Access to treatments

Why we need a new approach to assessing rare diseases

By Emily Reuben OBE, Co-founder and Chief Executive of Duchenne UK, who spoke about the need for a new approach at the Rare Disease Industry Group parliamentary reception on 20 March 2024

The challenges facing new treatments for rare diseases 

When my friend Alex Johnson and I set up Duchenne UK, I guess we were somewhat naïve. We thought the hard bit would be discovering compounds, funding clinical trials, and proving the efficacy of new treatments. Given the awful, disabling, and hopeless diagnosis we were given, we never for a moment doubted that life-saving medicines for our sons with Duchenne muscular dystrophy (DMD) wouldn’t be viewed as cost effective – and wouldn’t’ be available in our home country. How wrong we were.

The United States Food and Drug Administration estimates that just 5% of rare diseases have an approved treatment. And the UK lags behind even when approvals do exist. By early 2023, only 59% of treatments approved by the European Medicines Agency (EMA) between 2018-2021 had been reimbursed by the National Institute for Health and Care Excellence (NICE), compared to 86% in Germany. For some families, this is the difference between life and death.

While we understood that bodies like NICE help our health system assess medicines equally and bring value to the NHS, we were one of those many patient organisations who found the process of NICE appraisals confusing, the language used opaque and incomprehensible. In short, an overwhelming system that we struggled to understand.


We set up Project HERCULES in 2017 to address many of the issues we found with appraisal reimbursement. We – the patient community – brought together the main players; clinicians, academics, advisers, the regulators and even industry in a non-competitive collaborative environment. Project HERCULES developed tools and evidence to inform decisions about new treatments.

And what I’ve realised is being rare isn’t the issue. The issue is the characteristics shared by rare diseases. They are complex, about 75% of them affect children (a problem I explore below), and there are often huge uncertainties. A system designed to evaluate traditional medicines for the general population is not flexible enough to accommodate the challenges posed by rare diseases.

Assessing new treatments 

Increasingly, medicines for rare diseases like DMD are being assessed by NICE’s Single Technology Assessment (STA) appraisal. In STA, the same process is applied to childhood life-limiting progressive conditions and stable adult populations. But there are huge differences between the two. Take functional outcome measures – in paediatrics there is going to be variability and bias: is that child being encouraged to do better because of a Lego or cash bribe? How many cannulas did they have in clinic and has that put them in a mood to be non-compliant? Are they tired from the journey to clinic? More than likely yes, in each case. Yet the system can’t flex for this.

Most rare diseases tend to be progressive and disabling. As the child is growing and maturing, their bodies are weakening. As a result, there is a constantly moving baseline which makes it harder to assess the impact of a treatment. ‘Quality of life’ (QoL) – a foundational concept in assessing the cost effectiveness of a medicine – is measured in paediatrics like in adults, despite the huge differences between the two. You would think it would be simple to use paediatric QoL metrics for paediatric rare diseases, but through Project HERCULES we discovered that there are no decent QoL instruments in paediatrics. And we’re not alone. ISPOR’s Valuing Health-Related QoL of Children & Adolescents in Economic Evaluation (Paediatric Utilities) also agreed.

So, STA committees are making decisions on clinical evidence which need to be interpreted flexibly, and with QoL measures which are probably inadequate. Uncertainty does exist: but it isn’t caused by the prevalence of the disease. It’s caused by the challenges inherent in complex disease.

Needs a highly specialised approach

A disease as complex and desperate as DMD really needs a highly specialised approach. In fact, how can a disease that is as desperate as Duchenne, not be classed as needing special treatment? And an alternative to STA does exist: the Highly Specialised Technology (HST) route.

But under current NICE guidance, DMD – a disease with around 2,500 patients in the UK – is considered too common to be rare. DMD products cannot go through the HST route. Categorising like this based on patient numbers is wrong because these decisions are not meant to be about budget impact. But it’s also wrong because challenging paediatric life-limiting progressive diseases are complex and need to be treated differently. HST committees are used to dealing with uncertainty – they can approach these diseases with the pragmatism, sensitivity, and flexibility which the HST routes affords, and which a STA does not.

Carer QoL

Another key difference between adult and paediatric assessment is the QoL of the family unit and the caregivers – by which I mean parents. Carer QoL must be included. It’s sometimes considered in a qualitative way: but this means there is uncaptured value in a product which can’t be translated into anything that is useful for a quantitative-focused quality-adjusted life year (QALY). Because I guarantee you that if a caregiver QoL metric was included, the cost effectiveness arithmetic for rare disease medicines would change dramatically.

Carer QoL needs to be taken seriously, because in a paediatric population its adults of working age who’ve had their lives devastated. Even something like bereavement is different, as losing a child is not the same as losing a parent. But NICE conflates burden of care with quality of life. A possible, warped interpretation is if the child dies, the burden disappears. The assumption is that the grieving parent’s quality of life goes back up, because there’s no sick child to care for. It. Goes. Back. Up. And your child is dead. How can that be?

Finally, the disabling nature of these diseases adds physical and mental burden, and means the implications of care and cost reach far beyond the health system and into the social care system. We now have Integrated Care Boards (ICB) – which is a logical and positive step forward. But where is this being reflected in NICE? Where are the costs associated with social services and social care being included. The costs for instance of Personal Independent Payments, Education, Health and Care Plans, Disability Living Allowance.

A new health landscape

NICE has been very supportive of Duchenne UK and Project HERCULES. And we welcome the organisation’s work to simplify their processes for patient organisations: however NICE was designed for a different, simpler, health landscape from which society has moved on. Diseases and our health are more complex, nuanced, and challenging than before.

There are huge benefits to gain from holistic thinking on health, but NICE is hamstrung by the way it was set up and can’t adapt. Much of how it operates is set by the Government, and defined in law.

If we want our nation to be at the cutting edge of the newest and most exciting treatments – and if we want British patients to be at the front of the queue for those medicines – then our health systems needs the ability to adapt.

Published on 23 February 2024

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