Package: dfped 1.1

dfped: Extrapolation and Bridging of Adult Information in Early Phase Dose-Finding Paediatrics Studies

A unified method for designing and analysing dose-finding trials in paediatrics, while bridging information from adults, is proposed in the 'dfped' package. The dose range can be calculated under three extrapolation methods: linear, allometry and maturation adjustment, using pharmacokinetic (PK) data. To do this, it is assumed that target exposures are the same in both populations. The working model and prior distribution parameters of the dose-toxicity and dose-efficacy relationships can be obtained using early phase adult toxicity and efficacy data at several dose levels through 'dfped' package. Priors are used into the dose finding process through a Bayesian model selection or adaptive priors, to facilitate adjusting the amount of prior information to differences between adults and children. This calibrates the model to adjust for misspecification if the adult and paediatric data are very different. User can use his/her own Bayesian model written in Stan code through the 'dfped' package. A template of this model is proposed in the examples of the corresponding R functions in the package. Finally, in this package you can find a simulation function for one trial or for more than one trial. These methods are proposed by Petit et al, (2016) <doi:10.1177/0962280216671348>.

Authors:Artemis Toumazi <[email protected]>, Caroline Petit <[email protected]>, Sarah Zohar <[email protected]>

dfped_1.1.tar.gz
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dfped.pdf |dfped.html
dfped/json (API)

# Install 'dfped' in R:
install.packages('dfped', repos = c('https://artemis-toumazi.r-universe.dev', 'https://cloud.r-project.org'))

Peer review:

Bug tracker:https://github.com/artemis-toumazi/dfped/issues

On CRAN:

35 exports 0.93 score 52 dependencies 1 mentions 34 scripts 160 downloads

Last updated 6 years agofrom:197bd40f03. Checks:OK: 7. Indexed: yes.

TargetResultDate
Doc / VignettesOKSep 01 2024
R-4.5-winOKSep 01 2024
R-4.5-linuxOKSep 01 2024
R-4.4-winOKSep 01 2024
R-4.4-macOKSep 01 2024
R-4.3-winOKSep 01 2024
R-4.3-macOKSep 01 2024

Exports:albAgealpha1AGageCladuClch.AlloClch.LinearClch.MatClchuconcAdconcChcrmAtjdoseChoicedoseRangeFchfuChKCYP1A2KCYP2B6KCYP2C18_19KCYP2C8KCYP2C9KCYP2D6KCYP2E1KCYP3AKCYP3A4_5kickoffControlmetaPhaseplotEstimatespriorChoicesigmaEsssigmaHIsigmaLIsimusimulationskeletonwaicweightCYPsum

Dependencies:abindbackportsBHcallrcheckmateclicolorspacedescdistributionalfansifarvergenericsggplot2gluegridExtragtableinlineisobandlabelinglatticelifecycleloomagrittrMASSMatrixmatrixStatsmgcvmunsellnlmenumDerivpillarpkgbuildpkgconfigposteriorprocessxpsQuickJSRR6RColorBrewerRcppRcppEigenRcppParallelrlangrstanscalesStanHeaderstensorAtibbleutf8vctrsviridisLitewithr

Readme and manuals

Help Manual

Help pageTopics
Extrapolation and Bridging of Adult Information in Early Phase Dose-Finding Paediatrics Studiesdfped-package dfped
Concentration of albumin according to age.albAge
Concentration of alpha1-acid glycoprotein according to age.alpha1AGage
Clearance of the unbound fraction of a specific molecule for the adult population.Cladu
Paediatric clearance according to the allometry adjustment (AA) for a specific age.Clch.Allo
Paediatric clearance according to the linear adjustment (LA) for a specific age.Clch.Linear
Paediatric clearance according to the maturation adjustment (MA) for a specific age.Clch.Mat
Clearance of the unbound fraction of a specific molecule for the paediatric population.Clchu
Concentration of a specific molecule in plasma for the adult population.concAd
Concentration of a specific molecule in plasma for the paediatric population.concCh
Choice of the next given dose level.doseChoice
Dose-range for the paediatric population according to adult clearance, adult doses and paediatric clearance.doseRange
Paediatric bioavailability according to age.Fch
Unbound fraction of the molecule in the plasma for children.fuCh
Fraction of adult CYP1A2 abundance according to age.KCYP1A2
Fraction of adult CYP2B6 abundance according to age.KCYP2B6
Fraction of adult CYP2C18/CYP2C19 abundance according to age.KCYP2C18_19
Fraction of adult CYP2C8 abundance according to age.KCYP2C8
Fraction of adult CYP2C9 abundance according to age.KCYP2C9
Fraction of adult CYP2D6 abundance according to age.KCYP2D6
Fraction of adult CYP2E1 abundance according to age.KCYP2E1
Fraction of adult CYP3A abundance according to age.KCYP3A
Fraction of adult CYP3A4/CYP3A5 abundance according to age.KCYP3A4_5
Control for presence of at least toxicities and efficacies for the good run of bCRM model.kickoffControl
Meta-analysis function of dose-finding studies proposed by Zohar et al, (2011).metaPhase
Decision function for the choice of variance (sigmaHI or sigmaLI) in the adaptive prior variance calibration.priorChoice
The variance of the effective sample size (ESS).sigmaEss
Compute the informative prior variance for the adaptive prior.sigmaHI
Compute the least informative prior variance for the adaptive prior.sigmaLI
A simulation of a single dose-finding trials in paediatrics.crmAtj simu
Simulate one or "n" dose-finding trials in paediatrics.saveSimu simulation
Build a working model.plotEstimates skeleton
Function for the Watanabe-Akaike information criteria (WAIC)fitDataj waic
Proportion of the molecule metabolised by the CYPs for a child according to age.weightCYPsum