rxTest({ test_that("Test a matrix that needs nearPD", { rx1 <- RxODE({ cl <- tcl*(1+crcl.cl*(CLCR-65)) * exp(eta.v) v <- tv * WT * exp(eta.v) ka <- tka * exp(eta.ka) ipred <- linCmt() obs <- ipred * (1 + prop.sd) + add.sd }) theta <- c(tcl=2.63E+01, tv=1.35E+00, tka=4.20E+00, tlag=2.08E-01, prop.sd=2.05E-01, add.sd=1.06E-02, crcl.cl=7.17E-03, ## Note that since we are using the separation strategy the ETA variances are here too eta.cl=7.30E-02, eta.v=3.80E-02, eta.ka=1.91E+00) thetaMat <- lotri( tcl + tv + tka + tlag + prop.sd + add.sd + crcl.cl + eta.cl + eta.v + eta.ka ~ c(7.95E-01, ## 2.05E-02, 1.92E-03, --> Here I am assuming that the tv was fixed during estimation ## so that nonmem cov output is a low triangular matrix with a zero row 0, 0, 7.22E-02, -8.30E-03, 6.55E-01, -3.45E-03, -6.42E-05, 3.22E-03, 2.47E-04, 8.71E-04, 2.53E-04, -4.71E-03, -5.79E-05, 5.04E-04, 6.30E-04, -3.17E-06, -6.52E-04, -1.53E-05, -3.14E-05, 1.34E-05, -3.30E-04, 5.46E-06, -3.15E-04, 2.46E-06, 3.15E-06, -1.58E-06, 2.88E-06, -1.29E-03, -7.97E-05, 1.68E-03, -2.75E-05, -8.26E-05, 1.13E-05, -1.66E-06, 1.58E-04, -1.23E-03, -1.27E-05, -1.33E-03, -1.47E-05, -1.03E-04, 1.02E-05, 1.67E-06, 6.68E-05, 1.56E-04, 7.69E-02, -7.23E-03, 3.74E-01, 1.79E-03, -2.85E-03, 1.18E-05, -2.54E-04, 1.61E-03, -9.03E-04, 3.12E-01)) thetaMat1 <- thetaMat # Quick fix idea: add a very small (epsilon) diagonal term for thetaMat # so that there is "very small" uncertainty around tv thetaMat1[2, 2] <- 1e-06 evw <- et(amount.units="mg", time.units="hours") %>% et(amt=100) %>% ## For this problem we will simulate with sampling windows et(list(c(0, 0.5), c(0.5, 1), c(1, 3), c(3, 6), c(6, 12))) %>% et(id=1:1000) skip_on_os("windows") expect_error(rxSolve(rx1, theta, evw, nSub=100, nStud=10, thetaMat=thetaMat1, ## Match boundaries of problem thetaLower=0, sigma=c("prop.sd", "add.sd"), ## Sigmas are standard deviations sigmaXform="identity", # default sigma xform="identity" omega=c("eta.cl", "eta.v", "eta.ka"), ## etas are variances omegaXform="variance", # default omega xform="variance" iCov=data.frame(WT=rnorm(1000, 70, 15), CLCR=rnorm(1000, 65, 25)), dfSub=74, dfObs=476), NA) }) })