Cost-effectiveness of intravitreal aflibercept versus other treatments for wet age-related macular degeneration in Japan

Objective: This analysis estimated the cost-effectiveness of intravitreal aflibercept injection(s) (IAI) for wet age-related macular degeneration (wAMD) compared with other treatments in Japan.

Methods: This was a cost-utility analysis based on published data. A state-transition cohort model was constructed with six health states based on best-corrected visual acuity in the better-seeing eye. The cycle time was 4 weeks, and the time horizon was 12 years. The model compared IAI 2?mg every 8 weeks (2q8) for 2 years after three initial monthly injections, ranibizumab as needed, ranibizumab 0.5?mg every 4 weeks (0.5q4), pegaptanib sodium 0.3?mg every 6 weeks, verteporfin photodynamic therapy (PDT), and best supportive care, assumed to include medical management and monitoring, but no active therapy. Costs (expressed as Japanese yen [JPY]) and quality-adjusted life years (QALYs) gained were estimated for each treatment and discounted at 2.0%. Input data were obtained from clinical studies, the Japanese drug tariff and social insurance reimbursement schedule, and expert opinion. The analysis was conducted from the societal perspective, including medical costs as well as costs of blindness.

Results: IAI 2q8 was dominant (i.e. more effective in terms of QALYs and less costly) to all other comparators (ranibizumab as needed, ranibizumab 0.5q4, pegaptanib sodium, PDT, and best supportive care), as shown by the incremental cost-utility ratio (i.e. cost per QALY gained).

Limitations: The strengths of the analysis include the wide range of comparators evaluated and the use of Japanese-specific utility data. The limitations include the use of one eye, inclusion of published data up to 2 years only, and assumptions on disease course over 5 years.

Conclusions: IAI 2q8 was more effective in terms of QALYs and less costly compared with other treatments for wAMD in Japan.     

Differences in utility elicitation methods in cardiovascular disease: a systematic review

Aims: Utility values inform estimates of the cost-effectiveness of treatment for cardiovascular disease (CVD), but values can vary depending on the method used. The aim of this systematic literature review (SLR) was to explore how methods of elicitation impact utility values for CVD.

Materials and methods: This review identified English-language articles in Embase, MEDLINE, and the gray literature published between September 1992 and August 2015 using keywords for “utilities” and “stroke”, “heart failure”, “myocardial infarction”, or “angina”. Variability in utility values based on the method of elicitation, tariff, or type of respondent was then reported.

Results: This review screened 4,341 citations; 290 of these articles qualified for inclusion in the SLR because they reported utility values for one or more of the cardiovascular conditions of interest listed above. Of these 290, the 41 articles that provided head-to-head comparisons of utility methods for CVD were reviewed. In this sub-set, it was found that methodological differences contributed to variation in utility values. Direct methods often yielded higher scores than did indirect methods. Within direct methods, there were no clear trends in head-to-head studies (standard gamble [SG] vs time trade-off); but general population respondents often provided lower scores than did patients with the disease when evaluating the same health states with SG methods. When comparing indirect methods, the EQ-5D typically yielded higher values than the SF-6D, but also showed more sensitivity to differences in health states.

Conclusions: When selecting CVD utility values for an economic model, consideration of the utility elicitation method is important, as this review demonstrates that methodology of choice impacts utility values in CVD.     

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     

Assessing the impact of nocturia on health-related quality-of-life and utility: results of an observational survey in adults

Background and aim: The impact of nocturia (getting up at night to void) on health-related quality-of-life (HRQoL) is often under-estimated. This study investigated the relative burden in terms of HRQoL and utilities of nocturia in a real-world setting.

Methods: Patient data were collected from two surveys: a nocturia-specific, cross-sectional survey of physicians and their patients (DSP), and a general UK population health survey (HSFE). Utilities (EQ-5D-5L), productivity (Work Productivity and Activity Index), and the impact of nocturia symptoms (Nocturia Impact Diary and Overactive Bladder Questionnaires) were assessed against the number of voids. A robust linear regression model with propensity score weights was used to control for confounding factors in estimating utilities.

Results: Physician-recorded data were available from 8,738 patients across the US, Germany, Spain, France, and the UK; of these, 5,335 (61%) included patient-reported outcomes. In total, 6,302 controls were drawn from the two surveys and compared to 1,104 nocturia patients. Deterioration of HRQoL was associated with increasing number of night-time voids (p?p?p?Limitations: The cause of nocturia is multifactorial and the mostly elderly patients may have several concomitant diseases. The authors tried to adjust for the most common ones, but there may be diseases or unknown relationships not included.

Conclusions: Nocturia negatively affected HRQoL and patient utility. A clear effect is seen already at two voids per night. Every effort should, therefore, be made to reduce nocturia below the bother threshold of two voids per night.     

Irritable bowel syndrome with constipation: a European-focused systematic literature review of disease burden

Abstract

Objective:

To conduct a systematic literature review to assess burden of disease and unmet medical needs in patients with irritable bowel syndrome (IBS) with constipation (IBS-C), with a focus on five European countries (France, Germany, Italy, Spain, UK).

Methods:

MEDLINE, EMBASE, and grey literature searches were carried out using terms for IBS and constipation, to identify studies reporting epidemiological, clinical, humanistic, or economic outcomes for IBS-C, published between 2000 and 2010.

Results:

Searches identified 885 unique abstracts and 33 supplementary articles, of which 100 publications and six grey literature sources met the inclusion criteria. Among patients with IBS, the prevalence estimates of IBS-C ranged from 1 to 44%. Co-morbid conditions, such as personality traits, psychological distress, and stress, were common. Patients with IBS-C had lower health-related quality-of-life (HRQoL) compared with the general population, and clinical trials suggested that effectively treating IBS-C improves HRQoL. The European societal cost of IBS-C is largely unknown, as no IBS-C-specific European cost-of-illness studies were identified. Two cost analyses demonstrated the substantial societal impact of IBS-C, including reduced productivity at work and work absenteeism. Guidelines offered similar recommendations for the diagnosis and management of IBS; however, recommendations specifically for IBS-C varied by country. Current IBS-C treatment options have limited efficacy and the risk:benefit profile of early 5-HT₄ agonists restricts clinical use.

Conclusions:

This systematic review indicates a clear need for European-focused IBS-C burden-of-disease and cost-of-illness studies to address identified evidence gaps. There is a need for new therapies for IBS-C that are effective, well tolerated, and have a positive impact on HRQoL.     

The importance of accounting for the uncertainty around the preference-based health-related quality-of-life measures value sets: a systematic review

Preference-based measures of health-related quality-of-life including, but not limited to, the EQ-5D, HUI2 and the SF-6D have been increasingly used in calculations of quality-adjusted life years for cost effectiveness analyses. However, the uncertainty around the measures’ value sets is commonly ignored in economic evaluation. There are several types of uncertainties, including methodological, structural, and parameter uncertainties, with the latter being the focus of this review paper. The objective is to highlight the gap in the literature regarding the existence of uncertainty in the value sets, focusing mainly on the EQ-5D and SF-6D. To the best of the authors’ knowledge, this is the first systematic review revolving around uncertainty. After searching extensively for studies involving uncertainties in all preference-based measures, the results showed that uncertainty has been approached through different means, while parameter uncertainty has been ignored in most, if not all, cases. These findings suggest that uncertainty should be accounted for when using preference-based measures in economic evaluations. Ignoring this additional information could impact misleadingly on policy decisions.     

A systematic review of cost-effectiveness modeling of pharmaceutical therapies in neuropathic pain: variation in practice,key challenges,and recommendations for the future

Objectives: Complexities in the neuropathic-pain care pathway make the condition difficult to manage and difficult to capture in cost-effectiveness models. The aim of this study is to understand, through a systematic review of previous cost-effectiveness studies, some of the key strengths and limitations in data and modeling practices in neuropathic pain. Thus, the aim is to guide future research and practice to improve resource allocation decisions and encourage continued investment to find novel and effective treatments for patients with neuropathic pain.

Methods: The search strategy was designed to identify peer-reviewed cost-effectiveness evaluations of non-surgical, pharmaceutical therapies for neuropathic pain published since January 2000, accessing five key databases. All identified publications were reviewed and screened according to pre-defined eligibility criteria. Data extraction was designed to reflect key data challenges and approaches to modeling in neuropathic pain and based on published guidelines.

Results: The search strategy identified 20 cost-effectiveness analyses meeting the inclusion criteria, of which 14 had original model structures. Cost-effectiveness modeling in neuropathic pain is established and increasing across multiple jurisdictions; however, amongst these studies, there is substantial variation in modeling approach, and there are common limitations. Capturing the effect of treatments upon health outcomes, particularly health-related quality-of-life, is challenging, and the health effects of multiple lines of ineffective treatment, common for patients with neuropathic pain, have not been consistently or robustly modeled.

Conclusions: To improve future economic modeling in neuropathic pain, further research is suggested into the effect of multiple lines of treatment and treatment failure upon patient outcomes and subsequent treatment effectiveness; the impact of treatment-emergent adverse events upon patient outcomes; and consistent and appropriate pain measures to inform models. The authors further encourage transparent reporting of inputs used to inform cost-effectiveness models, with robust, comprehensive and clear uncertainty analysis and, where feasible, open-source modeling is encouraged.     

A systematic literature review identifying associations between outcomes and quality of life (QoL) or healthcare resource utilization (HCRU) in schizophrenia

Aims: There have been no systematic literature reviews (SLRs) evaluating the identified association between outcomes (e.g. clinical, functional, adherence, societal burden) and Quality-of-Life (QoL) or Healthcare Resource Utilization (HCRU) in schizophrenia. The objective of this study was to conduct a SLR of published data on the relationship between outcomes and QoL or HCRU.

Materials and methods: Electronic searches were conducted in Embase and Medline, for articles which reported on the association between outcomes and QoL or HCRU. Inclusion and exclusion criteria were applied to identify the most relevant articles and studies and extract their data. A summary table was developed to illustrate the strength of associations, based on p-values and correlations.

Results: One thousand and two abstracts were retrieved; five duplicates were excluded; 997 abstracts were screened and 95 references were retained for full-text screening. Thrirty-one references were included in the review. The most commonly used questionnaire, which also demonstrated the strongest associations (defined as a p?Limitations: This study included data from an 11-year period, and other instruments less frequently used may be further investigated.

Conclusions: The evidence suggests that the PANSS is the clinical outcome that currently provides the most frequent and systematic associations with HCRU and QoL endpoints in schizophrenia.