## ----include = FALSE----------------------------------------------------------
knitr::opts_chunk$set(
  collapse = TRUE,
  cache.path = 'cache/dynamicTreatmentSwitching/',
  comment = '#>',
  dpi = 300,
  out.width = '100%'
)

## ----setup, echo = FALSE, message = FALSE-------------------------------------
library(TrialSimulator)
library(mvtnorm)
library(kableExtra)

## ----eval=FALSE---------------------------------------------------------------
# treatment_allocator <- function(patient_data){...}
# time_selector <- function(patient_data){...}
# data_modifier <- function(patient_data){...}
# 
# regimen <- regimen(treatment_allocator, time_selector, data_modifier)

## ----eval=FALSE---------------------------------------------------------------
# trial <- trial(...)
# trial$add_regime(regimen)

## ----eval=FALSE---------------------------------------------------------------
# trial <- trial(...)
# trial$add_arms(sample_ratio, soc, low_dose, high_dose)
# trial$add_regime(regimen)

## ----echo=FALSE, error=TRUE---------------------------------------------------
try({
msg <- tryCatch(
  {
    stop(' Member function trial$add_regimen() must be called before trial$add_arms(). ', 
         'A good practice is to call trial$add_regimen() immediately after trial() is executed. ')
    NULL
  },
  error = function(e) {
    cat('Error in trial$add_regimen(regimen) :\n', 
        e$message)
  }
)
})

## ----eval=FALSE---------------------------------------------------------------
# treatment_allocator <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   switch_to <- sample(c('low', 'high', 'stay'), nrow(patient_data),
#                         replace = TRUE, prob = c(.3, .4, .3))
#   ## placebo patients who progressed before death (pfs < os) and were
#   ## assigned a dose are the switchers; the rest are simply not returned
#   is_switcher <- patient_data$arm == 'placebo' &
#     patient_data$pfs < patient_data$os & switch_to != 'stay'
#   sw <- patient_data[is_switcher, ]
#   data.frame(
#     patient_id    = sw$patient_id,
#     new_treatment = ifelse(switch_to[is_switcher] == 'low', 'low dose', 'high dose')
#   )
# 
# }

## ----eval=FALSE---------------------------------------------------------------
# time_selector <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   data.frame(
#     patient_id = patient_data$patient_id,
#     ## all patient in patient_data progress before die
#     ## thus pfs < os and can switch.
#     ## See treatment_allocator()
#     switch_time = patient_data$pfs
#   )
# 
# }

## ----eval=FALSE---------------------------------------------------------------
# time_selector <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   data.frame(
#     patient_id = patient_data$patient_id,
#     ## all patient in patient_data progress before die
#     ## thus pfs < os and can switch.
#     ## See treatment_allocator()
#     switch_time = runif(nrow(patient_data), min = patient_data$pfs, max = patient_data$os)
#   )
# 
# }

## ----eval=FALSE---------------------------------------------------------------
# data_modifier <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   f <- ifelse(patient_data$new_treatment == 'low dose', 1.1, 1.15)
#   data.frame(
#     patient_id = patient_data$patient_id,
#     ## other_endpoint = ...,
#     os = patient_data$switch_time + f * (patient_data$os - patient_data$switch_time)
#   )
# 
# }

## ----eval=FALSE---------------------------------------------------------------
# treatment_allocator <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   ## low-dose non-responders switch to high dose
#   sw <- patient_data[patient_data$arm == 'low dose' & patient_data$response == 0, ]
#   data.frame(
#     patient_id    = sw$patient_id,
#     new_treatment = 'high dose'
#   )
# 
# }

## ----eval=FALSE---------------------------------------------------------------
# time_selector <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   data.frame(
#     patient_id = patient_data$patient_id,
#     ## all patient in patient_data progress before die
#     ## thus pfs < os and can switch
#     switch_time = patient_data$response_readout
#   )
# 
# }

## -----------------------------------------------------------------------------
treatment_allocator <- function(patient_data){
  ## add break point to develop and debug
  # browser()
  ## all placebo patients switch
  sw <- patient_data[patient_data$arm == 'placebo', ]
  data.frame(
    patient_id    = sw$patient_id,
    new_treatment = 'new treatment'
  )

}

## ----eval=FALSE---------------------------------------------------------------
# time_selector <- function(patient_data){
#   ## add break point to develop and debug
#   # browser()
#   data.frame(
#     patient_id = patient_data$patient_id,
#     ## all patient in patient_data progress before die
#     ## thus pfs < os and can switch
#     switch_time = ifelse(patient_data$os <= 1, .9 * patient_data$os, patient_data$os - 1)
#   )
# 
# }

## ----eval=FALSE---------------------------------------------------------------
# what <- list(allocator1, allocator2, allocator3)
# when <- list(selector1, selector2, selector3)
# how <- list(modifier1, modifier2, modifier3)
# 
# regimen <- regimen(what, when, how)
# 
# trial <- trial(...)
# trial$add_regimen(regimen)