% Generated by roxygen2: do not edit by hand
% Please edit documentation in R/nlmixr.R
\name{nlmixr.mmkin}
\alias{nlmixr.mmkin}
\alias{print.nlmixr.mmkin}
\alias{nlmixr_model}
\alias{nlmixr_data}
\title{Fit nonlinear mixed models using nlmixr}
\usage{
\method{nlmixr}{mmkin}(
  object,
  data = NULL,
  est = NULL,
  control = list(),
  table = tableControl(),
  error_model = object[[1]]$err_mod,
  test_log_parms = TRUE,
  conf.level = 0.6,
  ...,
  save = NULL,
  envir = parent.frame()
)

\method{print}{nlmixr.mmkin}(x, digits = max(3, getOption("digits") - 3), ...)

nlmixr_model(
  object,
  est = c("saem", "focei"),
  degparms_start = "auto",
  test_log_parms = FALSE,
  conf.level = 0.6,
  error_model = object[[1]]$err_mod
)

nlmixr_data(object, ...)
}
\arguments{
\item{object}{An \link{mmkin} row object containing several fits of the same
\link{mkinmod} model to different datasets}

\item{est}{Estimation method passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}}

\item{control}{Passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}.}

\item{test_log_parms}{If TRUE, an attempt is made to use more robust starting
values for population parameters fitted as log parameters in mkin (like
rate constants) by only considering rate constants that pass the t-test
when calculating mean degradation parameters using \link{mean_degparms}.}

\item{conf.level}{Possibility to adjust the required confidence level
for parameter that are tested if requested by 'test_log_parms'.}

\item{\dots}{Passed to \link{nlmixr_model}}

\item{x}{An nlmixr.mmkin object to print}

\item{digits}{Number of digits to use for printing}

\item{degparms_start}{Parameter values given as a named numeric vector will
be used to override the starting values obtained from the 'mmkin' object.}

\item{solution_type}{Possibility to specify the solution type in case the
automatic choice is not desired}
}
\value{
An S3 object of class 'nlmixr.mmkin', containing the fitted
\link[nlmixr:nlmixr]{nlmixr::nlmixr} object as a list component named 'nm'. The
object also inherits from 'mixed.mmkin'.

An function defining a model suitable for fitting with \link[nlmixr:nlmixr]{nlmixr::nlmixr}.

An dataframe suitable for use with \link[nlmixr:nlmixr]{nlmixr::nlmixr}
}
\description{
This function uses \code{\link[nlmixr:nlmixr]{nlmixr::nlmixr()}} as a backend for fitting nonlinear mixed
effects models created from \link{mmkin} row objects using the Stochastic Approximation
Expectation Maximisation algorithm (SAEM).
}
\details{
An mmkin row object is essentially a list of mkinfit objects that have been
obtained by fitting the same model to a list of datasets using \link{mkinfit}.
}
\examples{
ds <- lapply(experimental_data_for_UBA_2019[6:10],
 function(x) subset(x$data[c("name", "time", "value")]))
names(ds) <- paste("Dataset", 6:10)
f_mmkin_parent <- mmkin(c("SFO", "FOMC", "DFOP", "HS"), ds, quiet = TRUE, cores = 1)
f_mmkin_parent_tc <- mmkin(c("SFO", "FOMC", "DFOP"), ds, error_model = "tc",
  cores = 1, quiet = TRUE)

f_nlmixr_sfo_saem <- nlmixr(f_mmkin_parent["SFO", ], est = "saem")
f_nlmixr_sfo_focei <- nlmixr(f_mmkin_parent["SFO", ], est = "focei")

f_nlmixr_fomc_saem <- nlmixr(f_mmkin_parent["FOMC", ], est = "saem")
f_nlmixr_fomc_focei <- nlmixr(f_mmkin_parent["FOMC", ], est = "focei")

f_nlmixr_dfop_saem <- nlmixr(f_mmkin_parent["DFOP", ], est = "saem")
f_nlmixr_dfop_focei <- nlmixr(f_mmkin_parent["DFOP", ], est = "focei")

f_nlmixr_hs_saem <- nlmixr(f_mmkin_parent["HS", ], est = "saem")
f_nlmixr_hs_focei <- nlmixr(f_mmkin_parent["HS", ], est = "focei")

f_nlmixr_fomc_saem_tc <- nlmixr(f_mmkin_parent_tc["FOMC", ], est = "saem")
f_nlmixr_fomc_focei_tc <- nlmixr(f_mmkin_parent_tc["FOMC", ], est = "focei")

AIC(
  f_nlmixr_sfo_saem$nm, f_nlmixr_sfo_focei$nm,
  f_nlmixr_fomc_saem$nm, f_nlmixr_fomc_focei$nm,
  f_nlmixr_dfop_saem$nm, f_nlmixr_dfop_focei$nm,
  f_nlmixr_hs_saem$nm, f_nlmixr_hs_focei$nm,
  f_nlmixr_fomc_saem_tc$nm, f_nlmixr_fomc_focei_tc$nm)

AIC(nlme(f_mmkin_parent["FOMC", ]))
AIC(nlme(f_mmkin_parent["HS", ]))

# nlme is comparable to nlmixr with focei, saem finds a better
# solution, the two-component error model does not improve it
plot(f_nlmixr_fomc_saem)

\dontrun{
sfo_sfo <- mkinmod(parent = mkinsub("SFO", "A1"),
  A1 = mkinsub("SFO"))
fomc_sfo <- mkinmod(parent = mkinsub("FOMC", "A1"),
  A1 = mkinsub("SFO"))
dfop_sfo <- mkinmod(parent = mkinsub("DFOP", "A1"),
  A1 = mkinsub("SFO"))

f_mmkin_const <- mmkin(list(
    "SFO-SFO" = sfo_sfo, "FOMC-SFO" = fomc_sfo, "DFOP-SFO" = dfop_sfo),
  ds, quiet = TRUE, error_model = "const")
f_mmkin_obs <- mmkin(list(
    "SFO-SFO" = sfo_sfo, "FOMC-SFO" = fomc_sfo, "DFOP-SFO" = dfop_sfo),
  ds, quiet = TRUE, error_model = "obs")
f_mmkin_tc <- mmkin(list(
    "SFO-SFO" = sfo_sfo, "FOMC-SFO" = fomc_sfo, "DFOP-SFO" = dfop_sfo),
  ds, quiet = TRUE, error_model = "tc")

# A single constant variance is currently only possible with est = 'focei' in nlmixr
f_nlmixr_sfo_sfo_focei_const <- nlmixr(f_mmkin_const["SFO-SFO", ], est = "focei")
f_nlmixr_fomc_sfo_focei_const <- nlmixr(f_mmkin_const["FOMC-SFO", ], est = "focei")
f_nlmixr_dfop_sfo_focei_const <- nlmixr(f_mmkin_const["DFOP-SFO", ], est = "focei")

# Variance by variable is supported by 'saem' and 'focei'
f_nlmixr_fomc_sfo_saem_obs <- nlmixr(f_mmkin_obs["FOMC-SFO", ], est = "saem")
f_nlmixr_fomc_sfo_focei_obs <- nlmixr(f_mmkin_obs["FOMC-SFO", ], est = "focei")
f_nlmixr_dfop_sfo_saem_obs <- nlmixr(f_mmkin_obs["DFOP-SFO", ], est = "saem")
f_nlmixr_dfop_sfo_focei_obs <- nlmixr(f_mmkin_obs["DFOP-SFO", ], est = "focei")

# Identical two-component error for all variables is only possible with
# est = 'focei' in nlmixr
f_nlmixr_fomc_sfo_focei_tc <- nlmixr(f_mmkin_tc["FOMC-SFO", ], est = "focei")
f_nlmixr_dfop_sfo_focei_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "focei")

# Two-component error by variable is possible with both estimation methods
# Variance by variable is supported by 'saem' and 'focei'
f_nlmixr_fomc_sfo_saem_obs_tc <- nlmixr(f_mmkin_tc["FOMC-SFO", ], est = "saem",
  error_model = "obs_tc")
f_nlmixr_fomc_sfo_focei_obs_tc <- nlmixr(f_mmkin_tc["FOMC-SFO", ], est = "focei",
  error_model = "obs_tc")
f_nlmixr_dfop_sfo_saem_obs_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "saem",
  error_model = "obs_tc")
f_nlmixr_dfop_sfo_focei_obs_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "focei",
  error_model = "obs_tc")

AIC(
  f_nlmixr_sfo_sfo_focei_const$nm,
  f_nlmixr_fomc_sfo_focei_const$nm,
  f_nlmixr_dfop_sfo_focei_const$nm,
  f_nlmixr_fomc_sfo_saem_obs$nm,
  f_nlmixr_fomc_sfo_focei_obs$nm,
  f_nlmixr_dfop_sfo_saem_obs$nm,
  f_nlmixr_dfop_sfo_focei_obs$nm,
  f_nlmixr_fomc_sfo_focei_tc$nm,
  f_nlmixr_dfop_sfo_focei_tc$nm,
  f_nlmixr_fomc_sfo_saem_obs_tc$nm,
  f_nlmixr_fomc_sfo_focei_obs_tc$nm,
  f_nlmixr_dfop_sfo_saem_obs_tc$nm,
  f_nlmixr_dfop_sfo_focei_obs_tc$nm
)
# Currently, FOMC-SFO with two-component error by variable fitted by focei gives the
# lowest AIC
plot(f_nlmixr_fomc_sfo_focei_obs_tc)
summary(f_nlmixr_fomc_sfo_focei_obs_tc)
}
}
\seealso{
\link{summary.nlmixr.mmkin} \link{plot.mixed.mmkin}
}