ewoc_d1classical function

Escalation With Overdose Control

Finding the next dose for a phase I clinical trial based on the Escalation with Overdose Control (EWOC) design considering the classical parametrization for binary responses and single agent.

ewoc_d1classical(
  formula,
  theta,
  alpha,
  mtd_prior,
  rho_prior,
  min_dose,
  max_dose,
  type = c("continuous", "discrete"),
  first_dose = NULL,
  last_dose = NULL,
  dose_set = NULL,
  max_increment = NULL,
  no_skip_dose = TRUE,
  rounding = c("down", "nearest"),
  n_adapt = 5000,
  burn_in = 1000,
  n_mcmc = 1000,
  n_thin = 1,
  n_chains = 1
)

Arguments

• formula: an object of class Formula: a symbolic description of the model to be fitted with only one regressor term corresponding to the dose for the right side and a numeric vector a response containing number of DLT for the left side.
• theta: a numerical value defining the proportion of expected patients to experience a medically unacceptable, dose-limiting toxicity (DLT) if administered the MTD.
• alpha: a numerical value defining the probability that the dose selected by EWOC is higher than the MTD.
• mtd_prior: a matrix 1 x 2 of hyperparameters for the Beta prior distribution associated with the parameter MTD.
• rho_prior: a matrix 1 x 2 of hyperparameters for the Beta prior distribution associated with the parameter rho.
• min_dose: a numerical value defining the lower bound of the support of the MTD.
• max_dose: a numerical value defining the upper bound of the support of the MTD.
• type: a character describing the type of the Maximum Tolerable Dose (MTD) variable.
• first_dose: a numerical value for the first allowable dose in the trial. It is only necessary if type = 'continuous'.
• last_dose: a numerical value for the last allowable dose in the trial. It is only necessary if type = 'continuous'.
• dose_set: a numerical vector of allowable doses in the trial. It is only necessary if type = 'discrete'.
• max_increment: a numerical value indicating the maximum increment from the current dose to the next dose. It is only applied if type = 'continuous'.
• no_skip_dose: a logical value indicating if it is allowed to skip doses. It is only necessary if type = 'discrete'. The default is TRUE.
• rounding: a character indicating how to round a continuous dose to the one of elements of the dose set. It is only necessary if type = 'discrete'.
• n_adapt: the number of iterations for adaptation. See adapt for details.
• burn_in: numerical value indicating the number of iterations before to start monitoring.
• n_mcmc: numerical value indicating the number of iterations to monitor.
• n_thin: numerical value corresponding to the thinning interval for monitors.
• n_chains: numerical value indicating the number of parallel chains for the model.

Returns

next_dose the next recommend dose.

mtd the posterior MTD distribution.

rho the posterior rho_0 distribution.

sample a list of the MCMC chains distribution.

trial a list of the trial conditions.

Examples

DLT <- 0
dose <- 20
test <- ewoc_d1classical(DLT ~ dose, type = 'discrete',
                      theta = 0.33, alpha = 0.25,
                      min_dose = 20, max_dose = 100,
                      dose_set = seq(20, 100, 20),
                      rho_prior = matrix(1, ncol = 2, nrow = 1),
                      mtd_prior = matrix(1, ncol = 2, nrow = 1),
                      rounding = "nearest")
summary(test)
plot(test)

References

Babb, J., Rogatko, A. and Zacks, S., 1998. Cancer phase I clinical trials: efficient dose escalation with overdose control. Statistics in medicine, 17(10), pp.1103-1120.