Quality of Life and Health State Utilities in Bladder Cancer

BACKGROUND: Bladder cancer treatments may variably impact health-related quality of life (QOL). OBJECTIVE: To characterize the quality of life of patients with bladder cancer at various time points across the continuum of bladder cancer care from non-muscle-invasive disease to metastatic bladder cancer and develop utility scores to inform cost-effective analyses. METHODS: We performed a cross-sectional survey of bladder cancer patients in the Bladder Cancer Advocacy Network Patient Survey Network. Participants were classified into mutually exclusive health states based upon non-muscle invasive (NMIBC), muscle-invasive (MIBC), or metastatic bladder cancer and completed surveys of generic cancer and bladder cancer-specific quality of life, financial toxicity, and work impairment. We constructed generalized linear mixed models to identify patient, clinical, and treatment factors associated with quality of life over time and derived health state utilities. RESULTS: Among 911 self-identified patients with bladder cancer, overall QOL scores and function domains were worse among those with advanced cancer. Financial toxicity was similar among non-metastatic disease states. Work and activity impairment increased with advancing disease (13%and 12%among non-recurrent NMIBC to 63%and 31%for metastatic disease respectively; p < 0.01). On multivariable analysis, bowel-related QOL was diminished among patients with MIBC, with urinary symptoms and physical function most diminished among patients with metastatic disease. Patients with metastatic and MIBC experienced worse emotional functioning (p = 0.04; p = 0.048). Health state utilities were calculated, highest among those with non-recurrent NMIBC and lowest among those with metastatic disease. CONCLUSION: Generic and bladder cancer-specific QOL diminishes with advancing disease. Health state utility estimates derived from this study can inform shared decision making with patients and may be used to inform future cost-effective analyses.

Cost-Effectiveness Analysis of Fourth- or Further-Line Ripretinib in Advanced Gastrointestinal Stromal Tumors

BackgroundThe INVICTUS trial assessed the efficacy and safety of ripretinib compared with placebo in the management of advanced gastrointestinal stromal tumors.MethodWe used a Markov model with three health states: progression-free disease, progression disease and death. We parameterized the model from time-to-event data (progression-free survival, overall survival) of ripretinib and placebo arms in the INVICTUS trial and extrapolated to a patient’s lifetime horizon. Estimates of health state utilities and costs were based on clinical trial data and the published literature. The outcomes of this model were measured in quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Uncertainty was tested via univariate and probabilistic sensitivity analyses.ResultsThe base-case model projected improved outcomes (by 0.29 QALYs) and additional costs (by $70,251) and yielded an ICER of $244,010/QALY gained for ripretinib versus placebo. The results were most sensitive to progression rates, the price of ripretinib, and health state utilities. The ICER was most sensitive to overall survival. When overall survival in the placebo group was lower, the ICER dropped to $127,399/QALY. The ICER dropped to $150,000/QALY when the monthly cost of ripretinib decreased to $14,057. Probabilistic sensitivity analyses revealed that ripretinib was the cost-effective therapy in 41.1% of simulations at the willingness-to-pay (WTP) threshold of $150,000.ConclusionAs the fourth- or further-line therapy in advanced gastrointestinal stromal tumors, ripretinib is not cost-effective in the US. Ripretinib would achieve its cost-effectiveness with a price discount of 56% given the present effectiveness.

Eliciting health state utilities for Aromatic L-amino Acid Decarboxylase (AADC) deficiency: a UK vignette study

Purpose The aim of this study was to generate health state utilities for aromatic L-amino acid decarboxylase (AADC) deficiency, a rare genetic, lifelong neurogenerative condition predominantly manifesting in young infants. Methods Participants were presented with health state vignettes. These had been previously developed based on published literature, clinician input, interviews with parents of AADC deficiency patients and expert opinion. A total of 5 health state vignettes were presented: bedridden, head control, sitting unsupported, standing with assistance and walking with assistance. Health state utilities (HSU) were elicited using time-trade off (TTO; 10-year time horizon) and the standard gamble (SG). The vignettes were completed online by panel participants drawn from a representative sample of the United Kingdom residential population. Results A total of 1598 participants completed the vignettes. Around 21% had incongruent responses (higher utilities for the bedridden compared to walking health states). Incongruent responses were associated with shorter task completion times, gender and parental status. These responses were removed from the analysis. Health state utilities (HSU) increased correspondingly as health states improved for both the TTO and SG. The mean HSU (standard deviation) for the TTO task were: bedridden state 0.49 (0.34); head control 0.54 (0.33), sitting unsupported 0.63 (0.31); standing with assistance 0.68 (0.31); and walking with assistance 0.73 (0.31). For the SG, mean health state utilities were: 0.56 (0.28), 0.57 (0.27), 0.67 (0.24), 0.70 (0.24), and 0.75 (0.25), respectively. Conclusion Health state utilities were derived for AADC deficiency through a vignette study. These will be used for a cost-effectiveness model of an AADC deficiency treatment.

Time trade-off with someone to live for: impact of having significant others on time trade-off valuations of hypothetical health states

Background The TTO task involves giving up life years, i.e. living a shorter life, to avoid an undesirable health state. Despite being a hypothetical task, some respondents take other life factors into account when completing the task. This study explored the effect of having children and/or a partner on TTO valuations of hypothetical EQ-5D-5L health states in a valuation study of the general population. Methods The study used TTO data collected in a Norwegian EQ-5D-5L valuation study in 2019–2020, by one-to-one pc-assisted interviews following the EQ-VT protocol. We used regression modelling to determine the effect of significant others (having children or a partner) on disutility per health state from the TTO valuations. Results 430 respondents were included [mean age 43.8 (SD 15.9) years, 58% female, 48% with children, 68% with a partner, 25% with neither children nor partner]. Having children and/or a partner was associated with lowered willingness to trade life years translating to higher elicited health state utilities (p < 0.01). Conclusion Having significant others, or the lack of having significant others, was associated with respondents’ valuation of hypothetical health states using TTO, more so than traditional sampling variables such as age and sex. Inadequate representativeness in terms of having significant others could bias health state preference values in valuation studies.

Real-world evidence: a practical toolbox for collecting health state utilities

Health state utilities (HSU) data collected in real-world evidence studies are at risk of bias. Although numerous guidance documents are available, practical advice to avoid bias in HSU studies is limited. Thus, the objective of this article was to develop a concise toolbox intended for investigators seeking to collect HSU in a real-world setting. The proposed toolbox builds on existing guidance and provides practical steps to help investigators perform good quality research. The toolbox aims at increasing the credibility of HSU data for future reimbursement decision making.

102Assessing the characteristics of health state utilities among people living with multiple sclerosis

Background While many studies have examined the impacts of multiple sclerosis (MS) on health-related quality-of-life (HRQoL), none have used the SF-6D multi-attribute utility instrument in a large international cohort (&gt;2,000 subjects) of people with MS. Our objective was to derive SF-6D health state utilities (HSUs) for participants of the HOLISM international cohort and to describe the distribution and determinants thereof. Methods HSUs were generated using the SF-6D for the Version-1 United States SF-36 for participants with sufficient SF-36 data (n = 2,185/2,466 (88.6%)). Determinants of HSU were evaluated by linear regression, adjusted for age, sex, MS type, disability (Patient-Determined MS Severity Scale), fatigue (Fatigue Severity Scale), and prescription antidepressant use. Results Mean HSU for the sample was 0.67 (SD = 0.13) and diminished with increasing MS-related disability. These findings were robust to adjustment, supporting the SF-6D’s discriminatory power in people with MS. Severe disability and clinically significant fatigue were each associated with 11%-lower HSU (95%CI=-0.13,-0.10 & -0.12,-0.10), and depression risk (Patient Health Questionnaire-2) with 10%-lower HSU (95%CI=-0.11,-0.08). Employment, higher socioeconomic and married/partnered statuses, larger social-network size, greater physical activity, vitamin D and omega-3 supplementations were associated with significantly higher HSU, and overweight/obese BMI and tobacco smoking with lower HSU. Age, sex, and education were not associated. Conclusions The SF-6D revealed significant discriminatory power for the HOLISM international cohort. Modifiable lifestyle factors including diet, physical activity and supplement use for the international cohort were robustly associated with increased HSU and thus HRQoL. Confirmatory longitudinal HSU evidence could provide further support to our baseline findings using the SF-6D. Key messages Health state utilities in this sample of people living with MS were moderate and were significantly lower among those with greater disability, fatigue, and depression, while some lifestyle factors like physical activity and supplement use were associated with higher utility scores.