease burden.

Methods: A population-based cross-sectional survey (Adelphi DSP) was conducted among patients with COPD in five European countries. Information was collected on demographic and clinical characteristics, reliever inhaler use, dyspnea (mMRC), health status (CAT, EQ-5D), sleep quality (JSEQ) and healthcare resource use including moderate–severe COPD exacerbations, physician visits, COPD medications and other COPD related resources. The humanistic and economic burden was compared between patients with infrequent reliever use (<1 occasion/week) and more frequent use (≥ 1 occasion/week). The association between increased reliever use and economic burden was also examined after matching patients based on propensity-scores balancing demographic and disease burden characteristics.

Results: Among the 1373 COPD patients prescribed a reliever inhaler, 29% reported using reliever medication ≥1 occasion/week. In the unmatched cohort, more frequent reliever use (n?=?377) compared to infrequent use (n?=?996) was linked to poorer health status (CAT: 25.7 vs 20.0; p?p?p?p?p?=?.0001). In the propensity-score matched population, more frequent reliever use was also associated with significantly higher annual costs for COPD management (€5,034 vs €3,705, p?=?.0327) compared to patients with infrequent reliever use.

Conclusion: In moderate-to-severe COPD, more frequent reliever use is associated with increased exacerbation risk and increased management costs.     

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.     

Factors associated with increased healthcare costs in Medicare Advantage patients with type 2 diabetes enrolled in a large representative health insurance plan in the US

Abstract

Aim:

The objective of this study was to apply quantile regression (QR) methodology to a population from a large representative health insurance plan with known skewed healthcare utilization attributes, co-morbidities, and costs in order to identify predictors of increased healthcare costs. Further, this study provides comparison of the results to those obtained using ordinary least squares (OLS) regression methodology.

Methods:

Members diagnosed with Type 2 Diabetes and with 24 months of continuous enrollment were included. Baseline patient demographic, clinical, consumer/behavioural, and cost characteristics were quantified. Quantile regression was used to model the relationship between the baseline characteristics and total healthcare costs during the follow-up 12 month period.

Results:

The sample included 83,705 patients (mean age?=?70.6 years, 48% male) residing primarily in the southern US (78.1%); 81.2% of subjects were on oral-only anti-diabetic therapy. Co-morbid conditions included nephropathy (43.5%), peripheral artery disease (26.4%), and retinopathy (18.0%). Variables with the strongest relationship with costs during the follow-up period included outpatient visits, ER visits, inpatient visits, and Diabetes Complications Severity Index score during the baseline period. In the top cost quantiles, each additional glycohemoglobin (HbA1c) test was associated with cost savings ($1400 in the 98th percentile). Stage 4 and Stage 5 chronic kidney disease were associated with an incremental cost increase of $33,131 and $106,975 relative to Stage 1 or no CKD in the 98th percentile ($US).

Conclusions:

These results demonstrate that QR provides additional insight compared to traditional OLS regression modeling, and may be more useful for informing resource allocation to patients most likely to benefit from interventions. This study highlights that the impact of clinical and demographic characteristics on the economic burden of the disease vary across the continuum of healthcare costs. Understanding factors that drive costs on an individual patient level provide important insights that will help in ameliorating the clinical, humanistic, and economic burden of diabetes.     

Treatment experience,burden, and unmet needs (TRIBUNE) in Multiple Sclerosis study: the costs and utilities of MS patients in The Netherlands

Abstract

Background:

Multiple sclerosis (MS) is an important, highly disabling neurological disease, common among young adults in The Netherlands. Nevertheless, only a few studies to date have measured the burden imposed by MS on society in The Netherlands.

Objectives:

To estimate the cost and quality-of-life associated with MS in The Netherlands, while focusing on the burden of relapses and increasing disease severity.

Methods:

MS patients in The Netherlands (n?=?263) completed a web-based questionnaire which captured information on demographics, disease characteristics and severity (Expanded Disability Status Scale [EDSS]), co-morbidities, relapses, resource consumption, utilities, fatigue and activities of daily living (ADL).

Results:

Most patients included in the study were receiving treatment for MS (76% of the sample). The mean cost per patient per year increased with worsening disability and was estimated at €30,938, €51,056, and €100,469 for patients with mild (EDSS 0–3), moderate (EDSS 4–6.5), and severe (EDSS 7–9) disability, respectively. The excess cost of relapses was estimated at €8195 among relapsing-remitting patients with EDSS score ≤5. The quality-of-life of patients decreased with disease progression and existence of relapses.

Conclusions:

The cost of MS in The Netherlands was higher compared to the results of previous studies. The TRIBUNE study provides an important update on the economic burden of MS in The Netherlands in an era of more widespread use of disease-modifying therapies. It explores the cost of MS linked to relapses and disease severity and examines the impact of MS on additional health outcomes beyond utilities such as ADL and fatigue.

Conclusions:

Study limitations:     

Converting EORTC QLQ-C30 scores to utility scores in the brigatinib ALTA study

Abstract

Aims: Health utilities summarize a patient’s overall health status. This study estimated utilities based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30), a widely used measure of health-related quality-of-life (HRQoL) in oncology, using published mapping algorithms.

Materials and methods: Data were from the Anaplastic Lymphoma Kinase (ALK) in Lung Cancer Trial of brigatinib (ALTA; NCT02094573), an open-label, international, phase 2 study. ALTA evaluated the efficacy and safety of two randomized dosing regimens of brigatinib in patients with locally advanced or metastatic ALK?+?non-small cell lung cancer (NSCLC) that had progressed on prior therapy with crizotinib. QLQ-C30 scores were mapped to European Quality-of-Life-5 Dimensions (EQ-5D) utility scores using two published algorithms (Khan et al. for EQ-5D-5L; Longworth et al. for EQ-5D-3L). The impact of brigatinib treatment on health utilities over time was assessed.

Results: The analysis included 208 subjects. Mean baseline utility scores for both algorithms ranged between 0.60???0.71 and increased to 0.78 by cycle 5. Utility improvements were sustained during most of the treatment, before disease progression. Minor variations were observed between utility scores; Khan et al. estimates were approximately 0.01 or 0.02 points lower than Longworth et al. estimates.

Limitations: Algorithms considered were limited to those available in the published literature at the time of the study. This utility analysis was exploratory, and the ALTA trial did not include an internal control group (i.e. standard of care) and was not powered to detect differences in QoL/utility outcomes between treatment arms.

Conclusions: Converting QLQ-C30 scores into utilities in trials using established mapping algorithms can improve evaluation of medicines from the patient perspective. Both algorithms suggested that brigatinib improved health utility in crizotinib-refractory ALK?+?NSCLC patients, and improvements were maintained during most of the treatment.

Clinicaltrials.gov identifier: NCT02094573     

Characteristics affecting health-related quality of life (HRQOL) in Japanese patients with reflux oesophagitis and the effect of lansoprazole on HRQOL

Abstract

Objectives: A survey of health-related quality of life (HRQOL) in the Japanese general population has suggested that HRQOL is affected by sex and age. We investigated whether there is any effect of baseline patients' characteristics on HRQOL of patients with reflux oesophagitis (RE), and its changes with lansoprazole (LPZ) treatment.

Research design and methods: This was a post hoc analysis of an open-label, multicentre, post-marketing, observational study which investigated the effect of LPZ (15 or 30 mg/day for 8 weeks) on HRQOL in patients with RE. At baseline, and after 4 and 8 weeks of treatment, HRQOL was assessed using a Japanese version of the 8-item Short-Form Health Survey (SF-8) and a newly-developed RE-specific questionnaire (RESQ). Stratified analysis of changes in HRQOL scores according to baseline patient characteristics such as sex, age and baseline severity of typical RE symptoms was performed.

Results: A total of 8,757 patients were included in the efficacy analysis. At baseline, physical component summary scores from the SF-8 were lower in older patients (≥60 years) than in younger patients (<60 years), and mental component summary scores were lower in younger patients than in older patients. These scores significantly improved after LPZ treatment regardless of sex and age. HRQOL scores were lower in patients with more severe typical RE symptoms at baseline. After LPZ treatment, HRQOL scores significantly improved to similar levels irrespective of the severity of the typical RE symptom at baseline.

Conclusions: This post hoc analysis suggests that sex, age and severity of typical RE symptoms affect HRQOL in patients with RE in Japan, and such factors do not affect the improvement of HRQOL with LPZ treatment. The present study suggests a positive impact of LPZ; however, it is difficult to estimate the degree of improvement in HRQOL that may have arisen from symptomatic relief as part of the natural history of the disease from the study. Our results may overestimate the efficacy of LPZ. Further well-controlled clinical studies are needed to confirm the efficacy of LPZ on HRQOL in patients with RE.     

Long-term disease history,clinical symptoms,health status,and healthcare utilization in patients suffering from Lambert Eaton myasthenic syndrome: Results of a patient interview survey in Germany

Abstract

Introduction:

The burden of disease in Lambert-Eaton myasthenic syndrome (LEMS) patients is unclear. This study focused on the patient’s perspective to obtain patient-reported information on clinical symptoms, burden of illness, impact of LEMS on activities of daily living (ADL), and management of LEMS.

Methods:

Semi-structured, face-to-face interviews with LEMS patients from two specialized centres in Germany between September and December 2010.

Results:

Twelve patients participated; mean age 66.7?±?9.8 years. First symptoms occurred at age 52.5?±?14.0 years. Mean time between first symptoms and diagnosis was 4.4?±?6.2 years. Patients reported neuromuscular, cranial, and autonomic symptoms plus general fatigue. Two-thirds of patients reported 10 or more symptoms. The most frequent symptoms were leg weakness (91.7%) and general fatigue (83.3%). Restrictions in ADL were reported always or often in 75% of patients. Over half of the patients (n?=?7) reported poor or very poor health status. Mean EQ-5D utility scores were 0.34?±?0.35, with little day-to-day variation. Patients visited a number of different clinicians; most had been hospitalized at some point in the course of their disease. The most frequent drug treatments were 3,4-diaminopyridine (3,4-DAP) (83.3%) and pyridostigmine (41.5%). The study has several limitations, including small sample size and the potential influence of recall bias.

Conclusion:

LEMS patients report long individual disease histories. Most patients suffer multiple symptoms which are frequently severe and troublesome, and almost all are restricted in ADL with poor health status. There is high utilization of healthcare resources from diagnosis to ongoing treatment. Physicians should be aware of this rare disease to ensure that patients receive an early diagnosis and prompt and appropriate treatment.     

The burden of immune thrombocytopenia in adults: Evaluation of the thrombopoietin receptor agonist romiplostim

Abstract

Background:

Immune thrombocytopenia (ITP) is a chronic, immune-mediated disease characterized by a transient or long-lasting decrease in platelet counts. ITP is associated with numerous serious clinical consequences. Discussed here are clinical aspects of ITP, the humanistic and economic burden of ITP, and current treatment options with a focus on romiplostim, a thrombopoietin (TPO) receptor agonist. The aim of this review is to provide decision-makers with the background information necessary to evaluate the value of romiplostim.

Scope:

PubMed was searched for relevant, English-language papers published from January 2006 through November 2011 relating to the epidemiology and treatment options of chronic ITP, and, focusing on the TPO mimetic romiplostim, patient-reported outcomes (PRO) and economic burden. Recent select conference abstracts were also reviewed.

Findings:

The initial clinical management of ITP (e.g., corticosteroids, immunoglobulins) is often associated with adverse events and recommended for short-term use only. Splenectomy, a potentially curative second-line treatment, is associated with increased risks of bleeding and infection, and patients often require additional long-term drug intervention. ITP and its sequelae are associated with a substantial burden on patients’ health-related quality-of-life (HRQoL) and increased medical costs. Use of TPO receptor agonists in ITP patients may represent a more efficient use of healthcare resources than existing therapies.

Conclusion:

While this literature review is not a systematic review, e.g., it considers only approved therapies and published literature written in English, it provides a comprehensive overview of the clinical, humanistic, and economic factors that should be considered in treating ITP, particularly with new agents such as romiplostim. Among the limited number of safe and effective therapies currently available for chronic ITP, highly effective and well-tolerated medications such as romiplostim may reduce the healthcare resource utilization associated with ITP while improving patients’ HRQoL.     

The societal impact of pain in the European Union: health-related quality of life and healthcare resource utilization

Abstract

Objectives:

This paper reports on the results of a series of quantitative assessments of the association of severe and frequent pain with health-related quality of life and healthcare resource utilization in five European countries.

Methods:

The analysis contrasts the contribution of the increasing severity and frequency of pain reported against respondents reporting no pain in the previous month. The data are taken from the 2008 National Health and Wellness Survey. Single-equation generalized linear regression models are used to evaluate the association of pain with the physical and mental component scores of the SF-12 questionnaire as well as health utilities generated from the SF-6D. In addition, the role of pain is assessed in its association with healthcare provider visits, emergency room visits and hospitalizations.

Results:

The results indicate that the experience of pain, notably severe and frequent pain, is substantial and is significantly associated with the SF-12 physical component scores, health utilities and all aspects of healthcare resource utilization, which far outweighs the role of demographic and socioeconomic variables, health risk factors (in particular body mass index) and the presence of comorbidities. In the case of severe daily pain, the marginal contribution of the SF-12 physical component score is a deficit of ?17.86 compared to those reporting no pain (population average score 46.49), while persons who are morbidly obese report a deficit of only ?6.63 compared to those who are normal weight. The corresponding association with health utilities is equally dramatic with a severe daily pain deficit of ?0.19 compared to those reporting no pain (average population utility 0.71).

Conclusions:

For the five largest EU countries, the societal burden of pain is considerable. The experience of pain far outweighs the contribution of more traditional explanations of HRQoL deficits as well as being the primary factor associated with increased provider visits, emergency room visits and hospitalizations.     

The impact of increasing neurological disability of multiple sclerosis on health utilities: a systematic review of the literature

Abstract

Background: Multiple sclerosis (MS) is a debilitating disease, accompanied by neurological symptoms of varying severity. Utilities are a key summary index measure used in assessing health-related quality of life in individuals with MS.

Objectives: To provide a systematic review of the literature on utilities of relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) patients and to review changes in utilities associated with the increasing neurological disability of different stages of MS, as measured by the Expanded Disability Status Scale (EDSS).

Methods: Employing pre-defined search terms and inclusion/exclusion criteria, systematic searches of the literature were conducted in EMBASE, MEDLINE, PsycINFO, the Health Economic Evaluation Database (HEED), and the NHS Economic Evaluations Database (NHS/EED). Proceedings for the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the European Society for Treatment and Research in MS (ECTRIMS), the American Society for Treatment and Research in MS (ACTRIMS), and the Latin American Society for Treatment and Research in MS (LACTRIMS) were reviewed in addition to the UK National Institute for Health and Clinical Excellence website and the table of contents of PharmacoEconomics and Value in Health.

Results: This review identified 18 studies reporting utilities associated with health states of MS. Utilities ranged from 0.80 to 0.92 for patients with an EDSS score of 1, from 0.49 to 0.71 for patients with an EDSS score of 3, from 0.39 to 0.54 for patients with an EDSS score of 6.5, and from –0.19 to 0.1 for patients with an EDSS score of 9.

Limitations: Several of the studies reviewed relied on data from patient organizations, which may not be fully representative of the general patient populations. Additionally, the majority of the studies relied on retrospective data collection.

Conclusions: Utilities decrease substantially with increasing neurological disability. Cross-country differences are minimal with utility scores following a similar pattern across countries for patients at similar disease severity levels. This consistency in findings is noteworthy, as there is a reliable evidence base for selecting utility values for economic evaluation analyses. However, more research is needed to explore potential differences in utilities between RRMS and SPMS patients.     

Elicitation of health state utilities associated with differing durations of morning stiffness in rheumatoid arthritis

Abstract

Objective:

Specific symptoms of rheumatoid arthritis (RA), including joint stiffness and functional disability, are most severe in the morning. ‘Morning stiffness’ has a negative impact on health-related quality-of-life (HRQoL); however, how HRQoL is correlated to morning stiffness duration is unknown. The objective of this study was to obtain population-based utility values associated with different durations of morning stiffness in RA.

Design and methods:

The time-trade-off (TTO) approach was used to elicit utility values for four different health states (HS), which differed in morning stiffness duration. One hundred and nine members of the UK general public rated each HS in individual face-to-face interviews with trained investigators. TTO scores were converted into utility values. Visual Analog Scale (VAS) scores were obtained to validate TTO scores.

Results:

On a scale of 0 (death) to 1 (full health), a mean utility value of 0.45?±?0.29 was elicited for ～3?h of morning stiffness (anchor HS), 0.50?±?0.28 for 2–3?h of morning stiffness (HS1), 0.61?±?0.25 for 1–2?h of morning stiffness (HS2) and 0.78?±?0.20 for <1?h of morning stiffness (HS3). The difference between each HS was statistically significant (p?<?0.01). Mean VAS utility scores followed the same trend. Utility incrementally increased with each HS associated with a shorter duration of morning stiffness. Limitations of this research include potential bias from the TTO method due to the discounting effect of time, scale compatibility, and loss aversion.

Conclusions:

The UK population-based utility values show a reduction in morning stiffness duration in RA is associated with improved HRQoL. Despite the impact of morning stiffness on HRQoL, it is rarely evaluated and little is known as to how it is affected by current treatments. The results of this study can be applied in future cost-utility analyses of healthcare interventions which target an improvement in morning stiffness duration for RA patients.     

Developing a preference-based utility scoring algorithm for the Psoriasis Area Severity Index (PASI)

Abstract

Introduction: It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI.

Methods: Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g. OLS linear, random effects, mean, robust, spline, quadratic).

Results: A total of 245 participants completed utility interviews (51.4% female; mean age?=?45.3?years). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g. R², mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R²?=?0.13; MAE?=?0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score.

Conclusions: The derived scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.     

Examining the association between pain severity and quality-of-life,work-productivity loss,and healthcare resource use among European adults diagnosed with pain

Objective: The goal of this research was to quantify the association between pain severity and several health outcomes in a large sample of patients diagnosed with some form of pain.

Methods: Responses from patients who had been diagnosed with some form of pain (n?=?14,459) were drawn from the 2013 EU National Health and Wellness Survey (NHWS; n?=?62,000). Respondents reported their subjective pain severity in the past week on a numerical rating scale (0–10) as well as the Medical Outcomes Study Short Form (SF-36), Work Productivity and Activity Impairment Questionnaire (WPAI), and healthcare resource utilization in the past 6 months (healthcare professional (HCP) visits, emergency room (ER) visits, and hospitalizations). Associations between pain severity and health outcomes were examined via a series of regression models controlling for a set of demographic and health-related covariates.

Results: After controlling for demographics and comorbidities, pain severity in the past week was shown to be significantly negatively associated with Health Utilities (b = ?0.022, p?b?=?0.18, p?b?=?0.13, p?b?=?0.14, p?b?=?0.08, p?Limitations: This study was a self-report cross-sectional study which may have biased the results and does not allow for causal inferences to be made. Finally, the regression models run were limited to available covariates and, hence, some potentially important covariates may not have been included in these models.

Conclusions: The findings suggest that reducing pain severity could result in an increase in patients’ quality-of-life and work productivity, and a decrease in healthcare resource use. The equations, linking pain and outcomes, were presented in an accessible format so they could be readily applied in healthcare decision-making.     

Cost per responder analysis in patients with secondary hyperparathyroidism on dialysis treated with cinacalcet

Abstract

Background:

Growing financial pressure on US dialysis providers requires economic efficiency considerations. The objective of this study was to examine short-term economic efficiencies of a cinacalcet-based treatment approach for secondary hyperparathyroidism.

Methods:

This study retrospectively assessed cost per biochemical response of the OPTIMA trial. OPTIMA was conducted in end-stage renal disease patients to compare biochemical control in patients receiving cinacalcet in addition to vitamin D sterols and phosphate binders vs patients receiving vitamin D sterol and phosphate binders alone. It explored three laboratory measurement response definitions from baseline to week 23: (1) decreases in parathyroid hormone (PTH) ≥30%; (2) PTH?≤?300?pg/ml; and (3) PTH?≤?300?pg/mL, calcium <9.5?mg/dL and phosphorus <5.5?mg/dL. Medication use and costs were measured to calculate average costs and incremental cost per responder. Stratification by lower and higher baseline PTH assessed cost per response by disease severity.

Results:

There were 38–77% more responders with cinacalcet vs control, depending on response definition. Mean (SD) per patient total medication costs were $5423 ($3698) for cinacalcet and $2633 ($2334) for control, leading to a mean difference of $2790 over 23 weeks. When response was defined as a decrease in PTH?≥?30% from baseline, the average cost per responder was $11,266 for control vs $7027 for cinacalcet. The incremental cost per incremental responder ranged from $5186–$9168. Across all response measures, cost per responder was lower in patients with lower baseline PTH.

Conclusions:

Representing a more efficient allocation of economic resources over the short-term, cinacalcet-based treatment algorithm led to a lower cost per biochemical response, particularly in patients with lower disease severity, vs vitamin D sterols and phosphate binders alone. These findings should be interpreted alongside the study limitation of converting international trial-based medication utilization into US costs.