applied_titecrm: Execute the TITE-CRM
In dtpcrm: Dose Transition Pathways for Continual Reassessment Method

Description Usage Arguments Details Value References Examples

applied_titecrm is used to execute the time-to-event continual reassessment method with specified design options to determine the dose for the next subject.

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applied_titecrm(prior, target, tox, level, followup, obswin,
    no_skip_esc = TRUE, no_skip_deesc = TRUE, global_coherent_esc = TRUE,
    stop_func = NULL, ...)

`prior`	A vector of prior estimates of toxicity probabilties for the dose levels.
`target`	The target DLT rate.
`tox`	A vector of subject outcomes; 1 indicates toxicity, 0 otherwise.
`level`	A vector of dose levels assigned to subjects. The length of level must be equal to that of tox.
`followup`	A vector of follow up times of subjects. The length must be equal to that of tox.
`obswin`	The observation period with respect to which DLT is assessed.
`no_skip_esc`	If FALSE, the method will not enforce no skipping of doses in escalation. Default is TRUE.
`no_skip_deesc`	If FALSE, the method will not enforce no skipping of doses in de-escalation. Default is TRUE.
`global_coherent_esc`	If FALSE, the method will not enforce global coherent escalation, that is, escalation if the overall rate of toxicity seen at the current dose level is above the target rate. Default is TRUE.
`stop_func`	An optional argument to provide a function which will utilised alongside the TITE-CRM to determine if the trial should be stopped.
`...`	Any other arguments detailed in dfcrm::titecrm.

The adaptive weighting scheme is given in Cheung and Chappell (2000) given in the reference list.

An object of class "mtd" is returned as per package "dfcrm", additional information is provided if a stopping function is used.

`prior`	Initial guesses of toxicity rates.
`target`	The target probability of toxicity at the MTD.
`ptox`	Updated estimates of toxicity rates.
`ptoxL`	Lower confidence/probability limits of toxicity rates.
`ptoxU`	Upper confidence/probability limits of toxicity rates.
`mtd`	The updated estimate of the MTD.
`prior.var`	The variance of the normal prior.
`post.var`	The posterior variance of the model parameter.
`estimate`	Estimate of the model parameter.
`method`	The method of estimation.
`model`	The working model.
`dosescaled`	The scaled doses obtained via backward substitution.
`tox`	subjects' toxicity indications.
`level`	Dose levels assigned to subjects.
`followup`	Follow-up times of subjects.
`obswin`	Observation window with respect to which DLT is assessed.
`weights`	Weights assigned to subjects.
`entry`	Entry times of subjects.
`exit`	Exit times of subjects.
`scheme`	Weighting scheme.
`stop`	A logical variable detailing if the trial should be stopped; TRUE to stop, FALSE otherwise
`stop_reason`	A detailed reason for why the trial should be stopped. Only provided if stop is TRUE

O'Quigley, J. O., Pepe, M., and Fisher, L. (1990). Continual reassessment method: A practical design for phase I clinical trials in cancer. Biometrics 46:33-48.

Cheung, Y. K. (2011). Dose Finding by the Continual Reassessment Method. New York: Chapman & Hall/CRC Press.

Cheung, Y. K. and Chappell, R. (2000). Sequential designs for phase I clinical trials with late-onset toxicities. Biometrics 56:1177-1182.

prior    <- c(0.1, 0.3, 0.5)
target   <- 0.2
tox      <- c(0, 0, 1, 0, 1, 1)
level    <- c(1, 1, 1, 2, 2, 2)
followup <- c(96, 82, 77, 60, 51, 44)
obswin   <- 80

applied_titecrm(prior = prior, target = target, tox = tox,level = level,
                followup = followup, obswin = obswin)