DTAT (version 0.3-4)

titrate: Perform neutrophil-guided dose titration of a chemotherapy drug.

Description

This is included in package DTAT mainly for archival purposes, with the aim to document a reproduction of Figure 5 from the 2017 F1000Research paper (referenced below), using a clearer and more general software design than is found in the online code supplement available at https://osf.io/vwnqz/.

Usage

titrate(draw.days = NULL, Ncycles = 10, doserange = c(50, 500), dta = NULL)

Value

A list with 2 components:

course

A data frame containing cycle-wise measures of each id's titration course

anc.ts

A data frame detailing high-frequency ANC measures for each id

Arguments

draw.days

Integer days on which ANC is to be measured

Ncycles

Number of chemo cycles through which to simulate titration

doserange

Range of doses to consider

dta

A Dose Titration Algorithm (DTA) to drive the titration

Author

David C. Norris

References

Norris DC. Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials. F1000Research. 2017;6:112. doi:10.12688/f1000research.10624.3. https://f1000research.com/articles/6-112/v3

Examples

if(interactive()){
# Reproduce Figure 5 from the F1000Research paper (run time > 10 s).
# 1. Set up sim$pop & sim$pkpd by running the repro for Figures 1 & 3:
example(topic="Onoue.Friberg", package="DTAT", ask=FALSE)
# 2. Do the neutrophil-nadir-guided dose titration:
chemo <- titrate(doserange = c(50, 3000),
                 dta=newton.raphson(dose1 = 50,
                                    omega = 0.75,
                                    slope1 = -2.0,
                                    slopeU = -0.2)
                 )
library(latticeExtra)
newton <- chemo$course
new.ts <- chemo$anc.ts
anc.tics <- c(200,500,1500,4000,10000)
right <- xYplot(ANC ~ time | id, data=new.ts
                , as.table=TRUE, type="l"
                , layout=c(5,5)
                , scales=list(y=list(log=TRUE, lim=c(100,1.5e4)
                                     , at=anc.tics
                                     , lab=as.character(anc.tics)),
                              x=list(at=seq(0,30,3)))
)
newton <- upData(newton
                 , time = 3*(cycle-1)
                 , labels = c(time="Time")
                 , units = c(time="weeks")
                 , print = FALSE)
dose.tics <- c(50, 200, 600, 1500, 3000)
left <- xYplot(scaled.dose ~ time | id, data=newton
               , as.table=TRUE, type='p', pch='+', cex=1.5
               , layout=c(5,5)
               , scales=list(y=list(lim=DTAT:::scaled(c(30,3200))
                                    , at=DTAT:::scaled(dose.tics)
                                    , lab=as.character(dose.tics)),
                             x=list(lim=c(-1,31)
                                    , at=seq(0,30,3)
                                    , lab=c('0','','6','','12','','18','','24','','30')))
)
update(doubleYScale(left, right, add.ylab2=TRUE)
       , par.settings = simpleTheme(col=brewer.pal(4,"PRGn")[c(4,1)])
)
}