Submitting Nonclinical Datasets for 
Evaluation of Rodent Carcinogenicity 
Studies of Pharmaceuticals
 
 
Guidance for Industry 
Technical Specifications Document 
 
For questions regarding this technical specifications document, contact 
CDER at cder-edata@fda.hhs.gov. 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
[May 2021] 
Technical Specifications Document 
 
 
 
  Revision History 
Date  Version  Summary of Revisions 
May 2021  1.0  Initial Version 
     
     
     
 
  Contains Nonbinding Recommendations 
 
Table of Contents 
1.0  Introduction ......................................................................................................................... 1 
2.0  Overview of the SEND Datasets......................................................................................... 2 
3.0  SEND Data Validation ........................................................................................................ 2 
4.0  Dataset Specifications for FDA Standard Format of Tumor Data (tumor.xpt) .................. 3 
4.1  Description of Tumor.xpt  Appendix A ............................................................................ 3 
4.2  Example of Reduced Tumor Data  Appendix B ............................................................... 4 
4.3  Business Rules for Datasets of Carcinogenicity Study  Appendix C ............................... 4 
5.0  Mapping Procedures From SEND to tumor.xpt ................................................................. 4 
5.1  Mapping From SEND to tumor.xpt  Appendix D ............................................................. 4 
5.2  Mapping From DSDECOD to DTHSACST ....................................................................... 4 
6.0  Appendix ............................................................................................................................. 6 
Appendix A: FDA Standard Format for Tumor Data (tumor.xpt) .............................................. 6 
Appendix B: Example of Reduced FDA Standard Format for Tumor Data (tumor.xpt) ............ 7 
Appendix C: Business Rules for Datasets of Carcinogenicity Study .......................................... 8 
Appendix D: Mapping from SEND to tumor.xpt ........................................................................ 9 
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  Contains Nonbinding Recommendations 
 
Submitting Nonclinical Datasets for Evaluation of Rodent 
Carcinogenicity Studies of Pharmaceuticals 
Guidance for Industry 
Technical Specifications Document1 
 
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 office 
responsible for this guidance as listed on the title page. 
 
 
1.0  Introduction 
This document provides detailed information and specifications for the content of datasets that 
should be submitted as part of the sponsors or applicants application for drugs that are assessed 
for their evaluation of rodent carcinogenicity studies of pharmaceuticals in nonclinical studies. 
These specifications also provide an opportunity for dialogue between the sponsor or applicant 
and reviewers to discuss issues with trial design or study conduct that may affect the content of 
the analysis datasets. These specifications were built to support the data standards and processes 
described in the FDA Study Data Technical Conformance Guide (TCG) and guidance for 
industry Providing Regulatory Submissions in Electronic Format  Standardized Study Data 
(October 2020).2 
For questions about a particular data standard implementation, send an email to cder-
edata@fda.hhs.gov. For more general recommendations on the use and submission of 
standardized study data, the sponsor or applicant should refer to the TCG.  
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 
 
1 This guidance was prepared by the Office of Biostatistics in the Center for Drug Evaluation and Research at the 
Food and Drug Administration. You may submit comments on this guidance at any time. Submit comments to 
Docket No. FDA-2018-D-1216 (available at https://www.regulations.gov/docket?D=FDA-2018-D-1216) (see the 
instructions for submitting comments in the docket). 
2 The FDA Study Data Technical Conformance Guide is available at https://www.fda.gov/industry/fda-resources-
data-standards/study-data-standards-resources. We update guidances periodically. For the most recent version of a 
guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents.   
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  Contains Nonbinding Recommendations 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
2.0  Overview of the SEND Datasets 
The Standard for Exchange of Nonclinical Data (SEND) provides the organization, structure, and 
format of standard nonclinical (animal toxicology studies) tabulation datasets for regulatory 
submission. The SEND Implementation Guide (SENDIG) provides specific domain models, 
assumptions, and examples for preparing standard tabulation datasets. It also guides the 
organization, structure, and format of standard nonclinical tabulation datasets for interchange 
between organizations and for submission to regulatory authorities. SENDIG v3.0 supports 
single-dose general toxicology, repeat-dose general toxicology, and carcinogenicity studies. 
SENDIG v3.1 additionally supports respiratory and cardiovascular safety pharmacology studies. 
According to the guidance for industry Providing Regulatory Submissions in Electronic Format 
 Standardized Study Data (October 2020), the version of SENDIG that the sponsors follow 
should be based on the nonclinical study initiation date. The ideal time to implement SEND is 

before conducting the study because it is very important that the results presented in the 
accompanying study report be traceable back to the original data collected (TCG section 4). Each 
submitted SEND dataset should have its contents described with complete metadata in the 
define.xml file (TCG section 4) and in the nonclinical Study Data Reviewers Guide (nSDRG) as 
appropriate (TCG section 2). 
3.0  SEND Data Validation 
FDA expects the sponsor to appropriately verify that the data in the SEND datasets are an 
accurate representation of the data in final reports.  
Sponsors should either correct any discrepancies between the SEND datasets and the Clinical 
Data Interchange Standards Consortium (CDISC) standards or the FDA Business Rules3, or 
explain meaningful discrepancies in the nSDRG. Additional information about conformance to 
the CDISC standards and FDA Business Rules and about establishing consistency and 
traceability between the study data and the study report should also be provided in the nSDRG 
(TCG section 8). This information is important for the reviewer to understand the context in 
which the SEND data are provided. If the reviewer is unable to trace study data from data 
collected in a study to the analysis of the overall study data, then the SEND data may be of 
limited utility. The sponsor should ensure the traceability of the SEND data to maximize their 
utility. 
 
3 See www.CDISC.org. The FDA Study Data Standards Resources web page provides links to the currently 
available FDA Business Rules. See https://www.fda.gov/industry/fda-resources-data-standards/study-data-
standards-resources.  
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For every submission, methods should be in place to check validity and accuracy of the SEND 
datasets, and the results from that verification are expected to be available in the event of Agency 
request. 
4.0  Dataset Specifications for FDA Standard Format of Tumor Data (tumor.xpt) 
Carcinogenicity studies should include an electronic dataset of tumor findings to allow for a 
complete review. Sponsors should continue to include the tumor.xpt and associated define.pdf 
files regardless of whether the study is submitted with the SEND dataset. When both tumor.xpt 
and SEND are submitted, the sponsor should ensure that the data are consistent and traceable 
between the tumor.xpt file and the SEND datasets, and consistent with the information specified 
in FDA Business Rules. Any information needed to establish traceability between the two 
datasets should be presented in the nSDRG (TCG section 4).  
The Tumor Findings dataset (tf.xpt) is necessary if the SEND datasets are the basis for creation 
of the tumor.xpt dataset. If sponsors choose not to submit the Tumor Findings dataset (tf.xpt) 
with the SEND submission, the algorithm used to calculate Time in days to detection of tumor 
should be included in the nSDRG (TCG section 4).  
For rodent carcinogenicity studies submitted in module 4.3.2.4 of the electronic Common 
Technical Document, the tumor.xpt file and its associated define.pdf should be placed in 
analysis/legacy/dataset subfolder under the study datasets folder (TCG section 7).  
4.1  Description of Tumor.xpt  Appendix A 
CDER statisticians perform analyses on the tumor data from each rodent carcinogenicity study, 
and the tumor data should be provided as an electronic analysis dataset. The tumor.xpt (see 
Appendix A) specifies the recommended data elements to be included in the analysis dataset. 
The dataset containing this information should be named tumor.xpt to aid in identification. 
The tumor.xpt file is a one-record-per-tumor finding per tissue/organ per subject dataset that 
contains tumor-level variables such as tumor detection date, tumor name, tumor code, tumor 
malignancy status, cause of death; tissue/organ-level variables such as tissue/organ microscopic 
examination status, organ name, organ code; and subject-level variables such as death or 
sacrifice date, death or sacrifice status, animal microscopic examination status, dosing group. 
This dataset is intended to provide data for primary tumors for statistical analysis. It should be 
prepared as described in the TCG (section 4). All variables provided in the tumor.xpt should be 
traceable to the submitted tabulations.  
For the tumor.xpt file, sponsors should include a data definition table to describe the format, the 
content, and the definitions of the variables in the dataset. The data definition table should be 
provided as a single PDF file named define.pdf and placed in the appropriate study, specific 
analysis type, or integrated summary folder in the datasets folder.  
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  Contains Nonbinding Recommendations 
4.2  Example of Reduced Tumor Data  Appendix B 
To illustrate the recommended approach to encode tumor data, a reduced example of tumor.xpt is 
provided in Appendix B. This reduced example contains only a few tumors per tissue/organ for 
one subject for illustration purposes. 
4.3  Business Rules for Datasets of Carcinogenicity Study  Appendix C 
Fourteen business rules (see Appendix C) were developed to support regulatory review and 
analysis of study data for carcinogenicity studies using tumor.xpt and SEND datasets. These 
business rules are part of the larger number of business requirements for regulatory review that 
constitute the FDA Business Rules. According to the TCG (section 8), all FDA Business Rules 
should be followed if applicable, and the information in SEND datasets should be consistent with 
those in tumor.xpt. Sponsors should explain any inconsistency in the nSDRG.  
5.0  Mapping Procedures From SEND to tumor.xpt  
The following domains should be used to create a tumor.xpt file:  
 DM (Demographics)  
 DS (Disposition)  
 EX (Exposure)  
 MI (Microscopic Findings)  
 TX (Trial Sets)  
 TF (Tumor Findings) * 
 
* TF domain is necessary if the SEND datasets are the basis for creation of the tumor.xpt dataset 
(SENDIGv3.1). If sponsors choose not to submit TF domain with the SEND submission, the 
algorithm used to calculate Time in days to detection of tumor should be included in the 
nSDRG (TCG section 4). 
 
5.1  Mapping From SEND to tumor.xpt  Appendix D 
The table in Appendix D describes the variables in the tumor.xpt and the SEND variables from 
which they are created. 
5.2  Mapping From DSDECOD to DTHSACST 
The tumor.xpt datasets DTHSACST (death or sacrifice status) variable may be mapped from the 
DS domains DSDECOD (standardized disposition term) variable. The following table gives the 
DSDECOD values and their DTHSACST equivalent. The DSDECOD values of MISSING, 
REMOVED FROM STUDY ALIVE, RECOVERY SACRIFICE, and NON-MORIBUND 
SACRIFICE do not map to the DTHSACST variable of the tumor.xpt. Subjects with these 
dispositions would not be relevant for tumor analysis. 
   
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DSDECOD   DTHSACST  
Value   Value   Meaning  
ACCIDENTAL DEATH   4   Accidental death  
FOUND DEAD   1   Natural death or moribund sacrifice  
MISSING   *   *  
MORIBUND SACRIFICE   1   Natural death or moribund sacrifice  
INTERIM SACRIFICE   3   Planned intermittent sacrifice  
RECOVERY SACRIFICE   *   *  
REMOVED FROM STUDY ALIVE   *   *  
NON-MORIBUND SACRIFICE   *   *  
* There are no mappings to the DTHSACST variable for these DSDECOD values. Subjects with these dispositions 
would not be relevant for tumor analysis 
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6.0  Appendix 
Appendix A: FDA Standard Format for Tumor Data (tumor.xpt) 
Variable 
Variable Label  Type  Code  Comments 
Name 
STUDYNUM  Study number  Char    3 
ANIMLNUM  Animal number  Char    1,3 
SPECIES  Animal Species  Char  M = Mouse; R = Rat   
SEX  Sex  Char  M = male   
F = female 
DOSEGP  Dose group  Num  0 = # milligram (mg)/kilogram (kg)/day (Group 1)   
1 = # mg/kg/day (Group 2) 
2 = # mg/kg/day (Group 3) 
3 = # mg/kg/day (Group 4) 
DTHSACTM  Time in days/weeks to death or  Num     
sacrifice 
DTHSACST  Death or sacrifice status  Num  1 = Natural death or moribund sacrifice   
2 = Terminal sacrifice 
3 = Planned intermittent sacrifice 
4 = Accidental death 
ANIMLEXM  Animal microscopic examination  Num  0 = No tissues were examined   
code  1 = At least one tissue was examined 
TUMORCOD  Tumor type code  Num    3,4 
TUMORNAM  Tumor name  Char    3,4 
ORGANCOD  Organ/tissue code  Char    3,5 
ORGANNAM  Organ/tissue name  Char  LN = Lymph node  3,5 
GL = Gland 
NONGL = Nonglandular SALIV GL,  
MANDIB = Mandibular salivary gland 
HEMATO=Hematopoietic 
DETECTTM  Time in days/weeks of detection of  Num     
tumor 
MALIGNST  Malignancy status  Num  1 = Malignant  4 
2 = Benign 
3 = Undetermined 
DEATHCAU  Cause of death  Num  1 = Tumor caused death  4 
2 = Tumor did not cause death 
3 = Undetermined 
ORGANEXM  Organ/tissue microscopic  Num  1 = Organ/tissue was examined and was usable   
examination code  2 = Organ/tissue was examined but was not usable 
(e.g., autolyzed tissue or tissue not found in section 
examined) 
3 = Organ/tissue was not examined 
1 Each animal in the study should have at least one record even if it does not have a tumor. 
2 Additional variables, as appropriate, can be added to the bottom of this dataset. 
3 STUDYNUM and ANIMLNUM limited to no more than 12 characters; ORGANCOD and TUMORCOD limited to no more 
than 8 characters; ORGANNAM and TUMOR should be as concise as possible. 
4 A missing value should be given for the variable MALIGNST, DEATHCAU, TUMORCOD, and TUMORNAM when the 
organ is unusable or not examined. 
5 Do not include a record for an organ that was useable and no tumor was found on examination. A record should be included for 
organs with a tumor, organs found unusable, and organs not examined. 
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Appendix B: Example of Reduced FDA Standard Format for Tumor Data (tumor.xpt)  
STUDYNUM ANIMLNUM SPECIES SEX  DOSEGP DTHSACTM DTHSACST ANIMLEXM TUMORCOD TUMORNAM  ORGANCOD ORGANNAM  DETECTTM MALIGNST DEATHCAU ORGANEXM 
xxxxxxx  1  R  M  1  550  1  1      BODA  body cavity, abdominal      3 
xxxxxxx  1  R  M  1  550  1  1      BODN  body cavity, nasal      3 
xxxxxxx  1  R  M  1  550  1  1      BODO  body cavity, oral      3 
xxxxxxx  1  R  M  1  550  1  1      BODT  body cavity, thoracic      3 
xxxxxxx  1  R  M  1  550  1  1  COAR  cortical adenoma GLAD  gland, adrenal  550  2  2  1 
xxxxxxx  1  R  M  1  550  1  1  ADEN  adenoma  GLPI  gland, pituitary  550  2  1  1 
xxxxxxx  1  R  M  1  550  1  1      HEMO  hemolymphoreticular tissue    1 
seminoma, 
xxxxxxx  1  R  M  1  550  1  1  SEBE  benign  TEST  testis  550  2  2  1 
xxxxxxx  2  R  M  1  498  1  1      BODA  body cavity, abdominal      3 
xxxxxxx  2  R  M  1  498  1  1      BODN  body cavity, nasal      3 
xxxxxxx  2  R  M  1  498  1  1      BODO  body cavity, oral      3 
xxxxxxx  2  R  M  1  498  1  1      BODT  body cavity, thoracic      3 
xxxxxxx  2  R  M  1  498  1  1  ADEN  adenoma  GLPI  gland, pituitary  498  2  1  1 
xxxxxxx  2  R  M  1  498  1  1      HEMO  hemolymphoreticular tissue    1 
xxxxxxx  3  R  M  1  644  1  1      BODA  body cavity, abdominal      3 
xxxxxxx  3  R  M  1  644  1  1      BODN  body cavity, nasal      3 
xxxxxxx  3  R  M  1  644  1  1      BODO  body cavity, oral      3 
xxxxxxx  3  R  M  1  644  1  1      BODT  body cavity, thoracic      3 
xxxxxxx  3  R  M  1  644  1  1  ADEN  adenoma  GLPI  gland, pituitary  644  2  1  1 
xxxxxxx  3  R  M  1  644  1  1      HEMO  hemolymphoreticular tissue    1 
xxxxxxx  4  R  M  1  581  1  1      BODA  body cavity, abdominal      3 
xxxxxxx  4  R  M  1  581  1  1      BODN  body cavity, nasal      3 
xxxxxxx  4  R  M  1  581  1  1      BODO  body cavity, oral      3 
xxxxxxx  4  R  M  1  581  1  1      BODT  body cavity, thoracic      3 
xxxxxxx  4  R  M  1  581  1  1  ADEN  adenoma  GLPI  gland, pituitary  581  2  1  1 
 
 
   
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Appendix C: Business Rules for Datasets of Carcinogenicity Study 
FDAB072  The microscopic examination findings for each organ/tissue should be consistent for each animal between 
the MI.xpt (SEND) and Tumor.xpt. Explain any terminology inconsistencies in the nSDRG. 
FDAB073  The number of animals with a specific tumor finding for each organ/tissue should be consistent between 
the MI.xpt (SEND) and Tumor.xpt for the same dose group and sex. Explain any inconsistencies in the 
nSDRG. 
FDAB074  The microscopic examination status of each organ/tissue should be consistent between the MI.xpt 
(MISTAT, MISPCUFL) and Tumor.xpt (ORGANEXM) for each animal. Explain any inconsistencies in 
the nSDRG. 
FDAB075  For a specific organ/tissue, the number of animals that were examined (ORGANEXM=1), that were 
examined but not usable (e.g., autolyzed tissue or tissue not found in section examined) 
(ORGANEXM=2), and that were not examined (ORGANEXM=3) should be consistent between the 
MI.xpt (MISTAT, MISPCUFL) and Tumor.xpt for the same dosing group and sex. Explain any 
inconsistencies in the nSDRG.  
FDAB076  The time in days/weeks to death or sacrifice and the status of death or sacrifice for each animal should be 
consistent between the SEND data and Tumor.xpt (DTHSACTM, DTHSACST). Explain any 
inconsistencies in the nSDRG. 
FDAB077  For each specific tumor, the relationship to death in MI.xpt (MIDTHREL) should match with cause of 
death for the same tumor in Tumor.xpt (DEATHCAU). Explain any inconsistencies in the nSDRG.  
FDAB078  For each specific tumor, the malignancy status should be consistent between the MI.xpt (MIRESCAT) and 
Tumor.xpt (MALIGNST). Explain any inconsistencies in the nSDRG. 
FDAB079  The interval of time to detection of a tumor for each organ/tissue should be consistent between SEND 
(TFDETECT) and Tumor.xpt (DETECTTM). Explain any inconsistencies in the nSDRG.  
FDAB080  The total number of animals assigned to each dose and sex group should be consistent between SEND and 
Tumor.xpt. Explain any inconsistencies in the nSDRG. 
FDAB081  The tumor detection time of a specific organ/tissue/tumor should not be later than the death or sacrifice 
time for each animal. 
FDAB082  For carcinogenicity studies, MIRESCAT should be populated unless MISTRESC has a value of 
UNREMARKABLE (for SENDIG v3.1) or NORMAL (for SENDIG v3.0) or MISTAT has a value of 
NOT DONE. 
FDAB083  If a specific organ was not examined in MI.xpt (MISTAT = NOT DONE), then a record should be 
included in tumor.xpt for the same specific organ indicating that this organ was not examined 
(ORGANEXM=3).  
FDAB084  If a specific organ was not examined in tumor.xpt (ORGANEXM=3), then a record should be included in 
MI.xpt (SEND) for the same specific organ indicating that this organ was not examined (MISTAT = 
NOT DONE). 
FDAB085  For findings in MISTRESC using the NEOPLASM controlled terminology list, malignancy status in 
MIRESCAT should align with any benign or malignant designation in the NEOPLASM. Explain any 
i nconsistencies in the nSDRG. 
 
 
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Appendix D: Mapping from SEND to tumor.xpt  
Variable  Label  Type  Codes  SEND Notes [SEND Source Domain  Variable (CT*)] 
STUDYNUM  Study number  Char    DM  STUDYID  
ANIMLNUM  Animal number  Char    DM  USUBJID  
SPECIES  Animal Species  Char  M = mouse, R = rat   DM  SPECIES  
SEX  Sex  Char  M = male, F = female  DM  SEX  
DOSEGP  Dose group  Num  Use 0, 1, 2, 3, 4,... In ascending  TX  TXPARMCD TXVAL SETCD  
order from control  DM  ARM (TK status) 
DTHSACTM  Time in days to death  Num    DS  DSSTDTC (Format - ISO 8601) 
or sacrifice  EX  EXSTDTC (Format - ISO 8601) 
DSSTDTC - EXSTDTC + 1  
DTHSACST  Death or sacrifice  Num  1 = Natural death or moribund  DS  DSDECOD  
status  sacrifice 
2 = Terminal sacrifice 
3 = Planned intermittent sacrifice 
4 = Accidental death 
ANIMLEXM  Animal  Num  0 = No tissues were examined  MI  MISTAT (CT* - ND) 
microscopic  1 = At least one tissue was 
examination code  examined 
TUMORCOD  Tumor type code  Num    Not available in SEND 
TUMORNAM  Tumor name  Char    MI  MISTRESC (CT - NEOPLASM) 
ORGANCOD  Organ/tissue code  Char    Not available in SEND 
ORGANNAM  Organ/tissue name  Char    MI  MISPEC (CT  SPEC) 
MALIGNST  Malignancy status  Num  1 = Malignant  MI  MIRESCAT (CT  MIRESCAT) 
2 = Benign 
3 = Undetermined 
DEATHCAU  Cause of death  Num  1 = Tumor caused death  MI  MIDTHREL (CT - NY) 
2 = Tumor did not cause death 
3 = Undetermined 
ORGANEXM  Organ/tissue  Num  1 = Organ/Tissue was examined and  MI  MISTAT (CT  ND) and MISPCUFL (CT  NY) 
microscopic  was usable  ORGANEXM=1 if MISTAT = null and MISPCUFL = null 
examination code  2 = Organ/tissue was examined but  ORGANEXM=2 if MISPCUFL = N 
was not usable (e.g., autolyzed tissue)   ORGANEXM=3 if MISTAT = NOT DONE and MISPCUFL = null  
3 = Organ/tissue was not examined 
DETECTTM  Time in days/weeks of  Num  The number of days relative to the  TF - TFDETECT or the following algorithm, if the tumor was  
detection of tumor  first day of treatment when the tumor   detected as a clinical sign (CL): (CLDTC  EXSTDTC) + 1 
was first detected   detected as a palpable mass (PM): (PMDTC  EXSTDTC) + 1  
 detected during necropsy (MA): (DSSTDTC  EXSTDTC) + 1  
 detected during histopathology examination (MI): (DSSTDTC  
EXSTDTC) + 1  
* CT: Controlled Terminology 
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