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.     

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     

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.     

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.     

Prospective utility study of patients with multiple cardiovascular events

Objectives: The effects of acute coronary syndrome (ACS) events on health-related quality-of-life (HRQoL) and the time dependency of these effects are unknown. This study aimed to characterize health utilities in ACS patients to aid development of future economic models estimating the cost per quality-adjusted life-year impact of ACS events and potential treatments.

Methods: Multi-center, non-interventional, longitudinal evaluation of health utility in patients experiencing ACS or stroke events. EuroQol-5 dimension 3 level (EQ-5D-3L) surveys were sent to patients (≥18 years) from three UK centers, 1 month after hospital discharge for myocardial infarction (MI), unstable angina (UA), or stroke. Patient demographics, lifestyle, and baseline utility score were collected in the first survey. Follow-up surveys were sent at 6, 12, 18, and 24 months to prospectively capture utility and subsequent health events. Two methods of patient identification were adopted—prospective, where the patient’s qualifying events occurred after the study index date, and retrospective, where the patient’s qualifying event occurred prior to the study index date. General healthy population utility values were assumed for pre-event HRQoL.

Results: Between January 2011 and March 2014, 2,103 prospectively (n?=?1,350)/retrospectively (n?=?753) identified patients (mean age?=?68.3 years; 67.9% male) responded: MI?=?55.9% (n?=?1,176), UA?=?42.7% (n?=?898), stroke?=?1.4% (n?=?29); 24% had type 2 diabetes. Post-event utility values were lower than general healthy population values, although significant differences in utility between subsequent 6 (n?=?1,031, change?=?–0.002), 12 (n?=?1,096, change?=?–0.008), 18 (n?=?1,246, change?=?–0.007), and 24 (n?=?1,277, change?=?–0.004) month timepoints were not detected. Through multivariate regression analyses, wheelchair use, current smoking, and secondary mental and joint health events were associated with the greatest statistically significant utility decrements.

Conclusions: This study indicates that health utility decreases following a cardiovascular event and, although some improvement occurs over the subsequent 24 months, general healthy population utility is not necessarily attained.     

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.     

Mapping AcroQoL scores to EQ-5D to obtain utility values for patients with acromegaly

Aims: To estimate a preference-based single index for the disease-specific instrument (AcroQoL) by mapping it onto the EQ-5D to assist in future economic evaluations.

Materials and methods: A sample of 245 acromegaly patients with AcroQoL and EQ-5D scores was obtained from three previously published European studies. The sample was split into two: one sub-sample to construct the model (algorithm construction sample, n?=?184), and the other one to confirm it (validation sample, n?=?61). Various multiple regression models including two-part model, tobit model, and generalized additive models were tested and/or evaluated for predictive ability, consistency of estimated coefficients, normality of prediction errors, and simplicity.

Results: Across these studies, mean age was 50–60 years and the proportion of males was 36–59%. At overall level the percentage of patients with controlled disease was 37.4%. Mean (SD) scores for AcroQoL Global Score and EQ-5D utility were 62.3 (18.5) and 0.71 (0.28), respectively. The best model for predicting EQ-5D was a generalized regression model that included the Physical Dimension summary score and categories from questions 9 and 14 as independent variables (Adj. R²?=?0.56, with mean absolute error of 0.0128 in the confirmatory sample). Observed and predicted utilities were strongly correlated (Spearman r?=?0.73, p?<?.001) and paired t-Student test revealed non-significant differences between means (p?>?.05). Estimated utility scores showed a minimum error of ≤10% in 45% of patients; however, error increased in patients with an observed utility score under 0.2. The model’s predictive ability was confirmed in the validation cohort.

Limitations and conclusions: A mapping algorithm was developed for mapping of AcroQoL to EQ-5D, using patient level data from three previously published studies, and including validation in the confirmatory sub-sample. Mean (SD) utilities index in this study population was estimated as 0.71 (0.28). Additional research may be needed to test this mapping algorithm in other acromegaly populations.     

Relationship between patient-reported disease severity and other clinical outcomes in osteoarthritis: a European perspective

Abstract

Objective:

To determine how patient-rated osteoarthritis (OA) severity correlates with other patient-reported and clinical outcomes in the European clinical setting.

Methods:

We used the Adelphi Arthritis VII (2008) Disease Specific Program (DSP). OA severity was patient-rated using the question ‘How bad would you say your arthritis is now?’ with responses of ‘mild,’ ‘moderate,’ and ‘severe.’ Patient-reported outcomes included a 0–100?mm pain visual analogue scale (VAS); questions on daily functioning; Work Productivity and Activity Impairment (WPAI) scale; and EuroQoL (EQ-5D). Regression models and chi-square analyses evaluated relationships between self-rated OA severity and other outcomes.

Results:

Patient-reported data were available from 1739 individuals (63.1% female, mean age 64.4 [standard deviation 11.9] years) from France, Germany, Italy, Spain, and the UK. With increasing OA severity; mild (24.5%), moderate (56.3%), severe (19.2%), statistically significant differences (p?<?0.05) were observed with higher pain VAS scores (28.3, 49.9, 69.2, respectively), reduced function, and greater overall work impairment due to OA (24.3%, 38.5%, 68.6%, respectively). Significant associations of patient-reported OA severity with function and health status were indicated, including the EQ-5D health state index; 0.77 (mild), 0.62 (moderate), 0.30 (severe) (p?<?0.0001). Physicians tended to overestimate patients who rated their OA as mild, and underrate patients who rated their OA as severe.

Conclusions:

In five European countries, patient-rated OA severity was associated with other patient-reported outcomes, and may be of benefit in the clinical setting when choosing treatment options aimed at improving pain, function and productivity, providing an accurate and tangible assessment of patient’s perceptions of their disease.     

The impact of different scenarios for intermittent bladder catheterization on health state utilities: results from an internet-based time trade-off survey

Aims: Intermittent catheterization (IC) is the gold standard for bladder management in patients with chronic urinary retention. Despite its medical benefits, IC users experience a negative impact on their quality of life (QoL). For health economics based decision making, this impact is normally measured using generic QoL measures (such as EQ-5D) that estimate a single utility score which can be used to calculate quality-adjusted life years (QALYs). But these generic measures may not be sensitive to all relevant aspects of QoL affected by intermittent catheters. This study used alternative methods to estimate the health state utilities associated with different scenarios: using a multiple-use catheter, one-time-use catheter, pre-lubricated one-time-use catheter and pre-lubricated one-time-use catheter with one less urinary tract infection (UTI) per year.

Methods: Health state utilities were elicited through an internet-based time trade-off (TTO) survey in adult volunteers representing the general population in Canada and the UK. Health states were developed to represent the catheters based on the following four attributes: steps and time needed for IC process, pain and the frequency of UTIs.

Results: The survey was completed by 956 respondents. One-time-use catheters, pre-lubricated one-time-use catheters and ready-to-use catheters were preferred to multiple-use catheters. The utility gains were associated with the following features: one time use (Canada: +0.013, UK: +0.021), ready to use (all: +0.017) and one less UTI/year (all: +0.011).

Limitations: Internet-based survey responders may have valued health states differently from the rest of the population: this might be a source of bias.

Conclusion: Steps and time needed for the IC process, pain related to IC and the frequency of UTIs have a significant impact on IC related utilities. These values could be incorporated into a cost utility analysis.     

Cost per additional responder for ixekizumab and other FDA-approved biologics in moderate-to-severe plaque psoriasis

Background: Evidence of the cost-efficacy of ixekizumab for the treatment of moderate-to-severe plaque psoriasis (PsO) in the US is limited.

Objective: To estimate the number needed to treat (NNT) and monthly cost of achieving one additional Psoriasis Area and Severity Index (PASI) 75, 90, and 100 responder for ixekizumab and other Food and Drug Administration (FDA)-approved biologics in PsO.

Methods: A network meta-analysis estimated the probability of achieving PASI 75, 90, or 100 response during induction for each biologic. NNTs were calculated using response difference of each respective biologic vs placebo at the end of induction. Monthly costs per additional PASI responder were based on FDA-approved doses, wholesale acquisition costs, and induction NNTs.

Results: Induction NNTs for ixekizumab 80?mg once every 2 weeks (Q2W) relative to placebo were consistently lower across all levels of clearance compared with the other biologics. Monthly cost per additional responder was lowest for ustekinumab 45?mg at PASI 75 and for secukinumab 300?mg and ixekizumab 80?mg Q2W at PASI 90. Ixekizumab 80?mg Q2W had the lowest cost for PASI 100.

Conclusion: In this analysis, ixekizumab is the most cost-efficient biologic in the US when targeting complete resolution, as measured by PASI 100 in PsO.     

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.     

A systematic literature review of utility weights in wet age-related macular degeneration

Abstract

Objective:

The objective of the study was to conduct a systematic review of utility weight estimates relevant to economic models for wet age-related macular degeneration (wAMD).

Methods:

A systematic literature search of PubMed, Embase, the Cochrane Library, and EconLit was performed (January 1995–December 2010) and then updated (October 2010–May 2012; February 2012–July 2013) identifying articles reporting utilities in patients with wAMD and visual impairment. Extracted studies were also assessed for compliance with the NICE reference case.

Results:

Of 2415 articles identified from the searches, 212 articles were reviewed in full, and 17 selected for data extraction. Most studies used time trade-off (TTO) techniques to estimate utilities; other methods included standard gamble, EuroQoL Health Questionnaire 5 Dimensions (EQ-5D); Short-Form 6D Health Status Questionnaire (SF-6D); and Health Utilities Index Mark III (HUI3). Correlation between utility estimates and visual acuity (VA) differed between the instruments. Time trade-off methods were more sensitive to VA changes than standard gamble methods. HUI3 estimates were most highly correlated with VA changes, followed by TTO; no trend was observed between VA and EQ-5D or SF-6D utility weights. Six of the 17 studies complied with the NICE reference case.

Conclusions:

Several instruments have been used to elicit utilities from patients with wAMD. Because TTO methods were more sensitive to VA changes than standard gamble and HUI3 estimates were most highly correlated with VA changes, TTO and HUI3 may be suitable methods for economic evaluations in these patients. The EQ-5D and SF-6D were poor indicators of the impact of VA on HRQL.     

Quality of life in relation to constipation among opioid users

Abstract

Objective: Opioid users often experience constipation. In this study the impact of constipation on QoL was assessed in patients using opioids either for non-advanced illness or advanced illness.

Methods: Patients using opioids, recruited via public pharmacies, were asked to complete questionnaires on opioid use, constipation and the EuroQol five-dimension questionnaire (EQ-5D). Patients with a severe non-curable disease and relatively short life-expectancy were classified as having an advanced illness; a disabling yet not directly life-threatening condition was defined as non-advanced illness. Constipation was assessed based on questions on opioid side-effects and laxative use. EQ-5D index scores were compared between patients with and without constipation using Wilcoxon two-samples test.

Results: Questionnaires were returned by 588 patients with non-advanced illness, of whom 326 (55%) were classified as having constipation and by 113 patients with advanced illness, of whom 76 (67%) were classified as having constipation. The median EQ-5D index, a weighted health state index score with 1 = full health, was lower in patients with constipation than in patients without constipation (0.31 vs. 0.65, p<?0.01 for non-advanced illness and 0.41 vs. 0.61, p=0.12 for advanced illness).

Conclusion: The results of this study suggest that, in patients using opioids either for non-advanced illness or advanced illness, constipation negatively influences QoL. By separately analysing patients with advanced illness and patients with non-advanced illness, possible selective non-response and confounding was accounted for, but not completely solved.     

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.     

Quality of life benefits and cost impact of prolonged release oxycodone/naloxone versus prolonged release oxycodone in patients with moderate-to-severe non-malignant pain and opioid-induced constipation: a UK cost-utility analysis

Abstract

Objective:

To compare the cost effectiveness of prolonged release oxycodone/naloxone (OXN) tablets (Targinact) and prolonged release oxycodone (OXY) tablets (OxyContin) in patients with moderate-to-severe non-malignant pain and opioid-induced constipation (OIC) from the perspective of the UK healthcare system.

Methods:

A cohort model used data from a phase III randomised, controlled trial (RCT). It calculated the cost difference between treatments by combining the cost of pain therapy with costs of laxatives and other resources used to manage constipated patients. SF-36 scores were converted into EQ-5D utility values to calculate the quality-adjusted life-year (QALY) gains. Deterministic and probabilistic sensitivity analyses were performed.

Results:

The incremental cost of OXN versus OXY was £159.68 for the average treatment duration of 301 days. OXN gave an incremental QALY gain of 0.0273. The estimated incremental cost-effectiveness ratio (ICER) was £5841.56 per QALY. Sensitivity analyses gave a maximum ICER of £10,347.03. In some scenarios, OXN dominated with a cost saving of up to £4254.70. Probabilistic sensitivity analysis showed that OXN had approximately 96.6% probability of cost effectiveness at the £20,000 threshold.

Limitations:

The model was conservative in predicting the probability of constipation beyond the 12-week RCT period. UK cost of constipation data were limited and based on primary care physician opinion.

Conclusions:

In the base case, direct treatment costs were slightly higher for patients treated with OXN than for those treated with OXY. However, patients treated with OXN experienced a quality of life gain, and had an ICER considerably below thresholds commonly applied in the UK. The model was most sensitive to the estimated cost of constipation with a number of realistic scenarios in the sensitivity analysis demonstrating a cost saving with OXN (OXN dominant). OXN is therefore estimated to be a cost-effective option for treating patients with severe non-malignant pain and OIC.     

Cost effectiveness of deferasirox compared to desferrioxamine in the treatment of iron overload in lower-risk,transfusion-dependent myelodysplastic syndrome patients

Abstract

Objective:

The study evaluated the cost effectiveness of deferasirox (Exjade) compared to non-proprietary desferrioxamine (DFO) for the control of transfusional iron overload in lower risk myelodysplastic syndromes (MDS) patients. A UK National Health Service perspective was adopted.

Methods:

Recent clinical evidence has demonstrated the efficacy and safety of deferasirox in transfusion-dependent MDS patients with elevated serum ferritin levels. An economic model was used to extrapolate the clinical benefits of iron chelation therapy (ICT) in a cohort of lower risk MDS patients. Costs for drug acquisition, drug administration and monitoring, and quality of life (utility) outcomes associated with mode of drug administration were derived from a variety of sources. The incremental cost per QALY gained for deferasirox was estimated. Costs and outcomes were discounted at 3.5% in line with UK standards.

Results:

The base-case cost effectiveness of deferasirox versus DFO was estimated to be £20,822 per QALY gained, the key driver being the additional quality of life benefits associated with a simpler mode of administration for deferasirox. A mean survival benefit for both forms of ICT of 4.5 years was estimated. The results were sensitive to drug dose, days of DFO administration, and patient weight.

Conclusions:

In the UK, a cost per QALY below £20,000–30,000 is considered cost effective. Hence, the results from this economic analysis suggest deferasirox is cost effective in lower risk, transfusion-dependent, MDS patients. Limitations with the analysis include a lack of comparative randomised controlled trial evidence, in particular to differentiate survival and clinical outcomes for deferasirox and DFO.     

An economic evaluation attached to a single-centre,parallel group,unmasked, randomized controlled trial of a 3-day intensive social cognitive treatment (can do treatment) in patients with relapsing remitting multiple sclerosis and low disability

Abstract

Aims: This trial-based economic evaluation (EE) assesses from a societal perspective the cost-effectiveness of an intensive 3-day cognitive theory-based intervention (CDT), compared to care-as-usual, in patients with relapsing remitting multiple sclerosis (RRMS) and low disability (Expanded Disability Status Scale [EDDS] score < 4.0).

Materials and methods: The trial of the EE was registered in the Dutch Trial Register: Trial NL5158 (NTR5298). The incremental cost-effectiveness ratio (ICER) was expressed in cost on the Control sub-scale of the Multiple Sclerosis Self-Efficacy Scale (MSSES) and the incremental cost-utility ratio (ICUR) in the cost per Quality Adjusted Life Years (QALY) using the EQ-5D-5L. Bootstrap, sensitivity, and sub-group analyses were performed to determine the robustness of the findings.

Results: The two groups of 79 patients were similar in baseline characteristics. The base case ICER is situated in the northeast quadrant (€72 (40.74/€2,948)) due to a higher MSSES Control score and higher societal costs in the CDT group. The ICUR is situated in the northwest (inferior) quadrant due to losses in QALY and higher societal costs for the CDT group (?0.02/€2,948). Overall, bootstrap, sensitivity, and sub-group analyses confirm the base case findings. However, when the SF-6D is used as a study outcome, there is a high probability that the ICUR is situated in the northeast quadrant.

Limitations: The relative short follow-up time (6?months) and the unexpected increase in MSSES Control in the control group.

Conclusions: When using the EQ-5D-5L to calculate a QALY, CDT is not a cost-effective alternative in comparison to care as usual. However, when using self-efficacy or SF-6D as outcomes, there is a probability that CDT is cost-effective. Based on the current results, CDT for patients with RRMS clearly show its potential. However, an extended follow-up for the economic evaluation is warranted before a final decision on implementation can be made.     

Matching-adjusted indirect comparison of adalimumab vs etanercept and infliximab for the treatment of psoriatic arthritis

Abstract

Objectives:

No head-to-head trial has compared the efficacy of adalimumab vs etanercept and infliximab for psoriatic arthritis (PsA). This study implements a matching-adjusted indirect comparison technique to address that gap.

Methods:

Patient-level data from a placebo-controlled trial of adalimumab (ADEPT) were re-weighted to match average baseline characteristics from pivotal published trials of etanercept and infliximab. ADEPT patients were re-weighted by odds of enrollment in comparator trials, estimated using logistic regression. Matched-on characteristics included PsA duration, age, gender, severity, active psoriasis, and concomitant treatment. After matching, placebo-adjusted treatment arms were compared at weeks 12 (or 14) and 24. Outcomes included ACR20/50/70, PsARC, HAQ, and modified TSS. PASI50/75/90 were compared for patients with active psoriasis. Cost per responder (CPR) was assessed in the US and Germany using matching-adjusted end-points and drug list prices. Statistical significance was assessed using weighted t-tests.

Results:

After matching, adalimumab-treated patients had greater placebo-adjusted rates of ACR70 and PASI50/75/90 at week 24 compared with etanercept (all p?<?0.05). Adalimumab patients had a higher placebo-adjusted rate of ACR70 than infliximab at week 14 (p?=?0.034). Adalimumab treatment had lower CPR for ACR70 and PASI50/75/90 compared with etanercept at week 24, in both the US and Germany (all p?<?0.02). Adalimumab had lower CPR than infliximab for all outcomes at week 24 (all p?<?0.05).

Conclusion:

Adalimumab is associated with higher ACR70 and PASI50/75/90 response rates than etanercept at week 24 and a higher ACR70 response rate than infliximab at week 14. Adalimumab has significant advantages over etanercept and infliximab in CPR across multiple end-points.

Key limitations:

The matching-adjusted indirect comparison method cannot account for unobserved differences in patient characteristics across trials, and only a head-to-head randomized clinical trial can fully avoid the limitations of indirect comparisons. CPR findings are limited to the US and German markets, and may not be generalizable to other markets with different relative pricing.     

A cost-utility analysis of adjunctive treatment with newer antiepileptic drugs in the UK

Summary

A recent review found that economic assessment of epilepsy treatment relies largely on hypothetical modelling of outcomes and combining these with resource and cost data from different sources. Prospective evaluations combining cost studies with outcome assessments are lacking. However, such a prospective observational study has been carried out previously, but only partially reported. We present a comprehensive cost-utility analysis of adjunctive newer antiepileptic drugs (AEDs) based on observational data from that study, and assess the uncertainty of the results using bootstrapping.

A total of 125 patients with intractable epilepsy were recruited. Each patient was about to start treatment with a new adjunctive AED [clobazam, (non-proprietary) gabapentin (Neurontin®, Parke-Davis, UK), lamotrigine (Lamictal®, GlaxoSmithKline, UK), topiramate (Topamax®, Janssen-Cilag, UK), or vigabatrin (Sabril®, Aventis Pharma, UK)]. Patients completed semi-structured interviews on resource use, side effects, and the EuroQol EQ-5D. Patients were followed up for 6 months. Patient-specific cost and utility data were analysed separately for each AED on an intent-to-treat basis. Uncertainty in the estimated incremental cost-utility ratios was quantified using the non-parametric bootstrap method, and cost-effectiveness acceptability curves were calculated.

At 6 months, 78 patients were still on their prescribed drug. Only topiramate and vigabatrin patients showed an increase in EQ-5D scores, and therefore dominated

other AEDs. Topiramate had an incremental cost-effectiveness ratio of £7,869/QALY compared with vigabatrin, and had more than a 50% chance of being optimal if the ceiling ratio was above £10,000/QALY.

Observational studies provide a valuable source of information for the economic evaluation of AEDs. In this study non-parametric bootstrapping was used to confirm the cost-effectiveness of adjunctive topiramate for patients with refractory epilepsy.