From: Design considerations for early-phase clinical trials of immune-oncology agents
Design Challenge | Design Recommendation | Endpoints | Model Assumptions | Available software |
---|---|---|---|---|
Late-onset DLTs | TITE-CRM [21] TITE-BOIN [23] | Binary toxicity | Probability of DLT increases with increasing dose level. | R Package dfcrm SAS macros https://sph.umich.edu/ccb/tite-resources.html www.trialdesign.org |
Additional endpoints | Wages & Tait [30] Zang et al. [29] Ursino et al. [55] | Binary toxicity and binary efficacy (biologic activity or clinical response) Binary toxicity and continuous PK measures (AUC) | Probability of DLT increases with increasing dose level. Probability of efficacy increases or plateaus with increasing dose level. Toxicity related to the PK measure & PK triggers toxicity when above a certain threshold | https://uvatrapps.shinyapps.io/wtdesign/ www.trialdesign.org R Package dfpk |
Drug combinations | POCRM [37] BOIN [39] PIPE [38] | Binary toxicity | Probability of DLT increases with increasing dose level of each agent for a fixed dose level of the other agent. | R Package pocrm www.trialdesign.org R package pipe.design |
Dose and schedule | Braun et al. [52] Wages et al. [54] | Binary toxicity | Probability of DLT increases with increasing dose level of each agent for a fixed schedule. | https://biostatistics.mdanderson.org/softwaredownload/SingleSoftware.aspx?Software_Id=75 R Package pocrm |