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[Experimental]

NextBestDualEndpoint is the class for next best dose that is based on the dual endpoint model.

Usage

NextBestDualEndpoint(
  target,
  overdose,
  max_overdose_prob,
  target_relative = TRUE,
  target_thresh = 0.01
)

.DefaultNextBestDualEndpoint()

Arguments

target

(numeric)
see slot definition.

overdose

(numeric)
see slot definition.

max_overdose_prob

(proportion)
see slot definition.

target_relative

(flag)
see slot definition.

target_thresh

(proportion)
see slot definition.

Details

Under this rule, at first admissible doses are found, which are those with toxicity probability to fall in overdose category and being below max_overdose_prob. Next, it picks (from the remaining admissible doses) the one that maximizes the probability to be in the target biomarker range. By default (target_relative = TRUE) the target is specified as relative to the maximum biomarker level across the dose grid or relative to the Emax parameter in case a parametric model was selected (i.e. DualEndpointBeta, DualEndpointEmax). However, if target_relative = FALSE, then the absolute biomarker range can be used as a target.

Slots

target

(numeric)
the biomarker target range that needs to be reached. For example, the target range \((0.8, 1.0)\) and target_relative = TRUE means that we target a dose with at least \(80\%\) of maximum biomarker level. As an other example, \((0.5, 0.8)\) would mean that we target a dose between \(50\%\) and \(80\%\) of the maximum biomarker level.

overdose

(numeric)
the overdose toxicity interval (lower limit excluded, upper limit included).

max_overdose_prob

(proportion)
maximum overdose probability that is allowed.

target_relative

(flag)
is target specified as relative? If TRUE, then the target is interpreted relative to the maximum, so it must be a probability range. Otherwise, the target is interpreted as absolute biomarker range.

target_thresh

(proportion)
a target probability threshold that needs to be fulfilled before the target probability will be used for deriving the next best dose (default to 0.01).

Note

Typically, end users will not use the .DefaultNextBestDualEndpoint() function.

Examples

# Target a dose achieving at least 0.9 of maximum biomarker level (efficacy)
# and with a probability below 0.25 that prob(DLT) > 0.35 (safety).
my_next_best <- NextBestDualEndpoint(
  target = c(0.9, 1),
  overdose = c(0.35, 1),
  max_overdose_prob = 0.25
)

# Now, using absolute target on the natural biomarker scale.
my_next_best_absolute <- NextBestDualEndpoint(
  target = c(200, 300),
  overdose = c(0.35, 1),
  max_overdose_prob = 0.25,
  target_relative = FALSE
)