if (rxode2hasLlik()) { nmTest({ test_that("test focei llik", { # dnorm() works one.cmt <- function() { ini({ ## You may label each parameter with a comment tka <- 0.45 # Ka tcl <- log(c(0, 2.7, 100)) # Log Cl ## This works with interactive models ## You may also label the preceding line with label("label text") tv <- 3.45; label("log V") ## the label("Label name") works with all models eta.ka ~ 0.6 eta.cl ~ 0.3 eta.v ~ 0.1 add.sd <- 0.7 }) model({ ka <- exp(tka + eta.ka) cl <- exp(tcl + eta.cl) v <- exp(tv + eta.v) linCmt() ~ add(add.sd) + dnorm() }) } skip_if_not(rxode2::.linCmtSensB()) f <- nlmixr(one.cmt, theo_sd, "focei") expect_true("CWRES" %in% names(f)) of1 <- f$objf etaMat1 <- as.matrix(f$eta[,-1]) theta1 <- f$theta omega1 <- f$omega etaO1 <- f$etaObf f <- nlmixr(one.cmt, theo_sd, "foce") expect_true("CWRES" %in% names(f)) of2 <- f$objf etaMat2 <- as.matrix(f$eta[,-1]) theta2 <- f$theta omega2 <- f$omega expect_error(nlmixr(one.cmt, theo_sd, "fo")) one.cmt.ll <- function() { ini({ ## You may label each parameter with a comment tka <- 0.45 # Ka tcl <- log(c(0, 2.7, 100)) # Log Cl ## This works with interactive models ## You may also label the preceding line with label("label text") tv <- 3.45; label("log V") ## the label("Label name") works with all models eta.ka ~ 0.6 eta.cl ~ 0.3 eta.v ~ 0.1 add.sd <- 0.7 }) model({ ka <- exp(tka + eta.ka) cl <- exp(tcl + eta.cl) v <- exp(tv + eta.v) cp <- linCmt() # Use same form as stan math # https://github.com/stan-dev/math/blob/231cbd0be4280eb95cbb367068573830a7feae50/stan/math/prim/prob/normal_lpdf.hpp#L76-L80 invSigma <- 1/add.sd yScaled <- (DV-cp)*invSigma yScaledSq <- yScaled*yScaled ll <- -0.5*yScaledSq - 0.5*log(2*pi) - log(add.sd) ll(err) ~ ll }) } one.cmt.ll %>% ini(theta1) %>% ini(omega1) -> one.cmt.ll f <- try(nlmixr(one.cmt.ll, theo_sd, "focei", control=foceiControl(etaMat=etaMat1, maxInnerIterations=0, maxOuterIterations=0))) expect_false(inherits(f, "try-error")) expect_equal(f$ll, f$IPRED) expect_false("CWRES" %in% names(f)) expect_equal(f$objf, of1) one.cmt.ll %>% ini(theta2) %>% ini(omega2) -> one.cmt.ll f <- try(nlmixr(one.cmt.ll, theo_sd, "foce", control=foceiControl(etaMat=etaMat2, maxInnerIterations=0, maxOuterIterations=0))) expect_false(inherits(f, "try-error")) expect_equal(f$ll, f$IPRED) expect_false("CWRES" %in% names(f)) expect_equal(f$objf, of2) # no etas test one.cmt.noeta <- function() { ini({ ## You may label each parameter with a comment tka <- 0.45 # Ka tcl <- log(c(0, 2.7, 100)) # Log Cl ## This works with interactive models ## You may also label the preceding line with label("label text") tv <- 3.45; label("log V") ## the label("Label name") works with all models add.sd <- 0.7 }) model({ ka <- exp(tka) cl <- exp(tcl) v <- exp(tv) linCmt() ~ add(add.sd) + dnorm() }) } f <- nlmixr(one.cmt.noeta, theo_sd, "focei") of1 <-f$objf theta1 <- f$theta one.cmt.ll.noeta <- function() { ini({ ## You may label each parameter with a comment tka <- 0.45 # Ka tcl <- log(c(0, 2.7, 100)) # Log Cl ## This works with interactive models ## You may also label the preceding line with label("label text") tv <- 3.45; label("log V") ## the label("Label name") works with all models add.sd <- 0.7 }) model({ ka <- exp(tka) cl <- exp(tcl) v <- exp(tv) cp <- linCmt() ll(err) ~ -log(add.sd) - 0.5*log(2*pi) - 0.5*((DV-cp)/add.sd)^2 }) } one.cmt.ll.noeta %>% ini(theta1) -> one.cmt.ll.noeta f <- nlmixr(one.cmt.ll.noeta, theo_sd, "focei", control=foceiControl(maxOuterIterations=0)) expect_equal(of1, f$objf) }) pk.turnover.emax3.n1 <- function() { ini({ tktr <- log(1) tka <- log(1) tcl <- log(0.1) tv <- log(10) ## eta.ktr ~ 1 eta.ka ~ 1 eta.cl ~ 2 eta.v ~ 1 prop.err <- 0.1 pkadd.err <- 0.1 ## temax <- logit(0.8) tec50 <- log(0.5) tkout <- log(0.05) te0 <- log(100) ## eta.emax ~ .5 eta.ec50 ~ .5 eta.kout ~ .5 eta.e0 ~ .5 ## pdadd.err <- 1 }) model({ ktr <- exp(tktr + eta.ktr) ka <- exp(tka + eta.ka) cl <- exp(tcl + eta.cl) v <- exp(tv + eta.v) emax = expit(temax+eta.emax) ec50 = exp(tec50 + eta.ec50) kout = exp(tkout + eta.kout) e0 = exp(te0 + eta.e0) ## DCP = center/v rPD=1-emax*DCP/(ec50+DCP) ## effect(0) = e0 kin = e0*kout ## d/dt(depot) = -ktr * depot d/dt(gut) = ktr * depot -ka * gut d/dt(center) = ka * gut - cl / v * center d/dt(effect) = kin*rPD -kout*effect ## cp = center / v cp ~ prop(prop.err) + add(pkadd.err) effect ~ add(pdadd.err) + dnorm() | pca }) } pk.turnover.emax3.n2 <- function() { ini({ tktr <- log(1) tka <- log(1) tcl <- log(0.1) tv <- log(10) ## eta.ktr ~ 1 eta.ka ~ 1 eta.cl ~ 2 eta.v ~ 1 prop.err <- 0.1 pkadd.err <- 0.1 ## temax <- logit(0.8) tec50 <- log(0.5) tkout <- log(0.05) te0 <- log(100) ## eta.emax ~ .5 eta.ec50 ~ .5 eta.kout ~ .5 eta.e0 ~ .5 ## pdadd.err <- 1 }) model({ ktr <- exp(tktr + eta.ktr) ka <- exp(tka + eta.ka) cl <- exp(tcl + eta.cl) v <- exp(tv + eta.v) emax = expit(temax+eta.emax) ec50 = exp(tec50 + eta.ec50) kout = exp(tkout + eta.kout) e0 = exp(te0 + eta.e0) ## DCP = center/v rPD=1-emax*DCP/(ec50+DCP) ## effect(0) = e0 kin = e0*kout ## d/dt(depot) = -ktr * depot d/dt(gut) = ktr * depot -ka * gut d/dt(center) = ka * gut - cl / v * center d/dt(effect) = kin*rPD -kout*effect ## cp = center / v cp ~ prop(prop.err) + add(pkadd.err) + dnorm() effect ~ add(pdadd.err) + dnorm() | pca }) } f <- nlmixr2(pk.turnover.emax3.n1) f2 <- nlmixr2(pk.turnover.emax3.n2) expect_equal(f$foceiModel0, f2$foceiModel0) expect_equal(f$foceModel0, f2$foceModel0) f <- nlmixr(pk.turnover.emax3.n1, nlmixr2data::warfarin, "focei", control=foceiControl(covMethod = "", maxOuterIterations=0)) of1 <- f$objf etaMat1 <- as.matrix(f$eta[,-1]) theta1 <- f$theta omega1 <- f$omega etaO1 <- f$etaObf pk.turnover.emax3.ll <- function() { ini({ tktr <- log(1) tka <- log(1) tcl <- log(0.1) tv <- log(10) ## eta.ktr ~ 1 eta.ka ~ 1 eta.cl ~ 2 eta.v ~ 1 prop.err <- 0.1 pkadd.err <- 0.1 ## temax <- logit(0.8) tec50 <- log(0.5) tkout <- log(0.05) te0 <- log(100) ## eta.emax ~ .5 eta.ec50 ~ .5 eta.kout ~ .5 eta.e0 ~ .5 ## pdadd.err <- c(0, 10) }) model({ ktr <- exp(tktr + eta.ktr) ka <- exp(tka + eta.ka) cl <- exp(tcl + eta.cl) v <- exp(tv + eta.v) emax = expit(temax+eta.emax) ec50 = exp(tec50 + eta.ec50) kout = exp(tkout + eta.kout) e0 = exp(te0 + eta.e0) ## DCP = center/v rPD=1-emax*DCP/(ec50+DCP) ## effect(0) = e0 kin = e0*kout ## d/dt(depot) = -ktr * depot d/dt(gut) = ktr * depot -ka * gut d/dt(center) = ka * gut - cl / v * center d/dt(effect) = kin*rPD -kout*effect ## cp = center / v cp ~ prop(prop.err) + add(pkadd.err) + dnorm() ll(pca) ~ -log(pdadd.err) - 0.5*log(2*pi) - 0.5 * ((DV - effect) / pdadd.err)^2 }) } pk.turnover.emax3.ll %>% ini(theta1) %>% ini(omega1) -> pk.turnover.emax3.ll f2 <- nlmixr(pk.turnover.emax3.ll, nlmixr2data::warfarin, "focei", control=foceiControl(etaMat=etaMat1, maxInnerIterations=0, maxOuterIterations=0, optimHessType="forward")) test_that("same values for omega, theta and eta, forward", { expect_equal(f$omega, f2$omega) expect_equal(f$theta, f2$theta) expect_equal(f$eta, f2$eta) }) f2 <- nlmixr(pk.turnover.emax3.ll, nlmixr2data::warfarin, "focei", control=foceiControl(etaMat=etaMat1, maxInnerIterations=0, maxOuterIterations=0, optimHessType="central")) test_that("same values for omega, theta and eta, central", { expect_equal(f$omega, f2$omega) expect_equal(f$theta, f2$theta) expect_equal(f$eta, f2$eta) }) test_that("objective values are equal for mixed ll", { expect_equal(f2$objf, of1) }) fll <- addNpde(f2) fnorm <- addNpde(f) f1 <- fll %>% dplyr::filter(CMT != "pca") f1norm <- fnorm %>% dplyr::filter(CMT != "pca") f2 <- fll %>% dplyr::filter(CMT == "pca") for (i in c("RES", "WRES", "IRES", "IWRES", "WRES", "IWRES", "CPRED", "CRES", "CWRES", "PRED", "IPRED", "EPRED", "ERES", "NPDE", "NPD", "PDE", "PD")) { test_that(paste0("res: ", i), { expect_false(any(is.na(f1[[i]]))) if (i %in% c("PRED", "IPRED")) { expect_false(any(is.na(f2[[i]]))) } else { expect_true(all(is.na(f2[[i]]))) } if (!(i %in% c("EPRED", "ERES", "NPDE", "NPD", "PDE", "PD"))) { expect_equal(f1[[i]], f1norm[[i]]) } }) } }) }