Exploratory Project Report: Individualised therapies and platform technologies: exploring methodological challenges for NICE project report

No named authors; MRC CoRE members contributed to the production of the report

Executive summary

This report has been prepared for NICE staff and stakeholders including system partners. It summarises the NICE HTA Lab’s project exploring the challenges of evaluating individualised medicines and the potential opportunities related to innovative platform therapies used to develop medicines. It also identifies potential responses to these challenges. This work aligns with the Medicines and Healthcare products Regulatory Agency’s policy paper on rare therapies (November 2025), which signals a lifecycle, patient-focused regulatory direction. Rare diseases, which are defined as affecting fewer than 1 in 2,000 people, collectively impact 1 in 17 people in the UK. Advances in genetic and molecular medicine are accelerating the development of increasingly targeted, ‘individualised’ therapies that may require NICE appraisal. The project outline is:

· Scope: medicines and platform-enabled individualised medicines (not health tech platforms).

· Status: exploratory synthesis to surface challenges and practical options for testing in the HTA Lab.

· Policy: not included. Any future consideration of methods or process changes would follow NICE’s governance and wider system coordination.

The project combined a horizon scan, a systematic literature review and 4 stakeholder workshops with clinicians, patients, system stakeholders, NICE staff, evaluation committee chairs, academic experts and industry. Key findings include:

· Evidence for individualised therapies can, particularly in rare and ultra-rare contexts, be limited, non-comparative and reliant on surrogate endpoints. This creates high levels of decision uncertainty for NICE.

· Limited natural history data and variability in model structures reduce generalisability and comparability across NICE evaluations.

· Managed access arrangements and appraisal processes also create challenges, including:

o limited ability to reuse anonymised evidence across related appraisals

o challenges in applying existing appraisal routes, because some individualised therapies may not clearly meet NICE’s highly specialised technologies (HST) criteria and cannot feasibly be appraised together under the multiple technology appraisal (MTA) process.

There is a risk that these issues may create inconsistencies and delays in decision-making for individualised therapies.

Stakeholders agreed that although NICE’s current framework can accommodate some individualised therapies, if NICE were asked to evaluate a growing number across multiple platforms, further methodological development may be needed and merits testing in a research setting first.

Recommendations for further applied research

The project identified 3 primary recommendations for applied research and scoping. These outline how NICE might feasibly seek to adapt its methods or processes, while continuing to engage system stakeholders to support wider solutions. They are designed to progress the key challenges identified through horizon scanning, the literature review and stakeholder engagement. Our recommendations for focused testing of identified potential solutions are:

· Pilot a NICE-facilitated precompetitive collaboration in which stakeholders can align on key modelling assumptions and methods for therapeutic pipelines characterised by high uncertainty, responding to duplication and inconsistency in modelling approaches across developers.

· Pilot a mock appraisal within the HTA sandbox for a platform technology under development for multiple related indications, testing approaches for using evidence across appraisals. This addresses challenges of evidence transferability, reliance on surrogate endpoints and managing asynchronous pipelines.

· Pilot an evaluation that focuses on structured threshold analysis under high uncertainty, using threshold analyses and expert elicitation to assess plausibility for high-uncertainty cases. This addresses the challenge of decision-making when evidence is highly uncertain or derived from small or single-arm studies.

These recommendations provide a starting point for NICE to test new methods, improve guidance and prepare for a growing pipeline of complex therapies while maintaining rigour and transparency. NICE should also continue engaging with system stakeholders to support a system-wide response to ensuring access to innovative, individualised therapies. This would address challenges that extend beyond NICE’s specific remit, such as data infrastructure and service readiness.

The stakeholders also advised that guidance from NICE on the following topics would be useful:

· The use of natural history data, to define consistent standards for data quality, representativeness and uncertainty.

· Ways to enhance NICE’s institutional memory, such as by creating and maintaining a register of key assumptions and decisions (for example, utility values and parameter ranges) in appraisals of rare diseases. This would support future evaluations.

This project has shown that NICE’s framework can accommodate some individualised therapies, but the growing scale and complexity of future pipelines may require focused solutions. The recommendations outlined here provide pragmatic options for piloting methods and improving consistency. Although the focus is on rare and ultra-rare contexts, we recognise that individualised approaches are also emerging in more prevalent conditions, such as oncology, which may need to be considered through other programmes.

Direct links:

Individualised therapies ​final report (Word)

• ​​​​Appendix A: Pipeline scan report​​​​ (Word)
• ​​​​Appendix B: Economic evidence review​​​​ (Word)
• Appendix C: Stakeholder engagement​ (Word)