Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma.

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Decomposition of Quality-Adjusted Life Expectancy Inequalities by Mortality and Health-Related Quality of Life Dimensions.

BACKGROUND: Quality-adjusted life expectancy (QALE) combines mortality risk and multidimensional health-related quality of life (HRQoL) information to measure healthy life expectancy in terms of quality-adjusted life years (QALYs). This paper estimates the relative importance of individual quality of life dimensions in explaining inequalities in QALE. METHODS: We combined EQ-5D-5L data from the Health Survey for England for 2017 and 2018 (N = 14,412) with full population mortality data from the Office for National Statistics to calculate QALE by age, sex and deprivation quintile. The effect of HRQoL dimensions on the socioeconomic gradient in QALE was decomposed using an iterative imputation approach, in which inequalities associated with socioeconomic status in each domain were removed by imputing the response distribution of the richest quintile for all participants. Sampling uncertainty in the HRQoL data was evaluated using bootstrapping. RESULTS: People in the least deprived fifth of neighbourhoods in England can expect to live 7.0 years longer and experience 11.1 more QALYs than those in the most deprived fifth. Inequalities in HRQoL accounted for 28.0% and 45.7% of QALE inequalities for males and females, respectively. Pain/discomfort, anxiety/depression and mobility were the most influential HRQoL domains. DISCUSSION: Our results identify the extent of inequalities associated with socioeconomic status in lifetime health and the relative importance of inequalities by mortality and HRQoL. The contributions of the individual dimensions of HRQoL towards lifetime inequalities vary substantially by sex. Our findings can help to identify the types of interventions most likely to alleviate health inequalities, which may be different for males and females.

Dynamic Mortality Modeling: Incorporating Predictions of Future General Population Mortality Into Cost-Effectiveness Analysis.

OBJECTIVES: Health economic models commonly apply observed general population mortality rates to simulate future deaths in a cohort. This is potentially problematic, because mortality statistics are records of the past, not predictions for the future. We propose a new dynamic general population mortality modeling approach, which enables analysts to implement predictions of future changes in mortality rates. The potential implications of moving from a conventional static approach to a dynamic approach are illustrated using a case study. METHODS: The model utilized in National Institute for Health and Care Excellence appraisal TA559, axicabtagene ciloleucel axi for diffuse large B-cell lymphoma, was replicated. National mortality projections were taken from the UK Office for National Statistics. Mortality rates by age and sex were updated each modeled year with the first modeled year using 2022 rates, the second modeled year 2023 and so on. A total of 4 different assumptions were made around age distribution: fixed mean age, lognormal, normal, and gamma. The dynamic model outcomes were compared with those from a conventional static approach. RESULTS: Including dynamic calculations increased the undiscounted life-years attributed to general population mortality by 2.4 to 3.3 years. This led to an increase in discounted incremental life-years within the case study of 0.38 to 0.45 years (8.1%-8.9%), and a commensurate impact on the economically justifiable price of £14 456 to £17 097. CONCLUSIONS: The application of a dynamic approach is technically simple and has the potential to meaningfully affect estimates of cost-effectiveness analysis. Therefore, we call on health economists and health technology assessment bodies to move toward use of dynamic mortality modeling in future.

Quality-Adjusted Life Expectancy Norms for the English Population.

OBJECTIVES: The National Institute for Health and Care Excellence in England has implemented severity-of-disease modifiers that give greater weight to health benefits accruing to patients who experience a larger shortfall in quality-adjusted life-years (QALYs) under current standard of care than healthy individuals. This requires an estimate of quality-adjusted life expectancy (QALE) of the general population based on age and sex. Previous QALE population norms are based on nearly 30-year-old assessments of health-related quality of life in the general population. This study provides updated QALE estimates for the English population based on age and sex. METHODS: 5-level version of EQ-5D data for 14 412 participants from the Health Survey for England (waves 2017 and 2018) were pooled, and health-related quality of life population norms were calculated. These norms were combined with official life tables from the Office for National Statistics for 2017 to 2019 using the Sullivan method to derive QALE estimates based on age and sex. Values were discounted using 0%, 1.5%, and 3.5% discount rates. RESULTS: QALE at birth is 68.24 QALYs for men and 68.21 QALYs for women. These values are significantly lower than previously published QALE population norms based on the older 3-level version of EQ-5D data. CONCLUSION: This study provides new QALE population norms for England that serve to establish absolute and relative QALY shortfalls for the purpose of health technology assessments.

Socioeconomic inequalities in HRQoL in England: an age-sex stratified analysis.

BACKGROUND: Socioeconomic status is a key predictor of lifetime health: poorer people can expect to live shorter lives with lower average health-related quality-of-life (HRQoL) than richer people. In this study, we aimed to improve understanding of the socioeconomic gradient in HRQoL by exploring how inequalities in different dimensions of HRQoL differ by age. METHODS: Data were derived from the Health Survey for England for 2017 and 2018 (14,412 participants). HRQoL was measured using the EQ-5D-5L instrument. We estimated mean EQ-5D utility scores and reported problems on five HRQoL dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) for ages 16 to 90+ and stratified by neighbourhood deprivation quintiles. Relative and absolute measures of inequality were assessed. RESULTS: Mean EQ-5D utility scores declined with age and followed a socioeconomic gradient, with the lowest scores in the most deprived areas. Gaps between the most and least deprived quintiles emerged around the age of 35, reached their greatest extent at age 60 to 64 (relative HRQoL of most deprived compared to least deprived quintile: females = 0.77 (95% CI: 0.68-0.85); males = 0.78 (95% CI: 0.69-0.87)) before closing again in older age groups. Gaps were apparent for all five EQ-5D dimensions but were greatest for mobility and self-care. CONCLUSION: There are stark socioeconomic inequalities in all dimensions of HRQoL in England. These inequalities start to develop from early adulthood and increase with age but reduce again around retirement age.

Does the UK-public's aversion to inequalities in health differ by group-labelling and health-gain type? A choice-experiment.

Public health policy has two primary aims: promoting population health and reducing health inequalities. When these aims conflict, policy-makers must determine the relative importance to place on each in decision-making. We conducted a computer-based, face-to-face, choice-experiment to explore how the UK-public think government should act in these situations; and to explore how "inequality-aversion" may differ depending on the groups between which a health inequality exists and type of health an intervention provides. We tested three hypotheses: (1) the UK-public are more averse to inequalities in health between socioeconomic groups than they are to inequalities in health between neutrally labelled groups; (2) this difference is, at least in part, driven by the role non-health information plays in determining aversion to inequalities in health between socioeconomic groups; and (3) the UK-public are more willing to prioritise groups with lower lifetime health over groups with higher lifetime health if an intervention improves life-expectancy than if it improves quality-of-life. Eighty people participated in Sheffield and Hull in May/June 2019. Each participant completed three Person-Trade-Off exercises between interventions that would improve population health and reduce health inequalities, or improve population health by a larger amount but increase health inequalities. Participants were randomised to exercises involving scenarios with socioeconomic groups or neutrally-labelled groups, and each answered questions about three health-benefit types: increased life-expectancy; pain-relief; and mobility-improvement. Following the exercises, participants provided rationales for their selections. Respondents were (1) more averse to inequalities in health between socioeconomic groups than neutrally labelled groups. Participant rationales suggest (2) this divergence is partly motivated by factors other than health: for example, financial inequality between socioeconomic groups. The sample was also (3) more willing to prioritise neutrally labelled groups with lower lifetime health if an intervention improves life-expectancy rather than if it improves quality-of-life.

Drinking contexts and their association with acute alcohol-related harm: A systematic review of event-level studies on adults' drinking occasions.

ISSUES: Event-level alcohol research can inform prevention efforts by determining whether drinking contexts-such as people or places-are associated with harmful outcomes. This review synthesises evidence on associations between characteristics of adults' drinking occasions and acute alcohol-related harm. APPROACH: We systematically searched Ovid MEDLINE, Ovid PsycInfo and the Web of Science Social Sciences Citation Index. Eligible papers used quantitative designs and event-level data collection methods. They linked one or more drinking contexts to acute alcohol-related harm. Following extraction of study characteristics, methods and findings, we assessed study quality and narratively synthesised the findings. PROSPERO ID: CRD42018119701. KEY FINDINGS: Searches identified 95 eligible papers, 65 (68%) of which study young adults and 62 (65%) of which are set in the United States, which limits generalisability to other populations. These papers studied a range of harms from assault to drink driving. Study quality is good overall although measures often lack validation. We found substantial evidence for direct effects of drinking context on harms. All of the contextual characteristics types studied (e.g. people, place, timing, psychological states, drink type) were consistently associated with harms. Certain contexts were frequently studied and associated with harms, in particular, weekend drinking, drinking in licensed premises and concurrent illicit drug use. IMPLICATIONS: The findings of our review indicate target drinking contexts for prevention efforts that are consistently associated with increased acute alcohol-related harm. CONCLUSION: A large range of contextual characteristics of drinking occasions are directly associated with acute alcohol-related harm, over and above levels of consumption.

How averse are the UK general public to inequalities in health between socioeconomic groups? A systematic review.

There is growing interest in the use of "distributionally-sensitive" forms of economic evaluation that capture both the impact of an intervention upon average population health and the distribution of that health amongst the population. This review aims to inform the conduct of distributionally sensitive evaluations in the UK by answering three questions: (1) How averse are the UK public towards inequalities in lifetime health between socioeconomic groups? (2) Does this aversion differ depending upon the type of health under consideration? (3) Are the UK public as averse to inequalities in health between socioeconomic groups as they are to inequalities in health between neutrally framed groups? EMBASE, MEDLINE, EconLit, and SSCI were searched for stated preference studies relevant to these questions in October 2017. Of the 2155 potentially relevant papers identified, 15 met the predefined hierarchical eligibility criteria. Seven elicited aversion to inequalities in health between socioeconomic groups, and eight elicited aversion between neutrally labelled groups. We find general, although not universal, evidence for aversion to inequalities in lifetime health between socioeconomic groups, albeit with significant variation in the strength of that preference across studies. Second, limited evidence regarding the impact of the type of health upon aversion. Third, some evidence that the UK public are more averse to inequalities in lifetime health when those inequalities are presented in the context of socioeconomic inequality than when presented in isolation.