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 defined by define_enroll_rate().

fail_rate

Failure and dropout rates defined by define_fail_rate().

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.

info_frac

Targeted information fraction at each analysis. See details for properly set it up.

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

Targeted time of analysis. See details for properly set it up.

binding

Indicator of whether futility bound is binding; default of FALSE is recommended.

upper

Function to compute upper bound.

gs_spending_bound(): alpha-spending efficacy bounds.
gs_b(): fixed efficacy bounds.

upar

Parameters passed to upper.

If upper = gs_b, then upar is a numerical vector specifying the fixed efficacy bounds per analysis.
If upper = gs_spending_bound, then upar is a list including
- sf for the spending function family.
- total_spend for total alpha spend.
- param for the parameter of the spending function.
- timing (not required for information-based spending) for the spending time if different from information-based spending.

lower

Function to compute lower bound, which can be set up similarly as upper. More details can be find in this vignette.

lpar

Parameters passed to lower, which can be set up similarly as upar.

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 as info 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 value FALSE indicated no lower bound; otherwise, a logical vector of the same length as info 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.

Value

A list with input parameters, enrollment rate, analysis, and bound.

Specification

The contents of this section are shown in PDF user manual only.

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: 0x556a47efdce8>
#> 
#> $input$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: 0x556a4c179560>
#> <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: 0x556a4997e328>
#> <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: 0x556a4c179560>
#> <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: 0x556a4997e328>
#> <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: 0x556a47efdce8>
#> 
#> $input$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: 0x556a4c179560>
#> <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: 0x556a4997e328>
#> <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: 0x556a4c179560>
#> <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: 0x556a4997e328>
#> <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: 0x556a47efdce8>
#> 
#> $input$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: 0x556a4c179560>
#> <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: 0x556a4997e328>
#> <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: 0x556a4c179560>
#> <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: 0x556a4997e328>
#> <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"