Revisions to NICE’s Highly Specialised Technologies Routing Criteria: What Will These Mean for Future Ultra-Orphan Technologies?

On 19^th December 2024, the National Institute for Health and Care Excellence (NICE) shared its draft, revised criteria for the routing of technologies to the Highly Specialised Technologies (HST) Programme, and we are pleased to have participated in the public consultation on these changes.

We have provided a top-line summary of NICE’s proposed changes to the criteria and our thoughts on what the revisions may mean for manufacturers of ultra-rare products.

Why is NICE updating the routing criteria?

NICE’s HST Programme is designed to evaluate technologies for severe, debilitating, ultra-rare diseases with limited treatment options using a higher willingness-to-pay threshold than in standard technology evaluations. Whilst NICE’s standard methods and processes are designed to be flexible enough for most orphan medicines, the deliberate, higher potential spend on HSTs encourages research and innovation specifically for ultra-rare conditions with an exceptionally high unmet need and with challenges in generating robust evidence for decision-making, securing fairer and more equitable treatment access.

The NICE prioritisation board identifies technologies suitable for the HST Programme by applying a set of routing criteria, last updated in 2022. However, feedback to NICE has highlighted challenges related to the clarity and objectivity of the routing criteria. Indeed, our research concluded that greater clarity and detail within the routing criteria wording may improve predictability in routing decisions; this would allow manufacturers to better assess the suitability of their treatments for the HST Programme, thereby offering efficiencies to all stakeholders.¹ In light of this feedback and to better align to the vision for the HST Programme, NICE has proposed refinements to the routing criteria.

What are the proposed changes to the routing criteria?

NICE has clarified some of the existing routing criteria by adding more detail and definitions, aiming to minimise ambiguity and subjectivity in the application of the criteria by the NICE prioritisation board. NICE has also added an additional criterion related to innovation, in keeping with the vision of the Programme. The graphic below summarises the overall changes to the routing criteria.

What might the changes mean for manufacturers?

Clarity on the criteria is welcome

In our experience, the outgoing HST routing criteria were subject to interpretation; when NICE assessed technologies against the criteria, it was clear that they consistently applied further context to the criteria, and this context was missing from the criteria wording.¹ Therefore, the addition of more detail and definitions to the routing criteria form a positive step, through which NICE has clarified exactly how the criteria are being applied. The revisions to the criteria have reduced subjectivity and will allow manufacturers to provide appropriate evidence to demonstrate the suitability of their technologies for the HST Programme.

Providing sufficient evidence to meet all four criteria will still be exceptionally difficult, and a degree of subjectivity is inevitable

In its revisions to criterion 1, NICE has clarified that a condition must have an “exceptional” negative impact and burden on people with the disease for a technology to be eligible for the HST Programme. This wording still carries a level of subjectivity; therefore, manufacturers may continue to find it difficult to ascertain whether a condition carries an exceptional burden in NICE’s eyes, highlighting the need for a proactive, patient-centred approach to generating the right evidence. The first criterion considers the prevalence and severity of the wider condition associated with an ICD-10/11 diagnosis code, and not specific subgroups that the technology may be indicated for, if they are not clinically meaningful. These clarifications align with how NICE was previously applying the criteria,¹ but may pose challenges. For example, a number of ultra-rare diseases which have suffered from a lack of recent innovation do not have unique ICD-10/11 codes, meaning that where appropriate, clinical validation will be required to evidence the clinical distinction between conditions or indicated subgroups.

In criterion 4, NICE has also clarified that a product must demonstrate “substantial additional benefit” compared with standard of care to qualify as an HST. The subjective nature of “substantial additional benefit” complicates this criterion, raising questions about the required strength of evidence, such as statistical significance or minimal clinically important differences. In our review of 11 prior HST checklists, NICE questioned the clinical significance of results for statistically significant benefit, indicating that they have always applied a level of subjectivity when assessing this criterion. NICE has specified that substantial additional benefit can be demonstrated using patient-reported outcome measure (PROM) and survival data; however, clinical evidence in ultra-rare conditions is often limited by short trial durations and PROMs that are not developed or validated for the specific condition. The revisions to this criterion highlight the need for comprehensive and compelling evidence supporting substantial additional benefit versus current standard of care, including PROM and survival data.

Another notable change to the fourth criterion is that substantial additional benefit versus standard of care must be shown in addition to demonstrating the inadequacy of current standard of care. Previously, meeting only one of these conditions was sufficient. Meeting both conditions will be exceptionally difficult. Our prior research examining 11 HST checklists indicated that despite the positive trial results reported by manufacturers for 6 interventions, NICE considered that none of these interventions offered significant benefit over existing treatments, and NICE determined that only three appraisals had no satisfactory treatments available. In addition, where a technology is indicated to treat a specific symptom, NICE now considers that the availability of any symptomatic treatment (regardless of its effectiveness) would be considered adequate, meaning that this condition would not be met. Based on our research and experience, manufacturers should centre arguments for the inadequacy of standard of care around a lack of clinical benefit (for example, looking at disease progression or quality of life under current treatment).

In order to demonstrate that a technology meets the revised HST criteria, we would encourage companies to consider:

• Ensuring key evidence is available at least 6 months ahead of the anticipated NICE submission, to enable a strong case for meeting all four HST criteria to be put forwards during the evaluation scoping phase
• Elicitation of patient and clinical expert opinion, to (i) appropriately characterise the burden of disease and provide evidence for the inadequacy of standard of care, (ii) ensure that appropriate and robust evidence for the efficacy of the technology, such as quality of life data, is generated to support “substantial additional benefit”, and (iii) substantiate the clinical distinction between the condition/subgroup relevant to the intervention, versus wider conditions/subgroups, for criterion 1
• Early modelling, allowing manufacturers to provide evidence for the severity of the condition over a lifetime, and survival and quality of life benefits of a technology

Issues with access to NHS services may contribute towards the inadequacy of standard of care

The revised fourth criterion is designed to address the lack of effective treatment and access to NHS services for some ultra-rare diseases. Highly specialised treatment centres for ultra-rare conditions may be situated very far from where people live, forming a barrier to access to high quality care, and a burden on people with the condition. Where a technology may offer benefits to access to care (such as a simplified treatment pathway or administration and monitoring in primary or local secondary care), manufacturers should not solely focus on effectiveness data when providing evidence for criterion 4. Manufacturers should also consider whether introduction of their treatment would offer substantial benefits in terms of access to treatment, versus current standard of care.