The National Institute of Health and Care Excellence (NICE) has published several updates and released insights into key appraisal tools for 2025, including a review of the severity modifier, refined highly specialised technologies (HST) criteria and the relaunch of the UK-wide Innovative Licensing and Access Pathway (ILAP). While the managed access agreement (MAA) process remains unchanged, it plays a crucial role in enabling access for treatments with unresolved uncertainties. This article outlines essential information to manufacturers and provides guidance on adapting their strategies under the current framework.
Severity modifier
In 2022, NICE introduced the severity modifier, an algorithm that adjusts the value rating of treatments depending on the severity of the disease.1 For example, in more severe diseases, the cost-effectiveness threshold of treatments can be increased, enabling more expensive treatments to be recommended. The severity modifier replaced the previous ‘end-of-life modifier’ and is ‘opportunity cost neutral’. This means that when applied to treatments already recommended, it does not increase the overall cost burden on the healthcare system.1
The severity modifier considers two measures of disease severity: ‘absolute quality adjusted life years (QALY) shortfalls’ (AS) and ‘proportional QALY shortfalls’ (PS).2 AS represents the quantity of future QALYs lost by individuals with the disease. Therefore, AS tend to be higher for younger patient populations since they are likely to lose more QALYs compared to older populations. PS represents the proportion of future QALYs lost by individuals with the disease.2 Consequently, PS typically scores higher for older patient populations as they have fewer remaining QALYs, indicating a higher proportion of loss compared to the younger population. NICE recommends that the severity modifier accounts for additional aspects, specifically the current standard of care (SoC). Therefore, technically the AS and PS scores represent the number and proportion of discounted future QALYs lost by people living with the disease and receiving the SoC.
In September 2024, NICE released a review of the severity modifier, which highlighted that applying the severity modifier resulted in a higher proportion of positive recommendations (84.4%) compared with the previous end-of-life modifier (82.7%).3 As a result, the severity modifier was reported to be working as intended and no changes are expected in the near future.
What this means for manufacturers?
- Manufacturers developing expensive treatments for severe diseases should push for the severity modifier to be applied to achieve the best chance of a positive recommendation
- Manufacturers should adjust their evidence and value proposition to robustly demonstrate disease burden and highlight severity as defined by the key QALY shortfalls used in the algorithm
Key actions that manufacturers should take
- Demonstrate severity – Calculate both AS and PS scores and comprehensively showcase the disease burden
- Prepare early – Engage with NICE, such as through early scientific advice, to discuss assumptions regarding the severity modifier and resolve any uncertainties that could impact the likelihood of its application
- Tailor clinical development – Ensure relevant trial endpoints capture long-term outcomes, survival, and health-related quality of life (HRQoL), which can be used to calculate AS and PS scores
Updated HST criteria
The HST process is specifically designed for evaluating medicines or technologies developed for ultra-rare diseases that meet the HST criteria. This process allows for a higher ICER threshold of £100,000, which may increase to £300,000 under exceptional circumstances.4 In December 2024, NICE held a consultation of the HST criteria, with the key objective being to better clarify and define the criteria to improve the efficiency of the decision-making process. Following this consultation, NICE announced several refinements to the HST routing criteria, which took effect in April 2025:4
Routing Criteria 1:
The disease is ultra-rare and debilitating, that is,
- 1A: it is defined as having a point prevalence of 1:50,000 or less in England
- 1B: it is lifelong after diagnosis with current treatment and has an exceptional negative impact and burden on people with the ultra-rare disease, and their carers and families
Routing Criteria 2:
The technology is an innovation for the ultra-rare disease.
Routing Criteria 3:
No more than 300 people in England are eligible for the technology in its licensed indication, and the technology is not an individualised medicine.
Routing Criteria 4:
The technology is likely to offer substantial additional benefit for people with the ultra-rare disease over existing established clinical management, and the existing established clinical management is considered inadequate.
For additional information clarifying the criteria definitions see here.
What this means for manufacturers?
- The refinements to the HST routing criteria make it easier for manufacturers to assess whether their pipeline products meet the criteria for the HST process
- By providing improved clarity, this streamlines the decision-making process, thereby positively impacting manufacturer pipelines through faster access and approval
Key actions that manufacturers should take
- Reassess their pipeline – Manufacturers should reassess the eligibility of their pipeline products to determine whether any qualify for the HST process based on the refined criteria
- Clearly demonstrate disease burden – Manufacturers should robustly demonstrate the burden of disease, highlight the unmet needs, and clearly define the patient population to ensure the HST criteria are met
- Tailor clinically relevant endpoints – As part of manufacturer’s evidence generation strategy, they should tailor clinically relevant endpoints that can demonstrate substantial additional benefit over the current SoC
Managed access agreements
MAAs are used when some drugs cannot be routinely funded due to uncertainty around their clinical or cost-effectiveness but already have marketing authorisation from the MHRA. Therefore, they are used to allow access to medicines whilst additional data are collected. They are different to interim funding agreements, which enable funding and access to treatments that receive a provisional positive NICE recommendation before the final guidance is determined (i.e., before routine reimbursement).
MAAs between the manufacturer and NHS England consist of 2 elements: a commercial access agreement and a data collection agreement.5 The commercial access is between NHS England and the company. It lays out the commercial terms on which the NHS will fund the treatment and considers the current data on cost-effectiveness. It also ensures that any identified uncertainties are mitigated against during managed access. The data collection agreement, which can last up to 5 years, outlines the additional data (i.e., clinical trial and real-world evidence) that will be collected to address current uncertainties and enable routine funding when the MAA finishes.5
Without routine reimbursement, treatments with a MAA can be funded by two dedicated funding sources: the innovative medicines fund (IMF) or the cancer drugs fund (CDF), each with an annual budget of £340 million.5 It is worth noting that non-oncology drugs, which are not deemed ‘innovative’, are at higher risk of not securing a MAA. This is because these drugs will not receive funding from the CDF and are unlikely to receive funding from the IMF, making it more likely that they would rely on the NHS England specialised-commissioning budget for funding.6
Once all the RWE/trial data has been collected, the manufacturer must prepare to be rescoped and resubmit their updated submission, where they may be compared against new therapies that have become the SoC since the previous submission.
What this means for manufacturers?
- Given the limited budgets of the CDF and IMF, there may be competition between potential treatments to receive funding
- Typically, only oncology or medicines deemed ‘innovative’ can obtain CDF and IMF funding which may result in manufacturers missing out on potential MAAs or facing higher scrutiny if alternative funding sources are required
- Manufactures have to undergo a resubmission at the end of the MAA where they may be compared against new therapies that have become the SoC since the previous submission
- RWE can play a critical role in data collection to overcome uncertainties and receive reimbursement following the MAA
Key actions that manufacturers should take
- Plan early – Manufacturers should plan early and determine if a MAA is required by assessing any uncertainties and gaps within the data, and include the application in the initial submission
- Data collection – Develop a robust data collection agreement to address NICE uncertainties
- Commercial access – Focus on modelling cost-effectiveness early to support commercial access negotiations
ILAP has been relaunched
In January 2025, the UK-wide ILAP was relaunched. This refreshed process aims to offer a streamlined service for manufacturers of transformative medicines and drug-device combinations, allowing them to engage with NICE, the SMC, the MHRA, and the NHS through a single point of contact from pre-pivotal trial to routine reimbursement.
Key changes to the new ILAP scheme include involving the NHS as a core partner, more selective entry criteria, specifically additional clarity around criteria 1-3, predictable delivery timelines enabling manufacturers to plan more effectively, early interaction with patients to assist with patient uptake a system-wide adoption, a single point of contact, future proofing to help accelerate access.7,8
Eligible products are rewarded with an innovation passport that enables them to work with ILAP partners to create a target development profile (TDP) within 6 months. The TDP helps support regulatory approval and market access by providing a roadmap that outlines key regulatory and developmental aspects.7 Innovative passport holders also have exclusive access to a range of services such as the ILAP joint scientific advice service, priority scheduling pass and the ILAP access forum which offers direction on where a new technology might fit in the care pathway (essential for complex care pathways or where a clinical trial was not conducted in the UK), service delivery implications for the NHS (including commissioning considerations, testing requirements, infrastructure changes), high-level HTA challenges and how commercial processes are likely to apply.9
What this means for manufacturers?
- Manufacturers will have to face stricter eligibility criteria in order to qualify for ILAP
- Having a single point of contact and more predictable timelines enables manufacturers to optimise decision making, allocate resources efficiently and synchronise UK-specific evidence generation with launch plans
- The new ILAP access forum offers system-wide insight to manufacturers enabling them to anticipate product placement, NHS service delivery needs and key HTA evidence hurdles
Key actions that manufacturers should take
- Plan early to ensure the eligibility criteria are met when applying for the innovation passport pre-clinical trial
- Evaluate pipeline for ILAP suitability
- Leverage the access forum and priority services
- Align clinical trial design with regulatory and reimbursement expectations per advice from the MHRA, NICE and NHS England
Conclusion:
The 2025 updates and insights into key appraisal tools provide greater clarity and direction, reinforcing the need for early, evidence-driven planning. While not all areas have changed, understanding how to leverage tools like the severity modifier, navigate the refined HST criteria, and engage through ILAP can improve submission outcomes. Manufacturers who align their strategies early and address evidentiary gaps proactively will be best positioned for successful access and reimbursement in the evolving UK landscape.
Remap Consulting offers strategic guidance and support to manufacturers navigating the latest UK access reforms, such as guiding products through the ILAP pathway, determining HST eligibility and managing the full HST submission, building cost-effectiveness models that incorporate severity modifiers, and developing robust MAA protocols. Please get in touch.
References:
- https://www.nice.org.uk/news/articles/nice-board-says-new-method-allowing-greater-weight-to-be-given-to-severe-diseases-is-working
- https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjqsrretaCOAxUMZ0EAHVk7HAEQFnoECB0QAQ&url=https%3A%2F%2Fwww.sheffield.ac.uk%2Fmedia%2F57671%2Fdownload%3Fattachment%3Fattachment&usg=AOvVaw2RKIMpLsVu2IeEdt4d69St&opi=89978449
- https://indepth.nice.org.uk/what-is-nices-severity-modifier/index.html
- https://rarerevolutionmagazine.com/nices-highly-specialised-technologies-hst-criteria-a-summary-and-impact-analysis/
- https://www.nice.org.uk/about/what-we-do/our-programmes/managed-access
- https://www.england.nhs.uk/commissioning/spec-services/key-docs/#manual
- https://www.gov.uk/government/publications/innovative-licensing-and-access-pathway-ilap/ilap-application-guidance#selection-criteria
- https://www.gov.uk/government/publications/statement-of-policy-intent-relaunch-of-the-innovative-licensing-and-access-pathway/statement-of-policy-intent-relaunch-of-the-innovative-licensing-and-access-pathway
- https://www.insideeulifesciences.com/2025/02/14/re-launch-of-uks-innovative-licensing-and-access-pathway-ilap/