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| |
| $LEVEL |
| |
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MEANING: Specifies Nested Random Levels Above Subject ID |
CONTEXT: NM-TRAN Control Record
USAGE:
$LEVEL item=(n1[m1] , n2[m2] ... ) ...
SAMPLE:
$LEVEL
DISCUSSION:
Identifies one or more Super ID data items.
item Item is the name of a data item listed on $INPUT. It defines an
additional nested random level. and is referred to as a "super
ID" data item. The first super ID item defines an additional
random nesting level above that of subject ID. More than one
super ID item may be listed on $LEVEL. Each subsequent super ID
item defines an additional nesting level above that of the previ-
ous nesting level, i.e., above the previous super ID.
nk[mk]
States that ETA(nk) is associated with this super ID item, and
ETA(mk) is nested within ETA(nk).
With NONMEM 7.4, a short-hand notation may be used to describe a |
series of values of nk. A sequence of values for nk can be described |
as |
start TO end BY interval |
TO is required. The character : may be used instead of TO. BY |
is optional. Default is 1. The value of BY may be negative. |
If the second value of BY differs, the same syntax may also be used |
for mk. |
Nesting levels below the subject ID is modelled as with previous ver-
sions of NONMEM.
(See Interoccasion_variability example).
The order that super ID's are listed on $LEVEL defines their nesting
level. The order that standard and super ID's are listed on $INPUT
(i.e., the order in which they appear in each record of the data set)
is immaterial.
When $LEVEL is used with FOCE ($ESTM METHOD=1), the SLOW option is
required, and MATRIX=R is required with $COV.
EXAMPLE:
$INPUT ... ID ... SID ... CID ...
...
$PK
MU_1=THETA(1)
MU_2=THETA(2)
CL=DEXP(MU_1+ETA(1)+ETA(5)+ETA(9))
V1=DEXP(MU_2+ETA(2)+ETA(6)+ETA(10))
...
$LEVEL
SID=(5[1],6[2])
CID=(9[5],10[6])
The data item named SID is the site ID. The data item named CID is
the country ID. There are several sites belonging to one country,
some other sites belonging to another country, etc. For clearance,
eta(9) is the country variability that has nested in it the site vari-
ability eta(5), which in turn has nested in it the subject variability
(the standard ID data) eta(1). For V1, eta(10) is the country vari-
ability that has nested in it the site variability eta(6), which in
turn has nested in it the subject variability (the standard ID data)
eta(2).
An alternate way of coding the $LEVEL records is |
SID=(5 to 6[1]) |
CID=(9 to 10[5]) |
NONMEM performs appropriate summary statistics for eta(5), and makes
the appropriate constraints on eta(5), so eta(5) changes by site, that
is, by every SID value change, and not by every ID value change.
The above method, using $LEVEL, is a linearized approximation at the
super ID level, and takes advantage of a dual OBJ function call,
freely allowing all etas to vary on the first call of OBJ, then aver-
aging the SID etas, fixing them to these averages, and going through
another OBJ call to allow the subject (ID) etas to be assessed. This
approximation method works very well for the EM and Monte Carlo meth-
ods, and reasonably well for the FOCE/Laplace methods.
To perform an exact analysis, separate thetas must be defined for each
value pertaining to a super ID data item, so that theta is shared only
by the subjects with the particular SID value. $LEVEL is not used.
(See superid3_6).
If there are multiple $PROBLEM records, $LEVEL should be restated |
with each problem for which it is still relevant. For example, this |
is the case with $SUPER problems and $LEVEL.
See also LEVWT option of the $ESTIMATION record (NM74). By default,
LEVWT=0, and weights each level value equally, regardless of number of
subjects per level value. If you wish to weight according to number of
subjects for that value, set LEVWT=1 on the $EST record.
REFERENCES: Guide Introduction_7
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Created by nmhelp2html v. 1.0 written by Niclas Jonsson (Modified by AJB 5/2006,11/2007,10/2012)