SFORB in saem, update for mhmkin and multistart

6 files changed, 94 insertions, 9 deletions

diff --git a/NAMESPACE b/NAMESPACE
index 3b4d2367..80fc927d 100644
--- a/NAMESPACE
+++ b/NAMESPACE
@@ -68,8 +68,10 @@ S3method(summary,mkinfit)
 S3method(summary,mmkin)
 S3method(summary,nlme.mmkin)
 S3method(summary,saem.mmkin)
+S3method(update,mhmkin)
 S3method(update,mkinfit)
 S3method(update,mmkin)
+S3method(update,multistart)
 S3method(update,nlme.mmkin)
 S3method(update,saem.mmkin)
 S3method(which.best,default)
diff --git a/R/mhmkin.R b/R/mhmkin.R
index 2df01f0c..542bddf7 100644
--- a/R/mhmkin.R
+++ b/R/mhmkin.R
@@ -207,6 +207,10 @@ BIC.mhmkin <- function(object, ...) {
 #' @export
 update.mhmkin <- function(object, ..., evaluate = TRUE) {
   call <- attr(object, "call")
+  # For some reason we get mhkin.list in call[[1]] when using mhmkin from the
+  # loaded package so we need to fix this so we do not have to export
+  # mhmkin.list in addition to the S3 method mhmkin
+  call[[1]] <- mhmkin
 
   update_arguments <- match.call(expand.dots = FALSE)$...
 
diff --git a/R/multistart.R b/R/multistart.R
index a788953e..11736670 100644
--- a/R/multistart.R
+++ b/R/multistart.R
@@ -71,6 +71,7 @@ multistart <- function(object, n = 50,
 #' @export
 multistart.saem.mmkin <- function(object, n = 50, cores = 1,
   cluster = NULL, ...) {
+  call <- match.call()
   if (n <= 1) stop("Please specify an n of at least 2")
 
   mmkin_parms <- parms(object$mmkin, errparms = FALSE,
@@ -90,6 +91,7 @@ multistart.saem.mmkin <- function(object, n = 50, cores = 1,
   }
   attr(res, "orig") <- object
   attr(res, "start_parms") <- start_parms
+  attr(res, "call") <- call
   class(res) <- c("multistart.saem.mmkin", "multistart")
   return(res)
 }
@@ -178,3 +180,30 @@ which.best.default <- function(object, ...)
   ll <- sapply(object, llfunc)
   return(which.max(ll))
 }
+
+#' @export
+update.multistart <- function(object, ..., evaluate = TRUE) {
+  call <- attr(object, "call")
+  # For some reason we get multistart.saem.mmkin in call[[1]] when using multistart
+  # from the loaded package so we need to fix this so we do not have to export
+  # multistart.saem.mmkin
+  call[[1]] <- multistart
+
+  update_arguments <- match.call(expand.dots = FALSE)$...
+
+  if (length(update_arguments) > 0) {
+    update_arguments_in_call <- !is.na(match(names(update_arguments), names(call)))
+  }
+
+  for (a in names(update_arguments)[update_arguments_in_call]) {
+    call[[a]] <- update_arguments[[a]]
+  }
+
+  update_arguments_not_in_call <- !update_arguments_in_call
+  if(any(update_arguments_not_in_call)) {
+    call <- c(as.list(call), update_arguments[update_arguments_not_in_call])
+    call <- as.call(call)
+  }
+  if(evaluate) eval(call, parent.frame())
+  else call
+}
diff --git a/R/saem.R b/R/saem.R
index 5256f6b5..dbc19dec 100644
--- a/R/saem.R
+++ b/R/saem.R
@@ -313,7 +313,7 @@ saemix_model <- function(object, solution_type = "auto",
     # Parent only
     if (length(mkin_model$spec) == 1) {
       parent_type <- mkin_model$spec[[1]]$type
-      if (length(odeini_fixed) == 1) {
+      if (length(odeini_fixed) == 1 && !grepl("_bound$", names(odeini_fixed))) {
         if (transformations == "saemix") {
           stop("saemix transformations are not supported for parent fits with fixed initial parent value")
         }
@@ -344,6 +344,9 @@ saemix_model <- function(object, solution_type = "auto",
           }
         }
       } else {
+        if (length(odeini_fixed) == 2) {
+          stop("SFORB with fixed initial parent value is not supported")
+        }
         if (parent_type == "SFO") {
           if (transformations == "mkin") {
             model_function <- function(psi, id, xidep) {
@@ -386,6 +389,38 @@ saemix_model <- function(object, solution_type = "auto",
             transform.par = c(0, 1, 1, 3)
           }
         }
+        if (parent_type == "SFORB") {
+          if (transformations == "mkin") {
+            model_function <- function(psi, id, xidep) {
+              k_12 <- exp(psi[id, 3])
+              k_21 <- exp(psi[id, 4])
+              k_1output <- exp(psi[id, 2])
+              t <- xidep[, "time"]
+
+              sqrt_exp = sqrt(1/4 * (k_12 + k_21 + k_1output)^2 + k_12 * k_21 - (k_12 + k_1output) * k_21)
+              b1 = 0.5 * (k_12 + k_21 + k_1output) + sqrt_exp
+              b2 = 0.5 * (k_12 + k_21 + k_1output) - sqrt_exp
+
+              psi[id, 1] * (((k_12 + k_21 - b1)/(b2 - b1)) * exp(-b1 * t) +
+                ((k_12 + k_21 - b2)/(b1 - b2)) * exp(-b2 * t))
+            }
+          } else {
+            model_function <- function(psi, id, xidep) {
+              k_12 <- psi[id, 3]
+              k_21 <- psi[id, 4]
+              k_1output <- psi[id, 2]
+              t <- xidep[, "time"]
+
+              sqrt_exp = sqrt(1/4 * (k_12 + k_21 + k_1output)^2 + k_12 * k_21 - (k_12 + k_1output) * k_21)
+              b1 = 0.5 * (k_12 + k_21 + k_1output) + sqrt_exp
+              b2 = 0.5 * (k_12 + k_21 + k_1output) - sqrt_exp
+
+              psi[id, 1] * (((k_12 + k_21 - b1)/(b2 - b1)) * exp(-b1 * t) +
+                ((k_12 + k_21 - b2)/(b1 - b2)) * exp(-b2 * t))
+            }
+            transform.par = c(0, 1, 1, 1)
+          }
+        }
         if (parent_type == "HS") {
           if (transformations == "mkin") {
             model_function <- function(psi, id, xidep) {
diff --git a/log/test.log b/log/test.log
index 6cd9e6a8..d7d623d7 100644
--- a/log/test.log
+++ b/log/test.log
@@ -1,11 +1,11 @@
 ℹ Testing mkin
 ✔ | F W S  OK | Context
 ✔ |         5 | AIC calculation
-✔ |         5 | Analytical solutions for coupled models [3.3s]
+✔ |         5 | Analytical solutions for coupled models [3.2s]
 ✔ |         5 | Calculation of Akaike weights
 ✔ |         3 | Export dataset for reading into CAKE
 ✔ |        12 | Confidence intervals and p-values [1.0s]
-✔ |     1  12 | Dimethenamid data from 2018 [31.1s]
+✔ |     1  12 | Dimethenamid data from 2018 [31.3s]
 ────────────────────────────────────────────────────────────────────────────────
 Skip (test_dmta.R:98:3): Different backends get consistent results for SFO-SFO3+, dimethenamid data
 Reason: Fitting this ODE model with saemix takes about 15 minutes on my system
@@ -28,24 +28,24 @@ Reason: Fitting with saemix takes around 10 minutes when using deSolve
 ✔ |         8 | mkinmod model generation and printing [0.2s]
 ✔ |         3 | Model predictions with mkinpredict [0.4s]
 ✔ |        16 | Evaluations according to 2015 NAFTA guidance [1.8s]
-✔ |         9 | Nonlinear mixed-effects models with nlme [8.5s]
-✔ |        16 | Plotting [9.8s]
+✔ |         9 | Nonlinear mixed-effects models with nlme [8.3s]
+✔ |        16 | Plotting [9.7s]
 ✔ |         4 | Residuals extracted from mkinfit models
-✔ |        35 | saemix parent models [189.7s]
+✔ |        37 | saemix parent models [208.2s]
 ✔ |         2 | Complex test case from Schaefer et al. (2007) Piacenza paper [1.4s]
 ✔ |        11 | Processing of residue series
 ✔ |         7 | Fitting the SFORB model [3.6s]
 ✔ |         1 | Summaries of old mkinfit objects
 ✔ |         5 | Summary [0.2s]
 ✔ |         4 | Results for synthetic data established in expertise for UBA (Ranke 2014) [2.1s]
-✔ |         9 | Hypothesis tests [7.8s]
+✔ |         9 | Hypothesis tests [7.6s]
 ✔ |         4 | Calculation of maximum time weighted average concentrations (TWAs) [2.1s]
 
 ══ Results ═════════════════════════════════════════════════════════════════════
-Duration: 286.0 s
+Duration: 304.2 s
 
 ── Skipped tests  ──────────────────────────────────────────────────────────────
 • Fitting this ODE model with saemix takes about 15 minutes on my system (1)
 • Fitting with saemix takes around 10 minutes when using deSolve (1)
 
-[ FAIL 0 | WARN 0 | SKIP 2 | PASS 253 ]
+[ FAIL 0 | WARN 0 | SKIP 2 | PASS 255 ]
diff --git a/tests/testthat/test_saemix_parent.R b/tests/testthat/test_saemix_parent.R
index ce776bf7..0579f22f 100644
--- a/tests/testthat/test_saemix_parent.R
+++ b/tests/testthat/test_saemix_parent.R
@@ -101,6 +101,21 @@ test_that("Parent fits using saemix are correctly implemented", {
   rel_diff_2 <- (s_dfop_s2$confint_back[, "est."] - dfop_pop) / dfop_pop
   expect_true(all(rel_diff_2 < 0.2))
 
+  # We use constant error for SFORB because tc is overparameterised (b.1 is ill-defined in saem)
+  mmkin_sforb_2 <- mmkin("SFORB", ds_dfop, quiet = TRUE, error_model = "const", cores = n_cores)
+  sforb_saemix_1 <- saem(mmkin_sforb_2, quiet = TRUE,
+    no_random_effect = c("parent_free_0", "k_parent_free_bound"),
+    transformations = "saemix")
+  sforb_saemix_2 <- saem(mmkin_sforb_2, quiet = TRUE,
+    no_random_effect = c("parent_free_0", "log_k_parent_free_bound"),
+    transformations = "mkin")
+  expect_equal(
+    log(endpoints(dfop_saemix_1)$distimes[1:2]),
+    log(endpoints(sforb_saemix_1)$distimes[1:2]), tolerance = 0.01)
+  expect_equal(
+    log(endpoints(sforb_saemix_1)$distimes[1:2]),
+    log(endpoints(sforb_saemix_2)$distimes[1:2]), tolerance = 0.01)
+
   mmkin_hs_1 <- mmkin("HS", ds_hs, quiet = TRUE, error_model = "const", cores = n_cores)
   hs_saem_1 <- saem(mmkin_hs_1, quiet = TRUE)
   hs_saem_2 <- saem(mmkin_hs_1, quiet = TRUE, transformations = "mkin")