Uncertainty in the input parameters was handled probabilistically, by assigning distributions to parameters (Table ?(Table1)1) . prioritization, Value of Information (VOI) analysis was performed. Results TIL is expected to generate more QALYs compared to ipilimumab (0.45 versus 0.38 respectively) at lower incremental cost (presently 81,140 versus 94,705 respectively) resulting in a dominant ICER (less costly and more effective). Based on current information TIL is dominating ipilimumab and has a probability of 86% for being cost effective at a cost/QALY threshold of 80,000. The Expected Value of Perfect Information (EVPI) amounted to 3?M. Conclusions TIL is expected to have the highest probability of being cost-effective in second line treatment for advanced melanoma compared to ipilimumab. To reduce decision uncertainty, a clinical trial investigating e.g. costs and survival seems most valuable. This is currently being undertaken as part of a CED program in the Netherlands Cancer Institute, Amsterdam, the Netherlands, in collaboration with Denmark. strong class=”kwd-title” Keywords: Tumor infiltrating lymphocytes, Ipilimumab, Advanced melanoma, Cost-effectiveness analysis, Coverage with evidence development, Personalized medicine Background Until recently metastatic melanoma was almost uniformly fatal, having a median survival of 9?weeks . In 2011 ipilimumab, a monoclonal antibody against CTLA-4 within the triggered T-lymphocyte was the 1st newly-introduced treatment that improved survival in this group of individuals. Very recently anti-programmed cell death-1 (PD-1) antibodies, such as nivolumab and pembrolizumab, were launched as first collection treatment, as these led to an even longer progression free and overall survival [2C5]. Therefore, ipilimumab is now most often used as second collection treatment. Normally, ipilimumab extends survival by 3.6?weeks (when compared to a gp100 peptide vaccine), and increases the 1-yr survival rate from previously 25.5% to 44% of patients . However, the treatment costs are high, around 80,000 per patient, and 10C20% of individuals treated with ipilimumab have serious immune-related adverse events. Adoptive T-cell therapy (Take action), in particular the Take action variant Tumor Infiltrating Lymphocytes (TIL) is definitely a powerful immunotherapy directed against metastatic melanoma. A number of nonrandomized clinical tests testing TIL have consistently found medical response rates of around 50% in metastatic melanoma individuals, accompanied by long progression-free survival Leflunomide (PFS). Indeed, total remission is accomplished in 10C20% of individuals treated with TIL. The overall response rates range from 35 to 72%, with more than 20% of the treated individuals surviving more than 3?years . Andersen et al. Leflunomide reported 1- and 3-yr survival rates of 72% and 40.8% Slc2a3 respectively . Additional studies have also established practical methods for the development (growth) of TILs from melanoma tumors with high success rates [9C11]. Side effects of TIL as observed in these tests were workable, and the costs for the treatment are around 60,000 per individual. Notwithstanding the expectation that TIL efficiently outperforms ipilimumab, it is a complex process. Stringent eligibility criteria apply for TIL, such as possessing a resectable tumor, adequate heart and lung function and no or very limited and asymptomatic mind metastases. This means that TIL can be used for approximately 50% of advanced melanoma individuals. On the resources part, Leflunomide as known for Advanced Restorative Medicinal Products (ATMPs), TIL requests substantial upfront purchases from the hospital in e.g. a specialised GMP laboratory necessary to tradition the TILs, expensive lab-equipment, qualified and experienced technical staff, as well as extremely limited hospital logistics . Because a cell product is being made specifically for every individual patient, such treatments Leflunomide may not be commercially interesting for the pharmaceutical companies to explore. The total trajectory of one TIL-treatment may take as long as 3?weeks of highly personalized, labour-intense treatment, including side effect management, which has to be provided partly inside a specialized inpatient setting. Therefore, TIL was first implemented in specialised cancer centres like the National Tumor Institute (Bethesda, USA) and some others worldwide, including the Netherlands.