library(coxme) # Test of refine.n option # Matches the first example in the laplace vignette # aeq <- function(x,y, ...) all.equal(as.vector(x), as.vector(y), ...) nsim <- 100 set.seed(1953) #an auspicious birth year :-) mkdata <- function(n, beta=c(.4, .1), sitehaz=c(.5,1.5, 2,1)) { nsite <- length(sitehaz) site <- rep(1:nsite, each=n) trt1 <- rep(0:1, length=n*nsite) hazard <- sitehaz[site] + beta[1]*trt1 + beta[2]*trt1 * (site-mean(site)) stime <- rexp(n*nsite, exp(hazard)) q80 <- quantile(stime, .8) data.frame(site=site, trt = trt1, trt2 = 1-trt1, futime= pmin(stime, q80), status= ifelse(stime>q80, 0, 1), hazard=hazard ) } trdata <- mkdata(150) #150 enrolled per site set.seed(12345) fit1 <- coxme(Surv(futime, status) ~ trt + (1| site/trt), trdata, refine.n=nsim, refine.detail=TRUE) hmatb <- fit1$hmat[1:12, 1:12] hmat.inv <- as.matrix(solve(hmatb)) chidf <- coxme.control()$refine.df set.seed(12345) bmat <- matrix(rnorm(12*nsim), ncol=nsim) b2 <- backsolve(hmatb, bmat, upper=TRUE) htran <- as(hmatb, "dtCMatrix") #verify that backsolve works correctly all.equal(as.matrix(htran %*% b2), bmat, check.attributes=FALSE) b2 <- scale(b2, center=F, scale=sqrt(rchisq(nsim, df=chidf)/chidf)) b3 <- b2 + unlist(ranef(fit1)) aeq(b3, fit1$refine.detail$bmat) # Check the fitted Cox models logvec <- double(nsim) indx <- -1 + trdata$trt + 2*trdata$site #random treatment effect index for (i in 1:nsim) { eta <- fixef(fit1) * trdata$trt + b3[indx, i] + b3[trdata$site+8,i] tfit <- coxph(Surv(futime, status) ~ offset(eta), data= trdata) logvec[i] <- tfit$loglik[1] } aeq(logvec, fit1$refine.detail$loglik) # The penalties temp <- unlist(VarCorr(fit1)) Ainv <- diag(rep(1/temp, c(8,4))) p1 <- diag(t(b3) %*% Ainv %*% b3)/2 aeq(p1, fit1$refine.detail$penalty1) p2 <- mahalanobis(t(b3), center=unlist(ranef(fit1)), cov=hmat.inv) p3 <- mahalanobis(t(b2), center=rep(0,12), cov=hmat.inv) aeq(p2, p3) aeq(p2/2, fit1$refine.detail$penalty2) # The log-density of the t require(mvtnorm) tdens <- dmvt(t(b3), delta=unlist(ranef(fit1)), sigma=hmat.inv, df=chidf) aeq(tdens, fit1$refine.detail$tdens) # The normalization constant for the Gaussian penalty # Determinants are easy for a diagonal matrix gnorm <- -(6*log(2*pi) - .5*sum(log(diag(Ainv)))) # My errhat vector t1 <- logvec + gnorm - (tdens + p1 + fit1$loglik[2]) t2 <- fit1$loglik[3] + gnorm - (tdens + p2/2 + fit1$loglik[2]) errhat <- exp(t1) - exp(t2) aeq(errhat, fit1$refine.detail$errhat)