OBJECTIVES. Health economic guidelines recommend to consider the effects of relevant adverse events (AE) of interventions in cost effectiveness analyses (CEA). The objective of this study was to review the approaches used for inclusion of AEs into CEA of innovative health products submitted by the manufacturers to the HAS.

METHODS. Fifty-one CEA published from January 2014 to April 2018 were analyzed. Letters of clarification and HAS efficiency opinions related to these CEAs were reviewed. Data on health products and informations on the methodology of incorporation of AEs were independently extracted by two authors into a predefined analysis grid. Disagreements were resolved through discussion.

RESULTS. The main therapeutic areas of CEAs were oncology (23 %) and cardiology (18 %). 69 % (35/51) of the CEAs included at least AEs in either costs or utilities inputs. Less than half of the CEAs (41%) included the impact of AEs on both costs and loss of quality of life (disutilities) in economic modeling. Only grades ≥ 3 of AEs were included in the cost and utility components in 44% and 36% of submissions incorporating AEs respectively. Among the CEAs including disutilities, 41% (9/22) did not provide information on the severity level of AEs. 53% (18/34) and 18% (4/22) of submissions did not provide any details on the duration or number of occurrence of AEs in the modelling of the cost and utility components respectively. The impact of AEs on cost data was only modelled during the first cycle or year in 75% (12/16) of submissions referring to modeling durations.

CONCLUSIONS. This study identified strong heterogeneity regarding technical details (frequently missing) and inclusion of AEs in the CEAs submitted to the HAS. Better practice guidelines for methodological standardization of the incorporation of AEs into economic evaluations are needed.