Description Usage Arguments Value Author(s) References See Also Examples

crmsim, crmsiminc1 and crmsiminc2 implement the continued reassessment method (CRM) for dose finding in Phase I clinical trials. The operating characteristics of CRM are summarized through simulations.

crmsim allows users to select a variety of cohort sizes. A cohort of subjects are treated at the same dose.

The cohort size is fixed to 1 in crmsiminc1 and crmsiminc2. crmsiminc1 implements an algorithm that allows a clinical trial to proceed to the next subject's dose assignment before observing the last subject's toxicity data. crmsiminc2 allows a clinical trial to proceed to the next subject's dose assignment before observing the last two subject's toxicity data (see Iasonos et al. for details).

1 2 3 4 5 6 | ```
crmsim(target,prior,true,rate,cycle,cohort=1,nsubject=24,nsim=1000,
model=1,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
crmsiminc1(target,prior,true,rate,cycle,nsubject=24,nsim=1000,
model=1,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
crmsiminc2(target,prior,true,rate,cycle,nsubject=24,nsim=1000,
model=1,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
``` |

`target` |
Target probability of toxicity. The value must be in (0, 1). |

`prior` |
Prior probabilities of toxicity for each dose. The values must be in (0,1) and in an ascending order. For example, prior=c(0.05,0.1,0.2,0.3,0.5,0.7),which corresponds to dose levels 1, 2, 3, 4, 5 and 6,respectively. |

`true` |
True probabilities of toxicity. The values must be in (0,1) and in an ascending order. e.g. (0.1,0.2,0,3,0.4,0.5,0.8) |

`rate` |
Recruitment/accrual rate of subjects in a 30 window. For example,if 1 subject can be recruited per 30 days, then set rate = 1/30 = 0.033; if 2 patients per 30 day then rate = 2/30 = 0.0667. |

`cycle` |
The length of treatment cycle in days. |

`cohort` |
Cohort size of subjects entering into the trials. Default is 1. The value for cohort must be less than or equal to the value for nsubject. |

`nsubject` |
Total number of subjects in one simulation(or trial). Default is 24. nsubject should be equal to n*cohort,where n is positive integer. |

`nsim` |
Total number of simulations. Default is 1000. |

`model` |
Dose-toxicity model. The value must be 1 (hyperbolic tangent model) or 2 (one-parameter logistic model). Default is 1. Hyperbolic tangent model: $p(y=1|x,a) = ((tanh(x)+1)/2)^a$. One-parameter logistic model: $p(y=1|x,a,b) = exp(b+ax)/(1+exp(b+ax))$. For both models, y=1 indicates toxicity is observed; a is the parameter that can be updated based on the outcome of the trail; b is a fixed parameter. The prior for a is exp(-a). |

`a0` |
Initial value for parameter a. Default is 1.0. |

`b` |
A fixed parameter for the one-parameter logistic model. Default is 3.0. |

`jump` |
jump=FALSE means NOT allowing that the proposed dose by the CRM program has an increase of more than one level than the previous level; jump=TRUE means allowing more-than-one-level increase of the proposed dose by the CRM program. |

`start.dose` |
Initial dose for each trial. Default is 1. |

`seed` |
Seed for the random number generator. Default is 777. |

SimResult is a matrix that summarizes the operating characteristics of CRM. The column names are the dose levels. The row names are the operating characteristics.

`% Selection` |
the percentage of selection of each dose as MTD |

`% Subjects Treated` |
the percentage of subjects treated at each dose |

`# Subjects Treated` |
the average number of subjects treated at each dose |

`Average Toxicities` |
the average toxicities per trial at each dose |

`True Probabilities` |
the true probability of toxicity of each dose |

TrialDuration is a table that summarizes the time needed for the trial based on the simulation.

Qianxing Mo; [email protected]

John O'Quigley, Margaret Pepe,and Lloyd Fisher. (1990). Continual
Reassessment Method: A Practical Design for Phase 1 Clinical Trials in Cancer.
*Biometrics*, 46, pp.33-48

Alexia Iasonos,Andrew S Wilton,Elyn R Riedel,Venkatraman E Seshan and
David R Spriggs. A comprehensive comparison of the continual
reassessment method to the standard 3+3 dose escalation scheme in
Phase I dose-finding studies. *Clinical Trials*,2008,nil:1-12

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 | ```
prior1 <- c(0.05,0.1,0.2,0.3,0.5,0.7)
true1 <- c(0.1,0.15,0.2,0.4,0.5,0.8)
### simulations using model 1 (hyperbolic tangent model)
### uncomment the following code to run ###
#crmsim(target=0.2,prior=prior1,true=true1,rate=0.1,cycle=21,cohort=1,nsubject=24,nsim=1000,
# model=1,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
#crmsiminc1(target=0.2,prior=prior1,true=true1,rate=0.1,cycle=21,nsubject=24,nsim=1000,
# model=1,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
#crmsiminc2(target=0.2,prior=prior1,true=true1,rate=0.1,cycle=21,nsubject=24,nsim=1000,
# model=1,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
# simulations using model 2 (one-parameter logistic model)
#crmsim(target=0.2,prior=prior1,true=true1,rate=0.1,cycle=21,cohort=1,nsubject=24,nsim=1000,
# model=2,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
#crmsiminc1(target=0.2,prior=prior1,true=true1,rate=0.1,cycle=21,nsubject=24,nsim=1000,
# model=2,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
#crmsiminc2(target=0.2,prior=prior1,true=true1,rate=0.1,cycle=21,nsubject=24,nsim=1000,
# model=2,a0=1,b=3,jump=FALSE,start.dose=1,seed=777)
``` |

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