GenToxProb {phase1RMD}

Toxicity Probability Matrices Generation for Trial Simulation

Description

A function to generate toxicity probability matrices employing proportional odds model, used as input for trial simulation. The generated matrices are a four-dimension array containing the probabilities of the occurrences of certain grades for certain types of toxicities, at each dose level and cycle under consideration. Dimension 1 refers to doses; dimension 2 corresponds to cycles of the treatment; dimension 3 regards the types of toxicities while dimenion 4 relates to grades.

Usage

GenToxProb(toxtype = c("Neurological", "Renal", "Hematological"), 
           intercept.alpha = c(2, 3, 4.2, 5.7), 
           coef.beta = c(-0.2, -0.4, -0.7), 
           cycle.gamma = 0, MaxCycle = 6, Numdose = 6)

Arguments

toxtype

A character vector, specifying toxicity types considered in the trial.

intercept.alpha

A four element numeric vector specifying the intercepts for the cumulative probabilities of the occurrences of grades 0-4 of toxicities in proportional odds model. See Details below.

coef.beta

A n numeric vector specifying the slope for dose in proportional odds model for n types of toxicities. See Details below.

cycle.gamma

A scalar controlling the cycle effect in simulation in proportional odds model. See Details below.

MaxCycle

Maximum of number of cycles of the treatment.

Numdose

The number of doses under investigation.

Details

The probability matrices of the occurrences of certain grades for certain types of toxicities, at each dose level and cycle are simulated from a proportional odds model that takes toxtype, intercept.alpha, coef.beta and cycle.gamma as the inputs. The model is as follows:

logit(c_j) = \alpha_j + \beta * dose + \gamma * cycle, j=0,1,2,3

where given a dose and cycle, c_j is the cumulative probabilities of occurrences of toxicities grades up to j; \alpha_0, \alpha_1, \alpha_2, \alpha_3 are the intercepts, making up intercept.alpha; coef.beta stores \beta for different types of toxicities while cycle.gamma acts as \gamma, controlling the cycle effect. The probability for the occurrence of a certain grade of a certain toxicity type at a given dose and cycle is obtained from taking the corresponding differences between cumulative probabilities.

Value

A four-dimension array where dimension 1 refers to doses; dimension 2 corresponds to cycles of the treatment; dimension 3 regards the types of toxicities while dimenion 4 relates to grades.

Examples

#tox.matrix <- GenToxProb()