rxodeTest(
{
if (requireNamespace("units", quietly = TRUE)) {
for (meth in c("liblsoda", "lsoda")) { ## Dop is very close but doesn't match precisely.
context(sprintf("Simple test for time-varying covariates (%s)", meth))
ode <- RxODE({
b <- -1
d / dt(X) <- a * X + Y * Z
d / dt(Y) <- b * (Y - Z)
d / dt(Z) <- -X * Y + c * Y - Z
printf("%.10f,%.10f\n", t, c)
})
et <- eventTable(time.units = "hr") # default time units
et$add.sampling(seq(from = 0, to = 100, by = 0.01))
cov <- data.frame(c = et$get.EventTable()$time + units::set_units(1, h))
et0 <- et
et <- cbind(et, cov)
cov.lin <- approxfun(et$time, et$c, yleft = et$c[1], yright = et$c[length(cov$c)])
t <- tempfile("temp", fileext = ".csv")
.rxWithSink(t, {
cat("t,c\n")
out <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
add.cov = TRUE,
covsInterpolation = "linear",
method = meth
)
})
lin.interp <- read.csv(t)
unlink(t)
lin.interp$c2 <- cov.lin(lin.interp$t)
test_that("time varying covariates output covariate in data frame", {
expect_equal(cov$c, out$c)
})
test_that("Linear Approximation matches approxfun.", {
expect_equal(lin.interp$c, lin.interp$c2)
})
## NONMEM interpolation
.rxWithSink(t, {
cat("t,c\n")
out <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
covs_interpolation = "NOCB", add.cov = TRUE,
method = meth
)
})
lin.interp <- read.csv(t)
unlink(t)
cov.lin <- approxfun(out$time, out$c,
yleft = cov$c[1], yright = cov$c[length(cov$c)],
method = "constant", f = 1
)
lin.interp$c2 <- cov.lin(lin.interp$t)
test_that("NOCB Approximation similar to approxfun.", {
expect_equal(lin.interp$c, lin.interp$c2)
})
## midpoint interpolation
.rxWithSink(t, {
cat("t,c\n")
out <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
covs_interpolation = "midpoint", add.cov = TRUE,
method = meth
)
})
lin.interp <- read.csv(t)
unlink(t)
cov.lin <- approxfun(out$time, out$c,
yleft = cov$c[1], yright = cov$c[length(cov$c)],
method = "constant", f = 0.5
)
lin.interp$c2 <- cov.lin(lin.interp$t)
test_that("midpoint Approximation similar to approxfun.", {
expect_equal(lin.interp$c, lin.interp$c2)
})
## covs_interpolation
.rxWithSink(t, {
cat("t,c\n")
out <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
covs_interpolation = "constant", add.cov = TRUE,
method = meth
)
})
lin.interp <- read.csv(t)
unlink(t)
cov.lin <- approxfun(out$time, out$c,
yleft = cov$c[1], yright = cov$c[length(cov$c)],
method = "constant"
)
lin.interp$c2 <- cov.lin(lin.interp$t)
test_that("Constant Approximation similar to approxfun.", {
expect_equal(lin.interp$c, lin.interp$c2)
})
out <- as.data.frame(out)
out <- out[, names(out) != "c"]
.rxWithSink(t, {
out1 <-
rxSolve(ode,
params = c(a = -8 / 3, b = -10, c = 0),
events = et,
inits = c(X = 1, Y = 1, Z = 1), add.cov = TRUE,
method = meth
)
})
unlink(t)
out1 <- as.data.frame(out1)
test_that("time varying covariates produce different outputs", {
expect_false(isTRUE(all.equal(out, out1)))
})
cov <- data.frame(
c = et0$get.EventTable()$time + units::set_units(1, hr),
a = -et0$get.EventTable()$time / units::set_units(100, hr)
)
et <- cbind(et0, cov)
.rxWithSink(t, {
out <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
add.cov = TRUE,
method = meth
)
out3 <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
add.cov = TRUE,
method = meth
)
})
unlink(t)
test_that("time varying covariates output covariate in data frame", {
expect_equal(cov$c[et0$get.obs.rec()], out$c)
expect_equal(cov$a[et0$get.obs.rec()], out$a)
})
cov <- data.frame(c = et0$get.EventTable()$time + units::set_units(1, hr))
et <- cbind(et0, cov)
.rxWithSink(t, {
out2 <- rxSolve(ode,
params = c(a = -8 / 3, b = -10),
events = et,
inits = c(X = 1, Y = 1, Z = 1),
add.cov = TRUE,
method = meth
)
})
unlink(t)
test_that("Before assinging the time varying to -8/3, out and out2 should be different", {
expect_false(isTRUE(all.equal(out, out2)))
})
context(sprintf("Test First Assignment (%s)", meth))
## Assign a time-varying to a simple parameter
.rxWithSink(t, {
out$a <- -8 / 3
})
unlink(t)
test_that("The out$a=-8/3 works.", {
expect_equal(as.data.frame(out), as.data.frame(out2))
})
context(sprintf("Test Second Assignment (%s)", meth))
.rxWithSink(t, {
out$a <- out3$a
})
unlink(t)
test_that("the out$a = time varying covariate works.", {
expect_equal(as.data.frame(out), as.data.frame(out3))
})
context(sprintf("Covariate solve with data frame event table (%s)", meth))
## Covariate solve for data frame
d3 <- structure(list(
TIME = c(0, 0, 2.99270072992701, 192, 336, 456),
AMT = c(137L, 0L, -137L, 0L, 0L, 0L),
V2I = c(909L, 909L, 909L, 909L, 909L, 909L),
V1I = c(545L, 545L, 545L, 545L, 545L, 545L),
CLI = c(471L, 471L, 471L, 471L, 471L, 471L),
EVID = c(10101L, 0L, 10101L, 0L, 0L, 0L)
),
class = "data.frame",
row.names = c(NA, -6L),
.Names = c("TIME", "AMT", "V2I", "V1I", "CLI", "EVID")
)
mod1 <- RxODE({
d / dt(A_centr) <- -A_centr * (CLI / V1I + 204 / V1I) + 204 * A_periph / V2I
d / dt(A_periph) <- 204 * A_centr / V1I - 204 * A_periph / V2I
d / dt(A_circ) <- -4 * A_circ * exp(-ETA[2] - THETA[2]) + 4 * A_tr3 * exp(-ETA[2] - THETA[2])
A_circ(0) <- exp(ETA[1] + THETA[1])
d / dt(A_prol) <- 4 * A_prol * Rx_pow(exp(ETA[1] + THETA[1]) / A_circ, exp(THETA[4])) * (-A_centr * exp(ETA[3] + THETA[3]) / V1I + 1) * exp(-ETA[2] - THETA[2]) - 4 * A_prol * exp(-ETA[2] - THETA[2])
A_prol(0) <- exp(ETA[1] + THETA[1])
d / dt(A_tr1) <- 4 * A_prol * exp(-ETA[2] - THETA[2]) - 4 * A_tr1 * exp(-ETA[2] - THETA[2])
A_tr1(0) <- exp(ETA[1] + THETA[1])
d / dt(A_tr2) <- 4 * A_tr1 * exp(-ETA[2] - THETA[2]) - 4 * A_tr2 * exp(-ETA[2] - THETA[2])
A_tr2(0) <- exp(ETA[1] + THETA[1])
d / dt(A_tr3) <- 4 * A_tr2 * exp(-ETA[2] - THETA[2]) - 4 * A_tr3 * exp(-ETA[2] - THETA[2])
A_tr3(0) <- exp(ETA[1] + THETA[1])
})
tmp <- rxSolve(mod1, d3, structure(c(2.02103, 4.839305, 3.518676, -1.391113, 0.108127023, -0.064170725, 0.087765769),
.Names = c(sprintf("THETA[%d]", 1:4), sprintf("ETA[%d]", 1:3))
),
add.cov = TRUE,
method = meth
)
test_that("Data Frame single subject solve", {
expect_equal(
tmp %>%
dplyr::select(CLI, V1I, V2I) %>% as.data.frame(),
d3 %>% dplyr::filter(EVID == 0) %>%
dplyr::select(CLI, V1I, V2I) %>% as.data.frame()
)
expect_equal(names(tmp$params), mod1$params[-(1:3)])
})
d3 <- structure(list(
ID = c(1L, 1L, 1L, 1L, 1L, 1L, 2L, 2L, 2L, 2L),
TIME = c(0, 0, 2.99270072992701, 192, 336, 456, 0, 0, 3.07272727272727, 432),
AMT = c(137L, 0L, -137L, 0L, 0L, 0L, 110L, 0L, -110L, 0L),
V2I = c(909L, 909L, 909L, 909L, 909L, 909L, 942L, 942L, 942L, 942L),
V1I = c(545L, 545L, 545L, 545L, 545L, 545L, 306L, 306L, 306L, 306L),
CLI = c(471L, 471L, 471L, 471L, 471L, 471L, 405L, 405L, 405L, 405L),
EVID = c(10101L, 0L, 10101L, 0L, 0L, 0L, 10101L, 0L, 10101L, 0L)
),
class = "data.frame", row.names = c(NA, -10L),
.Names = c("ID", "TIME", "AMT", "V2I", "V1I", "CLI", "EVID")
)
par2 <- matrix(c(
2.02103, 4.839305, 3.518676, -1.391113, 0.108127023, -0.064170725, 0.087765769,
2.02103, 4.839305, 3.518676, -1.391113, -0.064170725, 0.087765769, 0.108127023
),
nrow = 2, byrow = T,
dimnames = list(NULL, c(sprintf("THETA[%d]", 1:4), sprintf("ETA[%d]", 1:3)))
)
tmp <- rxSolve(mod1, d3, par2, add.cov = TRUE, cores = 2, method = meth)
test_that("Data Frame multi subject solve", {
expect_equal(
tmp %>%
dplyr::select(CLI, V1I, V2I) %>% as.data.frame(),
d3 %>%
dplyr::filter(EVID == 0) %>%
dplyr::select(CLI, V1I, V2I) %>% as.data.frame()
)
expect_equal(names(tmp$params)[-1], mod1$params[-(1:3)])
})
## Now check missing covariate values.
d3na <- structure(list(
ID = c(1L, 1L, 1L, 1L, 1L, 1L, 2L, 2L, 2L, 2L),
TIME = c(0, 0, 2.99270072992701, 192, 336, 456, 0, 0, 3.07272727272727, 432),
AMT = c(137L, 0L, -137L, 0L, 0L, 0L, 110L, 0L, -110L, 0L),
V2I = c(909L, NA_integer_, 909L, 909L, 909L, 909L, 942L, 942L, 942L, 942L),
V1I = c(545L, 545L, 545L, 545L, 545L, 545L, 306L, 306L, 306L, NA_integer_),
CLI = c(471L, 471L, 471L, 471L, NA_integer_, 471L, 405L, 405L, 405L, 405L),
EVID = c(10101L, 0L, 10101L, 0L, 0L, 0L, 10101L, 0L, 10101L, 0L)
),
class = "data.frame", row.names = c(NA, -10L),
.Names = c("ID", "TIME", "AMT", "V2I", "V1I", "CLI", "EVID")
)
tmp <- rxSolve(mod1, d3na, par2, add.cov = TRUE, cores = 2, method = meth)
tmp2 <- rxSolve(mod1, d3, par2, add.cov = TRUE, cores = 2, method = meth)
context(sprintf("Test NA extrapolation for %s solving", meth))
test_that("NA solve is the same", {
for (i in c("id", "time", "A_centr", "A_periph", "A_circ", "A_prol", "A_tr1", "A_tr2", "A_tr3")) {
expect_equal(tmp[[i]], tmp2[[i]])
}
})
d3na <- structure(list(
ID = c(1L, 1L, 1L, 1L, 1L, 1L, 2L, 2L, 2L, 2L),
TIME = c(0, 0, 2.99270072992701, 192, 336, 456, 0, 0, 3.07272727272727, 432),
AMT = c(137L, 0L, -137L, 0L, 0L, 0L, 110L, 0L, -110L, 0L),
V2I = c(909L, NA_integer_, 909L, 909L, 909L, 909L, 942L, 942L, 942L, 942L),
V1I = c(545L, 545L, 545L, 545L, 545L, 545L, NA_integer_, NA_integer_, NA_integer_, NA_integer_),
CLI = c(471L, 471L, 471L, 471L, NA_integer_, 471L, 405L, 405L, 405L, 405L),
EVID = c(10101L, 0L, 10101L, 0L, 0L, 0L, 10101L, 0L, 10101L, 0L)
),
class = "data.frame", row.names = c(NA, -10L),
.Names = c("ID", "TIME", "AMT", "V2I", "V1I", "CLI", "EVID")
)
test_that("All covariates are NA give a warning", {
expect_warning(
rxSolve(mod1, d3na, par2, add.cov = TRUE, cores = 2, method = meth),
"one or more covariates were all 'NA' for subject 'id=2'"
)
})
}
context("time-varying covariates work with ODEs")
test_that("time varying covariates lhs", {
dfadvan <- structure(list(
ID = c(
1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L,
1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L, 1L,
2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L,
2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L, 2L
),
TIME = c(
0L, 1L, 2L, 3L, 4L, 5L, 6L, 7L, 8L, 9L, 10L, 11L, 12L, 12L, 13L, 14L, 15L,
16L, 17L, 18L, 19L, 20L, 21L, 22L, 23L, 24L, 0L, 1L, 2L, 3L,
4L, 5L, 6L, 7L, 8L, 9L, 10L, 11L, 12L, 12L, 13L, 14L, 15L, 16L,
17L, 18L, 19L, 20L, 21L, 22L, 23L, 24L
), AMT = c(
100L, 0L, 0L,
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 100L, 0L, 0L, 0L, 0L,
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 100L, 0L, 0L, 0L, 0L, 0L, 0L,
0L, 0L, 0L, 0L, 0L, 0L, 100L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L,
0L, 0L, 0L, 0L
), MDV = c(
1L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L,
0L, 0L, 0L, 0L, 1L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L,
0L, 1L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 1L, 0L,
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L
), CLCR = c(
120L, 120L,
120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L,
120L, 120L, 120L, 30L, 30L, 30L, 30L, 30L, 30L, 30L, 30L, 30L,
30L, 30L, 30L, 30L, 30L, 30L, 120L, 120L, 120L, 120L, 120L, 120L,
120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L, 120L,
120L, 120L, 120L, 120L
)
),
row.names = c(NA, -52L), class = "data.frame"
)
mod <- RxODE({
CLpop <- 2 # clearance
Vpop <- 10 # central volume of distribution
CL <- CLpop * (CLCR / 100)
V <- Vpop
})
mod2 <- RxODE({
CLpop <- 2 # clearance
Vpop <- 10 # central volume of distribution
CL <- CLpop * (CLCR / 100)
V <- Vpop
d / dt(matt) <- 0
})
x1 <- rxSolve(mod, dfadvan, keep = "CLCR")
x2 <- expect_warning(rxSolve(mod2, dfadvan, keep = "CRCL"))
expect_equal(x1$CL, x2$CL)
})
}
},
silent = TRUE,
test = "lvl2"
)
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