OBJECTIVES: Since 2013, the CEESP evaluates the efficiency dossier of innovative and high-budget-impact health products and publishes their opinion on the methodological compliance with their guidelines. The objective of this study is to review the published opinions in the indication of advanced melanoma and to synthetize the deviations.

METHODS: All publically available CEESP decisions were collected from the HAS website as per June 2017. The deviations were classified in categories and quantified. In-depth qualitative analysis was conducted in order to highlight major causes of deviation. The options to consider for dossier related to the advanced melanoma were also tracked.

RESULTS: Three published opinions were identified, for one targeted therapy (trametinib) and two immunotherapies (nivolumab, pembrolizumab). The BRAF mutation and line of treatment are key points to define the population and the relevant comparators. The number of deviations ranged from 11 to 18 (minor: 8 to 15; important: 2 to 4; major: 0 to 1). The highest number of deviations were related for all three opinions to modelling. The weakness of indirect comparison is crucial and is a major influential factor of efficiency results. It is due to short follow-ups of the clinical trials and efficacy of the drugs inducing that the median overall survivals are not always reached. Since the publication of the opinions, clinical data with longer follow-ups were made available and could be used to reduce the uncertainty. Sophisticated statistical methods were implemented in the indirect comparison that are not presented in the related HAS guidelines.

CONCLUSIONS: The low number of trials and the short follow-up period of the available clinical trials contributed to a weak clinical evidence and induced important and major deviations. The opinions illustrate the uncertainty induced by a submission of efficiency dossier with early clinical results from a CEESP point of view.