rxode2 covariate sync

[mattfidler]

library(rxode2)
#> Warning: package 'rxode2' was built under R version 4.3.1
#> rxode2 2.0.13 using 4 threads (see ?getRxThreads)
#>   no cache: create with `rxCreateCache()`

dat <- 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, 
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, 2L, 3L, 3L, 3L, 3L, 
3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 3L, 
3L, 3L, 3L, 3L, 3L, 3L, 3L), TIME = c(0, 0, 0, 0.5, 0.5, 1, 1, 
1.5, 1.5, 2, 2, 2.5, 2.5, 3, 3, 3.5, 3.5, 4, 4, 4.5, 4.5, 5, 
5, 5.5, 5.5, 6, 6, 0, 0, 0, 0.5, 0.5, 1, 1, 1.5, 1.5, 2, 2, 2.5, 
2.5, 3, 3, 3.5, 3.5, 4, 4, 4.5, 4.5, 5, 5, 5.5, 5.5, 6, 6, 0, 
0, 0, 0.5, 0.5, 1, 1, 1.5, 1.5, 2, 2, 2.5, 2.5, 3, 3, 3.5, 3.5, 
4, 4, 4.5, 4.5, 5, 5, 5.5, 5.5, 6, 6), EVID = c(80101L, 60101L, 
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 80101L, 60101L, 0L, 0L, 0L, 
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 
0L, 0L, 0L, 0L, 0L, 0L, 80101L, 60101L, 0L, 0L, 0L, 0L, 0L, 0L, 
0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 0L, 
0L, 0L, 0L), AMT = c(10, 10, NA, NA, NA, NA, NA, NA, NA, NA, 
NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 
NA, 10, 10, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 
NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 10, 10, NA, NA, 
NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, NA, 
NA, NA, NA, NA, NA, NA, NA), II = c(0, 0, 0, 0, 0, 0, 0, 0, 0, 
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 
0, 0, 0, 0, 0, 0, 0, 0, 0), DV = c(NA, NA, 0, 3.8, 0.9, 5.8, 
2.5, 3.2, 3.2, 1.8, 2.9, 1, 2.2, 0.5, 1.6, 0.3, 1.1, 0.2, 0.8, 
0.1, 0.5, 0, 0.3, 0, 0.2, 0, 0.1, NA, NA, 0, 3.4, 0.7, 7.3, 2.4, 
2.8, 2.5, 1.3, 2.7, 1, 1.6, 0.6, 1.1, 0.3, 0.8, 0.2, 0.8, 0.1, 
0.5, 0, 0.3, 0, 0.2, 0, 0.2, NA, NA, 0, 2.8, 1.1, 6.7, 2.7, 3.9, 
3.6, 1.5, 3.1, 0.7, 2.4, 0.5, 1.5, 0.3, 1.2, 0.1, 0.5, 0.1, 0.6, 
0.1, 0.4, 0, 0.2, 0, 0.2), CMT = c(1L, 1L, 4L, 3L, 4L, 3L, 4L, 
3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 
3L, 4L, 3L, 4L, 1L, 1L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 
4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 1L, 
1L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 
3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L, 3L, 4L), nlmixrRowNums = c(1, 
NA, 14, 2, 15, 3, 16, 4, 17, 5, 18, 6, 19, 7, 20, 8, 21, 9, 22, 
10, 23, 11, 24, 12, 25, 13, 26, 27, NA, 40, 28, 41, 29, 42, 30, 
43, 31, 44, 32, 45, 33, 46, 34, 47, 35, 48, 36, 49, 37, 50, 38, 
51, 39, 52, 53, NA, 66, 54, 67, 55, 68, 56, 69, 57, 70, 58, 71, 
59, 72, 60, 73, 61, 74, 62, 75, 63, 76, 64, 77, 65, 78)), class = "data.frame", row.names = c(NA, 
-81L))

par <- structure(c(0, 0, 0, 0.693147180559945, 0.693147180559945, 0.693147180559945, 
2.30258509299405, 2.30258509299405, 2.30258509299405, 2.30258509299405, 
2.30258509299405, 2.30258509299405, 0, 0, 0, 1, 1, 1, 1, 1, 1, 
-1.86782087447842, 0, 0, -2.44813462994314, 0, 0, 0.0831313226164289, 
0, 0, -2.28843604434224, 0, 0, 1.97816823869187e-05, 0, 0), dim = c(3L, 
12L), dimnames = list(NULL, c("THETA[1]", "THETA[2]", "THETA[3]", 
"THETA[4]", "THETA[5]", "THETA[6]", "THETA[7]", "ETA[1]", "ETA[2]", 
"ETA[3]", "ETA[4]", "ETA[5]")))

rx <- rxode2({
    param(THETA[1], THETA[2], THETA[3], THETA[4], THETA[5], THETA[6], 
        THETA[7], ETA[1], ETA[2], ETA[3], ETA[4], ETA[5])
    cmt(center)
    cmt(meta)
    rx_expr_5 ~ ETA[3] + THETA[1]
    rx_expr_6 ~ ETA[1] + THETA[2]
    rx_expr_7 ~ ETA[2] + THETA[4]
    rx_expr_10 ~ exp(rx_expr_5)
    d/dt(center) = -rx_expr_10 * center - exp(rx_expr_6 - (rx_expr_7)) * 
        center
    rx_expr_8 ~ ETA[5] + THETA[5]
    rx_expr_11 ~ exp(rx_expr_8)
    dur(center) = rx_expr_11
    rx_expr_9 ~ ETA[4] + THETA[3]
    d/dt(meta) = rx_expr_10 * center - exp(rx_expr_9 - (rx_expr_7)) * 
        meta
    center(0) = 0
    meta(0) = 0
    rx_expr_0 ~ CMT == 4
    rx_expr_1 ~ CMT == 3
    rx_expr_2 ~ 1 - (rx_expr_0)
    rx_yj_ ~ 2 * (rx_expr_2) * (rx_expr_1) + 2 * (rx_expr_0)
    rx_expr_3 ~ (rx_expr_0)
    rx_expr_4 ~ (rx_expr_2)
    rx_expr_12 ~ rx_expr_4 * (rx_expr_1)
    rx_lambda_ ~ rx_expr_12 + rx_expr_3
    rx_hi_ ~ rx_expr_12 + rx_expr_3
    rx_low_ ~ 0
    rx_expr_13 ~ exp(-(rx_expr_7))
    rx_expr_14 ~ rx_expr_13 * meta
    rx_expr_15 ~ rx_expr_13 * center
    rx_expr_17 ~ rx_expr_14 * (rx_expr_0)
    rx_expr_18 ~ rx_expr_15 * (rx_expr_2)
    rx_expr_19 ~ rx_expr_18 * (rx_expr_1)
    rx_pred_ = (rx_expr_0) * (rx_expr_17 + rx_expr_19) + rx_expr_18 * 
        Rx_pow_di((rx_expr_1), 2)
    rx_r_ = (rx_expr_0) * Rx_pow_di(((rx_expr_17 + rx_expr_19) * 
        THETA[7]), 2) + (rx_expr_2) * Rx_pow_di((rx_expr_15 * 
        THETA[6] * (rx_expr_1)), 2) * (rx_expr_1)
    tkm = THETA[1]
    tcl = THETA[2]
    tclm = THETA[3]
    tv = THETA[4]
    tdur0 = THETA[5]
    prop.err = THETA[6]
    prop.err2 = THETA[7]
    eta.cl = ETA[1]
    eta.v = ETA[2]
    eta.km = ETA[3]
    eta.clm = ETA[4]
    eta.dur0 = ETA[5]
    km = rx_expr_10
    cl = exp(rx_expr_6)
    clm = exp(rx_expr_9)
    v = exp(rx_expr_7)
    dur0 = rx_expr_11
    cp = rx_expr_15
    cm = rx_expr_14
    tad = tad()
    dosenum = dosenum()
    cmt(cp)
    cmt(cm)
    dvid(3, 4)
}) 
#> using C compiler: 'gcc.exe (GCC) 12.2.0'

s <- rxSolve(rx, dat, par, returnType="data.frame", keep=c("nlmixrRowNums", "DV"), subsetNonmem=TRUE, addCov=TRUE)

s %>% dplyr::filter(time==0.5) %>% dplyr::pull(CMT)
#> [1] 4 4 4 4 4 4

^{Created on 2023-09-11 with reprex v2.0.2}

Smaller reprex

[mattfidler]

Addresses nlmixr2/nlmixr2est#394

[mattfidler]

Should have 3 and 4

[mattfidler]

FYI @Lee21A