Increasing the efficiency of oncology basket trials using a Bayesian approach
Increasing the efficiency of oncology basket trials using a Bayesian approach
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DOI：
10.1016/j.cct.2017.06.009
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发表时间：
2017-12-01
影响因子：
2.2
通讯作者：
Vonk, Richardus
中科院分区：
文献类型：
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作者：
Liu, Rong;Liu, Zheyu;Vonk, Richardus
随着靶向治疗和免疫肿瘤治疗的快速发展，需要新的统计设计方法来提高早期肿瘤试验的灵活性和效率。篮子试验招募具有明确生物学缺陷但具有多种组织学肿瘤类型（或适应症）的患者，以发现药物在哪些适应症中有效。在这样的设计中，通常独立地分析不同的适应症。然而，这忽略了潜在的生物学相似性之间的适应症，我们的研究提供了一种统计方法，以加强这样的篮子试验，通过评估在中期分析的反应率之间的适应症的同质性，并在第二阶段应用贝叶斯分层建模方法，如果疗效被认为是合理同质的适应症。这通过允许具有相似响应率的适应症相互借用信息来增加研究的效力。通过模拟，我们量化了我们提出的方法相对于传统的并行方法的效率增益。我们的方法的操作特性取决于不同适应症之间的响应率的相似性。如果在接受研究药物治疗后，大多数或所有适应症的缓解率相当，则与传统方法相比，可以获得有效性的大幅增加，因为需要的患者更少或获得更高的把握度。我们还证明，如果肿瘤类型之间的反应率差异很大，则疗效再次降低，但仍优于传统方法。
With the rapid growth of targeted and immune-oncology therapies, novel statistical design approaches are needed to increase the flexibility and efficiency of early phase oncology trials.Basket trials enroll patients with defined biological deficiencies, but with multiple histologic tumor types (or indications), to discover in which indications the drug is active. In such designs different indications are typically analyzed independently. This, however, ignores potential biological similarities among the indications.Our research provides a statistical methodology to enhance such basket trials by assessing the homogeneity of the response rates among indications at an interim analysis, and applying a Bayesian hierarchical modeling approach in the second stage if the efficacy is deemed reasonably homogenous across indications. This increases the power of the study by allowing indications with similar response rates to borrow information from each other. Via simulations, we quantify the efficiency gain of our proposed approach relative to the conventional parallel approach. The operating characteristics of our method depend on the similarity of the response rates between the different indications. If the response rates are comparable in most or all indications after treatment with the investigational drug, a substantial increase in efficiency as compared to the conventional approach can be obtained as fewer patients are required or a higher power is attained. We also demonstrate that efficacy again decreases if the response rates vary considerably among tumor types but it is still better than the conventional approach.