When bringing a new health technology to market in England, pharmaceutical and biotech companies must contend with the National Institute for Health and Care Excellence (NICE) appraisal system. Two distinct pathways exist for evaluating the value of new therapies – the Highly Specialised Technologies (HST) programme and the Single Technology Appraisal (STA) route.1,2 While the STA is the default for most products, HST is reserved for a narrow set of therapies targeting very rare diseases.1,2 Selecting the correct route is not simply procedural, it can make or break a product’s market access success. This article demystifies how NICE selects between these two pathways, outlines key differences, and offers guidance for companies preparing for either scenario.
HST vs STA – What are the key differences?
The HST programme and STA route differ in terms of eligibility criteria, process timelines, assessment expectations, and acceptance thresholds. Understanding these distinctions is crucial to identifying the optimal path for a therapy. Table 1 summarises the primary differences:
Table 1: Summary of the key differences between the two NICE processes (HST & STA)
| Criteria | HST | STA |
|---|---|---|
| Prevalence / eligible patients | Disease prevalence < 1 in 50,000 and usually ≤ 300 eligible patients in England1 Routing criteria 3: The very rare disease for which the technology is indicated significantly shortens life or severely impairs quality of life1 Routing criteria 4: There are no other satisfactory treatment options, or the technology is likely to offer significant additional benefit over existing treatment options1 | No upper prevalence cap, though very common diseases may prompt extra scrutiny2 |
| Timing from scoping to final guidance | Once the invitation to participate is issued, final HST guidance is typically published within 39–43 weeks3 | 38-47 weeks depending on whether FDG or DG is produced; an extra two months if a technical-engagement round is needed2 |
| Base ICER threshold | 100,000/QALY is the threshold but can go up to ~£300,000/QALY with modifiers4 | Standard ICER threshold: £20,000–£30,000/QALY4 |
| Evaluation fee (2024/25–2025/26) | Same fee structure, but payment is phased (40% on evidence submission, 50% pre-committee, 10% pre-publication)6 | £186,100 for large companies; 75% discount for SMEs5 |
| Decision-making body | HST Committee (augmented by ultra-rare-disease experts) | Technology Appraisal Committee |
| Commercial levers | No separate budget-impact test; bespoke deals negotiated because volumes are inherently low | Commercial Access Agreements; budget-impact safeguard at £20 m a year triggers NHS England negotiations7 |
Why Selecting the Correct Route is Critical
Since 2024, NICE’s single Topic Prioritisation Board has taken on central responsibility for deciding appraisal routes. Securing the right routing decision early, ideally before the Phase III trial design is finalised, can dramatically affect two strategic levers for a company:
- Timelines and launch sequencing: STA guidance can be published within 90 days of MHRA approval if the evidence package is complete.8 In contrast, HST guidance typically arrives no earlier than 12 months after receiving MA, extending the revenue timeline.9 This delay can be especially burdensome for smaller biotech’s that rely on early cash flow.
- Cost-effectiveness: A product just over the HST prevalence threshold may still be routed to STA, exposing it to the conventional £30,000/quality adjusted life year (QALY) threshold.4 On the other hand, seeking HST designation without genuine eligibility can be risky if uncertainties push the case incremental cost effectiveness ratio (ICER) above £100,000/QALY, even after applying modifiers.4
Misaligning a product with the wrong appraisal pathway can therefore result in substantial commercial, operational, and reputational costs. A product eligible for HST that mistakenly enters the STA route may be assessed against inappropriate thresholds and be undervalued due to insufficient recognition of its rarity and clinical complexity. The reverse scenario, in which a product more suited for STA is forced into the HST process, risks rejection by NICE and inefficient resource use.
Companies are strongly encouraged to engage with NICE early through Scientific Advice or a topic routing request. These steps can provide clarity and ensure alignment between clinical, economic, and regulatory strategies, helping avoid costly missteps.
Preparing for STA vs HST
If HST Criteria Are in Reach
To support a successful HST evaluation, manufacturers should begin preparation well in advance of the Topic Prioritisation Board meeting. Between six and nine months before the meeting, it is essential to prepare a dossier that robustly addresses all four HST routing criteria (see Table 2). These criteria determine whether the technology qualifies for HST rather than standard appraisal, and the strength of evidence provided will influence routing decisions.
Table 2: HST ROUTING CRITERIA1
| Routing criteria 1 | The disease is very rare ‘Very rare’ is defined as a disease that has a prevalence in England lower than 1 in 50,000 people, or about 1,100 people |
| Routing criteria 2 | Normally, no more than 300 people in England are eligible for the technology in its licensed indication and no more than 500 across all its indications |
| Routing criteria 3 | The very rare disease for which the technology is indicated significantly shortens life or severely impairs quality of life The terms ‘significantly’ and ‘severely’ are not defined because they require judgement |
| Routing criteria 4 | There are no other satisfactory treatment options, or the technology is likely to offer significant additional benefit over existing treatment options |
Given the rarity and complexity of many conditions assessed under the HST pathway, conventional randomised controlled trials may be impractical or unethical. Therefore, early investment in natural history cohorts or disease registries is vital. These sources can provide critical data to inform both clinical and economic models, particularly where comparator data or long-term outcomes are limited.
Bayesian modelling techniques are commonly used in HST evaluations to integrate limited clinical trial data with expert elicitation. While this approach can strengthen the credibility of evidence in areas of uncertainty, manufacturers must still ensure that the resulting base case ICER falls below the £100,000/QALY threshold for their technology to be considered cost effective.
Lastly, co-developing the value proposition with patient organisations is strongly recommended. When there is high uncertainty in cost effectiveness evidence, the appraisal committee places considerable weight on qualitative evidence about the burden of illness. Patient narratives can play a pivotal role in illustrating unmet need, disease severity, and the impact of current care limitations.
If an STA Looks Likely
To optimise the likelihood of a positive outcome during a NICE STA appraisal, manufacturers should initiate strategic planning well in advance of submission. A critical first step is identifying appropriate real-world comparators through engagement with clinical advisors, ideally via clinical advisory boards, at least 18 months before submission. NICE typically expects either direct head-to-head trial data or robust indirect comparisons against all routinely used treatment options in the NHS. Early alignment on comparators will ensure that clinical and economic evidence meets these expectations.
Alongside comparator selection, manufacturers should begin developing the cost effectiveness model in accordance with NICE’s reference case requirements. This includes adopting:
- A lifetime time horizon to capture all relevant costs and health outcomes
- An NHS and Personal Social Services (PSS) perspective for both cost and resource use
- A 3.5% annual discount rate applied to both costs and outcomes10
Where relevant, companies should also explore the impact of disease severity modifiers, particularly the application of severity weightings such as 1.2 and 1.7, which NICE uses to reflect greater value for treatments targeting patients with higher unmet need based on the extent of health loss without treatment.11 These scenario analyses can demonstrate how the value of the technology may vary for patients with higher disease burden, in line with NICE’s severity modifiers for QALY weighting, which can influence acceptability within the standard £20,000–£30,000 per QALY cost-effectiveness threshold.4
Budget impact is another important consideration. If the anticipated budget impact exceeds £20,000,000 per year during any of the first three years of launch, companies are expected to propose a Commercial Access Agreement.12 This should be developed confidentially and in parallel with the appraisal to avoid delays in final guidance, which can otherwise result from late-stage price negotiations.
Conclusion
NICE’s dual appraisal framework is more than a procedural formality. It is a strategic crossroad that influences how a therapy is developed, valued, and ultimately accessed by patients in England. While the STA route remains the standard pathway for most technologies, the HST programme offers a distinct and more flexible route for therapies targeting very rare and complex conditions. Each pathway comes with its own expectations, timelines, and decision thresholds, and the implications for market access success are substantial.
With routing decisions now centralised under NICE’s Topic Prioritisation Board, companies must engage early and plan proactively. Selecting the appropriate appraisal route before finalising Phase III trial designs help avoid mismatches between evidence and expectations, minimises late-stage course corrections, and supports more efficient pricing, budgeting, and stakeholder engagement. Misalignment can lead to failed submissions, costly redesigns, and delays in patient access. Conversely, getting the route right and preparing accordingly enables companies to navigate the system with confidence, credibility, and commercial clarity.
In the race to secure NHS access, knowing your appraisal route is not just good planning. It is competitive advantage. Get it right, and you accelerate time to market, reduce uncertainty, and deliver value where it matters most. Get it wrong, and you risk losing both time and trust.
Remap Consulting supports companies in navigating this critical decision early, from shaping early access and value strategies, to guiding you through the HST or STA process with robust, evidence-led submissions aligned to NICE expectations. Get in touch here.
References
- National Institute for Health and Care Excellence (NICE). Highly Specialised Technologies. NICE. Published October 2022. Accessed May 29, 2025. https://www.nice.org.uk/process/pmg37/chapter/highly-specialised-technologies
- National Institute for Health and Care Excellence (NICE). Single Technology Appraisal Timeline. NICE. Accessed May 29, 2025. https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/technology-appraisal-guidance/process/sta-timeline
- National Institute for Health and Care Excellence (NICE). Technology appraisal and highly specialised technologies charging timelines and process [Internet]. London: NICE; 2024. Available from: https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/technology-appraisal-guidance/ta-hst-charging-process.pdf
- Hellmund C. The NICE HST process (1/3) – origins and current state of affairs [Internet]. Source Health Economics; 2019 Jun 2 [cited 2025 Jun 12]. Available from: https://source-he.com/the-nice-hst-process-1-3-origins-and-current-state-of-affairs/#:~:text=In%202017%2C%20NICE%20introduced%20a,Technology%20Appraisal%20(STA)%20process.
- National Institute for Health and Care Excellence (NICE). Charging for NICE Technology Appraisal Guidance. NICE. Accessed May 29, 2025. https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-technology-appraisal-guidance/charging
- National Institute for Health and Care Excellence (NICE). Charging Procedure for HST Guidance. NICE. Accessed May 29, 2025. https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisal-guidance/HST-charging-procedure.pdf
- National Institute for Health and Care Excellence (NICE). Guide to the Processes of Technology Appraisal: April 2018 Update. NICE. Published April 2018. Accessed May 29, 2025. https://www.nice.org.uk/Media/Default/About/what-we-do/NICE-guidance/NICE-technology-appraisals/technology-appraisal-processes-guide-apr-2018.pdf
- National Institute for Health and Care Excellence (NICE). UK licensing and technology appraisals [Internet]. London: NICE; 2024 [cited 2025 Jun 12]. Available from: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/technology-appraisal-guidance/uk-licensing-and-technology-appraisals
- National Institute for Health and Care Excellence (NICE). Highly specialised technologies guidance [Internet]. London: NICE; 2024 [cited 2025 Jun 12]. Available from: https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/nice-highly-specialised-technologies-guidance
- National Institute for Health and Care Excellence (NICE). Economic Evaluation. In: NICE Health Technology Evaluations: The Manual. NICE. Published January 2024. Accessed May 29, 2025. https://www.nice.org.uk/process/pmg36/chapter/economic-evaluation-2
- National Institute for Health and Care Excellence (NICE). NICE Health Technology Evaluations: The Manual. NICE. Published January 2024. Accessed May 29, 2025. https://www.nice.org.uk/process/pmg36/resources/nice-health-technology-evaluations-the-manual-pdf-72286779244741
- Wills E, Charles A, Jefferies D, Watkins E. Access to new medicines in the English NHS [Internet]. London: The King’s Fund; 2025 May 28 [cited 2025 Jun 12]. Available from: https://www.kingsfund.org.uk/insight-and-analysis/long-reads/access-new-medicines-english-nhs