Uncertainty Appraisal in Economic Opinions of the French National Authority for Health

OBJECTIVES: The French Commission for Economic and Public Health Evaluation (CEESP) appraises the manufacturers’ incremental cost-effectiveness ratio (ICER) validity. The ICERs are valid if there is no mention of major methodological reservation or uncertainty. Although ICERs have been invalidated for the latter reason since 2014, it wasn't until 2021 that the CEESP doctrine clarified the reasons that could lead to major uncertainty.

The aim is to quantify and analyze invalidations exclusively due to uncertainty in CEESP opinions.

METHODS: Economic evaluations invalidated by the CEESP exclusively on grounds of uncertainty over the period 01/2014 to 03/2024 were analyzed. One evaluation is related to one indication.

RESULTS: Since 2014, 32/229 evaluations were invalidated due exclusively to major uncertainty, including 19/151 (13%) before 2021 and 13/82 (16%) after 2021. During this period, orphan drugs accounted for 39% of evaluations invalidated due to uncertainty, and 26% of assessment without major uncertainty. The main therapeutic areas concerned before 2021 were onco-hematology (25%) and oncology (25%) aligned with the overrepresentation of these areas in submissions. After 2021, evaluations in COVID-19 account for 31% of invalidations for uncertainty.

After 2021, the average of important reservations is higher in evaluations with major uncertainty (6.4 with vs 3.5 without) and the proportion of opinions with at least 5 important reservations was also higher (77% vs 33%). However, CEESP justified the major uncertainty by accumulating reservations only in 3 opinions. In its conclusion, the main argument is the uncertainty in estimating certain key parameters (7/13, 54%). Moreover, 39% (5/13) of opinions mentioned that uncertainty cannot be assessed. These different reasons aren’t mutually exclusive.

CONCLUSIONS: The definition of major uncertainty in the CEESP doctrine seems to have led to more invalidations on the grounds of uncertainty, with an increase from 13% to 16% of opinions. This trend should be confirmed over time.