OBJECTIVES : In France, economic evaluation is conducted by the Committee of Economic and Public Health (CEESP). HTA framework for OD follows the same approach as for common diseases. The CEESP assesses the robustness of the submitted analyses and issues methodological objections (can be minor, important or major). Major objections invalid the submitted analysis and may have an impact on price negotiations. Due to difficulties in collecting robust clinical data and the high unmet needs, ODs are often evaluated based on unmatured results from early phase clinical trials. The objective of this paper was to analyze clinical data used in economic submissions and associated methodological objections issued by the CEESP.

METHODS : All the publicly available OD opinions until May 2019 were identified from the official website. The following relevant information were extracted for each opinion: drug indication, description of submitted clinical data (including evidence synthesis methods if relevant) and methodological objections.

RESULTS : In total, 83 health-economic opinions were found, among which 19 related to ODs. From the 19 submissions, 10 were based on a direct comparison and 9 used indirect comparison methods. A total of 8 objections related to the clinical data or comparison methods were issued by the CEESP (2 minor, 4 important, 2 major). The main reason for major objections was the lack of robustness of the efficacy data. In case of a non-comparative study, a Matched Adjusted Indirect Comparison (MAIC) was commonly used. Several submissions initially based on a naïve comparison were rejected by the CEESP and alternative methods were used in final submission.

CONCLUSIONS : Economic assessment of OD drugs remains challenging. Naïve comparisons are not considered by the CEESP. Alternative methods such as MAIC may be an option to avoid major objections.