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Documenting Electronic Data Files 
and Statistical Analysis Programs 
Guidance for Industry 
This version of the guidance replaces the version made available December 2015.  The 
document has been revised to clarify existing language, remove recommendations that are no 
longer applicable, and provide additional details on the README file. 
Submit comments on this guidance at any time.  Submit electronic comments to 
https://www.regulations.gov.  Submit written comments to the Dockets Management Staff 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD  
20852.  All comments should be identified with the docket number FDA-2009-D-0052. 
For further information regarding this document, contact AskCVM@fda.hhs.gov. 
Additional copies of this guidance document may be requested from the Policy and Regulations 
Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 7500 Standish 
Place, Rockville MD 20855, and may be viewed on the Internet at either 
https://www.fda.gov/animal-veterinary or https://www.regulations.gov. 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
November 2020  Contains Nonbinding Recommendations 
Table of Contents 
I.  Introduction .......................................................................................................................... 3 
II.  Background ........................................................................................................................... 3 
III.  Structure and Content of README Files ......................................................................... 4 
A.  The README File ......................................................................................................... 4 
B.  Structure of README Files .......................................................................................... 5 
1.  Electronic Data Files ................................................................................................ 5 
2.  Audit Trail Files ........................................................................................................ 7 
3.  Data Analysis Programs ........................................................................................... 9 
IV.  Data and Analysis Programs: Additional Comments ..................................................... 11 
Appendix ...................................................................................................................................... 12 
   
2    Contains Nonbinding Recommendations 
Documenting Electronic Data Files 
and Statistical Analysis Programs 
 
Guidance for Industry 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on FDA 
or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
responsible for this guidance as listed on the title page. 
 
I.  Introduction 
 
This guidance is provided to inform sponsors of recommendations for documenting electronic 
data files and statistical analyses submitted to the Center for Veterinary Medicine (CVM) to 
support new animal drug applications.  These recommendations are intended to reduce the 
number of revisions that may be required for CVM to effectively review data submissions.  They 
are also intended to simplify submission preparation for sponsors by providing a suggested 
documentation framework, including a sample structure on how to describe and organize the 
information regarding the electronic data files and statistical analysis programs. 
 
The determination of what data and analysis are needed to support a new animal drug application 
may vary depending on many factors and is outside the scope of this document.  You should 
refer only to those portions of this guidance that are applicable to your particular submission. 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
II.  Background  
 
For new animal drug applications, FDA requires full reports of investigations which have been 
conducted to show a drug is safe and effective for use [section 512(b)(1)(A) of the Federal Food, 
Drug, and Cosmetic Act (the FD&C Act)].  Additionally, section 512(n)(1)(E) of the FD&C Act 
requires that abbreviated applications for the approval of a new animal drug contain information 
to show that the new animal drug is bioequivalent to the approved new animal drug. 
 
Submissions to CVM in support of new animal drug applications generally include a Final Study 
Report (FSR)1 for one or more studies.  For each study that includes electronic data files, CVM 
                                                 
1 For the purpose of this guidance, supporting study reports (e.g., statistical or bioanalytical phase reports) appended 
to the FSR are considered part of the FSR.  
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needs information regarding the process for data generation and the statistical analysis conducted 
to review submissions and verify that there is sufficient quality and detail of evidence to support 
an animal drug application.  An adequately documented submission should include readable 
electronic data files, a description of how the data were processed, and a description of the 
statistical analyses employed to support your conclusions. 
 
Your submission should clearly describe the entire process by which the data were collected 
(e.g., transcribed or electronic data capture), including a record of all changes to the data, starting 
from the electronic data files created from transcribed case report forms, or from electronic data 
capture (EDC) systems, to the completed statistical analyses which form the basis for your 
studys conclusions.  To understand the process by which you compiled the data and conducted 
the statistical analysis, CVM needs to understand the contents of each electronic data file, the 
computer programs that processed all the electronic data files for analysis, and the programs that 
implemented the statistical analyses.  The information that should be submitted to CVM, 
together with the FSR and electronic data files, are described in sections III. Structure and 
Content of README Files and IV. Data and Analysis Programs: Additional Comments.  Section 
III describes recommendations for how README files should be organized and completed to 
describe the data files and analyses, and section IV contains additional recommendations 
regarding statistical analysis programs. 
 
III.  Structure and Content of README Files 
 
Data submissions to CVM via eSubmitter2 typically include data in Statistical Analysis System 
(SAS) transport XPORT (XPT) or eXtensible Markup Language (XML) format, analysis 
programming files in XML format, and documents in Portable Document Format (PDF).  A 
manual or instructional resource that contains important information about the electronic data 
files in the submission should be submitted to CVM in a README file.  This section describes 
the information that should be in the README file for CVM to evaluate the electronic data files.  
Electronic data files, in the context of this guidance, refer to the XPT and XML files included in 
a submission.  If any of the information described below is contained within the FSR it does not 
need to be repeated in the README file.  Instead, the README file may reference the 
corresponding location of the information in the FSR. 
 
A.  The README File 
 
An overview of electronic data files, documentation, and programming files included in the 
submission helps CVM assess the submission and the files for review.  The README file 
contains information about the electronic data files and programming files in a submission.  
The README file explains how the data files are organized and describes the programs 
used for data file generation and data analysis.  An effective README file should quickly 
orient the user to crucial information needed to understand the electronic data files in a 
submission. 
 
                                                 
2 For current eSubmitter file specifications, see CVM Recommended File Specifications in the CVM eSubmitter 
Resource Center: https://www.fda.gov/industry/fda-esubmitter/cvm-esubmitter-resource-center. 
4    Contains Nonbinding Recommendations 
The README file is typically a PDF file with the filename README.pdf.  The README 
file should not contain data, interpretation of the data, literature, references, notes to file, 
protocol-associated documents, communication records, personnel records, information not 
needed to interpret the data provided in the submission, or other information needed for the 
technical section. 
 
A submission may contain one or more README files depending on the organization and 
complexity of the submission.  README file(s) should be separate from the FSR. 
 
B.  Structure of README Files 
 
The README file should include a brief introduction that includes the study number or 
other identifier, and study descriptor along with general orientation, background, and other 
information relevant to analyzing and interpreting the data for each study.  A description of 
how the data were processed for analysis could also be included, such as how data were 
captured and merged to derive the analysis data files or audit trail processes. 
 
The following describes the README file and a sample structure. 
 
1.  Electronic Data Files 
 
a.  List of Electronic Data Files 
 
In this section, you should provide a table listing the electronic data files submitted 
in XML or XPT file format with brief descriptions.  This table should include the 
file name, a brief description of contents, name of data collection form(s), if 
applicable, and information on how the data were collected or any reference to 
location of information in the FSR that is needed to interpret the data (e.g., 
reference ranges or scoring definitions).  See Example Table 1a. Listing of XML and 
XPT Data Files. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Example Table 1a. Listing of XML and XPT Data Files. 
 
File Name1  File contents  Name of Data  Comments2 
Collection Form 
(e.g., Case Report 
Form) 
ClinObs.xml  Daily clinical  Observation Form  Clin Obs were collected 
observations during  via [name of data 
hospitalization  capture system] 
OwnerObs.xpt  Owner observation  Owner Diary  Recorded manually and 
results for individual  transcribed 
animals 
PlateletMan.xpt  Secondary variable:  Clinical Pathology  Reference ranges 
Manual platelet count  Form  available in Appendix 
G of Final Study Report 
1 File name extension included in order to identify the file as XML or XPT. 
2 Information included on how data were collected (paper data collection forms or EDC 
system) or any reference(s) to location of information in the FSR (e.g., reference ranges or 
scoring definitions) that are needed to interpret the data file. 
 
b.  Electronic Data File Contents 
 
For each data file submitted, you should provide a table that includes the variable 
names, the abbreviations used in the file, variable label or description, and 
additional details (e.g., description of coded values, unit of measure, formatting 
information), if applicable.  See Example Table 1b. Contents of 
DataFileName.XML.  Results from the CONTENTS procedure in SAS are not 
sufficient.  You may choose to use a standardized internal file format [e.g., Clinical 
Data Interchange Standards Consortium-Study Data Tabulation Model (SDTM) and 
Standard Exchange for Nonclinical Data (SEND)]3 to be submitted along with audit 
trail information if data were collected using EDC (described below). 
 
   
                                                 
3 See Study Data Standards Resources: https://www.fda.gov/industry/fda-resources-data-standards/study-data-
standards-resources. 
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Example Table 1b. Contents of DataFileName.XML (number of observations=, 
number of variables=). 
 
Variable  Variable Label or  Additional Details 
Name  Description  (e.g., descriptions of coded values, 
units of measure, formatting 
information) 
Animal  Animal Identification   
Dot  Day of treatment  Study day formatted as mm/dd/yyyy 
Trt  Treatment  T01=Placebo; T02=Drug 
Dscore  Daily Depression Score  0=normal; 1=slight; etc. 
Overallscore  Overall Depression Score  Sum of Daily Depression scores 
(Day 1 to 5) 
 
2.  Audit Trail Files 
 
This section only applies to studies that include audit trail files as part of the controls 
that ensure the authenticity and integrity of records in EDC systems.4  The audit trail is 
a portion of the raw data5 that includes the original recorded data value and any changes 
to the data value, the identification of individuals that entered or changed data in the 
EDC system, the date and time the data value was entered or changed, the reason for 
each change, and the date when the database was locked.6  If you are submitting audit 
trails on specified variables, the electronic audit trails should be submitted in an 
eSubmitter acceptable file format. 
 
CVM prefers to receive one copy of the EDC study database that includes the final 
variable observations (e.g., the electronic data files (see footnote 2) described in 
section III.B.1 Electronic Data Files above) and associated audit trail information, 
described in this section, together in one electronic data file or set of data files.  If you 
submit these combined data files, you should also submit the programs needed to create 
data files that contain the final observations suitable for review and statistical analysis.  
If you are unable to submit one copy of the EDC study database with associated audit 
trail information, submission of separate data files for analysis and electronic audit trail 
files is acceptable. 
 
                                                 
4 Electronic Data Capture (EDC) or Electronically Captured Data (ECD) refers to data that was electronically 
captured at first observation (e.g., web-based software or analytical instrument). 
5 As defined in 21 CFR 58.3(k) and in FDA Guidance for Industry #85 (VICH GL9), Good Clinical Practice 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-85-vich-gl9-good-clinical-
practice). 
6 See Guidance for Industry, Computerized Systems Used in Clinical Investigations, dated May 2007. 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/computerized-systems-used-clinical-
investigations) 
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a.  Audit Trail File Listing 
 
If you are submitting the electronic audit trail separately from the data files for 
review and statistical analysis, you should provide a table listing the audit trail files 
submitted.  This table should include the file name, the description of the file 
including EDC system name, and any information necessary for review.  See 
Example Table 2a. Listing of Audit Trail Files. 
 
Example Table 2a. Listing of Audit Trail Files. 
 
File Name  Description  Comments 
Site_A_Audit.xml  Audit trail of Site A  [name of EDC system] 
Site_B_Audit.xml  Audit trail of Site B  [name of EDC system] 
 
b.  Audit Trail File Contents 
 
For each audit trail file submitted, you should provide a table that includes the 
variable names, variable label or description (e.g., description of coded values, unit 
of measure, formatting information), and other information necessary for review.  
See Example Table 2b. Contents of AuditTrailFile.XML.  Each audit trail file 
submitted should include every original and updated value, operator identification 
and date and time stamps for each data entry and any change, and reason for each 
change.  Additional columns may be added as needed. 
 
Example Table 2b. Contents of AuditTrailFile.XML (number observations=, 
number of variables=). 
 
Variable Name  Description 
animalid  Animal identification number 
formname  Name of the data collection form 
entryfield  Name of entry field from data collection form 
entrytype  Type of entry field (e.g., numeric, text, radio button, or 
checkbox) 
entry  Data entry [include explanation if applicable (e.g., on = 
radio button was selected, off = radio button not selected; if 
blank, no data entered)] 
operatorid  Individual entering data 
entrydate  Date/time stamp when the data were entered 
reason  Reason for change, if applicable 
lockdate  Date and time when the database was locked 
 
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3.  Data Analysis Programs 
 
a.  Program File Listing 
 
In this section, you should provide a table listing the programs used to perform 
randomization, process the data, generate summaries, and perform the statistical 
analysis.  This table should include the file name, the purpose of the program, the 
electronic data files accessed and generated by each program, a list of any results 
(tables/graphs) generated, and software used, if applicable.  See Example Table 3. 
Listing of Program Files. 
 
Example Table 3. Listing of Program Files. 
 
Program File  Purpose  Data File(s)  Data File(s)  Results or  Comments 
Name  Used in  Created  Tables/ 
Program  (Output)  Graphs 
(Input)  Created 
setup.xml  Sets up  Effect_data.xpt  Effect.sas7bdat  None  Run this 
needed  AE_all.xpt  AE.sas7bdat  program 
libraries and  Clinobs_all.xpt  ClinObs.sas7bdat   first before 
data formats.   running any 
Creates all  analysis 
temporary  programs 
data files 
used in the 
analysis 
s_clinobs.xml  Summarizes  ClinObs.sas7bdat None  Summary  Table X 
clinical  of clinical  provided in 
observations  observa-  Final Study 
tions  Report 
 
Profile 
plots 
effect_prog.xml  Summarizes  Effect.sas7bdat  Success.sas7bdat  None  Details of 
effectiveness  success/ 
variables and  failure 
determine  evaluation. 
success/  Table Y 
failure  provided in 
Final Study 
Report. 
prim_anlys.xml  Conducts  Success.sas7bdat None  Primary   
primary  analysis 
analysis  results 
 
b.  Overview of Data and Analysis Flow 
 
You should provide a general overview of the data and analysis process used in the 
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study and submission.  For example, you should describe whether data files were 
directly downloaded from data management systems and whether any processing 
(merging, validation, editing) were performed prior to analysis. 
 
For electronic databases that do not store or directly export data in XPT or XML 
formats, conversion from another file format (e.g., XLSX, CSV, or SAS7bdat) will 
be needed in order to submit to CVM via eSubmitter (see footnote 2).  If conversion 
is necessary, CVM expects that electronic data files will be converted into XPT or 
XML format without modification (e.g., no column changes or calculations).  The 
Appendix has examples of SAS programs that convert data files to acceptable 
formats.  The program used to make the conversion should be provided to CVM in 
XML format.  If a system limitation precludes the creation of XPT or XML 
formatted files, you should contact CVM.  Additionally, CVM encourages you to 
evaluate/analyze the data using the same file that is submitted to CVM.  For 
example, if the study data are submitted to CVM in file ALLDATA.XML, the 
programs submitted should use this file for analysis. 
 
Submitted data files should be unmodified after export from the database.  If a data 
file was modified for analysis (e.g., addition or edit of variable names, variables or 
animals excluded, or coded information reformatted as text), a description of the 
changes and the computer program used to create the changes should be included, 
but the modified data files should not be submitted.  The logic or coding that was 
used in creating the modified data files should be documented in the computer 
program and clearly detailed in the submission so that CVM may recreate and verify 
the modifications. 
 
c.  Instructions for Running Programs 
 
You should describe the sequence of program calls needed for CVM to run your 
programs.  Starting with the first program to be run, you should describe calls to 
other programs and custom functions. 
 
So that CVM can understand and verify your analysis process, for each program you 
should document all directories and files referenced to access or store data, 
including directory and file names, locations, and aliases, if used.  Describe 
programs defining custom styles or formats or, if such styles or formats are 
predefined, you should provide instructions for their installation.  If the programs 
were designed to call other programs or access data in specific folders or directory 
structures, you should describe this structure so that CVM can verify your analysis 
process. 
 
d.  Randomization Programs 
 
Electronic data files of all randomization schedules used (e.g., animal to treatment, 
procedure order) should be included in the submission and listed in the README 
file.  These files should contain all variables specified in restrictions to 
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randomization, for example, any stratification variables (e.g., weight, sex) or if 
treatments were balanced by one or more factors (e.g., room, cohort).  If available, 
programs used to generate random assignments, including the randomization 
seed(s), should be included in the submission and listed in the README file. 
 
Detailed descriptions of all randomization processes should be included in the FSR. 
 
IV.  Data and Analysis Programs: Additional Comments 
 
Submission of a separate document (e.g., Statistical Report) as an appendix in the FSR that 
provides details on the statistical analysis as well as additional analysis results and summaries is 
acceptable. As is the case with all README file content described in this document, if the FSR 
contains the information regarding program files and program execution as described in 
section III.B.3. Data Analysis Programs above, then the information does not have to be 
repeated in the README file. Instead, the README file can refer to the corresponding 
section(s) of the FSR.  
 
CVMs verification of the analysis process will be facilitated by submission of well-documented 
analysis programs. You should describe the general purpose of each program in the beginning of 
the statistical program. Within the program, you should include sufficient comments to explain 
complex sections, for example, if a program will call certain macros or subroutines. 
 
You should not submit electronic files generated by the statistical analysis, such as tables of 
descriptive summaries or least squares means, in data format (e.g., XML or XPT).  Documents 
containing these summaries may be included or appended to the FSR as appropriate.  For 
example, a listing of subject success/failure outcomes should be included in the FSR, but the 
secondary electronic data file derived from the initially collected data should not be submitted.  
 
Descriptions of derived variables and corresponding formulas or complex transformations should 
be described in the FSR or contributing scientist report and documented in the analysis program.  
If values were computed, derived, or transformed from other variables, the equation(s) for each 
variable, descriptions of calculations, and a table of the calculated values should be in the FSR.  
recFormulas for standard conversions (e.g., lb to kg; mg to kg) do not need to be provided.  
 
Additionally, you should not submit outputs from running the analysis, for example, the outputs 
and log files produced when running SAS. 
 
   
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Appendix  
 
Examples of SAS codes that convert data files to acceptable formats 
1.  SAS code to generate XML files  
 
libname in 'file location'; 
libname out xml 'file location\filename1.xml'; 
data out.dataset1; set in.filename; run; 
2.  SAS code to generate XPT files  
 
libname in 'file location'; 
libname out xport 'file location\filename1.xpt';  
data out.filename1; set in.filename; run; 
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