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

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

Arguments

model_switch

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

groupsize

A vector of the number of individuals in each group.

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.

bpop

The fixed effects parameter values. Supplied as a vector.

d

A between subject variability matrix (OMEGA in NONMEM).

sigma

A residual unexplained variability matrix (SIGMA in NONMEM).

docc

A between occasion variability matrix.

poped.db

A PopED database.

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(), efficiency(), evaluate.e.ofv.fim(), evaluate.fim(), gradf_eps(), mf3(), mf7(), ofv_criterion(), ofv_fim()

Examples

library(PopED) ############# START ################# ## Create PopED database ## (warfarin model for optimization) ##################################### ## 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 samples). ## find the parameters that are needed to define from the structural model ff.PK.1.comp.oral.sd.CL
#> function (model_switch, xt, parameters, poped.db) #> { #> with(as.list(parameters), { #> y = xt #> y = (DOSE * Favail * KA/(V * (KA - CL/V))) * (exp(-CL/V * #> xt) - exp(-KA * xt)) #> return(list(y = y, poped.db = poped.db)) #> }) #> } #> <bytecode: 0x7fe20a979808> #> <environment: namespace:PopED>
## -- 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_fun=ff.PK.1.comp.oral.sd.CL, fg_fun=sfg, fError_fun=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(prop=0.01,add=0.25), groupsize=32, xt=c( 0.5,1,2,6,24,36,72,120), minxt=0.01, maxxt=120, a=c(DOSE=70), mina=c(DOSE=0.01), maxa=c(DOSE=100)) ############# END ################### ## Create PopED database ## (warfarin model for optimization) ##################################### mftot(model_switch=poped.db$design$model_switch, groupsize=poped.db$design$groupsize, ni=poped.db$design$ni, xt=poped.db$design$xt, x=poped.db$design$x, a=poped.db$design$a, bpop=poped.db$parameters$param.pt.val$bpop, d=poped.db$parameters$param.pt.val$d, sigma=poped.db$parameters$sigma, docc=poped.db$parameters$param.pt.val$docc, poped.db)["ret"]
#> $ret #> [,1] [,2] [,3] [,4] [,5] [,6] #> [1,] 17141.83891 20.838375 10.011000 0.000000e+00 0.000000 0.00000000 #> [2,] 20.83837 17.268051 -3.423641 0.000000e+00 0.000000 0.00000000 #> [3,] 10.01100 -3.423641 49.864697 0.000000e+00 0.000000 0.00000000 #> [4,] 0.00000 0.000000 0.000000 2.324341e+03 9.770352 0.03523364 #> [5,] 0.00000 0.000000 0.000000 9.770352e+00 19083.877564 11.72131703 #> [6,] 0.00000 0.000000 0.000000 3.523364e-02 11.721317 38.85137516 #> [7,] 0.00000 0.000000 0.000000 7.268410e+02 9656.158553 64.78095548 #> [8,] 0.00000 0.000000 0.000000 9.062739e+01 266.487127 2.94728469 #> [,7] [,8] #> [1,] 0.00000 0.000000 #> [2,] 0.00000 0.000000 #> [3,] 0.00000 0.000000 #> [4,] 726.84097 90.627386 #> [5,] 9656.15855 266.487127 #> [6,] 64.78096 2.947285 #> [7,] 192840.20092 6659.569867 #> [8,] 6659.56987 475.500111 #>