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-rw-r--r--NAMESPACE2
-rw-r--r--R/dimethenamid_2018.R14
-rw-r--r--R/summary.nlmixr.mmkin.R14
-rw-r--r--R/tffm0.R6
-rw-r--r--R/transform_odeparms.R13
-rw-r--r--check.log11
-rw-r--r--man/dimethenamid_2018.Rd36
-rw-r--r--man/nlmixr.mmkin.Rd15
-rw-r--r--man/tffm0.Rd42
-rw-r--r--test.log45
-rw-r--r--tests/testthat/test_nlmixr.r194
11 files changed, 243 insertions, 149 deletions
diff --git a/NAMESPACE b/NAMESPACE
index 0f61396d..aa40b570 100644
--- a/NAMESPACE
+++ b/NAMESPACE
@@ -62,6 +62,7 @@ export(f_time_norm_focus)
export(get_deg_func)
export(ilr)
export(invilr)
+export(invtffm0)
export(loftest)
export(logistic.solution)
export(lrtest)
@@ -101,6 +102,7 @@ export(saem)
export(saemix_data)
export(saemix_model)
export(sigma_twocomp)
+export(tffm0)
export(transform_odeparms)
import(deSolve)
import(graphics)
diff --git a/R/dimethenamid_2018.R b/R/dimethenamid_2018.R
index 76b98efe..6e0bda0c 100644
--- a/R/dimethenamid_2018.R
+++ b/R/dimethenamid_2018.R
@@ -31,6 +31,7 @@
#' dmta_ds[["Elliot"]] <- rbind(dmta_ds[["Elliot 1"]], dmta_ds[["Elliot 2"]])
#' dmta_ds[["Elliot 1"]] <- NULL
#' dmta_ds[["Elliot 2"]] <- NULL
+#' \dontrun{
#' dfop_sfo3_plus <- mkinmod(
#' DMTA = mkinsub("DFOP", c("M23", "M27", "M31")),
#' M23 = mkinsub("SFO"),
@@ -42,12 +43,15 @@
#' list("DFOP-SFO3+" = dfop_sfo3_plus),
#' dmta_ds, quiet = TRUE, error_model = "tc")
#' nlmixr_model(f_dmta_mkin_tc)
-#' f_dmta_nlmixr_saem <- nlmixr(f_dmta_mkin_tc, est = "saem",
-#' control = saemControl(print = 500))
-#' summary(f_dmta_nlmixr_saem)
-#' plot(f_dmta_nlmixr_saem)
#' f_dmta_nlmixr_focei <- nlmixr(f_dmta_mkin_tc, est = "focei",
-#' control = foceiControl(print = 500))
+#' control = nlmixr::foceiControl(print = 500))
#' summary(f_dmta_nlmixr_focei)
#' plot(f_dmta_nlmixr_focei)
+#' # saem has a problem with this model/data combination, maybe because of the
+#' # overparameterised error model, to be investigated
+#' #f_dmta_nlmixr_saem <- nlmixr(f_dmta_mkin_tc, est = "saem",
+#' # control = saemControl(print = 500))
+#' #summary(f_dmta_nlmixr_saem)
+#' #plot(f_dmta_nlmixr_saem)
+#' }
"dimethenamid_2018"
diff --git a/R/summary.nlmixr.mmkin.R b/R/summary.nlmixr.mmkin.R
index f2d7c607..a023f319 100644
--- a/R/summary.nlmixr.mmkin.R
+++ b/R/summary.nlmixr.mmkin.R
@@ -85,11 +85,11 @@ summary.nlmixr.mmkin <- function(object, data = FALSE, verbose = FALSE, distimes
mod_vars <- names(object$mkinmod$diffs)
- pnames <- names(object$mean_dp_start)
- np <- length(pnames)
-
conf.int <- confint(object$nm)
- confint_trans <- as.matrix(conf.int[pnames, c(1, 3, 4)])
+ dpnames <- setdiff(rownames(conf.int), names(object$mean_ep_start))
+ ndp <- length(dpnames)
+
+ confint_trans <- as.matrix(conf.int[dpnames, c(1, 3, 4)])
colnames(confint_trans) <- c("est.", "lower", "upper")
bp <- backtransform_odeparms(confint_trans[, "est."], object$mkinmod,
@@ -100,7 +100,7 @@ summary.nlmixr.mmkin <- function(object, data = FALSE, verbose = FALSE, distimes
# with the exception of sets of formation fractions (single fractions are OK).
f_names_skip <- character(0)
for (box in mod_vars) { # Figure out sets of fractions to skip
- f_names <- grep(paste("^f", box, sep = "_"), pnames, value = TRUE)
+ f_names <- grep(paste("^f", box, sep = "_"), dpnames, value = TRUE)
n_paths <- length(f_names)
if (n_paths > 1) f_names_skip <- c(f_names_skip, f_names)
}
@@ -109,7 +109,7 @@ summary.nlmixr.mmkin <- function(object, data = FALSE, verbose = FALSE, distimes
dimnames = list(bpnames, colnames(confint_trans)))
confint_back[, "est."] <- bp
- for (pname in pnames) {
+ for (pname in dpnames) {
if (!pname %in% f_names_skip) {
par.lower <- confint_trans[pname, "lower"]
par.upper <- confint_trans[pname, "upper"]
@@ -131,7 +131,7 @@ summary.nlmixr.mmkin <- function(object, data = FALSE, verbose = FALSE, distimes
object$corFixed <- array(
t(varFix/stdFix)/stdFix,
dim(varFix),
- list(pnames, pnames))
+ list(dpnames, dpnames))
object$confint_trans <- confint_trans
object$confint_back <- confint_back
diff --git a/R/tffm0.R b/R/tffm0.R
index 25787962..bb5f4cf5 100644
--- a/R/tffm0.R
+++ b/R/tffm0.R
@@ -13,7 +13,8 @@
#'
#' @param ff Vector of untransformed formation fractions. The sum
#' must be smaller or equal to one
-#' @param ff_trans
+#' @param ff_trans Vector of transformed formation fractions that can be
+#' restricted to the interval from 0 to 1
#' @return A vector of the transformed formation fractions
#' @export
#' @examples
@@ -33,7 +34,8 @@ tffm0 <- function(ff) {
return(res)
}
#' @rdname tffm0
-#' @return
+#' @export
+#' @return A vector of backtransformed formation fractions for natural use in degradation models
invtffm0 <- function(ff_trans) {
n <- length(ff_trans)
res <- numeric(n)
diff --git a/R/transform_odeparms.R b/R/transform_odeparms.R
index 4fe4e5c2..174e7c2d 100644
--- a/R/transform_odeparms.R
+++ b/R/transform_odeparms.R
@@ -229,13 +229,18 @@ backtransform_odeparms <- function(transparms, mkinmod,
if (length(trans_f) > 0) {
if(transform_fractions) {
if (any(grepl("qlogis", names(trans_f)))) {
- parms[f_names] <- plogis(trans_f)
+ f_tmp <- plogis(trans_f)
+ if (any(grepl("_tffm0_.*_qlogis$", names(f_tmp)))) {
+ parms[f_names] <- invtffm0(f_tmp)
+ } else {
+ parms[f_names] <- f_tmp
+ }
} else {
- f <- invilr(trans_f)
+ f_tmp <- invilr(trans_f)
if (spec[[box]]$sink) {
- parms[f_names] <- f[1:length(f)-1]
+ parms[f_names] <- f_tmp[1:length(f_tmp)-1]
} else {
- parms[f_names] <- f
+ parms[f_names] <- f_tmp
}
}
} else {
diff --git a/check.log b/check.log
index 2627695d..df344926 100644
--- a/check.log
+++ b/check.log
@@ -57,10 +57,7 @@ Maintainer: ‘Johannes Ranke <jranke@uni-bremen.de>’
* checking data for ASCII and uncompressed saves ... OK
* checking installed files from ‘inst/doc’ ... OK
* checking files in ‘vignettes’ ... OK
-* checking examples ... NOTE
-Examples with CPU (user + system) or elapsed time > 5s
- user system elapsed
-nlmixr.mmkin 8.129 0.375 5.384
+* checking examples ... OK
* checking for unstated dependencies in ‘tests’ ... OK
* checking tests ... SKIPPED
* checking for unstated dependencies in vignettes ... OK
@@ -71,9 +68,5 @@ nlmixr.mmkin 8.129 0.375 5.384
* checking for detritus in the temp directory ... OK
* DONE
-Status: 1 NOTE
-See
- ‘/home/jranke/git/mkin/mkin.Rcheck/00check.log’
-for details.
-
+Status: OK
diff --git a/man/dimethenamid_2018.Rd b/man/dimethenamid_2018.Rd
index b6f761e8..93fcad26 100644
--- a/man/dimethenamid_2018.Rd
+++ b/man/dimethenamid_2018.Rd
@@ -31,5 +31,41 @@ specific pieces of information in the comments.
}
\examples{
print(dimethenamid_2018)
+dmta_ds <- lapply(1:8, function(i) {
+ ds_i <- dimethenamid_2018$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$title)
+dmta_ds[["Borstel"]] <- rbind(dmta_ds[["Borstel 1"]], dmta_ds[["Borstel 2"]])
+dmta_ds[["Borstel 1"]] <- NULL
+dmta_ds[["Borstel 2"]] <- NULL
+dmta_ds[["Elliot"]] <- rbind(dmta_ds[["Elliot 1"]], dmta_ds[["Elliot 2"]])
+dmta_ds[["Elliot 1"]] <- NULL
+dmta_ds[["Elliot 2"]] <- NULL
+\dontrun{
+dfop_sfo3_plus <- mkinmod(
+ DMTA = mkinsub("DFOP", c("M23", "M27", "M31")),
+ M23 = mkinsub("SFO"),
+ M27 = mkinsub("SFO"),
+ M31 = mkinsub("SFO", "M27", sink = FALSE),
+ quiet = TRUE
+)
+f_dmta_mkin_tc <- mmkin(
+ list("DFOP-SFO3+" = dfop_sfo3_plus),
+ dmta_ds, quiet = TRUE, error_model = "tc")
+nlmixr_model(f_dmta_mkin_tc)
+f_dmta_nlmixr_focei <- nlmixr(f_dmta_mkin_tc, est = "focei",
+ control = nlmixr::foceiControl(print = 500))
+summary(f_dmta_nlmixr_focei)
+plot(f_dmta_nlmixr_focei)
+# saem has a problem with this model/data combination, maybe because of the
+# overparameterised error model, to be investigated
+#f_dmta_nlmixr_saem <- nlmixr(f_dmta_mkin_tc, est = "saem",
+# control = saemControl(print = 500))
+#summary(f_dmta_nlmixr_saem)
+#plot(f_dmta_nlmixr_saem)
+}
}
\keyword{datasets}
diff --git a/man/nlmixr.mmkin.Rd b/man/nlmixr.mmkin.Rd
index 4ab30272..0f4f41a2 100644
--- a/man/nlmixr.mmkin.Rd
+++ b/man/nlmixr.mmkin.Rd
@@ -16,6 +16,8 @@
error_model = object[[1]]$err_mod,
test_log_parms = TRUE,
conf.level = 0.6,
+ degparms_start = "auto",
+ eta_start = "auto",
...,
save = NULL,
envir = parent.frame()
@@ -27,7 +29,8 @@ nlmixr_model(
object,
est = c("saem", "focei"),
degparms_start = "auto",
- test_log_parms = FALSE,
+ eta_start = "auto",
+ test_log_parms = TRUE,
conf.level = 0.6,
error_model = object[[1]]$err_mod,
add_attributes = FALSE
@@ -58,6 +61,13 @@ 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}}
@@ -68,9 +78,6 @@ for parameter that are tested if requested by 'test_log_parms'.}
\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{add_attributes}{Should the starting values used for degradation model
parameters and their distribution and for the error model parameters
be returned as attributes?}
diff --git a/man/tffm0.Rd b/man/tffm0.Rd
new file mode 100644
index 00000000..46978d5e
--- /dev/null
+++ b/man/tffm0.Rd
@@ -0,0 +1,42 @@
+% 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{
+The transformed fractions can be restricted between 0 and 1 in model
+optimisations. Therefore this transformation was used originally in mkin. 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, this 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.
+}
+\examples{
+ff_example <- c(
+ 0.10983681, 0.09035905, 0.08399383
+)
+ff_example_trans <- tffm0(ff_example)
+invtffm0(ff_example_trans)
+}
diff --git a/test.log b/test.log
index f2a60729..6ef8191f 100644
--- a/test.log
+++ b/test.log
@@ -3,17 +3,17 @@ Loading required package: parallel
ℹ Testing mkin
✔ | OK F W S | Context
✔ | 5 | AIC calculation
-✔ | 5 | Analytical solutions for coupled models [3.3 s]
+✔ | 5 | Analytical solutions for coupled models [3.5 s]
✔ | 5 | Calculation of Akaike weights
✔ | 2 | Export dataset for reading into CAKE
-✔ | 12 | Confidence intervals and p-values [1.3 s]
+✔ | 12 | Confidence intervals and p-values [1.0 s]
✔ | 14 | Error model fitting [4.7 s]
✔ | 5 | Time step normalisation
-✔ | 4 | Calculation of FOCUS chi2 error levels [0.5 s]
+✔ | 4 | Calculation of FOCUS chi2 error levels [0.6 s]
✔ | 14 | Results for FOCUS D established in expertise for UBA (Ranke 2014) [0.8 s]
✔ | 4 | Test fitting the decline of metabolites from their maximum [0.3 s]
✔ | 1 | Fitting the logistic model [0.2 s]
-✔ | 35 1 | Nonlinear mixed-effects models [27.1 s]
+✔ | 35 1 | Nonlinear mixed-effects models [26.9 s]
────────────────────────────────────────────────────────────────────────────────
Skip (test_mixed.R:161:3): saem results are reproducible for biphasic fits
Reason: Fitting with saemix takes around 10 minutes when using deSolve
@@ -21,33 +21,36 @@ Reason: Fitting with saemix takes around 10 minutes when using deSolve
✔ | 2 | Test dataset classes mkinds and mkindsg
✔ | 10 | Special cases of mkinfit calls [0.4 s]
✔ | 1 | mkinfit features [0.3 s]
-✔ | 8 | mkinmod model generation and printing [0.3 s]
+✔ | 8 | mkinmod model generation and printing [0.2 s]
✔ | 3 | Model predictions with mkinpredict [0.3 s]
-✔ | 16 | Evaluations according to 2015 NAFTA guidance [1.7 s]
-✔ | 9 | Nonlinear mixed-effects models with nlme [8.1 s]
-✖ | 14 2 | Plotting [1.9 s]
+✔ | 14 2 | Evaluations according to 2015 NAFTA guidance [1.3 s]
────────────────────────────────────────────────────────────────────────────────
-Failure (test_plot.R:40:5): Plotting mkinfit, mmkin and mixed model objects is reproducible
-Figures don't match: mixed-model-fit-for-saem-object-with-saemix-transformations.svg
-
-
-Failure (test_plot.R:55:5): Plotting mkinfit, mmkin and mixed model objects is reproducible
-Figures don't match: mixed-model-fit-for-saem-object-with-mkin-transformations.svg
+Skip (test_nafta.R:25:5): Test data from Appendix B are correctly evaluated
+Reason: getRversion() >= "4.1.0" is TRUE
+Skip (test_nafta.R:53:5): Test data from Appendix D are correctly evaluated
+Reason: getRversion() >= "4.1.0" is TRUE
+────────────────────────────────────────────────────────────────────────────────
+✔ | 9 | Nonlinear mixed-effects models with nlme [8.1 s]
+✔ | 0 1 | Plotting [0.8 s]
+────────────────────────────────────────────────────────────────────────────────
+Skip (test_plot.R:18:3): Plotting mkinfit, mmkin and mixed model objects is reproducible
+Reason: getRversion() >= "4.1.0" is TRUE
────────────────────────────────────────────────────────────────────────────────
✔ | 4 | Residuals extracted from mkinfit models
✔ | 2 | Complex test case from Schaefer et al. (2007) Piacenza paper [1.5 s]
-✔ | 7 | Fitting the SFORB model [3.9 s]
+✔ | 7 | Fitting the SFORB model [3.8 s]
✔ | 1 | Summaries of old mkinfit objects
✔ | 4 | Summary [0.1 s]
-✔ | 4 | Results for synthetic data established in expertise for UBA (Ranke 2014) [2.2 s]
-✔ | 9 | Hypothesis tests [8.2 s]
-✔ | 4 | Calculation of maximum time weighted average concentrations (TWAs) [2.4 s]
+✔ | 4 | Results for synthetic data established in expertise for UBA (Ranke 2014) [2.3 s]
+✔ | 9 | Hypothesis tests [8.5 s]
+✔ | 4 | Calculation of maximum time weighted average concentrations (TWAs) [2.2 s]
══ Results ═════════════════════════════════════════════════════════════════════
-Duration: 70.0 s
+Duration: 68.2 s
── Skipped tests ──────────────────────────────────────────────────────────────
-● Fitting with saemix takes around 10 minutes when using deSolve (1)
+• Fitting with saemix takes around 10 minutes when using deSolve (1)
+• getRversion() >= "4.1.0" is TRUE (3)
-[ FAIL 2 | WARN 0 | SKIP 1 | PASS 204 ]
+[ FAIL 0 | WARN 0 | SKIP 4 | PASS 188 ]
diff --git a/tests/testthat/test_nlmixr.r b/tests/testthat/test_nlmixr.r
index e3bd3d66..dcbb50ac 100644
--- a/tests/testthat/test_nlmixr.r
+++ b/tests/testthat/test_nlmixr.r
@@ -1,99 +1,99 @@
-dmta_ds <- lapply(1:8, 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[["Borstel"]] <- rbind(dmta_ds[["Borstel 1"]], dmta_ds[["Borstel 2"]])
-dmta_ds[["Borstel 1"]] <- NULL
-dmta_ds[["Borstel 2"]] <- NULL
-dmta_ds[["Elliot"]] <- rbind(dmta_ds[["Elliot 1"]], dmta_ds[["Elliot 2"]])
-dmta_ds[["Elliot 1"]] <- NULL
-dmta_ds[["Elliot 2"]] <- NULL
-dfop_sfo3_plus <- mkinmod(
- DMTA = mkinsub("DFOP", c("M23", "M27", "M31")),
- M23 = mkinsub("SFO"),
- M27 = mkinsub("SFO"),
- M31 = mkinsub("SFO", "M27", sink = FALSE),
- quiet = TRUE
-)
-f_dmta_mkin_tc <- mmkin(
- list("DFOP-SFO3+" = dfop_sfo3_plus),
- dmta_ds, quiet = TRUE, error_model = "tc")
-
-d_dmta_nlmixr <- nlmixr_data(f_dmta_mkin_tc)
-m_dmta_nlmixr <- function ()
-{
- ini({
- DMTA_0 = 98.7697627680706
- eta.DMTA_0 ~ 2.35171765917765
- log_k_M23 = -3.92162409637283
- eta.log_k_M23 ~ 0.549278519419884
- log_k_M27 = -4.33774620773911
- eta.log_k_M27 ~ 0.864474956685295
- log_k_M31 = -4.24767627688461
- eta.log_k_M31 ~ 0.750297149164171
- f_DMTA_tffm0_1_qlogis = -2.092409
- eta.f_DMTA_tffm0_1_qlogis ~ 0.3
- f_DMTA_tffm0_2_qlogis = -2.180576
- eta.f_DMTA_tffm0_2_qlogis ~ 0.3
- f_DMTA_tffm0_3_qlogis = -2.142672
- eta.f_DMTA_tffm0_3_qlogis ~ 0.3
- log_k1 = -2.2341008812259
- eta.log_k1 ~ 0.902976221565793
- log_k2 = -3.7762779983269
- eta.log_k2 ~ 1.57684519529298
- g_qlogis = 0.450175725479389
- eta.g_qlogis ~ 3.0851335687675
- sigma_low_DMTA = 0.697933852349996
- rsd_high_DMTA = 0.0257724286053519
- sigma_low_M23 = 0.697933852349996
- rsd_high_M23 = 0.0257724286053519
- sigma_low_M27 = 0.697933852349996
- rsd_high_M27 = 0.0257724286053519
- sigma_low_M31 = 0.697933852349996
- rsd_high_M31 = 0.0257724286053519
- })
- model({
- DMTA_0_model = DMTA_0 + eta.DMTA_0
- DMTA(0) = DMTA_0_model
- k_M23 = exp(log_k_M23 + eta.log_k_M23)
- k_M27 = exp(log_k_M27 + eta.log_k_M27)
- k_M31 = exp(log_k_M31 + eta.log_k_M31)
- k1 = exp(log_k1 + eta.log_k1)
- k2 = exp(log_k2 + eta.log_k2)
- g = expit(g_qlogis + eta.g_qlogis)
- f_DMTA_tffm0_1 = expit(f_DMTA_tffm0_1_qlogis + eta.f_DMTA_tffm0_1_qlogis)
- f_DMTA_tffm0_2 = expit(f_DMTA_tffm0_2_qlogis + eta.f_DMTA_tffm0_2_qlogis)
- f_DMTA_tffm0_3 = expit(f_DMTA_tffm0_3_qlogis + eta.f_DMTA_tffm0_3_qlogis)
- f_DMTA_to_M23 = f_DMTA_tffm0_1
- f_DMTA_to_M27 = (1 - f_DMTA_tffm0_1) * f_DMTA_tffm0_2
- f_DMTA_to_M31 = (1 - f_DMTA_tffm0_1) * (1 - f_DMTA_tffm0_2) * f_DMTA_tffm0_3
- d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 -
- g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 -
- g) * exp(-k2 * time))) * DMTA
- d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) +
- k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
- (1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23
- d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) +
- k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
- (1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 +
- k_M31 * M31
- d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) +
- k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
- (1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31
- DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA)
- M23 ~ add(sigma_low_M23) + prop(rsd_high_M23)
- M27 ~ add(sigma_low_M27) + prop(rsd_high_M27)
- M31 ~ add(sigma_low_M31) + prop(rsd_high_M31)
- })
-}
-m_dmta_nlmixr_mkin <- nlmixr_model(f_dmta_mkin_tc, test_log_parms = TRUE)
-f_dmta_nlmixr_saem <- nlmixr(f_dmta_mkin_tc, est = "saem", control = saemControl(print = 250))
-f_dmta_nlmixr_focei <- nlmixr(f_dmta_mkin_tc, est = "focei", control = foceiControl(print = 250))
-plot(f_dmta_nlmixr_saem)
-plot(f_dmta_nlmixr_focei)
-
+# dmta_ds <- lapply(1:8, 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[["Borstel"]] <- rbind(dmta_ds[["Borstel 1"]], dmta_ds[["Borstel 2"]])
+# dmta_ds[["Borstel 1"]] <- NULL
+# dmta_ds[["Borstel 2"]] <- NULL
+# dmta_ds[["Elliot"]] <- rbind(dmta_ds[["Elliot 1"]], dmta_ds[["Elliot 2"]])
+# dmta_ds[["Elliot 1"]] <- NULL
+# dmta_ds[["Elliot 2"]] <- NULL
+# dfop_sfo3_plus <- mkinmod(
+# DMTA = mkinsub("DFOP", c("M23", "M27", "M31")),
+# M23 = mkinsub("SFO"),
+# M27 = mkinsub("SFO"),
+# M31 = mkinsub("SFO", "M27", sink = FALSE),
+# quiet = TRUE
+# )
+# f_dmta_mkin_tc <- mmkin(
+# list("DFOP-SFO3+" = dfop_sfo3_plus),
+# dmta_ds, quiet = TRUE, error_model = "tc")
+#
+# d_dmta_nlmixr <- nlmixr_data(f_dmta_mkin_tc)
+# m_dmta_nlmixr <- function ()
+# {
+# ini({
+# DMTA_0 = 98.7697627680706
+# eta.DMTA_0 ~ 2.35171765917765
+# log_k_M23 = -3.92162409637283
+# eta.log_k_M23 ~ 0.549278519419884
+# log_k_M27 = -4.33774620773911
+# eta.log_k_M27 ~ 0.864474956685295
+# log_k_M31 = -4.24767627688461
+# eta.log_k_M31 ~ 0.750297149164171
+# f_DMTA_tffm0_1_qlogis = -2.092409
+# eta.f_DMTA_tffm0_1_qlogis ~ 0.3
+# f_DMTA_tffm0_2_qlogis = -2.180576
+# eta.f_DMTA_tffm0_2_qlogis ~ 0.3
+# f_DMTA_tffm0_3_qlogis = -2.142672
+# eta.f_DMTA_tffm0_3_qlogis ~ 0.3
+# log_k1 = -2.2341008812259
+# eta.log_k1 ~ 0.902976221565793
+# log_k2 = -3.7762779983269
+# eta.log_k2 ~ 1.57684519529298
+# g_qlogis = 0.450175725479389
+# eta.g_qlogis ~ 3.0851335687675
+# sigma_low_DMTA = 0.697933852349996
+# rsd_high_DMTA = 0.0257724286053519
+# sigma_low_M23 = 0.697933852349996
+# rsd_high_M23 = 0.0257724286053519
+# sigma_low_M27 = 0.697933852349996
+# rsd_high_M27 = 0.0257724286053519
+# sigma_low_M31 = 0.697933852349996
+# rsd_high_M31 = 0.0257724286053519
+# })
+# model({
+# DMTA_0_model = DMTA_0 + eta.DMTA_0
+# DMTA(0) = DMTA_0_model
+# k_M23 = exp(log_k_M23 + eta.log_k_M23)
+# k_M27 = exp(log_k_M27 + eta.log_k_M27)
+# k_M31 = exp(log_k_M31 + eta.log_k_M31)
+# k1 = exp(log_k1 + eta.log_k1)
+# k2 = exp(log_k2 + eta.log_k2)
+# g = expit(g_qlogis + eta.g_qlogis)
+# f_DMTA_tffm0_1 = expit(f_DMTA_tffm0_1_qlogis + eta.f_DMTA_tffm0_1_qlogis)
+# f_DMTA_tffm0_2 = expit(f_DMTA_tffm0_2_qlogis + eta.f_DMTA_tffm0_2_qlogis)
+# f_DMTA_tffm0_3 = expit(f_DMTA_tffm0_3_qlogis + eta.f_DMTA_tffm0_3_qlogis)
+# f_DMTA_to_M23 = f_DMTA_tffm0_1
+# f_DMTA_to_M27 = (1 - f_DMTA_tffm0_1) * f_DMTA_tffm0_2
+# f_DMTA_to_M31 = (1 - f_DMTA_tffm0_1) * (1 - f_DMTA_tffm0_2) * f_DMTA_tffm0_3
+# d/dt(DMTA) = -((k1 * g * exp(-k1 * time) + k2 * (1 -
+# g) * exp(-k2 * time))/(g * exp(-k1 * time) + (1 -
+# g) * exp(-k2 * time))) * DMTA
+# d/dt(M23) = +f_DMTA_to_M23 * ((k1 * g * exp(-k1 * time) +
+# k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
+# (1 - g) * exp(-k2 * time))) * DMTA - k_M23 * M23
+# d/dt(M27) = +f_DMTA_to_M27 * ((k1 * g * exp(-k1 * time) +
+# k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
+# (1 - g) * exp(-k2 * time))) * DMTA - k_M27 * M27 +
+# k_M31 * M31
+# d/dt(M31) = +f_DMTA_to_M31 * ((k1 * g * exp(-k1 * time) +
+# k2 * (1 - g) * exp(-k2 * time))/(g * exp(-k1 * time) +
+# (1 - g) * exp(-k2 * time))) * DMTA - k_M31 * M31
+# DMTA ~ add(sigma_low_DMTA) + prop(rsd_high_DMTA)
+# M23 ~ add(sigma_low_M23) + prop(rsd_high_M23)
+# M27 ~ add(sigma_low_M27) + prop(rsd_high_M27)
+# M31 ~ add(sigma_low_M31) + prop(rsd_high_M31)
+# })
+# }
+# m_dmta_nlmixr_mkin <- nlmixr_model(f_dmta_mkin_tc, test_log_parms = TRUE)
+# f_dmta_nlmixr_saem <- nlmixr(f_dmta_mkin_tc, est = "saem", control = saemControl(print = 250))
+# f_dmta_nlmixr_focei <- nlmixr(f_dmta_mkin_tc, est = "focei", control = foceiControl(print = 250))
+# plot(f_dmta_nlmixr_saem)
+# plot(f_dmta_nlmixr_focei)
+#

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