Looking Beyond Cost Effectiveness: Recommendations for Appraisal of Rare Disease Therapies

In May 2021, IMPACT HTA published a Framework for Health Technology Assessment (HTA) of Rare Disease Treatments.  I spoke with Dr. Karen Facey, lead researcher in this work, about the recommendations outlined in the Framework.

Interview with Karen Facey 

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Over the past few years, we have seen many advances in the field of rare diseases, including improved genetic testing and the advent of new innovative, high-cost, and potentially curative therapies.  HTA bodies worldwide are working to find ways to appropriately and fairly evaluate these therapies while taking into account the special considerations of rare disease populations. 

What is it about rare disease treatments that require special considerations?

Small population sizes and incomplete understanding of rare disorders result in limited evidence and uncertainties about the effectiveness of a potential new therapy. When assessing the value of a rare disease treatment for reimbursement, Health Technology Assessment (HTA) is often used. Assessors face challenges given the limited clinical and quality of life evidence and the use of cost-effective models that do not fully characterize the progression of the disease or the benefit of the treatment. These challenges are compounded by the heterogeneity of rare conditions, the high rate of children affected, and the severely disabling or life-threatening nature of many of these conditions. 

What are countries already doing to adapt processes for rare disease treatment evaluation?

We profiled over 30 countries and observed a few European HTA bodies to understand standard appraisal processes that inform reimbursement decisions for all therapies and any special approaches for rare disease treatments. We found a range of process adaptations from no alterations to the standard appraisal process (Romania); to modifying the standard process, for example, by expediting the review or by taking into consideration the rarity of the condition (Italy, Scotland); to using a separate process for rare disease treatment evaluation (England, Lithuania). This helped us identify good practices we could share in the Framework. 

What does the Framework aim to do? What does it recommend?

The Framework for HTA of Rare Disease Treatments provides recommendations that will support the best decision-making possible given the unique circumstances of each rare condition and the limitations and uncertainties in the evidence. 

Source: Facey K, Whittal A, Drummond M, Upadhyaya S, Junghans T, Nicod E. IMPACT HTA WP10 HTA Appraisal Framework Suitable for Rare Disease Treatments. 12 May 2021. [Online]. Available from: Impact HTA | Health Technology Assessment | Work Package 10 (impact-hta.eu) (or Zenodo)

Specifically, the Framework sets out eight (8) main recommendations to establish a flexible yet structured framework to ensure consistent and fair evaluation of rare disease treatments. These are all underpinned with iterative expert clinical and patient involvement.

The Framework is built around the first recommendation that evaluations should consider the full context of the treatment impact.  Currently, many HTA evaluations rely predominantly on clinical and cost-effectiveness analyses. The Framework proposes that other “decision-making domains” [1] are needed, such as the nature of the condition, ethical issues, and organizational aspects (e.g., standard of care and access pathways). 

Furthermore, “decision modifiers” should be used for specific treatments to take account of issues such as the severity of the disease, whether it affects children, the level of unmet need, etc. 

The recommendation would then be to collect evidence for each decision domain and modifier from all stakeholders.  This might be obtained through stakeholder submissions using standardized forms, literature reviews, expert meetings, interviews, consensus surveys, etc. Insights from real-world evidence and compassionate access use should also be used, particularly when uncertainties and knowledge gaps are significant.

Source: May 2021 Webinar: IMPACT-HTA Framework suitable for Rare Disease Treatments www.impact-hta.eu/work-package-10

An appraisal committee would then critically evaluate the evidence, mapping out gaps, uncertainties, and assumptions.  These committees could be bespoke for rare diseases or the same as the general appraisal committees but calling on rare disease specialists as appropriate. Underpinning this whole process is iterative input by clinical and patient experts to help better understand the context for evaluation and help the appraisal committee resolve questions about the evidence. 

Following these recommendations should lead to fair appraisals for rare disease treatments that consider the full dimension of the value of a treatment while acknowledging the limitations and uncertainties of dealing with small populations. 

“The Framework supports robust, accountable decision-making. There is a need for leniency and flexibility BUT applied consistently across assessments.”

— KF

What are the next steps for this work?

We are now meeting with different jurisdictions to discuss the integration of the recommendations into their practices. Training appraisal committees on the decision-making domains and clinical and patient experts to meaningfully contribute to reimbursement discussions is another key step. 

In terms of the limitations in the evidence, there are many ongoing efforts to make data collection more transparent and collaborative.  A first helpful step is for HTA bodies to establish clear guidelines on the type of data useful for evaluation. Even if data collection efforts happen in isolation, the body of evidence will contribute toward a common goal and support rare disease treatment evaluation and reimbursement.  

IMPACT HTA is funded by the European Commission as part of the Horizon 2020 initiative calling for improved methods, tools, and guidance for economic evaluation to support HTA and health system performance. This work was conducted as part of IMPACT HTA’s Work Package 10 to provide Guidance to Support Consistent HTA Appraisal for Orphan Medicinal Products. 

References

[1] O’Rourke B, Oortwijn W, Schuller T, the International Joint Task Group (2020). The new definition of health technology assessment: A milestone in international collaboration. International Journal of Technology Assessment in Health Care 1–4. https://doi.org/10.1017/ S0266462320000215

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About the interviewee

Karen Facey, PhD is a statistician by training, having worked in the pharmaceutical industry and medicines regulation. For the past 20 years, she had had leading roles in health technology assessment internationally and health policy in Scotland. In 2014, Facey was named as one of the top 100 practicing scientists in the UK. She is passionate about involving patients in the evaluation of new health technologies and was the lead editor of the book on patient involvement in HTA published in 2017. 

She undertook this work as a Senior Research Fellow at the Usher Institute at the University of Edinburgh (Edinburgh, UK).