Objective: Currently there are no disease-specific approved therapies for non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH); however, several treatments are under development. This study aimed to estimate the cost-effectiveness of hypothetical innovative therapies compared with lifestyle intervention alone and combined with pioglitazone, and assess the health economic consequences of their future availability for patients. Methods: A Markov cohort model was developed, considering fourteen disease health states and one absorbing state representing death. Transition probabilities, costs, utilities, and treatment efficacy were based on published data and assumptions. Four treatment strategies were considered, including two existing therapies (lifestyle intervention, small molecule treatment) and two hypothetical interventions (biological and curative therapy). The analysis was performed from the US third-party payer perspective. Results: The curative treatment with the assumed efficacy of 70% of patients cured and assumed price of $500,000 was the only cost-effective option. Although it incurred higher costs (a difference of $188,771 vs. lifestyle intervention and $197,702 vs. small molecule), it generated more QALYs (a difference of 1.58 and 1.38 QALYs, respectively), resulting in an ICER below the willingness-to-pay threshold of $150,000 per QALY. The sensitivity analyses showed that the results were robust to variations in model parameters. Conclusions: This study highlighted the potential benefits of therapies aimed at curing a disease rather than stopping its progression. Nonetheless, each of the analyzed therapies could be cost-effective compared with lifestyle intervention at a relatively high price.

The European Parliament, in its resolution of March 2nd, 2017, on European Union (EU) options for improving access to medicines, called on the Commission to propose legislation on a European system for health technology assessment (HTA) to harmonize transparent HTA criteria to assess the added therapeutic value and relative effectiveness of health technologies compared with the best available alternative (1). In December 2021, the EU-HTA R, formally known as ‘Regulation (EU) 2021/2282 of the European Parliament and of the Council of December 15th, 2021’ (2), on HTA and amending Directive 2011/24/EU (3) was adopted. It entered into force with implementation starting in January 2022 for oncology products and advanced therapeutic medicinal products (ATMP) in January 2028 for orphan designated products and in January 2030 for all products.

Bulgaria is assumed to be the country with the lowest COVID-19 vaccination coverage in the EU. The present study aims to highlight the economic impact of vaccine hesitancy. The period analyzed is from 1 January 2021 to 31 December 2021, examining hospitalization costs for COVID-19 patients, vaccine application costs, and vaccine type and dose administered. Results demonstrate a net impact of BGN 97 686 089 (€49 946 104) if 30% of the eligible population had been vaccinated and BGN 146 529 133 (€74 919 156) if a 45% rate had been achieved. In addition, 5.1 million unused doses were scrapped—more than those administered. The public health impact of vaccine hesitancy in Bulgaria led to a preventable medical crisis, substantial economic losses due to avoidable hospitalizations, and significant additional costs associated with the destruction of unused vaccines.

The practice of Health Technology Assessment (HTA) inherently involves moral, epistemological, and ontological commitments, which shape how assessments are conducted, interpreted, and used for decision-making

The Joint Clinical Assessment (JCA) report on tovorafenib (Ojemda), the first assessment of an orphan oncology medicinal product completed under Regulation (EU) 2021/2282 [1], conformed closely to predictions made across our earlier work. This Perspective argues that the outcome was foreseeable from the framework’s design rather than from any feature of the product. We characterise the JCA as an audit that confronts developer-submitted evidence against a corpus of EUnetHTA methodological guidance whose scientific validity and development process have been widely contested. Four structural features explain the result: the referential cannot function as a settled gold standard; the assessment omits the interpretive, context-dependent judgment that gives evidence meaning, on the assumption — specific to one national tradition — that assessment can be separated from appraisal and conducted free of judgment; products supported only by single-arm trials are predictably assessed negatively, as Ojemda illustrates; and the framework departs from the tripod of evidence-based medicine by marginalising clinicians and patients. By multiplying PICOs, subgroups and outcomes and then criticising the resulting analyses as post hoc, the JCA generates its own limitations and ultimately cannot state a degree of certainty of relative effectiveness. We conclude that single-arm-supported products should fall outside the JCA’s remit and that the framework requires a transparent route from documented uncertainty to a stated certainty.