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#' @title Bootstrapped TOST with log transformed t-tests
#' @description
#' `r lifecycle::badge('stable')`
#'
#' A function for a bootstrap method for TOST with all types of t-tests.
#' @inheritParams boot_t_TOST
#' @inheritParams log_TOST
#' @return An S3 object of class
#' `"TOSTt"` is returned containing the following slots:
#'
#' - "TOST": A table of class `"data.frame"` containing two-tailed t-test and both one-tailed results.
#' - "eqb": A table of class `"data.frame"` containing equivalence bound settings.
#' - "effsize": table of class `"data.frame"` containing effect size estimates.
#' - "hypothesis": String stating the hypothesis being tested.
#' - "smd": List containing the results of the means ratio calculation.
#' - Items include: d (means ratio estimate), dlow (lower CI bound), dhigh (upper CI bound), d_df (degrees of freedom for SMD), d_sigma (SE), d_lambda (non-centrality), J (bias correction), smd_label (type of SMD), d_denom (denominator calculation)
#' - "alpha": Alpha level set for the analysis.
#' - "method": Type of t-test.
#' - "decision": List included text regarding the decisions for statistical inference.
#' - "boot": List containing the bootstrap samples.
#'
#' @details The implemented test(s) corresponds to the proposal of Chapter 16 of Efron and Tibshirani (1994),
#' and recommended by He et al (2022).
#' Returns TOSTt class object with bootstrapped based results.
#' This is approximately equivalent to the percentile bootstrap method mentioned by He et al (2014).
#'
#' For two-sample tests, the test is of \eqn{\bar log(x) - \bar log(y)} (mean of x minus mean of y).
#' For paired samples, the test is of the difference scores (z),
#' wherein \eqn{z = log(x) - log(y) = log(x)/log(y)}, and the test is of \eqn{\bar z} (mean of the difference/ratio scores).
#'
#'
#'
#' For details on the calculations in this function see `vignette("robustTOST")`.
#' @references
#' Efron, B., & Tibshirani, R. J. (1994). An introduction to the bootstrap. CRC press
#'
#' He, Y., Deng, Y., You, C., & Zhou, X. H. (2022). Equivalence tests for ratio of means in bioequivalence studies under crossover design. Statistical Methods in Medical Research, 09622802221093721.
#'
#' Food and Drug Administration (2014). Bioavailability and Bioequivalence Studies Submitted in NDAs or INDs — General Considerations.
#' Center for Drug Evaluation and Research. Docket: FDA-2014-D-0204.
#' https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bioavailability-and-bioequivalence-studies-submitted-ndas-or-inds-general-considerations
#' @importFrom stats var quantile
#' @name boot_log_TOST
#' @family Robust tests
#' @family TOST
#' @export boot_log_TOST
boot_log_TOST <- function(x, ...){
UseMethod("boot_log_TOST")
}
#' @rdname boot_log_TOST
#' @method boot_log_TOST default
#' @export
boot_log_TOST.default <- function(x,
y = NULL,
hypothesis = c("EQU","MET"),
paired = FALSE,
var.equal = FALSE,
eqb = 1.25,
alpha = 0.05,
null = 1,
R = 1999, ...){
hypothesis = match.arg(hypothesis)
if(!missing(null) && (length(null) != 1 || is.na(null))) {
stop("'null' must be a single number")
}
if(any(x < 0) || any(y < 0)){
stop("Negative values detected. Values must be on ratio scale (true zero).")
}
if(!missing(alpha) && (length(alpha) != 1 || !is.finite(alpha) ||
alpha < 0 || alpha > 1)) {
stop("'alpha' must be a single number between 0 and 1")
}
if(!is.numeric(eqb) || length(eqb) > 2){
stop(
"eqb must be a numeric of a length of 1 or 2"
)
}
if(length(eqb) == 1){
if(eqb > 1){
high_eqbound = eqb
low_eqbound = 1/eqb
} else{
high_eqbound = 1/eqb
low_eqbound = eqb
}
} else {
high_eqbound = max(eqb)
low_eqbound = min(eqb)
}
if (!is.null(y)) {
dname <- paste(deparse(substitute(x)), "and",
deparse(substitute(y)))
x = log(x)
y = log(y)
}
else {
stop("One sample tests not supported at this time.")
}
#if (paired) {
# stop("'y' is missing for paired test")
#}
xok <- !is.na(x)
yok <- NULL
x <- x[xok]
if(paired){
x <- x - y
y <- NULL
}
nx <- length(x)
mx <- mean(x)
vx <- var(x)
if(!paired){
nullTOST = log_TOST(x = exp(x),
y = exp(y),
hypothesis = hypothesis,
paired = paired,
var.equal = var.equal,
eqb = eqb,
alpha = alpha,
null = null)
} else {
nullTOST = log_pair(x = x,
hypothesis = hypothesis,
eqb = eqb,
alpha = alpha,
null = null)
}
d_vec <- rep(NA, times=length(R)) # smd vector
m_vec <- rep(NA, times=length(R)) # mean difference vector
#t_vec <- rep(NA, times=length(R)) # t-test vector
#tl_vec <- rep(NA, times=length(R)) # lower bound vector
#tu_vec <- rep(NA, times=length(R)) # upper bound vector
conf.level = 1-alpha*2
if(!is.null(y)){
dname <- paste(deparse(substitute(x)), "and", deparse(substitute(y)))
if (paired) {
i1 <- y
i2 <- x
data <- data.frame(i1 = i1, i2 = i2)
data <- na.omit(data)
y <- data$i1
x <- data$i2
}
yok <- !is.na(y)
xok <- !is.na(x)
y <- y[yok]
}
x <- x[xok]
nx <- length(x)
mx <- mean(x)
vx <- var(x)
# Paired ----
if (is.null(y)) {
if (nx < 2)
stop("not enough 'x' observations")
df <- nx - 1
stderr <- sqrt(vx/nx)
if (stderr < 10 * .Machine$double.eps * abs(mx)){
stop("data are essentially constant")
}
#tstat <- (mx - mu)/stderr
#tstat_low = (mx - low_eqbound)/stderr
#tstat_high = (mx - high_eqbound)/stderr
method <- "Bootstrapped Log Paired t-test" # else "Bootstrapped One Sample t-test"
#estimate <- setNames(mx, if (paired) "mean of the differences" else "mean of x")
#x.cent <- x - mx # remove to have an untransformed matrix
X <- matrix(sample(x, size = nx*R, replace = TRUE), nrow = R)
MX <- rowMeans(X - mx)
VX <- rowSums((X - MX) ^ 2) / (nx - 1)
STDERR <- sqrt(VX/nx)
TSTAT <- (MX)/STDERR
#TSTAT_low <- (MX-low_eqbound)/STDERR
#TSTAT_high <- (MX-high_eqbound)/STDERR
EFF <- MX+mx
for(i in 1:nrow(X)){
dat = X[i,]
runTOST = log_pair(
x = dat,
hypothesis = hypothesis,
eqb = eqb,
alpha = alpha,
null = null
)
d_vec[i] <- runTOST$smd$d # smd vector
m_vec[i] <- runTOST$effsize$estimate[1] # mean difference vector
#t_vec[i] <- runTOST$TOST$t[1] - mx # t-test vector
#tl_vec[i] <- runTOST$TOST$t[2] - mx # lower bound vector
#tu_vec[i] <- runTOST$TOST$t[3] - mx # upper bound vector
}
}
# Two sample ----
if(!is.null(y)){
ny <- length(y)
if(nx < 1 || (!var.equal && nx < 2))
stop("not enough 'x' observations")
if(ny < 1 || (!var.equal && ny < 2))
stop("not enough 'y' observations")
if(var.equal && nx + ny < 3)
stop("not enough observations")
my <- mean(y)
vy <- var(y)
method <- paste("Bootstrapped Log", paste(if (!var.equal) "Welch", "Two Sample t-test"))
estimate <- c(mx, my)
names(estimate) <- c("mean of x", "mean of y")
if(var.equal){
df <- nx + ny - 2
v <- 0
if (nx > 1){
v <- v + (nx - 1) * vx
}
if (ny > 1){
v <- v + (ny - 1) * vy
}
v <- v/df
stderr <- sqrt(v * (1/nx + 1/ny))
z <- c(x, y)
mz <- mean(z)
#Z <- matrix(sample(z, size = (nx+ny)*R, replace = TRUE), nrow = R)
X <- matrix(sample(x, size = nx*R, replace = TRUE), nrow = R)
Y <- matrix(sample(y, size = ny*R, replace = TRUE), nrow = R)
MX <- rowMeans(X - mx + mz)
MY <- rowMeans(Y - my + mz)
V <- (rowSums((X-MX)^2) + rowSums((Y-MY)^2))/df
STDERR <- sqrt(V*(1/nx + 1/ny))
EFF <- (MX+mx) - (MY+my)
#d_vec <- rep(NA, times=length(R))
for(i in 1:nrow(X)){
#dat = Z[i,]
dat_x = X[i,]#dat[1:nx]
dat_y = Y[i,]#dat[(nx+1):(nx+ny)]
runTOST = log_TOST(x = exp(dat_x),
y = exp(dat_y),
hypothesis = hypothesis,
paired = paired,
var.equal = var.equal,
eqb = eqb,
alpha = alpha,
null = null)
d_vec[i] <- runTOST$smd$d # smd vector
m_vec[i] <- runTOST$effsize$estimate[1] # mean difference vector
#t_vec[i] <- runTOST$TOST$t[1] # t-test vector
#tl_vec[i] <- runTOST$TOST$t[2] # lower bound vector
#tu_vec[i] <- runTOST$TOST$t[3] # upper bound vector
}
}else{
stderrx <- sqrt(vx/nx)
stderry <- sqrt(vy/ny)
stderr <- sqrt(stderrx^2 + stderry^2)
df <- stderr^4/(stderrx^4/(nx - 1) + stderry^4/(ny - 1))
z <- c(x, y)
mz <- mean(z)
x.cent <- x - mx + mz
y.cent <- y - my + mz
X <- matrix(sample(x, size = nx*R, replace = TRUE), nrow = R)
Y <- matrix(sample(y, size = ny*R, replace = TRUE), nrow = R)
MX <- rowMeans(X - mx + mz)
MY <- rowMeans(Y - my + mz)
VX <- rowSums((X-MX)^2)/(nx-1)
VY <- rowSums((Y-MY)^2)/(ny-1)
STDERR <- sqrt(VX/nx + VY/ny)
EFF <- (MX+mx) - (MY+my)
for(i in 1:nrow(X)){
#dat = Z[i,]
dat_x = X[i,]#dat[1:nx]
dat_y = Y[i,]#dat[(nx+1):(nx+ny)]
runTOST = log_TOST(x = exp(dat_x),
y = exp(dat_y),
hypothesis = hypothesis,
paired = paired,
var.equal = var.equal,
eqb = eqb,
alpha = alpha,
null = null)
d_vec[i] <- runTOST$smd$d # smd vector
m_vec[i] <- runTOST$effsize$estimate[1] # mean difference vector
#t_vec[i] <- runTOST$TOST$t[1] # t-test vector
#tl_vec[i] <- runTOST$TOST$t[2] # lower bound vector
#tu_vec[i] <- runTOST$TOST$t[3] # upper bound vector
}
}
if (stderr < 10 * .Machine$double.eps * max(abs(mx), abs(my))){
stop("data are essentially constant")
}
tstat <- (mx - my - null)/stderr
#TSTAT <- (MX - MY)/STDERR
TSTAT <- (MX-MY)/STDERR
#TSTAT_low <- (MX-low_eqbound)/STDERR
#TSTAT_high <- (MX-high_eqbound)/STDERR
}
tstat = nullTOST$TOST$t[1]
tstat_l = nullTOST$TOST$t[2]
tstat_u = nullTOST$TOST$t[3]
#m_vec = append(m_vec, nullTOST$effsize$estimate[1])
#d_vec = append(d_vec, nullTOST$effsize$estimate[2])
boot.pval <- 2 * min(mean(TSTAT <= tstat), mean(TSTAT > tstat))
if(hypothesis == "EQU"){
p_l = mean(TSTAT > tstat_l)
p_u = mean(TSTAT < tstat_u)
} else{
p_l = mean(TSTAT < tstat_l)
p_u = mean(TSTAT > tstat_u)
}
boot.se = sd(m_vec)
boot.cint <- quantile(m_vec, c(alpha, 1 - alpha ))
d.cint <- quantile(d_vec, c(alpha, 1 - alpha ))
d.se = sd(d_vec)
TOST = nullTOST$TOST
TOST$p.value = c(boot.pval, p_l, p_u)
effsize = nullTOST$effsize
effsize$SE = c(boot.se,d.se)
effsize$lower.ci = c(boot.cint[1],
d.cint[1])
effsize$upper.ci = c(boot.cint[2],
d.cint[2])
pTOST = max(p_l,p_u)
TOSToutcome<-ifelse(pTOST<alpha,"significant","non-significant")
testoutcome<-ifelse(boot.pval<alpha,"significant","non-significant")
if(hypothesis == "EQU"){
pTOST = max(p_l,
p_u) # get highest p value for TOST result
tTOST = ifelse(abs(tstat_l) < abs(tstat_u),
tstat_l,
tstat_u) #Get lowest t-value for summary TOST result
} else {
pTOST = min(p_l,
p_u) # get highest p value for TOST result
tTOST = ifelse(abs(tstat_l) > abs(tstat_u),
tstat_l,
tstat_u) #Get lowest t-value for summary TOST result
}
# Change text based on two tailed t test if mu is not zero
if(null == 1){
mu_text = "1"
} else {
mu_text = null
}
if(hypothesis == "EQU"){
#format(low_eqbound, digits = 3, nsmall = 3, scientific = FALSE)
TOST_restext = paste0("The equivalence test was ",TOSToutcome,", t(",round(df, digits=2),") = ",format(tTOST, digits = 3, nsmall = 3, scientific = FALSE),", p = ",format(pTOST, digits = 3, nsmall = 3, scientific = TRUE),sep="")
} else {
TOST_restext = paste0("The minimal effect test was ",
TOSToutcome,", t(",round(df, digits=2),") = ",
format(tTOST, digits = 3, nsmall = 3,
scientific = FALSE),", p = ",
format(pTOST, digits = 3, nsmall = 3,
scientific = TRUE),
sep="")
}
ttest_restext = paste0("The null hypothesis test was ",
testoutcome,", t(",round(df, digits=2),") = ",
format(tstat, digits = 3, nsmall = 3,
scientific = FALSE),", p = ",
format(boot.pval, digits = 3, nsmall = 3,
scientific = TRUE),sep="")
combined_outcome = tost_decision(hypothesis = hypothesis,
alpha = alpha,
pvalue = boot.pval,
pTOST = pTOST,
mu_text = mu_text)
decision = list(
TOST = TOST_restext,
ttest = ttest_restext,
combined = combined_outcome
)
rval = list(
TOST = TOST,
eqb = nullTOST$eqb,
alpha = alpha,
method = method,
hypothesis = nullTOST$hypothesis,
effsize = effsize,
smd = nullTOST$smd,
decision = decision,
boot = list(SMD = d_vec,
raw = m_vec),
data.name = dname,
call = match.call()
)
class(rval) = "TOSTt"
return(rval)
}
#' @rdname boot_log_TOST
#' @method boot_log_TOST formula
#' @export
#'
boot_log_TOST.formula <- function (formula, data, subset, na.action, ...){
if(missing(formula)
|| (length(formula) != 3L)
|| (length(attr(terms(formula[-2L]), "term.labels")) != 1L))
stop("'formula' missing or incorrect")
m <- match.call(expand.dots = FALSE)
if(is.matrix(eval(m$data, parent.frame())))
m$data <- as.data.frame(data)
## need stats:: for non-standard evaluation
m[[1L]] <- quote(stats::model.frame)
m$... <- NULL
mf <- eval(m, parent.frame())
DNAME <- paste(names(mf), collapse = " by ")
names(mf) <- NULL
response <- attr(attr(mf, "terms"), "response")
g <- factor(mf[[-response]])
if(nlevels(g) != 2L)
stop("grouping factor must have exactly 2 levels")
DATA <- setNames(split(mf[[response]], g), c("x", "y"))
y <- do.call("boot_log_TOST", c(DATA, list(...)))
y$data.name <- DNAME
y
}
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