Khanal Manoj, Logan Brent R, Banerjee Anjishnu, Fang Xi, Ahn Kwang Woo
Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Department of Biostatistics, Yale University, New Haven, Connecticut, USA.
Pharm Stat. 2025 Jan-Feb;24(1):e2464. doi: 10.1002/pst.2464.
Clinical trials (CTs) often suffer from small sample sizes due to limited budgets and patient enrollment challenges. Using historical data for the CT data analysis may boost statistical power and reduce the required sample size. Existing methods on borrowing information from historical data with right-censored outcomes did not consider matching between historical data and CT data to reduce the heterogeneity. In addition, they studied the survival outcome only, not competing risk outcomes. Therefore, we propose a clustering-based commensurate prior model with random effects for both survival and competing risk outcomes that effectively borrows information based on the degree of comparability between historical and CT data. Simulation results show that the proposed method controls type I errors better and has a lower bias than some competing methods. We apply our method to a phase III CT which compares the effectiveness of bone marrow donated from family members with only partially matched bone marrow versus two partially matched cord blood units to treat leukemia and lymphoma.
由于预算有限和患者招募困难,临床试验(CTs)常常面临样本量较小的问题。使用历史数据进行CT数据分析可能会提高统计功效并减少所需的样本量。现有的利用带有右删失结局的历史数据来借鉴信息的方法没有考虑历史数据与CT数据之间的匹配以减少异质性。此外,它们仅研究了生存结局,而非竞争风险结局。因此,我们提出了一种基于聚类的相称先验模型,该模型对生存和竞争风险结局均具有随机效应,能基于历史数据与CT数据之间的可比程度有效地借鉴信息。模拟结果表明,与一些竞争方法相比,所提出的方法能更好地控制I型错误且偏差更低。我们将我们的方法应用于一项III期CT,该试验比较了来自家庭成员的仅部分匹配的骨髓与两个部分匹配的脐血单位治疗白血病和淋巴瘤的有效性。