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Table 1 Design challenges, recommendations, assumptions, and available software for early-phase trials of imunne-oncology agents

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