Session (CTI)

Issue: Assessing treatments for rare diseases presents fundamental challenges for HTA. Small populations with systemic, evolving, life-limiting diseases with a range of symptoms make it difficult to plan and execute sufficiently large randomized-controlled trials (RCTs). As a result, evidence is typically generated through small, short-term RCTs or single-arm trials, with outcomes that may not best reflect patient benefit. These may be augmented by evidence from patient registries, case series, case reports, patient experience data, etc. but such evidence is considered unreliable in existing HTA frameworks. This often results in high uncertainty about added benefit for high-cost therapies and negative recommendations for use. Overview: HTA critical assessment methods are rooted in the discipline of evidence-based medicine, guided by standards such as the Cochrane Handbook and GRADE. GRADE uses a hierarchy of evidence to judge the certainty of the treatment effect based on the entire body of evidence. This is up- or down-graded, depending on a range of factors. This hierarchy and adjustment factors are challenging for rare diseases. This panel will present ongoing work proposing novel approaches to evidence assessment that are better aligned with the nature of evidence available for rare disease therapies. After the moderator’s brief introduction, in 10-minute presentations, Drs Caro and Tunis will present research that has led to development of novel approaches to use the totality of evidence available from a range of sources to evaluate and communicate the added benefit of rare disease treatments. Dr Goetz will critique the practical application of the frameworks in an HTA system, reflecting on his experience in the Austrian HTA system and plans for EU Joint Clinical Assessments. In the final 25-minutes, the moderator will orchestrate audience discussion about feasibility of the new approaches and what is needed to operationalize a new paradigm for evidence assessment in rare diseases.