Health State Utility Research Articles

Early Cost-Utility Analysis of Ataluren and Eteplirsen in the Treatment of Duchenne Muscular Dystrophy in Egypt

ObjectivesAtaluren and eteplirsen are orphan drugs that delay progression of Duchenne muscular dystrophy in mutation-specific subgroups. They have yet to be approved in Egypt but are expected to reach the market soon. This study describes 2 cost-utility models comparing the drugs with the standard of care. MethodsWe used a partition-survival model with 5 states based on the ambulatory status to model a cohort of ambulatory patients at the age of 5 years. Baseline curves were obtained from a published model; then the ambulation loss curve was updated using the Kaplan-Meier curve of the standard of care from a study by McDonald et al. Other curves were updated by calibration to this curve. Costs and utilities were from a local study. Deterministic and probabilistic sensitivity analyses were conducted. Prices were estimated based on other orphan drugs’ prices. ResultsIn the base case, ataluren 1000 mg and eteplirsen 50 mg/mL resulted in an incremental cost-effectiveness ratio of EGP 51 745 605 and EGP 69 652 533/quality-adjusted life-year, respectively, at their hypothetical prices of EGP 308 600 for ataluren 30-sachet pack and EGP 62 800 for eteplirsen 10 mL vial. The incremental cost-effectiveness ratio was sensitive to health state utilities but not to state costs. At EGP 911 719/quality-adjusted life-year threshold, the value-based prices were EGP 4680 for ataluren 1000 mg and EGP 733 for eteplirsen 10 mL vial. ConclusionsBased on these models, there is a huge gap between the prices of orphan drugs and their value-based prices, which highlights the need for major policy reforms in the assessment and pricing of orphan drugs.

Health state utility and health-related quality of life measures in patients with advanced ovarian cancer

PurposeMeasuring health-related quality of life (HRQoL) in ovarian cancer patients is critical to understand the impact of disease and treatment. Preference-based HRQoL measures, called health state utilities, are used specifically in health economic evaluations. Real-world patient-reported data on HRQoL and health state utilities over the long-term course of ovarian cancer are limited. This study aims to determine HRQoL and health state utilities in different health states of ovarian cancer. MethodsThis cross-sectional, multicenter study included patients with stage III-IV ovarian cancer in six health states: at diagnosis, during chemotherapy, after cytoreductive surgery (CRS), after chemotherapy, in remission, and at first recurrence. HRQoL was measured using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30, and the ovarian cancer-specific module OV28. Health state utilities were assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire. Descriptive analyses were performed for each health state. ResultsTwo hundred thirty-two patients participated, resulting in 319 questionnaires. Median age was 66 years. The lowest HRQoL was observed during chemotherapy and shortly after CRS. Physical and role functioning were most affected and the highest symptom prevalence was observed in the fatigue, nausea, pain, dyspnea, gastrointestinal, neuropathy, attitude, and sexuality domains. Patients in remission had the best HRQoL. Mean utility values ranged from 0.709 (±0.253) at diagnosis to 0.804 (±0.185) after chemotherapy. ConclusionsThis study provides clinicians with a valuable resource to aid in patient counseling and clinical decision-making. The utilities, in particular, are crucial for researchers conducting economic analyses to inform policy decisions.

Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): A Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Low or Intermediate Risk Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer diagnosed among men in the United States, and the majority of patients are diagnosed with localized disease. Men with localized prostate cancer have several treatment options including external beam radiotherapy with either photons or protons. Proton beam therapy (PBT) has certain dosimetric advantages and the potential to reduce treatment-associated morbidity and improve oncologic outcomes, but current PBT is significantly more costly than intensity-modulated radiotherapy (IMRT). The PARTIQoL trial (NCT01617161) is the first multicenter phase 3 randomized trial comparing protons to photons in the treatment of localized prostate cancer. Patients with low or intermediate risk prostate cancer (Stage T1c-T2c, PSA < 20, Gleason score ≤ 7) are randomized to receive either PBT or IMRT, with targeted recruitment efforts for minority populations. A companion registry study has concurrently enrolled patients who declined randomization or whose insurance denied coverage for PBT. Patients are stratified by clinical site, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). Participants are followed longitudinally to assess patient-reported outcomes (PROs) of bowel, urinary, and erectile function for 60 months after completion of radiotherapy (with an option for additional follow up through 10 years). Participants may also participate in correlative studies, including serial CT imaging during treatment and analyses of biopsy tissue, blood and urine specimens. The primary objective is to compare PROs of bowel function using the EPIC score at 24 months following completion of radiation. Secondary objectives are to assess treatment-related differences in urinary and erectile functions, adverse events, efficacy endpoints (biochemical control, metastasis-free survival, disease-specific survival, and overall survival), health state utilities, perceptions of care, late effects, cost-effectiveness, association between radiotherapy dose distribution and PROs, and to identify biomarkers of radiation response and toxicity. The randomized trial has completed accrual, with 450 patients enrolled at 27 sites between June 2012 and November 2021. 20.3% of patients enrolled are non-white. Accrual on the companion registry is active, with 354 patients enrolled as of February 2023. Follow-up for the primary endpoint on the randomized trial will be reached in 2024. The PARTIQoL randomized clinical trial will rigorously assess the clinical benefits of PBT relative to IMRT and results will inform decision making by patients, providers, policymakers, and payers.

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy.

Abemaciclib was recently approved by the European Medicines Agency in combination with adjuvant endocrine therapy (ET) for adult patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive early breast cancer (EBC) at high risk of recurrence. To evaluate the cost-effectiveness of abemaciclib plus ET vs. ET alone in patients with HR+, HER2-, node-positive EBC at high risk of disease recurrence, from the Italian healthcare system perspective. A cohort state transition model was developed with five states: invasive disease-free survival (IDFS), nonmetastatic recurrence, remission, metastatic recurrence, and death. The analysis had a time horizon of 30years. Individual patient-level data from the monarchE trial (NCT03155997) were used to generate IDFS estimates. Resource use included drug acquisition/administration, best supportive care, terminal care, adverse events, hospitalization, post-progression therapy, and associated resource use in the metastatic disease health state. Health state utilities were derived from monarchE patient-level data and other sources, applying Italian tariffs where feasible. The estimated total discounted costs (€39,249 vs. €16,806; difference: €22,443) and quality-adjusted life years (QALYs) (11.49 vs. 10.50; difference: 0.99) were higher for abemaciclib plus ET compared with ET alone. The incremental cost-effectiveness ratio was €22,651 per QALY gained. The likelihood of abemaciclib plus ET being cost-effective vs. ET alone was 99% at a willingness-to-pay threshold of €30,000 per QALY gained. Abemaciclib plus ET is a cost-effective treatment option vs. ET alone for those with HR+, HER2- node-positive EBC at high risk of recurrence in Italy.

Scale agreement, ceiling and floor effects, construct validity, and relative efficiency of the PROPr and EQ-5D-3L in low back pain patients

BackgroundThe PROMIS Preference score (PROPr) is a new health state utility (HSU) score that aims to comprehensively incorporate the biopsychosocial model of health and apply favorable psychometric properties from the descriptive PROMIS system to HSU measurements. However, minimal evidence concerning comparisons to the EQ-5D-3L and the PROPr’s capability to differentiate clinical severity are available. Therefore, the aim of this study was to compare the PROPr to the EQ-5D-3L in terms of scale agreement, ceiling/floor effects, distribution, construct validity, discriminatory power, and relative efficiency (RE) in terms of the Oswestry Disability Index (ODI) for patients with low back pain (LBP).MethodsWe used intra-class correlation coefficients (ICC) and Bland–Altman plots to compare the PROPr and EQ-5D-3L with regared to scale agreement in a cross-sectional routine sample of LBP patients. For distribution, we used the Pearson’s coefficient for skewness and for ceiling/floor effects, a 15%-top/bottom threshold. For convergent validity, we used Pearson’s correlation coefficients. For known-groups validity, we applied a linear regression with interaction terms (predictors sex, age, and ODI level) and an analysis of variance (ANOVA). For discriminatory power, we calculated the effect size (ES) using Cohen’s d and the ratio of the area under the receiver-operating characteristics curves (AUROC-ratio = AUROCPROPr/AUROCEQ-5D-3L). RE was measured using the ratio of F-values (RE = FPROPr/FEQ-5D-3L).ResultsOf 218 LBP patients, 50.0% were female and the mean age was 61.8 years. The mean PROPr (0.20, 95%CI: 0.18; 0.22) and EQ-5D-3L scores (0.55, 95%CI: 0.51; 0.58) showed low agreement (d = 0.35, p < 0.001; ICC 0.27, 95%CI: -0.09; 0.59). The PROPr’s distribution was positively skewed, whereas the EQ-5D-3L’s was negative. Neither tool showed ceiling/floor effects, but all EQ-5D-3L dimensions did. Pearson correlation was r = 0.66 (95%CI: 0.58; 0.73). Differences were invariant to sex and age but not to ODI severity: ESEQ-5D-3L > ESPROPr and RE < 1 in higher ODI severity; ESEQ-5D-3L < ESPROPr and RE > 1 in lower ODI severity. AUROC-ratios did not show significant differences in terms of ODI severity.ConclusionsAll PROPr and EQ-5D-3L biopsychosocial dimensions of health showed impairment in LPB patients. The capability of EQ-5D-3L and PROPr to differentiate ODI levels depends on ODI severity. Joint application of both tools may provide additional information.

Biomarkers-Based Cost-Effectiveness of Toripalimab Plus Chemotherapy for Patients with Treatment-Naive Advanced Non-Small Cell Lung Cancer.

This study examined the cost-effectiveness of first-line toripalimab plus chemotherapy (TC) for patients with advanced non-small cell lung cancer (NSCLC), excluding patients with nonsquamous NSCLC and EGFR/ALK mutations. It further analyzed the cost-effectiveness of this strategy in biomarker-based subgroups, all within the context of the Chinese healthcare system. Eighteen Markov models with 21-day Markov cycle lengths and 30-year time horizons were constructed in this study. Clinical effectiveness data were derived from the CHOICE-01 trial. Health state utilities and costs data were obtained from various sources. The primary outputs were the calculation of incremental cost-effectiveness ratios (ICERs), which were then compared to a willingness-to-pay (WTP) threshold of $17,961 per quality-adjusted life-year (QALY). This comparison was used to determine the treatment that offered greater cost-effectiveness. To account for uncertainty in the model, sensitivity analyses were conducted. For the overall patient population, the estimated ICER between first-line TC and placebo plus chemotherapy (PC) was $9445/QALY, significantly lower than the WTP threshold used in the model. In subgroups based on pathologic types, first-line TC had an ICER of $16,757/QALY for patients with nonsquamous NSCLC, slightly below the WTP threshold; first-line TC demonstrated dominance in patients with squamous NSCLC, indicating both better effectiveness and lower costs compared to first-line PC. In biomarkers-based subgroups, first-line TC was dominant over first-line PC in the subgroups with programmed cell death ligand1 (PD-L1) expression ≥ 50% and SMARCA4 mutations. Moreover, first-line TC had ICERs lower than the WTP threshold in other subgroups, except for the subgroup with RB1 mutations. Sensitivity analysis confirmed the robustness of these findings. From the perspective of the Chinese healthcare system, this study's findings suggested that first-line TC represents a cost-effective strategy for patients with advanced NSCLC. However, the cost-effectiveness of first-line TC varied across different subgroups when considering predictive biomarkers.

Modelling Health State Utilities as a Transformation of Time to Death in Patients with Non-Small Cell Lung Cancer.

When utilities are analyzed by time to death (TTD), this has historically been implemented by 'grouping' observations as discrete time periods to create health state utilities. We extended the approach to use continuous functions, avoiding assumptions around groupings. The resulting models were used to test the concept with data from different regions and different country tariffs. Five-year follow-up in advanced non-small cell lung cancer (NSCLC) was used to fit six continuous TTD models using generalized estimating equations, which were compared with progression-based utilities and previously published TTD groupings. Sensitivity analyses were performed using only patients with a confirmed death, the last year of life only, and artificially censoring data at 24 months. The statistically best-fitting model was then applied to data subsets by region and different EQ-5D-3L country tariffs. Continuous (natural) [Formula: see text] and [Formula: see text] models outperformed other continuous models, grouped TTD, and progression-based models in statistical fit (mean absolute error and Quasi Information Criterion). This held through sensitivity and scenario analyses. The pattern of reduced utility as a patient approaches death was consistent across regions and EQ-5D tariffs using the preferred [Formula: see text] model. The use of continuous models provides a statistically better fit than TTD groupings, without the need for strong assumptions about the health states experienced by patients. Where a TTD approach is merited for use in modelling, continuous functions should be considered, with the scope for further improvements in statistical fit by both widening the number of candidate models tested and the therapeutic areas investigated.

Cost-effectiveness of pemigatinib as a second-line treatment for advanced intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 fusions in Taiwan: from the evidence of the phase II trial and the perspective of Taiwan's National Health Insurance Administration

BackgroundIn December 2022, the Taiwan National Health Insurance Administration (NHIA) announced the reimbursement of three dosages of pemigatinib 4.5 mg, 9 mg, and 13.5 mg for treating advanced intrahepatic cholangiocarcinoma (ICC) with fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements and set the reimbursement price for pemigatinib 4.5 mg at NT$6600. This study aims to analyze the cost-effectiveness of pemigatinib 13.5 mg as a second-line treatment compared to mFOLFOX and 5-FU chemotherapy for advanced ICC patients with FGFR2 fusions/rearrangements from the perspective of Taiwan’s NHIA.MethodsThis study used a 3-state partitioned survival model to analyze the 5 year cost-effectiveness of pemigatinib as a second-line treatment for advanced ICC patients in whom first-line gemcitabine-based chemotherapy failed and to compare the results with those for the mFOLFOX and 5-FU chemotherapy regimens. Overall survival and progression-free survival were estimated from the FIGHT-202 trial (pemigatinib), ABC-06 trial (mFOLFOX), and NIFTY trial (5-FU). The price of pemigatinib 13.5 mg was set at the potentially highest listing price (NT$17,820). Other parameters of utility, disutility, and costs related to advanced ICC were obtained from the published literature. The willingness-to-pay threshold was three times the forecasted gross domestic product per capita in 2022 (NT$2,928,570). A 3% discount rate was applied to quality-adjusted life-years (QALYs) and costs. Several scenario analyses were performed, including a gradual price reduction for pemigatinib. Deterministic sensitivity analysis, probabilistic sensitivity analysis (PSA), and value of information were performed to assess uncertainty.ResultsPemigatinib was not cost-effective compared to mFOLFOX or 5-FU in the base-case analysis. When the price of pemigatinib was reduced by 50% or more, pemigatinib gained a positive net monetary benefit (mFOLFOX: NT$55,374; 5-FU: NT$92,437) and a 72% (mFOLFOX) and 77.1% (5-FU) probability of being cost-effective. Most of the uncertainty came from the medication cost of pemigatinib, health state utility, and the overall survival associated with pemigatinib.ConclusionsAccording to the NCCN guidelines, the daily use of pemigatinib 13.5 mg at the hypothesized NHIA price of NT$17,820/13.5 mg was not cost-effective compared to mFOLFOX or 5-FU. The price reduction scenario suggested a 50% price reduction, NT$8910 per 13.5 mg, for advanced ICC patients with FGFR2 fusions/rearrangements.

Association of body mass index from childhood to mid-adulthood with health-related quality of life in mid-adulthood

PurposeMost studies regarding the association of obesity with health-related quality of life (HRQoL) have assessed obesity at only one or two time points. We aimed to examine the associations of life course body mass index (BMI) from childhood with health-related quality of life (HRQoL) in mid-adulthood.MethodsData were from a cohort study of Australian children (n = 2254, mean baseline age 12.0 (2.0) years in 1985, 46.8% male). Weight and height were measured at baseline and measured or self-reported on average 20, 25, and 30 years later. Age and sex-standardised BMI-z score was calculated at each time point. Physical and mental HRQoL and health state utilities (HSUs) were measured by SF-12 and SF-6D at the last adult follow-up. Linear regression was used to examine the associations adjusting for age, sex, and childhood health status.ResultsHigher BMI-z score in childhood (βadjusted − 1.39, 95% CI − 1.73 to − 1.05) and increasing BMI-z score from childhood to young adulthood (βadjusted − 1.82, 95% CI − 2.17 to − 1.46) and from young to mid-adulthood (βadjusted − 1.77, 95% CI − 2.28 to − 1.26) were associated with lower physical HRQoL in mid-adulthood. Similar results were found for mid-adulthood HSUs (βadjusted ranged − 0.006 to − 0.014, all P < 0.05). Only increasing BMI-z score from young to mid-adulthood significantly related to poorer mental HRQoL (βadjusted − 0.74, 95% CI − 1.29 to − 0.19) in mid-adulthood.ConclusionHigh BMI from childhood to mid-adulthood had only modest associations with HRQoL and HSUs, with effects on physical HRQoL most apparent.

Can Independently Elicited Adult- and Child-Perspective Health-State Utilities Explain Priority Setting?

ObjectivesTime trade-off (TTO) utilities for EQ-5D-Y-3L health states valued by adults taking a child’s perspective are generally higher than their valuations of the same state for themselves. Ceteris paribus, the use of these utilities in economic evaluation implies that children gain less from treatments returning them to full health for a specified amount of time than adults. In this study, we explore if this implication affects individuals’ views of priority-setting choices between treatments for adults and children. MethodsWe elicited TTO utilities for 4 health states in online interviews, in which respondents valued states for a 10-year-old child and another adult their age. Views on priority setting were studied with person trade-off (PTO) tasks involving the same health states. We tested the ability of the subjects’ TTO utilities to predict these societal choices in PTO. ResultsThere are no significant differences between adult and child health state valuations in our study, but we do observe a substantial preference for treating children over adults in the PTO task. ConclusionsOur findings suggest that perspective-dependent health-state utilities only explain a small part of views on priority setting between adults and children. External equity weights might be useful to better explain the higher priority given to children.

Disutilities Associated with Intravenous Iron Infusions: Results from a Time Trade-off Survey and Diminishing Marginal Utility Model for Treatment Attributes in China.

Treatment process attributes can affect health state utilities associated with therapy. For intravenous iron, used to treat iron deficiency and iron deficiency anemia, research into process attributes is still lacking. This study estimated utilities associated with process attributes for intravenous iron infusions. An online survey including seven health state vignettes and time trade-off tasks was administered to participants, who were not patients living with iron deficiency or iron deficiency anemia, from a Chinese online panel. Vignettes used an identical description of iron deficiency and iron deficiency anemia but differed in the annual number of infusions, infusion duration, and infusion-associated risk of hypophosphatemic osteomalacia. Disutilities and their rate of change as the number of infusions increased were examined using a power model. The survey was completed by 1091 participants. The highest utilities were observed for one annual infusion of 15-30 minutes or 30-60 minutes, without risk of hypophosphatemic osteomalacia (0.754 and 0.746, respectively). In comparison, more infusions and infusions with a risk of hypophosphatemic osteomalacia were associated with lower utilities. Utility continued to decrease, but at a diminishing rate, as the annual number of infusions increased, with utility decrements of 0.006 and 0.002, respectively, when going from zero to one and from four to five infusions per year. All marginal disutilities were small (values <0.01). This study suggested that treatment attributes of intravenous iron infusions affect health state utilities. Using intravenous iron formulations that allow for fewer and shorter infusions without the risk of hypophosphatemic osteomalacia can reduce the number of visits required and increase patients' quality of life.

Cost-effectiveness of nivolumab and ipilimumab versus pembrolizumab and axitinib in advanced renal cell carcinoma with intermediate or poor prognostic risk: a Brazilian private healthcare system perspective

ObjectiveNivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) have demonstrated significant clinical benefits as first-line (1 L) treatments for intermediate/poor-risk advanced renal cell carcinoma (aRCC) patients. This study aimed to assess the cost-effectiveness of NIVO + IPI versus PEM + AXI from a Brazilian private healthcare system perspective, utilizing a novel approach to estimate comparative efficacy between the treatments.MethodsA three-state partitioned survival model (progression-free, progressed, and death) was developed to estimate costs, life-years (LYs), quality-adjusted LYs (QALYs), and the incremental cost-utility ratio (ICUR) over a 40-year time horizon. In the absence of head-to-head comparisons between NIVO + IPI and PEM + AXI, clinical data for NIVO + IPI was obtained from CheckMate 214 (NCT02231749) and for PEM + AXI from KEYNOTE-426 (NCT02853331). A matching-adjusted indirect comparison was conducted to account for the imbalance of treatment effect modifiers between the trials. Patient characteristics, resource use, health state utilities, and costs were based on Brazilian-specific sources. Costs and health outcomes were both discounted by 5% annually in line with Brazilian guidelines. The robustness of the results was evaluated through extensive sensitivity analysis and scenario analyses.ResultsWhen comparing the matched versus unmatched OS, PFS, and TTD curves there was no noteworthy difference. NIVO + IPI was associated with cost savings (R$ 350,232), higher LYs (5.54 vs. 4.61), and QALYs (4.74 vs. 3.76) versus PEM + AXI, resulting in NIVO + IPI dominating PEM + AXI. Key model drivers were the treatment duration for PEM, NIVO, and AXI. NIVO + IPI remained dominant in all scenario analyses, which indicated that model results were robust to alternative modelling inputs or assumptions.ConclusionsThis analysis shows that NIVO + IPI is estimated to be a life-extending and potentially cost-saving 1 L treatment option when compared with PEM + AXI for intermediate/poor-risk a RCC patients in the Brazilian private healthcare system.

Obtaining SF-6D utilities from FACT-H&N in thyroid carcinoma patients: development and results from a mapping study.

There is limited evidence for mapping clinical tools to preference-based generic tools in the Chinese thyroid cancer patient population. The current study aims to map the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck Cancer) to the SF-6D (Short Form Six-Dimension), which will inform future cost-utility analyses related to thyroid cancer treatment. A total of 1050 participants who completed the FACT-H&N and SF-6D questionnaires were included in the analysis. Four methods of direct and indirect mapping were estimated: OLS regression, Tobit regression, ordered probit regression, and beta mixture regression. We evaluated the predictive performance in terms of root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the correlation between the observed and predicted SF-6D scores. The mean value of SF-6D was 0.690 (SD = 0.128). The RMSE values for the fivefold cross-validation as well as the 30% random sample validation for multiple models in this study were 0.0833-0.0909, MAE values were 0.0676-0.0782, and CCC values were 0.6940-0.7161. SF-6D utility scores were best predicted by a regression model consisting of the total score of each dimension of the FACT-H&N, the square of the total score of each dimension, and covariates including age and gender. We proposed to use direct mapping (OLS regression) and indirect mapping (ordered probit regression) to establish a mapping model of FACT-H&N to SF-6D. The mean SF-6D and cumulative distribution functions simulated from the recommended mapping algorithm generally matched the observed ones. In the absence of preference-based quality of life tools, obtaining the health status utility of thyroid cancer patients from directly mapped OLS regression and indirectly mapped ordered probit regression is an effective alternative.

Assessing health state utilities for people with myalgic encephalomyelitis/chronic fatigue syndrome in Australia using the EQ-5D-5L, AQoL-8D and EQ-5D-5L-psychosocial instruments

PurposeMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition with a constellation of symptoms presenting as severe and profound fatigue of ≥ 6 months not relieved by rest. ME/CFS affects health-related quality of life (HRQoL), which can be measured using multi-attribute health state utility (HSU) instruments. The aims of this study were to quantify HSUs for people living with ME/CFS, and to identify an instrument that is preferentially sensitive for ME/CFS.MethodsCross-sectional national survey of people with ME/CFS using the AQoL-8D and EQ-5D-5L. Additional questions from the AQoL-8D were used as ‘bolt-ons’ to the EQ-5D-5L (i.e., EQ-5D-5L-Psychosocial). Disability and fatigue severity were assessed using the De Paul Symptom Questionnaire-Short Form (DSQ-SF). HSUs were generated using Australian tariffs. Mean HSUs were stratified for sociodemographic and clinical factors. Bland–Altman plots were used to compare the three HSU instruments.ResultsFor the 198 participants, mean HSUs (95% confidence intervals) were EQ-5D-5L: 0.46 (0.42–0.50); AQoL-8D: 0.43 (0.41–0.45); EQ-5D-5L-Psychosocial: 0.44 (0.42–0.46). HSUs were substantially lower than population norms: EQ-5D-5L: 0.89; AQoL-8D: 0.77. As disability and fatigue severity increased, HSUs decreased in all three instruments. Bland–Altman plots revealed interchangeability between the AQoL-8D and EQ-5D-5LPsychosocial. Floor and ceiling effects of 13.5% and 2.5% respectively were observed for the EQ-5D-5L instrument only.ConclusionsME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably: the latter represents a reduced participant burden.

A Health State Utility Study to Elicit Societal Values Associated with Pulmonary Hypertension.

Pulmonary hypertension (PH) is a rare, severe, and progressive pulmonary vascular disease, which includes five subgroups with similar presentation. Symptoms include dyspnea, and fatigue, and can significantly impact one's health-related quality of life (HRQL). Although treatments are mainly medical, PH group 4, chronic thromboembolic pulmonary hypertension (CTEPH), can be managed with procedures, ie pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA). Currently, drugs in Europe are only approved for pulmonary arterial hypertension (PAH), and CTEPH therefore the aim of this study was to elicit novel societal health state utilities in the UK for PAH and CTEPH based on disease severity, functional class (FC), clinical events, and treatment procedures specifically for CTEPH. Six health states were defined: World Health Organization (WHO)-FC II, WHO-FC III, and WHO-FC IV [defined by the New York Heart Association (NYHA)]; PH-related hospitalization; and "BPA procedure and recovery" and "PEA surgery and recovery". Health states were based on a targeted literature review and two rounds of interviews with clinical experts (N = 4) and patients (N = 6). Draft health states were validated in cognitive debriefing interviews with clinical experts (N = 3). Health states were valued by the UK general public (n = 200), using a visual analogue scale (VAS) and time trade-off (TTO) assessment with the lead time method. The mean TTO values/utilities were 0.81 (FC II), 0.80 (BPA), 0.78 (PEA), 0.59 (FC III), 0.28 (FC IV), and 0.25 (PH-related hospitalization). Each progression in FC was associated with worse TTO scores. This study reports societal utility values for PAH and CTEPH in the UK. It provides first utility estimates for states such as BPA procedure and recovery, PEA surgery and recovery and PH-related hospitalization for this population. The results show important distinctions between FC, treatment procedures, and hospitalization, and the significant burden of disease on HRQL.

Cost-effectiveness analysis of PCV20 to prevent pneumococcal disease in the Canadian pediatric population

ABSTRACT This study assessed the cost-effectiveness of the 20-valent pneumococcal conjugate vaccine (PCV20) in Canadian infants aged <2 years versus the standard of care (SoC), a 13-valent pneumococcal conjugate vaccine (PCV13), or a potential 15-valent pneumococcal conjugate vaccine (PCV15). A decision-analytic Markov model was developed to compare PCV20 with PCV13 or PCV15 in a 2 + 1 schedule over 10 years. Vaccine effect estimates (direct and indirect) across all ages were informed by PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies. Epidemiologic, clinical, health state utilities, utility decrements, cost per event, and list price data were from Canadian sources where available. Clinical and economic outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and simple and complex otitis media (OM) were calculated for each strategy. Cost-effectiveness was evaluated from the publicly funded healthcare system perspective. Over 10 years, PCV20 versus PCV13 was estimated to avert over 11,000 IPD cases, 316,000 hospitalized and non-hospitalized pneumonia cases, 335,000 simple and complex OM cases, and 15,000 deaths, resulting in cost savings of over 3.2 billion Canadian dollars (CAD) and 47,000 more quality-adjusted life years (i.e. dominant strategy). Compared with PCV15, PCV20 was estimated to result in over 1.4 billion CAD in cost savings and 21,000 more QALYs (i.e. dominant strategy). PCV20 was dominant over both PCV13 and PCV15. Given broader serotype coverage, substantial incremental benefits and cost-savings, PCV20 should be considered as a replacement for the SoC in the publicly funded Canadian infant immunization program.

Estimating the disutility of relapse in relapsing–remitting and secondary progressive multiple sclerosis using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-psychosocial, and SF-6D: implications for health economic evaluation models

Background and aimsRelapses are an important clinical feature of multiple sclerosis (MS) that result in temporary negative changes in quality of life (QoL), measured by health state utilities (HSUs) (disutilities). We aimed to quantify disutilities of relapse in relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and relapse onset MS [ROMS (including both RRMS and SPMS)] and examine these values by disability severity using four multi-attribute utility instruments (MAUIs).MethodsWe estimated (crude and adjusted and stratified by disability severity) disutilities (representing the mean difference in HSUs of ‘relapse’ and ‘no relapse’ groups as well as ‘unsure’ and ‘no relapse’ groups) in RRMS (n = 1056), SPMS (n = 239), and ROMS (n = 1295) cohorts from the Australian MS Longitudinal Study’s 2020 QoL survey, using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-Psychosocial, and SF-6D MAUIs.ResultsAdjusted mean overall disutilities of relapse in RMSS/SPMS/ROMS were − 0.101/− 0.149/− 0.129 (EQ-5D-5L), − 0.092/− 0.167/− 0.113 (AQoL-8D), − 0.080/− 0.139/− 0.097 (EQ-5D-5L-Psychosocial), and − 0.116/− 0.161/− 0.130 (SF-6D), approximately 1.5 times higher in SPMS than in RRMS, in all MAUI. All estimates were statistically significant and/or clinically meaningful. Adjusted disutilities of RRMS and ROMS demonstrated a U-shaped relationship between relapse disutilities and disability severity. Relapse disutilities were higher in ‘severe’ disability than ‘mild’ and ‘moderate’ in the SPMS cohort.ConclusionMS-related relapses are associated with substantial utility decrements. As the type and severity of MS influence disutility of relapse, the use of disability severity and MS-type-specific disutility inputs is recommended in future health economic evaluations of MS. Our study supports relapse management and prevention as major mechanisms to improve QoL in people with MS.

The Cost-Effectiveness of Sugemalimab Plus Chemotherapy as First-Line Treatment for Metastatic Squamous and Non-squamous NSCLC in China.

Sugemalimab is the first China-developed programmed death-ligand 1 inhibitor that has proved to be effective as a first-line treatment for both metastatic squamous and non-squamous non-small cell lung cancer (NSCLC) when used in combination with chemotherapy. This study compared the cost-effectiveness of sugemalimab plus chemotherapy (sugema + chemo) with placebo plus chemotherapy (placebo + chemo) among metastatic squamous and nonsquamous NSCLC, respectively. Separate Markov models were constructed to generate the cumulative healthcare costs and quality-adjusted life-years (QALYs) associated with two treatment strategies over a 20-year time horizon. Transition probabilities were estimated using survival data reported in the GEMSTONE-302 trial. Health state utilities and costs were derived from published literature, national databases, and local general hospitals. Sensitivity analyses were performed to test the robustness of our conclusions. Compared with first-line placebo + chem, sugema + chemo achieved an incremental cost-effectiveness ratio (ICER) of $57,842/QALY for patients with metastatic squamous NSCLC and achieved an ICER of $78,249/QALY for patients with metastatic non-squamous NSCLC. In our sensitivity analyses of a willingness-to-pay (WTP) threshold of $35,663 per QALY, the first-line sugema + chemo was only cost-effective for patient groups when the price of sugemalimab decreased. Sugema + chemo was not cost-effective as a first-line treatment for either metastatic squamous or metastatic nonsquamous NSCLC in Chinese patients compared with placebo + chemo. However, we found that sugema + chemo would be cost-effective in patients withmetastatic squamous and non-squamous NSCLC when sugemalimab's price was decreased by > 39.0% and 64.8%, respectively.

Psychometric properties and comparison of four health utility approaches among myopia patients in China

BackgroundThe increased prevalence of myopia creates and earlier age of onset has created public health concerns for the long-term eye health, vision impairment and carries with it a significant economic burden. The quality of the economic evaluation is dependent on the sensitivity and validity of the approaches. Nowadays, there are many approaches to measure patients’ health state utility (HSU). However, little is known regarding the performance of direct approach and indirect approach in people with myopia. This study is aimed to compare the psychometric properties of four HSU approaches among patients with myopia in mainland China, including two direct approaches (TTO and SG), the generic preference-based measures (PBM) (AQoL-7D) and the disease-specific PBM (VFQ-UI).MethodsA convenience sampling framework was used to recruit patients with myopia who attended a large ophthalmic hospital in Jinan, China. Spearman’s rank correlations coefficient was used to assess concurrent validity. Known-group validity was analyzed by: (1) whether the patients wear corrective devices; (2) severity of myopia as low or moderate to high of the better eye; (3) duration of myopia as ≤ 10 years or > 10 years. Effect size (ES), relative efficiency (RE) statistic and the largest area under the receiver operating characteristic curve (AUC) were used to assess sensitivity. The intra-class correlation coefficient (ICC) and Bland–Altman plots were used to assess agreement.ResultsA valid sample size of 477 myopia patients was analyzed (median duration: 10 years). The mean HSU scores between TTO and SG were similar (0.95) and higher than AQoL-7D (0.89) and VFQ-UI (0.83). Overall, the VFQ-UI had the best performance based on the psychometric analysis. The agreement indicated that there was no pair of approaches that could be used interchangeably.ConclusionsThe VFQ-UI showed better psychometric properties than other three approaches for providing health state utility in Chinese myopia patients. Given the widespread use and its generic nature of the AQoL-7D, it could be used alongside with VFQ-UI to provide complementary health state utility from a generic and disease-specific perspective for economic evaluation. More evidence on the responsiveness of four health utility approaches in myopia patients is required.

Assessing utilities for muscle-invasive bladder cancer-related health states

ObjectivesHow patients value functional outcomes against oncologic outcomes during decision-making for muscular-invasive bladder cancer (MIBC) remains unclear. We sought to quantify individuals’ preferences on a scale of 0 to 1, where 1 represents perfect health and 0 represents death. MethodsDescriptions of 6 hypothetical health states were developed. These included: Neoadjuvant chemotherapy followed by radical cystectomy with ileal conduit (IC) or with neobladder reconstruction (NB), Transurethral resection and chemotherapy/radiation (CRT), CRT requiring salvage cystectomy (SC), Recurrent/metastatic bladder cancer after local therapy (RMBC), and Metastatic bladder cancer (MBC). Descriptions consisted of diagnosis, treatments, adverse effects, follow-up protocol, and prognosis and were reviewed for accuracy by expert panel. Included individuals were asked to evaluate states using the visual analog scale (VAS) and standard gamble (SG) methods. ResultsFifty-four individuals were included for analysis. No score differences were observed between IC, NB, and CRT on VAS or SG. On VAS, SC (value = 0.429) was rated as significantly worse (P < 0.001) than NB (value = 0.582) and CRT (value = 0.565). However, this was not the case using the SG method. Both RMBC (VAS value = 0.178, SG value = 0.631) and MBC (VAS value = 0.169, SG value = 0.327) rated as significantly worse (P < 0.001) than the other states using both VAS and SG. ConclusionsWithin this sample of the general population, preferences for local treatments including IC, NB, and CRT were not found to be significantly different. These values can be used to calculate quality-adjusted life expectancy in future cost-effectiveness analyses.