Unlocking Access: The Role of Patient Engagement in Rare Disease HTA 

AUTHORS: ​Joyce Atim, Rahul Vadehra​

Rare diseases have a significant impact on people worldwide and have a high level of unmet needs. During the past 5 years, there has been a huge effort to develop new treatments for rare disease, with orphan drug medicines representing 45% of all approvals in Europe and 53% new active substance approvals in the US.¹ Despite these initiatives, rare diseases present unique challenges to health technology assessment (HTA), impacting the reimbursement process for medications treating such conditions. Limited patient populations, limited data, the heterogeneous nature of rare diseases and the lack defined access routes across countries make it challenging to assess treatment value the traditional HTA methods.² In this context, patient engagement is critical and can affect reimbursement by providing tailored messaging that addresses the unmet needs and burdens of rare diseases to improve access. 

What are the key challenges impacting HTA in rare diseases?  

Clinical value and evidence considerations 

HTA for rare diseases is challenged by the clinical development process, where demonstrating efficacy and safety through traditional trials is difficult.³ Due to small patient populations, trials for rare disease often rely on single-arm designs and surrogate endpoints, increasing uncertainty for payers.⁴ This lack of comparative data makes it harder to prove meaningful clinical improvement, affecting reimbursement decisions and willingness to pay premium prices.  

Economic value considerations  

Challenges in clinical development impact the feasibility of economic modelling for rare diseases. The absence of comparator data, reliance on single-arm trial designs, heterogeneity within trial populations, and limited clinical outcomes contribute to uncertainty when evaluating mortality, efficacy, and treatment impacts in rare diseases.^5,6 This often leads to reimbursement barriers. Patient engagement can help by providing insights into disease burden and societal impact, though not all HTA bodies consider these broader factors in decision-making.  

Access challenges 

Access to orphan drugs remains challenging, as few countries have specific pathways for rare diseases.⁷ England’s Highly Specialised Technologies (HST) program, the Netherlands’ orphan drug access protocol pilot, and Sweden’s staircase model for ultra-rare diseases offer more tailored solutions.^8,9 Other countries, including Italy, France, Germany, and Spain, have adapted processes but still require strict economic evaluations, often disregarding surrogate measures. This highlights the need for stronger patient engagement to advocate for improved access.  

Why is patient engagement important in HTA for Rare Diseases? 

Patient engagement is essential in HTA for rare diseases, as traditional cost-effectiveness models often fail to capture the full impact of these conditions. Rare diseases by definition, have small patient populations, leading to limited clinical trial data. Therefore, patient insights are critical in demonstrating the true burden of disease, emphasising the urgency of treatment, and highlighting the impact beyond conventional clinical endpoints. Without patient input, HTA bodies may overlook key factors that determine whether a treatment is deemed valuable.¹⁰  

A structured approach to patient engagement ensures that HTA frameworks assess treatments holistically. Standard cost-effectiveness models often disadvantage rare disease therapies due to high development costs. However, patient insights can be used to highlight broader benefits, such as improved quality of life, reduced caregiver burden and long-term societal gains. These factors are hard to measure with gold standard methods, but patient perspectives offer a more balanced assessment of a treatment’s value.¹¹ 

Timely patient engagement is also crucial in accelerating access to innovative therapies. Many rare diseases are progressively debilitating, meaning that delays in treatment can lead to irreversible decline or even death. Countries that integrate patient perspectives early in the process are more likely to implement flexible access pathways, ensuring life changing treatments reach those who need them.¹¹ 

Beyond access, patient engagement enhances equity in decision-making. If HTA bodies solely focus on cost-effectiveness, treatments for larger populations often take priority, while rare diseases therapies are deprioritised due to budget constraints. By embedding patient perspectives in the HTA process, healthcare systems can ensure that rare disease treatments receive fair considerations, preventing a situation where small patient populations are systematically disadvantaged.¹¹  

Without patient engagement in HTA for rare diseases, treatments may be undervalued, delayed, or not approved, adversely affecting patients’ quality of life and survival. The perspectives of patients are crucial in rare diseases to ensure access to essential, life-changing treatments. 

What role is patient engagement playing in EU4 + UK HTA? 

Most of the countries that were reviewed recognise the importance of patient engagement in HTA for rare disease treatments. However, approaches vary, as some countries have developed structured programmes, while others offer regional voting rights with no national framework in place (Table 1):

• Scotland (Scottish Medicines Consortium [SMC]): Patients can present experiences at committee meetings, and patient and clinician engagement (PACE) gives stronger decision-making influence for ultra-orphan/orphan drugs when standard criteria are unmet. 

• England (National Institute for Health and Care Excellence [NICE]): Patient and Public Involvement Programme (PPIP) ensures continuous patient involvement in HTA, and HST allows greater flexibility for rare disease treatments with incremental cost-effectiveness ratio (ICERs) ≤£100,000 per quality-adjusted life year (QALY). 

• France (Haute Autorité de Santé [HAS]): Patient representatives participate in all discussions and votes, but input is broadly sought for all medicines, with no rare disease-specific flexibility. 

• Italy (Agenzia Italiana del Farmaco [AIFA]): Recent reforms introduced structured patient engagement via a national HTA stakeholder network, AIFA Ascolta help desk, and new legal mandates requiring patient input, particularly for rare diseases. 

• Germany (Gemeinsamer Bundesausschuss [G-BA]/Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen [IQWiG]): Patients contribute via direct and indirect channels, with significantly higher involvement in advanced therapy medicinal product (ATMP) evaluations for rare diseases due to greater reliance on stakeholder input. 

• Spain (Agencia Española de Medicamentos y Productos Sanitarios [AEMPS]/Regional HTAs): No national patient involvement, but Catalonia integrates patient representatives at all medicine appraisal stages, including voting rights

Conclusion and Impact

Patient engagement is essential in addressing the challenges of HTA for rare diseases, where traditional cost-effectiveness models often fail to capture the full impact of treatments. Limited trial data, small patient populations, and high development costs make it difficult for rare disease treatments to meet conventional clinical and economic requirements, often leading to delays or rejection in reimbursement decisions. By integrating patient insights, HTA bodies can gain a more comprehensive understanding of disease burden, the urgency of treatment, and broader societal benefits such as improved quality of life and reduced caregiver strain. Countries that embed structured patient engagement early in the process can create more flexible access pathways, accelerating approvals and ensuring that life-changing treatments reach those who need them.

Without a strong patient voice in HTA, rare disease therapies risk being deprioritised, exacerbating health inequalities and leaving patients without viable treatment options. Moving forward, collaboration between HTA bodies, manufacturers, and policymakers is crucial to embedding patient perspectives in decision-making, ensuring a more equitable and inclusive approach to rare disease treatment access. 

Citations and Reference List

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