crm {CRM}

A function for the continued reassessment method (CRM) used in Phase I clinical trials

Description

Function crm implement the continued reassessment method (CRM) for dose finding in Phase I clinical trials.

Usage

crm(target,prior,ptdata,model=1,a0=1,b=3)

Arguments

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.

ptdata

A n by 2 matrix in which the first column contains dose levels and the second column contains toxicity indicators. Dose levels must be integers (e.g., 1, 2, 3, ..., N). Toxicity indicators must be 0 and 1, where 0 indicates no toxicity and 1 indicates toxicity.

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.

Value

A list with the following two objects:

MTD

The dose level proposed as the maximum tolerated dose (MTD) based on the patient data

a

The updated value for parameter a

Author(s)

Qianxing Mo; [e-mail]

References

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

See Also

crmsim, crmsiminc1, crmsiminc2

Examples

#The table 1 in O'Quingley et al.'s paper, page 40
#This example is used to illustrate how the program is used to find
#the MTD and the updated parameter 
 
target <- 0.2
prior <- c(0.05,0.1,0.2,0.3,0.5,0.7)
x <- c(3,4,4,3,3,2,1,1,1,2,2,2,2,2,2,2,2,2,2,2,2,2,2,2,1)
y <- c(0,0,1,0,1,1,0,0,0,0,0,0,1,0,0,0,0,0,1,0,0,1,0,1,1)
ptdata <- cbind(x,y)
for(i in 1:25){
  if(i == 1){
    cat(1,1,3,0,"\n")
  }
  res <- crm(target,prior,ptdata[1:i,],model=1,a0=1)
  if(i < 25){
    cat(i+1,res$a,res$MTD,ptdata[i+1,2],"\n")
  }else {
    cat(i+1,res$a,res$MTD,"\n")
  }
}

#the proposed MTD is
res$MTD