From 0b754ffa91b9496bdd2f892cf3ca2bd887028dea Mon Sep 17 00:00:00 2001 From: Johannes Ranke Date: Tue, 27 Jul 2021 18:22:01 +0200 Subject: Fix dimethenamid vignette problems and update docs --- docs/dev/reference/nlmixr.mmkin.html | 28 ++++++++++++++-------------- 1 file changed, 14 insertions(+), 14 deletions(-) (limited to 'docs/dev/reference/nlmixr.mmkin.html') diff --git a/docs/dev/reference/nlmixr.mmkin.html b/docs/dev/reference/nlmixr.mmkin.html index d09f2ad4..328bad43 100644 --- a/docs/dev/reference/nlmixr.mmkin.html +++ b/docs/dev/reference/nlmixr.mmkin.html @@ -74,7 +74,7 @@ Expectation Maximisation algorithm (SAEM)." /> mkin - 1.0.5 + 1.1.0 @@ -4501,7 +4501,7 @@ obtained by fitting the same model to a list of datasets using k_A1=rx_expr_11; #> f_parent=1/(1+exp(-(ETA[4]+THETA[4]))); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 5.607 0.474 6.078
f_nlmixr_fomc_sfo_focei_const <- nlmixr(f_mmkin_const["FOMC-SFO", ], est = "focei") +#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 5.548 0.415 5.961
f_nlmixr_fomc_sfo_focei_const <- nlmixr(f_mmkin_const["FOMC-SFO", ], est = "focei")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); #> rx_expr_6~ETA[1]+THETA[1]; @@ -4550,7 +4550,7 @@ obtained by fitting the same model to a list of datasets using beta=exp(rx_expr_8); #> f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 6.853 0.393 7.242
f_nlmixr_dfop_sfo_focei_const <- nlmixr(f_mmkin_const["DFOP-SFO", ], est = "focei") +#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 6.895 0.416 7.309
f_nlmixr_dfop_sfo_focei_const <- nlmixr(f_mmkin_const["DFOP-SFO", ], est = "focei")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); #> rx_expr_6~ETA[1]+THETA[1]; @@ -4607,10 +4607,10 @@ obtained by fitting the same model to a list of datasets using f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> g=1/(rx_expr_20); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 15.18 0.414 15.6
+#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 15.03 0.478 15.51
# Variance by variable is supported by 'saem' and 'focei' f_nlmixr_fomc_sfo_saem_obs <- nlmixr(f_mmkin_obs["FOMC-SFO", ], est = "saem") -
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> → generate SAEM model
#> ✔ done
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 1.22 0.089 1.31
f_nlmixr_fomc_sfo_focei_obs <- nlmixr(f_mmkin_obs["FOMC-SFO", ], est = "focei") +
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> → generate SAEM model
#> ✔ done
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 1.294 0.134 1.427
f_nlmixr_fomc_sfo_focei_obs <- nlmixr(f_mmkin_obs["FOMC-SFO", ], est = "focei")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); #> rx_expr_6~ETA[1]+THETA[1]; @@ -4659,8 +4659,8 @@ obtained by fitting the same model to a list of datasets using beta=exp(rx_expr_8); #> f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 6.784 0.418 7.2
f_nlmixr_dfop_sfo_saem_obs <- nlmixr(f_mmkin_obs["DFOP-SFO", ], est = "saem") -
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> → generate SAEM model
#> ✔ done
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 1.357 0.096 1.452
f_nlmixr_dfop_sfo_focei_obs <- nlmixr(f_mmkin_obs["DFOP-SFO", ], est = "focei") +#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 6.584 0.393 6.976
f_nlmixr_dfop_sfo_saem_obs <- nlmixr(f_mmkin_obs["DFOP-SFO", ], est = "saem") +
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> → generate SAEM model
#> ✔ done
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 1.302 0.142 1.443
f_nlmixr_dfop_sfo_focei_obs <- nlmixr(f_mmkin_obs["DFOP-SFO", ], est = "focei")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); #> rx_expr_6~ETA[1]+THETA[1]; @@ -4717,7 +4717,7 @@ obtained by fitting the same model to a list of datasets using f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> g=1/(rx_expr_19); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 15.17 0.353 15.52
+#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 14.58 0.482 15.06
# 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") @@ -4771,7 +4771,7 @@ obtained by fitting the same model to a list of datasets using beta=exp(rx_expr_8); #> f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 8.708 0.429 9.135
f_nlmixr_dfop_sfo_focei_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "focei") +#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 8.484 0.401 8.883
f_nlmixr_dfop_sfo_focei_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "focei")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); #> rx_expr_6~ETA[1]+THETA[1]; @@ -4830,12 +4830,12 @@ obtained by fitting the same model to a list of datasets using f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> g=1/(rx_expr_21); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 18.05 0.446 18.5
+#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 18.44 0.438 18.87
# 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") -
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 0.763 0.036 0.799
f_nlmixr_fomc_sfo_focei_obs_tc <- nlmixr(f_mmkin_tc["FOMC-SFO", ], est = "focei", +
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 0.784 0.028 0.812
f_nlmixr_fomc_sfo_focei_obs_tc <- nlmixr(f_mmkin_tc["FOMC-SFO", ], est = "focei", error_model = "obs_tc")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); @@ -4887,9 +4887,9 @@ obtained by fitting the same model to a list of datasets using beta=exp(rx_expr_8); #> f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 8.196 0.388 8.584
f_nlmixr_dfop_sfo_saem_obs_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "saem", +#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 8.157 0.51 8.664
f_nlmixr_dfop_sfo_saem_obs_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "saem", error_model = "obs_tc") -
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 0.843 0.028 0.871
f_nlmixr_dfop_sfo_focei_obs_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "focei", +
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#>
#> Error in configsaem(model = model, data = dat, inits = inits, mcmc = .mcmc, ODEopt = .ODEopt, seed = .seed, distribution = .dist, DEBUG = .DEBUG, addProp = .addProp, tol = .tol, itmax = .itmax, type = .type, powRange = .powRange, lambdaRange = .lambdaRange): covariate(s) not found: f_parent_to_A1
#> Timing stopped at: 0.81 0.045 0.854
f_nlmixr_dfop_sfo_focei_obs_tc <- nlmixr(f_mmkin_tc["DFOP-SFO", ], est = "focei", error_model = "obs_tc")
#> ℹ parameter labels from comments are typically ignored in non-interactive mode
#> ℹ Need to run with the source intact to parse comments
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → creating full model...
#> → pruning branches (`if`/`else`)...
#> ✔ done
#> → loading into symengine environment...
#> ✔ done
#> → calculate jacobian
#>
#> → calculate sensitivities
#>
#> → calculate ∂(f)/∂(η)
#>
#> → calculate ∂(R²)/∂(η)
#>
#> → finding duplicate expressions in inner model...
#>
#> → optimizing duplicate expressions in inner model...
#>
#> → finding duplicate expressions in EBE model...
#>
#> → optimizing duplicate expressions in EBE model...
#>
#> → compiling inner model...
#>
#> ✔ done
#> → finding duplicate expressions in FD model...
#>
#> → optimizing duplicate expressions in FD model...
#>
#> → compiling EBE model...
#>
#> ✔ done
#> → compiling events FD model...
#>
#> ✔ done
#> Model:
#> cmt(parent); #> cmt(A1); @@ -4949,7 +4949,7 @@ obtained by fitting the same model to a list of datasets using f_parent=1/(1+exp(-(ETA[3]+THETA[3]))); #> g=1/(rx_expr_19); #> tad=tad(); -#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 17.73 0.411 18.14
+#> dosenum=dosenum();
#> Needed Covariates:
#> [1] "f_parent_to_A1" "CMT"
#> Error in (function (data, inits, PKpars, model = NULL, pred = NULL, err = NULL, lower = -Inf, upper = Inf, fixed = NULL, skipCov = NULL, control = foceiControl(), thetaNames = NULL, etaNames = NULL, etaMat = NULL, ..., env = NULL, keep = NULL, drop = NULL) { set.seed(control$seed) .pt <- proc.time() RxODE::.setWarnIdSort(FALSE) on.exit(RxODE::.setWarnIdSort(TRUE)) loadNamespace("n1qn1") if (!RxODE::rxIs(control, "foceiControl")) { control <- do.call(foceiControl, control) } if (is.null(env)) { .ret <- new.env(parent = emptyenv()) } else { .ret <- env } .ret$origData <- data .ret$etaNames <- etaNames .ret$thetaFixed <- fixed .ret$control <- control .ret$control$focei.mu.ref <- integer(0) if (is(model, "RxODE") || is(model, "character")) { .ret$ODEmodel <- TRUE if (class(pred) != "function") { stop("pred must be a function specifying the prediction variables in this model.") } } else { .ret$ODEmodel <- TRUE model <- RxODE::rxGetLin(PKpars) pred <- eval(parse(text = "function(){return(Central);}")) } .square <- function(x) x * x .ret$diagXformInv <- c(sqrt = ".square", log = "exp", identity = "identity")[control$diagXform] if (is.null(err)) { err <- eval(parse(text = paste0("function(){err", paste(inits$ERROR[[1]], collapse = ""), "}"))) } .covNames <- .parNames <- c() .ret$adjLik <- control$adjLik .mixed <- !is.null(inits$OMGA) && length(inits$OMGA) > 0 if (!exists("noLik", envir = .ret)) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ssAtol <- rep(control$ssAtol, length(RxODE::rxModelVars(model)$state)) .ssRtol <- rep(control$ssRtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = (control$derivMethod == 2L), pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, interaction = (control$interaction == 1L), only.numeric = !.mixed, run.internal = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol .ssAtol <- c(.ssAtol, rep(control$ssAtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssAtol))) .ssRtol <- c(.ssRtol, rep(control$ssRtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.ssRtol))) .ret$control$rxControl$ssAtol <- .ssAtol .ret$control$rxControl$ssRtol <- .ssRtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { if (.ret$noLik) { .atol <- rep(control$atol, length(RxODE::rxModelVars(model)$state)) .rtol <- rep(control$rtol, length(RxODE::rxModelVars(model)$state)) .ret$model <- RxODE::rxSymPySetupPred(model, pred, PKpars, err, grad = FALSE, pred.minus.dv = TRUE, sum.prod = control$sumProd, theta.derivs = FALSE, optExpression = control$optExpression, run.internal = TRUE, only.numeric = TRUE, addProp = control$addProp) if (!is.null(.ret$model$inner)) { .atol <- c(.atol, rep(control$atolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.atol))) .rtol <- c(.rtol, rep(control$rtolSens, length(RxODE::rxModelVars(.ret$model$inner)$state) - length(.rtol))) .ret$control$rxControl$atol <- .atol .ret$control$rxControl$rtol <- .rtol } .covNames <- .parNames <- RxODE::rxParams(.ret$model$pred.only) .covNames <- .covNames[regexpr(rex::rex(start, or("THETA", "ETA"), "[", numbers, "]", end), .covNames) == -1] colnames(data) <- sapply(names(data), function(x) { if (any(x == .covNames)) { return(x) } else { return(toupper(x)) } }) .lhs <- c(names(RxODE::rxInits(.ret$model$pred.only)), RxODE::rxLhs(.ret$model$pred.only)) if (length(.lhs) > 0) { .covNames <- .covNames[regexpr(rex::rex(start, or(.lhs), end), .covNames) == -1] } if (length(.covNames) > 0) { if (!all(.covNames %in% names(data))) { message("Model:") RxODE::rxCat(.ret$model$pred.only) message("Needed Covariates:") nlmixrPrint(.covNames) stop("Not all the covariates are in the dataset.") } message("Needed Covariates:") print(.covNames) } .extraPars <- .ret$model$extra.pars } else { .extraPars <- NULL } } .ret$skipCov <- skipCov if (is.null(skipCov)) { if (is.null(fixed)) { .tmp <- rep(FALSE, length(inits$THTA)) } else { if (length(fixed) < length(inits$THTA)) { .tmp <- c(fixed, rep(FALSE, length(inits$THTA) - length(fixed))) } else { .tmp <- fixed[1:length(inits$THTA)] } } if (exists("uif", envir = .ret)) { .uifErr <- .ret$uif$ini$err[!is.na(.ret$uif$ini$ntheta)] .uifErr <- sapply(.uifErr, function(x) { if (is.na(x)) { return(FALSE) } return(!any(x == c("pow2", "tbs", "tbsYj"))) }) .tmp <- (.tmp | .uifErr) } .ret$skipCov <- c(.tmp, rep(TRUE, length(.extraPars))) .ret$control$focei.mu.ref <- .ret$uif$focei.mu.ref } if (is.null(.extraPars)) { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA))) } else { .nms <- c(sprintf("THETA[%s]", seq_along(inits$THTA)), sprintf("ERR[%s]", seq_along(.extraPars))) } if (!is.null(thetaNames) && (length(inits$THTA) + length(.extraPars)) == length(thetaNames)) { .nms <- thetaNames } .ret$thetaNames <- .nms .thetaReset$thetaNames <- .nms if (length(lower) == 1) { lower <- rep(lower, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { print(inits$THTA) print(lower) stop("Lower must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (length(upper) == 1) { upper <- rep(upper, length(inits$THTA)) } else if (length(lower) != length(inits$THTA)) { stop("Upper must be a single constant for all the THETA lower bounds, or match the dimension of THETA.") } if (!is.null(.extraPars)) { .ret$model$extra.pars <- eval(call(control$diagXform, .ret$model$extra.pars)) if (length(.ret$model$extra.pars) > 0) { inits$THTA <- c(inits$THTA, .ret$model$extra.pars) .lowerErr <- rep(control$atol[1] * 10, length(.ret$model$extra.pars)) .upperErr <- rep(Inf, length(.ret$model$extra.pars)) lower <- c(lower, .lowerErr) upper <- c(upper, .upperErr) } } if (is.null(data$ID)) stop("\"ID\" not found in data") if (is.null(data$DV)) stop("\"DV\" not found in data") if (is.null(data$EVID)) data$EVID <- 0 if (is.null(data$AMT)) data$AMT <- 0 for (.v in c("TIME", "AMT", "DV", .covNames)) { data[[.v]] <- as.double(data[[.v]]) } .ret$dataSav <- data .ds <- data[data$EVID != 0 & data$EVID != 2, c("ID", "TIME", "AMT", "EVID", .covNames)] .w <- which(tolower(names(data)) == "limit") .limitName <- NULL if (length(.w) == 1L) { .limitName <- names(data)[.w] } .censName <- NULL .w <- which(tolower(names(data)) == "cens") if (length(.w) == 1L) { .censName <- names(data[.w]) } data <- data[data$EVID == 0 | data$EVID == 2, c("ID", "TIME", "DV", "EVID", .covNames, .limitName, .censName)] .w <- which(!(names(.ret$dataSav) %in% c(.covNames, keep))) names(.ret$dataSav)[.w] <- tolower(names(.ret$dataSav[.w])) if (.mixed) { .lh <- .parseOM(inits$OMGA) .nlh <- sapply(.lh, length) .osplt <- rep(1:length(.lh), .nlh) .lini <- list(inits$THTA, unlist(.lh)) .nlini <- sapply(.lini, length) .nsplt <- rep(1:length(.lini), .nlini) .om0 <- .genOM(.lh) if (length(etaNames) == dim(.om0)[1]) { .ret$etaNames <- .ret$etaNames } else { .ret$etaNames <- sprintf("ETA[%d]", seq(1, dim(.om0)[1])) } .ret$rxInv <- RxODE::rxSymInvCholCreate(mat = .om0, diag.xform = control$diagXform) .ret$xType <- .ret$rxInv$xType .om0a <- .om0 .om0a <- .om0a/control$diagOmegaBoundLower .om0b <- .om0 .om0b <- .om0b * control$diagOmegaBoundUpper .om0a <- RxODE::rxSymInvCholCreate(mat = .om0a, diag.xform = control$diagXform) .om0b <- RxODE::rxSymInvCholCreate(mat = .om0b, diag.xform = control$diagXform) .omdf <- data.frame(a = .om0a$theta, m = .ret$rxInv$theta, b = .om0b$theta, diag = .om0a$theta.diag) .omdf$lower <- with(.omdf, ifelse(a > b, b, a)) .omdf$lower <- with(.omdf, ifelse(lower == m, -Inf, lower)) .omdf$lower <- with(.omdf, ifelse(!diag, -Inf, lower)) .omdf$upper <- with(.omdf, ifelse(a < b, b, a)) .omdf$upper <- with(.omdf, ifelse(upper == m, Inf, upper)) .omdf$upper <- with(.omdf, ifelse(!diag, Inf, upper)) .ret$control$nomega <- length(.omdf$lower) .ret$control$neta <- sum(.omdf$diag) .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) lower <- c(lower, .omdf$lower) upper <- c(upper, .omdf$upper) } else { .ret$control$nomega <- 0 .ret$control$neta <- 0 .ret$xType <- -1 .ret$control$ntheta <- length(lower) .ret$control$nfixed <- sum(fixed) } .ret$lower <- lower .ret$upper <- upper .ret$thetaIni <- inits$THTA .scaleC <- double(length(lower)) if (is.null(control$scaleC)) { .scaleC <- rep(NA_real_, length(lower)) } else { .scaleC <- as.double(control$scaleC) if (length(lower) > length(.scaleC)) { .scaleC <- c(.scaleC, rep(NA_real_, length(lower) - length(.scaleC))) } else if (length(lower) < length(.scaleC)) { .scaleC <- .scaleC[seq(1, length(lower))] warning("scaleC control option has more options than estimated population parameters, please check.") } } .ret$scaleC <- .scaleC if (exists("uif", envir = .ret)) { .ini <- as.data.frame(.ret$uif$ini)[!is.na(.ret$uif$ini$err), c("est", "err", "ntheta")] for (.i in seq_along(.ini$err)) { if (is.na(.ret$scaleC[.ini$ntheta[.i]])) { if (any(.ini$err[.i] == c("boxCox", "yeoJohnson", "pow2", "tbs", "tbsYj"))) { .ret$scaleC[.ini$ntheta[.i]] <- 1 } else if (any(.ini$err[.i] == c("prop", "add", "norm", "dnorm", "logn", "dlogn", "lnorm", "dlnorm"))) { .ret$scaleC[.ini$ntheta[.i]] <- 0.5 * abs(.ini$est[.i]) } } } for (.i in .ini$model$extraProps$powTheta) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- 1 } .ini <- as.data.frame(.ret$uif$ini) for (.i in .ini$model$extraProps$factorial) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i] + 1)) } for (.i in .ini$model$extraProps$gamma) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- abs(1/digamma(.ini$est[.i])) } for (.i in .ini$model$extraProps$log) { if (is.na(.ret$scaleC[.i])) .ret$scaleC[.i] <- log(abs(.ini$est[.i])) * abs(.ini$est[.i]) } for (.i in .ret$logitThetas) { .b <- .ret$logitThetasLow[.i] .c <- .ret$logitThetasHi[.i] .a <- .ini$est[.i] if (is.na(.ret$scaleC[.i])) { .ret$scaleC[.i] <- 1 * (-.b + .c) * exp(-.a)/((1 + exp(-.a))^2 * (.b + 1 * (-.b + .c)/(1 + exp(-.a)))) } } } names(.ret$thetaIni) <- sprintf("THETA[%d]", seq_along(.ret$thetaIni)) if (is.null(etaMat) & !is.null(control$etaMat)) { .ret$etaMat <- control$etaMat } else { .ret$etaMat <- etaMat } .ret$setupTime <- (proc.time() - .pt)["elapsed"] if (exists("uif", envir = .ret)) { .tmp <- .ret$uif$logThetasList .ret$logThetas <- .tmp[[1]] .ret$logThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasList .ret$logitThetas <- .tmp[[1]] .ret$logitThetasF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListLow .ret$logitThetasLow <- .tmp[[1]] .ret$logitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$logitThetasListHi .ret$logitThetasHi <- .tmp[[1]] .ret$logitThetasHiF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasList .ret$probitThetas <- .tmp[[1]] .ret$probitThetasF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListLow .ret$probitThetasLow <- .tmp[[1]] .ret$probitThetasLowF <- .tmp[[2]] .tmp <- .ret$uif$probitThetasListHi .ret$probitThetasHi <- .tmp[[1]] .ret$probitThetasHiF <- .tmp[[2]] } else { .ret$logThetasF <- integer(0) .ret$logitThetasF <- integer(0) .ret$logitThetasHiF <- numeric(0) .ret$logitThetasLowF <- numeric(0) .ret$logitThetas <- integer(0) .ret$logitThetasHi <- numeric(0) .ret$logitThetasLow <- numeric(0) .ret$probitThetasF <- integer(0) .ret$probitThetasHiF <- numeric(0) .ret$probitThetasLowF <- numeric(0) .ret$probitThetas <- integer(0) .ret$probitThetasHi <- numeric(0) .ret$probitThetasLow <- numeric(0) } if (exists("noLik", envir = .ret)) { if (!.ret$noLik) { .ret$.params <- c(sprintf("THETA[%d]", seq_along(.ret$thetaIni)), sprintf("ETA[%d]", seq(1, dim(.om0)[1]))) .ret$.thetan <- length(.ret$thetaIni) .ret$nobs <- sum(data$EVID == 0) } } .ret$control$printTop <- TRUE .ret$control$nF <- 0 .est0 <- .ret$thetaIni if (!is.null(.ret$model$pred.nolhs)) { .ret$control$predNeq <- length(.ret$model$pred.nolhs$state) } else { .ret$control$predNeq <- 0L } .fitFun <- function(.ret) { this.env <- environment() assign("err", "theta reset", this.env) while (this.env$err == "theta reset") { assign("err", "", this.env) .ret0 <- tryCatch({ foceiFitCpp_(.ret) }, error = function(e) { if (regexpr("theta reset", e$message) != -1) { assign("zeroOuter", FALSE, this.env) assign("zeroGrad", FALSE, this.env) if (regexpr("theta reset0", e$message) != -1) { assign("zeroGrad", TRUE, this.env) } else if (regexpr("theta resetZ", e$message) != -1) { assign("zeroOuter", TRUE, this.env) } assign("err", "theta reset", this.env) } else { assign("err", e$message, this.env) } }) if (this.env$err == "theta reset") { .nm <- names(.ret$thetaIni) .ret$thetaIni <- setNames(.thetaReset$thetaIni + 0, .nm) .ret$rxInv$theta <- .thetaReset$omegaTheta .ret$control$printTop <- FALSE .ret$etaMat <- .thetaReset$etaMat .ret$control$etaMat <- .thetaReset$etaMat .ret$control$maxInnerIterations <- .thetaReset$maxInnerIterations .ret$control$nF <- .thetaReset$nF .ret$control$gillRetC <- .thetaReset$gillRetC .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillRet <- .thetaReset$gillRet .ret$control$gillDf <- .thetaReset$gillDf .ret$control$gillDf2 <- .thetaReset$gillDf2 .ret$control$gillErr <- .thetaReset$gillErr .ret$control$rEps <- .thetaReset$rEps .ret$control$aEps <- .thetaReset$aEps .ret$control$rEpsC <- .thetaReset$rEpsC .ret$control$aEpsC <- .thetaReset$aEpsC .ret$control$c1 <- .thetaReset$c1 .ret$control$c2 <- .thetaReset$c2 if (this.env$zeroOuter) { message("Posthoc reset") .ret$control$maxOuterIterations <- 0L } else if (this.env$zeroGrad) { message("Theta reset (zero gradient values); Switch to bobyqa") RxODE::rxReq("minqa") .ret$control$outerOptFun <- .bobyqa .ret$control$outerOpt <- -1L } else { message("Theta reset (ETA drift)") } } } if (this.env$err != "") { stop(this.env$err) } else { return(.ret0) } } .ret0 <- try(.fitFun(.ret)) .n <- 1 while (inherits(.ret0, "try-error") && control$maxOuterIterations != 0 && .n <= control$nRetries) { message(sprintf("Restart %s", .n)) .ret$control$nF <- 0 .estNew <- .est0 + 0.2 * .n * abs(.est0) * stats::runif(length(.est0)) - 0.1 * .n .estNew <- sapply(seq_along(.est0), function(.i) { if (.ret$thetaFixed[.i]) { return(.est0[.i]) } else if (.estNew[.i] < lower[.i]) { return(lower + (.Machine$double.eps)^(1/7)) } else if (.estNew[.i] > upper[.i]) { return(upper - (.Machine$double.eps)^(1/7)) } else { return(.estNew[.i]) } }) .ret$thetaIni <- .estNew .ret0 <- try(.fitFun(.ret)) .n <- .n + 1 } if (inherits(.ret0, "try-error")) stop("Could not fit data.") .ret <- .ret0 if (exists("parHistData", .ret)) { .tmp <- .ret$parHistData .tmp <- .tmp[.tmp$type == "Unscaled", names(.tmp) != "type"] .iter <- .tmp$iter .tmp <- .tmp[, names(.tmp) != "iter"] .ret$parHistStacked <- data.frame(stack(.tmp), iter = .iter) names(.ret$parHistStacked) <- c("val", "par", "iter") .ret$parHist <- data.frame(iter = .iter, .tmp) } if (.mixed) { .etas <- .ret$ranef .thetas <- .ret$fixef .pars <- .Call(`_nlmixr_nlmixrParameters`, .thetas, .etas) .ret$shrink <- .Call(`_nlmixr_calcShrinkOnly`, .ret$omega, .pars$eta.lst, length(.etas$ID)) .updateParFixed(.ret) } else { .updateParFixed(.ret) } if (!exists("table", .ret)) { .ret$table <- tableControl() } if (control$calcTables) { .ret <- addTable(.ret, updateObject = "no", keep = keep, drop = drop, table = .ret$table) } .ret})(data = dat, inits = .FoceiInits, PKpars = .pars, model = .mod, pred = function() { return(nlmixr_pred) }, err = uif$error, lower = uif$focei.lower, upper = uif$focei.upper, fixed = uif$focei.fixed, thetaNames = uif$focei.names, etaNames = uif$eta.names, control = control, env = env, keep = .keep, drop = .drop): Not all the covariates are in the dataset.
#> Timing stopped at: 17.34 0.397 17.73
AIC( f_nlmixr_sfo_sfo_focei_const$nm, f_nlmixr_fomc_sfo_focei_const$nm, -- cgit v1.2.1