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  • Using R package to implement Bayesian phase I/II dose-finding design for three outcom

    Dear all,

    I am trying to implement the work done by Suyu Liu, "A Bayesian Phase I/II Trial Design for Immunotherapy", using R, since the code attached with that work takes a lot of time (more than 20 hours, and the code not complete). So that I tried to use trialr package since it used rstan, but this package allowed me to use two outcomes ( toxicity, efficacy ) and the work of Liu used three outcomes (immune response, toxicity, and efficacy).

    I tried to use the R package trialr for two outcomes using the utility for sensitivity analysis written in R code below (table 1 in the article), I want to see if I used the correct utility and to see how to add a third outcome ( immune response ) to the model

    and thanks in advance.

    Here is the work of Liu:



    ````

    ### My code###
    rm(list = ls())
    library(trialr)

    #Utility
    Uti <- array(0,c(2,3,2)) # order: tox, eff, immuno
    Uti[,,1] <- matrix(c(0,0,50,10,80,35),nrow=2)
    Uti[,,2] <- matrix(c(5,0,70,20,100,45),nrow=2)
    N.max= 60 # patients
    outcomes <- '1NNN 2NNT 3NNT 4NNN 5NTN'
    doses = c(.1,.3,.5,.7,.9)


    fit <- stan_efftox(outcomes,
    real_doses =doses,
    efficacy_hurdle = 0.5, toxicity_hurdle = 0.3,
    p_e = 0.1, p_t = 0.1,
    eff0 = 0.5, tox1 = 0.65,
    eff_star = 0.7, tox_star = 0.25,
    alpha_mean = -7.9593, alpha_sd = 3.5487,
    beta_mean = 1.5482, beta_sd = 3.5018,
    gamma_mean = 0.7367, gamma_sd = 2.5423,
    zeta_mean = 3.4181, zeta_sd = 2.4406,
    eta_mean = 0, eta_sd = 0.2,
    psi_mean = 0, psi_sd = 1,
    seed = 123)

    ndoses <- length(fit$prob_tox)
    plot(1:ndoses, fit$prob_tox, type="b", pch=19, xlab="Dose level", ylab="Probability of toxicity", ylim=c(0,max(fit$prob_tox) + 0.15), col="green")
    points(1:ndoses,fit$prob_eff, type="b", pch=18, col="blue")
    abline(h=0.3, lwd=2, lty=4, col = "red")
    legend(1, 0.4, legend=c("Toxicity", "Effecacy"),
    col=c("green", "blue"), lty=1:2, cex=0.8)

    ````

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