适应性丰富允许在整个临床试验过程中对预先定义的感兴趣的患者亚组进行研究。这些设计近年来引起了人们的关注，因为它们有可能缩短试验的持续时间并确定针对特定患者群体的有效疗法。我们描述了考虑长期事件发生时间结果的富集试验，但也纳入了来自常规收集的纵向生物标志物的额外短期信息。这些方法适用于亚组之间生物标志物轨迹可能不同的情况，并且据信长期终点受到治疗、亚组和生物标志物的影响。当大多数患者至少在两个时间点进行生物标志物测量时，该方法最有希望。我们对纵向数据和事件时间数据进行联合建模，以定义子组选择和停止标准，并且我们表明，族错误率在强意义上受到保护。为了评估结果，我们进行了一项模拟研究，发现与忽略纵向生物标志物观察的研究相比，纳入生物标志物信息会导致功效增加，并且真正受益于实验治疗的（子）群体被富含更高浓度的物质。中期分析的概率。这些研究的动机是一项治疗转移性乳腺癌的试验，模拟研究的参数值是使用真实世界数据得出的，其中每个患者都可以获得重复的循环肿瘤 DNA 测量和 HER2 状态，并用作我们的纵向数据和子组标识符，分别。

Adaptive enrichment allows for pre-defined patient subgroups of interest to be investigated throughout the course of a clinical trial. These designs have gained attention in recent years because of their potential to shorten the trial's duration and identify effective therapies tailored to specific patient groups. We describe enrichment trials which consider long-term time-to-event outcomes but also incorporate additional short-term information from routinely collected longitudinal biomarkers. These methods are suitable for use in the setting where the trajectory of the biomarker may differ between subgroups and it is believed that the long-term endpoint is influenced by treatment, subgroup and biomarker. Methods are most promising when the majority of patients have biomarker measurements for at least two time points. We implement joint modelling of longitudinal and time-to-event data to define subgroup selection and stopping criteria and we show that the familywise error rate is protected in the strong sense. To assess the results, we perform a simulation study and find that, compared to the study where longitudinal biomarker observations are ignored, incorporating biomarker information leads to increases in power and the (sub)population which truly benefits from the experimental treatment being enriched with higher probability at the interim analysis. The investigations are motivated by a trial for the treatment of metastatic breast cancer and the parameter values for the simulation study are informed using real-world data where repeated circulating tumour DNA measurements and HER2 statuses are available for each patient and are used as our longitudinal data and subgroup identifiers, respectively.