PopED (version 0.1.1)

mftot: Evaluate the Fisher Information Matrix (FIM)

Description

Compute the FIM given specific model(s), parameters, design and methods.

Usage

mftot(model_switch, groupsize, ni, xt, x, a, bpop, d, sigma, docc, poped.db)

Arguments

poped.db

A PopED database.

bpop

The fixed effects parameter values. Supplied as a vector.

d

A between subject variability matrix (OMEGA in NONMEM).

docc

A between occasion variability matrix.

sigma

A residual unexplained variability matrix (SIGMA in NONMEM).

model_switch

A matrix that is the same size as xt, specifying which model each sample belongs to.

ni

A vector of the number of samples in each group.

xt

A matrix of sample times. Each row is a vector of sample times for a group.

x

A matrix for the discrete design variables. Each row is a group.

a

A matrix of covariates. Each row is a group.

groupsize

A vector of the numer of individuals in each group.

Value

• As a list:
• ret
  The FIM
• poped.db
  A PopED database

See Also

For an easier function to use, please see evaluate.fim.

Other FIM: LinMatrixH; LinMatrixLH; LinMatrixL_occ; calc_ofv_and_fim; ed_laplace_ofv; ed_mftot; evaluate.e.ofv.fim; evaluate.fim; gradf_eps; mf3; mf5; mf6; mf7; mf8; mftot0; mftot1; mftot2; mftot3; mftot4; mftot5; mftot6; mftot7; mf; ofv_criterion; ofv_fim

Examples

## Warfarin example from software comparison in:
## Nyberg et al., "Methods and software tools for design evaluation 
##   for population pharmacokinetics-pharmacodynamics studies", 
##   Br. J. Clin. Pharm., 2014. 

## Optimization using an additive + proportional reidual error to 
##   avoid sample times at very low concentrations (time 0 or very late samoples).
library(PopED)

## find the parameters that are needed to define from the structural model
ff.PK.1.comp.oral.sd.CL

## -- parameter definition function 
## -- names match parameters in function ff
sfg <- function(x,a,bpop,b,bocc){
  parameters=c(CL=bpop[1]*exp(b[1]),
               V=bpop[2]*exp(b[2]),
               KA=bpop[3]*exp(b[3]),
               Favail=bpop[4],
               DOSE=a[1])
  return(parameters) 
}

## -- Define initial design  and design space
poped.db <- create.poped.database(ff_file="ff.PK.1.comp.oral.sd.CL",
                                  fg_file="sfg",
                                  fError_file="feps.add.prop",
                                  bpop=c(CL=0.15, V=8, KA=1.0, Favail=1), 
                                  notfixed_bpop=c(1,1,1,0),
                                  d=c(CL=0.07, V=0.02, KA=0.6), 
                                  sigma=c(0.01,0.25),
                                  groupsize=32,
                                  xt=c( 0.5,1,2,6,24,36,72,120),
                                  minxt=0,
                                  maxxt=120,
                                  a=70,
                                  mina=0,
                                  maxa=100)
# warfarin optimization model



mftot(model_switch=poped.db$global_model_switch,
      groupsize=poped.db$groupsize,
      ni=poped.db$gni,
      xt=poped.db$gxt,
      x=poped.db$gx,
      a=poped.db$ga,
      bpop=poped.db$param.pt.val$bpop,
      d=poped.db$param.pt.val$d,
      sigma=poped.db$sigma,
      docc=poped.db$param.pt.val$docc,
      poped.db)["ret"]