Liverpool Reviews and Implementation Group, University of Liverpool, 2nd Floor, Whelan Building, The Quadrangle, Brownlow Hill, Liverpool, L69 3 GB, UK.
Pharmacoeconomics. 2013 May;31(5):403-13. doi: 10.1007/s40273-013-0043-8.
The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of rituximab (RTX) [Roche] to submit evidence for the clinical and cost effectiveness of RTX as first-line maintenance treatment for patients with follicular non-Hodgkin's lymphoma (fNHL) whose disease has responded to induction therapy with RTX plus cytotoxic chemotherapy (R-CTX) in accordance with the Institute's Single Technology Appraisal (STA) process. The Liverpool Reviews and Implementation Group (LRiG) at the University of Liverpool was commissioned to act as the Evidence Review Group (ERG). This article summarizes the ERG's review of the evidence submitted by the manufacturer and provides a summary of the Appraisal Committee's (AC) decision. The clinical evidence was derived from a multi-centred, open-label, randomized phase III study (PRIMA) comparing first-line maintenance treatment with RTX with observation only in 1,018 patients with previously untreated advanced fNHL. Median time to event (MTE) for the primary endpoint of progression-free survival (PFS) in the RTX arm was not estimable due to data immaturity; median PFS in the observation arm was 48.36 months. A statistically significant benefit of RTX maintenance therapy for PFS was reported (hazard ratio [HR] 0.55, 95 % CI 0.44-0.68; p < 0.0001). Statistically significant differences in favour of RTX were also reported for a range of secondary endpoints. Assessment of overall survival benefit could be not made due to insufficient events. The ERG's main concern with the clinical-effectiveness data presented was their lack of maturity. The submitted incremental cost-effectiveness ratio was within the NICE threshold. The ERG questioned the model on a number of grounds, particularly the use of Markov methodology rather than patient simulations, the impact of patient age on the outcome and the projective PFS modelling. The ERG considered it impossible to draw firm conclusions regarding the clinical or cost effectiveness of the intervention as the dataset was as yet too immature. At a third meeting, the AC concluded that RTX could be recommended as first-line maintenance treatment for patients with fNHL whose disease has responded to induction R-CTX.
英国国家卫生与临床优化研究所（NICE）邀请利妥昔单抗（RTX）制造商[罗氏]根据研究所的单一技术评估（STA）流程，提交关于 RTX 作为滤泡性非霍奇金淋巴瘤（fNHL）患者一线维持治疗的临床和成本效益的证据，这些患者对 RTX 联合细胞毒性化疗（R-CTX）诱导治疗有反应。利物浦审查和实施小组（LRiG）在利物浦大学被委托作为证据审查小组（ERG）。本文总结了 ERG 对制造商提交的证据的审查，并提供了评估委员会（AC）决策的摘要。临床证据来自一项多中心、开放标签、随机 III 期研究（PRIMA），该研究比较了 1018 例未经治疗的晚期 fNHL 患者一线维持治疗与仅观察的效果，主要终点无进展生存期（PFS）的 RTX 臂的中位无事件时间（MTE）由于数据不成熟而无法估计；观察臂的中位 PFS 为 48.36 个月。报告了 RTX 维持治疗对 PFS 的显著获益（风险比[HR]0.55，95%CI0.44-0.68；p<0.0001）。还报告了一系列次要终点对 RTX 的统计学显著获益。由于事件不足，无法对总生存获益进行评估。ERG 对提交的临床有效性数据的主要关注是其不成熟。提交的增量成本效益比在 NICE 阈值内。ERG 在许多方面对模型提出了质疑，特别是使用马尔可夫方法而不是患者模拟、患者年龄对结果的影响和 PFS 预测模型。ERG 认为，由于数据集仍不成熟，不可能对干预措施的临床或成本效益得出明确结论。在第三次会议上，AC 得出结论，RTX 可作为对 R-CTX 诱导治疗有反应的 fNHL 患者的一线维持治疗。
