An ultra-orphan condition is an extremely rare, often genetic or chronic disease affecting fewer than 1 in 50,000 people. YHEC Director of Pharmaceutical Consulting, Stuart Mealing, is a member of the National Institute for Health and Care Excellence’s (NICE’s) Highly Specialised Technologies Evaluation Committee (HSTEC), which considers health technology assessments (HTAs) for ultra-orphan conditions. We sat down with him to find out more about the committee and its processes, and how these differ from those used for non-ultra-orphan conditions. Stuart also reflects on his own experiences as a member of the committee.
What makes ultra-orphan conditions challenging for HTA bodies, such as NICE?
Ultra-orphan conditions present several challenges for formal HTA. These include, but are by no means limited to, scarce to non-existent comparative clinical data, trials with very small patient numbers, complex multidisciplinary care pathways and little to no formal patient reported outcomes data collected using generic instruments.
What’s the background to the Highly Specialised Technologies Evaluation Committee?
In recognition that the conventional single technology appraisal (STA) process was not necessarily well suited to the assessment of ultra-orphan conditions, in 2013 the UK NICE established the Highly Specialised Technologies (HST) appraisal stream, alongside a dedicated committee (the Highly Specialised Technologies Evaluation Committee; HSTEC).
While the composition of HSTEC was intended to be similar to that of a typical STA committee, with strong representation from clinicians, NHS commissioners, health economists and industry/life sciences experts, it is notably smaller in terms of standing membership. It also has a higher proportion of lay and patient members compared with an STA committee and is mandated to include a medical ethicist.
The appraisal stream was given its own methods guide, which uses a cost-effectiveness threshold of £100,000 per quality-adjusted life year (QALY) gained, with a mechanism to adjust this threshold up to £300,000 per QALY gained, rather than the £20,000 per QALY gained that underpins the STA process. The committee was given a remit to take a broader approach to evidence uncertainty, unmet need and product value.
However, to access this appraisal stream, a health technology must meet a set of strictly defined criteria relating to rarity, setting of use, acquisition cost, current treatment landscape, and the severity of the underlying condition. In practice, therefore, the HST route is largely reserved for cell, gene or enzyme-based interventions.
How does a HSTEC meeting differ from a STA meeting?
While the company submission templates and appraisal timelines for both appraisal streams are very similar, the nature of the evidence underpinning a HST submission as well as the complexity of the underlying condition means that, in my mind, the meetings themselves are very different.
The key difference is that there is a greater level of oral evidence delivered during the meeting. In order to truly understand the underlying treatment landscape and care pathway, we lean heavily on the nominated clinical representatives who are also an important source of information on the likely long-term clinical efficacy of the product we are looking to assess. This is important because in any given meeting, the HSTEC is likely to be assessing a potentially curative technology which only has short-term clinical data collected in a handful of patients.
What are the implications of this for patient voice in the process?
A NICE committee meeting has two parts. The first (part A) is held in public and the second (part B) is held in private. Part B is where the decision making happens. In HST, there is much higher patient engagement in the part A public conversation than there is in STA. The high priority given to patient voice in the NICE technology appraisal process is already world leading, but for HSTs, the absence, or near absence of any meaningful patient reported outcomes data means that it is essential to hear first person testimonies on what it is like to live with the condition. The patient voice is also crucial in teasing out key aspects of the care pathway and highlighting any uncaptured benefits not included in the company’s economic model.
As a result of this, HSTEC meetings are definitely longer and feel more intense than an STA meeting, and it is uncommon to have a final position after one meeting. In general, the first meeting focusses on the committee developing its preferred set of assumptions and input values based on the evidence and testimony it has heard, with the final decision being made at the second and sometimes even third committee meeting.
How has the HSTEC changed since you’ve been a member?
I’ve been a HSTEC member for nearly four years and during that time I have seen the scope of the work we undertake broaden out so that if not in name, in spirit, we are the de facto rare diseases committee. Personally, I think this is a superb development as there are many orphan conditions who share many of the characteristics of an ultra-orphan indication but do not meet the HST criteria and so are evaluated via STA. Having a standing panel of individuals with the skills and experience of evaluating such evidence, regardless of which appraisal route is being used is clearly of beneficial to the rare disease community as a whole, but also to the wider NHS.
Can you give us some personal reflections on membership of the HSTEC?
On a personal level, I joined the committee because I was keen to use my skills to have a direct and, hopefully positive, impact on the NHS. During my time, the experience has been both challenging and energising. As a committee, we regularly find ourselves wrestling with difficult scientific, ethical, and practical considerations, working collectively to reach consensus decisions that can genuinely move the needle forward for patients with ultra-rare conditions.
Those interactions with fellow committee members have been hugely valuable for me. Engaging month after month with colleagues from different disciplines, each bringing their own perspective, has broadened my thinking and made me a more rounded analyst. It has also given me a deeper appreciation of the strategic dimensions of HTA, particularly in areas where the evidence base is evolving and the traditional frameworks used for more mainstream assessments don’t always neatly apply. That perspective has been particularly valuable for my work in rare diseases, where clients often need clear, high-quality analytical thinking to navigate uncertainty and develop evidence that will stand up to scrutiny.
Would you recommend joining a NICE Committee?
I have recently renewed my commitment to NICE for another three years. Despite the number of weekends and evenings spent reading endless committee papers, I would fully recommend that anyone who has the opportunity to join a NICE committee should say ‘yes!’.
Contact us
YHEC has a long-standing history of supporting NICE across various programmes, helping to ensure that guidance is based on the most rigorous evidence available. As well as Stuart’s membership of the HSTEC, YHEC is an External Assessment Group for NICE’s HealthTech programme. This direct experience provides us with a deeper insight into the criteria and considerations that drive NICE’s recommendations, helping our clients navigate the UK HTA landscape more effectively. Contact us for more information.