Remove nlmixr interface for release of mkin 1.1.0

I am postponing my attempts to get the nlmixr interface to CRAN, given
some problems with nlmixr using R-devel under Windows, see
https://github.com/nlmixrdevelopment/nlmixr/issues/596
and
https://github.com/r-hub/rhub/issues/512,
which is fixed by the removal of nlmixr from the testsuite.

For the tests to be more platform independent, the biphasic mixed
effects models test dataset was defined in a way that fitting
should be more robust (less ill-defined).

6 files changed, 3 insertions, 426 deletions

diff --git a/man/endpoints.Rd b/man/endpoints.Rd
index a37ff98d..75fa9503 100644
--- a/man/endpoints.Rd
+++ b/man/endpoints.Rd
@@ -8,8 +8,8 @@ with mkinfit}
 endpoints(fit)
 }
 \arguments{
-\item{fit}{An object of class \link{mkinfit}, \link{nlme.mmkin}, \link{saem.mmkin} or
-\link{nlmixr.mmkin}. Or another object that has list components
+\item{fit}{An object of class \link{mkinfit}, \link{nlme.mmkin} or \link{saem.mmkin},
+or another object that has list components
 mkinmod containing an \link{mkinmod} degradation model, and two numeric vectors,
 bparms.optim and bparms.fixed, that contain parameter values
 for that model.}
diff --git a/man/intervals.nlmixr.mmkin.Rd b/man/intervals.nlmixr.mmkin.Rd
deleted file mode 100644
index e6da8901..00000000
--- a/man/intervals.nlmixr.mmkin.Rd
+++ /dev/null
@@ -1,25 +0,0 @@
-% Generated by roxygen2: do not edit by hand
-% Please edit documentation in R/intervals.R
-\name{intervals.nlmixr.mmkin}
-\alias{intervals.nlmixr.mmkin}
-\title{Confidence intervals for parameters in nlmixr.mmkin objects}
-\usage{
-\method{intervals}{nlmixr.mmkin}(object, level = 0.95, backtransform = TRUE, ...)
-}
-\arguments{
-\item{object}{The fitted saem.mmkin object}
-
-\item{level}{The confidence level.}
-
-\item{backtransform}{Should we backtransform the parameters where a one to
-one correlation between transformed and backtransformed parameters exists?}
-
-\item{\dots}{For compatibility with the generic method}
-}
-\value{
-An object with 'intervals.saem.mmkin' and 'intervals.lme' in the
-class attribute
-}
-\description{
-Confidence intervals for parameters in nlmixr.mmkin objects
-}
diff --git a/man/nlmixr.mmkin.Rd b/man/nlmixr.mmkin.Rd
deleted file mode 100644
index c1a203eb..00000000
--- a/man/nlmixr.mmkin.Rd
+++ /dev/null
@@ -1,245 +0,0 @@
-% 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]]$err_mod,
-  test_log_parms = TRUE,
-  conf.level = 0.6,
-  degparms_start = "auto",
-  eta_start = "auto",
-  ...,
-  save = NULL,
-  envir = parent.frame()
-)
-
-\method{print}{nlmixr.mmkin}(x, digits = max(3, getOption("digits") - 3), ...)
-
-nlmixr_model(
-  object,
-  est = c("saem", "focei"),
-  degparms_start = "auto",
-  eta_start = "auto",
-  test_log_parms = TRUE,
-  conf.level = 0.6,
-  error_model = object[[1]]$err_mod,
-  add_attributes = FALSE
-)
-
-nlmixr_data(object, ...)
-}
-\arguments{
-\item{object}{An \link{mmkin} row object containing several fits of the same
-\link{mkinmod} model to different datasets}
-
-\item{data}{Not used, as the data are extracted from the mmkin row object}
-
-\item{est}{Estimation method passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}}
-
-\item{control}{Passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}}
-
-\item{table}{Passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}}
-
-\item{error_model}{Optional argument to override the error model which is
-being set based on the error model used in the mmkin row object.}
-
-\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{degparms_start}{Parameter values given as a named numeric vector will
-be used to override the starting values obtained from the 'mmkin' object.}
-
-\item{eta_start}{Standard deviations on the transformed scale given as a
-named numeric vector will be used to override the starting values obtained
-from the 'mmkin' object.}
-
-\item{\dots}{Passed to \link{nlmixr_model}}
-
-\item{save}{Passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}}
-
-\item{envir}{Passed to \link[nlmixr:nlmixr]{nlmixr::nlmixr}}
-
-\item{x}{An nlmixr.mmkin object to print}
-
-\item{digits}{Number of digits to use for printing}
-
-\item{add_attributes}{Should the starting values used for degradation model
-parameters and their distribution and for the error model parameters
-be returned as attributes?}
-}
-\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) or First Order Conditional
-Estimation with Interaction (FOCEI).
-}
-\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{
-\dontrun{
-ds <- lapply(experimental_data_for_UBA_2019[6:10],
- function(x) subset(x$data[c("name", "time", "value")]))
-names(ds) <- paste("Dataset", 6:10)
-
-f_mmkin_parent <- mmkin(c("SFO", "FOMC", "DFOP", "HS"), ds, quiet = TRUE, cores = 1)
-f_mmkin_parent_tc <- mmkin(c("SFO", "FOMC", "DFOP"), ds, error_model = "tc",
-  cores = 1, quiet = TRUE)
-
-library(nlmixr)
-f_nlmixr_sfo_saem <- nlmixr(f_mmkin_parent["SFO", ], est = "saem",
-  control = saemControl(print = 0))
-f_nlmixr_sfo_focei <- nlmixr(f_mmkin_parent["SFO", ], est = "focei",
-  control = foceiControl(print = 0))
-
-f_nlmixr_fomc_saem <- nlmixr(f_mmkin_parent["FOMC", ], est = "saem",
-  control = saemControl(print = 0))
-f_nlmixr_fomc_focei <- nlmixr(f_mmkin_parent["FOMC", ], est = "focei",
-  control = foceiControl(print = 0))
-
-f_nlmixr_dfop_saem <- nlmixr(f_mmkin_parent["DFOP", ], est = "saem",
-  control = saemControl(print = 0))
-f_nlmixr_dfop_focei <- nlmixr(f_mmkin_parent["DFOP", ], est = "focei",
-  control = foceiControl(print = 0))
-
-f_nlmixr_hs_saem <- nlmixr(f_mmkin_parent["HS", ], est = "saem",
-  control = saemControl(print = 0))
-f_nlmixr_hs_focei <- nlmixr(f_mmkin_parent["HS", ], est = "focei",
-  control = foceiControl(print = 0))
-
-f_nlmixr_fomc_saem_tc <- nlmixr(f_mmkin_parent_tc["FOMC", ], est = "saem",
-  control = saemControl(print = 0))
-f_nlmixr_fomc_focei_tc <- nlmixr(f_mmkin_parent_tc["FOMC", ], est = "focei",
-  control = foceiControl(print = 0))
-
-AIC(
-  f_nlmixr_sfo_saem$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", ]))
-
-# The FOCEI fit of FOMC with constant variance or the tc error model is best
-plot(f_nlmixr_fomc_saem_tc)
-
-sfo_sfo <- mkinmod(parent = mkinsub("SFO", "A1"),
-  A1 = mkinsub("SFO"), quiet = TRUE)
-fomc_sfo <- mkinmod(parent = mkinsub("FOMC", "A1"),
-  A1 = mkinsub("SFO"), quiet = TRUE)
-dfop_sfo <- mkinmod(parent = mkinsub("DFOP", "A1"),
-  A1 = mkinsub("SFO"), quiet = TRUE)
-
-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")
-
-nlmixr_model(f_mmkin_const["SFO-SFO", ])
-
-# 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)
-
-# Two parallel metabolites
-dmta_ds <- lapply(1:7, function(i) {
-  ds_i <- dimethenamid_2018$ds[[i]]$data
-  ds_i[ds_i$name == "DMTAP", "name"] <-  "DMTA"
-  ds_i$time <- ds_i$time * dimethenamid_2018$f_time_norm[i]
-  ds_i
-})
-names(dmta_ds) <- sapply(dimethenamid_2018$ds, function(ds) ds$title)
-dmta_ds[["Elliot"]] <- rbind(dmta_ds[["Elliot 1"]], dmta_ds[["Elliot 2"]])
-dmta_ds[["Elliot 1"]] <- NULL
-dmta_ds[["Elliot 2"]] <- NULL
-sfo_sfo2 <- mkinmod(
-  DMTA = mkinsub("SFO", c("M23", "M27")),
-  M23 = mkinsub("SFO"),
-  M27 = mkinsub("SFO"),
-  quiet = TRUE
-)
-f_dmta_sfo_sfo2 <- mmkin(
-  list("SFO-SFO2" = sfo_sfo2),
-  dmta_ds, quiet = TRUE, error_model = "obs")
-nlmixr_model(f_dmta_sfo_sfo2)
-nlmixr_focei_dmta_sfo_sfo2 <- nlmixr(f_dmta_sfo_sfo2, est = "focei")
-}
-}
-\seealso{
-\link{summary.nlmixr.mmkin} \link{plot.mixed.mmkin}
-}
diff --git a/man/reexports.Rd b/man/reexports.Rd
index dfbb76a7..43d27ac1 100644
--- a/man/reexports.Rd
+++ b/man/reexports.Rd
@@ -1,13 +1,11 @@
 % Generated by roxygen2: do not edit by hand
-% Please edit documentation in R/intervals.R, R/lrtest.mkinfit.R,
-%   R/nlme.mmkin.R, R/nlmixr.R
+% Please edit documentation in R/intervals.R, R/lrtest.mkinfit.R, R/nlme.mmkin.R
 \docType{import}
 \name{reexports}
 \alias{reexports}
 \alias{intervals}
 \alias{lrtest}
 \alias{nlme}
-\alias{nlmixr}
 \title{Objects exported from other packages}
 \keyword{internal}
 \description{
@@ -18,7 +16,5 @@ below to see their documentation.
   \item{lmtest}{\code{\link[lmtest]{lrtest}}}
 
   \item{nlme}{\code{\link[nlme]{intervals}}, \code{\link[nlme]{nlme}}}
-
-  \item{nlmixr}{\code{\link[nlmixr]{nlmixr}}}
 }}
 
diff --git a/man/summary.nlmixr.mmkin.Rd b/man/summary.nlmixr.mmkin.Rd
deleted file mode 100644
index ab8abd5d..00000000
--- a/man/summary.nlmixr.mmkin.Rd
+++ /dev/null
@@ -1,103 +0,0 @@
-% Generated by roxygen2: do not edit by hand
-% Please edit documentation in R/summary.nlmixr.mmkin.R
-\name{summary.nlmixr.mmkin}
-\alias{summary.nlmixr.mmkin}
-\alias{print.summary.nlmixr.mmkin}
-\title{Summary method for class "nlmixr.mmkin"}
-\usage{
-\method{summary}{nlmixr.mmkin}(object, data = FALSE, verbose = FALSE, distimes = TRUE, ...)
-
-\method{print}{summary.nlmixr.mmkin}(x, digits = max(3, getOption("digits") - 3), verbose = x$verbose, ...)
-}
-\arguments{
-\item{object}{an object of class \link{nlmixr.mmkin}}
-
-\item{data}{logical, indicating whether the full data should be included in
-the summary.}
-
-\item{verbose}{Should the summary be verbose?}
-
-\item{distimes}{logical, indicating whether DT50 and DT90 values should be
-included.}
-
-\item{\dots}{optional arguments passed to methods like \code{print}.}
-
-\item{x}{an object of class \link{summary.nlmixr.mmkin}}
-
-\item{digits}{Number of digits to use for printing}
-}
-\value{
-The summary function returns a list obtained in the fit, with at
-least the following additional components
-\item{nlmixrversion, mkinversion, Rversion}{The nlmixr, mkin and R versions used}
-\item{date.fit, date.summary}{The dates where the fit and the summary were
-produced}
-\item{diffs}{The differential equations used in the degradation model}
-\item{use_of_ff}{Was maximum or minimum use made of formation fractions}
-\item{data}{The data}
-\item{confint_back}{Backtransformed parameters, with confidence intervals if available}
-\item{ff}{The estimated formation fractions derived from the fitted
-model.}
-\item{distimes}{The DT50 and DT90 values for each observed variable.}
-\item{SFORB}{If applicable, eigenvalues of SFORB components of the model.}
-The print method is called for its side effect, i.e. printing the summary.
-}
-\description{
-Lists model equations, initial parameter values, optimised parameters
-for fixed effects (population), random effects (deviations from the
-population mean) and residual error model, as well as the resulting
-endpoints such as formation fractions and DT50 values. Optionally
-(default is FALSE), the data are listed in full.
-}
-\examples{
-# Generate five datasets following DFOP-SFO kinetics
-sampling_times = c(0, 1, 3, 7, 14, 28, 60, 90, 120)
-dfop_sfo <- mkinmod(parent = mkinsub("DFOP", "m1"),
- m1 = mkinsub("SFO"), quiet = TRUE)
-set.seed(1234)
-k1_in <- rlnorm(5, log(0.1), 0.3)
-k2_in <- rlnorm(5, log(0.02), 0.3)
-g_in <- plogis(rnorm(5, qlogis(0.5), 0.3))
-f_parent_to_m1_in <- plogis(rnorm(5, qlogis(0.3), 0.3))
-k_m1_in <- rlnorm(5, log(0.02), 0.3)
-
-pred_dfop_sfo <- function(k1, k2, g, f_parent_to_m1, k_m1) {
-  mkinpredict(dfop_sfo,
-    c(k1 = k1, k2 = k2, g = g, f_parent_to_m1 = f_parent_to_m1, k_m1 = k_m1),
-    c(parent = 100, m1 = 0),
-    sampling_times)
-}
-
-ds_mean_dfop_sfo <- lapply(1:5, function(i) {
-  mkinpredict(dfop_sfo,
-    c(k1 = k1_in[i], k2 = k2_in[i], g = g_in[i],
-      f_parent_to_m1 = f_parent_to_m1_in[i], k_m1 = k_m1_in[i]),
-    c(parent = 100, m1 = 0),
-    sampling_times)
-})
-names(ds_mean_dfop_sfo) <- paste("ds", 1:5)
-
-ds_syn_dfop_sfo <- lapply(ds_mean_dfop_sfo, function(ds) {
-  add_err(ds,
-    sdfunc = function(value) sqrt(1^2 + value^2 * 0.07^2),
-    n = 1)[[1]]
-})
-
-\dontrun{
-# Evaluate using mmkin and nlmixr
-f_mmkin_dfop_sfo <- mmkin(list(dfop_sfo), ds_syn_dfop_sfo,
-  quiet = TRUE, error_model = "tc", cores = 5)
-f_saemix_dfop_sfo <- mkin::saem(f_mmkin_dfop_sfo)
-f_nlme_dfop_sfo <- mkin::nlme(f_mmkin_dfop_sfo)
-f_nlmixr_dfop_sfo_saem <- nlmixr(f_mmkin_dfop_sfo, est = "saem")
-# The following takes a very long time but gives
-f_nlmixr_dfop_sfo_focei <- nlmixr(f_mmkin_dfop_sfo, est = "focei")
-AIC(f_nlmixr_dfop_sfo_saem$nm, f_nlmixr_dfop_sfo_focei$nm)
-summary(f_nlmixr_dfop_sfo_sfo, data = TRUE)
-}
-
-}
-\author{
-Johannes Ranke for the mkin specific parts
-nlmixr authors for the parts inherited from nlmixr.
-}
diff --git a/man/tffm0.Rd b/man/tffm0.Rd
deleted file mode 100644
index 89bee7d9..00000000
--- a/man/tffm0.Rd
+++ /dev/null
@@ -1,46 +0,0 @@
-% Generated by roxygen2: do not edit by hand
-% Please edit documentation in R/tffm0.R
-\name{tffm0}
-\alias{tffm0}
-\alias{invtffm0}
-\title{Transform formation fractions as in the first published mkin version}
-\usage{
-tffm0(ff)
-
-invtffm0(ff_trans)
-}
-\arguments{
-\item{ff}{Vector of untransformed formation fractions. The sum
-must be smaller or equal to one}
-
-\item{ff_trans}{Vector of transformed formation fractions that can be
-restricted to the interval from 0 to 1}
-}
-\value{
-A vector of the transformed formation fractions
-
-A vector of backtransformed formation fractions for natural use in degradation models
-}
-\description{
-This transformation was used originally in mkin, in order to implement a
-constraint for the sum of formation fractions to be smaller than 1.  It was
-later replaced by the \link{ilr} transformation because the ilr transformed
-fractions can assumed to follow normal distribution. As the ilr
-transformation is not available in \link{RxODE} and can therefore not be used in
-the nlmixr modelling language, the original transformation is currently used
-for translating mkin models with formation fractions to more than one target
-compartment for fitting with nlmixr in \link{nlmixr_model}. However, this
-implementation cannot be used there, as it is not accessible from RxODE.
-}
-\details{
-If the transformed formation fractions are restricted to the interval
-between 0 and 1, the sum of backtransformed values is restricted
-to this interval.
-}
-\examples{
-ff_example <- c(
-  0.10983681, 0.09035905, 0.08399383
-)
-ff_example_trans <- tffm0(ff_example)
-invtffm0(ff_example_trans)
-}