Bridging the Regulatory-HTA divide

Bringing together regulatory, clinical operations, and HTA expertise across organisations, Ellie McDermott, Senior Regulatory Executive at G&L Scientific, in collaboration with Joanne Noble-Longster, Head of Clinical Operations at Tolley, and Emma Prentice, Senior HTA Consultant at Tolley, provide a cross-disciplinary perspective on how the UK’s Aligned Pathway is reshaping the interface between marketing authorisation and NHS access.

The UK’s Aligned Pathway represents a structural shift in how medicines progress from regulatory approval to NHS use.

Developed collaboratively by the Medicines and Healthcare products Regulatory Agency (MHRA) and the National Institute for Health and Care Excellence (NICE), the pathway is designed to synchronise regulatory review with Health Technology Assessment (HTA) replacing the traditional sequential model with a coordinated parallel process.

Historically, marketing authorisations for pharmaceutical innovative treatments have operated on separate timelines, often creating avoidable delays between licence and NHS access. The Aligned Pathway seeks to reduce this friction by aligning evidence requirements, decision points, and planning processes, with the objective of maintaining rigorous standards of safety, quality, clinical and cost effectiveness.

The pathway is currently being piloted with selected early-access products and will apply to all eligible technologies from April 2026. Its impact is expected to be most pronounced in areas of high unmet need, including rare diseases, where delays to patient access have been particularly significant.

A central feature of the pathway is the requirement for pharma and biotech companies to register products on UK PharmaScan at least three years prior to the anticipated marketing authorisation.

This early visibility enables regulators, HTA bodies, and the NHS to plan proactively for assessment and resourcing of upcoming technologies. Although early registration may present challenges to developers, it also creates an opportunity as early engagement encourages timely consideration of HTA evidence needs that might otherwise be overlooked.

The coordinated approach allows NICE to schedule evaluations in advance and align them with the MHRA decision timelines. By removing the traditional 90-day gap between regulatory approval and HTA guidance, the pathway is expected to bring new medicines to NHS patients three to six months earlier.

Additionally, a fully integrated joint scientific advice service will be available to encourage early engagement between developers, MRHA, and NICE, supporting the generation of evidence that meets the needs of both regulatory and HTA evaluations.

Some developers may find aspects of the alignment process challenging to resource, particularly where dedicated HTA, reimbursement, or HEOR expertise is not yet established internally. In such cases, drawing on external regulatory and HTA insight, via the joint scientific advice service, could help bridge potential gaps in requirements.

Importantly, statutory responsibilities remain distinct. The MHRA continues to assess safety, quality, and efficacy, while NICE evaluates clinical and cost effectiveness.

The Aligned Pathway does not merge these functions, it coordinates them. The result is greater predictability, reduced administrative burden, and improved system readiness for NHS planning and commissioning.

By synchronising timelines, aligning evidence requirements, and fostering earlier dialogue, the Aligned Pathway directly addresses long-standing disconnects between regulatory approval and market access.

It offers a more transparent, efficient, and patient-centred approach from development to real-world adoption in the NHS, which will in turn strengthen the UK’s position as an attractive environment for life sciences innovation.

Gaps in the UK Regulatory–HTA landscape

To understand the significance of this reform, it is important to recognise the structural disconnects that have historically contributed to delays in UK market access.

A key issue has been the disconnect between the evidence generated for regulatory approval and the evidence required for evaluation of cost effectiveness during HTA. Clinical studies designed to meet regulatory standards do not always provide the type or depth of data needed for reimbursement decisions, creating uncertainty during HTA evaluations.

This misalignment can delay or complicate market access, ultimately slowing patient access to innovative therapies. Recurring evidence gaps commonly encountered across regulatory and HTA processes include:

• Patient populations – trial populations are often highly selective, including participants that are more homogenous, lacking the complex comorbidities and diversity that would be found in real-world patients. Regulatory bodies are typically accepting of these controlled populations, whereas NICE prefers populations to be representative of UK clinical practice, with regards to disease severity, patient demographics, and treatment history.
• Patient-relevant outcomes – surrogate endpoints are increasingly being used in place of direct clinical outcomes in regulatory submissions to accelerate marketing authorisation, particularly in rare diseases. Trials with surrogate endpoints are often shorter, smaller, and more cost effective, reducing the cost and resource burden to the technology developer. However, HTA bodies place more weight on disease-relevant direct clinical outcomes, quality of life, and long-term durability of effect, to permit robust cost-effectiveness modelling.
• Comparators – placebo-controlled trials are often acceptable in regulatory submissions; however, NICE require robust comparisons versus current NHS standard of care either from direct, head-to-head clinical trial data, or robust indirect treatment comparisons. Lack of head-to-head evidence and the requirement for indirect treatment comparisons leads to uncertainty in relative clinical effectiveness which contributes to price erosion and delayed patient access.
• Study design and data maturity – short-term data can be sufficient to establish benefit–risk profile; however, long-term efficacy data are required to meet the needs of robust cost-effectiveness modelling, as well as additional data collection for cost and resource use and health-related quality of life model inputs.

Products likely to benefit most

The pathway will be particularly advantageous for products where early, coordinated evidence generation is critical to demonstrating value, such as orphan drugs and drugs for rare diseases.

By aligning regulatory and HTA expectations from the outset, the pathway supports a smoother trajectory for products whose success depends on timely, well-coordinated evaluation. Patients with rare diseases, who often have no existing treatment alternatives, may therefore benefit most, as the pathway has the potential to expedite access to novel therapies.

The integration of the International Recognition Procedure (IRP) within the pathway may help to reduce administrative burden and further shorten timelines to patient access. The combined use of the IRP and the Aligned Pathway may help create a more coordinated and accessible route to authorisation and assessment, which could support the needs of smaller biotech developers navigating these evolving processes.

Conclusion

The introduction of the Aligned Pathway represents a meaningful evolution in the UK market access framework.

By synchronising regulatory and HTA processes, embedding significant scientific dialogue, and promoting proactive and targeted evidence generation, it addresses longstanding structural inefficiencies between licence and reimbursement.

Beyond its structural reforms, the Aligned Pathway offers an opportunity to embed a more collaborative, evidence‑driven approach across the lifecycle of new therapies, one that ultimately enables earlier and more equitable access for the patients who need it most. This is especially important in areas such as rare diseases, where evidence gaps are common and delays to access can have profound consequences.

As the Aligned Pathway evolves, continued engagement from developers, regulators, and HTA bodies will be essential to realising its full potential and shaping a system that is both responsive and sustainable for the future.