OBJECTIVES:To assess how frequently QALY-based and LY-based incremental health benefits meaningfully differ and whether those differences affect cost-effectiveness conclusions; how these differences vary across disease categories and what disease severity composition underlies this variation; and whether the QALY-LY difference is associated with baseline disease severity. METHODS:We analyzed 167 treatment-comparator assessment pairs from 71 Institute for Clinical and Economic Review reports (2017-2025), spanning 65 conditions across eight disease categories. We compared incremental QALYs and LYs, assessed cost-effectiveness concordance at $100,000 and $150,000 thresholds, and examined cross-category variation. In a restricted sample of 82 pairs, we assessed associations between severity measures and the QALY-LY difference using linear regression and Spearman rank correlation. RESULTS:QALYs showed greater incremental gains than LYs in 59% of assessments; LYs were greater in 22%. Cost-effectiveness conclusions were highly concordant (92.2% at $100,000; 87.4% at $150,000), though QALYs classified 20-32% more interventions as cost-effective. The QALY-LY difference varied significantly across disease categories (p<0.001), reflecting differences in disease burden composition. Neither LY lost nor evLY lost was meaningfully associated with the QALY-LY difference. The only significant association emerged for baseline health-related quality of life under standard care, where greater impairment was associated with larger incremental gains with QALYs relative to LYs. Both metrics scaled proportionally with disease severity. CONCLUSIONS:QALY-based cost-effectiveness does not systematically disadvantage treatments for more severe disease. Replacing QALYs with LYs would omit therapeutic value most relevant to high-morbidity populations, potentially working against the interests of the patient populations this policy debate seeks to protect.
Introduction Extended cost-effectiveness analysis (ECEA) incorporates financial risk protection (FRP) and distributional outcomes across socioeconomic groups. This study assessed FRP outcomes and synthesized the landscape of ECEA applications. Methods A systematic literature search was conducted in PubMed, Scopus, INAHTA's International HTA Database, and Tufts Medical Center's CEA Registry from January 1, 2010, to June 1, 2025. Studies were included if they report FRP outcomes such as out-of-pocket expenditure (OOPE), cases of catastrophic health expenditure (CHE), cases of poverty, value of insurance, or indirect costs. Study quality was appraised using the ECOBIAS checklist. The distribution of FRP outcomes across socioeconomic groups was assessed to determine whether benefits were pro-poor or pro-rich. Results Thirty-nine studies were included from 5,212 records screened. Most studies evaluated OOPE (n = 31), followed by CHE cases (n = 22), poverty cases (n = 16), value of insurance (n = 9), and indirect costs (n = 3). Pro-poor FRP impacts were consistently reported for tobacco taxation, immunization, and other infectious disease interventions. In contrast, some interventions, such as alcohol pricing and unhealthy diet policies, showed mixed effects depending on the FRP metric applied and the income setting. Overall, study quality was generally high, although methodological approaches and outcome definitions varied across studies. Conclusion ECEA has expanded in scope and application, demonstrating its value in identifying interventions that reduce financial hardship. FRP benefits represent a critical dimension for promoting equity. Policymakers should incorporate ECEA to ensure that financial protection is evaluated alongside other values.
OBJECTIVES:Opportunistic salpingectomy (OS), the additional removal of the fallopian tubes during abdominal surgery, is a preventive strategy against tubo-ovarian carcinoma. Little is known about the economic impact of OS during nongynecological surgeries. METHODS:Markov state transition models were created comparing the addition of OS in women aged 35 to 65 during cholecystectomy, bariatric surgery, nephrectomy for renal cell carcinoma, and colectomy for colorectal cancer to no addition of OS. Quality-adjusted life-years (QALYs) and healthcare costs were modeled over a lifetime horizon, and uncertainty was assessed with sensitivity analyses. A willingness-to-pay threshold of €20 000 was applied. RESULTS:OS during cholecystectomy and bariatric surgery resulted in a QALY gain of 0.033 and 0.034, and a cost reduction of €12 and €7 per patient, respectively. The probability that OS is cost-effective exceeded 99%. OS during nephrectomy for renal cell carcinoma or colectomy for colorectal cancer yielded a QALY gain of 0.012 and 0.016 and a cost increase of €39 and €25 per patient, respectively. The probability that OS is cost-effective was 94.2% and 96.6%. CONCLUSION:Modeling OS during nongynecological surgeries for benign indications suggests that the procedure may be cost-effective, resulting in QALY gain and potential cost savings. For oncologic indications OS appears to be cost-effective, yielding a gain in QALYs, while also leading to an increase in costs. However, the results should be considered exploratory and interpreted with caution in light of the model assumptions.
Objectives This retrospective, real-world analysis aimed to evaluate healthcare resource utilization (HCRU) and associated costs for patients with short bowel syndrome with intestinal failure (SBS-IF), who are dependent on parenteral support (PS), to provide insights into the disease burden. Methods A rules-based algorithm identified and characterized patients with SBS-IF from 2019 to 2023 using Komodo Healthcare Map™ administrative claims data. HCRU and cost data were analyzed across the full cohort and sub-cohorts of age (3–17, 18–44, ≥45 years), nutrition claims/week (<0.5, 0.5–0.99, ≥1), and time since SBS surgery (<6 months versus >12 months since PS start). Results Among 1587 patients with SBS-IF (mean follow-up 2.75 years), comorbidities included esophageal disorders, anxiety/depression, and liver and kidney disorders. SBS-IF management carried mean annualized costs of $166 483 for the full cohort, and up to $200 000 in the sub-cohort with ≥1 nutritional claim/week. Inpatient costs were highest, followed by home care costs. Overall mean annualized home care costs were $29 819. Patients with ≥1 nutrition claim/week had the highest nutrition costs ($68 235), driven by parenteral nutrition costs ($55 349). Bloodstream infections (BSIs) occurred in 47% of patients. Patients with BSIs had higher mean annualized costs of $241 868 and a longer median length of stay versus the full cohort (14 vs 8.1 days). Conclusions SBS-IF represents a considerable burden, particularly in younger patients and those with greater nutritional needs, with high healthcare resource use, and substantial associated costs.
BACKGROUND:This study aimed to systematically review the cost-effectiveness analyses of epigenetic drugs, an emerging class of therapies in oncology. METHODS:A systematic search was conducted in Medline, Scopus and Embase database for references published from January 2000 to November 2024, reporting an economic evaluation on an epigenetic drug regardless of the oncologic or onco-hematologic indication. Eligible studies were cost-effectiveness analysis or cost-utility analysis reporting outcomes in cost per quality adjusted life year (QALY) or cost per life year gained (LYG). The reporting quality was assessed using the CHEERS checklist and the methodological quality with the ISPOR checklist. All costs were converted into 2023 US dollars using purchasing power parity (PPP). RESULTS:Of 541 articles, abstracts, posters and letters identified, 19 articles were included, encompassing 32 comparisons across seven epidrugs (azacitidine, decitabine, panobinostat, ivosidenib, tazemetostat, enasidenib, vorinostat) in six distinct indications in oncology. Overall reporting quality was high, 16 out of 19 studies meeting at least 70% of CHEERS recommendations) and the relevance and credibility were sufficient. Differences in QALYs ranged from -7.71 to 2.6 QALY and cost differences from -$173,300 to $867,500. Base-case results for the incremental cost-effectiveness ratio (ICER) in terms of cost per QALY ranged from -$129,848/QALY to $1,323,228/QALY. CONCLUSION:This systematic review offers a comprehensive synthesis of current economic evaluations of epidrugs in oncology. The wide variability in ICERs and methodological approaches underscores the need for more standardized and robust evaluations to clarify the economic value of epigenetic drugs.
OBJECTIVES:We examine if tolerance for a fixed health inequality varies by whether it is caused by differences in: household income, freely-chosen lifestyles, or genetics. Distributional Cost Effectiveness Analysis (DCEA) uses equity weights to reflect societal preferences over improving total health and reducing health inequality, and cause-specific tolerance can ground DCEA in empirical preferences. METHODS:Using Benefit Trade-Off (BTO) tasks in an unassisted online survey, respondents recruited from the Spanish public (n=497) chose between hypothetical options that traded total health for reduced health inequality between two equally sized population halves. For a given inequality in healthy life years, we use the social marginal rate of substitution (SMRS) as a direct measure of tolerance. We elicited indifference points (IPs), compared paired IP distributions non-parametrically, and estimated implied SMRS with individual fixed-effects regressions. RESULTS:Most respondents traded total health for equality with a sizeable non-trading minority. Implied mean SMRS by cause were 3.60 (Income), 3.25 (Genetics), and 1.75 (Lifestyles). Income-Lifestyles and Genetics-Lifestyles differences were significant (p<0.001); Income-Genetics difference was not (p=0.512). Results were robust to scenario order and to re-coding IPs for non-traders. CONCLUSIONS:Tolerance for a given health inequality depends on its perceived cause: tolerance was higher when inequality was caused by lifestyles than income or genetics, between which no significant difference was found. Thus, "natural" (genetics-caused) inequalities are not viewed as more legitimate than income-caused ones. Cause-specific SMRS can help inform the calibration of DCEA equity weights to capture not only the extent of inequality but also its cause.
OBJECTIVES:Policy makers need information on how members of the public value improving population health (efficiency) relative to reducing socioeconomic health inequality (equity). Quantitative evidence of the trade-off using Benefit Trade-Off (BTO) is emerging, but not qualitative or mixed-method evidence. This mixed method study aimed to elicit distributional preferences among the general population in Japan over socioeconomic inequality in lifetime health using BTO tasks, and to understand the underlying reasonings. METHODS:Individual online interviews (n=50) were conducted in 2022, comprising two main elements: 1) BTO tasks; and 2) qualitative questions regarding the participant's understanding and reasonings behind their BTO task choices. RESULTS:The median BTO response was inequality averse (prioritarian). The qualitative analysis found: the relevance of non-health considerations such as prioritising the health of the rich because they make more tax contributions; violating the symmetry assumption of the standard BTO; self-interested motivations despite the exercise using a social perspective; indecisive choices; and inconsistent reasonings across BTO subtasks. CONCLUSIONS:This is the first mixed-method interview study on BTO preferences of the public, involving an in-depth qualitative component. Some of the reasonings observed were similar to those in existing qualitative studies, albeit based on non-BTO methods. The findings also suggest heterogeneous reasonings by participant gender and geographic region. Some participants gave coherent explanations for behaviour such as choosing a more unequal distribution in favour of the rich ("inequality seeking") or choosing a less unequal distribution even when nobody is better off (violation of monotonicity).
Real-world evidence (RWE) plays an expanding role in regulatory, health technology assessment, and lifecycle decision making, prompting a rapid increase in guidance documents intended to support its generation and use. This commentary argues that additional guidance is not redundant; rather, it is necessary to sustain consistency, credibility, and confidence as RWE methods become more specialized and operationally complex. Recent advances, including pragmatic and registry-based trials, hybrid randomized-real-world designs, external control arms, artificial intelligence and machine learning applications, digital health data, synthetic controls, and data tokenization, have outpaced the scope of many existing frameworks. Although recent reporting initiatives and international harmonization efforts have improved transparency and reproducibility, important gaps remain in implementation-focused guidance on issues such as causal inference, dynamic borrowing, linkage validation, algorithm auditability, reproducibility, and distributed data environments. The need is further amplified by heterogeneity across regulatory and health technology assessment agencies, for which differing evidentiary expectations can create uncertainty and inefficiency, and by the limited availability of context-appropriate guidance for low- and middle-income countries, where structural data and infrastructure constraints may hinder RWE generation and use. Future progress should emphasize targeted, modular, and potentially "living" guidance that is updated as methods evolve, while also improving uptake of existing frameworks through clearer reporting expectations, education, and stakeholder collaboration. More guidance, when focused and implementation oriented, can better translate methodological principles into decision-grade RWE.
OBJECTIVES:This study aimed to examine how governmental, industry, academic, consultancy, journalistic, and international health technology assessment (HTA) stakeholders framed the cost-effectiveness threshold (CET) uplift announced for the National Institute for Health and Care Excellence (NICE) in December 2025 during the early phase of policy debate. METHODS:A qualitative documentary content analysis was conducted following the READ framework (Ready your materials, Extract data, Analyse data, and Distil your findings) for systematic document analysis in health policy research. Twenty-seven publicly available documents published between October 2025 and March 2026 were purposively sampled across government, NICE, industry, academia, consultancy, journalism, civil society, and international HTA actors. Data were analyzed through iterative coding and thematic synthesis. RESULTS:The 2025 to 2026 debate extended beyond technical discussions of cost-effectiveness and revealed 5 interrelated themes. First, government documents explicitly reframed the CET as an instrument of industrial policy, economic growth, and pharmaceutical competitiveness. Second, substantial disagreement emerged regarding HTA governance and ministerial involvement in threshold setting. Third, stakeholders advanced competing interpretations of the consequences of the reform, with government and industry emphasizing innovation access, whereas academic and public-interest sources highlighted opportunity costs, service displacement, and population-health impacts. Fourth, many documents situated the reform within broader geopolitical and pharmaceutical-policy dynamics, including trade negotiations, investment incentives, and potential international spillovers. Finally, stakeholders expressed contrasting views regarding transparency, consultation, and procedural legitimacy. CONCLUSIONS:The NICE threshold uplift was framed as a politically mediated reform with implications for industrial strategy, HTA governance, healthcare resource allocation, and public trust. The findings demonstrate how CETs can become sites of broader political, economic, and institutional contestation, extending beyond their conventional role within health-economic evaluation.
The global use of real-world data and real-world evidence (RWE) in regulatory and health technology assessment decisions has led to a crucial need for alignment on what constitutes high-quality RWE. Regulators, health technology assessment bodies, and professional societies have issued an abundance of guidance documents, resulting in a state of guidance oversaturation. The existence of multiple initiatives to track this guidance is itself indicative of the challenge researchers face in interpreting and aligning with decision-maker expectations. Although the proliferation of guidance forces researchers into exhaustive "compare and contrast" exercises, multiple publications have documented substantial alignment on core principles, including study design, data quality, the importance of fit-for-purpose data, and methodological rigor. For example, the fundamental requirements for real-world data quality are similar between the Food and Drug Administration and European Medicines Agency. This convergence suggests that additional, redundant guidance is not the answer to addressing remaining gaps. Instead of producing new, high-level guidance, future efforts should pivot toward 2 critical areas. First, global harmonization of existing guidance is necessary to reduce the resource burden on sponsors and prevent evidentiary fragmentation across jurisdictions. Second, a transparent, annotated repository of diverse case studies must be developed to build operational transparency in RWE use and decision making. This repository should capture why specific data and methodological decisions were made, how the evidence was evaluated, and how it was ultimately used in decision making. By shifting the focus from guidance to transparent, precedent-based learning and harmonized standards, the industry can establish a more predictable and efficient pathway for decision-grade RWE integration.
OBJECTIVE:This study aimed to assess the psychometric properties of two versions of EQ-5D-Y (Y-3L and Y-5L) in children with attention-deficit/hyperactivity disorder (ADHD) and to compare their performance across self- and proxy-reported responses. METHODS:Overall, 188 child-caregiver dyads (mean age 9 years with a clinical ADHD diagnosis) completed a cross-sectional survey, followed by a two-week assessment to examine test-retest reliability. Outcome measures included the Y-3L and Y-5L, Child Health utility 9D (CHU-9D), Child Behaviour Checklist (CBCL) and the Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) for ADHD severity. Ceiling, informativity, convergent and known-group validity, patient-proxy agreement and test-retest reliability were assessed. RESULTS:Self-reported Y-3L (48%) and Y-5L (28%) had higher ceilings than proxy versions (32% and 25%), and the Y-5L showed higher absolute informativity for both self- and proxy-reports. Self-reports correlated more strongly with the child-completed CHU-9D, while proxy-reports were more aligned with CBCL. Self-report version showed good known-groups validity: the Y-3L discriminated 11 of 14 groups, and the Y-5L discriminated 13 of 14. The proxy versions showed slightly weaker discrimination. Item-level test-retest reliability and patient-proxy agreement were good (Gwet's AC 0.71-0.98 and 0.70-0.97), but scale-level reliability and agreement were lower. CONCLUSION:In Chinese children with ADHD, the Y-3L appears more suitable for self-report, whereas the Y-5L may be better for proxy report, but depending on the population and study aims. Further research is needed to identify the optimal version across age groups and clinical conditions.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This letter has been retracted at the request of the Editors-in-Chief. The undisclosed use of artificial intelligence in the preparation of this work represents a clear violation of the journal's editorial policies and publishing ethics standards. Apologies to the readers of the journal that this was not detected during the submission process.
OBJECTIVES:Despite the growing interest in cost-effectiveness analysis in China, evidence to support robust economic evaluation remains limited. This study aimed to assess health-related quality of life (HRQoL) in Chinese patients with non-small-cell lung cancer (NSCLC) and generate utility values for economic evaluations. METHODS:We conducted a multicenter cross-sectional survey in 20 hospitals across China from October 2022 to March 2024. Demographic characteristics, clinical details, and HRQoL data using EQ-5D-5L, SF-6D and QLQ-C30. Mean and standard deviation (SD) of utility index scores were reported. Determinants of utility were examined using ordinary least squares regression with bias-corrected bootstrapped cluster-robust standard errors. RESULTS:A total of 947 patients were included (mean age 61.6 years; 36.3% female). Most had stage III or IV cancer (83.1%), with58.3% and 21.7% receiving first-line and second-line treatment, respectively. The mean EQ-5D-5L utility index score was 0.801 (SD:0.273) overall, and 0.889 (SD:0.141), 0.814 (SD:0.255) and 0.776 (SD:0.298) for stage I/II, III, and IV, respectively. Across lines of treatment, the EQ-5D-5L utility index scores ranged from 0.809 (SD:0.271, first-line) to 0.742 (SD:0.291, fourth-line and above). The mean SF-6D and QLU-C10D utility index scores (0.644, SD:0.254; 0.754, SD:0.205) were lower than that of the EQ-5D-5L. Pain/discomfort was the most impaired EQ-5D dimension, whereas physical functioning was the worst SF-6D and QLU-C10D dimension. CONCLUSION:This study provides EQ-5D-5L, SF-6D, and QLU-C10D utility values for Chinese NSCLC patients, noting instrument-dependent differences and cross-sectional limitation, to inform cost-effectiveness analyses.
OBJECTIVE:This systematic literature review synthesizes findings from health economic evaluations in older adults receiving oral nutrition supplement (ONS) interventions. METHODS:Six databases (PubMed, Embase, EconLit, CINAHL, Cochrane, and Scopus) were searched for health economic evaluations published 2014-2024 comparing ONS with any comparator in populations with mean age ≥60 years. The Consolidated Health Economic Evaluation Reporting Standards checklist informed data extraction and reporting quality. Methodological quality was assessed using the Drummond checklist. This study was registered with PROSPERO (CRD42023459161). RESULTS:Of 1,459 records identified, 12 studies met the inclusion criteria: four cost-effectiveness analyses (CEA), two cost-utility analyses (CUA), three budget-impact analyses (BIA), one cost-minimization analysis (CMA), one CEA plus CUA, and one BIA plus CEA. Most studies were conducted in hospital (n=4) or community settings (n=4) with time horizons ≤6 months (n=10). Most were trial based (n=8), used usual care comparators (n=8), and included both healthcare and intervention costs (n=11). Seven studies reported ONS intervention-arm cost savings up to US$1,988/patient), primarily from reduced healthcare resource utilization, while five studies reported cost increases (as low as 2024 US$356/patient), mainly from intervention-related costs. Main health outcomes and utilization were favorable in nine studies, while three studies reported mixed findings across several main outcomes. Studies concluded ONS interventions were cost-effective or cost-saving; however, comparability was limited by heterogeneity in methods, settings, and outcomes. CONCLUSIONS:ONS interventions were generally associated with short-term improvements in patient outcomes with minimal incremental costs, but evaluations with longer time horizons are needed to characterize longer-term impacts.
