context("Dimethenamid data from 2018") # Data 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"]] <- dmta_ds[["Elliot 2"]] <- NULL # mkin dmta_dfop <- mmkin("DFOP", dmta_ds, quiet = TRUE) dmta_dfop_tc <- mmkin("DFOP", dmta_ds, error_model = "tc", quiet = TRUE) test_that("Different backends get consistent results for DFOP tc, dimethenamid data", { # nlme expect_warning( nlme_dfop_tc <- nlme(dmta_dfop_tc), "Iteration 3, .* false convergence") ints_nlme <- intervals(nlme_dfop_tc) # saemix saem_saemix_dfop_tc <- saem(dmta_dfop_tc) ints_saemix <- intervals(saem_saemix_dfop_tc) # saemix mkin transformations saem_saemix_dfop_tc_mkin <- saem(dmta_dfop_tc, transformations = "mkin") ints_saemix_mkin <- intervals(saem_saemix_dfop_tc_mkin) # nlmixr saem saem_nlmixr_dfop_tc <- nlmixr(dmta_dfop_tc, est = "saem", control = nlmixr::saemControl(nBurn = 300, nEm = 100, nmc = 9, print = 0)) ints_nlmixr_saem <- intervals(saem_nlmixr_dfop_tc) # nlmixr focei # We get three warnings about nudged etas, the initial optimization and # gradient problems with initial estimate and covariance # We need to capture output, otherwise it pops up in testthat output expect_warning(tmp <- capture_output(focei_nlmixr_dfop_tc <- nlmixr( dmta_dfop_tc, est = "focei", control = nlmixr::foceiControl(print = 0), all = TRUE))) ints_nlmixr_focei <- intervals(focei_nlmixr_dfop_tc) # Fixed effects ## saemix vs. nlme expect_true(all(ints_saemix$fixed[, "est."] > backtransform_odeparms(ints_nlme$fixed[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_saemix$fixed[, "est."] < backtransform_odeparms(ints_nlme$fixed[, "upper"], dmta_dfop$mkinmod))) ## saemix mkin vs. nlme expect_true(all(ints_saemix_mkin$fixed[, "est."] > backtransform_odeparms(ints_nlme$fixed[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_saemix_mkin$fixed[, "est."] < backtransform_odeparms(ints_nlme$fixed[, "upper"], dmta_dfop$mkinmod))) ## nlmixr saem vs. nlme expect_true(all(ints_nlmixr_saem$fixed[, "est."] > backtransform_odeparms(ints_nlme$fixed[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_nlmixr_saem$fixed[, "est."] < backtransform_odeparms(ints_nlme$fixed[, "upper"], dmta_dfop$mkinmod))) ## nlmixr focei vs. nlme expect_true(all(ints_nlmixr_focei$fixed[, "est."] > backtransform_odeparms(ints_nlme$fixed[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_nlmixr_focei$fixed[, "est."] < backtransform_odeparms(ints_nlme$fixed[, "upper"], dmta_dfop$mkinmod))) # Random effects ## for saemix with saemix transformations, the comparison would be complicated... ## saemix mkin vs. nlme expect_true(all(ints_saemix$random[, "est."] > backtransform_odeparms(ints_nlme$reStruct$ds[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_saemix$fixed[, "est."] < backtransform_odeparms(ints_nlme$fixed[, "upper"], dmta_dfop$mkinmod))) ## nlmixr saem vs. nlme expect_true(all(ints_nlmixr_saem$random[, "est."] > backtransform_odeparms(ints_nlme$reStruct$ds[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_nlmixr_saem$random[, "est."] < backtransform_odeparms(ints_nlme$reStruct$ds[, "upper"], dmta_dfop$mkinmod))) ## nlmixr focei vs. nlme expect_true(all(ints_nlmixr_focei$random[, "est."] > backtransform_odeparms(ints_nlme$reStruct$ds[, "lower"], dmta_dfop$mkinmod))) expect_true(all(ints_nlmixr_focei$random[, "est."] < backtransform_odeparms(ints_nlme$reStruct$ds[, "upper"], dmta_dfop$mkinmod))) # Variance function skip_on_travis() # For some reason this fails on Travis # saemix vs. nlme expect_true(all(ints_saemix[[3]][, "est."] > ints_nlme$varStruct[, "lower"])) expect_true(all(ints_saemix[[3]][, "est."] < ints_nlme$varStruct[, "upper"])) # saemix with mkin transformations vs. nlme expect_true(all(ints_saemix_mkin[[3]][, "est."] > ints_nlme$varStruct[, "lower"])) expect_true(all(ints_saemix_mkin[[3]][, "est."] < ints_nlme$varStruct[, "upper"])) # nlmixr saem vs. nlme expect_true(all(ints_nlmixr_saem[[3]][, "est."] > ints_nlme$varStruct[, "lower"])) expect_true(all(ints_nlmixr_saem[[3]][, "est."] < ints_nlme$varStruct[, "upper"])) # nlmixr focei vs. nlme # We only test for the proportional part (rsd_high), as the # constant part (sigma_low) obtained with nlmixr/FOCEI is below the lower # bound of the confidence interval obtained with nlme expect_true(ints_nlmixr_focei[[3]]["rsd_high", "est."] > ints_nlme$varStruct["prop", "lower"]) expect_true(ints_nlmixr_focei[[3]]["rsd_high", "est."] < ints_nlme$varStruct["prop", "upper"]) }) # Compared to the 2020 paper https://doi.org/10.3390/environments8080071 # the data are different, as there was an error in the handling of the # Borstel data in the mkin package at the time. # The model called DFOP-SFO3+ in the paper appears to be overparameterised with # the corrected data, we get lots of problems trying to use it with mmkin, nlme # and saemix sfo_sfo3p <- mkinmod( DMTA = mkinsub("SFO", c("M23", "M27", "M31")), M23 = mkinsub("SFO"), M27 = mkinsub("SFO"), M31 = mkinsub("SFO", "M27", sink = FALSE), quiet = TRUE ) dmta_sfo_sfo3p_tc <- mmkin(list("SFO-SFO3+" = sfo_sfo3p), dmta_ds, error_model = "tc", quiet = TRUE) test_that("Different backends get consistent results for SFO-SFO3+, dimethenamid data", { expect_warning(nlme_sfo_sfo3p_tc <- nlme(dmta_sfo_sfo3p_tc, start = mean_degparms(dmta_sfo_sfo3p_tc, test_log_parms = TRUE)), "Iteration 5, LME step.*not converge") ints_nlme_mets <- intervals(nlme_sfo_sfo3p_tc, which = "fixed") # The saem fit with nlmixr takes only about 15 seconds tmp <- capture.output( saem_nlmixr_sfo_sfo3p_tc <- nlmixr(dmta_sfo_sfo3p_tc, est = "saem", control = nlmixr::saemControl(print = 0))) ints_nlmixr_saem_mets <- intervals(saem_nlmixr_sfo_sfo3p_tc) # We need to exclude the ilr transformed formation fractions in these # tests, as they do not have a one to one relation in the transformations expect_true(all(ints_nlmixr_saem_mets$fixed[, "est."][-c(6, 7, 8)] > backtransform_odeparms(ints_nlme_mets$fixed[, "lower"][-c(6, 7, 8)], sfo_sfo3p))) expect_true(all(ints_nlmixr_saem_mets$fixed[, "est."][-c(6, 7, 8)] < backtransform_odeparms(ints_nlme_mets$fixed[, "upper"], sfo_sfo3p)[-c(6, 7, 8)])) skip("Fitting this ODE model with saemix takes about 15 minutes on my system") # As DFOP is overparameterised and leads to instabilities and errors, we # need to use SFO. # saem_saemix_sfo_sfo3p_tc <- saem(dmta_sfo_sfo3p_tc) # The fit above, using SFO for the parent leads to low values of DMTA_0 # (confidence interval from 84.4 to 92.8) which is not consistent with what # we know about this value. Therefore, we fix it to the initial estimate # obtained from the separate fits (95.6) saem_saemix_sfo_sfo3p_tc_DMTA_0_fixed <- saem(dmta_sfo_sfo3p_tc, fixed.estim = c(0, rep(1, 7))) ints_saemix_mets <- intervals(saem_saemix_sfo_sfo3p_tc_DMTA_0_fixed) # Again, we need to exclude the ilr transformed formation fractions in these # tests, as they do not have a one to one relation in the transformations expect_true(all(ints_saemix_mets$fixed[, "est."][-c(6, 7, 8)] > backtransform_odeparms(ints_nlme_mets$fixed[, "lower"][-c(6, 7, 8)], sfo_sfo3p))) expect_true(all(ints_saemix_mets$fixed[, "est."][-c(6, 7, 8)] < backtransform_odeparms(ints_nlme_mets$fixed[, "upper"], sfo_sfo3p)[-c(6, 7, 8)])) })