Cost-utility analysis on robot-assisted and laparoscopic prostatectomy based on long-term functional outcomes.

Robot-Assisted Radical Prostatectomy (RARP) is one of the standard treatment options for prostate cancer. However, controversy still exists on its added value. Based on a recent large-sample retrospective cluster study from the Netherlands showing significantly improved long-term urinary functioning after RARP compared to Laparoscopic RP (LRP), we evaluated the cost-effectiveness of RARP compared to LRP. A decision tree was constructed to measure the costs and effects from a Dutch societal perspective over a ~ 7 year time-horizon. The input was based on the aforementioned study, including patient-reported consumption of addition care and consumed care for ergonomic issues reported by surgeons. Intervention costs were calculated using a bottom-up costing analysis in 5 hospitals. Finally, a probabilistic-, one-way sensitivity- and scenario analyses were performed to show possible decision uncertainty. The intervention costs were €9964 for RARP and €7253 for LRP. Total trajectory costs were €12,078 for RARP and €10,049 for LRP. RARP showed higher QALYs compared to LRP (6.17 vs 6.11). The incremental cost-utility ratio (ICUR) was €34,206 per QALY gained, in favour of RARP. As a best-case scenario, when RARP is being centralized (> 150 cases/year), total trajectory costs decreased to €10,377 having a higher utilization, and a shorter procedure time and length of stay resulting in an ICUR of €3495 per QALY gained. RARP showed to be cost-effective compared to LRP based on data from a population-based, large scale study with 7 years of follow-up. This is a clear incentive to fully reimburse RARP, especially when hospitals provide RARP centralized.

Treatment With Tumor-infiltrating Lymphocytes in Advanced Melanoma: Evaluation of Early Clinical Implementation of an Advanced Therapy Medicinal Product.

Tumor-infiltrating lymphocytes (TIL)-therapy in advanced melanoma is an advanced therapy medicinal product (ATMP) which, despite promising results, has not been implemented widely. In a European setting, TIL-therapy has been in use since 2011 and is currently being evaluated in a randomized controlled trial. As clinical implementation of ATMPs is challenging, this study aims to evaluate early application of TIL-therapy, through the application of a constructive technology assessment (CTA). First the literature on ATMP barriers and facilitators in clinical translation was summarized. Subsequently, application of TIL-therapy was evaluated through semistructured interviews with 26 stakeholders according to 6 CTA domains: clinical, economic, patient-related, organizational, technical, and future. In addition, treatment costs were estimated. A number of barriers to clinical translation were identified in the literature, including: inadequate financial support, lack of regulatory knowledge, risks in using live tissues, and the complex path to market approval. Innovative reimbursement procedures could particularly facilitate translation. The CTA survey of TIL-therapy acknowledged these barriers, and revealed the following facilitators: the expected effectiveness resulting in institutional support for an internal pilot, the results of which led to the inclusion of TIL-therapy in a national coverage with evidence development program, the availability of an in-house pharmacist, quality assurance expertise and a TIL-skilled technician. Institutional and national implementation of TIL-therapy remains complex. The promising clinical effectiveness is expected to facilitate the adoption of TIL-therapy, especially when validated through a randomized controlled trial. Innovative and conditional reimbursement procedures, together with the organization of knowledge transfer, could support and improve clinical translation of TIL and ATMPs.

Early cost-effectiveness of tumor infiltrating lymphocytes (TIL) for second line treatment in advanced melanoma: a model-based economic evaluation.

BACKGROUND: An emerging immunotherapy is infusion of tumor infiltrating Lymphocytes (TIL), with objective response rates of around 50% versus 19% for ipilimumab. As an Advanced Therapeutic Medicinal Products (ATMP), TIL is highly personalized and complex therapy. It requests substantial upfront investments from the hospital in: expensive lab-equipment, staff expertise and training, as well as extremely tight hospital logistics. Therefore, an early health economic modelling study, as part of a Coverage with Evidence Development (CED) program, was performed. METHODS: We used a Markov decision model to estimate the expected costs and outcomes (quality-adjusted life years; QALYs) for TIL versus ipilimumab for second line treatment in metastatic melanoma patients from a Dutch health care perspective over a life long time horizon. Three mutually exclusive health states (stable disease (responders)), progressive disease and death) were modelled. To inform further research 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.