Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate. In order to test that hypothesis, we retrospectively applied a Bayesian approach to the HOVON 132 trial, in which 800 newly diagnosed AML patients aged 18 to 65 years were randomly assigned to a “7 + 3” induction with or without lenalidomide. Five years after the first patient was recruited, the trial was negative for its primary endpoint with no difference in event-free survival (EFS) between experimental and control groups (hazard ratio [HR] 0.99, p = 0.96) in the final conventional analysis. We retrospectively simulated interim analyses after the inclusion of 150, 300, 450, and 600 patients using a Bayesian methodology to detect early lack of efficacy signals. The HR for EFS comparing the lenalidomide arm with the control treatment arm was 1.21 (95% CI 0.81–1.69), 1.05 (95% CI 0.86–1.30), 1.00 (95% CI 0.84–1.19), and 1.02 (95% CI 0.87–1.19) at interim analysis 1, 2, 3 and 4, respectively. Complete remission rates were lower in the lenalidomide arm, and early deaths more frequent. A Bayesian approach identified that the probability of a clinically relevant benefit for EFS (HR < 0.76, as assumed in the statistical analysis plan) was very low at the first interim analysis (1.2%, 0.6%, 0.4%, and 0.1%, respectively). Similar observations were made for low probabilities of any benefit regarding CR. Therefore, Bayesian analysis significantly adds to conventional methods applied for interim analysis and may thereby accelerate the performance and completion of phase III trials.

随机对照试验（RCT）是确定新药获益风险比的黄金标准。然而，成熟成果的评估往往需要多年时间。我们假设在中期分析时间点添加贝叶斯推理方法可能会加速并强化此类试验可能产生的知识。为了检验这一假设，我们回顾性地将贝叶斯方法应用于 HOVON 132 试验，其中 800 名年龄在 18 至 65 岁之间的新诊断 AML 患者被随机分配到使用或不使用来那度胺的“7 + 3”诱导组。招募第一位患者五年后，该试验的主要终点结果为阴性，在最终常规分析中，实验组和对照组之间的无事件生存期 (EFS) 没有差异（风险比 [HR] 0.99， p = 0.96 ）。我们使用贝叶斯方法回顾性模拟了纳入 150、300、450 和 600 名患者后的中期分析，以检测早期缺乏疗效信号。来那度胺组与对照治疗组比较的 EFS HR 为 1.21 (95% CI 0.81–1.69)、1.05 (95% CI 0.86–1.30)、1.00 (95% CI 0.84–1.19) 和 1.02 (95% CI) 0.87–1.19) 分别在中期分析 1、2、3 和 4 中。来那度胺组的完全缓解率较低，且早期死亡更为频繁。贝叶斯方法发现，第一次中期分析时，EFS 产生临床相关获益的概率（HR < 0.76，如统计分析计划中假设的那样）非常低（分别为 1.2%、0.6%、0.4% 和 0.1%） ）。对于与 CR 相关的任何益处的可能性很低，也进行了类似的观察。因此，贝叶斯分析显着增加了用于中期分析的传统方法，从而可以加速 III 期试验的执行和完成。