The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA.
Genentech Inc., South San Francisco, CA, USA.
Pharmacoeconomics. 2022 Jun;40(6):623-631. doi: 10.1007/s40273-022-01147-5. Epub 2022 May 9.
A drug that improves survival and/or disease progression can create real option value (ROV)-the additional health gain from future innovations enabled by a longer survival. ROV can be a relevant consideration for both clinical and payer decision-makers. We aimed to estimate the ex ante ROV for first-line (1L) alectinib in anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC).
We developed a Markov model to estimate life-years (LYs) and quality-adjusted life-years (QALYs) gained with 1L alectinib versus 1L crizotinib due to potential future second-line (2L) drugs. Transition probabilities were derived from the phase 3 trial of 1L alectinib and phase 2 trial of 2L brigatinib. We identified drugs being studied in phase 2 and 3 trials in ALK-positive NSCLC at the time of alectinib's 1L approval and projected the likelihood and timing of their arrival and their potential efficacy based on publicly available data.
The discounted incremental LYs and QALYs for alectinib increased by 12.9% (95% CR - 2.96%, 34.82%; 1.25 vs. 1.11) and 11.2% (95% CR - 2.14%, 29.29%; 1.03 vs. 0.92), respectively, after accounting for ROV. The incremental ROV of alectinib was sensitive to the projected efficacy of future drugs, uptake level, and the hazard ratio of progression-free survival of alectinib (vs. crizotinib).
Ex ante ROV can be a significant value consideration in therapeutic areas with high levels of expected innovation. The potential efficacy of future drugs and incremental survival with alectinib at the projected time of arrival are important considerations in assessing ROV.
能够提高生存率和/或疾病进展的药物可以创造实际期权价值（ROV）——通过延长生存时间为未来的创新带来的额外健康收益。ROV 可能是临床和支付方决策者都需要考虑的因素。我们旨在评估一线（1L）艾乐替尼在间变性淋巴瘤激酶（ALK）阳性非小细胞肺癌（NSCLC）中的预期提前 ROV。
我们开发了一个马尔可夫模型，以估计与一线 1L 克唑替尼相比，一线 1L 艾乐替尼因潜在的二线（2L）药物而获得的生命年（LY）和质量调整生命年（QALY）。转移概率来自于 1L 艾乐替尼的 III 期试验和 2L 布加替尼的 II 期试验。我们确定了在艾乐替尼一线获批时正在进行的 ALK 阳性 NSCLC 的 II 期和 III 期试验中的药物，并根据公开数据预测了它们的到达概率、时间及其潜在疗效。
考虑到 ROV，艾乐替尼的折扣增量 LY 和 QALY 分别增加了 12.9%（95%可信区间 -2.96%，34.82%；1.25 对 1.11）和 11.2%（95%可信区间 -2.14%，29.29%；1.03 对 0.92）。艾乐替尼的增量 ROV 对未来药物的预计疗效、吸收率以及艾乐替尼（与克唑替尼相比）无进展生存期的风险比敏感。
在预期创新水平较高的治疗领域，预期提前 ROV 可能是一个重要的价值考虑因素。未来药物的潜在疗效和艾乐替尼在预计到达时间的增量生存是评估 ROV 的重要考虑因素。
