A software tool for both the maximum tolerated dose and the optimal biological dose finding trials in early phase...

Phase I and/or I/II oncology trials are conducted to find the maximum tolerated dose (MTD) and/or optimal biological dose (OBD) of a new drug or treatment. In these trials, for cytotoxic agents, the primary aim of the single-agent or drug-combination is to find the MTD with a certain target toxicity rate, while for the cytostatic agents, a more appropriate target is the OBD, which is often defined by considering of toxicity and efficacy simultaneously. Accessible software packages to achieve both these aims are needed.

The objective of this study is to develop a software package that can provide tools for both MTD- and OBD-finding trials, which implements the Keyboard design for single-agent MTD-finding trials as reported by Yan et al. (2017), the Keyboard design for drug-combination MTD-finding trials by Pan et al. (2020), and a phase I/II OBD-finding method by Li et al. (2017) in a single R package, called Keyboard. For each of the designs, the Keyboard package provides corresponding functions such as get.boundary ( $$ ) for deriving the optimal dose escalation and de-escalation boundaries, select.mtd ( $$ ) for selecting the MTD when the trial is completed, select.obd ( $$ ) for selecting the OBD at the end of a trial, and get.oc ( $$ ) for generating the operating characteristics.

The Keyboard R package developed herein provides convenient tools for designing, conducting and analyzing single-agent, drug-combination, phase I/II OBD-finding trials.