Department of Biomedical Data Science, Stanford University, Stanford, CA, USA.
Pfizer Research & Development, Pfizer Inc, Groton, CT, USA.
Clin Trials. 2024 Oct;21(5):541-552. doi: 10.1177/17407745241264188. Epub 2024 Aug 8.
Duration of response is an important endpoint used in drug development. Prolonged duration for response is often viewed as an early indication of treatment efficacy. However, there are numerous difficulties in studying the distribution of duration of response based on observed data subject to right censoring in practice. The most important obstacle is that the distribution of the duration of response is in general not identifiable in the presence of censoring due to the simple fact that there is no information on the joint distribution of time to response and time to progression beyond the largest follow-up time. In this article, we introduce the restricted duration of response as a replacement of the conventional duration of response. The distribution of restricted duration of response is estimable and we have proposed several nonparametric estimators in this article. The corresponding inference procedure and additional downstream analysis have been developed. Extensive numerical simulations have been conducted to examine the finite sample performance of the proposed estimators. It appears that a new regression-based two-step estimator for the survival function of the restricted duration of response tends to have a robust and superior performance, and we recommend its use in practice. A real data example from oncology has been used to illustrate the analysis for restricted duration of response.
缓解持续时间是药物开发中一个重要的终点指标。缓解持续时间延长通常被视为治疗效果的早期迹象。然而，在实际中，基于观察到的数据并受到右删失的影响，研究缓解持续时间的分布存在许多困难。最重要的障碍是，由于简单的事实，即在最大随访时间之后，没有关于缓解时间和进展时间的联合分布的信息，因此在删失存在的情况下，缓解持续时间的分布通常是不可识别的。在本文中，我们引入了受限缓解持续时间作为传统缓解持续时间的替代。受限缓解持续时间的分布是可估计的，我们在本文中提出了几种非参数估计量。还开发了相应的推断程序和额外的下游分析。进行了广泛的数值模拟，以检查所提出估计量的有限样本性能。似乎，受限缓解持续时间的生存函数的新回归两步估计量具有稳健且优越的性能，我们建议在实践中使用它。来自肿瘤学的一个真实数据示例被用于说明受限缓解持续时间的分析。
