Freitag Michaela Maria, Zocholl Dario, Meyer Elias Laurin, Gold Stefan M, Roig Marta Bofill, De Smedt Heidi, Posch Martin, König Franz
Institute of Biometry and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Institute for Medical Biometry, Informatics and Epidemiology, Faculty of Medicine, University of Bonn, Bonn, Germany.
Pharm Stat. 2025 Sep-Oct;24(5):e70025. doi: 10.1002/pst.70025.
Major depressive disorder (MDD) is one of the leading causes of disability globally. Despite its prevalence, approximately one-third of patients do not benefit sufficiently from available treatments, and few new drugs have been developed recently. Consequently, more efficient methods are needed to evaluate a broader range of treatment options quickly. Platform trials offer a promising solution, as they allow for the assessment of multiple investigational treatments simultaneously by sharing control groups and by reducing both trial activation and patient recruitment times. The objective of this simulation study was to support the design and optimisation of a phase II superiority platform trial for MDD, considering the disease-specific characteristics. In particular, we assessed the efficiency of platform trials compared to traditional two-arm trials by investigating key design elements, including allocation and randomisation strategies, as well as per-treatment arm sample sizes and interim futility analyses. Through extensive simulations, we refined these design components and evaluated their impact on trial performance. The results demonstrated that platform trials not only enhance efficiency but also achieve higher statistical power in evaluating individual treatments compared to conventional trials. The efficiency of platform trials is particularly prominent when interim futility analyses are performed to eliminate treatments that have either no or a negligible treatment effect early. Overall, this work provides valuable insights into the design of platform trials in the superiority setting and underscores their potential to accelerate therapy development in MDD and other therapeutic areas, providing a flexible and powerful alternative to traditional trial designs.
重度抑郁症（MDD）是全球导致残疾的主要原因之一。尽管其发病率很高，但约有三分之一的患者无法从现有治疗中充分获益，且近年来几乎没有开发出新药。因此，需要更有效的方法来快速评估更广泛的治疗选择。平台试验提供了一个有前景的解决方案，因为它们通过共享对照组以及减少试验启动和患者招募时间，能够同时评估多种研究性治疗。本模拟研究的目的是考虑到疾病的特定特征，支持MDD的II期优效性平台试验的设计和优化。具体而言，我们通过研究关键设计要素，包括分配和随机化策略、每个治疗组的样本量以及中期无效性分析，评估了平台试验与传统双臂试验相比的效率。通过广泛的模拟，我们优化了这些设计组件，并评估了它们对试验性能的影响。结果表明，与传统试验相比，平台试验不仅提高了效率，而且在评估个体治疗时具有更高的统计效力。当进行中期无效性分析以早期排除那些没有治疗效果或治疗效果可忽略不计的治疗时，平台试验的效率尤为突出。总体而言，这项工作为优效性环境下的平台试验设计提供了有价值的见解，并强调了它们在加速MDD和其他治疗领域治疗开发方面的潜力，为传统试验设计提供了一种灵活且强大的替代方案。
