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NICE and ‘ultra orphans’

NICE and its processes for ‘highly specialised therapies’


The UK's health technology assessment (HTA) landscape for orphan drugs changed in April last year as reverberations from the 2012 Health and Social Care Act, which ushered in the biggest set of health reforms in the country since the National Health Service was set up more than 60 years ago, continued to be felt. 

The changes contained within the reforms included one to NICE's remit, which has been expanded to include passing judgement on high-cost drugs for rare conditions. This is work that had previously been managed by the Advisory Group for National Specialised Services (AGNSS) and ministers had already foreshadowed its closure and the handover with a July 2012 announcement.

In transferring the responsibility to NICE the government said it wanted to ensure assessments would be “robust, independent and transparent”.

Given the rarity of highly specialised, or ultra orphan, therapies, this process is even further from the mainstream than orphan drugs usually are. 

It won't, for example, affect medicines such as Novartis' treatment for myelofibrosis, a rare blood cancer of which there are only around 0.4 cases of the condition per 100,000 people. Jakavi, in common with most orphan drugs, was assessed under NICE's existing arrangements, though also in common with rare disease treatments such as Roche's MabThera and Celgene's Revlimid, it has faced questions about the data that was available to back its submission. Indeed, producing its final guidance on Jakavi in June, NICE said it considered the drug to be an innovative treatment that offered a step change in treatment, but concluded that, although clinically effective, it was not a cost-effective use of NHS resources.

Such considerations will certainly be a focus for NICE and its forthcoming assessment procedure for highly specialist therapies (HST), which will see the Institute tasked with appraising medicines that are likely to come in well-above its usual cost-effectiveness thresholds.

NICE is currently planning to consult on the shape this new process will need to take and when it does will seek input from patients, carers, clinicians, commissioners and industry. NICE told PME: “It is anticipated that the full HST programme process and methods guide will be the subject of public consultation in late 2014.” 

Interim measures
Ahead of the consultation on the best process to apply to highly specialised therapies, and then its eventual implementation, NICE has put some interim measures in place.

These follow an 11-stage process (see page 10), not dissimilar to the general NICE technology appraisal process, that leads up to final NICE guidance being produced, starting with a topic being chosen for evaluation by the Department of Health.

NICE anticipates the core process will take around 17 weeks from receipt of submissions from stakeholders, but that excludes any consultation, reconsideration or appeal requirements. If public consultations occur the process will be extended to 27 weeks and appeals will further lengthen it.

The decision-making framework to be used by the Highly Specialised Technologies Evaluation Committee builds on the work by AGNSS, and incorporates NICE's 2004 exploratory work on 'ultra-orphan drugs'. In its report on this work NICE concluded that its processes did not need to change for the appraisal of 'conventional' orphan drugs, but acknowledged there would be problems in the judging (ultra orphan) drugs for very rare diseases, largely because of their exceptionally high costs. Its a group that NICE suggested at the time should be defined by a prevelance of less than 1 in 50,000.

In its new role assessing 'highly specialised technologies', the interim process for NICE's appraisal committee will look to take account of a criteria such as: 

  • Impact of the disease on carers' quality of life 
  • Overall magnitude of health benefits to patients and, when relevant, carers 
  • Whether there are significant benefits other than health, including whether a substantial proportion of the costs or benefits are incurred outside the NHS and personal and social services
  • The potential for long-term benefits to the NHS of research and innovation 
  • Staffing and infrastructure requirements, including training and planning for expertise.
It is anticipated the full NICE process for highly specialised therapies will be the subject of public consultation in late 2014

Cost-effectiveness still an issue
The interim measures took effect in April, at which point AGNSS ceased to exist, and the first topic ministers nominated for NICE consideration under the new highly specialised technologies programme was Soliris (eculizumab).

The first-in-class terminal complement inhibitor is manufactured by US biopharma company Alexion and famous for being the industry's most expensive drug at more than $409,000 for a year's treatment of paroxysymal nocturnal haemoglobinuria. NICE, however, has been asked to consider its use to treat atypical haemolytic uraemic syndrome (aHUS), a very rare - and life-threatening - condition which affects small blood vessels throughout the body.

There are currently around 140 people diagnosed with aHUS in England, but and at least another 140 people are estimated to have the condition but be undiagnosed. Patients face a poor prognosis, with early mortality rates that range from 10 to 15 per cent, and most progress to end-stage renal failure.

The drug had been assessed in aHUS by AGNSS, which was convinced of its clinical effectiveness. But, in a decision that has been criticised by patient groups, ministers said that because AGNSS also noted its very high cost (with an incremental cost-effectiveness ratio of up to £521,000 per QALY gained), the drug needed to be referred to NICE for further assessment.

NICE expects to issue its guidance on Soliris by July 2014 and in the meantime NHS England will continue to fund the drug's use for new and existing aHUS patients.

Soliris remains the only drug so far to be put through NICE's highly specialised technologies programme and its example may seem like an extreme one, in terms of cost and patient population. Nevertheless, the challenges ultra orphan drugs like Soliris face in going through the HTA process should hold some valuable lessons for any company seeking to bring an orphan drug to market.

Highly specialised technologies
A single HST evaluation can only cover a single technology for a single indication and follows the following process:

  1. Provisional evaluation topics chosen by the Department of Health (DH) 
  2. Consultees and commentators identified
  3. Scope prepared by NICE and DH
  4. Evaluation topics officially referred to NICE by DH
  5. Evidence submitted by manufacturer or sponsor and non-manufacturer consultees can also make submissions
  6. NICE's Evidence Review Group (ERG) report prepared
  7. Evaluation report prepared with all the evidence the Evaluation Committee will look at
  8. NICE's independent advisory committee considers evaluation report and hold public discussions of the evidence
  9. The Evaluation Committee makes provisional recommendations in an Evaluation consultation document (ECD), but only if they are restrictive
  10. Final evaluation determination (FED) produced, though can be appealed
  11. If there are no appeals, or an appeal is not upheld, the final recommendations are issued as NICE guidance.

10th March 2014

10th March 2014

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