From: "Stuyckens, Kim [PRDBE]" KSTUYCK1@PRDBE.JNJ.COM
Subject:  [NMusers] SS indication for dataset with BID dose and AM dose different from PM dose.
Date: Tue, 11 Jul 2006 17:46:43 +0200

Dear Colleagues,

I have a flexible dosing BID study where the AM dose is different from PM dose.
At the time PK samples are collected, we are at the steady state condition.

Is there anyone familiar with the use of SS and II in this situation? If so, could
you show me how SS and II would be implemented in the dataset (please use the
example I put below)?

In the example below we know that the AM dose is 0.5 and PM dose is 0.8 for more
than 10 days (SS is reached after 5 days for this compound)

ID      DV      AMT     DATE            TIME    SS      II
1       0       0.8     01/01/2006      20:00
1       0       0.5     01/02/2006      08:00
1       15      0       01/01/2006      08:01

Thanks in advance for the input.

Kind regards,
Kim

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From: "Bill Bachman" 
Subject: RE: [NMusers] SS indication for dataset with BID dose and AM dose different from PM dose.
Date: Tue, 11 Jul 2006 12:12:20 -0400

I think that all you are missing is the ss=1 and ii=24 for lines 1 and 2 (0 for both on line 3).
Like anything else you get for free, test it to be sure it does what you expect.  (I am hedging
because, I have done this with ADDL before, but not SS.  Looks like it would work.)

J
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From: Mark Sale - Next Level Solutions mark@nextlevelsolns.com
Subject: RE: [NMusers] SS indication for dataset with BID dose and AM dose different from PM dose.
Date: Tue, 11 Jul 2006 09:31:01 -0700

Kim,
  This is pretty easy (which is the only reason I know the answer).  You give two doses, with
  different doses, as you have, each with II = 24.  The only issue is that you have to use a value
  of 2 for the second SS dose.  Normally (SS = 1), it basically erases all previous doses, and uses
  only and infinite series of doses (backwards not forwards),  So, the first dose (probably) has
  SS=1, erasing all previous doses, and the second has SS=2, giving this dose, on top of the
  previous dose.  But, you will also have to put them in chronological order. (or is the date
  on the DV record of 1/1/2006 incorrect - it is before the first dose?)
 
 
 
ID      DV      AMT     DATE            TIME    SS      II 
1       15      0       01/01/2006      08:01         .     .
1       0       0.8     01/01/2006      20:00       1    24 
1       0       0.5     01/02/2006      08:00       2    24
 
 
SS labels PREDPP's steady-state (SS) data item.  The steady-state data
item is optional. It can take one of three values in any event record.

0    indicates that the dose is not a steady state dose.

1    indicates that the dose is a steady state dose, and that the com-
      partment  amounts  are  to  be  reset to the steady-state amounts
      resulting from the given  dose.   Compartment  amounts  resulting
      from  prior dose event records are "zeroed out," and infusions in
      progress or pending additional doses are cancelled.   The  system
      is  not  totally  reset:   the  on/off status of the compartments
      remains as it was at the time of the prior event record (if any),
      and  the value of time must be greater than or equal to its value
      on the prior event record (if any).

2    indicates that the dose is a steady state dose and that the  com-
      partment  amounts  are  to  be set to the sum of the steady-state
      amounts resulting from the given dose plus whatever those amounts
      would  have been at the event time were the steady-state dose not
      given.  I.e., letting t be the time on the event record, then the
      amounts in the compartments are updated to amounts valid for time
      t, and next, these amounts are added to the steady-state amounts.
      This is meaningful when kinetics are linear and the superposition
      principle holds.


Mark Sale MD
Next Level Solutions, LLC
www.NextLevelSolns.com

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From: Paul Hutson prhutson@pharmacy.wisc.edu
Subject: RE: [NMusers] SS indication for dataset with BID dose and AM dose different from PM dose. 
Date: Tue, 11 Jul 2006 13:36:17 -0500

Mark:
Like Bill, I have only used ADDL in the past.  I would expect, though, to set up SS before the
non-zero DV, and then to add doses if needed for subsequent DV values.  Do I understand
correctly then, that the infinite number of prior doses inferred by SS=1 or =2 is
understood when preceding DV items are evaluated?
Thanks for your insight.
Paul

-- 

Paul R. Hutson, Pharm.D.
Associate Professor
UW School of Pharmacy
777 Highland Avenue
Madison WI 53705-2222
Tel  608.263.2496
Fax 608.265.5421
Pager 608.265.7000, p7856
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