Optimizing dose-schedule regimens with bayesian adaptive designs: opportunities and challenges

• Main Authors: Xin Chen (Author), Ruyue He (Author), Xinyi Chen (Author), Liyun Jiang (Author), Fei Wang (Author)
• Format: Book
• Published: Frontiers Media S.A., 2023-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1663-9812; 10.3389/fphar.2023.1261312
• Keywords: dose-schedule regimen; adaptive design; dosage optimization; bayesian method; early phase clinical trial; Therapeutics. Pharmacology; RM1-950
• Source: Frontiers in Pharmacology, Vol 14 (2023)

Due to the small sample sizes in early-phase clinical trials, the toxicity and efficacy profiles of the dose-schedule regimens determined for subsequent trials may not be well established. The recent development of novel anti-tumor treatments and combination therapies further complicates the problem. Therefore, there is an increasing recognition of the essential place of optimizing dose-schedule regimens, and new strategies are now urgently needed. Bayesian adaptive designs provide a potentially effective way to evaluate several doses and schedules simultaneously in a single clinical trial with higher efficiency, but real-world implementation examples of such adaptive designs are still few. In this paper, we cover the critical factors associated with dose-schedule optimization and review the related innovative Bayesian adaptive designs. The assumptions, characteristics, limitations, and application scenarios of those designs are introduced. The review also summarizes some unresolved issues and future research opportunities for dose-schedule optimization.