PHMR Limited, Berkeley Works, London, England, UK.
PHMR Limited, Berkeley Works, London, England, UK; Department of Health Services Research and Policy, The Australian National University, Canberra, Australia.
Value Health. 2022 Jul;25(7):1205-1211. doi: 10.1016/j.jval.2022.01.022. Epub 2022 Apr 2.
Treatment switching from control to treatment after disease progression is common in oncology trials. Analyses of survival data typically adjust for this bias, but such adjustments are rarely performed in analyses of patient-reported outcomes. This analysis aimed to examine the impact of adjusting for treatment switching on estimated treatment effects on 5-level version of EQ-5D (EQ-5D-5L) utilities and quality-adjusted life-years (QALYs). The AURA3 trial (NCT02151981) was a randomized controlled trial comparing osimertinib with platinum-based doublet chemotherapy (standard care) in patients with locally advanced or metastatic epidermal growth factor receptor mutant- and T790M-positive nonsmall cell lung cancer whose disease has progressed with previous epidermal growth factor receptor tyrosine kinase inhibitor therapy.
Descriptive analyses were used to compare treatment arms. The primary analysis used a 2-stage least squares instrumental variable regression to estimate treatment effect adjusting for treatment crossover. Time to deterioration, defined from baseline to minimally important deterioration in EQ-5D-5L utility, was assessed using a rank preserving structural failure time model.
Intention-to-treat analysis of imputed data showed incremental QALYs for osimertinib of 0.23 at 60 weeks. Accounting for treatment switching increased this to 0.52 in the primary analysis and to 0.63 QALYs in sensitivity analysis at 150 weeks. Time to deterioration analysis showed longer health-related quality of life maintenance with osimertinib, of 12.76 weeks, although this was at the borderline of statistical significance (acceleration factor, ψ = -0.275; 95% confidence interval -0.50 to 0.00).
This analysis demonstrates methods to adjust for treatment switching in the analysis of EQ-5D-5L from clinical trials. Failure to account for crossover substantially underestimated the QALY gain for osimertinib.
在肿瘤学试验中，疾病进展后从对照治疗转换为治疗是很常见的。生存数据分析通常会对此偏差进行调整，但在患者报告结局分析中很少进行此类调整。本分析旨在研究调整治疗转换对 5 级版 EQ-5D（EQ-5D-5L）效用和质量调整生命年（QALY）估计治疗效果的影响。AURA3 试验（NCT02151981）是一项随机对照试验，比较奥希替尼与铂类双联化疗（标准治疗）在先前表皮生长因子受体酪氨酸激酶抑制剂治疗后疾病进展且存在局部晚期或转移性表皮生长因子受体突变和 T790M 阳性非小细胞肺癌患者中的疗效。
描述性分析用于比较治疗组。主要分析采用两阶段最小二乘法工具变量回归，调整治疗交叉进行治疗效果估计。从基线到 EQ-5D-5L 效用最小重要恶化的恶化时间使用秩保持结构失效时间模型进行评估。
意向治疗分析表明，奥希替尼在 60 周时的增量 QALY 为 0.23。在主要分析中，考虑到治疗转换，这一数字增加到 0.52，在 150 周时的敏感性分析中增加到 0.63 QALY。恶化时间分析表明，奥希替尼可维持更长时间的健康相关生活质量，为 12.76 周，尽管这处于统计学意义的边缘（加速因子，ψ=-0.275；95%置信区间-0.50 至 0.00）。
本分析展示了在临床试验中调整 EQ-5D-5L 分析中治疗转换的方法。未考虑交叉会大大低估奥希替尼的 QALY 获益。
