R/convertEmax.R

In nlmixr2lib: A Model Library for 'nlmixr2'

#' Convert linear effect to Emax effect
#'
#' @param ui rxode2 model
#'
#' @param emax Emax parameter
#' @param ec50 EC50 parameter
#' @param imax Imax parameter used when input model contains "Ik"
#'   instead of "Ek"
#' @param ic50 IC50 parameter used when input model contains "Ik"
#'   instead of "Ek"
#' @inheritParams addIndirectLin
#'
#' @family PD
#'
#' @return Model with the linear effect converted to an Emax effect
#'
#' @export
#' @author Matthew L. Fidler
#' @examples
#'
#' readModelDb("PK_2cmt_no_depot") |>
#'   addIndirectLin(stim="in") |>
#'   convertEmax()
#'
#' # When emax=1
#' readModelDb("PK_2cmt_no_depot") |>
#'   addIndirectLin(stim="in") |>
#'   convertEmax(emax=1)
#'
convertEmax <- function(ui, emax="Emax", ec50="EC50",
                        imax="Imax", ic50="IC50",
                        ek=c("Ik", "Ek"), cc=c("Ec", "Cc")) {
  .ui <- rxode2::assertRxUi(ui)
  cc <- rxode2::assertExists(.ui, cc)
  ek <- rxode2::assertVariableExists(.ui, ek)
  if (ek == "Ik") {
    emax <- imax
    ec50 <- ic50
  }
  if (inherits(emax, "character")) {
    rxode2::assertVariableNew(.ui, emax)
    .emaxMult <- paste0(emax, "*")
  } else if (is.numeric(emax) && emax == 1.0) {
    .emaxMult <- ""
  } else {
    stop("'", emax, "' not specified correctly",
         call.=FALSE)
  }
  rxode2::assertVariableNew(.ui, ec50)
  .modelLines <- .replaceMult(.ui$lstExpr,
                              v1=ek, v2=cc,
                              ret=paste0(.emaxMult,
                                         cc, "/(", cc, "+", ec50, ")"))
  .tmp <- .getEtaThetaTheta1(.ui)
  .iniDf <- .tmp$iniDf
  .theta <- .tmp$theta
  .theta1 <- .tmp$theta1
  .eta <- .tmp$eta
  .tmp <- .dropLines(.ui, .modelLines, .theta, .eta, ek)
  .modelLines <- .tmp$modelLines
  .theta <- .tmp$theta
  .eta <- .tmp$eta

  if (length(.theta$ntheta) == 0) {
    .ntheta <- 0
  } else {
    .ntheta <- max(.theta$ntheta)
  }

  .emaxLine <- NULL
  if (.emaxMult != "") {
    .emaxLine <- list(str2lang(paste0(emax, "<- exp(l", emax, ")")))
    .thetaEmax <- .get1theta(emax, .theta1, .ntheta,
                             label=paste0("Maximum effect (", emax, ")"))
    .ntheta <- .ntheta + 1
  } else {
    .thetaEmax <- NULL
  }

  .thetaEc50 <- .get1theta(ec50, .theta1, .ntheta,
                           label=paste0("Concentration of 50% ", emax,
                                        " (", emax, ")"))
  .ntheta <- .ntheta + 1

  .ui <- rxode2::rxUiDecompress(.ui)
  .ui$iniDf <- rbind(.theta,
                     .thetaEmax,
                     .thetaEc50,
                     .eta)
  if (exists("description", envir=.ui$meta)) {
    rm("description", envir=.ui$meta)
  }
  rxode2::model(.ui) <- c(.emaxLine,
                          list(str2lang(paste0(ec50, "<- exp(l", ec50, ")"))),
                          .modelLines)
  .ui
}

#'  Convert linear effect to Emax-Hill effect
#'
#' @inheritParams convertEmax
#' @param g hill coefficient
#' @return Model with the linear effect converted to an Emax effect
#' @export
#' @author Matthew L. Fidler
#' @examples
#'
#' readModelDb("PK_2cmt_no_depot") |>
#'   addIndirectLin(stim="in") |>
#'   convertEmaxHill()
#'
#' # can also specify as emax=1
#'
#' readModelDb("PK_2cmt_no_depot") |>
#'   addIndirectLin(stim="in") |>
#'   convertEmaxHill(emax=1)
#'
convertEmaxHill <- function(ui, emax="Emax", ec50="EC50", g="g",
                            imax="Imax", ic50="IC50",
                            ek=c("Ik", "Ek"), cc=c("Ec", "Cc")) {
  .ui <- rxode2::assertRxUi(ui)
  cc <- rxode2::assertExists(.ui, cc)
  ek <- rxode2::assertVariableExists(.ui, ek)
  if (ek == "Ik") {
    emax <- imax
    ec50 <- ic50
  }
  .emaxMult <- paste0(emax, "*")
  if (inherits(emax, "character")) {
    rxode2::assertVariableNew(.ui, emax)
  } else if (is.numeric(emax) && emax == 1.0) {
    .emaxMult <- ""
  } else {
    stop("'", emax, "' not specified correctly",
         call.=FALSE)
  }
  rxode2::assertVariableNew(.ui, ec50)

  .modelLines <- .replaceMult(.ui$lstExpr,
                              v1=ek, v2=cc,
                              ret=paste0(.emaxMult, cc, "^", g,
                                         "/(", cc, "^", g,
                                         "+", ec50, "^", g, ")"))
  .tmp <- .getEtaThetaTheta1(.ui)
  .iniDf <- .tmp$iniDf
  .theta <- .tmp$theta
  .theta1 <- .tmp$theta1
  .eta <- .tmp$eta
  .tmp <- .dropLines(.ui, .modelLines, .theta, .eta, ek)
  .modelLines <- .tmp$modelLines
  .theta <- .tmp$theta
  .eta <- .tmp$eta

  if (length(.theta$ntheta) == 0) {
    .ntheta <- 0
  } else {
    .ntheta <- max(.theta$ntheta)
  }

  .emaxLine <- NULL
  if (.emaxMult != "") {
    .emaxLine <- list(str2lang(paste0(emax, "<- exp(l", emax, ")")))
    .thetaEmax <- .get1theta(emax, .theta1, .ntheta,
                             label=paste0("Maximum effect (", emax, ")"))
    .ntheta <- .ntheta + 1
  } else {
    .thetaEmax <- NULL
  }

  .thetaEc50 <- .get1theta(ec50, .theta1, .ntheta,
                           label=paste0("Concentration of 50% ", emax,
                                        " (", emax, ")"))
  .ntheta <- .ntheta + 1

  .thetaEc50 <- .get1theta(ec50, .theta1, .ntheta,
                           label=paste0("Concentration of 50% ", emax,
                                        " (", emax, ")"))
  .ntheta <- .ntheta + 1

  .thetaG <- .get1theta(g, .theta1, .ntheta, name=paste0("lg", g),
                        est=logit(1, 0.1, 10),
                        label=paste0("logit-constrained Hill coefficient ", g))
  .ntheta <- .ntheta + 1


  .ui <- rxode2::rxUiDecompress(.ui)
  .ui$iniDf <- rbind(.theta,
                     .thetaEmax,
                     .thetaEc50,
                     .thetaG,
                     .eta)
  if (exists("description", envir=.ui$meta)) {
    rm("description", envir=.ui$meta)
  }
  rxode2::model(.ui) <- c(.emaxLine,
                          list(str2lang(paste0(ec50, "<- exp(l", ec50, ")")),
                               str2lang(paste0(g, "<- expit(lg", g, ", 0.1, 10)"))),
                          .modelLines)
  .ui
}