The National Institute for Health and Care Excellence (NICE) is taking a pre-emptive strike at one of healthcare’s most under-recognized burdens, metabolic dysfunction-associated steatohepatitis (MASH). The organization has launched a comprehensive evaluation framework aimed at smoothing the path for the first wave of MASH medicines expected to be worth billions globally before they reach regulators.
The initiative, spearheaded by NICE’s Health Technology Assessment (HTA) Innovation Laboratory, establishes a standard economic model for assessing new treatments for MASH, formerly known as non-alcoholic steatohepatitis (NASH). It represents a proactive bid to eliminate inconsistencies in how future therapies are judged for cost-effectiveness and value to the NHS.
“By using the same model concept to develop and assess evidence submissions, manufacturers and committees can work from the same playbook,” said NICE’s senior scientific adviser Jamie Elvidge in an October 2025 blog announcing the initiative
A growing, overlooked crisis
MASH affects roughly 5% of the UK population around 3.3 million people but remains largely underdiagnosed. The condition, part of the metabolic dysfunction-associated steatotic liver disease (MASLD) spectrum, leads to chronic inflammation, fibrosis and, ultimately, cirrhosis or liver failure. Beyond the liver, MASH is linked to type 2 diabetes, obesity, cardiovascular disease and chronic kidney disease.
Despite its prevalence, there are no licensed treatments in the UK. Current management revolves around lifestyle modification and monitoring. However, a surge of drug candidates from GLP-1 agonists like semaglutide to thyroid receptor β-agonists, FGF-21 analogues and PPAR polyagonists is now moving through clinical pipelines.
Industry analysts estimate that successful entrants could create a global market exceeding $30 billion by the end of the decade. For NICE, that potential comes with a looming evaluation challenge: multiple mechanisms of action, diverse surrogate endpoints and complex trial designs.
NICE’s proactive strike
Recognizing those complexities, NICE’s HTA Lab began developing a shared evaluation blueprint as early as 2024. The project culminated in June 2025 with the release of Evaluating Metabolic Dysfunction-Associated Steatohepatitis (MASH) Treatments a technical report co-created with clinicians, economists, and industry stakeholders.
The Lab’s remit was clear: anticipate the methodological hurdles that could slow NICE’s appraisals once MASH therapies arrive. Among the issues identified:
| Challenge Area | Description | Impact on Assessment |
|---|---|---|
| Structural uncertainty | Variations in how manufacturers build cost-effectiveness models lead to inconsistent assumptions about disease progression, treatment response, and healthcare utilization. | Reduces comparability across submissions and undermines confidence in cost-effectiveness conclusions. |
| Limited long-term data | Clinical studies for MASH often have short follow-up periods, lacking real-world or longitudinal data on disease progression and durability of treatment effects. | Increases uncertainty in projecting lifetime outcomes and long-term cost savings. |
| Reliance on surrogate endpoints | Most trials use fibrosis stage improvement or histologic resolution as primary endpoints to infer survival benefit. | Creates uncertainty about how short-term biomarker changes translate into long-term patient outcomes. |
| High comorbidity overlap | Strong correlations with obesity, cardiovascular disease, and type 2 diabetes complicate attribution of clinical and quality-of-life improvements to MASH treatment alone. | Blurs incremental benefit estimates and complicates health utility modeling. |
To tackle these, NICE proposes a common state-transition model that tracks progression through defined fibrosis stages (F0–F4), cirrhosis, liver cancer and transplant. The design also integrates non-hepatic outcomes, stroke or myocardial infarction via validated risk equations.
A unified model for a fragmented field
The framework sets out specifications for transparency, proportionality and adaptability. NICE encourages manufacturers to calibrate their models with UK-relevant data and to apply consistent assumptions on natural history, mortality, and treatment effect duration.
A key recommendation uses a shared natural history model to avoid divergent baselines. Once one MASH drug has been evaluated, subsequent submissions must test their models against those reference transitions to maintain comparability.
The guidance also underscores infrastructure costs such as expanding access to non-invasive diagnostics like FibroScan and Enhanced Liver Fibrosis (ELF) tests and the potential need for multidisciplinary NHS teams for MASH management.
By pre-defining these parameters, NICE hopes to compress evaluation timelines that often stretch beyond a year, cutting lag between marketing authorization and patient access.
This collaborative model exemplifies NICE’s evolution from a traditional gatekeeper to an enabler of innovation, an approach increasingly necessary as multi-modal therapies and precision medicine reshape drug evaluation.
The framework reduces the guesswork in designing submissions. Knowing NICE’s preferred structure and parameters early can save months in economic modelling and iteration. Moreover, it signals NICE’s willingness to engage pre-submission, mirroring adaptive regulatory efforts seen at EMA and FDA. By anticipating the evaluation challenges ahead, NICE aims to make the UK a more attractive launch market for next-generation metabolic therapies. This could translate to faster access to life-changing drugs targeting fibrosis and inflammation in MASH a disease that often goes undiagnosed until advanced stages.