Design and Analysis of Basket and Umbrella Trials

在药物投放市场之前，它们要经过严格的临床试验测试。患者对此类治疗的反应可能因其内在因素而异，因此需要针对呈现不同特征的患者进行针对性治疗。为了解决这个问题，提出了所谓的篮子和保护伞审判。一揽子试验包括对具有共同特征但患有不同疾病的不同患者群体进行单一治疗。保护伞试验是由多种治疗方法组成的，这些治疗方法在患有相同疾病但呈现不同基因构成的患者身上并行进行测试。我们还必须考虑到，尽管试验的主要目标是确定最有效的治疗方法，但次要目标是在试验中为患者提供最佳治疗。这是通过反应适应性随机化来实现的，这是一种根据试验中先前治疗的患者的数据改变分配治疗的机会的技术。stori和罗氏公司合作创建了一个项目，旨在回答以下问题：在篮子试验中，我们如何在治疗组之间借鉴信息？我们如何利用反应适应性随机化来提高从试验中受益的患者数量？最后，为了纳入新确定的靶向治疗，我们如何在总括性试验中改变子研究的研究人群？为了解决这些问题，我们首先关注子研究之间的借鉴信息，以及如何在这种借鉴结构中有效地将子组添加到篮子试验中。增加亚组是上述试验设计的一个非常有益的特征，因为新的患者群体可能在试验的一部分被确定。在此之后，我们将探讨反应适应性随机化的操作特征，以及它如何受到疾病或医疗保健提供的时间变化的影响。与罗氏公司合作。

Prior to treatments' release onto the market, they undergo rigorous testing in clinical trials. Patients responses to such treatments can vary based on their intrinsic factors, and thus it is desirable to target treatments to patient's presenting different characteristics. To address this issue, so-called basket and umbrella trials are proposed. Basket trials consist of a single treatment applied to different patient groups who share a common characteristic but suffer from different diseases. Umbrella trials are composed of multiple treatments tested in parallel on patients who share the same disease but present a different genetic make-up. We must also consider that, although the primary goal of a trial is to identify the most effective treatment, a secondary goal is to deliver the best treatment to patients within the trial. This is achieved through response-adaptive randomisation, a technique that alters the chance of being allocated a treatment on the basis of data from previously treated patients within the trial. STOR-i and Roche have collaborated to create a project that aims to answer the following questions: How do we borrow information between treatment groups in basket trials? How can we utilize response-adaptive randomisation to improve the number of patients benefiting from the trial? And finally, how can we change the study populations of sub-studies within umbrella trials in order to incorporate newly identified targeted treatments? To tackle these problems, we first focus in on borrowing information between sub-studies and how to efficiently add a sub-group to a basket trial within this borrowing structure. Adding a sub-group is a highly beneficial feature of the aforementioned trial designs, as a new patient population may be identified part way through the trial. Following this, we will explore the operating characteristics of response-adaptive randomisation and how it is impacted on by temporal changes in the disease or health care provision. In partnership with Roche.