OBJECTIVES: The objective of this study is to evaluate the level of evidentiary requirements required for the health technology assessment (HTA) of orphan medical products (OMPs) in selected countries. This study highlights some of the differences and similarities in the clinical aspect of HTA appraisals in Bulgaria, France, Germany, Sweden, and the UK (England).

METHODS: A comparative analysis of the published regulatory requirements regarding the level of evidence necessary for reimbursement approval was conducted for Bulgaria, France, Germany, Sweden, and the UK (England). The choice of countries was founded on the mandatory condition for HTA approval in Bulgaria which states that at least one positive opinion by an HTA body from the other countries must exist. Bibliographic databases, online sources, and government/HTA organization websites were searched. The collected data was synthesized in Excel and used for qualitative comparative analyses.

RESULTS: The clinical assessment of OMPs is similar in the analyzed countries. Germany and Sweden lack official guidance for a more lenient level of evidence for rare diseases, but OMP appraisals in the two countries take into consideration the limited availability of data. France and the UK (England) formally require the same level of clinical evidence; however, the specific characteristics of rare diseases lead to the acceptance of data coming outside of randomized clinical trials (RCTs). Bulgaria also accommodates OMP applications with the acceptance non-RCT and, similarly to other countries, requires this aspect of the application to be well-justified. Even though differences between countries exist, quality of life is part of HTA in all analyzed countries.

CONCLUSIONS: This study highlights that government institutions (in selected countries) responsible for the appraisal of rare disease therapies are more flexible, whether officially or unofficially, to the level of clinical evidence regarding rare diseases.