Combination therapies are increasingly central to modern pharmacotherapy, particularly in oncology and other high-burden diseases. However, pharmaceutical pricing and reimbursement systems remain largely designed for single-product-single-indication interventions. When multiple patented medicines are used together, especially when owned by different manufacturers, conventional pricing frameworks may struggle to align prices with the value of the combination while preserving incentives for innovation and timely patient access. To identify, describe, and critically assess the methods, models, and policy frameworks proposed in the literature to establish prices for combination therapies, with particular attention to value attribution mechanisms, cost-sharing arrangements between manufacturers, and budget impact considerations. A systematic literature review was conducted in accordance with PRISMA guidelines and a pre-registered Open Science Framework protocol. Searches were performed in MEDLINE, Scopus, Web of Science, EconLit, CRD databases, and grey literature sources for publications up to July 2025. Eligible studies analysed pricing approaches, economic models, reimbursement mechanisms, or policy frameworks relevant to combination therapies, including more recent multi-indication pricing literature. Given the heterogeneity of the literature, findings were synthesized using a structured narrative and thematic approach. Sixty-nine studies met the inclusion criteria. The literature was dominated by conceptual and policy analyses, with relatively few empirical or implementation-oriented studies. Value attribution emerged as the central methodological challenge in pricing combination therapies. Several complementary approaches were proposed to operationalise value attribution, including adaptations of indication- or pathway-based pricing, manufacturer cost-sharing arrangements, managed entry agreements, and outcome-based reimbursement mechanisms. Empirical evidence suggests that health systems continue to rely primarily on pragmatic and often partial solutions rather than fully specified pricing frameworks. A complementary review of the multi-indication pricing literature indicates that, although the two fields address different pricing problems, they share important methodological and institutional lessons that can inform the development of pricing frameworks for combination therapies. The literature provides a growing repertoire of conceptual approaches for pricing combination therapies but limited empirical evidence on implementation. Pricing frameworks should place value attribution at their core while combining complementary policy mechanisms adapted to national pricing and reimbursement systems. Lessons from multi-indication pricing provide a valuable foundation but require additional governance mechanisms to address value attribution, multi-manufacturer negotiation, and implementation challenges specific to combination therapies.
Job stress has become an increasing public health concern worldwide, affecting a substantial proportion of the workforce and contributing to significant morbidity. Although extensive evidence has documented its adverse health effects, much less is known about how occupational stress translates into healthcare utilization, which is essential for assessing its economic burden on healthcare systems and informing public policy. To our knowledge, this study provides the first systematic review of empirical evidence linking job stress and burnout to healthcare utilization. Following PRISMA guidelines, 533 articles published between January 1990 and February 2026 were identified in MEDLINE, Web of Science and SciELO databases and screened. After applying the eligibility criteria, based on peer-reviewed articles published in English or Spanish examining healthcare utilization among employed individuals exposed to job stress or burnout, 18 studies were included, highlighting the limited empirical evidence currently available. All studies were conducted in high-income countries; 72
RSVpreF is a vaccine that immunises against respiratory syncytial virus (RSV), a seasonal respiratory virus, that can lead to lower respiratory tract infections. In Switzerland, RSVpreF is indicated for the passive protection of infants against RSV following maternal immunisation. The Swiss Federal Office of Public Health commissioned a health technology assessment (HTA) of RSVpreF for maternal vaccination, evaluating the clinical and cost effectiveness of the vaccine compared with nirsevimab (administered directly to newborns and infants) or no RSV prophylaxis. This study reports the cost-effectiveness model developed for the Swiss HTA. The model used a Markov model structure, a 1-year time horizon, a one-month cycle length, a Swiss healthcare payers' perspective, and a 3
Comprehensive understanding of the economic impacts of COVID-19 over time remains limited, with recent estimates lacking both broad population coverage and detailed assessment of disease severity. To provide updated estimates on healthcare utilization and costs associated with COVID-19 during both pandemic and post-pandemic periods using administrative claims data. This retrospective observational study used administrative medical claims data in the USA from the Merative™ MarketScan® databases to evaluate healthcare utilization and costs across various settings: outpatient, inpatient without intensive care unit (ICU) use, inpatient with ICU but without ventilation, and inpatient with both ICU and ventilation. The study population included enrollees with COVID-19–related medical encounters from July 2021 through June 2025. The period from July 2021 to June 2023 was classified as the pandemic period, and July 2023 to June 2025 as the post-pandemic period. Outcome measures included hospitalization and outpatient case rates, frequency of ICU admissions and ventilation utilization, mean hospital lengths of stay, and direct medical costs (reported in 2025 USD). From July 2021 to June 2025, approximately 64,000 COVID-19–related hospitalizations and 4.2 million outpatient cases were identified based on primary diagnoses. Hospitalization rates ranged from 3.0 to 1037.8 per 100,000 enrollee-years, and outpatient rates ranged from 10.4 to 122.1 per 1000 enrollee-years, peaking in early 2022 and declining thereafter with seasonal fluctuations. Hospitalization rates decreased across all age groups, although adults aged ≥ 65 years maintained the highest burden (312.6 per 100,000 enrollee-years in July 2024–June 2025). Mean length of stay and hospitalization costs declined across most adult groups, particularly for ICU-related cases. In the post-pandemic period, mean hospitalization costs ranged from 16,149 to213,740 with a mean length of stay from 2.6 to 22.6 days. The mean outpatient costs ranged from 361 to770 per case. Nationally, annual direct medical costs were estimated to be as high as 38.7 billion during the pandemic period and as high as8.6 billion in 2024–2025, with adults aged ≥ 65 years accounting for approximately half of total expenditures. COVID-19 continues to impose a substantial and persistent economic burden, even in the post-pandemic period, underscoring the importance of ongoing mitigation strategies and efficient healthcare resource planning.
Active transport can increase physical activity at the population level, thereby improving population health. Knowing the health and related economic benefits of infrastructure measures that change physical activity may help underpin the case for investment, but valuing such benefits is challenging. The aim of this study was to develop a model to estimate the health benefits of changes in active transport behaviour and translate these to an economic value. We applied the model to the state of New South Wales, Australia. The The Active Transport Health Model is a proportional multi-state lifetable model that quantifies the health impacts of changes in active transport behaviour over a population’s lifetime. Health outcomes related to physical activity, air pollution and road trauma are modelled. Model outputs include age- and sex-specific changes in disease incidence, prevalence and mortality, summarised as health-adjusted life-years, which are translated to monetary terms. Changes in healthcare costs are also modelled. Values per additional person-kilometres of walking and cycling are reported (in Australian dollars). A 5
This methodological paper reflects on how people with lived experience of dementia contributed to the development and refinement of a survey intended to identify priorities for future economic evaluation in dementia research. Although Patient and Public Involvement (PPI) is increasingly recognised as essential for producing relevant and ethical health research, people living with dementia are rarely included in PPI activities related to health economics, where outcomes are often predetermined by decision-making bodies. To support the development and refinement of the survey, a small bespoke PPI group comprising four individuals with lived experience in England reviewed draft survey materials through online meetings and helped ensure the survey was accessible and meaningful through feedback on survey clarity, accessibility, and response options. PPI contributions led to important refinements, including simplifying terminology, removing ambiguous or burdensome items, and enhancing overall usability. The findings demonstrated the significant value of involving PPI contributors early and collaboratively, showing that co-design approaches enrich the relevance and sensitivity of research tools. The experience also highlighted the need for tailored support and an accessible introduction to health economic concepts for PPI contributors, alongside broader participation across study stages and engagement in dissemination activities.
Global population ageing continues to place pressure on health and care systems. In Australia, the increasing integration of health and aged care systems is a rising policy approach to alleviating the burden on the health system and improving the quality of care for older people. Preference-based instruments (PBMs) have become increasingly important as a tool to enable quality assessment and economic evaluation of both health and aged care services. Given the changing policy context towards more integrated services and older peoples’ frequent movement across both health and aged care settings, it is important that PBMs are applicable across different care settings. This literature review aimed to assess the application of generic PBMs with older people across health and aged care settings. A systematic search of three databases for studies utilising PBMs with older people in health or aged care settings resulted in 204 articles included for review. The EQ-5D instruments were the most frequently utilised instrument across studies, followed by the Quality of Life-Aged Care Consumers (QOL-ACC). Most instruments were applied in either health or aged care settings, with few being used across both. The measurement of quality of life in older people across these settings using PBMs requires consideration of several issues particularly pertinent to this population, including the appropriateness, relevance and comprehensiveness of dimensions, the use of a suitable recall period and enabling self-report for people with cognitive impairment.
Within the European Union (EU), pricing and reimbursement decisions for new medicines are the responsibility of individual Member States. The presence of many regulated prices for medicines within the EU single market drives strategic decisions by payers and manufacturers, resulting, among other things, in launch delays and unequal patient access across European countries. To increase equity in patient access, we propose strengthening collaboration on medicines procurement among Member States beyond emergency situations. Joint initiatives undertaken by groups of countries have demonstrated their potential to deliver benefits, and the need for common procurement initiatives has become apparent during the coronavirus disease 2019 (COVID-19) pandemic. We present our proposal within the context of the current European regulatory framework and the recently proposed “Critical Medicines Act”, emphasising the key legislative provisions that can be invoked to support a common procurement initiative. We also provide relevant, actionable options for designing such initiatives. Strong political commitment and agreement on equity and solidarity principles would be needed for the successful implementation of the proposal.
ObjectivesTo examine whether higher national list prices for new medicines are associated with faster patient access across 18 European countries.MethodsData were drawn from the 2023 European Federation of Pharmaceutical Industries & Associations (EFPIA) Patients Waiting to Access Innovative Therapies (WAIT) Indicator Survey and the Swedish TLV's 2023 international price index. Time to availability was defined as the number of days between marketing authorisation and national reimbursement access. A multivariable linear regression model was applied, controlling for gross domestic product (GDP) per capita, population size, health technology assessment (HTA) duration, and the use of Managed Entry Agreements (MEAs). To address endogeneity, a two-stage least squares (2SLS) regression was conducted using a composite headquarters (HQ) Index as an instrumental variable for national list prices.ResultsIn the multivariable model, each one-point increase in the list price index (European average = 100) was associated with a 7.9-day reduction in time to availability (p = 0.091). A slow HTA/reimbursement process was significantly associated with longer delays (p = 0.022). Managed entry agreement intensity was positively associated with longer delays but did not reach statistical significance (p = 0.103). In the 2SLS model, a one-point increase in the instrumented list price was associated with a 14.1-day reduction in access delays in the preferred parsimonious specification (p = 0.011). Sensitivity analyses showed that the negative association was generally preserved across alternative instrumental variable specifications and after exclusion of Poland, although effect sizes and first-stage strength varied.ConclusionsHigher national list prices may be associated with faster patient access to new medicines in European markets. Although the findings are consistent with a possible causal effect, they should be interpreted with caution given the sensitivity of the estimates to specification and sample composition, as well as concerns about instrument validity and strength. The results highlight a potential policy trade-off between affordability and timely availability in pharmaceutical pricing and access frameworks.
Deprescribing is increasingly promoted to address polypharmacy and medication-related harm in older adults. However, its economic value as a distinct intervention remains unclear, as prior reviews have often conflated deprescribing with broader medication optimisation strategies. This systematic review synthesises the economic evidence on deprescribing using a strict conceptual definition. A systematic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted from January 2000 to June 2025. Studies were included if they reported full economic evaluations (cost-effectiveness, cost-utility, cost-benefit, or cost-consequence analyses) of interventions explicitly involving medication discontinuation in adults aged ≥ 65 years. The methodological quality of included studies was assessed using the Consensus on Health Economic Criteria (CHEC) checklist, and reporting quality was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 statement. Cost data were standardised to 2024 US dollars using purchasing power parity where feasible. Eight studies were included (two trial-based, six model-based). Deprescribing interventions targeting medications with well-established harm profiles, such as sedatives, non-steroidal anti-inflammatory drugs, and proton pump inhibitors (prolonged use), were most consistently cost-saving or dominant, primarily through reductions in adverse drug events. In contrast, evidence for antihypertensive deprescribing was limited and context dependent, with one model-based study suggesting potential long-term harms under specific assumptions. Across studies, economic outcomes were strongly influenced by intervention design and implementation, with structured, multi-component approaches demonstrating greater effectiveness. Quality assessment indicated generally robust methodological foundations but identified gaps in the handling of uncertainty, transparency in reporting, and the inclusion of broader cost components. Deprescribing can represent good value for money when targeted to high-risk medications and supported by structured implementation strategies. Its economic value is not universal but depends on patient context, medication class, and intervention design. Future research should prioritise methodologically rigorous, transparent, and context-sensitive economic evaluations to inform policy and practice.
BACKGROUND:Universal health coverage has become central to health policy debates, particularly as a strategy to protect households from financial hardship and impoverishment related to out-of-pocket (OOP) spending. Many low- and middle-income countries (LMICs), including India, have relied predominantly on publicly funded health insurance (PFHI) to improve financial protection against OOP spending. PFHI generally covers low-frequency, high-cost hospitalization expenses, even though non-hospitalization expenses are the main contributors to OOP. Global evidence suggests that stronger primary health care (PHC) provision is crucial for reducing catastrophic health expenditure (CHE). This issue becomes particularly important in the context of climate-sensitive diseases (CSDs), whose incidence is increasing due to more frequent and extreme weather events, which may increase the risk of CHE. OBJECTIVE:This study estimates the causal impact of publicly provided PHC and PFHI on CHE arising from CSDs. METHODS:Using district-level data for all 640 Census districts in India, we applied propensity score matching and inverse probability weighting to compare the effects of PHC and PFHI on CHE associated with CSDs. RESULTS:The findings show that strengthened PHC substantially reduces OOP spending and CHE associated with CSDs, whereas PFHI shows no statistically significant effect. CONCLUSION:These results highlight the need to prioritize climate-resilient PHC systems to address the escalating health impacts of climate change and advance equitable progress toward universal health coverage in LMICs.
Breast cancer screening is vital for early detection and improved health outcomes but requires robust health economic evaluations to guide implementation. This systematic review examines the methodology, quality, and results of health economic evaluations of screening strategies to support decision making and future research. A literature search was performed in PubMed, Embase, Web of Science, EconLit, and the HTA database. Health economic evaluations of breast cancer screening strategies using imaging modalities were included and screened independently by two reviewers. Data on study design, screening strategies, and outcomes were extracted and synthesized. Quality was assessed using the ISPOR checklist for model-based studies and the Consensus on Health Economics criteria (CHEC-extended) checklist for empirical data–based studies. All results were made publicly accessible via an interactive platform and the Open Science Framework, providing an open resource that facilitates transparency, reuse, and future updates. The review included 128 studies, comprising 96 model-based studies, 14 empirical data-based studies, 15 studies combining empirical data with extrapolation using a modeling approach, and 3 studies with unclear methods. Microsimulation and cohort simulation were used in 47 and 53 studies, respectively. Incremental cost-effectiveness ratios varied widely across studies depending on the screening modality, risk factors, age range of screening, and screening interval. Most studies found mammography to be cost effective compared with no screening, while some studies showed it as being not cost effective, especially for women at average risk of breast cancer, in young screening ages (40–49 years), or with an annual interval. Ultrasound-based screening programs were generally cost effective compared with no screening in the women with average risk of breast cancer. Supplementing magnetic resonance imaging (MRI) with mammography was generally cost effective in women with dense breasts and a family history of breast or ovarian cancer but not cost effective in women with previous treatment using radiation therapy. The median quality score was 55
BackgroundCountries have implemented different assessment pathways for public funding of drugs for rare diseases, resulting in inequities in access. Understanding public preferences for these processes could enhance decision-making legitimacy and acceptance.ObjectiveWe aimed to elicit societal preferences for different assessment pathways that lead to public reimbursement to drugs for rare diseases.MethodsA discrete choice experiment was conducted among adults from the general population in Australia who were asked to assume the role of a government advisor and chose between two different assessment pathways. Attributes describing the assessment pathways were identified through a literature review and expert focus groups. Each respondent completed eight choice tasks. Data were analysed using conditional logit, mixed logit and latent class models. Willingness to wait was calculated as the ratio of attribute coefficients to access time.ResultsThere were 1099 respondents who completed the survey. Overall, respondents preferred assessment pathways that incorporated comprehensive evidence and stakeholder input. The mixed logit model revealed preference heterogeneity across four of the five attributes, with the latent class analysis identifying three groups: Class 1 (28.1%) preferred use of all available evidence, Class 3 (20.2%) opposed long wait times, and Class 2 (52%) showed no strong preferences. On average, respondents were willing to wait 32 additional months to incorporate all types of evidence into the decision-making process, and an additional 14 months for broad stakeholder involvement. Acceptable delays indicate the value placed on greater certainty and broader consultation rather than recommended policy waiting times.ConclusionsThis study examined societal preferences for assessment pathways for rare disease medicines. Robust evidence, covering safety, clinical effectiveness and cost effectiveness, and enhanced stakeholder involvement were the most influential factors. Respondents were also willing to delay patient access to ensure decisions were supported by strong evidence.
Health technology assessment (HTA) informs evidence-based decision-making for resource allocation in healthcare; however, the topic selection phase that determines which technologies proceed to full assessment is underexplored and often lacks fairness and transparency, particularly disadvantaging orphan medicinal products (OMPs) for rare diseases. We drew on selectively identified literature and illustrative HTA experiences to advance an opinion-driven argument about equity in topic selection for OMPs, grouping insights into three domains: structural challenges, conceptual frameworks and policy strategies. Structural barriers in topic selection include a lack of institutionalised, participatory processes, overreliance on prioritisation criteria implicitly aligned with population-wide impact and minimal engagement with stakeholders representing the rare disease community, resulting in the systematic under-prioritisation of OMPs. Procedural and value frameworks, including multi-criteria decision analysis (MCDA), evidence-informed deliberative processes (EDPs), accountability for reasonableness (A4R), equity weighting and Health Equity Impact Assessment (HEIA), can help agencies incorporate social value and fairness before formal appraisal, but remain unevenly operationalised. Policy strategies such as equity-oriented horizon scanning, open nomination systems, and special pathways for OMPs are highlighted as feasible approaches to promote fairness. Achieving equity in HTA topic selection for OMPs requires both policy and cultural change, and embedding pluralistic value frameworks, engaging stakeholders and adopting specific policy tools are essential steps towards ensuring that rarity is met with heightened ethical attention rather than exclusion.
Background Extrapolation of overall survival in health technology assessment (HTA) is a key area of uncertainty, as equally well-fitting models can generate divergent lifetime projections. This can lead to significant implications for decision-making. Subject experts are often consulted on the plausibility of survival projections, but input is rarely obtained in a robust manner. Objective This case study applies guidance from the National Institute for Health and Care Excellence Decision Support Unit Technical Support Document (TSD) on using structured expert elicitation for long-term survival estimation (TSD 26). This study focuses on its feasibility of implementation from the perspective of a company preparing a HTA submission. Methods The REVEL trial, evaluating ramucirumab plus docetaxel for stage IV non-small cell lung cancer, was selected as a case study. The elicitation was based on the Sheffield Elicitation Framework (SHELF) and undertaken in accordance with TSD 26. Results Five experts from four countries attended across three virtual workshops. Experts provided quantitative judgements on overall survival at 4 years for the intervention and comparator from the REVEL trial. Qualitative discussion of the change in hazard and scenario testing demonstrated the internal consistency of experts' judgments and provided valuable context for expert judgements. Group discussion in separate workshops posed challenges when the facilitation team had to relay the views of absent experts. Conclusions This case study demonstrates that it is feasible to follow the recommendations provided in TSD 26 when conducting elicitation for long-term survival outcomes and highlights the critical role of discussing the hazard function in group discussions.
Modelling approaches that consider system-wide delivery platforms rather than single diseases can be instrumental in economic evaluation and forward-looking policy formulation. This study develops a costing approach tailored to the Thanzi La Onse (TLO) model of Malawi’s healthcare system, with general applicability to other health system models. We developed a mixed-method costing approach to estimate the total cost of healthcare delivery (excluding high-level administrative costs) in Malawi using the TLO model, from a healthcare provider perspective. Through iterative adjustments of key parameters, we aligned model-based estimates as closely as possible with real-world expenditure and budget data. Costs were projected for 2023–2030 under alternative scenarios of health system capacity. A comparison with expenditure and budget data suggests our costing method is broadly reliable for the conditions captured by the model, though some mismatches remain owing to data limitations and definitional inconsistencies. Under current system capacity, total healthcare delivery costs for 2023–2030 were estimated at 2.83 billion US dollars [95
Endovascular thrombectomy is standard for acute large-vessel occlusion stroke, but the value of endovascular thrombectomy in patients with large ischemic regions remains uncertain from a US healthcare payer perspective. This study evaluated the cost effectiveness of endovascular thrombectomy plus medical management (MM) versus MM alone in patients with large ischemic regions, synthesizing data from a recent meta-analysis of all available randomized trials. We developed a decision tree linked to a Markov model to perform a cost-utility analysis of endovascular thrombectomy plus MM versus MM alone from a US healthcare payer perspective over 90-day, 1-year, 5-year, and 20-year horizons. The target population was adults with acute ischemic stroke from large-vessel occlusion and Alberta Stroke Program Early CT Score (ASPECTS) < 6 or infarct core volume ≥ 50 mL. Clinical inputs came from a systematic review of randomized trials. The primary outcome was the incremental cost-effectiveness ratio, expressed as cost per quality-adjusted life-year (QALY) gained. Scenario analyses (90-day, 1-year, 5-year, and 20-year horizons) and sensitivity analyses evaluated uncertainty. Over 20 years, endovascular thrombectomy plus MM yielded 0.44 additional QALYs and US dollars 19,611 higher costs versus MM alone, with an incremental cost-effectiveness ratio of US dollars 45,117 per QALY. Endovascular thrombectomy plus MM was cost effective in 59.4
Cardiovascular diseases (CVDs) are a leading contributor to morbidity, mortality, and healthcare spending in low- and middle-income countries (LMICs). Despite this burden, economic evidence on system-level interventions to strengthen hypertension and CVD care in sub-Saharan Africa remains limited. This study estimates the costs and budget impact of the Ghana Heart Initiative (GHI), a multi-component health systems strengthening intervention. We conducted a retrospective cost analysis from the health system perspective using an activity-based costing approach. We estimated the financial and economic costs incurred during the design (2018–2019) and initial implementation phase (2020–2022) of the GHI across 42 public health facilities in the Greater Accra Region. Costs were disaggregated by activity cluster and input category. We then projected the budget impact of hypothetical national scale-up under three implementation scenarios that varied in scope and cost-sharing assumptions. All costs were inflation-adjusted and reported in 2024 US dollars (US ). The total economic cost of designing and implementing the GHI over 4 years was US1.96 million, of which 91.5
Preference-based measures (PBMs) of quality of life are an important tool to inform the evaluation of health and social care interventions and services. Traditionally, PBMs have tended to be developed in a single country, therefore, reflecting the linguistic and cultural norms of that country. Given increases in the cultural and linguistic diversity of populations in many countries, it is important that PBMs are culturally and linguistically adapted. Linguistic adaptation ensures the translated words are correct and accurate, whilst cultural adaptation ensures the meaning and relevance of the concepts are understood as intended by the target audience. Several different guidelines for translation and cultural adaptation exist, including the guidelines developed by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). The aim of this scoping review was to outline which PBMs have been translated and/or culturally adapted and specify any guidelines that have been followed. Four databases (PubMed, SCOPUS, Web of Science, CINAHL) were searched (February 2025) along with grey literature to identify studies that had translated and/or culturally adapted PBMs. Forty-seven articles were included in the review. Translations of PBMs were common, but there was typically limited information about whether PBMs had been culturally adapted. The studies varied significantly as to whether guidelines had been followed and what steps were taken in the process. This review highlights the variable transparency and inconsistency in the methods adopted for the translation and cultural adaptation of PBMs. The application of standardised translation and cultural adaptation guidelines, such as the ones developed by ISPOR, would enhance the methodological quality and cultural validity of PBMs.
