Group sequential design using weighted log-rank test under non-proportional hazards
Source:R/gs_design_wlr.R
gs_design_wlr.Rd
Group sequential design using weighted log-rank test under non-proportional hazards
Usage
gs_design_wlr(
enroll_rate = define_enroll_rate(duration = c(2, 2, 10), rate = c(3, 6, 9)),
fail_rate = tibble(stratum = "All", duration = c(3, 100), fail_rate = log(2)/c(9, 18),
hr = c(0.9, 0.6), dropout_rate = rep(0.001, 2)),
weight = wlr_weight_fh,
approx = "asymptotic",
alpha = 0.025,
beta = 0.1,
ratio = 1,
info_frac = NULL,
info_scale = c("h0_h1_info", "h0_info", "h1_info"),
analysis_time = 36,
binding = FALSE,
upper = gs_spending_bound,
upar = list(sf = gsDesign::sfLDOF, total_spend = alpha),
lower = gs_spending_bound,
lpar = list(sf = gsDesign::sfLDOF, total_spend = beta),
test_upper = TRUE,
test_lower = TRUE,
h1_spending = TRUE,
r = 18,
tol = 1e-06,
interval = c(0.01, 1000)
)
Arguments
- enroll_rate
Enrollment rates.
- fail_rate
Failure and dropout rates.
- weight
Weight of weighted log rank test:
"1"
= unweighted."n"
= Gehan-Breslow."sqrtN"
= Tarone-Ware."FH_p[a]_q[b]"
= Fleming-Harrington with p=a and q=b.
- approx
Approximate estimation method for Z statistics.
"event_driven"
= only work under proportional hazard model with log rank test."asymptotic"
.
- alpha
One-sided Type I error.
- beta
Type II error.
- ratio
Experimental:Control randomization ratio (not yet implemented).
- info_frac
Targeted information fraction at each analysis.
- info_scale
Information scale for calculation. Options are:
"h0_h1_info"
(default): variance under both null and alternative hypotheses is used."h0_info"
: variance under null hypothesis is used."h1_info"
: variance under alternative hypothesis is used.
- analysis_time
Minimum time of analysis.
- binding
Indicator of whether futility bound is binding; default of
FALSE
is recommended.- upper
Function to compute upper bound.
- upar
Parameters passed to
upper
.- lower
Function to compute lower bound.
- lpar
Parameters passed to
lower
.- test_upper
Indicator of which analyses should include an upper (efficacy) bound; single value of
TRUE
(default) indicates all analyses; otherwise, a logical vector of the same length asinfo
should indicate which analyses will have an efficacy bound.- test_lower
Indicator of which analyses should include an lower bound; single value of
TRUE
(default) indicates all analyses; single valueFALSE
indicated no lower bound; otherwise, a logical vector of the same length asinfo
should indicate which analyses will have a lower bound.- h1_spending
Indicator that lower bound to be set by spending under alternate hypothesis (input
fail_rate
) if spending is used for lower bound.- r
Integer value controlling grid for numerical integration as in Jennison and Turnbull (2000); default is 18, range is 1 to 80. Larger values provide larger number of grid points and greater accuracy. Normally,
r
will not be changed by the user.- tol
Tolerance parameter for boundary convergence (on Z-scale).
- interval
An interval that is presumed to include the time at which expected event count is equal to targeted event.
Examples
library(dplyr)
library(mvtnorm)
library(gsDesign)
library(gsDesign2)
# set enrollment rates
enroll_rate <- define_enroll_rate(duration = 12, rate = 1)
# set failure rates
fail_rate <- define_fail_rate(
duration = c(4, 100),
fail_rate = log(2) / 15, # median survival 15 month
hr = c(1, .6),
dropout_rate = 0.001
)
# Example 1 ----
# Information fraction driven design
gs_design_wlr(
enroll_rate = enroll_rate,
fail_rate = fail_rate,
ratio = 1,
alpha = 0.025, beta = 0.2,
weight = function(x, arm0, arm1) {
wlr_weight_fh(x, arm0, arm1, rho = 0, gamma = 0.5)
},
upper = gs_spending_bound,
upar = list(sf = gsDesign::sfLDOF, total_spend = 0.025),
lower = gs_spending_bound,
lpar = list(sf = gsDesign::sfLDOF, total_spend = 0.2),
analysis_time = 36,
info_frac = c(0.6, 1)
)
#> $input
#> $input$enroll_rate
#> # A tibble: 1 × 3
#> stratum duration rate
#> <chr> <dbl> <dbl>
#> 1 All 12 1
#>
#> $input$fail_rate
#> # A tibble: 2 × 5
#> stratum duration fail_rate dropout_rate hr
#> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 All 4 0.0462 0.001 1
#> 2 All 100 0.0462 0.001 0.6
#>
#> $input$weight
#> function (x, arm0, arm1)
#> {
#> wlr_weight_fh(x, arm0, arm1, rho = 0, gamma = 0.5)
#> }
#> <environment: 0x55567ba6bb58>
#>
#> $input$approx
#> [1] "asymptotic"
#>
#> $input$alpha
#> [1] 0.025
#>
#> $input$beta
#> [1] 0.2
#>
#> $input$ratio
#> [1] 1
#>
#> $input$info_frac
#> [1] 0.6 1.0
#>
#> $input$analysis_time
#> [1] 36
#>
#> $input$upper
#> function (k = 1, par = list(sf = gsDesign::sfLDOF, total_spend = 0.025,
#> param = NULL, timing = NULL, max_info = NULL), hgm1 = NULL,
#> theta = 0.1, info = 1:3, efficacy = TRUE, test_bound = TRUE,
#> r = 18, tol = 1e-06)
#> {
#> if (length(test_bound) == 1 && k > 1) {
#> test_bound <- rep(test_bound, k)
#> }
#> if (!is.null(par$timing)) {
#> timing <- par$timing
#> }
#> else {
#> if (is.null(par$max_info)) {
#> timing <- info/max(info)
#> }
#> else {
#> timing <- info/par$max_info
#> }
#> }
#> spend <- par$sf(alpha = par$total_spend, t = timing, param = par$param)$spend
#> old_spend <- 0
#> for (i in 1:k) {
#> if (test_bound[i]) {
#> xx <- spend[i] - old_spend
#> old_spend <- spend[i]
#> spend[i] <- xx
#> }
#> else {
#> spend[i] <- 0
#> }
#> }
#> spend <- spend[k]
#> if (!efficacy) {
#> if (spend <= 0) {
#> return(-Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> a <- qnorm(spend) + sqrt(info[k]) * theta[k]
#> if (k == 1) {
#> return(a)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> adelta <- 1
#> j <- 0
#> while (abs(adelta) > tol) {
#> hg <- hupdate(theta = theta[k], info = info[k], a = -Inf,
#> b = a, thetam1 = theta[k - 1], im1 = info[k -
#> 1], gm1 = hgm1, r = r)
#> i <- length(hg$h)
#> pik <- sum(hg$h)
#> adelta <- spend - pik
#> dplo <- hg$h[i]/hg$w[i]
#> if (adelta > dplo) {
#> adelta <- 1
#> }
#> else if (adelta < -dplo) {
#> adelta <- -1
#> }
#> else {
#> adelta <- adelta/dplo
#> }
#> a <- a + adelta
#> if (a > extreme_high) {
#> a <- extreme_high
#> }
#> else if (a < extreme_low) {
#> a <- extreme_low
#> }
#> if (abs(adelta) < tol) {
#> return(a)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> else {
#> if (spend <= 0) {
#> return(Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> b <- qnorm(spend, lower.tail = FALSE)
#> if (k == 1) {
#> return(b)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> bdelta <- 1
#> j <- 1
#> while (abs(bdelta) > tol) {
#> hg <- hupdate(theta = 0, info = info[k], a = b, b = Inf,
#> thetam1 = 0, im1 = info[k - 1], gm1 = hgm1, r = r)
#> pik <- sum(hg$h)
#> bdelta <- spend - pik
#> dpikdb <- hg$h[1]/hg$w[1]
#> if (bdelta > dpikdb) {
#> bdelta <- 1
#> }
#> else if (bdelta < -dpikdb) {
#> bdelta <- -1
#> }
#> else {
#> bdelta <- bdelta/dpikdb
#> }
#> b <- b - bdelta
#> if (b > extreme_high) {
#> b <- extreme_high
#> }
#> else if (b < extreme_low) {
#> b <- extreme_low
#> }
#> if (abs(bdelta) < tol) {
#> return(b)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> }
#> <bytecode: 0x55567f49ce00>
#> <environment: namespace:gsDesign2>
#>
#> $input$upar
#> $input$upar$sf
#> function (alpha, t, param = NULL)
#> {
#> checkScalar(alpha, "numeric", c(0, Inf), c(FALSE, FALSE))
#> checkVector(t, "numeric", c(0, Inf), c(TRUE, FALSE))
#> if (is.null(param) || param < 0.005 || param > 20)
#> param <- 1
#> checkScalar(param, "numeric", c(0.005, 20), c(TRUE, TRUE))
#> t[t > 1] <- 1
#> if (param == 1) {
#> rho <- 1
#> txt <- "Lan-DeMets O'Brien-Fleming approximation"
#> parname <- "none"
#> }
#> else {
#> rho <- param
#> txt <- "Generalized Lan-DeMets O'Brien-Fleming"
#> parname <- "rho"
#> }
#> z <- -qnorm(alpha/2)
#> x <- list(name = txt, param = param, parname = parname, sf = sfLDOF,
#> spend = 2 * (1 - pnorm(z/t^(rho/2))), bound = NULL, prob = NULL)
#> class(x) <- "spendfn"
#> x
#> }
#> <bytecode: 0x555678e89928>
#> <environment: namespace:gsDesign>
#>
#> $input$upar$total_spend
#> [1] 0.025
#>
#>
#> $input$lower
#> function (k = 1, par = list(sf = gsDesign::sfLDOF, total_spend = 0.025,
#> param = NULL, timing = NULL, max_info = NULL), hgm1 = NULL,
#> theta = 0.1, info = 1:3, efficacy = TRUE, test_bound = TRUE,
#> r = 18, tol = 1e-06)
#> {
#> if (length(test_bound) == 1 && k > 1) {
#> test_bound <- rep(test_bound, k)
#> }
#> if (!is.null(par$timing)) {
#> timing <- par$timing
#> }
#> else {
#> if (is.null(par$max_info)) {
#> timing <- info/max(info)
#> }
#> else {
#> timing <- info/par$max_info
#> }
#> }
#> spend <- par$sf(alpha = par$total_spend, t = timing, param = par$param)$spend
#> old_spend <- 0
#> for (i in 1:k) {
#> if (test_bound[i]) {
#> xx <- spend[i] - old_spend
#> old_spend <- spend[i]
#> spend[i] <- xx
#> }
#> else {
#> spend[i] <- 0
#> }
#> }
#> spend <- spend[k]
#> if (!efficacy) {
#> if (spend <= 0) {
#> return(-Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> a <- qnorm(spend) + sqrt(info[k]) * theta[k]
#> if (k == 1) {
#> return(a)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> adelta <- 1
#> j <- 0
#> while (abs(adelta) > tol) {
#> hg <- hupdate(theta = theta[k], info = info[k], a = -Inf,
#> b = a, thetam1 = theta[k - 1], im1 = info[k -
#> 1], gm1 = hgm1, r = r)
#> i <- length(hg$h)
#> pik <- sum(hg$h)
#> adelta <- spend - pik
#> dplo <- hg$h[i]/hg$w[i]
#> if (adelta > dplo) {
#> adelta <- 1
#> }
#> else if (adelta < -dplo) {
#> adelta <- -1
#> }
#> else {
#> adelta <- adelta/dplo
#> }
#> a <- a + adelta
#> if (a > extreme_high) {
#> a <- extreme_high
#> }
#> else if (a < extreme_low) {
#> a <- extreme_low
#> }
#> if (abs(adelta) < tol) {
#> return(a)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> else {
#> if (spend <= 0) {
#> return(Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> b <- qnorm(spend, lower.tail = FALSE)
#> if (k == 1) {
#> return(b)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> bdelta <- 1
#> j <- 1
#> while (abs(bdelta) > tol) {
#> hg <- hupdate(theta = 0, info = info[k], a = b, b = Inf,
#> thetam1 = 0, im1 = info[k - 1], gm1 = hgm1, r = r)
#> pik <- sum(hg$h)
#> bdelta <- spend - pik
#> dpikdb <- hg$h[1]/hg$w[1]
#> if (bdelta > dpikdb) {
#> bdelta <- 1
#> }
#> else if (bdelta < -dpikdb) {
#> bdelta <- -1
#> }
#> else {
#> bdelta <- bdelta/dpikdb
#> }
#> b <- b - bdelta
#> if (b > extreme_high) {
#> b <- extreme_high
#> }
#> else if (b < extreme_low) {
#> b <- extreme_low
#> }
#> if (abs(bdelta) < tol) {
#> return(b)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> }
#> <bytecode: 0x55567f49ce00>
#> <environment: namespace:gsDesign2>
#>
#> $input$lpar
#> $input$lpar$sf
#> function (alpha, t, param = NULL)
#> {
#> checkScalar(alpha, "numeric", c(0, Inf), c(FALSE, FALSE))
#> checkVector(t, "numeric", c(0, Inf), c(TRUE, FALSE))
#> if (is.null(param) || param < 0.005 || param > 20)
#> param <- 1
#> checkScalar(param, "numeric", c(0.005, 20), c(TRUE, TRUE))
#> t[t > 1] <- 1
#> if (param == 1) {
#> rho <- 1
#> txt <- "Lan-DeMets O'Brien-Fleming approximation"
#> parname <- "none"
#> }
#> else {
#> rho <- param
#> txt <- "Generalized Lan-DeMets O'Brien-Fleming"
#> parname <- "rho"
#> }
#> z <- -qnorm(alpha/2)
#> x <- list(name = txt, param = param, parname = parname, sf = sfLDOF,
#> spend = 2 * (1 - pnorm(z/t^(rho/2))), bound = NULL, prob = NULL)
#> class(x) <- "spendfn"
#> x
#> }
#> <bytecode: 0x555678e89928>
#> <environment: namespace:gsDesign>
#>
#> $input$lpar$total_spend
#> [1] 0.2
#>
#>
#> $input$test_upper
#> [1] TRUE
#>
#> $input$test_lower
#> [1] TRUE
#>
#> $input$h1_spending
#> [1] TRUE
#>
#> $input$binding
#> [1] FALSE
#>
#> $input$info_scale
#> [1] "h0_h1_info"
#>
#> $input$r
#> [1] 18
#>
#> $input$tol
#> [1] 1e-06
#>
#>
#> $enroll_rate
#> # A tibble: 1 × 3
#> stratum duration rate
#> <chr> <dbl> <dbl>
#> 1 All 12 24.1
#>
#> $fail_rate
#> # A tibble: 2 × 5
#> stratum duration fail_rate dropout_rate hr
#> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 All 4 0.0462 0.001 1
#> 2 All 100 0.0462 0.001 0.6
#>
#> $bounds
#> # A tibble: 4 × 7
#> analysis bound probability probability0 z `~hr at bound` `nominal p`
#> <int> <chr> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 upper 0.0884 0.00381 2.67 0.645 0.00381
#> 2 1 lower 0.101 0.504 0.0102 0.998 0.496
#> 3 2 upper 0.800 0.0249 1.98 0.751 0.0238
#> 4 2 lower 0.200 0.974 1.96 0.754 0.0253
#>
#> $analysis
#> # A tibble: 2 × 10
#> analysis time n event ahr theta info info0 info_frac info_frac0
#> <int> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 25.2 289. 148. 0.661 0.414 9.63 9.88 0.612 0.600
#> 2 2 36 289. 192. 0.639 0.732 15.7 16.5 1 1
#>
#> attr(,"class")
#> [1] "non_binding" "wlr" "gs_design" "list"
# Example 2 ----
# Calendar time driven design
gs_design_wlr(
enroll_rate = enroll_rate,
fail_rate = fail_rate,
ratio = 1,
alpha = 0.025, beta = 0.2,
weight = function(x, arm0, arm1) {
wlr_weight_fh(x, arm0, arm1, rho = 0, gamma = 0.5)
},
upper = gs_spending_bound,
upar = list(sf = gsDesign::sfLDOF, total_spend = 0.025),
lower = gs_spending_bound,
lpar = list(sf = gsDesign::sfLDOF, total_spend = 0.2),
analysis_time = c(24, 36),
info_frac = NULL
)
#> $input
#> $input$enroll_rate
#> # A tibble: 1 × 3
#> stratum duration rate
#> <chr> <dbl> <dbl>
#> 1 All 12 1
#>
#> $input$fail_rate
#> # A tibble: 2 × 5
#> stratum duration fail_rate dropout_rate hr
#> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 All 4 0.0462 0.001 1
#> 2 All 100 0.0462 0.001 0.6
#>
#> $input$weight
#> function (x, arm0, arm1)
#> {
#> wlr_weight_fh(x, arm0, arm1, rho = 0, gamma = 0.5)
#> }
#> <environment: 0x55567ba6bb58>
#>
#> $input$approx
#> [1] "asymptotic"
#>
#> $input$alpha
#> [1] 0.025
#>
#> $input$beta
#> [1] 0.2
#>
#> $input$ratio
#> [1] 1
#>
#> $input$info_frac
#> [1] 0.5525079 1.0000000
#>
#> $input$analysis_time
#> [1] 24 36
#>
#> $input$upper
#> function (k = 1, par = list(sf = gsDesign::sfLDOF, total_spend = 0.025,
#> param = NULL, timing = NULL, max_info = NULL), hgm1 = NULL,
#> theta = 0.1, info = 1:3, efficacy = TRUE, test_bound = TRUE,
#> r = 18, tol = 1e-06)
#> {
#> if (length(test_bound) == 1 && k > 1) {
#> test_bound <- rep(test_bound, k)
#> }
#> if (!is.null(par$timing)) {
#> timing <- par$timing
#> }
#> else {
#> if (is.null(par$max_info)) {
#> timing <- info/max(info)
#> }
#> else {
#> timing <- info/par$max_info
#> }
#> }
#> spend <- par$sf(alpha = par$total_spend, t = timing, param = par$param)$spend
#> old_spend <- 0
#> for (i in 1:k) {
#> if (test_bound[i]) {
#> xx <- spend[i] - old_spend
#> old_spend <- spend[i]
#> spend[i] <- xx
#> }
#> else {
#> spend[i] <- 0
#> }
#> }
#> spend <- spend[k]
#> if (!efficacy) {
#> if (spend <= 0) {
#> return(-Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> a <- qnorm(spend) + sqrt(info[k]) * theta[k]
#> if (k == 1) {
#> return(a)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> adelta <- 1
#> j <- 0
#> while (abs(adelta) > tol) {
#> hg <- hupdate(theta = theta[k], info = info[k], a = -Inf,
#> b = a, thetam1 = theta[k - 1], im1 = info[k -
#> 1], gm1 = hgm1, r = r)
#> i <- length(hg$h)
#> pik <- sum(hg$h)
#> adelta <- spend - pik
#> dplo <- hg$h[i]/hg$w[i]
#> if (adelta > dplo) {
#> adelta <- 1
#> }
#> else if (adelta < -dplo) {
#> adelta <- -1
#> }
#> else {
#> adelta <- adelta/dplo
#> }
#> a <- a + adelta
#> if (a > extreme_high) {
#> a <- extreme_high
#> }
#> else if (a < extreme_low) {
#> a <- extreme_low
#> }
#> if (abs(adelta) < tol) {
#> return(a)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> else {
#> if (spend <= 0) {
#> return(Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> b <- qnorm(spend, lower.tail = FALSE)
#> if (k == 1) {
#> return(b)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> bdelta <- 1
#> j <- 1
#> while (abs(bdelta) > tol) {
#> hg <- hupdate(theta = 0, info = info[k], a = b, b = Inf,
#> thetam1 = 0, im1 = info[k - 1], gm1 = hgm1, r = r)
#> pik <- sum(hg$h)
#> bdelta <- spend - pik
#> dpikdb <- hg$h[1]/hg$w[1]
#> if (bdelta > dpikdb) {
#> bdelta <- 1
#> }
#> else if (bdelta < -dpikdb) {
#> bdelta <- -1
#> }
#> else {
#> bdelta <- bdelta/dpikdb
#> }
#> b <- b - bdelta
#> if (b > extreme_high) {
#> b <- extreme_high
#> }
#> else if (b < extreme_low) {
#> b <- extreme_low
#> }
#> if (abs(bdelta) < tol) {
#> return(b)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> }
#> <bytecode: 0x55567f49ce00>
#> <environment: namespace:gsDesign2>
#>
#> $input$upar
#> $input$upar$sf
#> function (alpha, t, param = NULL)
#> {
#> checkScalar(alpha, "numeric", c(0, Inf), c(FALSE, FALSE))
#> checkVector(t, "numeric", c(0, Inf), c(TRUE, FALSE))
#> if (is.null(param) || param < 0.005 || param > 20)
#> param <- 1
#> checkScalar(param, "numeric", c(0.005, 20), c(TRUE, TRUE))
#> t[t > 1] <- 1
#> if (param == 1) {
#> rho <- 1
#> txt <- "Lan-DeMets O'Brien-Fleming approximation"
#> parname <- "none"
#> }
#> else {
#> rho <- param
#> txt <- "Generalized Lan-DeMets O'Brien-Fleming"
#> parname <- "rho"
#> }
#> z <- -qnorm(alpha/2)
#> x <- list(name = txt, param = param, parname = parname, sf = sfLDOF,
#> spend = 2 * (1 - pnorm(z/t^(rho/2))), bound = NULL, prob = NULL)
#> class(x) <- "spendfn"
#> x
#> }
#> <bytecode: 0x555678e89928>
#> <environment: namespace:gsDesign>
#>
#> $input$upar$total_spend
#> [1] 0.025
#>
#>
#> $input$lower
#> function (k = 1, par = list(sf = gsDesign::sfLDOF, total_spend = 0.025,
#> param = NULL, timing = NULL, max_info = NULL), hgm1 = NULL,
#> theta = 0.1, info = 1:3, efficacy = TRUE, test_bound = TRUE,
#> r = 18, tol = 1e-06)
#> {
#> if (length(test_bound) == 1 && k > 1) {
#> test_bound <- rep(test_bound, k)
#> }
#> if (!is.null(par$timing)) {
#> timing <- par$timing
#> }
#> else {
#> if (is.null(par$max_info)) {
#> timing <- info/max(info)
#> }
#> else {
#> timing <- info/par$max_info
#> }
#> }
#> spend <- par$sf(alpha = par$total_spend, t = timing, param = par$param)$spend
#> old_spend <- 0
#> for (i in 1:k) {
#> if (test_bound[i]) {
#> xx <- spend[i] - old_spend
#> old_spend <- spend[i]
#> spend[i] <- xx
#> }
#> else {
#> spend[i] <- 0
#> }
#> }
#> spend <- spend[k]
#> if (!efficacy) {
#> if (spend <= 0) {
#> return(-Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> a <- qnorm(spend) + sqrt(info[k]) * theta[k]
#> if (k == 1) {
#> return(a)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> adelta <- 1
#> j <- 0
#> while (abs(adelta) > tol) {
#> hg <- hupdate(theta = theta[k], info = info[k], a = -Inf,
#> b = a, thetam1 = theta[k - 1], im1 = info[k -
#> 1], gm1 = hgm1, r = r)
#> i <- length(hg$h)
#> pik <- sum(hg$h)
#> adelta <- spend - pik
#> dplo <- hg$h[i]/hg$w[i]
#> if (adelta > dplo) {
#> adelta <- 1
#> }
#> else if (adelta < -dplo) {
#> adelta <- -1
#> }
#> else {
#> adelta <- adelta/dplo
#> }
#> a <- a + adelta
#> if (a > extreme_high) {
#> a <- extreme_high
#> }
#> else if (a < extreme_low) {
#> a <- extreme_low
#> }
#> if (abs(adelta) < tol) {
#> return(a)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> else {
#> if (spend <= 0) {
#> return(Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> b <- qnorm(spend, lower.tail = FALSE)
#> if (k == 1) {
#> return(b)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> bdelta <- 1
#> j <- 1
#> while (abs(bdelta) > tol) {
#> hg <- hupdate(theta = 0, info = info[k], a = b, b = Inf,
#> thetam1 = 0, im1 = info[k - 1], gm1 = hgm1, r = r)
#> pik <- sum(hg$h)
#> bdelta <- spend - pik
#> dpikdb <- hg$h[1]/hg$w[1]
#> if (bdelta > dpikdb) {
#> bdelta <- 1
#> }
#> else if (bdelta < -dpikdb) {
#> bdelta <- -1
#> }
#> else {
#> bdelta <- bdelta/dpikdb
#> }
#> b <- b - bdelta
#> if (b > extreme_high) {
#> b <- extreme_high
#> }
#> else if (b < extreme_low) {
#> b <- extreme_low
#> }
#> if (abs(bdelta) < tol) {
#> return(b)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> }
#> <bytecode: 0x55567f49ce00>
#> <environment: namespace:gsDesign2>
#>
#> $input$lpar
#> $input$lpar$sf
#> function (alpha, t, param = NULL)
#> {
#> checkScalar(alpha, "numeric", c(0, Inf), c(FALSE, FALSE))
#> checkVector(t, "numeric", c(0, Inf), c(TRUE, FALSE))
#> if (is.null(param) || param < 0.005 || param > 20)
#> param <- 1
#> checkScalar(param, "numeric", c(0.005, 20), c(TRUE, TRUE))
#> t[t > 1] <- 1
#> if (param == 1) {
#> rho <- 1
#> txt <- "Lan-DeMets O'Brien-Fleming approximation"
#> parname <- "none"
#> }
#> else {
#> rho <- param
#> txt <- "Generalized Lan-DeMets O'Brien-Fleming"
#> parname <- "rho"
#> }
#> z <- -qnorm(alpha/2)
#> x <- list(name = txt, param = param, parname = parname, sf = sfLDOF,
#> spend = 2 * (1 - pnorm(z/t^(rho/2))), bound = NULL, prob = NULL)
#> class(x) <- "spendfn"
#> x
#> }
#> <bytecode: 0x555678e89928>
#> <environment: namespace:gsDesign>
#>
#> $input$lpar$total_spend
#> [1] 0.2
#>
#>
#> $input$test_upper
#> [1] TRUE
#>
#> $input$test_lower
#> [1] TRUE
#>
#> $input$h1_spending
#> [1] TRUE
#>
#> $input$binding
#> [1] FALSE
#>
#> $input$info_scale
#> [1] "h0_h1_info"
#>
#> $input$r
#> [1] 18
#>
#> $input$tol
#> [1] 1e-06
#>
#>
#> $enroll_rate
#> # A tibble: 1 × 3
#> stratum duration rate
#> <chr> <dbl> <dbl>
#> 1 All 12 23.2
#>
#> $fail_rate
#> # A tibble: 2 × 5
#> stratum duration fail_rate dropout_rate hr
#> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 All 4 0.0462 0.001 1
#> 2 All 100 0.0462 0.001 0.6
#>
#> $bounds
#> # A tibble: 4 × 7
#> analysis bound probability probability0 z `~hr at bound` `nominal p`
#> <int> <chr> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 upper 0.299 0.00257 2.80 0.620 0.00257
#> 2 1 lower 0.0866 0.812 0.886 0.860 0.188
#> 3 2 upper 0.800 0.0223 1.97 0.748 0.0242
#> 4 2 lower 0.198 0.975 1.92 0.753 0.0273
#>
#> $analysis
#> # A tibble: 2 × 10
#> analysis time n event ahr theta info info0 info_frac info_frac0
#> <int> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 24 278. 137. 0.666 0.765 8.56 8.76 0.565 0.553
#> 2 2 36 278. 184. 0.639 0.732 15.1 15.9 1 1
#>
#> attr(,"class")
#> [1] "non_binding" "wlr" "gs_design" "list"
# Example 3 ----
# Both calendar time and information fraction driven design
gs_design_wlr(
enroll_rate = enroll_rate,
fail_rate = fail_rate,
ratio = 1,
alpha = 0.025, beta = 0.2,
weight = function(x, arm0, arm1) {
wlr_weight_fh(x, arm0, arm1, rho = 0, gamma = 0.5)
},
upper = gs_spending_bound,
upar = list(sf = gsDesign::sfLDOF, total_spend = 0.025),
lower = gs_spending_bound,
lpar = list(sf = gsDesign::sfLDOF, total_spend = 0.2),
analysis_time = c(24, 36),
info_frac = c(0.6, 1)
)
#> $input
#> $input$enroll_rate
#> # A tibble: 1 × 3
#> stratum duration rate
#> <chr> <dbl> <dbl>
#> 1 All 12 1
#>
#> $input$fail_rate
#> # A tibble: 2 × 5
#> stratum duration fail_rate dropout_rate hr
#> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 All 4 0.0462 0.001 1
#> 2 All 100 0.0462 0.001 0.6
#>
#> $input$weight
#> function (x, arm0, arm1)
#> {
#> wlr_weight_fh(x, arm0, arm1, rho = 0, gamma = 0.5)
#> }
#> <environment: 0x55567ba6bb58>
#>
#> $input$approx
#> [1] "asymptotic"
#>
#> $input$alpha
#> [1] 0.025
#>
#> $input$beta
#> [1] 0.2
#>
#> $input$ratio
#> [1] 1
#>
#> $input$info_frac
#> [1] 0.6 1.0
#>
#> $input$analysis_time
#> [1] 24 36
#>
#> $input$upper
#> function (k = 1, par = list(sf = gsDesign::sfLDOF, total_spend = 0.025,
#> param = NULL, timing = NULL, max_info = NULL), hgm1 = NULL,
#> theta = 0.1, info = 1:3, efficacy = TRUE, test_bound = TRUE,
#> r = 18, tol = 1e-06)
#> {
#> if (length(test_bound) == 1 && k > 1) {
#> test_bound <- rep(test_bound, k)
#> }
#> if (!is.null(par$timing)) {
#> timing <- par$timing
#> }
#> else {
#> if (is.null(par$max_info)) {
#> timing <- info/max(info)
#> }
#> else {
#> timing <- info/par$max_info
#> }
#> }
#> spend <- par$sf(alpha = par$total_spend, t = timing, param = par$param)$spend
#> old_spend <- 0
#> for (i in 1:k) {
#> if (test_bound[i]) {
#> xx <- spend[i] - old_spend
#> old_spend <- spend[i]
#> spend[i] <- xx
#> }
#> else {
#> spend[i] <- 0
#> }
#> }
#> spend <- spend[k]
#> if (!efficacy) {
#> if (spend <= 0) {
#> return(-Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> a <- qnorm(spend) + sqrt(info[k]) * theta[k]
#> if (k == 1) {
#> return(a)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> adelta <- 1
#> j <- 0
#> while (abs(adelta) > tol) {
#> hg <- hupdate(theta = theta[k], info = info[k], a = -Inf,
#> b = a, thetam1 = theta[k - 1], im1 = info[k -
#> 1], gm1 = hgm1, r = r)
#> i <- length(hg$h)
#> pik <- sum(hg$h)
#> adelta <- spend - pik
#> dplo <- hg$h[i]/hg$w[i]
#> if (adelta > dplo) {
#> adelta <- 1
#> }
#> else if (adelta < -dplo) {
#> adelta <- -1
#> }
#> else {
#> adelta <- adelta/dplo
#> }
#> a <- a + adelta
#> if (a > extreme_high) {
#> a <- extreme_high
#> }
#> else if (a < extreme_low) {
#> a <- extreme_low
#> }
#> if (abs(adelta) < tol) {
#> return(a)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> else {
#> if (spend <= 0) {
#> return(Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> b <- qnorm(spend, lower.tail = FALSE)
#> if (k == 1) {
#> return(b)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> bdelta <- 1
#> j <- 1
#> while (abs(bdelta) > tol) {
#> hg <- hupdate(theta = 0, info = info[k], a = b, b = Inf,
#> thetam1 = 0, im1 = info[k - 1], gm1 = hgm1, r = r)
#> pik <- sum(hg$h)
#> bdelta <- spend - pik
#> dpikdb <- hg$h[1]/hg$w[1]
#> if (bdelta > dpikdb) {
#> bdelta <- 1
#> }
#> else if (bdelta < -dpikdb) {
#> bdelta <- -1
#> }
#> else {
#> bdelta <- bdelta/dpikdb
#> }
#> b <- b - bdelta
#> if (b > extreme_high) {
#> b <- extreme_high
#> }
#> else if (b < extreme_low) {
#> b <- extreme_low
#> }
#> if (abs(bdelta) < tol) {
#> return(b)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> }
#> <bytecode: 0x55567f49ce00>
#> <environment: namespace:gsDesign2>
#>
#> $input$upar
#> $input$upar$sf
#> function (alpha, t, param = NULL)
#> {
#> checkScalar(alpha, "numeric", c(0, Inf), c(FALSE, FALSE))
#> checkVector(t, "numeric", c(0, Inf), c(TRUE, FALSE))
#> if (is.null(param) || param < 0.005 || param > 20)
#> param <- 1
#> checkScalar(param, "numeric", c(0.005, 20), c(TRUE, TRUE))
#> t[t > 1] <- 1
#> if (param == 1) {
#> rho <- 1
#> txt <- "Lan-DeMets O'Brien-Fleming approximation"
#> parname <- "none"
#> }
#> else {
#> rho <- param
#> txt <- "Generalized Lan-DeMets O'Brien-Fleming"
#> parname <- "rho"
#> }
#> z <- -qnorm(alpha/2)
#> x <- list(name = txt, param = param, parname = parname, sf = sfLDOF,
#> spend = 2 * (1 - pnorm(z/t^(rho/2))), bound = NULL, prob = NULL)
#> class(x) <- "spendfn"
#> x
#> }
#> <bytecode: 0x555678e89928>
#> <environment: namespace:gsDesign>
#>
#> $input$upar$total_spend
#> [1] 0.025
#>
#>
#> $input$lower
#> function (k = 1, par = list(sf = gsDesign::sfLDOF, total_spend = 0.025,
#> param = NULL, timing = NULL, max_info = NULL), hgm1 = NULL,
#> theta = 0.1, info = 1:3, efficacy = TRUE, test_bound = TRUE,
#> r = 18, tol = 1e-06)
#> {
#> if (length(test_bound) == 1 && k > 1) {
#> test_bound <- rep(test_bound, k)
#> }
#> if (!is.null(par$timing)) {
#> timing <- par$timing
#> }
#> else {
#> if (is.null(par$max_info)) {
#> timing <- info/max(info)
#> }
#> else {
#> timing <- info/par$max_info
#> }
#> }
#> spend <- par$sf(alpha = par$total_spend, t = timing, param = par$param)$spend
#> old_spend <- 0
#> for (i in 1:k) {
#> if (test_bound[i]) {
#> xx <- spend[i] - old_spend
#> old_spend <- spend[i]
#> spend[i] <- xx
#> }
#> else {
#> spend[i] <- 0
#> }
#> }
#> spend <- spend[k]
#> if (!efficacy) {
#> if (spend <= 0) {
#> return(-Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> a <- qnorm(spend) + sqrt(info[k]) * theta[k]
#> if (k == 1) {
#> return(a)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> adelta <- 1
#> j <- 0
#> while (abs(adelta) > tol) {
#> hg <- hupdate(theta = theta[k], info = info[k], a = -Inf,
#> b = a, thetam1 = theta[k - 1], im1 = info[k -
#> 1], gm1 = hgm1, r = r)
#> i <- length(hg$h)
#> pik <- sum(hg$h)
#> adelta <- spend - pik
#> dplo <- hg$h[i]/hg$w[i]
#> if (adelta > dplo) {
#> adelta <- 1
#> }
#> else if (adelta < -dplo) {
#> adelta <- -1
#> }
#> else {
#> adelta <- adelta/dplo
#> }
#> a <- a + adelta
#> if (a > extreme_high) {
#> a <- extreme_high
#> }
#> else if (a < extreme_low) {
#> a <- extreme_low
#> }
#> if (abs(adelta) < tol) {
#> return(a)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> else {
#> if (spend <= 0) {
#> return(Inf)
#> }
#> if (length(theta) == 1)
#> theta <- rep(theta, length(info))
#> b <- qnorm(spend, lower.tail = FALSE)
#> if (k == 1) {
#> return(b)
#> }
#> mu <- theta[k] * sqrt(info[k])
#> extreme_low <- mu - 3 - 4 * log(r)
#> extreme_high <- mu + 3 + 4 * log(r)
#> bdelta <- 1
#> j <- 1
#> while (abs(bdelta) > tol) {
#> hg <- hupdate(theta = 0, info = info[k], a = b, b = Inf,
#> thetam1 = 0, im1 = info[k - 1], gm1 = hgm1, r = r)
#> pik <- sum(hg$h)
#> bdelta <- spend - pik
#> dpikdb <- hg$h[1]/hg$w[1]
#> if (bdelta > dpikdb) {
#> bdelta <- 1
#> }
#> else if (bdelta < -dpikdb) {
#> bdelta <- -1
#> }
#> else {
#> bdelta <- bdelta/dpikdb
#> }
#> b <- b - bdelta
#> if (b > extreme_high) {
#> b <- extreme_high
#> }
#> else if (b < extreme_low) {
#> b <- extreme_low
#> }
#> if (abs(bdelta) < tol) {
#> return(b)
#> }
#> j <- j + 1
#> if (j > 20) {
#> stop(paste("gs_spending_bound(): bound_update did not converge for lower bound calculation, analysis",
#> k, " !"))
#> }
#> }
#> }
#> }
#> <bytecode: 0x55567f49ce00>
#> <environment: namespace:gsDesign2>
#>
#> $input$lpar
#> $input$lpar$sf
#> function (alpha, t, param = NULL)
#> {
#> checkScalar(alpha, "numeric", c(0, Inf), c(FALSE, FALSE))
#> checkVector(t, "numeric", c(0, Inf), c(TRUE, FALSE))
#> if (is.null(param) || param < 0.005 || param > 20)
#> param <- 1
#> checkScalar(param, "numeric", c(0.005, 20), c(TRUE, TRUE))
#> t[t > 1] <- 1
#> if (param == 1) {
#> rho <- 1
#> txt <- "Lan-DeMets O'Brien-Fleming approximation"
#> parname <- "none"
#> }
#> else {
#> rho <- param
#> txt <- "Generalized Lan-DeMets O'Brien-Fleming"
#> parname <- "rho"
#> }
#> z <- -qnorm(alpha/2)
#> x <- list(name = txt, param = param, parname = parname, sf = sfLDOF,
#> spend = 2 * (1 - pnorm(z/t^(rho/2))), bound = NULL, prob = NULL)
#> class(x) <- "spendfn"
#> x
#> }
#> <bytecode: 0x555678e89928>
#> <environment: namespace:gsDesign>
#>
#> $input$lpar$total_spend
#> [1] 0.2
#>
#>
#> $input$test_upper
#> [1] TRUE
#>
#> $input$test_lower
#> [1] TRUE
#>
#> $input$h1_spending
#> [1] TRUE
#>
#> $input$binding
#> [1] FALSE
#>
#> $input$info_scale
#> [1] "h0_h1_info"
#>
#> $input$r
#> [1] 18
#>
#> $input$tol
#> [1] 1e-06
#>
#>
#> $enroll_rate
#> # A tibble: 1 × 3
#> stratum duration rate
#> <chr> <dbl> <dbl>
#> 1 All 12 24.1
#>
#> $fail_rate
#> # A tibble: 2 × 5
#> stratum duration fail_rate dropout_rate hr
#> <chr> <dbl> <dbl> <dbl> <dbl>
#> 1 All 4 0.0462 0.001 1
#> 2 All 100 0.0462 0.001 0.6
#>
#> $bounds
#> # A tibble: 4 × 7
#> analysis bound probability probability0 z `~hr at bound` `nominal p`
#> <int> <chr> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 upper 0.0884 0.00381 2.67 0.645 0.00381
#> 2 1 lower 0.101 0.504 0.0102 0.998 0.496
#> 3 2 upper 0.800 0.0249 1.98 0.751 0.0238
#> 4 2 lower 0.200 0.974 1.96 0.754 0.0253
#>
#> $analysis
#> # A tibble: 2 × 10
#> analysis time n event ahr theta info info0 info_frac info_frac0
#> <int> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl> <dbl>
#> 1 1 25.2 289. 148. 0.661 0.414 9.63 9.88 0.612 0.600
#> 2 2 36 289. 192. 0.639 0.732 15.7 16.5 1 1
#>
#> attr(,"class")
#> [1] "non_binding" "wlr" "gs_design" "list"