Reni Michele, Wan Yin, Solem Caitlyn, Whiting Scott, Ji Xiang, Botteman Marc
San Raffaele Scientific Institute , Milano , Italy.
J Med Econ. 2014 May;17(5):338-46. doi: 10.3111/13696998.2014.903122. Epub 2014 Mar 21.
To use the Quality-Adjusted Time Without Symptoms or Toxicities (Q-TWiST) methodology to compare the quality-of-life and survival benefits associated with the combination of albumin-bound (nab)-paclitaxel and gemcitabine vs gemcitabine alone in the first-line treatment of metastatic pancreatic adenocarcinoma.
Total survival time through 45 months was partitioned into time before disease progression without toxicity grade ≥3 (TWiST), time with adverse event grade ≥3 (TOX), and time of disease progression (REL). Mean Q-TWiST was calculated by multiplying time spent in each health state by its respective utility (i.e., TWiST = 1.00; TOX/REL = 0.50, 0-1 in sensitivity analyses). Non-parametric bootstrap 95% confidence intervals (CI) were derived to assess the significance of between-treatment differences in TOX, TWiST, REL, and Q-TWiST. A relative gain in Q-TWiST (vs mean overall survival of gemcitabine) of ≥10% and ≥15% was defined as clinically important and clearly clinically important, respectively.
Patients on nab-paclitaxel + gemcitabine spent a significantly longer time in every state and experienced significantly greater overall Q-TWiST (+1.7 months [95% CI = 0.8, 2.7]) than those receiving gemcitabine alone (8.2 months [95% CI = 7.5, 8.9] vs 6.5 months [95% CI = 5.8, 7.0]), assuming base-case utilities of TOX/REL = 0.50. This Q-TWiST gain ranged from 1.0 month (95% CI = 0.1, 1.9), when REL/TOX utilities were both 0, to 2.5 months (95% CI = 1.3, 3.7), when REL/TOX utilities were both 1. Relative gains in Q-TWiST were 21% in favor of nab-paclitaxel + gemcitabine in the base case, and ranged from 12-30% in sensitivity analyses.
There are limitations to Q-TWiST analyses, e.g., imprecision when defining duration/severity of TOX and lack of prospective collection of utilities. This analysis addressed these issues via sensitivity analyses and conservative assumptions to show that nab-paclitaxel + gemcitabine results in statistically significant and clinically important gains in quality-adjusted survival, when compared to gemcitabine alone, in treatment-naive metastatic pancreatic adenocarcinoma patients.
运用质量调整无症状或毒性时间（Q-TWiST）方法，比较在转移性胰腺腺癌一线治疗中，白蛋白结合型（nab）紫杉醇与吉西他滨联合用药和单独使用吉西他滨在生活质量和生存获益方面的差异。
将45个月的总生存时间分为疾病进展前无≥3级毒性的时间（TWiST）、有≥3级不良事件的时间（TOX）和疾病进展时间（REL）。通过将每个健康状态所花费的时间乘以其各自的效用值来计算平均Q-TWiST（即，TWiST = 1.00；TOX/REL = 0.50，敏感性分析中为0 - 1）。采用非参数自助法95%置信区间（CI）来评估治疗组间在TOX、TWiST、REL和Q-TWiST方面差异的显著性。Q-TWiST相对增益（相对于吉西他滨的平均总生存期）≥10%和≥15%分别被定义为具有临床重要性和明显临床重要性。
假设TOX/REL效用值为0.50，与单独接受吉西他滨治疗的患者相比，接受nab紫杉醇 + 吉西他滨治疗的患者在每个状态下花费的时间显著更长，且总体Q-TWiST显著更高（增加1.7个月[95% CI = 0.8, 2.7]）（吉西他滨组为8.2个月[95% CI = 7.5, 8.9]，nab紫杉醇 + 吉西他滨组为6.5个月[95% CI = 5.8, 7.0]）。当REL/TOX效用值均为0时，这种Q-TWiST增益为1.0个月（95% CI = 0.1, 1.9）；当REL/TOX效用值均为1时，增益为2.5个月（95% CI = 1.3, 3.7）。在基础病例中，Q-TWiST相对增益有利于nab紫杉醇 + 吉西他滨的为21%，在敏感性分析中范围为12% - 30%。
Q-TWiST分析存在局限性，例如在定义TOX持续时间/严重程度时不够精确，以及缺乏效用值的前瞻性收集。本分析通过敏感性分析和保守假设解决了这些问题，结果表明，与单独使用吉西他滨相比，nab紫杉醇 + 吉西他滨在初治转移性胰腺腺癌患者的质量调整生存方面具有统计学显著且临床重要的获益。
