phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints

Jun Yin, Yu Du, Rui Qin, Shihao Shen, Sumithra Mandrekar

Research output: Contribution to journalArticlepeer-review


Traditional dose-finding designs are substantially inefficient for targeted agents and cancer immunotherapies by failing to incorporate efficacy signals, mild and moderate adverse events, and late, cumulative toxicities. However, the lack of user-friendly software is a barrier to the practical use of the novel phase I designs, despite their demonstrated superiority of traditional 3+3 designs. To overcome these barriers, we present an R package, phase1RMD, which provides a comprehensive implementation of novel designs with repeated toxicity measures and early efficacy. A novel phase I repeated measures design that used a continuous toxicity score from multiple treatment cycles was implemented. Furthermore, in studies where preliminary efficacy is evaluated, an adaptive, multi-stage design to identify the most efficacious dose with acceptable toxicity was demonstrated. Functions are provided to recommend the next dose based on the data collected in a phase I trial, as well as to assess trial characteristics given design parameters via simulations. The repeated measure designs accurately estimated both the magnitude and direction of toxicity trends in late treatment cycles, and allocated more patients at therapeutic doses. The R package for implementing these designs is available from the Comprehensive R Archive Network. To our best knowledge, this is the first software that implement novel phase I dose-finding designs that simultaneously accounts for the multiple-grade toxicity events over multiple treatment cycles and a continuous early efficacy outcome. With the software published on CRAN, we will pursue the implementation of these designs in phase I trials in real-life settings.

Original languageEnglish (US)
Article numbere0256391
JournalPloS one
Issue number9 September
StatePublished - Sep 2021

ASJC Scopus subject areas

  • General


Dive into the research topics of 'phase1RMD: An R package for repeated measures dose-finding designs with novel toxicity and efficacy endpoints'. Together they form a unique fingerprint.

Cite this