Extrapolation and Bridging of Adult Information in Early Phase Dose-Finding Paediatrics Studies
Concentration of albumin according to age.
Concentration of alpha1-acid glycoprotein according to age.
Clearance of the unbound fraction of a specific molecule for the adult...
Paediatric clearance according to the allometry adjustment (AA) for a ...
Paediatric clearance according to the linear adjustment (LA) for a spe...
Paediatric clearance according to the maturation adjustment (MA) for a...
Clearance of the unbound fraction of a specific molecule for the paedi...
Concentration of a specific molecule in plasma for the adult populatio...
Concentration of a specific molecule in plasma for the paediatric popu...
Extrapolation and Bridging of Adult Information in Early Phase Dose-Fi...
Choice of the next given dose level.
Dose-range for the paediatric population according to adult clearance,...
Paediatric bioavailability according to age.
Unbound fraction of the molecule in the plasma for children.
Fraction of adult CYP1A2 abundance according to age.
Fraction of adult CYP2B6 abundance according to age.
Fraction of adult CYP2C18/CYP2C19 abundance according to age.
Fraction of adult CYP2C8 abundance according to age.
Fraction of adult CYP2C9 abundance according to age.
Fraction of adult CYP2D6 abundance according to age.
Fraction of adult CYP2E1 abundance according to age.
Fraction of adult CYP3A abundance according to age.
Fraction of adult CYP3A4/CYP3A5 abundance according to age.
Control for presence of at least toxicities and efficacies for the goo...
Meta-analysis function of dose-finding studies proposed by Zohar et al...
Decision function for the choice of variance (sigmaHI or sigmaLI) in t...
The variance of the effective sample size (ESS).
Compute the informative prior variance for the adaptive prior.
Compute the least informative prior variance for the adaptive prior.
A simulation of a single dose-finding trials in paediatrics.
Simulate one or "n" dose-finding trials in paediatrics.
Build a working model.
Function for the Watanabe-Akaike information criteria (WAIC)
Proportion of the molecule metabolised by the CYPs for a child accordi...
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>.