Calculation Of Quality-adjusted Life-years Research Articles

Differences in health utilities between cancer patients and the general population: The case of Quebec using the SF-6Dv2

A considerable debate persists in the literature about whose preferences should be considered in the calculation of quality-adjusted life-years. Some suggest considering only the preferences of the general population, while others advocate for the consideration of those of patients or a combination of both. This study aims to inform and measure the differences in health preferences between cancer patients and the general population in Quebec. A total of 60,976 observations representing the preferences of the general population for various health states were collected and used to develop a new value set using the SF-6Dv2. This value set was generated by combining 34,299 observations with time trade-off (TTO) and 26,677 observations with discrete choice experiment (DCE). Utility scores derived from this value set were compared to those of patients' preferences from a new value set in breast and colorectal patients for the SF-6Dv2. For both patients and the general population, the ‘Pain’ dimension was the highest contributor to the utility score. However, noticeable differences were observed in the estimates. Estimates of levels 2 and 3 were generally lower for cancer patients, while they were more likely to have greater estimates in severe levels. Significant differences in utility scores were also noticed with the general population showing higher mean utility scores for the same health states. These differences increased as the health states worsened. This study sheds light on the existing differences in preferences between cancer patients and the general population of Quebec for a better consideration in healthcare decision-making.

Fair Funding Decisions: Consistency of the Time Horizons Used in the Calculation of Quality-Adjusted Life Years for Therapies for Very Rare Diseases by the National Institute for Health and Care Excellence in England.

The National Institute for Health and Care Excellence (NICE) in England uses quality-adjusted life years (QALYs) to assess the cost-effectiveness of treatments. A QALY is a measure that combines the size of the clinical benefit of a treatment with the time the patient benefits from it, i.e., the time horizon. We wanted to know how consistently QALY gains are calculated at NICE. Therefore, we have analysed information on the time horizons used for the QALY calculations of the concluded evaluations conducted under the Highly Specialised Technologies programme for treatments of very rare diseases at NICE. For treatments with final guidance published by December 2023 (n = 29), a time horizon of median 97.5 years (range: 35 to 125 years) was used to calculate the QALY gains. For most QALY calculations, the accepted time horizon was longer than either the expected treatment duration or the estimated life expectancy. In contrast, for the only technology with a final negative funding decision, i.e., afamelanotide for treating the lifelong chronic disease erythropoietic protoporphyria, a time horizon that was shorter than the expected treatment duration was used. The fairness and consistency of the evaluation process of treatments for very rare diseases at NICE should be reviewed.

Are the Newest Anti-Alzheimer’s Medicines Being Evaluated Under Outdated Pricing Paradigms?

The 2021 approval of aducanumab in the United States, was not followed by approvals in Europe, Canada, Australia or elsewhere; nonetheless, the initial pricing of $56,00.00/year created a firestorm of controversy. The 2023 Food and Drug Administration approval of lecanemab has been followed by approvals in Japan and China. The current (2024) costs are $26,500 in USA, $20,438 (National Health Insurance) in Japan and $28,180 (private market) in China. In Europe, a health technology assessment will drive coverage decisions and set single-payer prices for each health system for lecanemab and subsequently approved new treatments. For comparison, 2024 average pricing for the top five selling drugs for cancer [$198,273], arthritis [$83,666], hepatitis C [$75,118] and multiple sclerosis [$86,765] far exceed lecanemab’s annual cost. Could there be an anti-brain-health bias? The International Consortium for Health Outcomes Measurement notes that patient-centered outcome measures represent the ultimate measure of quality and they are always multi-dimensional. Quality-adjusted life-years (QALY) seem to be absent from the computation of pricing for anti-dementia treatments. Although global consensus on QALY calculations remains elusive, currently extant data are compelling. The QALY calculation is the change in utility value induced by the treatment, which is then multiplied by the duration of treatment effect to provide the number of QALYs gained. QALY ranges differ quite significantly, even amongst the most industrialized nations. Value-based pricing from double-blind, placebo-controlled trial results, demonstrating statistically significant beneficial effects on cognition and/or global function, would reward manufacturers for innovation whilst also enabling payer systems to remain solvent. Now that the first truly disease-modifying treatment for Alzheimer’s (lecanemab) has been approved, a second disease-modifying treatment (donanemab) appears to be heading for regulatory approval as well. The full value of these newest anti-dementia treatments may be understated when quantified under older pricing models and, hence, could unwittingly be a disincentive to further innovation. We now have disease-modifying and symptomatic relief treatments for Alzheimer’s disease to be included within the treating clinicians’ armamentarium and, when priced appropriately, access should be widely available whilst also encouraging further innovative anti-Alzheimer’s clinical research.

Prediction of the SF-6D utility score from Lung cancer FACT-L: a mapping study in China

ObjectiveTo develop a mapping algorithm for generating the Short Form Six-Dimension (SF-6D) utility score based on the Functional Assessment of Cancer Therapy-Lung (FACT-L) of lung cancer patients.MethodsData were collected from 625 lung cancer patients in mainland China. The Spearman rank correlation coefficient and principal component analysis were used to evaluate the conceptual overlap between the FACT-L and SF-6D. Five model specifications and four statistical techniques were used to derive mapping algorithms, including ordinary least squares (OLS), Tobit and beta-mixture regression models, which were used to directly estimate health utility, and ordered probit regression was used to predict the response level. The prediction performance was evaluated using the correlations between the root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the observed and predicted SF-6D scores. A five-fold cross-validation method was used to test the universality of each model and select the best model.ResultsThe average FACT-L score was 103.024. The average SF-6D score was 0.774. A strong correlation was found between FACT-L and SF-6D scores (ρ = 0.797). The ordered probit regression model with the total score of each dimension and its square term, as well as age and sex as covariates, was most suitable for mapping FACT-L to SF-6D scores (5-fold cross-validation: RMSE = 0.0854; MAE = 0.0655; CCC = 0.8197; AEs > 0.1 (%) = 53.44; AEs > 0.05 (%) = 21.76), followed by beta-mixture regression for direct mapping. The Bland‒Altman plots showed that the ordered probit regression M5 had the lowest proportion of prediction scores outside the 95% agreement limit (-0.166, 0.163) at 4.96%.ConclusionsThe algorithm reported in this paper enables lung cancer data from the FACT-L to be mapped to the utility of the SF-6D. The algorithm allows the calculation of quality-adjusted life years for cost-utility analyses of lung cancer.

Transitional Care Model in Germany: Findings from an economic analysis of a randomized controlled trial

IntroductionThe statutory discharge management system in German hospitals does not provide adequate transitional care for geriatric patients. The American Transitional Care Model (TCM), where a qualified professional supports the patient for a period before, during, and after discharge, could help to address this problem. In this study, we compared both approaches from an economic perspective. Our research questions were: (1) How do treatment costs per person differ when geriatric patients are supported according to the TCM compared with routine discharge management? (2) What are the intervention costs? MethodsThe present economic analysis was part of a randomized controlled trial conducted at a hospital in Germany. In this study, geriatric patients in the intervention group received care according to TCM and those in the control group received routine care. We obtained data from the hospital and a health insurance company. In a cost-cost analysis, we compared the treatment costs per patient incurred in both study groups. In cases where higher costs occurred in the intervention group, we also conducted a cost-utility analysis, using the 12-Item Short Form Survey questionnaire to collect quality of life data for the Quality Adjusted Life Years calculation. Intervention costs were calculated on the basis of staff salaries, working hours, and the cost of acquiring the necessary equipment. ResultsThe intervention group consisted of 109 geriatric patients, the control group of 119. The average quality of life score was slightly higher in the intervention group, but the difference was not significant. On average, the intervention group was less expensive. However, for individual cost types (e.g., rehabilitation), the intervention group incurred higher costs than the control group. The differences between the study groups were not significant for all cost types (p > 0.05). Intervention costs were estimated to be approximately 800 euros per patient. DiscussionThe TCM approach leads to savings. However, the amount of savings will depend on intervention costs, which vary in practice. After outlier exclusion, an unfavorable incremental cost-effectiveness ratio is observed for the TCM approach. ConclusionFrom an economic perspective, TCM in its present form provides no additional value to patient care compared with routine discharge management. However, we see an urgent need to optimize the existing discharge management system to ensure better transitional care for those affected. Therefore, we recommend that different TCM components should be tested in further studies to address the questions that could not be clarified in the present study.

Health-state utilities in long-term advanced melanoma survivors comparable with the general population.

Checkpoint inhibitors have been shown to substantially improve the survival of patients with advanced melanoma. With this growing group of survivors treated with immunotherapies, assessing their health-state utilities is essential and can be used for the calculation of quality-adjusted life years and for cost-effectiveness analyses. Therefore, we evaluated the health-state utilities in long-term advanced melanoma survivors. Health-state utilities were evaluated in a cohort of advanced melanoma survivors 24-36months (N = 37) and 36-plus months (N = 47) post-ipilimumab monotherapy. In addition, the health-state utilities of the 24-36months survivor group were assessed longitudinally, and utilities of the combined survival groups (N = 84) were compared with a matched control population (N = 168). The EQ-5D was used to generate health-state utility values, and quality-of-life questionnaires were used to establish correlations and influencing factors of utility scores. Health-state utility scores were similar between the 24-36months'- and the 36-plus months' survival group (0.81 vs 0.86; p = .22). In survivors, lower utility scores were associated with symptoms of depression (β = -.82, p = .022) and fatigue burden (β = -.29, p = .007). Utility scores did not significantly change after 24-36months of survival, and the utilities of survivors were comparable to the matched control population (0.84 vs 0.87; p = .07). Our results show that long-term advanced melanoma survivors treated with ipilimumab monotherapy experience relatively stable and high health-state utility scores.

IMMEDIATE WEIGHT BEARING FOLLOWING ANKLE FRACTURE FIXATION IS LESS COSTLY AND MORE EFFECTIVE THAN NON-WEIGHT BEARING: INWN TRIAL RESULT

Is Non-Weight-Bearing Necessary? (INWN) is a pragmatic multicentre randomised controlled trial comparing immediate protected weight-bearing (IWB) with non-weight-bearing cast immobilisation (NWB) following ankle fracture fixation (ORIF). This trial compares; functional outcomes, complication rates and performs an economic analysis to estimate cost-utility.IWB within 24hrs was compared to NWB, following ORIF of all types of unstable ankle fractures. Skeletally immature patients and tibial plafond fractures were excluded. Functional outcomes were assessed by the Olerud-Molander Ankle Score (OMAS) and RAND-36 Item Short Form Survey (SF-36) taken at regular follow-up intervals up to one year. A cost-utility analysis via decision tree modelling was performed to derive an incremental cost effectiveness ratio (ICER). A standard gamble health state valuation model utilising SF-36 scores was used to calculate Quality Adjusted Life Years (QALYs) for each arm.We recruited 160 patients (80 per arm), aged 15 to 94 years (M = 45.5), 54% female. Complication rates were similar in both groups. IWB demonstrated a consistently higher OMAS score, with significant values at 6 weeks (MD=10.4, p=0.005) and 3 months (MD 12.0, p=0.003). Standard gamble utility values demonstrated consistently higher values (a score of 1 equals perfect health) with IWB, significant at 3 months (Ẋ = 0.75 [IWB] / 0.69 [NWB], p=0.018). Cost-utility analysis demonstrated NWB is €798.02 more expensive and results in 0.04 fewer QALYs over 1 year. This results in an ICER of −€21,682.42/QALY. This negative ICER indicates cost savings of €21,682.42 for every QALY (25 patients = 1 QALY gain) gained implementing an IWB regime.IWB demonstrates a superior functional outcome, greater cost savings and similar complication rates, compared to NWB following ankle fracture fixation.

Quality-Adjusted Life Years in Erythropoietic Protoporphyria and Other Rare Diseases: A Patient-Initiated EQ-5D Feasibility Study

Erythropoietic protoporphyria (EPP) is an ultra-rare inborn error of metabolism characterised by painful phototoxic burn injuries after short exposure times to visible light. Patients with EPP are highly adapted to their condition which makes the quantification of their health-related quality of life (QoL) challenging. In the presented patient-initiated feasibility study, we describe a new approach to assess treatment benefits in EPP by measuring QoL with the generic EQ-5D instrument in five patients under long-term (≥two years) treatment with afamelanotide, the first approved therapy for EPP. For the study, we selected patients with EPP who in addition were affected by an involuntary treatment interruption (caused by a temporary reimbursement suspension) because we hypothesized that individuals who had previously unlearned their adaptation are better able to assess their life without treatment than treatment-naïve patients. QoL under treatment was comparable to the age-matched population norm, and retrospective results for a treatment interruption and phototoxic reaction time point were comparable to the QoL of patients with chronic neuropathic pain and acute burn injuries, respectively. The results were accepted by the National Institute for Health and Care Excellence in England for their evaluation of the cost-effectiveness of afamelanotide, i.e., the calculation of quality-adjusted life years.

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

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

Economic burden of the novel coronavirus infection: a systematic review

Background. The sudden emergence and rapid spread of the novel coronavirus infection (COVID-19) caused tremendous burden on the health care system including the economic one. In this regard, many questions concerning the prioritization of funding for various restrictive and preventive procedures have arisen; also the introduction of various intervention methods for monitoring and timely treatment of post-COVID consequences became an urgent problem. These challenges actualized the development of pharmacoeconomic methods that improve the quality of decisions making in such extreme conditions.Objective: to systematize available studies on the assessment of the global economic burden of the novel coronavirus infection.Material and methods. A feature of the proposed review design was the highlighting of the observed shortcomings and areas in which scientists make additions to the assessment methods taking into account the chronology of the pandemic determining changes in the information field. Therefore, an analysis was made of 80 studies published in 2020–2022 and dedicated to the assessment and forecast of the global economic burden of COVID-19. The main inclusion criteria for the studies was the estimation of COVID-19 global burden. The search was carried out in PubMed/MEDLINE, Web of Science, Scopus, and eLibrary databases. Using a predefined data collection form, two reviewers independently extracted information characterizing the studies.Results. An analysis of the publications showed a fairly wide variety of studies in the field of the COVID-19 burden, including those determined by the difference in observation objects, analysis methods, factors taken into account, etc. Scientists actively use international (73.8%) and national (90%) databases, and surveys (57.5%). Predominantly, the estimates involve the calculation of quality-adjusted life years lost (QALY) (66.3%), 37.6% of the studies are based on the results of constructing scenario models, 28.8% consume algorithms of epidemiological SIR (susceptible, infected, or recovered) models, and 66.3% provide for cost assessment. As part of the estimated economic burden, the loss of productivity (26.3% of publications), the introduction of vaccination (32.5%), comorbidity (25%), post-COVID complications (17.5%) are considered.Conclusion. A significant interest of the world scientific community in assessing the COVID-19 global burden is observed, determined by the search for the most effective study methods. Further investigations in this area should focus on detailing within the estimated economic burden of losses associated with post-COVID-19 complications, including their various combinations, as well as on the analysis of the correlation and mutual compensation of effects from various types of treatment, with a deeper study of indirect losses. The results of this work will be also useful in conducting similar studies, including for determining their design and applying modern mathematical modeling tools.

Value Set for the EQ-5D-Y-3L in Hungary.

BackgroundThe Hungarian health technology assessment guidelines recommend the use of the EuroQol instrument family in quality-adjusted life-year calculations. However, no national value set exists for the EQ-5D-Y-3L or any other youth-specific instrument.ObjectiveThis study aims to develop a national value set of the EQ-5D-Y-3L for Hungary based on preferences of the general adult population.MethodsThis study followed the international valuation protocol for the EQ-5D-Y-3L. Two independent samples, representative of the Hungarian general adult population in terms of age and sex were recruited to complete online discrete choice experiment (DCE) tasks and composite time trade-off (cTTO) tasks by computer-assisted personal interviews. Adults valued hypothetical EQ-5D-Y-3L health states considering the health of a 10-year-old child. DCE data were modelled using a mixed logit model with random-correlated coefficients. Latent DCE utility estimates were mapped onto mean observed cTTO utilities using ordinary least squares regression.ResultsOverall, 996 and 200 respondents completed the DCE and cTTO surveys, respectively. For each domain, the value set resulted in larger utility decrements with more severe response levels. The relative importance of domains by level 3 coefficients was as follows: having pain or discomfort > feeling worried, sad or unhappy > mobility > doing usual activities > looking after myself. Overall, 12.3% of all health states had negative utilities in the value set, with the worst health state having the lowest predicted utility of − 0.485.ConclusionThis study developed a national value set of the EQ-5D-Y-3L for Hungary. The value set enables to evaluate the cost utility of health technologies for children and adolescents based on societal preferences in Hungary.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01190-2.

Development of a balanced instrument to measure global health-related quality of life: The 13-MD.

Generic instruments are of interest in measuring global health-related quality of life (GHRQoL). Their applicability to all patients, regardless of their health profile, allows program comparisons of whether the patients share the same disease or not. In this setting, quality-adjusted life-year (QALY) instruments must consider GHRQoL to allow the best programs to emerge for more efficiency in health resource utilization. However, many differences may be perceived among the existing generic instruments relative to their composition, where dimensions related to physical aspects of health are generally depicted more often than dimensions related to mental or social aspects. The objective of this study was to develop a generic instrument that would be complete in its covered meta-dimensions and reflect, in a balanced way, the important aspects of GHRQoL. To this end, a Delphi procedure was held in four rounds, gathering 18 participants, including seven patients, six caregivers, and five citizens. The structure of the instrument derived from the Delphi procedure was submitted to psychometric tests using data from an online survey involving the general population of Quebec, Canada (n = 2,273). The resulting questionnaire, the 13-MD, showed satisfying psychometric properties. It comprises 33 items or dimensions, with five to seven levels each. The 13-MD reflects, in a balanced form, the essential aspects of GHRQoL by including five meta-dimensions for physical health, four meta-dimensions for mental health, three meta-dimensions for social health, and one meta-dimension for sexuality and intimacy. The next step will involve the development of a value set for the 13-MD to allow QALY calculation.

Is EQ-5D-5L Better Than EQ-5D-3L Over Time? A Head-to-Head Comparison of Responsiveness of Descriptive Systems and Value Sets from Nine Countries.

ObjectivesThe aim of this study was to compare the responsiveness of EQ-5D-3L (3L) with EQ-5D-5L (5L) descriptive systems and value sets in two independent samples (rehabilitation and stroke patients).MethodsDescriptive system results were compared cross-sectionally, and descriptive responsiveness was tested by calculating changed level responses (‘moves’) from baseline to follow-up, proportion of improved patients, Paretian Classification of Health Change (PCHC), and probability of superiority (PS). Responsiveness of values based on nine country-specific value sets was assessed by standardized response mean (SRM) and standardized effect size (SES). Relative efficiency of 5L over 3L was assessed by calculating ratios of the SRM and SES statistics.ResultsDescriptive comparisons confirmed earlier evidence and showed a consistent overestimation of health problems in 3L. Descriptive responsiveness improved with 5L in terms of moves per respondent, proportions of improved patients and PS, whereas PCHC showed mixed results. Better value responsiveness statistics were observed for 5L in rehabilitation patients for all value sets. In stroke patients, 3L showed better responsiveness statistics compared with 5L. Relative efficiency results were moderately to strongly better with 5L for rehabilitation, and slightly to moderately better with 3L for stroke.ConclusionsDescriptive results were the main driver of 3L–5L responsiveness differences. Responsiveness of 3L was influenced by the ‘confined to bed’ label and the overestimation bias of 3L, which affected all responsiveness results. This may impact quality-adjusted life-year (QALY) estimations, leading to over- or underestimations of QALYs gained, depending on the condition and condition severity. QALY calculations based on 5L data will result in more accurate estimates.

Valuing the Quality-of-Life Aged Care Consumers (QOL-ACC) Instrument for Quality Assessment and Economic Evaluation.

ObjectiveThis paper reports on the valuation of the classification system for the Quality-of-Life Aged Care Consumers (QOL-ACC) instrument using a discrete choice experiment (DCE) with duration with a large sample of older people receiving aged care services.MethodsA DCE with 160 choice sets of two quality-of-life state–survival duration combinations blocked into 20 survey versions, with eight choice sets in each version, was designed and administered through an on-line survey to older Australians receiving aged care services in home and via interviewer facilitation with older people in residential aged care settings. Model specifications investigating preferences with respect to survival duration and interactions between QOL-ACC dimension levels were estimated. Utility weights were developed, with estimated coefficients transformed to the 0 (being dead) to 1 (full health) scale to generate a value set suitable for application in quality assessment and for the calculation of quality-adjusted life-years for use in economic evaluation.ResultsIn total, 953 older people completed the choice experiment with valid responses. The estimation results from econometric model specifications indicated that utility increased with survival duration and decreased according to quality-of-life impairment levels. An Australian value set (range − 0.56 to 1.00) was generated for the calculation of utilities for all QOL-ACC states.ConclusionThe QOL-ACC is unique in its focus on measuring and valuing quality of life from the perspective of older people themselves, thereby ensuring that the preferences of aged care service users are the primary focus for quality assessment and economic evaluation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40273-022-01158-2.

MO214: Health-Related Quality of Life Among Patients With Anca Vasculitis

BACKGROUND AND AIMSAnti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a debilitating disease that can have a significant impact on a patient's quality of life. The aim of this study was to assess the longitudinal quality of life amongst those diagnosed with AAV using the EQ-5D instrument, which allows for calculation of quality-adjusted life years (QALYs.)METHODA total of 343 patients with AAV participated in this study, of which 191 (55.7%) were male, resulting in 2746 episodes. The EQ-5D-5L standardised instrument was used to evaluate health-related quality of life in the domains of mobility, self-care, usual activities, pain/discomfort, anxiety/depression and to generate a summary index score. Overall health was also rated using a visual analogue scale (0–100). EQ-5D questionnaires were completed during routine nephrology clinic attendances and through a vasculitis patient support smartphone app. We used a random effects model to control for multiple entries relating to individual patients.RESULTSA lower quality of life was seen amongst those with AAV (median index value 0.80, overall population average 0.856). The mean visual analogue scale score was 75.6 ± 17.3 (overall population average 82.8, Fig. 1). Patients’ pain and discomfort level (mean 1.95) was most affected while self-care (mean 1.33) was least affected (Fig. 1). An increase in BVAS tightly correlated with a reduction in quality of life. Using the random effects model, the index score was seen to decrease with increasing age with a 2.7% reduction in index score per decade. A 7% reduction in index score was seen during periods of disease activity compared with periods of remission. Patients with end-stage kidney disease requiring dialysis had an 8% reduction in index score. A reduced quality of life was seen following COVID-19 lockdown with a 5% reduction in index score seen. Using a median survival rate of 6.16 years for patients with small vessel vasculitis, we calculated the QALYs for this population as 4.9 years.FIGURE 1:(A) Domain-specific EQ5D levels and (B) visual analogue score. Both graphs reflect mean and 95% confidence interval.CONCLUSIONWe have defined for the first time the EQ-5D index value over the full disease course in patients with AAV. Notably, we have identified a reduction in quality of life during periods of disease activity. Other studies have demonstrated a reduction in quality of life during active disease using the AAV–PRO questionnaire and the Medical Outcomes Study Short Form-36. A decrease in work productivity has also been noted. Previously reported mean index values of 0.72 and 0.76 were lower than our observed values, although both are significantly reduced compared with population norms. In conclusion, this research highlights the negative impact of AAV on patients’ lives.

The long life-time shadow of bullying: cost-effectiveness of KiVa to reduce bullying in primary schools

BackgroundThe ‘long shadow’ of childhood bullying can extend beyond immediate adverse mental health and educational outcomes well into adulthood, with associated long-term health and social care costs. Reducing bullying is therefore a public health priority. KiVa, a school-based anti-bullying programme, is effective in reducing bullying in schools in Finland and is currently being tested in the UK through the large-scale Stand Together trial. MethodsThe Stand Together trial is a two-arm, pragmatic multicentre cluster randomised controlled trial (RCT) to test the effectiveness and cost-effectiveness of KiVa in reducing bullying in UK primary schools compared to usual practice over one academic year. The trial is targeting approximately 13,000 7- to 11-year-olds in 116 primary schools across England and Wales, including North Wales, the West Midlands, South East- and South West England. Usual practice is defined as the delivery of the Personal and Social Education (PSE) curriculum in Wales and the Personal, Social, Health and Economic (PSHE) Education in England. To assess cost-effectiveness, we are conducting a cost-utility analysis and wider cost-consequence analysis from a school and societal perspective. Pupil self-reported health-related quality of life (CHU9D) is the primary outcome to enable the calculation of quality-adjusted life years (QALYs) in an Incremental Cost Effectiveness Ratio (ICER). The cost-consequence analysis will consider other outcomes such as pupil self-reported bullying-victimisation, pupil absence and bullying-related service use, teacher wellbeing and the frequency of parent-school meetings regarding bullying. Cost calculations will include the time and resources required to implement KiVa in schools versus usual practice, including the cost of resources and training. We will undertake sensitivity analysis to explore the impact of assumptions about dose of intervention, adherence, and costs of delivery. Our analyses will provide the first large-scale RCT-based evidence of the cost-effectiveness of KiVa in UK primary schools.

Periviable Breech Delivery Decision Analysis

Background/Objective: The optimal mode of delivery (MOD) for malpresentation in periviable deliveries (22-24 weeks), remains a source of debate. Neonatal and maternal complications can arise from both vaginal (VD) and cesarean delivery (CD), and the threat of maternal morbidity extends to subsequent pregnancies. It has been difficult to compare these risks while counseling patients about MOD options, so we sought to create a decision tree that maps probable outcomes associated with breech deliveries at 23- and 24-weeks’ gestation, as well as complications posed for subsequent pregnancies. 
 
 Methods: An extensive literature review was conducted to identify risk estimates of periviable maternal and neonatal outcomes, along with elective repeat CD (ERCD) and trial of labor after cesarean (TOLAC) for subsequent pregnancies. Probabilities were inputted into TreeAge software, starting with primary maternal health states that may result from CD and VD – “death”, “hysterectomy”, or “no hysterectomy”, followed by the probability of neonatal health states– “death”, “severe morbidity”, or “no severe morbidity”. The likelihood of placenta previa or normal placenta was considered for subsequent pregnancies. We factored in the possibility of ERCD or TOLAC and the associated maternal and neonatal risks for each. 
 
 Results: Final design of the tree is complete and risk estimates have been inputted. Primary analysis and sensitivity analyses are planned for August 2021. Ultimately, we will also be able to use measured utility values to calculate quality adjusted life years (QALYs) for each health state. 
 
 Conclusion and Clinical Impact: Whether CD or VD is optimal for breech presentation in periviable delivery is influenced by a complex array of factors, including future reproductive plans and maternal values related to potential neonatal and maternal morbidity and mortality. Quantifying risks associated with each MOD will aid providers in their efforts to help families make informed decisions and reduce morbidity across the reproductive lifespan.

The remarkably frequent use of EQ-5D in non-economic research

IntroductionEQ-5D is an instrument which has been utilized for a variety of purposes, including in health-economic appraisals as an input into quality-adjusted life year (QALY) calculations. Indeed, it is the most-widely applied instrument for health-economic appraisal worldwide, and is recommended for use in QALY calculations by many national Health Technology Assessment (HTA) agencies. There is also a growing body of evidence for its usefulness in a variety of settings other than economic appraisals, but such use has not been well-documented. This study addresses this issue and documents how EQ-5D has been applied in both the non-economic and economic contexts.MethodsThe PubMed database was searched using the terms ‘EQ-5D’, ‘EQ-5D AND cost’, and ‘EQ-5D AND cost AND QALY’ from 1 January 1980 to 31 December 2019. We concentrated on 2019 publications for more detailed analyses. All the data collected for 2019 were downloaded and collected in EndNote. For 2019 only, we classified economic and non-economic use based on the inclusion of ‘cost’. We also checked by manual inspection whether the search terms were suitable in correctly identifying economic and non-economic use. Variants of the non-economic use of EQ-5D were classified as follows: (a) as a quality of life outcome measure; (b) as a tool for methodological research; (c) methodological issues of EQ-5D itself; (d) comparisons with other quality of life questionnaires; (e) mapping studies; (f) value sets; (g) alongside costs but no QALY calculated; and (h) other.ResultsThe first publication found was from 1990. Up to and including 2019, 10,817 publications were identified, of which more than two in three did not contain any reference to costs or QALYs. In 2019, a total of 1409 manuscripts were identified, of which 239 were specifically for EQ-5D-5L. Four hundred and seven (28.9%) included some form of ‘costs’ and 157 (11.1%) both ‘costs’ AND ‘QALYs’ terms. For EQ-5D-5L, the corresponding numbers were 104 (43.5%) and 29 (12.1%), respectively. After manually checking all the 1409 papers, three were duplicated records, which were omitted. In the remaining 1406 papers, only 40 (2.8%) contained the term ‘cost’, but not ‘cost per QALY’, and only 117 (8.3%) were identifiable as economic evaluations using the term ‘cost per QALY’. Most non-economic use of EQ-5D was as a quality-of-life outcome measure (72.8%). Other applications were: as a tool for methodological research (6.7%); comparison studies (3.7%); EQ-5D methodological issues (3.5%); containing costs but not QALYs (2.8%); mapping (1.3%); value sets (0.4%); and other papers (0.4%).ConclusionsThe majority of the studies retrieved, covering a wide variety of research areas, reported upon the non-economic use of EQ-5D. Despite being the most-used instrument worldwide for QALY calculations, economic appraisal accounted for only a small, but important, part of published use.

Utility Estimation of Rituximab Versus Bendamustine-Rituximab Induction in Indolent Non-Hodgkin Lymphomas Using Patient-Reported Quality of Life Survey Data

BackgroundRituximab induction (RI) and bendamustine-rituximab (BR) induction are both options for the frontline management of indolent non-Hodgkin lymphomas (NHLs). Although BR induces longer progression-free survival than RI, BR confers more toxicity and a longer duration of initial induction than RI. The effects of RI versus BR on health-related quality of life (HRQoL) after induction treatment, and the implications on patient utility and quality-adjusted life-years (QALYs), have not been previously studied. We conducted a cost-utility analysis of RI versus BR utilizing patient-reported HRQoL survey data.MethodsPatient-reported utility data were collected from the Hoogland Lymphoma Biobank, which enrolls patients with lymphoma at the University of Chicago and prospectively administers serial patient-level HRQoL surveys utilizing the Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-Lymphoma (FACT-LYM) instruments. Patients with indolent NHLs (follicular lymphoma, marginal zone lymphoma, and lymphoplasmacytic lymphoma) who were treated with frontline RI (4 doses of weekly rituximab) or BR (6 months of monthly BR) and who had completed HRQoL surveys at both of the following timepoints were included: within 6 months of treatment completion (timepoint 1) and 6-12 months after treatment completion (timepoint 2). Individual FACT-G scores were converted into EQ-5D utility index scores using a United States-based validated mapping algorithm (Teckle et al., Health Qual Life Outcomes, 2013). Cost-utility analysis was performed by trial-based methodology in which patient-level QALYs are estimated using area-under-the-curve (AUC) between timepoints 1 and 2. Incremental cost utility ratio (ICUR) was calculated utilizing cost and life years gained inputs of RI and BR from previous cost-effectiveness literature. All HRQoL scores for RI versus BR at both timepoints were compared with unpaired two-tailed t-tests.ResultsThere were 19 patients treated with RI and 13 patients treated with BR (Table 1). At timepoint 1, the BR cohort had significantly worse physical and emotional wellbeing on the FACT-G compared to the RI cohort, with emotional wellbeing significantly worse in the BR cohort at timepoint 2 (Table 2). EQ-5D utility index was stable at both timepoints for the RI cohort, and was initially lower in the BR cohort at timepoint 1 compared to RI but improved by timepoint 2 (Table 2). During the initial 12-month observation period after treatment completion, quality of life was higher for RI compared to BR (+0.02); however, when accounting for life years gained, the BR cohort had more QALYs (+1.53) (Table 3). Compared with RI, BR had an ICUR of $37,442.ConclusionsAlthough HRQoL was inferior in the BR cohort in the first year after treatment completion, particularly in the emotional wellbeing domain on FACT-G, BR induction conferred higher QALYs owing to more life years gained as compared to RI induction. Given a cost-effectiveness threshold of $100,000 in the United States (Vanness et al., Ann Intern Med, 2021), BR induction is likely to be cost effective when considering patient-reported HRQoL over the first year after treatment completion. The present analysis is limited by the small number of patients from which utility values at each timepoint were derived; however, calculation of QALYs using a database of prospectively-collected HRQoL data is feasible. Further incorporation of patient-reported outcomes into cost-utility analysis is warranted, particularly with larger datasets. [Display omitted] DisclosuresSmith: Alexion, AstraZeneca Rare Disease: Other: Study investigator; Celgene, Genetech, AbbVie: Consultancy.

Inequality and heterogeneity in health-related quality of life: findings based on a large sample of cross-sectional EQ-5D-5L data from the Swedish general population

PurposeThis study aimed to investigate inequality and heterogeneity in health-related quality of life (HRQoL) and to provide EQ-5D-5L population reference data for Sweden.MethodsBased on a large Swedish population-based survey, 25,867 respondents aged 30‒104 years, HRQoL is described by sex, age, education, income, economic activity, health-related behaviours, self-reported diseases and conditions. Results are presented by EQ-5D-5L dimensions, respondents rating of their overall health on the EQ visual analogue scale (EQ VAS), VAS index value and TTO (time trade-off) index value allowing for calculation of quality-adjusted life years (QALYs). Ordinary Least Squares and multivariable logistic regression analyses were used to study inequalities in observed EQ VAS score between socioeconomic groups and the likelihood to report problems on the dimensions, respectively, adjusted for confounders.ResultsIn total, 896 different health states were reported; 24.1% did not report any problems. Most problems were reported with pain/discomfort. Women reported worse HRQoL than men, and health deteriorated with age. The strongest association between diseases and conditions and EQ VAS score was seen for depression and mental health problems. There was a socioeconomic gradient in HRQoL; adjusting for health-related behaviours, diseases and conditions slightly reduced the differences between educational groups and income groups, but socioeconomic inequalities largely remained.ConclusionEQ-5D-5L population reference (norms) data are now available for Sweden, including socioeconomic differentials. Results may be used for comparisons with disease-specific populations and in health economic evaluations. The observed socioeconomic inequality in HRQoL should be of great importance for policy makers concerned with equity aspects.