Objectives: Challenges exist in the development and use of patient reported outcome measures (PROMs) and health state utility values (HSUVs) in rare diseases due to small and heterogeneous populations, and lack of disease knowledge and expertise. This research aims to understand how PROMs and HSUVs are being considered in health technology assessment (HTA) of non-oncological rare disease medicines.

Methods: Data were extracted from NICE appraisals of all non-oncological medicines with an EMA orphan designation (n=24), together with corresponding appraisals from the Netherlands, France and Germany. Document analysis of appraisal reports and supporting materials was conducted. Information about types of PROMs/HSUVs and impact on decision was extracted, and key learnings were derived.

Results: Of the NICE appraisals, 25% (6/24) did not consider any PROMs and 42% (10/24) any generic PROMs (e.g. EQ-5D). Consideration of PROMs had a clear impact on decisions in 8% (2/24) of cases, and in 38% (9/24) was used to derive HSUVs. 29% (7/24) used EQ-5D directly, 25% (6/24) used ‘mapping’ and 21% used (5/24) vignettes to derive HSUVs. Only a few of these demonstrated significant change due to lack of sensitivity or content validity, short term data, or possible implausible health states. Patient input (e.g. via surveys or as experts) was used to inform decisions in 33% (8/24) of cases, specifically when PROMs/HSUVs were unavailable or deemed unsuitable. The analysis of appraisals in the other study countries revealed similar issues.

Conclusions: This study highlights some of the limitations and contrasts across countries in use of PROMs/HSUVs in HTA for rare disease treatments. Greater consideration should be given to the use of other techniques such as patient input and vignettes, often not accepted by HTA bodies. Patients should be better informed on the different types of evidence useful for decision-making.