intervals() methods, more DFOP/tc variants

1 files changed, 179 insertions, 0 deletions

diff --git a/R/intervals.R b/R/intervals.R
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+#' @importFrom nlme intervals
+#' @export
+nlme::intervals
+
+#' Confidence intervals for parameters in saem.mmkin objects
+#'
+#' @param object The fitted saem.mmkin object
+#' @param level The confidence level. Must be the default of 0.95 as this is what
+#'   is available in the saemix object
+#' @param backtransform In case the model was fitted with mkin transformations,
+#'  should we backtransform the parameters where a one to one correlation
+#'  between transformed and backtransformed parameters exists?
+#' @return An object with 'intervals.saem.mmkin' and 'intervals.lme' in the
+#'  class attribute
+#' @export
+intervals.saem.mmkin <- function(object, level = 0.95, backtransform = TRUE, ...)
+{
+  if (!identical(level, 0.95)) {
+    stop("Confidence intervals are only available for a level of 95%")
+  }
+
+  mod_vars <- names(object$mkinmod$diffs)
+
+  pnames <- names(object$mean_dp_start)
+
+  # Confidence intervals are available in the SaemixObject, so
+  # we just need to extract them and put them into a list modelled
+  # after the result of nlme::intervals.lme
+
+  conf.int <- object$so@results@conf.int
+  rownames(conf.int) <- conf.int$name
+  colnames(conf.int)[2] <- "est."
+  confint_trans <- as.matrix(conf.int[pnames, c("lower", "est.", "upper")])
+
+  # Fixed effects
+  # In case objects were produced by earlier versions of saem
+  if (is.null(object$transformations)) object$transformations <- "mkin"
+
+  if (object$transformations == "mkin" & backtransform) {
+    bp <- backtransform_odeparms(confint_trans[, "est."], object$mkinmod,
+      object$transform_rates, object$transform_fractions)
+    bpnames <- names(bp)
+
+    # Transform boundaries of CI for one parameter at a time,
+    # with the exception of sets of formation fractions (single fractions are OK).
+    f_names_skip <- character(0)
+    for (box in mod_vars) { # Figure out sets of fractions to skip
+      f_names <- grep(paste("^f", box, sep = "_"), pnames, value = TRUE)
+      n_paths <- length(f_names)
+      if (n_paths > 1) f_names_skip <- c(f_names_skip, f_names)
+    }
+
+    confint_back <- matrix(NA, nrow = length(bp), ncol = 3,
+      dimnames = list(bpnames, colnames(confint_trans)))
+    confint_back[, "est."] <- bp
+
+    for (pname in pnames) {
+      if (!pname %in% f_names_skip) {
+        par.lower <- confint_trans[pname, "lower"]
+        par.upper <- confint_trans[pname, "upper"]
+        names(par.lower) <- names(par.upper) <- pname
+        bpl <- backtransform_odeparms(par.lower, object$mkinmod,
+                                              object$transform_rates,
+                                              object$transform_fractions)
+        bpu <- backtransform_odeparms(par.upper, object$mkinmod,
+                                              object$transform_rates,
+                                              object$transform_fractions)
+        confint_back[names(bpl), "lower"] <- bpl
+        confint_back[names(bpu), "upper"] <- bpu
+      }
+    }
+    confint_ret <- confint_back
+  } else {
+    confint_ret <- confint_trans
+  }
+  attr(confint_ret, "label") <- "Fixed effects:"
+
+  # Random effects
+  ranef_ret <- as.matrix(conf.int[paste0("SD.", pnames), c("lower", "est.", "upper")])
+  rownames(ranef_ret) <- paste0(gsub("SD\\.", "sd(", rownames(ranef_ret)), ")")
+  attr(ranef_ret, "label") <- "Random effects:"
+
+
+  # Error model
+  enames <- if (object$err_mod == "const") "a.1" else c("a.1", "b.1")
+  err_ret <- as.matrix(conf.int[enames, c("lower", "est.", "upper")])
+
+  res <- list(
+    fixed = confint_ret,
+    random = ranef_ret,
+    errmod = err_ret
+  )
+  class(res) <- c("intervals.saemix.mmkin", "intervals.lme")
+  attr(res, "level") <- level
+  return(res)
+}
+
+#' Confidence intervals for parameters in nlmixr.mmkin objects
+#'
+#' @param object The fitted saem.mmkin object
+#' @param level The confidence level.
+#' @param backtransform Should we backtransform the parameters where a one to
+#'   one correlation between transformed and backtransformed parameters exists?
+#' @importFrom nlme intervals
+#' @return An object with 'intervals.saem.mmkin' and 'intervals.lme' in the
+#'  class attribute
+#' @export
+intervals.nlmixr.mmkin <- function(object, level = 0.95, backtransform = TRUE, ...)
+{
+
+  # Fixed effects
+  mod_vars <- names(object$mkinmod$diffs)
+
+  conf.int <- confint(object$nm)
+  dpnames <- setdiff(rownames(conf.int), names(object$mean_ep_start))
+  ndp <- length(dpnames)
+
+  confint_trans <- as.matrix(conf.int[dpnames, c(3, 1, 4)])
+  colnames(confint_trans) <- c("lower", "est.", "upper")
+
+  if (backtransform) {
+    bp <- backtransform_odeparms(confint_trans[, "est."], object$mkinmod,
+      object$transform_rates, object$transform_fractions)
+    bpnames <- names(bp)
+
+    # Transform boundaries of CI for one parameter at a time,
+    # with the exception of sets of formation fractions (single fractions are OK).
+    f_names_skip <- character(0)
+    for (box in mod_vars) { # Figure out sets of fractions to skip
+      f_names <- grep(paste("^f", box, sep = "_"), dpnames, value = TRUE)
+      n_paths <- length(f_names)
+      if (n_paths > 1) f_names_skip <- c(f_names_skip, f_names)
+    }
+
+    confint_back <- matrix(NA, nrow = length(bp), ncol = 3,
+      dimnames = list(bpnames, colnames(confint_trans)))
+    confint_back[, "est."] <- bp
+
+    for (pname in dpnames) {
+      if (!pname %in% f_names_skip) {
+        par.lower <- confint_trans[pname, "lower"]
+        par.upper <- confint_trans[pname, "upper"]
+        names(par.lower) <- names(par.upper) <- pname
+        bpl <- backtransform_odeparms(par.lower, object$mkinmod,
+                                              object$transform_rates,
+                                              object$transform_fractions)
+        bpu <- backtransform_odeparms(par.upper, object$mkinmod,
+                                              object$transform_rates,
+                                              object$transform_fractions)
+        confint_back[names(bpl), "lower"] <- bpl
+        confint_back[names(bpu), "upper"] <- bpu
+      }
+    }
+    confint_ret <- confint_back
+  } else {
+    confint_ret <- confint_trans
+  }
+  attr(confint_ret, "label") <- "Fixed effects:"
+
+  # Random effects
+  ranef_ret <- as.matrix(data.frame(lower = NA, 
+      "est." = sqrt(diag(object$nm$omega)), upper = NA))
+  rownames(ranef_ret) <- paste0(gsub("eta\\.", "sd(", rownames(ranef_ret)), ")")
+  attr(ranef_ret, "label") <- "Random effects:"
+
+  # Error model
+  enames <- names(object$nm$sigma)
+  err_ret <- as.matrix(conf.int[enames, c(3, 1, 4)])
+  colnames(err_ret) <- c("lower", "est.", "upper")
+
+  res <- list(
+    fixed = confint_ret,
+    random = ranef_ret,
+    errmod = err_ret
+  )
+  class(res) <- c("intervals.nlmixr.mmkin", "intervals.lme")
+  attr(res, "level") <- level
+  return(res)
+}