Objectives: The Tunisian National Authority for Assessment and Accreditation has published in 2018 its first HTA report, aimed at informing the national payer on the effectiveness and cost-effectiveness of trastuzumab, the first agent targeting HER2 positive breast cancer, representing its biggest budgetary expenditure since 2008. Methods: A systematic litterature review of recent clinical practice guidelines on management of breast cancer was performed to extract best available evidence on effectiveness and risks related to trastuzumab. The recommendations of the Tunisian Society of Oncology were compared with SIGN and NICE guidelines. A benchmark of ex-factory prices of trastuzumab in different countries was carried out along with a survey among INAHTA members to collect prices' information, reimbursement and treatment management modalities. To determine the cost effectiveness of trastuzumab at the 2018 selling price, an adaptation of a Latin American cost-effectiveness study was conducted, followed by a sensitivity analysis and the estimation of the cost effectiveness price. Results: Trastuzumab significantly improves DFS and OS compared to chemotherapy alone, however it increases the risk of congestive heart failure. According to the benchmark, the 2018 ex-factory price of trastuzumab in Tunisia remains higher than most of high income countries. From the ministry of health's perspective, the ICER of trastuzumab was 49 670,67 USD/QALY, representing 4,5 times the 3 GDPPC/QALY threshold suggested by WHO. From the national payer's perspective, the ICER was 75 386,18 USD/QALY, representing 6,8 times the threshold. Probabilistic sensitivity analysis showed 0 % probability of trastuzumab being costeffective considering the same threshold. A discount of 78% on trastuzumab's acquisition price is required to reach cost-effectiveness threshold. These results provided a set of recommendations for the payer and informed the negociation of the biosimilar's price. Conclusions: This first INEAS HTA report clearly illustrates the central role of HTA at informing decision-makers in terms of price negotiations and reimbursement decisions.

Objectives: Malignant melanoma is the most serious form of skin cancer. The prognosis for patients at metastatic or unresectable stage remains poor. Dacarbazine is the standard of care in Tunisia despite low response rates. INEAS, the Tunisian HTA body has just finalized, at the national payer's request, an HTA report aiming to inform reimbursement decision for two new drugs as monotherapies for advanced melanoma in adults ; nivolumab and vemurafenib (only for BRAF V600 mutationpositive patients). Methods: A review of HTA reports and systematic reviews was conducted to synthesize clinical evidence. A Cost utility analysis was performed through collaboration between INEAS and IECS, to estimate costs and QALYs from a healthcare perspective with different treatment scenarios ; 1-All population under dacarbazine, 2-All population under nivolumab 3-Population with BRAF V600 mutation under vemurafenib and population without mutation under dacarbazine, 4-Population with BRAF V600 mutation under vemurafenib and population without mutation under nivolumab. A survey among INAHTA members resulted also in collecting relevant pricing and reimbursement information. Results: The two drugs significantly improve PFS and OS compared to dacarbazine. Nivolumab has a higher probability of good performance for OS and a lower probability of severe adverse events than other alternatives. Cost utility analysis has shown that scenario 4 (nivolumab+vemurafenib) is dominated by scenario 2 (nivolumab for all). 3rd scenario is less costly but less effective than the nivolumab scenario. The ICER of scenario 2 against first scenario is around 20 times the GDPPC. Sensitivity analysis has shown that OS hazard ratios and acquisition prices were the most influential parameters on results. Important price cuts on these drugs would be necessary to be cost effective at what has been considered a reasonable WTP in Tunisia. Conclusions: These recommendations demonstrate the central role of INEAS as an HTA body in supporting evidence based decision and in facilitating access to innovation.