NICE and Highly Specialised Technologies: three years on

Since the National Institute for Health and Care Excellence (NICE) formally took on the appraisal of Highly Specialised Technologies (HSTs) for the rarest conditions in April 2013, just two drugs have received final guidance. Leela Barham examines the process.

The underpinning legislation for a Highly Specialised Technology (HST) describes it as 'a health technology intended for use in the provision of services for rare and very rare conditions'. This means that, unlike European legislation for orphan drugs, there is no clear prevalence given to help draw the line between common and rare (and, indeed, very rare) diseases, to know when NICE will opt to apply the HST process. However, prevalance of around 1 in 100,000 patients, or less than 500 across England, has been used to refer to ultra-orphan drugs, which HSTs appear to address.

In practice, NICE has made final recommendations on two drugs under HST; Eculizumab (Soliris) for atypical haemolytic uraemic syndrome (aHUS) and elosulfase alfa (Vimzim) for mucopolysaccharidosis type IVa (MPS IVa or Morquio A syndrome). aHUS has an incidence of around 25 new cases a year in England, so is very rare indeed. Even rarer is Morquio A syndrome, with around three new cases a year.

Wider appraisal framework for HSTs

An interim process and methods guide (dating back to May 2013) sets out how NICE appraises HSTs. There are both similarities with, and differences to, its approach for more common diseases. Similarities include:

• Scoping phase
• Manufacturer submission
• Consultation, including submissions from patients, clinicians and other interested parties
• Deliberation by an Appraisal Committee (although HST does have its own Committee).

A key difference is a much wider framework to appraise HSTs. It includes six main domains, and criteria within each:

1. Nature of the condition, including impact on patients and carers
2. Impact of the new technology, including health benefits and robustness of the evidence
3. Cost, including budget impact and the option for companies to offer patient access agreements
4. Value for money, including the budget impact of the new technology on the budget available for specialised services
5. Impact of the new technology beyond direct health benefits, including benefits outside the NHS and personal social services
6. Impact of the technology on the delivery of the specialised service, including training staff.

In the eyes of NICE, drugs for very rare diseases need a 'different' approach. Sir Andrew Dillon, Chief Executive of NICE, said that, "in evaluating [HST] drugs, NICE takes into account a greater range of criteria about the benefits and costs of HSTs than is the case with its appraisals of mainstream drugs and treatments. This is because applying our standard approach to treatments for very small groups of patients would results in us always recommending against their use. This would be unfair."

NICE took on much of what its predecessor in the field, the Advisory Group for National Specialised Services (AGNSS) had developed and is, to a degree, continuing that approach.

'Yes, but' recommendations

Though NICE has given final approvals to both Soliris and Vimizim, these are more 'yes, but' style of recommendation, with each having criteria to be met before the NHS will pick up the cost.

In the case of Soliris, those criteria include prescription via an expert centre, monitoring to collect data on dose and duration of treatment, a national protocol for starting and stopping use, plus a research programme to evaluate starting, stopping and adjustment of dose.

Vimizim use is via a managed access agreement. This includes requirements for monitoring patients, including collection of standard EuroQol five dimensions questionnaire (EQ-5D) data (plus lots of other data), a commercial agreement between the manufacturer and NHS England, as well as a further NICE review based on the data collected after five years. If things go well, Vimizim will continue to be funded by the NHS (although this is not automatic; a commercial deal will still need to be agreed). If not, the NHS won't pay for any new patients.

NICE has also said yes to ataluren (Translarna) in Duchenne muscular dystrophy (nonsense mutation) in a Final Evaluation Determination (FED). As long as the company and NHS England can agree all the details, final guidance will follow. Otherwise, NICE may not publish final guidance at all. The FED states that Translarna will be provided with a discount through a Patient Access Scheme (PAS).

It will also be used within a managed access agreement with NHS England, the plan being to follow up with patients and assess their health outcomes. The scheme goes beyond those being treated too; carers' utility values will be collected, reflecting the impact on parents of looking after young boys who lose mobility progressively. As with Vimizim, the agreement should last for five years, with the possibility that, if value for money isn't established after those five years, no patients will be able to access Translarna with NHS funding.

NICE has also been consulting on another recommendation (consultation closed on 25 May 2016) – a 'minded' no for sebelipase alfa (Kanuma) for babies with rapidly progressive Lysosomal Acid Lipase deficiency (LAL-D). NICE recognises the compelling clinical need but, since the company has not estimated costs and benefits for a managed access scheme, it cannot come to a conclusion on value for money.

Questions about cost

NICE aspires to produce three pieces of HST guidance a year. However, it has only produced final recommendations for two products in the three years that the programme has been running. Part of the reason for this appears to stem from the need to ask further questions about cost. Though the hope was for each to take 27 weeks, the reality is somewhat different.

NICE's assessment of Soliris began in 2013 and it took until January 2015 for final guidance to be published. That reflects the need for two consultations; the first, which closed in March 2014, highlighted that the Committee had not been "presented with an adequate explanation for its considerable cost" and asking for more information from the manufacturer. The cost of Soliris was estimated at £340,200 for the first year of treatment for an adult. At the same time, the Committee also asked for advice from NHS England on what considerations for budget impact it needed to take into account when formulating its recommendation.

The second, which closed in December 2014, essentially set out the criteria taken forward into final guidance in January 2015, but also stated that "the long-term budget impact... is uncertain but will be considerable. NHS England and the company should consider what opportunities might exist to reduce the cost of eculizumab to the NHS". While Soliris was going through the NICE process, NHS England provided interim funding.

The timeline for Vimizim began in March 2014, with final guidance following in December 2015. As with Soliris the appraisal underwent two consultations. The first, which closed in June 2015, suggested that NICE was minded to say 'no', with the Committee asking for more information from the manufacturer, including an explanation of cost. The cost was high, estimated at £394,680 per patient (although a confidential discount was offered too as part of a PAS). In this case, the Committee explicitly called for additional economic analysis and further budget impact estimates. The second consultation, which closed in September 2015, first mooted the managed access scheme that now applies.

Access to Vimizim faced much scrutiny as it moved through the NICE process. Parliamentary questions were raised, for example, asking why it was taking so long post marketing authorisation for a decision to be made about NHS funding for Vimizim and calling for interim funding from NHS England. Funding was essentially via the company, which took on the cost of continuing treatment even as the clinical trial ended. Others suggested that there was a lack of ethics, compassion and a threat to the nation's interests in agencies taking so long to come to a decision.

Wider impact

NICE HST recommendations may impact patient access beyond England's borders. The All Wales Medicines Strategy Group (AWMSG), for example, will consider how NICE HST guidance fits the NHS in Wales, and whether the same commissioning approach should be adopted there. Plus, so many people abroad look at what NICE says that there must be international ripples.

A controversial future for HSTs?

NICE is currently working on four other pieces of HST guidance; migalastat for Fabry disease, eliglustat in type 1 Gaucher disease, asfotase alfa in paediatric-onset hypophosphatasia and, as mentioned, sebelipase alfa in LAL-D.

These will reveal whether appraisal under HST will continue to take over a year and focus on cost. Time will tell, too, whether the managed access approach becomes the norm as NICE and NHS England try to balance access and affordability.

Whatever lies ahead, debate over how NICE appraises drugs for some of the rarest conditions, and how much it costs to bring them to market, will continue. Last but not least, is the question of whether the price is worth paying?

About the author:

Leela Barham is an independent health economist and policy expert who has worked with all stakeholders across the health care system, both in the UK and internationally. Leela works on a variety of issues: from the health and wellbeing of NHS staff to pricing and reimbursement of medicines and policies such as the Cancer Drugs Fund and Patient Access Schemes. Find out more here and contact Leela on leels@btinternet.com.