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.
stop_when_tox_ci_covered( parent_selector_factory, dose, lower, upper, width = 0.9 )
Object of type
Stop when lower interval bound exceeds this value
Stop when upper interval bound is less than this value
Width of the uncertainty interval. Default is 0.9, i.e. a range from the 5th to the 95th percentiles.
an object of type
selector_factory that can fit a
dose-finding model to outcomes.
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
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
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()#>  3fit1 %>% continue()#>  TRUE# The second does not advocate stopping either: fit2 %>% recommended_dose()#>  3fit2 %>% continue()#>  TRUE# This is because the CI is too wide: fit2 %>% prob_tox_quantile(p = 0.05)#>  0.005596063 0.018576910 0.090744056 0.204717651 0.413022708fit2 %>% prob_tox_quantile(p = 0.95)#>  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()#>  3fit3 %>% continue()#>  FALSE# To verify the veracity, inspect the quantiles: fit3 %>% prob_tox_quantile(p = 0.05)#>  0.005596063 0.018576910 0.090744056 0.204717651 0.413022708fit3 %>% prob_tox_quantile(p = 0.95)#>  0.1509501 0.2337941 0.4168693 0.5608330 0.7243968