summary-DualSimulations-method: Summarize the dual-endpoint design simulations, relative to...

summary,DualSimulations-methodR Documentation

Summarize the dual-endpoint design simulations, relative to given true dose-toxicity and dose-biomarker curves

Description

Summarize the dual-endpoint design simulations, relative to given true dose-toxicity and dose-biomarker curves

Usage

## S4 method for signature 'DualSimulations'
summary(object, trueTox, trueBiomarker, target = c(0.2, 0.35), ...)

Arguments

object

the DualSimulations object we want to summarize

trueTox

a function which takes as input a dose (vector) and returns the true probability (vector) for toxicity.

trueBiomarker

a function which takes as input a dose (vector) and returns the true biomarker level (vector).

target

the target toxicity interval (default: 20-35%) used for the computations

...

Additional arguments can be supplied here for trueTox and trueBiomarker

Value

an object of class DualSimulationsSummary

Examples

# Define the dose-grid.
emptydata <- DataDual(doseGrid = c(1, 3, 5, 10, 15, 20, 25, 40, 50, 80, 100))


# Initialize the CRM model.
my_model <- DualEndpointRW(
  mean = c(0, 1),
  cov = matrix(c(1, 0, 0, 1), nrow = 2),
  sigma2betaW = 0.01,
  sigma2W = c(a = 0.1, b = 0.1),
  rho = c(a = 1, b = 1),
  rw1 = TRUE
)

# Choose the rule for selecting the next dose.
my_next_best <- NextBestDualEndpoint(
  target = c(0.9, 1),
  overdose = c(0.35, 1),
  max_overdose_prob = 0.25
)

# Choose the rule for stopping.
my_stopping1 <- StoppingTargetBiomarker(
  target = c(0.9, 1),
  prob = 0.5
)

# For illustration stop with 6 subjects.
my_stopping <- my_stopping1 | StoppingMinPatients(6) | StoppingMissingDose()

# Choose the rule for dose increments.
my_increments <- IncrementsRelative(
  intervals = c(0, 20),
  increments = c(1, 0.33)
)

# Initialize the design.
design <- DualDesign(
  model = my_model,
  data = emptydata,
  nextBest = my_next_best,
  stopping = my_stopping,
  increments = my_increments,
  cohort_size = CohortSizeConst(3),
  startingDose = 3
)

# Define scenarios for the TRUE toxicity and efficacy profiles.
beta_mod <- function(dose, e0, eMax, delta1, delta2, scal) {
  maxDens <- (delta1^delta1) * (delta2^delta2) / ((delta1 + delta2)^(delta1 + delta2))
  dose <- dose / scal
  e0 + eMax / maxDens * (dose^delta1) * (1 - dose)^delta2
}

true_biomarker <- function(dose) {
  beta_mod(dose, e0 = 0.2, eMax = 0.6, delta1 = 5, delta2 = 5 * 0.5 / 0.5, scal = 100)
}

true_tox <- function(dose) {
  pnorm((dose - 60) / 10)
}

# Draw the TRUE profiles.
par(mfrow = c(1, 2))
curve(true_tox(x), from = 0, to = 80)
curve(true_biomarker(x), from = 0, to = 80)

# Run the simulation on the desired design.
# For illustration purposes 1 trial is simulated with 5 burn-ins to generate 20 samples.
my_sims <- simulate(
  object = design,
  trueTox = true_tox,
  trueBiomarker = true_biomarker,
  sigma2W = 0.01,
  rho = 0,
  nsim = 1,
  parallel = FALSE,
  seed = 3,
  startingDose = 6,
  mcmcOptions = McmcOptions(
    burnin = 5,
    step = 1,
    samples = 20
  )
)

# Summarize the results of the simulations.
summary(
  my_sims,
  trueTox = true_tox,
  trueBiomarker = true_biomarker
)

Roche/crmPack documentation built on April 30, 2024, 3:19 p.m.