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MEANING: ERROR subroutine
CONTEXT: User-supplied subroutine; for use with PREDPP
USAGE:
SUBROUTINE ERROR (ICALL,IDEF,THETA,IREV,EVTREC,NVNT,INDXS,F,G,HH)
INTEGER ICALL,IDEF,IREV,NVNT,INDXS
DIMENSION IDEF(*),THETA(*),EVTREC(IREV,*),INDXS(*),G(LVR,*)
DIMENSION HH(LVR,*)
(If double precision is to be used):
DOUBLE PRECISION THETA, F, G, HH
(If single precision is to be used):
REAL THETA, F, G, HH
The value of LVR must be the same as that found in file SIZES
(See sizes).
DISCUSSION:
The ERROR subroutine is called by PREDPP to model intra-individual
error in observed values. It can also be used to to convert predic-
tions from PREDPP, i.e., scaled drug amounts, to other types of pred-
ictions (for example, to obtain the prediction of a drug effect as a
function of concentration, in a pharmacodynamic study).
Input argument:
ICALL
ICALL=1: ERROR has been called for initialization at the begin-
ning of a NONMEM problem; one such call per problem. EVTREC con-
tains the first event record. THETA contains the initial esti-
mates. ERROR must return values in IDEF which inform PREDPP what
tasks it will perform at later calls. It may also set elments of
HH to the appropriate derivatives, when it has requested that
ERROR be called only once per problem.
ICALL=2: ERROR has been called to obtain the modeled value; mul-
tiple calls occur. ERROR should compute derivatives of F for HH.
If ERROR changes F, it should also change the derivates of F in
G.
ICALL=4: ERROR has been called during the Simulation Step; multi-
ple calls occur. ERROR should compute simulated observations and
store them in F.
ICALL=5: ERROR has been called during the computation of expecta-
tions; multiple calls occur. Such calls occur when the marginal
(MRG_) data item is defined in the data set and has non-zero
values for some records. If the MRG_ data item has the value 1
or 2, expectations are computed for that record, and the value
returned by ERROR in F contributes to the expectation that is
being computed for the PRED data item. The value of an ERROR-
defined item contributes to the expectation computed for the
item.
ICALL=6: ERROR has been called during the computation of raw data
averages; multiple calls occur. Such calls occur when the raw-
data (RAW_) data item is defined in the data set and has the
value 1 for some records (See template). ERROR may re-compute DV
when the value of DV in the data record is not the quantity to be
included in the average. ERROR may return a value of 1 in F if
no DV item is to be included in the average with the particular
record.
THETA
The NONMEM THETA vector.
EVTREC
The PREDPP event record.
INDXS
The values specified in the $INDEX record of the NM-TRAN control
stream. (This is the NONMEM INDXS array starting at position 12,
the first position beyond those positions used by PREDPP itself.)
Output argument:
IDEF
ERROR should store values in IDEF only when ICALL=1. A value of
1 in IDEF(1) indicates that ERROR will store the derivatives of
log y in HH (which causes PREDPP to multiply each element of HH
by F). That is, PREDPP understands that the "error in log y" is
modeled.
The value in IDEF(2) describes when ERROR should be called:
-1 call with every event record.
0 call once per observation record.
1 call once per individual record.
2 call once per problem.
The value in IDEF(3) describes whether ERROR uses derivatives of
compartment amounts (i.e. whether compartment amounts themselves
are used as random variables in arithmetic statements in ERROR).
-1 ERROR may use derivatives of A.
0 ERROR does not use derivatives A.
1 ERROR does use derivatives of A.
The default used by PREDPP is IDEF(3)=-1. However, when ERROR
does not use A, then if IDEF(3) is set to 0, PREDPP can avoid
some time-consuming processing. Indeed, when $ERROR abbreviated
code is supplied, and there is no reference to a compartment
amount A(n) (as a random variable in an arithmetic statement) in
the abbreviated code (or to its derivatives in verbatim code),
then NM-TRAN sets IDEF(3)=0.
Input/Output argument:
F On input, the prediction based on the pharmacokinetic model,
i.e., the value of the scaled drug amount in the observation com-
partment. On output, F may be unchanged, or it may be modified,
e.g., when a PD prediction is needed. If ERROR modifies F and
uses population eta variables to do so, then at ICALL=2 ERROR
must call GETETA to obtain eta values prior to modifying F. When
ICALL=4, ERROR should calculate the simulated observation (after
calling SIMETA and/or SIMEPS to obtain simulated etas and epsi-
lons, as necessary) and place its value in F. With the Simula-
tion Step, ERROR may return the simulated observation as the DV
data item, rather than in the argument F. With odd-type data the
simulated observation must be returned as the DV data item.
(See $estimation).
G On input, at ICALL=2 when the data are population, an array of
partial derivatives of F with respect to etas
G (i,1) is the partial derivative of F with respect to eta(i).
G (i,j+1) is the second derivative of F with respect to eta(i),
eta(j) (lower-triangular; j=1, ..., i).
(Second derivatives are only needed with estimation by the Lapla-
cian method.)
On input, G contains zeros when the data are single-subject data.
At ICALL=2, ERROR must modify G when it has changed F and has
thus changed the derivatives of F with respect to the population
etas.
HH An array of partial derivatives of F with respect to etas (when
the data are single-subject data) or epsilons (when the data are
population). Values should be stored when ICALL=2 and also when
ICALL=1 if ERROR sets IDEF(2)=2.
HH(i,1) is the derivative of F with respect to eta(i) or eps(i).
HH(i,j+1) is the derivative of H(i,1) with respect to eta(j) (but
are only needed with conditional estimation when the dependence
on etas of the variance of intra-individual random error should
be preserved in the computation of the objective function; see
the INTERACTION option (See $ESTIMATION).
Also see NONMEM read-only commons (of the form ROCMn), NONMEM-PRED
commons (of the form NMPRDn), and PREDPP read-only commons (of the
form PROCMn).
REFERENCES: Guide IV Section V.C.6
REFERENCES: Guide V Section 8
REFERENCES: Guide VI Section IV
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