UK NHS: 4 Updates to NICE’s Manual for Methods

The UK’s National Institute of Health and Care Excellency (NICE) – an agency of the country’s National Health Service – has updated its methods. Experts Katerina Stavri, Sathushi Theivendran, and Rebecca Ford outline what changes have been implemented and what this means for UK healthcare. 

In January 2022, the National Institute of Health and Care Excellence (NICE) completed the first major update of its methods and processes since 2013, with changes coming into effect earlier this year. This brief summarizes the four key changes outlined in NICE’s updated manual.

Change 1 – Valuation of benefits: Introduction of the severity of a disease modifier in place of previous end-of-life criteria

A severity modifier replaces end-of-life criteria, in an aim to prioritize and improve access for treatments for severe conditions.

NICE’s end-of-life: Treatments for patients with short life expectancy can exceed NICE’s cost effectiveness (CE) threshold. This was provided that they were for patients with a short life expectancy (< 24 months) and that the technology extended life by at least three months vs. current NHS treatment. They were also only applicable for a small patient population. 

NICE’s new severity modifier considers two different measures: Absolute and proportional quality-adjusted life years (QALY) shortfalls.

• Absolute QALY shortfall is the total amount of future health lost due to a patient’s condition, compared to the expected future health without the condition
• Proportional QALY shortfall represents the proportion of QALYs lost because of the condition, relative to their remaining life expectancy

NICE will apply a QALY weight to one of the proportional and the absolute shortfall weights, depending on which is higher. The applied QALY weight corresponds to the observed shortfall level and will increase the cost-effectiveness threshold from £30,000 (for a standard NICE technology appraisal) to £36,000 and to £50,000 (for QALY weights of x1.2 and x1.7, respectively).

Table 1 represents the weighting applied with shortfall level:

Change 2 – Evidence generation and use: Enhanced role for non-RCT evidence sources 

NICE has adopted a new approach for evidence consideration, in an aim to increase flexibility for circumstances where data generation is complex, difficult, and further data collection to resolve uncertainty may not be possible. Randomised controlled trial (RCT) based evidence will continue to be the evidence source of choice. However, non-randomised studies, real world evidence (RWE), and unpublished studies will have an enhanced role.

The use of non-RCT data should be carried out iteratively, with more robust forms of non-randomized evidence (including RWE) being prioritized over less reliable study designs. A new preliminary framework has also been developed to support the use of RWE, providing information on study design, data standards, use cases, research governance and statistical analysis.

These changes are expected to provide greater clarity for manufacturers and decision-makers and to allow patients earlier access to innovative new treatments.

Change 3 – Appraisal uncertainty: Greater flexibility in assessment of uncertainty and the effect on cost-effectiveness

A higher degree of uncertainty is now accepted in cases where evidence generation is particularly difficult and further data collection is unrealistic, including:

• Rare diseases
• In a predominantly paediatric population (under-18s)
• Highly innovative and complex technologies

While the need for a probabilistic base case exists, methods used to capture uncertainty are being developed – including more refined sensitivity analysis and the inclusion of expert elicitation in the absence of evidence. The nature, scale, context, and consequences of uncertainty to patients and the NHS will also be assessed in order to define the best route forward for the technology.

If after review, evidence is still considered to be highly uncertain, recommendations for alternative routes can be made, including the use of managed access agreements, data collection or further research. In particular with the updated manual, NICE appears to place a greater emphasis on using managed access agreements in cases of uncertainty.

Change 4 – Highly Specialised Technologies (HST) routing criteria: Adoption of clearer HST eligibility criteria

To overcome difficulties in topic selection for the HST programme, a new set of four eligibility criteria have been introduced:

1. The disease is ‘very rare’ i.e., a prevalence of < 1 in 50,000 or ~1,100 people*
2. No more than 300 people are eligible for the technology in its licensed indication and no more than 500 across all its indications*
3. The disease has a severe impact on quality of life or significantly shortens lifespan
4. There are no other satisfactory treatment options, or the technology offers significant additional benefits over existing treatments

*For these criteria exceptions may apply in some circumstances, however criteria for exceptions have not been defined

Key Takeaways

Changes were implemented with the aim to clarify the selection process for manufacturers, increase predictability and transparency among decision-makers, and ultimately facilitate earlier access to valuable innovative treatments.

Although the impact of the updated NICE methods on actual HTAs remains to be seen, the updated methods provide a step in the right direction allowing for greater flexibility and case-by-case assessment, particularly for rare and paediatric disease drugs, and highly innovative therapies such as cell and gene therapies.

The impact of changes such as the severity modifier remains in question. These changes may create increased opportunities for manufacturers bringing treatments to market, however new challenges in unlocking incremental cost-effectiveness ratio (ICER) flexibility may also arise.