SAS program or SAS macro to prepare NonMem ready data

From: "Munsanje, Elliot [CNTUS]" EMunsanj@CNTUS.JNJ.COM Subject: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Tue, December 7, 2004 3:38 pm Dear NMusers: I am new to using NonMem. Does anyone have a SAS code that formats a data set to be used in NonMeM. If not, which software is recommended to make this ready-to go NonMem data. Elliot

From: "Nick Holford" n.holford@auckland.ac.nz Subject: Re: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Tue, December 7, 2004 3:59 pm Elliot, There is no such thing as automatic, ready to go preparation of NONMEM data files. The structure and content of a NONMEM data file is intimately tied up with the exact NONMEM model that will be run. Typically I get data from SAS or other databases in a plain text ASCII format and use awk to format it for NONMEM. This allows me to automate the creation of NONMEM data sets that are fine tuned for different models that I want to try. Keep dreaming :-) Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

From: mark.e.sale@gsk.com Subject: Re: [NMusers] SAS program or SAS macro to prepare NonMem readydata Date: Tue, December 7, 2004 4:16 pm Elliot, I have an Excel macro (I know Nick, real pop kineticists use Splus not Excel macros) that seems to work pretty well, and is pretty general. I'm happy to share, but won't use the bandwidth to send to out. Contact me if you want it. Of course, undocumented, unvalidated, not part 11, CFR 21 compliant etc. But, it only does the work, you have to know what you want the data set to look like. As Nick points out, the structure of the data set is closely related to the model, so you typically need multiple data sets for the many model in an analysis. Mark Sale M.D. Global Director, Research Modeling and Simulation GlaxoSmithKline 919-483-1808 Mobile 919-522-6668

From: "Munsanje, Elliot [CNTUS]" EMunsanj@cntus.jnj.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 10:01 am Nick: I think that is within the capabilities of SAS. A SAS macro may be customized to accomodate this intimate tie of structure and content of a NONMEM file to the model. Already this is done using excel macros. By the number of responses, may be very few people use SAS to generate NONMEM data sets. May be this is due to specialization either in programming or Modeling and rarely a combination of these skills. Elliot

From: mike.k.smith@pfizer.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 10:38 am Elliot, I think Nick's point is valid. The way that dosing histories and regimens are coded within the dataset and given the flexibility that that allows, coming up with a "catch-all" SAS macro to accommodate all possible data structures would take some effort. Using macro variables and switches it would certainly be possible to come up with a simple SAS macro to cope with simple cases. I suspect that there are many people within pharma-companies using SAS to prepare NONMEM datasets, but where these are either bespoke pieces of code for the given situation or perhaps they are considered intellectual property and not available for dissemination. Regards, Mike

From: From: "Bonate, Peter" pbonate@ilexonc.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 11:25 am The SAS code to generate a NONMEM data set is actually very easy. Suppose you have a data set (called DATA) sorted by id, time with variables ID TIME CONC DOSE. Dose can occur on every record or not as long as it has a value for the first record for each subject. Then you can generate the data within a data step. Here is a sample code for an oral dose given every 24 hours with observations at steady-state. Each subject has data collected on one occasion. proc sort data=data; by id time; run; quit; data nonmem; set data; by id; if first.id then do; evid = 1; mdv = 1; ii = 24; ss = 2; dv = 0; cmt = 1; amt = dose; output; amt = .; ii = .; ss = .; evid = 0; dv = conc; if dv = . then mdv = 1; else mdv = 0; cmt = 2; end; else do; amt = .; ii = .; ss = .; evid = 0; dv = conc; if dv = . then mdv = 1; else mdv = 0; cmt = 2; end; run; quit; Now suppose you have data on multiple occasions coded by a new variable 'OCC'. The code would be the same except for the following: 1.) Change proc sort data=data; by id time; run; quit; to proc sort data=data; by id occ time; run; quit; 2.) change if first.id then do; to if first.occ then do; You may need to tweak it a little bit for specific cases but this should do the trick. Pete Bonate Peter L. Bonate, PhD, FCP Director, Pharmacokinetics ILEX Oncology 4545 Horizon Hill Blvd San Antonio, TX 78229 phone: 210-949-8662 fax: 210-949-8219 email: pbonate@ilexonc.com

From: "Wang, Yaning" WangYA@cder.fda.gov Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem readyda ta Date: Wed, December 8, 2004 11:30 am I almost exclusively use SAS to generate all kinds of NONMEM data set. I believe Splus can do the work too. But the sort function in Splus is too slow for large dataset. Many other softwares (Excel, Systat, Awk, etc.) can do the work. It is only a matter of how familiar someone is with a specific software. Yaning Wang, PhD Pharmacometrician, OCPB, FDA

From: "Sam Liao" sliao@pharmaxresearch.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 12:04 pm Hi Elliot: We used SAS in NONMEM data preparation. But each SAS program has to adapt to the structure of available SAS data sets and the nmv model of the study. I may have a SAS program that you can use as a template to develop a SAS program for your study. But it will require some experience in SAS programming. Please give me a call if you need a template. Sam Liao PharMax Research 732-3029550

From: Michael.J.Fossler@gsk.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 12:08 pm Although I am sure that vB and SAS do a fine job of building NM datasets, if you are a new user looking to develop some programming skills in this area, I would recomend that you give S-plus (or its open-source version, R) a serious look. S was design to perform data manipulation, particularly data arranged in columns. The advantage of this data vector orientation is that there are many simple "one-step" commands in S+ that will do what many lines of a traditional programming language (where you might need many for-next loops) can accomplish. This is just my perception, but it seems to me that far too many modelers still build datasets by hand in Excel, particularly in small companies or in academia where there aren't SAS programmers for hire. Not only is this prone to error, but it's way too much work!! If you are new to population PK, take the time to learn a tool to help you with this important step - it will pay off quickly. Mike ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Michael J. Fossler, Pharm. D., Ph. D., F.C.P. Principal Clinical Pharmacokineticist Clinical Pharmacokinetics, Modeling & Simulation GlaxoSmithKline (610) 270 - 4797 FAX: (610) 270-5598 Cell: (443) 350-1194 Michael_J_Fossler@gsk.com ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~

From: "Leonid Gibiansky" leonidg@metrumrg.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 12:14 pm Just checked: S+ 6.1 Release 1 for Windows (2 Gig processor) took 3 sec to sort 1 million random numbers, 12 sec to sort 1 million character variables (the same numbers transformed to character variables) Not too bad: never had problems with data creation in S+ Leonid

From: "Sam Liao" sliao@pharmaxresearch.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 12:39 pm Hi Yaning: Do you mind if I ask your opinion from regulatory stand point? I am not sure how we can be sure the integrity of the data when other softwares were used in nmv data preparation. For NONMEM analysis which will be a part of regulatory submission, SAS can provide a log file that keeps track of all the data manipulation and derivation. Sam Liao PharMax Research

From: "Beasley, Bach Nhi t" BEASLEYN@cder.fda.gov Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 12:45 pm HI Elliot, I use SAS to format datasets for Nonmem. There are a few lines that I consistently use, but I have not worked with one dataset yet that allowed me to reuse an entire code. These lines really won't save you any time, but you can contact me if you'd like. In addition to what's already been mentioned, another problem is that datasets are set up in so many different ways and can be inconsistent within themselves (different formats used within one column) that I've always had to write a separate code for each NM dataset. Not to be cynical, but I just don't see it happening in the near future. Good luck! On another note, my personal bias is to stick with programs like SAS, SPlus, etc.. for your programming since these programs leave you a "string" as opposed to cutting and pasting in programs like Excel where mistakes have a greater potential to happen. Nhi Beasley, Pharm.D. Pharmacometrics FDA beasleyn@cder.fda.gov

From: "Wang, Yaning" WangYA@cder.fda.gov Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 1:34 pm First of all, I want to clarify that all my posts here only reflect my personal opinion. As far as I know, there is no regulatory preference for any commercial software for data manipulation. On the other hand, it is a good practice to use softwares that can keep track of all the data manipulation steps so that we can easily reproduce the results or make further changes. SAS may be the most popular software for data manipulation here in FDA since all the data files are submitted as SAS transport files. But some of my colleagues use S+ because they are more familiar with S+. Also some of my colleagues use a program called JMP. Leonid: My earlier comment on S+ sort function was based on my experience with S+ two years ago on S+2000 (bound with TS2). I was trying to sort a large simulated data frame based on two columns (ID TIME). It was much slower compared with SAS at that time. Maybe I was not using the most efficient command or S+ 6.1 improves this function. Anyway, I am more comfortable with SAS.

From: "Chapel, Sunny" Sunny.Chapel@pfizer.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 2:03 pm I use SAS and Splus for Nonmem datasets, but I just want to point out that WinNonlin has some functionality for Nonmem data creation. (I don't know how good it is, though.) Splus is convenient but it doesn't handle large datasets very well because of its notorious "memory leak" problem. In other words, Splus keeps copies of intermediate datasets during calculation in the memory until it is sure that they are unnecessary. No loops with large objects! When Splus shows the "insufficient dynamic memory" message, the only way to be able to use Splus is to quit Splus and restart it. I'm a big fan of Splus, but I tend to use SAS more and more for data manipulation as the datasets I deal with become larger and larger. If I were new and needed to learn how to create Nonmem datasets, I would stick with SAS. I also think that the dream of automating Nonmem data creation won't come true soon. Sunny Chapel, PhD Clinical PK/PD Pfizer Ann Arbor Laboratory Sunny.Chapel@Pfizer.com

From: "Nick Holford" n.holford@auckland.ac.nz Subject: Re: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Wed, December 8, 2004 2:04 pm Elliot, I am sure SAS (or almost any other programming language) can be used to write code to format data for NONMEM. However, as several people have pointed out their is no single piece of code that can do this for any input. There are many things that I do while formatting data for NONMEM -- this includes consistency checking (e.g. are weights in a reasonable range?), putting out error messages for invalid data (e.g. positive concentration of drug before any dose has been given), transformation of values (e.g. some data sets have weights in both kg and pounds [and if one is lucky a units indicator too!]), making decisions based on all the records for a given individual (e.g. dosing records are supplied but no conc records so I drop all these records from the NONMEM dataset because they add nothing to a PK analysis). In addition to these data driven needs there are model specific items that need to be put in the data set e.g. CMT items depend on the model structure, additional records are required to initialize differential equations. IMHO the programming challenges for dealing with real NONMEM data sets and non-trivial models (i.e. more than simple PK) demand the NONMEM analyst either writes his/her own data formatting code or works with someone with these skills. The ability to automate data formatting (and therefore demonstrate exactly how original data is transformed) is an essential part of any quality based NONMEM analysis. Manual manipulation of data items in Excel should be discouraged. Nick -- Nick Holford, Dept Pharmacology & Clinical Pharmacology University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556 http://www.health.auckland.ac.nz/pharmacology/staff/nholford/

From: david_john.garbutt@pharma.novartis.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Thu, December 9, 2004 9:53 am Hi, I think the issue is more subtle that this refutation purports to show. The way SAS (in the data step) processes data means that it generally needs an amount of memory proportional to the size of one observation. The same SAS program will run on any size of dataset (the limit is the disk space you have). S-Plus (and other packages keeping data in memory, like minitab ;-)) need memory proportional to the size of the whole dataset. Therefore they will not be able to run a given program for some finite data size. As it happens this critical size is these days larger. But it still exists and it can be a practical problem. And it is therefore a reason to choose SAS over others. regards, Dave Garbutt http://public.xdi.org/=djg

From: "Bachman, William (MYD)" bachmanw@iconus.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Thu, December 9, 2004 10:22 am I don't really see a need to choose one program over the other, at least not in an all or none sense. In the realm of dataset preparation, SAS, in my opinion, is superior to S-Plus. It is the overall industry standard, it does handle large data sets better than S-Plus and statisticians and data management people have a long history with it. On the down-side, $A$ gouges the industry on a yearly basis. In favor of S-Plus, it has a strong foothold in the population analysis niche primarily because it has fabulous graphics capabilities. On the Windows platform, you buy it once and you own it (as long as you don't want or need to upgrade). The language is very powerful but the learning curve is VERY steep. But like SAS you can script it to automate procedures and if you have an in-house S-Plus guru - don't let him leave! (S-Plus scripts perform the same function as SAS macros with respect to documentation of process). Bottom line, use the best tool for the particular problem.

From: "Leonid Gibiansky" leonidg@metrumrg.com Subject: RE: [NMusers] SAS program or SAS macro to prepare NonMem ready data Date: Sat, December 11, 2004 12:23 am Do not get me wrong: I am not arguing against SAS or for S+: I think, this is a matter of preference and depends on the problems that you need to solve. I was commenting on a particular question: data set creation for PK/PD modeling. In this setting, S+ memory problems/limitations do not manifest itself. Even if they would, this is not related to the performance of the sort function but rather to memory management. For data set creation, data diagnostics and NONMEM model output diagnostics S+ (or R) should be adequate. If you try to analyze results of 1000 simulations of the trail with 1000 patients you better use SAS: most likely, S+ will not be able to handle it. To me, the major limitation of SAS is cost while S+ is not expensive and R is free. Leonid _______________________________________________________