NICE consultations on methods and processes – what they mean and next steps
Since the creation of NICE in 1999 as the National Institute for Clinical Excellence its remit has been considerably widened to include all new medicines, social care (hence its current title of the National Institute for Health and Care Excellence), taking over the work of the Cancer Drugs Fund and becoming involved in the drafting and use of the Voluntary Scheme for Branded Medicines Pricing and Access (VPAS). Since 2005 the NHS in England and Wales has been legally obliged to provide funding for medicines and treatments recommended by NICE. In practice, this can create problems when assessing expensive treatments given NHS funding constraints, and renegotiation of these drug prices before NICE issues final guidance is increasingly common. As it has expanded, and as treatments and devices have often become more complex, NICE has developed a more complicated and bureaucratic structure and the purpose of its two consultations on methods and processes has been to update its current arrangements. Its appraisals of new and existing medicines, treatment and procedures are still central to NICE, but a number of the proposed changes will be important for the life sciences industry in England and Wales and quite possibly other countries, given NICE’s international standing.
One of NICE’s merits is its genuine willingness to listen to industry. NICE’s intention is to bring together the conclusions of the two consultations on methods and processes (as well as an earlier consultation on topic selection) in a draft programme manual in August, which will itself be subject to consultation. It is understood that at (or about) the same time, there will be consultation papers on highly specialised technologies and on the Innovative Medicines Fund, which will replace the Cancer Drugs Fund. At the end of 2021 and into 2022, NICE expects to have completed its programme manual and put an implementation plan into place.
NICE methods consultation
The consultation of NICE methods in November 2020 was the first reassessment since the ‘Guide to the methods of technology appraisal 2013’ and was widely welcomed. Its purpose was to better support technological change and innovation and ease certain restrictive practices. In its submission to NICE, on behalf of its clients, MAP stated that: ‘In particular, the proposals to replace the end-of-life modifier with a severity modifier, reduce the discount rate to 1.5%, accept greater levels of uncertainty and be more flexible in respect to evidence will all contribute to addressing the challenges faced by innovative technologies, accelerating and increasing patient access to treatments’.The points below expand on this and examine some related issues.
One of the factors (called ‘modifiers’ by NICE) taken into account by Appraisal Committees is end-of-life criteria, which enables greater weight for treatments in the later stages of terminal diseases. Criteria include patients whose life expectancy is normally less than 24 months and for whom the treatment is expected to extend life by at least three months. However, in cases of drugs for patients where severity of disease and end-of-life apply, NICE’s consultation paper helpfully proposed replacing the end-of-life modifier with a modifier to focus on the severity of the condition (although severity has yet to be defined and presented for public consultation).
The discount rate
The costs and health outcomes that are predicted to occur in the future are usually valued less than present costs, so they are discounted in analysis for all government departments. This is usually achieved by expressing the results as a series of health outcomes and costs over time applying a discounted factor to each value. Up to now NICE has recommended that the discount should be 3.5% per year. For example, one quality-adjusted life year (QALY) or £100 experienced/spent in Year 2 would have a present value of 0.966 QALY or £96.62. For Year 11, the present values would be 0.709 QALY or £70.89 (York Health Economic Consortium, 2016). The level of discount is of particular importance in preventive healthcare interventions. The use of a lower discount rate would result in greater value being attached to costs and health outcomes in the future. The use of discounts is therefore of considerable relevance for NICE Appraisal Committees. The Treasury Green Book 2020, which issues guidance on how to appraise policies, programmes and projects, states that ‘The recommended discount rate for risk for health and life values is 1.5’. Although NICE accepted in the consultation that ‘there is a case for changing the reference case (i.e. the preferred rate) from 3.5% to 1.5%, for both costs and health effects’ it avoided any decision on the grounds that it raised several policy and affordability challenges. This was highlighted as a missed opportunity by MAP in its consultation submission.
NICE recognises uncertainty is conceptually different from other modifiers, but that Appraisal Committees should be able to be more flexible in accepting uncertainty where evidence is complex and difficult, such as rare diseases, or in other circumstances such as with innovative technologies. This has been welcomed and the forthcoming manual may provide greater detail.
MAP has called for a rarity modifier to reduce the inequalities faced by rare diseases. The consultation rejected the proposal at the time on the grounds that a more ‘adopting attitude’ to uncertainty would support these rare disease technologies.
The evidence base
The consultation identified several cases for changes in sourcing, assessing and presenting evidence – two of these, on real-world evidence (RWE) and surrogates, are set out below.NICE recognises the need for it to make greater use of RWE, meaning observational data obtained outside the context of randomised controlled trials. RWE is generated in ways such as analysing data stored in electronic health records, medical claims, registries, patient-generated data and mobile devices and can be particularly important when patients are in distant geographical regions. They can also be relevant in rare disease areas where there are small populations, or for longer-term or rare outcomes that can be difficult to observe during randomised clinical trials.The use of surrogates is defined as biomarkers or laboratory measures used as substitutes for final patient-relevant outcomes in clinical trials in order to assess the efficacy of health technologies. NICE expects these to become increasingly common and its requirements for decision-making may therefore need to become more explicit.
NICE review of the health technology evaluation processes
NICE states that its health technology evaluation processes should be ‘fast, flexible and responsive, to support rapid patient access to clinically and cost-effective health technologies in the ever-changing health and care landscape’. The purpose of the review, which began in February 2021, was to set out ways of adapting and updating these processes. As with the other consultation, there are some important changes, as set out below.
The fast track appraisal process (FTA)
Over five years, only six topics have been formally appraised using the FTA process. The review recognised that the Scottish Medicines Consortium (SMC) encouraged sponsors to use an abbreviated submission process for new medicines where alternatives within the same therapeutic class have been previously accepted by the SMC. The review helpfully states that there may be an argument for NICE to consider a similar approach for fast cost comparison appraisal, allowing companies to decide to convert from an STA to an FTA. This was welcomed by MAP in its response to the review.
Managed access agreements (MAAs)
MAAs have become increasingly important for the treatment of rare and ultra-rare diseases. MAAs are agreements between NICE, NHS England and NHS Improvement, the manufacturer, patient organisation and clinicians to enable a drug to become available for a limited time period at a discounted price. This allows patients to access a drug whilst further RWE is gathered. The review admits that the current status of a recommendation for managed access is unclear and needs to be resolved.MAP welcome the proposal in the review to try to develop a more streamlined market access process, which would accelerate patient access to new treatments. Also helpful is the suggestion that NICE may make recommendations where there are immature data and/or significant clinical uncertainties, without requiring a full health technology evaluation.The ending of a market access agreement scheme can throw the health system into a moral quandary. Patients may suffer unfairly when a medicine is withdrawn. The review recommended that there should be a full STA at the end of the MAA period. MAP opinion is that whether this is the right way forward will depend on details yet to be published, but any reassessment should be light touch, which would be less burdensome to stakeholders.
Highly specialised technologies (HST) programme
The review on the HST programme is brief and restates existing policies. It is hoped the forthcoming HST consultation paper will help fill in the gaps.The HST process was introduced in 2013, with only 13 HST recommendations published at the time of the review. Even though NICE admits that there are a rising number of treatments in development for rare diseases, the review does not expect the HST numbers to increase. Given the considerable interest, analyses and proposals in this area, this is a disproportionate response from NICE. Although the standard NICE cost-effectiveness threshold is £20,000–£30,000/QALY, with HST there is a more generous threshold applied of £100,000 per QALY gained, rising in some circumstances to £300,000. This creates obvious financial pressures on the NHS and helps to explain NICE’s comment that ‘sometimes we do not recommend an intervention because it does not provide enough benefit to justify its cost. It also means that we cannot apply the ‘rule of rescue’ which refers to the desire to help an identifiable person whose life is in danger no matter what it costs. In the meantime MAP has called for changes to the HST criteria to take into account the new treatments in development and to adapt processes for orphan treatments that do not meet the strict HST eligibility criteria. MAP add that it might also be worth considering if there is a more appropriate path, outside of NICE, that could be used for the national commissioning of innovative technologies for ultra-rare diseases.