Medium rare. [R for BE/BA]

posted by Helmut Homepage – Vienna, Austria, 2020-07-13 13:52 (138 d 05:00 ago) – Posting: # 21684
Views: 9,749

Hi ElMaestro,

» Job done?

I prefer medium rare over well done (aka quick and dirty or clean and never)!
Below my more R-ish code. Changes:
TODO:

###############################
# Section 1: Household things #
###############################

GetData <- function(path, sep, dec) {
  # read data from a CSV-file
  if (missing(sep)) sep <- ","
  if (!sep %in% c(",", ";", "t"))
    stop("Column separator must be any of ',', ';', 't'.")
  if (sep == "t") sep <- "\t"
  if (missing(dec)) dec <- "."
  if (!dec %in% c(".", ","))
    stop("Decimal separator must be '.', or ','.")
  # strip quotes and skip eventual commentary lines
  D        <- read.csv(path, sep = sep, dec = dec,
                       quote = "", comment.char = "#")
  names(D) <- c("Subj", "Per", "Seq", "Trt", "Y")
  cols     <- c("Subj", "Per", "Seq", "Trt")
  D[cols]  <- lapply(D[cols], factor)
  return(invisible(D))
}

CreateX <- function(D) {
  # first the two treatments
  TrtT <- as.numeric(as.character(D$Trt) == "T")
  TrtR <- as.numeric(as.character(D$Trt) == "R")
  X <- cbind(TrtT, TrtR)
  R <- qr(X)$rank
  # now the periods
  for (p in unique(D$Per)) {
    v  <- as.numeric(D$Per == p)
    XX <- data.frame(X, v)
    names(XX)[ncol(XX)] <- paste0("P", p)
    rnk <- qr(XX)$rank
    if (rnk > R) {
      X <- XX
      R <- rnk
    }
  }
  for (q in unique(D$Seq)) {
    v  <- as.numeric(D$Seq == q)
    XX <- data.frame(X, v)
    names(XX)[ncol(XX)] <- paste0("Q", q)
    rnk <- qr(XX)$rank
    if (rnk > R) {
      X <- XX
      R <- rnk
    }
  }
  return(as.matrix(X))
}
Create.CovM <- function(Params) {
  # block diagonal covariance matrix
  varT  <- Params[1]
  varBR <- Params[2]
  varWR <- Params[3]
  varRT <- Params[4]
  Nobs  <- length(D$Y)
  V     <- matrix(0, ncol = Nobs, nrow = Nobs)
  for (iRow in 1:Nobs) {
    for (iCol in 1:Nobs) {
      if (iCol == iRow) { # diagonal elements
        if (D$Trt[iRow] == "T") {
          V[iRow, iCol] <- V[iRow, iCol] + varT
        } else {
          V[iRow, iCol] <- V[iRow, iCol] + varWR + varBR
        }
      } else {            # off diagonal elements
        if (D$Subj[iRow] == D$Subj[iCol]) {
          if (D$Trt[iCol] == D$Trt[iRow]) {
            V[iRow, iCol] <- V[iRow, iCol] + varBR
          } else {
            V[iRow, iCol] <- V[iRow, iCol] + varRT
          }
        }
      }
    }
  }
  return(V)
}

############################
# Section 2: Matrix things #
############################
Obj.F12 <- function(Pars) {
  # this is line 3 of page 10 of:
  # http://people.csail.mit.edu/xiuming/docs/tutorials/reml.pdf
  CovM  <- Create.CovM(Pars)
  A     <- -0.5*log(det(CovM))
  # TODO: NaNs produced in the next line cause t(X) is not a square matrix
  B     <- -0.5*log(det(t(X) %*% solve(CovM) %*% X))
  est.b <- solve(t(X) %*% solve(CovM) %*% X) %*% t(X) %*% solve(CovM) %*% y
  tmp   <- y - X %*% est.b
  C     <- -0.5 *(t(tmp) %*% solve(CovM) %*% tmp)
  C     <- as.numeric(C) # make a scalar for other solvers
  return(A+B+C)
}

########################
# Section 3: Execution #
########################
Some.Initial.Guesses <- function() {
  # design (all possible ones, error handling, full or partial)
  subjs <- unique(as.numeric(D$Subj))
  trts  <- sort(unique(as.character(D$Trt)), decreasing = TRUE)
  if (!length(trts) == 2) stop("Only two treatments supported.")
  if (sum(!trts %in% c("T", "R")) !=0)
    stop("treatments must be coded as 'T' and 'R'.")
  seqs  <- sort(unique(as.character(D$Seq)), decreasing = TRUE) # T first
  type  <- paste(seqs, collapse = "|") # identifier
  nseq  <- length(unique(as.character(D$Seq)))
  nper  <- length(unique(as.numeric(D$Per)))
  nsubj <- length(subjs)
  if (nchar(type) == 19) {  # 4-period 4-sequence full replicate designs
    if (nper != 4) stop("4 periods required in this full replicate design.")
    if (nseq != 4) stop("4 sequences required in this full replicate design.")
    des <- "full"
  }
  if (nchar(type) == 9) {  # 4-period full replicate designs
    if (nper != 4) stop("4 periods required in this full replicate design.")
    if (nseq != 2) stop("2 sequences required in this full replicate design.")
    des <- "full"
  }
  if (nchar(type) == 7) {  # 3-period replicates
    if (type %in% c("TRT|RTR", "TRR|RTT")) {
      if (nper != 3) stop("3 periods required in this full replicate design.")
      if (nseq != 2) stop("2 sequences required in this full replicate design.")
      des <- "full"
    }
    if (type == "TRR|RTR") {
      if (nper != 3) stop("3 periods required in the extra-reference design.")
      if (nseq != 2) stop("2 sequences required in the extra-reference design.")
      des <- "partial"
    }
  }
  if (nchar(type) == 11) { # Balaam's design or 3-sequence partial
    if (!type == "TR|RT|TT|RR") { # Balamm's
      if (nper != 3) stop("3 periods required in this partial replicate design.")
      if (nseq != 3) stop("3 sequences required in this partial replicate design.")
      des <- "partial"
    } else {                      # TRT|RTR|RRT
      if (nper != 2) stop("2 periods required in Balaam's design.")
      if (nseq != 4) stop("4 sequences required in Balaam's design.")
      des <- "full"
    }
  }
  if (type == "TR|RT") stop("TR|RT design not supported yet.")
  gm.T <- gm.R <- numeric(nsubj) # vector of geometric means
  for (subj in seq_along(subjs)) {
    gm.T[subj] <- mean(log(D$Y[which(D$Subj == subj & D$Trt == "T")]))
    gm.R[subj] <- mean(log(D$Y[which(D$Subj == subj & D$Trt == "R")]))
  }
  # get rid of missings
  gm.T <- gm.T[!is.na(gm.T)]  
  gm.R <- gm.R[!is.na(gm.R)]  
  if (des == "partial") { # guess varT (between + within)
    m    <- lm(log(Y) ~ Seq+Per, data = D[D$Trt == "T", ])
    varT <- anova(m)["Residuals", "Mean Sq"]
  } else {                # guess VarWT
    m     <- lm(log(Y) ~ Seq+Per+Subj, data = D[D$Trt == "T", ])
    varWT <- anova(m)["Residuals", "Mean Sq"]
  }
  # guess VarWR
  m     <- lm(log(Y) ~ Seq+Per+Subj, data = D[D$Trt == "R", ])
  varWR <- anova(m)["Residuals", "Mean Sq"]   # guess varBR
  varBR <- var(gm.R)-varWR
  # TODO: full replicates
  varRT <- 0.5*(varT+varBR)
  rslt  <- c(varT, varBR, varWR, varRT)
  return(rslt)
}
MyREML <- function() {
  Ini <- Some.Initial.Guesses()
  F   <- optim(par = Ini, fn = Obj.F12,
               control = list(reltol = 1e-12, trace = 0, fnscale = -1))
  Nms <- c("var_T", "var_bR", "var_wR", "covar_bTbR")
  X   <- data.frame(Nms, F$par, Ini)
  names(X) <- c("Component", "Estimate", "Initial")
  cat("Maximum         :", F$value,
    "\nEvaluations     :", F$counts[["function"]],
    "\nConvergence code:", F$convergence, "\n")
  return(X)
}

# Data has to have five columns in this order:
#   Subject (numeric), Period (numeric), Sequence (character),
#   Treatment (character), Response (numeric)
# Column separator 'sep' comma (default), semicolon, or t (tab)
# Decimal separator 'dec' period (default) or comma
# path <- "https://bebac.at/downloads/ds01.csv" # EMA full replicate
path <- "https://bebac.at/downloads/ds02.csv" # EMA partial replicate
D   <- NULL # nullify eventual previous one
D   <- GetData(path)
X   <- CreateX(D)
y   <- log(D$Y)
# the workhorse
res <- MyREML() # patience!
G.matrix <- data.frame(c(NA, res$Estimate[4]),
                       c(res$Estimate[4], res$Estimate[2]))
names(G.matrix) <- 1:2
print(res, row.names = FALSE); cat("G matrix:\n"); print(G.matrix)


Gives:
Maximum         : 75.98722
Evaluations     : 197
Convergence code: 0
Warning message:
In log(det(t(X) %*% solve(CovM) %*% X)) : NaNs produced

  Component   Estimate    Initial
      var_T 0.07049482 0.06841615
     var_bR 0.03621594 0.02776728
     var_wR 0.01324652 0.01240137
 covar_bTbR 0.04563735 0.04809171
G matrix:
           1          2
1         NA 0.04563735
2 0.04563735 0.03621594

Dif-tor heh smusma 🖖
Helmut Schütz
[image]

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

Activity
 Admin contact
21,216 posts in 4,427 threads, 1,482 registered users;
online 21 (0 registered, 21 guests [including 11 identified bots]).
Forum time: Saturday 17:53 CET (Europe/Vienna)

Science may be described as the art of systematic over-simplification –
the art of discerning what we may with advantage omit.    Karl R. Popper

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5