Gao Jingya, Hu Feifang, Ma Wei
School of Mathematics and Physics, University of Science and Technology Beijing, Beijing, China.
Department of Statistics, George Washington University, Washington, DC.
Stat Med. 2024 Dec 30;43(30):5911-5921. doi: 10.1002/sim.10286. Epub 2024 Nov 25.
In clinical trials, subjects are usually recruited sequentially. According to the outcomes amassed thus far in a trial, the response-adaptive randomization (RAR) design has been shown to be an advantageous treatment assignment procedure that skews the treatment allocation proportion to pre-specified objectives, such as sending more patients to a more promising treatment. Unfortunately, there are circumstances under which very few data of the primary endpoints are collected in the recruitment period, such as circumstances relating to public health emergencies and chronic diseases, and RAR is thus difficult to apply in allocating treatments using available outcomes. To overcome this problem, if an informative surrogate endpoint can be acquired much earlier than the primary endpoint, the surrogate endpoint can be used as a substitute for the primary endpoint in the RAR procedure. In this paper, we propose an RAR procedure that relies only on surrogate endpoints. The validity of the statistical inference on the primary endpoint and the patient benefit of this approach are justified by both theory and simulation. Furthermore, different types of surrogate endpoint and primary endpoint are considered. The results reassure that RAR with surrogate endpoints can be a viable option in some cases for clinical trials when primary endpoints are unavailable for adaptation.
在临床试验中，受试者通常是按顺序招募的。根据一项试验到目前为止积累的结果，响应自适应随机化（RAR）设计已被证明是一种有利的治疗分配程序，它会使治疗分配比例偏向于预先设定的目标，比如将更多患者分配到更有前景的治疗组。不幸的是，在某些情况下，例如与突发公共卫生事件和慢性病相关的情况，在招募期间收集到的主要终点数据非常少，因此RAR很难应用于利用现有结果进行治疗分配。为克服这一问题，如果能比主要终点更早地获得一个信息性替代终点，那么该替代终点可在RAR程序中用作主要终点的替代。在本文中，我们提出一种仅依赖替代终点的RAR程序。对主要终点进行统计推断的有效性以及这种方法对患者的益处均通过理论和模拟得到了验证。此外，还考虑了不同类型的替代终点和主要终点。结果表明，在某些临床试验中，当无法获得主要终点用于适应性调整时，使用替代终点的RAR可能是一种可行的选择。
