Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital (NKI-AVL), Plesmanlaan 121, 1066, CX, Amsterdam, the Netherlands.
Department of Health Technology and Services Research, University of Twente, Postbus 217, 7500, AE, Enschede, the Netherlands.
BMC Cancer. 2018 Sep 15;18(1):895. doi: 10.1186/s12885-018-4788-5.
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.
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.
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.
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.
一种新兴的免疫疗法是输注肿瘤浸润淋巴细胞（TIL），客观缓解率约为 50%，而伊匹单抗为 19%。作为一种先进的治疗性药物产品（ATMP），TIL 是一种高度个性化和复杂的治疗方法。它要求医院在昂贵的实验室设备、人员专业知识和培训以及极其严格的医院物流方面进行大量前期投资。因此，作为证据开发（CED）计划的一部分，进行了一项早期健康经济学建模研究。
我们使用马尔可夫决策模型来估计从荷兰医疗保健角度来看，转移性黑色素瘤患者二线治疗中 TIL 相对于伊匹单抗的预期成本和结果（质量调整生命年；QALYs），在终身时间范围内。建模了三种互斥的健康状态（稳定疾病（应答者））、进展性疾病和死亡）。为了进一步确定研究优先级，进行了价值信息（VOI）分析。
与伊匹单抗相比，TIL 预计会产生更多的 QALYs（分别为 0.45 和 0.38），增量成本更低（目前分别为 81140 欧元和 94705 欧元），导致增量成本效益比（更便宜且更有效）占主导地位。根据当前信息，TIL 优于伊匹单抗，在成本/QALY 阈值为 80000 欧元时，具有 86%的成本效益概率。完全信息的预期价值（EVPI）达到 300 万欧元。
与伊匹单抗相比，TIL 预计在晚期黑色素瘤二线治疗中最有可能具有成本效益。为了降低决策不确定性，似乎最有价值的是进行一项临床试验，例如成本和生存。这是目前正在荷兰阿姆斯特丹的荷兰癌症研究所作为 CED 计划的一部分与丹麦合作进行的。
