Stop when uncertainty interval of prob tox is covered. — stop_when_tox_ci

This method stops a dose-finding trial when the symmetric uncertainty interval for the probability of toxicity falls within a range. This allows trials to be stopped when sufficient precision on the pobability of toxicity has been achieved. See Details.

Usage

stop_when_tox_ci_covered(
  parent_selector_factory,
  dose,
  lower,
  upper,
  width = 0.9
)

Arguments

parent_selector_factory: Object of type selector_factory.
dose: 'any' to stop when the interval for any dose is covered; 'recommended' to stop when the interval for the recommended dose is covered ; or an integer to stop when the interval for a particular dose-level is covered.
lower: Stop when lower interval bound exceeds this value
upper: Stop when upper interval bound is less than this value
width: Width of the uncertainty interval. Default is 0.9, i.e. a range from the 5th to the 95th percentiles.

Value

an object of type selector_factory that can fit a dose-finding model to outcomes.

Details

The method for calculating probability mass for toxicity rates will ultimately be determined by the dose-finding model used and the attendant inferential mechanism. For instance, the crm function in the dfcrm package calculates the posterior expected mean and variance of the slope parameter in a CRM model. It does not use MCMC to draw samples from the posterior distribution. Thus, to perform inference on the posterior probability of toxicity, this package assumes the dfcrm slope parameter follows a normal distribution with the mean and variance calculated by dfcrm. In contrast, the stan_crm function in the trialr package needs no such assumption because it samples from the posterior parameter distribution and uses those samples to infer on the posterior probability of toxicity at each dose, dependent on the chosen model for the dose-toxicity curve.

Examples

skeleton <- c(0.05, 0.1, 0.25, 0.4, 0.6)
target <- 0.25

# We compare a CRM model without this stopping rule:
model1 <- get_dfcrm(skeleton = skeleton, target = target)
# To two with it, the first demanding a relatively tight CI:
model2 <- get_dfcrm(skeleton = skeleton, target = target) %>%
  stop_when_tox_ci_covered(dose = 'recommended', lower = 0.15, upper = 0.35)
# and the second demanding a relatively loose CI:
model3 <- get_dfcrm(skeleton = skeleton, target = target) %>%
  stop_when_tox_ci_covered(dose = 'recommended', lower = 0.05, upper = 0.45)

outcomes <- '1NNN 2NNN 3NNT 3NNN 3TNT 2NNN'
fit1 <- model1 %>% fit(outcomes)
fit2 <- model2 %>% fit(outcomes)
fit3 <- model3 %>% fit(outcomes)

# Naturally the first does not advocate stopping:
fit1 %>% recommended_dose()
#> [1] 3
fit1 %>% continue()
#> [1] TRUE

# The second does not advocate stopping either:
fit2 %>% recommended_dose()
#> [1] 3
fit2 %>% continue()
#> [1] TRUE
# This is because the CI is too wide:
fit2 %>% prob_tox_quantile(p = 0.05)
#> [1] 0.005596063 0.018576910 0.090744056 0.204717651 0.413022708
fit2 %>% prob_tox_quantile(p = 0.95)
#> [1] 0.1509501 0.2337941 0.4168693 0.5608330 0.7243968

# However, the third design advocates stopping because the CI at the
# recommended dose is covered:
fit3 %>% recommended_dose()
#> [1] 3
fit3 %>% continue()
#> [1] FALSE
# To verify the veracity, inspect the quantiles:
fit3 %>% prob_tox_quantile(p = 0.05)
#> [1] 0.005596063 0.018576910 0.090744056 0.204717651 0.413022708
fit3 %>% prob_tox_quantile(p = 0.95)
#> [1] 0.1509501 0.2337941 0.4168693 0.5608330 0.7243968