Technical Specifications for 
Submitting Clinical Trial Data Sets 
for Treatment of Noncirrhotic 
Nonalcoholic Steatohepatitis 
(NASH)  
 
Guidance for Industry 
Technical Specifications Document 
 
 
 
 
 
For questions regarding this technical specification 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) 
 
January 2022 
Technical Specifications Document 
   
Revision History 
 
Date  Version  Summary of Revisions 
August 2021  1.0  Initial Version 
Section 5.0  Added language about CDISC Controlled 
Terminology 
January 2022  1.1 
Revisions made to Section 5.1.4 - Corrected test code 
values for Ascites and Encephalopathy Grade. 
 
  Contains Nonbinding Recommendations 
Table of Contents 
 
1.0  INTRODUCTION.............................................................................................................. 1 
2.0  RELEVANT ACRONYMS ............................................................................................... 2 
3.0  FDA DATA STANDARDS CATALOG .......................................................................... 3 
4.0  OVERVIEW OF DATA SETS ......................................................................................... 3 
4.1  SDTM Domains .............................................................................................................................. 4 
4.2  ADaM Data Sets ............................................................................................................................. 5 
5.0  OVERVIEW OF DATA SET SPECIFICATIONS ........................................................ 6 
5.1   SDTM Domains ............................................................................................................................. 7 
5.1.1  Biospecimen Events (BE) Domain ........................................................................................ 7 
5.1.2  Biospecimen Findings (BS) Domain ..................................................................................... 7 
5.1.3  Microscopic Findings (MI) Domain ..................................................................................... 8 
5.1.4  Supplemental Microscopic Findings (SUPPMI) Domain ................................................... 11 
5.1.5  Disease Response and Clinical Classifications (RS) Domain ............................................ 12 
5.1.6  Imaging Results (ZI) Domain .............................................................................................. 13 
5.1.7  Adjudication (ZA) Domain .................................................................................................. 14 
5.1.8  Concomitant Medications (CM) Domain ............................................................................ 17 
5.1.9  Medical History (MH) Domain ........................................................................................... 17 
5.1.10  Laboratory (LB) Domain .................................................................................................... 17 
5.1.11  Microbiology Specimens (MB) Domain .............................................................................. 19 
5.1.12  Substance Use (SU) Domain ............................................................................................... 20 
5.1.13  Trial Summary (TS) Domain ............................................................................................... 20 
5.1.14  RELREC Domain ................................................................................................................ 20 
5.1.15  Other SDTM Considerations .............................................................................................. 21 
5.1.15.1  Gastroesophageal varices ............................................................................................ 21 
5.1.15.2  All-cause mortality ...................................................................................................... 21 
5.2  ADaM Data Sets ........................................................................................................................... 21 
5.2.1   Subject-Level Analysis Data Set (ADSL) ............................................................................ 22 
5.2.2   Occurrence Data Structure (OCCDS) Data Sets ................................................................ 26 
5.2.2.1   Adverse Event Analysis Data Set (ADAE) ................................................................. 26 
5.2.3   Basic Data Structure (BDS) Data Sets................................................................................ 27 
5.2.3.1   Laboratory Analysis Data Set (ADLB) ....................................................................... 27 
5.2.3.2   Drug Induced Liver Injury Analysis Data Set (ADDILI) ........................................... 30 
5.2.3.3   Microscopic Findings Analysis Data Set (ADMI) ...................................................... 33 
5.2.3.4   Non-Invasive Serum Biomarkers of Liver Fibrosis and NASH Analysis Data  
  Set (ADRS) ................................................................................................................. 34 
5.2.4   Time-to-Event Analysis Data Set ........................................................................................ 36 
APPENDIX .................................................................................................................................. 38 
Example ADLB and ADDILI Data Sets ............................................................................................. 38 
Example MI and SUPPMI Domains ................................................................................................... 39 
  Contains Nonbinding Recommendations 
Technical Specifications for Submitting Clinical Trial Data Sets for 
Treatment of Nonalcoholic Steatohepatitis (NASH)  
 
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 
 
Nonalcoholic steatohepatitis (NASH) is a subcategory of nonalcoholic fatty liver disease 
(NAFLD). NASH carries a significant disease burden as it can progress to cirrhosis and liver 
failure and is associated with an increase incidence of liver cancer. Currently, the U.S. Food and 
Drug Administration (FDA) has not approved any therapies for NASH.  
 
The Division of Hepatology and Nutrition (DHN) serves as the clinical review division in the 
Office of New Drugs (OND) for review of drug products for treatment of liver fibrosis due to 
NASH. In December 2018, FDA issued a draft guidance outlining recommendations for clinical 
development of drugs intended for treatment of noncirrhotic NASH with liver fibrosis.2 The 
2018 draft guidance for industry acknowledges that subjects with NASH fibrosis have unique 
challenges (e.g., underlying hepatic dysfunction) during drug development. Furthermore, 
evaluation of potential drug-induced liver injury (DILI) in this population is challenging because 
the risk of DILI in subjects with underlying liver disease has not been fully characterized and it 
can be difficult to differentiate between progression of liver disease and DILI. 
 
This document provides detailed information and specifications for the content of the tabulated 
domains and analysis data sets submitted to FDA as part of the sponsors/applicants application 
for drugs intended to treat noncirrhotic NASH. This guidance does not provide recommendations 
 
1 This guidance has been prepared by the Division of Hepatology and Nutrition 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 See the draft guidance for industry Noncirrhotic Nonalcoholic Steatohepatitis With Liver Fibrosis: Developing 
Drugs for Treatment (December 2018). When final, this guidance will represent the FDAs current thinking on this 
topic. 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. 
1 
  Contains Nonbinding Recommendations 
for clinical development of drugs intended for treatment of NASH, or assessment of potential 
DILI.   
 
The recommendations outlined in the guidance pertain to submission of the sponsors tabulated 
and analysis data sets in order to improve reviewability. These specifications also provide an 
opportunity for dialogue between the sponsor and DHN to discuss issues related to trial design or 
conduct that may affect the content of these data sets. These specifications are intended to 
support the draft guidance for industry Noncirrhotic Nonalcoholic Steatohepatitis With Liver 
Fibrosis: Developing Drugs for Treatment2 (NASH Guidance) and reflect the data standards and 
processes described in the FDA Study Data Technical Conformance Guide.3 
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract. This document is intended 
only to provide clarity to the public regarding existing requirements under the law. FDA 
guidance documents, including this guidance, should be viewed only as recommendations, unless 
specific regulatory or statutory requirements are cited. The use of the word should in Agency 
guidance means that something is suggested or recommended, but not required. 
 
2.0  Relevant Acronyms 
 
Abbreviation  Description 
ADaM  Analysis Data Model 
ADRG  Analysis Data Reviewers Guide 
APRI  Aspartate Aminotransferase-to-Platelet Ratio Index 
BDS  Basic Data Structure 
CAC  Cardiac Adjudication Committee 
CDISC  Clinical Data Interchange Standards Consortium 
CK-18  Cytokeratin-18 
CRN  Clinical Research Network 
DHN  Division of Hepatology and Nutrition 
DILI  Drug-Induced Liver Injury 
ELF  Enhanced Liver Fibrosis 
FDA  Food and Drug Administration 
HAC  Hepatic Adjudication Committee 
 
3 Available at https://www.fda.gov/industry/fda-resources-data-standards/study-data-standards-resources.  
2 
  Contains Nonbinding Recommendations 
Abbreviation  Description 
MACE  Major Adverse Cardiac Events 
MedDRA  Medical Dictionary for Regulatory Activities 
MELD  Model for End-Stage Liver Disease 
NAS  NAFLD Activity Score 
NASH  Nonalcoholic Steatohepatitis 
NCI EVS  National Cancer Institute Enterprise Vocabulary Services 
OCCDS  Occurrence Data Structure 
PRO-C3  N-terminal propeptide of type III collagen 
RELREC  Related Records Domain 
SDRG  Study Data Reviewers Guide 
SDTM  Study Data Tabulation Model 
SMQ  Standardized MedDRA Query 
TAUG  Therapeutic Area User Guide 
 
3.0  FDA Data Standards Catalog 
 
This technical specification has been drafted in accordance with the currently supported versions 
of the Study Data Tabulation Model (SDTM) Implementation Guide and Analysis Data Model 
(ADaM) Implementation Guide as noted in the FDA Data Standards Catalog.4 As new versions 
of the respective implementation guides become available and supported by FDA, this technical 
specification may change to align to the newly supported implementation guide(s). 
 
Sponsors should review the FDA Data Standards Catalog to ensure data submissions follow 
FDA-supported standards.  
 
4.0  Overview of Data Sets 
 
This technical specification contains guidance for 20 data sets (14 SDTM domains and 7 ADaM 
data sets) relevant to noncirrhotic NASH development programs briefly described below. The 
subsequent sections provide more detailed descriptions regarding the information to be collected 
and stored in each domain and/or data set. Sponsors should submit all required data sets, 
including those not discussed in this technical specification. 
 
 
4 Available at https://www.fda.gov/industry/fda-resources-data-standards/study-data-standards-resources. 
3 
  Contains Nonbinding Recommendations 
4.1 SDTM Domains 
 
This technical specification provides guidance for providing 14 SDTM domains. Sponsors 
should still provide standard SDTM domains in addition to those listed below, including but not 
limited to Demographics (DM), Adverse Events (AE), Disposition (DS), Death Details (DD), 
Subject Visits (SV), Exposure (EX), Comments (CO), etc.  
 
Biospecimen Events (BE) domain: This domain contains information related to the 
collection of biological specimens. It is an events domain structured as one record per 
biospecimen event per biospecimen identifier per subject, and links to the Biospecimen 
Findings (BS) domains. 
 
Biospecimen Findings (BS) domain: This findings domain contains information related 
to observations of specimen quality and characteristics of collected biospecimens. This 
information is collected to assess the adequacy of the biopsies that are used for analysis 
and is structured as one record per measurement per biospecimen identifier per subject.   
 
Microscopic Findings (MI) domain: This domain contains all information related to 
histologic characteristics of liver biopsies. This domain is structured as a Clinical Data 
Interchange Standards Consortium (CDISC) findings domain and is structured as one 
record per subject per test per collection.  
 
Supplemental Microscopic Findings (SUPPMI) domain: This domain contains 
supplemental information related to the biopsies, specifically the sponsors assessment of 
slide adequacy. Justification should be provided in this domain for specimens deemed 
inadequate. 
 
Disease Response and Clinical Classifications (RS) domain: This domain contains 
information related to disease response to therapy that includes clinical classification 
based on published criteria and captures results of Model for End-Stage Liver Disease 
(MELD) scoring5 and Child-Pugh Classification. This findings domain is structured as 
one record per response or clinical classification assessment timepoint per visit per 
subject per assessor per medical evaluator. 
 
Imaging Results (ZI) domain: This custom domain contains results of imaging 
procedures done to assess liver steatosis, inflammation, and fibrosis. Sponsors may 
choose the tests and data points to collect from imaging procedures, but this domain 
provides guidance to ensure the data is submitted to the FDA in a consistent manner.  
 
Adjudication (ZA) domain: This domain contains results of assessments of individual 
adjudicators as it pertains to potential DILI and other clinical events and outcomes. This 
domain is structured similar to the MI domain, where the evaluator information is stored 
in ZAEVAL and ZAEVALID to account for intra- and inter-observer variability.  
 
 
5 Individual components of MELD scoring are captured elsewhere, but final calculation for MELD is placed in the 
RS domain. 
4 
  Contains Nonbinding Recommendations 
Additional information, instructions, and CDISC Controlled Terminology are included in 
individual subsections pertaining to the Concomitant Medications (CM), Medical History (MH), 
Laboratory (LB), Microbiology Specimens (MB), Substance Use (SU), and Trial Summary (TS) 
domains. 
 
4.2 ADaM Data Sets 
 
ADaM data sets include variables that represent derived study days. It is assumed that the anchor 
date for study day 1 is Date of First Exposure to Treatment (TRTSDT) and this date of first dose 
is identical to Date of Randomization (RANDDT). If the Date of First Exposure to Treatment 
and Date of Randomization differ, sponsors should provide an explanation for this discrepancy. 
All ADaM data sets should be accompanied by informative metadata, as provided in a compliant 
ADaM define.xml document and Analysis Data Reviewers Guide (ADRG) that describes the 
source and derivation of the variables. In addition, programs used to create ADaM data sets 
should be submitted.  
 
Subject-Level Analysis Data Set (ADSL): This data set contains one record per subject. 
This data set provides information about the subjects demographics, treatment arm, trial 
start and end dates, and summary baseline characteristics. Many of the baseline 
characteristic variables in this data set are calculated or derived values from other data 
sets (e.g., baseline alanine aminotransferase (ALT)) and an associated categorization of 
that value. The notes in the ADSL table provided within this document should be 
considered a guide and a baseline instruction set; sponsors should submit additional 
variables and derivations as they see fit. Specific sections of the ADSL should be carried 
into other ADaM data sets for analysis purposes (e.g., Basic Demographic Variables, 
Treatment Arms, etc.), and are noted in the full description of the ADaM data sets. All 
derivations should be noted in the define.xml file, and additional notes about the data set 
included in the ADRG.  
 
Adverse Event Analysis Data Set (ADAE): This data set contains one record per 
adverse event (AE) per subject. All AEs reported for a subject during their participation 
in the trial should be recorded. It also includes additional variables and specific 
derivations requested by the review division to aid in review, such as sponsor derived 
Standardized Medical Dictionary for Regulatory Activities Query (MedDRA SMQ) flags 
and/or custom MedDRA queries for DILI.     
 
Laboratory Analysis Data Set (ADLB): This data set contains one record per lab test, 
per collection, per subject data set. The laboratory tests of most interest are noted below 
in the full description for SDTM.LB, but this specification contains additional analysis 
variables to be submitted in ADLB. However, it is acceptable for additional laboratory 
tests to be included. If the submitted data set is greater than 5 GB, the data set should be 
split according to laboratory panels of hematology, chemistry, urinalysis, and other (if 
necessary, for miscellaneous tests). This data set is designed to be equivalent to an ADaM 
compliant Basic Data Structure (BDS) laboratory data set with additional review division 
specific variables.   
 
5 
  Contains Nonbinding Recommendations 
Drug-Induced Liver Injury Analysis Data Set (ADDILI): This custom data set 
contains one record per parameter per subject, where each subject should have a 
minimum of one parameter to evaluate potential DILI. Subjects deemed to have potential 
DILI should have two additional parameters: one to list the action taken and another to 
list the outcome. This data set also contains variables derived from pertinent data from 
the ADLB data set, such as post-baseline maximum values for each of the liver enzymes. 
In addition, this data set contains flags to indicate any additional work-up conducted to 
evaluate potential DILI. Sponsors may create new variables to support the analysis or 
additional parameters using the existing variables (or both) in consultation with the FDA.  
 
Microscopic Findings Analysis Data Set (ADMI): This custom data set contains one 
record per biopsy parameter, per evaluator, per collection, per subject. This data set is 
meant to capture all source biopsy records and evaluate subjects with respect to the 
histological endpoints as designated by the study protocol. Each histological endpoint is 
given its own parameter and evaluated as Y or N in AVALC. Additional criteria and 
analysis flags should also be included as needed from the sponsor. This data should be 
submitted when the histological data are collected and reported to FDA. 
 
Non-Invasive Serum Biomarkers of Liver Fibrosis and NASH Analysis Data Set 
(ADRS): The ADRS data set contains the non-invasive NASH and fibrosis serum 
biomarkers sponsors may wish to evaluate such as Cytokeratin-18 (CK-18), MELD 
score, Enhanced Liver Fibrosis (ELF) score, Liver Fibrosis (FIB-4) score, Aspartate 
Aminotransferase-to-Platelet Ratio Index (APRI), etc. Measurements may be derived as 
calculations from datapoints in other data sets such as SDTM.LB or SDTM.RS. This data 
set follows the same structure as the SDTM.RS domain but contains additional 
parameters; each non-invasive endpoint (e.g., MELD Score from Baseline <12 to >=15 
post-baseline) is given its own parameter and evaluated as Y or N in AVALC. 
Additional criteria and analysis flags should be included as the sponsor sees fit. This data 
should be submitted when the non-invasive serum biomarkers are collected and reported 
to FDA.  
 
Analysis Time to Event Data Set (ADTTE): This data set is one record per parameter 
per subject. Sponsors should use this data set to evaluate time-to-event endpoints for all 
treated subjects. This guidance contains sample parameters, but sponsors should consult 
with the FDA on the specific parameters relevant to their program.  
 
5.0  Overview of Data Set Specifications 
 
Each section below provides specifications and/or appropriate CDISC Controlled Terminology 
that describes the desired content and structure of the data set. The variable names and associated 
metadata are based on current CDISC SDTM and ADaM standards where possible. If any 
variable is unclear, sponsors are encouraged to discuss the expectations with DHN.   
 
Sponsors are strongly encouraged to seek DHN input for additional custom data sets and 
variables to support determination of efficacy and/or safety. Though sponsors should consider 
6 
  Contains Nonbinding Recommendations 
the data sets referenced in this guidance as the FDAs recommendation to support regulatory 
review, some variables may not be appropriate for all clinical trials.   
 
CDISC Controlled Terminology developed and maintained by CDISC and National Cancer 
Institute Enterprise Vocabulary Services (NCI EVS)6 should be used where applicable, but 
codelists may be extensible. If a submission used alternate controlled terminology or extended 
any codelist, then sponsors should indicate this in the define.xml document. The variable labels 
and the variable type noted in the specifications should be used. As updates are made to CDISC 
Controlled Terminology, sponsors should use the current version provided by CDISC and NCI 
EVS. 
 
5.1   SDTM Domains 
 
5.1.1  Biospecimen Events (BE) Domain 
 
The BE domain should contain information regarding the collection of specimens that are used 
for histologic assessment within the Microscopic Findings (MI) domain, including the anatomic 
location from which the specimen was collected. The collection event is linked to the 
Biospecimen Findings (BS) domain that stores information regarding any measurements 
performed on the specimens. For example, a tissue sample that is collected, extracted, frozen, 
shipped, and thawed should have five records, each with a BEDECOD value of 
COLLECTING, EXTRACTING, FREEZING, SHIPPING and THAWING 
respectively.  
 
A complete listing of the variables to be included in the BE domain is located on the CDISC 
website (SDTMIG-PGx v1.0).7 The NCI EVS contains a complete codelist for the terminology 
of the events to be captured (BEDECOD) in the BE domain.  
 
5.1.2  Biospecimen Findings (BS) Domain 
 
Sponsors should provide a complete listing of all characteristics of biospecimens and extracted 
samples used for analysis in the Microscopic Findings (MI) domain. These measurements are 
used to assess the adequacy and integrity of the samples collected. 
 
A complete listing of the variables to be included in the BS domain is located on the CDISC 
website (SDTMIG-PGx v1.0).8 Sponsors should collect and submit information for the following 
Biospecimen Characteristics Test Name (BSTEST) values: 
 
 
6 Available at https://evs.nci.nih.gov/ftp1/CDISC/SDTM/SDTM%20Terminology.pdf.  
 
7 The BE domain is included in the SDTMIG-PGx v1.0. Future versions of the SDTMIG may include the BE 
domain (instead of in a separate SDTMIG-PGx). Available at https://www.cdisc.org/standards/foundational/pgx-
sdtmig/sdtmig-pgx-v1-0-impending-deprecation.  
 
8 The BS domain is included in the SDTMIG-PGx v1.0. Future versions of the SDTMIG may include the BS 
domain (instead of in a separate SDTMIG-PGx). Available at https://www.cdisc.org/standards/foundational/pgx-
sdtmig/sdtmig-pgx-v1-0-impending-deprecation.  
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  Contains Nonbinding Recommendations 
Table 1: Biospecimen Domain Test Values 
 
BSTESTCD  BSTEST  BSORRES  Notes 
DIAMETER  Diameter    This test is extended from the BSTEST codelist.  
 
LENGTH  Length  The result should be reported in millimeters (mm). 
The unit of NEEDLE GAUGE would be captured 
NEEDSIZE  Needle Size  e.g., 16  under BSORRESU. This test is extended from the 
BSTEST codelist. 
 
It is important to note that sponsors may submit additional tests to support the decision to include 
or exclude the sample from analysis. In addition, sponsors may use the Related Records 
(RELREC) domain to connect the specimens between the BS and MI domains.  
 
5.1.3  Microscopic Findings (MI) Domain 
 
Currently, the surrogate endpoints that are acceptable to DHN for a phase 3 trial to support 
approval for treatment of noncirrhotic NASH with fibrosis under the accelerated approval 
pathway (Subpart H) are biopsy-based. A semi-quantitative scoring system that considers a core 
set of histological features known as the NASH Clinical Research Network (CRN) Scoring 
System is used to assess NASH. Sponsors may provide data for additional scoring systems 
conforming to CDISC standards.9   
 
Subjects should have an overall histological diagnosis of NASH with liver fibrosis before the 
NASH CRN Score applies. The NASH CRN Scoring System consists of an evaluation of fibrosis 
using the NASH CRN Fibrosis Stage and the NAFLD Activity Score (NAS), where NAS is a 
composite assessment of degrees of steatosis, lobular inflammation, and hepatocellular 
ballooning.10 For drug development programs intended for treatment of noncirrhotic NASH with 
liver fibrosis, FDA has accepted as critical inclusion criteria in NASH trials a NAS greater than 
or equal to 4 with at least 1 point each in inflammation and ballooning along with a NASH CRN 
fibrosis score greater than stage 1 fibrosis but less than stage 4 fibrosis.  
 
Liver biopsy data can be tabulated using CDISCs MI Domain. The MI domain is designed to 
hold information generated from histological, pathological, and immunohistological images 
obtained via microscopic evaluations of tissue samples. The MI domain provides a record for 
each microscopic finding observed, where multiple microscopic tests on a specimen may be 
conducted.  
 
As the biopsy tissue may be processed into multiple slides prior to histopathological evaluation, 
each individual slide may be assessed for individual NASH components. Sponsors should 
 
9 Available at https://www.cdisc.org/standards. 
 
10 DE Kleiner, EM Brunt, M VanNata, et al., 2005, Design and Validation of a Histological Scoring System for 
Nonalcoholic Fatty Liver Disease, Hepatology, 41(6):1313-1321. 
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  Contains Nonbinding Recommendations 
determine whether or not the individual slides are adequate for assessment and record those 
results in the Supplemental MI (SUPPMI) domain. Sponsors should also link records within the 
MI, BS, and BE domains via a RELREC domain. Based on the specifications of the MI domain 
and the CDISC Controlled Terminology approved thus far for liver fibrosis scoring, each specific 
component of the NAS should be recorded using the Microscopic Findings Test Detail 
(MITSTDTL) variable. Likewise, the total or composite NAS score is represented with 
MITSTDTL of Total Score with the criteria (NAS) being held in Microscopic Findings Test 
Code (MITESTCD) and Microscopic Findings Test (MITEST) variables, to group the individual 
components and composite score of NAS.   
 
Given that histological assessments of NAFL and NASH are subject to inter- and intra-observer 
variability,11 sponsors should capture the observer details in the MI domain using the Evaluator 
(MIEVAL) and Evaluator ID (MIEVALID) variables. The measure evaluator is stored in 
MIEVAL, and within the MIEVALID variable when distinction between multiple evaluators 
with the same role is necessary. Where MIEVALID is populated, MIEVAL should exist and 
have a non-null value. CDISC Controlled Terminology should be used to populate the values for 
these variables. In cases where multiple evaluators provide assessments for a given time point 
measurement or for an overall assessment, an independent assessor identifies one of multiple 
measurements to be the accepted one and should be indicated through use of the Accepted 
Record Flag variable (MIACPTFL). Values for this variable are not meant to be derived by the 
sponsor. 
 
CDISC Controlled Terminology provides values of Fibrosis within MITESTCD and MITEST. 
While there is currently no specified terminology published by CDISC for the NASH CRN 
Fibrosis Stage, CDISC does provide terminology for other liver fibrosis scoring criteria for use 
with the Microscopic Findings Test Detail (MITSTDTL) variable. MITSTDTL is a qualifier 
variable for MITESTCD and MITEST. Based on this, it is recommended to specify NASH CRN 
Fibrosis Stage in MITSTDTL, used in conjunction with MITESTCD and MITEST of Fibrosis. 
Results from the biopsy can be specified using the Microscopic Findings Original Result 
(MIORRES) variable.  
 
A list of the relevant variables to be included in the MI domain is available in the SDTM 
Implementation Guide.12 Tables 2 (recommended) and 3 (permissible) below contain a 
representation of concepts for the MI domain. Sponsors should discuss with the review division 
if any of the permissible tests are required for an individual trial. Sponsors should store any 
comments about the biopsy or slide readings in a Comments (CO) domain.  
 
 
11 DE Kleiner, HR Makhlouf, 2016, Histology of NAFLD and NASH in Adults and Children, Clin Liver Dis, 
20(2):293312. 
 
12 Available at https://www.cdisc.org/standards/foundational/sdtmig/sdtmig-v3-3. 
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  Contains Nonbinding Recommendations 
Table 2. Recommended Microscopic Findings Test Codes, Tests, Test Details and Results13 
 
MITESTCD  MITEST  MITSTDTL  MIORRES 
Histological Presence of 
NASHIND  NASH with Fibrosis    Yes, No 
Indicator 
NAS  NAFLD Activity Score  STEATOSIS  0, 1, 2, 3 
LOBULAR 
NAS  NAFLD Activity Score  0, 1, 2, 3 
INFLAMMATION 
NAS  NAFLD Activity Score  BALLOONING  0, 1, 2 
NAS  NAFLD Activity Score  TOTAL SCORE  0, 1, 2, 3, 4, 5, 6, 7, 8 
STEAT  Steatosis  STEATOSIS GRADE  <5%, 5-33%, >33-66%, >66% 
STEAT  Steatosis  STEATOSIS LOCATION  Zone 3, Zone 1, Azonal, Panacinar 
MICROVESICULAR 
STEAT  Steatosis  Present, Absent 
STEATOSIS 
None, Mild zone3, Moderate zone 
NASH CRN FIBROSIS 
FIBROSIS  Fibrosis  3, Portal/periportal, Zone 3 & 
STAGE 
Periportal, Bridging, Cirrhosis 
LOBULAR 
INFLAM  Inflammation  No foci, <2 foci, 2-4 foci, >4 foci 
INFLAMMATION 
PORTAL 
INFLAM  Inflammation  None to minimal, >Minimal 
INFLAMMATION14 
BALLOONING 
HCCINJ  Hepatocellular Injury  None, Few, Many 
DEGENERATION 
PTNUM  Number of Portal Tracts     
 
Table 3. Permissible Microscopic Findings Test Codes, Tests, Test Details and Results 
 
MITESTCD  MITEST  MITSTDTL  MIORRES 
FIBROSIS  Fibrosis  ISHAK FIBROSIS SCORE  0-18 
INFLAM  Inflammation  MICROGRANULOMAS  Present, Absent 
 
13 Note: The terminology listed in the table below is proposed terminology. 
 
14 Portal Inflammation is recommended for pediatric trials and permissible for adult trials. 
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  Contains Nonbinding Recommendations 
MITESTCD  MITEST  MITSTDTL  MIORRES 
HCCINJ  Hepatocellular Injury  ACIDOPHIL BODIES  None to rare, Many 
HCCINJ  Hepatocellular Injury  MALLORY BODIES  None to rare, Many 
PIGMENTEED 
HCCINJ  Hepatocellular Injury  None to rare, Many 
MACROPHAGES 
HCCINJ  Hepatocellular Injury  MEGAMITOCHONDRIA  None to rare, Many 
 
5.1.4  Supplemental Microscopic Findings (SUPPMI) Domain 
 
Sponsors should provide a Supplemental Microscopic Findings (SUPPMI) domain with a 
parameter to assess the adequacy of biopsy sample(s) collected for analysis. Adequacy of the 
slide(s) created for evaluating the histopathological features (e.g., ballooning, steatosis) should 
be established based on results collected in the BS and MI domains. Sponsors should provide 
their rationale in the supplemental qualifier Image Condition for slides determined to be not 
adequate for analysis. If there are multiple reasons, Image Condition should take a value of 
MULTIPLE with the individual reasons listed in QVAL for Image Condition 1 and Image 
Condition 2. Sponsors may provide additional slide-level data points in the SUPPMI domain as 
they see fit (e.g., evaluator name, container name). The table below provides the variables and 
terminology to be used for assessing adequacy of the sample. 
 
Table 4. Terminology for SUPPMI Domain 
 
RDOMAIN  IDVAR  IDVARVAL  QNAM  QLABEL  QVAL 
MI  MIOIQ  Overall Image  Expected Values: Adequate, 
Quality  Not Adequate 
MI  MIIMCND  Image Condition  e.g., Blurry Image, Cracked 
Slide, Multiple 
Use these variables to 
link back to MI domain 
MI  MIIMCND1  Image Condition 1  List Condition 1 if Multiple 
Conditions 
MI  MIIMCND2  Image Condition 2  List Condition 2 if Multiple 
Conditions 
 
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  Contains Nonbinding Recommendations 
5.1.5  Disease Response and Clinical Classifications (RS) Domain 
CDISC provides specific guidance for characterizing and recording clinical indicators of hepatic 
disease progression including MELD Scoring,15 West Haven Hepatic Encephalopathy Grade,16 
and Child-Pugh Classification17 in the RS domain. 
  MELD and MELD Sodium (MELD-Na): While there are no current CDISC guidance 
for MELD-Na, sponsors should follow a similar modeling strategy as MELD scoring as 
shown in Table 5. Individual laboratory test result values (e.g., Creatinine, Bilirubin, 
INR) should be represented in the LB domain and composite scoring in the RS domain 
where the linkage is represented using the --LNKID variable. The relationship between 
the two domains is stored in the RELREC domain.  
 
  West Haven Hepatic Encephalopathy Grade: The measure evaluator is stored in 
Evaluator (RSEVAL), and if distinction between multiple evaluators with the same role 
is necessary this information is stored within the Evaluator ID (RSEVALID) variable. 
Where RSEVALID is populated, RSEVAL should exist and have a non-null value. 
Results should be populated in the Original (RSORRES) and Standard Character 
(RSSTRESC) Results variables, and take values of GRADE 0, GRADE 1, GRADE 
2, GRADE 3, or GRADE 4. 
 
  Child-Pugh Classification: Guidance provided by CDISC provides a way to represent 
the individual laboratory test result values in the LB domain collection of ascites 
information in the CE domain, and composite scoring in the RS domain where the 
linkage is represented using the --LNKID variable from each of the domains. For 
example, a serum bilirubin result of 2.3 mg/dL would result in a RSORRES of 2 to 3 
and a RSSTRESN value of 2 where RSTEST = CPS01-Serum Bilirubin. The 
relationship between the two domains is represented in a RELREC domain. Since the 
input to the Child-Pugh Encephalopathy Grade parameter originates from the West 
Haven Hepatic Encephalopathy Grade that is also modeled in the RS domain (see above 
section on West Haven Hepatic Encephalopathy Grade), the guidance further provides 
linking of these two RS records through the use of the RSGRPID variable. 
 
The table below provides CDISC Controlled Terminology that has been developed for RSCAT, 
RSTESTCD and RSTEST. Refer to the current version of the NCI EVS to ensure no changes to 
the terminology relevant to the RS domain. 
 
 
15 Available at https://www.cdisc.org/standards/foundational/qrs/model-end-stage-liver-disease. 
 
16 Available on the https://www.cdisc.org/ website after login at 
https://www.cdisc.org/system/files/members/standard/foundational/qrs/SDTM%20RS-
WH%20Hepatic%20Encephalopathy%20Grade%20v1%20Public%20Domain.pdf.  
 
17 Available on the https://www.cdisc.org/ website after login at 
https://www.cdisc.org/system/files/members/standard/foundational/qrs/SDTM%20RS-Child-
Pugh%20v1%20Public%20Domain.pdf. 
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  Contains Nonbinding Recommendations 
Table 5. CDISC Controlled Terminology Disease Response and Clinical Classifications 
(RS) Domain18 
 
RSCAT  RSTESTCD  RSTEST  CDISC Definition (taken from CDISC 
Controlled Terminology) 
MELD  MELD0101  MELD-01 Score  Model for End Stage Liver DiseaseMELD 
Score.  
MELD-NA  MELD0201  MELD-02 Score  Model for End Stage Liver Disease-Sodium  
MELD-Na Score. 
WEST HAVEN  WHEG0101  WHEG01-WH  West Haven Hepatic Encephalopathy Grade  
HEPATIC  Hepatic  Grade.  
ENCEPHALOPATHY  Encephalopathy 
GRADE  Grade 
CHILD-PUGH  CPS0101  CPS01-  Child-Pugh Classification - Encephalopathy 
CLASSIFICATION  Encephalopathy  Grade. 
Grade 
CPS0102  CPS01-Ascites  Child-Pugh Classification - Ascites. 
CPS0103  CPS01-Grade  Child-Pugh Classification - Child-Pugh grade. 
CPS0104  CPS01-PT, INR  Child-Pugh Classification - Prothrombin time, 
international normalized ratio (INR). 
CPS0105A  CPS01-PT, Sec  Child-Pugh Classification - Prothrombin time, 
Prolonged  sec prolonged. 
CPS0105B  CPS01-Serum  Child-Pugh Classification - Serum albumin, 
Albumin  g/dL. 
CPS0106  CPS01-Serum  Child-Pugh Classification - Serum bilirubin, 
Bilirubin  mg/dL. 
CPS0107  CPS01-Total Score  Child-Pugh Classification - Child-Pugh total 
score. 
 
5.1.6  Imaging Results (ZI) Domain19 
 
The custom ZI domain captures results of liver imaging procedures (e.g., MRI or CT scan). 
 
 
18 Note: MELD-NA terminology is proposed terminology and not listed in the NCI EVS.  
 
19 Note: Future releases of the SDTMIG may contain a Gastrointestinal System Findings (GI) domain as discussed 
in the Crohns Disease Therapeutic Area User Guide (TAUG). If and when the GI domain becomes available in a 
future version of the SDTMIG and if the FDA supports that new version, sponsors may choose to submit ZI findings 
into the GI domain. 
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  Contains Nonbinding Recommendations 
Sponsors may choose to conduct imaging procedures to further investigate the liver during the 
clinical trial, including measurements for liver steatosis, inflammation, and/or fibrosis. Imaging-
based biomarkers are currently not accepted by DHN to support primary efficacy assessments in 
trials intending to support a marking application; however, they can be used to assess efficacy in 
early phase trials and as exploratory or secondary endpoints to provide supportive evidence. It is 
therefore important for these data points to be submitted consistently. The procedure itself should 
be recorded in the Procedures (PR) domain and results of the procedure should be recorded in 
this custom Imaging Results (ZI) domain. Information on the device(s) used to capture images 
from MRIs and other imaging-related data should be captured in domains as prescribed by the 
SDTMIG for Medical Devices (SDTMIG-MD).20  
 
The ZI domain takes the structure of a findings domain and should contain variables such as 
Imaging Results Test (ZITEST), Imaging Results Test Code (ZITESTCD), and Imaging Results 
Original Result (ZIORRES). Sponsors may use their discretion regarding which data points to 
collect and submit from the imaging procedure(s). Recording of the procedure in the PR domain 
and results of that procedure in the ZI domain may be linked via the RELREC domain.   
 
5.1.7  Adjudication (ZA) Domain 
 
Sponsor protocols may specify for certain events and/or clinical outcomes to be adjudicated by 
investigator(s) and/or committee(s). Sponsors should create a custom Adjudication (ZA) domain 
to provide assessments by individual adjudicators as it relates to certain events (e.g., DILI).  
Examples of adjudicated events in NASH development programs may include DILI, Liver-
Related Death, Hepatic Decompensation Events, Major Adverse Cardiac Events (MACE) and 
Cardiac-Related Death. All potential events sent for adjudication should be included in the data 
set regardless of the adjudication outcome.   
 
The ZA domain should follow the structure of a Findings About Events or Interventions (FA) 
domain. An FA domain utilizes the SDTM findings class structure with the addition of an 
Object (--OBJ) variable that serves to specialize the topic being measured within the --
TESTCD/--TEST variable.   
 
Sponsors should specify in their protocol and in the ZA domain the event that is being 
adjudicated, type of investigator assessing the event as well as the committee responsible for 
resolving any discrepancies between individual adjudicators. For example, the custom ZA 
Domain may provide DILI assessments and/or Liver-Related Death/Clinical Outcomes by 
individual hepatologists and a Hepatic Adjudication Committee (HAC), if applicable. MACE 
and Cardiac-Related Death events may be adjudicated by a Cardiac Adjudication Committee 
(CAC).  
 
The date of the adjudicators assessment may be stored in ZADTC. The earliest date that the 
assessor determines the subject to have met the criteria should be modeled as its own record with 
ZATEST value of EVALUATED EVENT ONSET DATE with the date value stored in 
ZAORRES. The Object (ZAOBJ) variable should hold the name of the event being evaluated, 
such as DILI or CARDIAC MACE. Each block of records resulting from the assessment of 
 
20 Available at https://www.cdisc.org/standards/foundational/medical-devices-sdtmig/sdtmig-medical-devices-v1-1.  
14 
  Contains Nonbinding Recommendations 
a single adjudicator per adjudication event should be grouped using a unique Repetition Number 
(ZAREPNUM) variable. The Category (ZACAT) variable may be used to distinguish if the 
adjudication is a FIRST ADJUDICATION or a READJUDICATION. 
 
For assessing potential DILI, each adjudicators assessment should include a category of 
likelihood that the investigational or study product caused DILI. We recommend the likelihood 
categories used by the Drug-Induced Liver Injury Networks21 numeric score of 1 to 6 (1 = 
Definite, 2 = Highly Likely, 3 = Probable, 4 = Possible, 5 = Unlikely, or 6 = Indeterminate). If a 
HAC was used, then consensus assignment of likelihood category should also be provided (and 
noted in the ZAEVAL variable). If the adjudicator is reviewing lab data to determine whether the 
subject meets potential DILI injury, the records from the LB domain and the record(s) in the ZA 
domain may be linked using the RELREC domain.  
 
For assessing whether a subject meets given criteria (e.g., cardiac-related death), sponsors should 
include in their study protocol the specific criteria being used for the event being adjudicated. 
The Test (ZATEST) variable may take a value such as EVENT CRITERIA MET with the 
event itself stored in the ZAOBJ variable. The result variable (ZAORRES) may take values of 
Yes or No. Any comments made by an adjudicator or an adjudication committee the sponsor 
wishes to submit should be stored in the Comments (CO) domain, linked to the ZA domain via 
the RELREC domain.  
 
For assessing hepatic decompensation events requiring adjudication, the ZAOBJ variable could 
take a value of HEPATIC DECOMPENSATION EVENT. The adjudicators assessment of the 
specific event causing the subject to reach the endpoint is stored in ZAORRES where ZATEST = 
ADJUDICATION OUTCOME with the adjudicators assessment of when the subject reached 
that endpoint stored in ZAORRES where ZATEST = EVALUATED EVENT ONSET DATE.  
 
Table 6 contains the variables and subsequent comments, and Table 7 contains example 
terminology for adjudicated events and outcomes.  
 
Table 6. ZA Variables 
 
Variable Name  Variable Label  Type  Comments 
Adjudication Test and Results 
ZATESTCD  Adjudication Test Code  Char  See Table 7. 
ZATEST  Adjudication Test  Char  See Table 7. 
Sponsors may include additional tests beyond what is listed in 
Table 7. Additional tests can apply to all objects or some 
objects (i.e. sponsors are permitted to submit an object-specific 
test).  
ZAOBJ  Object of Interest  Char  See Table 7. 
The category of event that is being adjudicated, e.g., DILI, 
CARDIAC MACE. 
 
21 Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637941/pdf/nihms-444700.pdf.  
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  Contains Nonbinding Recommendations 
Variable Name  Variable Label  Type  Comments 
If the trial protocol calls for additional events or outcomes to be 
adjudicated, sponsors may extend the codelist beyond what is 
listed in Table 7. 
ZACAT  Category  Char  Used to define if the adjudication is a first adjudication or re-
adjudication. 
ZAORRES  Original Result  Char  The adjudicators assessment of ZATEST. 
ZASTRESC  Standard Character  Char  Standardized Result of the adjudicators assessment of 
Result  ZATEST. 
Adjudicator Information 
ZAEVAL  Evaluator  Char  Role of the person who provided the evaluation. Used only for 
results that are subjective (e.g., assigned by a person or a 
group). Should be null for records that contain collected or 
derived data. Examples: INVESTIGATOR, ADJUDICATION 
COMMITTEE, VENDOR. 
ZAEVALID  Evaluator Identifier  Char  Used to distinguish multiple evaluators with the same role 
recorded in ZAEVAL. Examples: Hepatologist 1, 
Hepatologist 2. ZAEVAL should be populated when 
ZAEVALID is populated.  
Other Flags 
ZAACPTFL  Accepted Record Flag  Char  The Acceptance Flag identifies those records that have been 
determined to be the accepted assessment by an independent 
assessor. This flag would be provided by an independent 
assessor and when multiple evaluators (e.g., Hepatologist 1, 
Hepatologist 2, and Hepatic Adjudication Committee) 
provide assessment or evaluations at the same time point or an 
overall evaluation.  
 
Table 7. Example Terminology for Adjudicated Events and Outcomes 
 
ZAOBJ  ZATESTCD  ZATEST  ZAORRES 
ADJDILI  DILI ADJUDICATION SCORE  1-6 
DILI 
EVALUATED EVENT ONSET  Adjudicators assessment of when the 
ADJDATE 
DATE  subject met event criteria 
ADJCRIT  EVENT CRITERIA MET  Yes, No 
CARDIAC MACE 
EVALUATED EVENT ONSET  Adjudicators assessment of when the 
ADJDATE 
DATE  subject met event criteria 
ADJCRIT  EVENT CRITERIA MET  Yes, No 
CARDIAC DEATH 
EVALUATED EVENT ONSET 
ADJDATE  Date of Death 
DATE 
ADJCRIT  EVENT CRITERIA MET  Yes, No 
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  Contains Nonbinding Recommendations 
ZAOBJ  ZATESTCD  ZATEST  ZAORRES 
LIVER-RELATED  EVALUATED EVENT ONSET 
ADJDATE  Date of Death 
DEATH  DATE 
Adjudicators assessment of cause of 
ADJOUT  ADJUDICATION OUTCOME 
death 
CAUSE OF DEATH 
EVALUATED EVENT ONSET 
ADJDATE  Date of Death 
DATE 
HEPATIC ENCEPHALOPATHY, 
ASCITES, VARICEAL BLEED, 
ADJOUT  ADJUDICATION OUTCOME 
HEPATIC  SPONTANEOUS BACTERIAL 
DECOMPENSATION  PERITONITIS 
EVENT 
EVALUATED EVENT ONSET  Adjudicators assessment of when the 
ADJDATE 
DATE  subject met event criteria 
 
5.1.8  Concomitant Medications (CM) Domain 
 
Sponsors should provide a complete list of all Concomitant Medications data for all subjects in 
accordance with existing CDISC standards. In addition to prescription medications, sponsors 
should include any over the counter medications (e.g., weight loss medication, dietary and herbal 
medications). Of particular interest are lipid-lowering agents, statins, antihypertensive, 
antidiabetic, thiazolidinediones, vitamin E, and anticoagulants and antiplatelets. Data relating to 
concomitant medications should be captured and recorded during scheduled visits as reflected in 
the trial protocol and when the subject is undergoing evaluation for potential DILI. 
 
5.1.9  Medical History (MH) Domain 
 
Sponsors should provide a complete listing of all Medical History data for all subjects in 
accordance with existing CDISC standards. Of particular interest are preexisting medical 
conditions that may impact NASH disease progression and/or DILI assessment (e.g., diabetes, 
primary liver cancers, alcohol/substance use disorder, gallstone disease, heart failure, etc.). 
Sponsors should refer to the draft NASH Guidance regarding recommendations for trial 
enrollment depending on the phase of drug development. Additionally, sponsors should include a 
record in the MH domain for any condition that precludes a subject from participating in the 
study, in addition to their record in the Inclusion/Exclusion (IE) domain.  
 
5.1.10 Laboratory (LB) Domain 
 
Sponsors should provide the complete tabulated data for all lab measurements recorded, 
including central and local labs (denoted using LBNAM variable) as well as scheduled and 
unscheduled visits. All lab data should be provided in accordance with CDISC Standards and 
Controlled Terminology. Sponsors should discuss specific laboratory parameters to be collected 
with DHN. Recommended parameters are listed below:  
 
17 
  Contains Nonbinding Recommendations 
  Hematology parameters (e.g., white blood cell, hemoglobin, platelets) 
 
  Metabolic parameters (e.g., electrolytes, hemoglobin A1C, creatine kinase, lactate 
dehydrogenase) 
 
  Liver parameters including bilirubin fractions22 (e.g., direct and indirect or conjugated 
and unconjugated) 
 
  Renal parameters (e.g., creatinine, estimated glomerular filtration rate) 
 
  Lipid parameters 
 
  Coagulation parameters (e.g., prothrombin time/international normalized ratio) 
 
  Autoimmune parameters (e.g., Antinuclear antibody (ANA), anti-smooth muscle 
antibody (ASMA), Total IgG levels) 
 
In addition to the above tests, sponsors may wish to include other serum biomarkers that may be 
relevant to understanding NASH, fibrosis, and/or DILI (e.g., ELF,23 CK-18, APRI, FIB-4, N-
terminal propeptide of type III collagen (PRO-C3)). Note that individual components of 
calculated serum biomarkers should have their own record(s) in the LB domain. Any biomarker 
that is derived from individual components should store the analytical method used for 
calculation stored in the Analysis Method variable (LB.LBANMETH). Terminology for the 
components of and results for the afore mentioned example serum biomarkers are provided 
below in Table 8. All lab parameters submitted to FDA should follow CDISC Controlled 
Terminology.  
 
Table 8. CDISC Controlled Terminology for Example Liver Serum Biomarkers in LB 
Domain24 
 
LBTESTCD  LBTEST  NCI Code  CDISC Definition 
ELF Components 
Tissue Inhibitor of  A measurement of the tissue inhibitor of metalloproteinase 
TIMP1  Metalloproteinase 1  C82036  1 in a biological specimen. 
Procollagen 1 N-Terminal  A measurement of the procollagen 1 N-terminal propeptide 
P1NP  Propeptide  C96625  in a biological specimen. 
A measurement of hyaluronic acid in a biological 
HYALUAC  Hyaluronic Acid  C112319  specimen. 
 
22 Sponsors should use appropriate terminology to clearly reflect the method used to assess bilirubin fractions (i.e., 
conjugated vs. direct). 
 
23 If the ELF Score is calculated histologically, the result should be stored in the MI domain for MI.MIORRES 
under MI.MITSTDTL = ENHANCED LIVER FIBROSIS SCORE and MI.MITESTCD = FIBROSIS. 
 
24 The line item for Enhanced Liver Fibrosis is proposed terminology in the LB domain as a calculation from the 
individual components (TIMP1, P1NP, HYALUAC). 
18 
  Contains Nonbinding Recommendations 
LBTESTCD  LBTEST  NCI Code  CDISC Definition 
Example Liver Serum Biomarkers 
ELF  Enhanced Liver Fibrosis     
A calculation that indicates the likely presence of liver 
cirrhosis and fibrosis, measured as the relative 
measurement of aspartate aminotransferase (AST) to AST 
upper limit of normal, divided by the platelet count, and 
APRI  AST to Platelet Ratio Index  C156512  multiplied by 100. 
A measurement of the cytokeratin 18 fragment in a 
CYFRA18  Cytokeratin 18 Fragment  C130160  biological specimen. 
A scoring system that evaluates liver pathology through the 
assessment of multiple blood test parameters, taking into 
account additional demographic factors such as the age 
LVFBRSC  Liver Fibrosis Score  C147385  and/or gender of the subject. 
Procollagen 3 N-Terminal  A measurement of the procollagen 3 N-terminal propeptide 
P3NP  Propeptide  C128973  in a biological specimen. 
 
5.1.11 Microbiology Specimens (MB) Domain 
 
Sponsors should use the MB domain to provide serologic test results for hepatitis (hepatitis A, B, 
C, and E) serology tests collected as part of the trial entry evaluation and during potential DILI 
assessments, if applicable. CDISC Controlled Terminology for the hepatitis tests are provided 
below: 
 
Table 9. CDISC Controlled Terminology for Hepatitis Serology in Microbiology Specimens 
Domain 
 
MBTESTCD  MBTEST  NCI Code  CDISC Definition 
A measurement of the hepatitis A virus antibody in a 
HAAB  Hepatitis A Virus Antibody  C92534  biological specimen. 
Hepatitis A Virus IgM  A measurement of hepatitis A virus IgM antibody in a 
HAIGMAB  Antibody  C92271  biological specimen. 
Hepatitis B Virus Surface  A measurement of the surface antigen reaction of a 
HBSAG  Antigen  C64850  biological specimen to the hepatitis B virus. 
Hepatitis B Virus Core IgM  A measurement of the hepatitis B virus core antibody in a 
HBCAB  Antibody  C96660  biological specimen. 
A measurement of the hepatitis C virus antibody in a 
HCAB  Hepatitis C Virus Antibody  C92535  biological specimen. 
A measurement of the hepatitis C virus RNA in a biological 
HCRNA  Hepatitis C Virus RNA  C142330  specimen. 
Hepatitis E Virus IgG  A measurement of IgG antibody to the hepatitis E virus in a 
HEIGGAB  Antibody  C106526  biological specimen. 
Hepatitis E Virus IgM  A measurement of IgM antibody to the hepatitis E virus in a 
HEIGMAB  Antibody  C96665  biological specimen. 
A measurement of the hepatitis E virus RNA in a biological 
HERNA  Hepatitis E Virus RNA  C142331  specimen. 
 
19 
  Contains Nonbinding Recommendations 
5.1.12 Substance Use (SU) Domain 
 
Data related to substance use (e.g., alcohol use) should be collected as part of the NASH clinical 
trial and DILI evaluation. The extent of prior alcohol use should be assessed at baseline, during 
protocol-defined scheduled visits, and in suspected cases of DILI. Data collected should be 
recorded in the SU domain and included in the Inclusion/Exclusion (IE) domain as appropriate. 
Other substances such as tobacco or caffeine usage should also be recorded in the SU domain. 
For example, a subject who consumes one, regular-sized beer per day may contain the following 
data points: 
 
  SUTRT: BEER 
  SUCAT: ALCOHOL 
  SUDOSE: 12 
  SUDOSU: OUNCES 
  SUDOSFRQ: QD 
 
The full list of variables to be included in the SU domain is located in the SDTM Implementation 
Guide. 
 
5.1.13 Trial Summary (TS) Domain 
 
Data related to the trial summary should be collected and stored in the Trial Summary (TS) 
domain. Of particular interest to FDA is the frequency that this technical specification is used in 
creating and submitted trial data. Per the FDA Study Data Technical Conformance Guide, 
sponsors may include an additional parameter in their TS domain to note that this technical 
specification was used for the study. The parameter and associated value sponsors should use is 
noted below: 
 
  TSPARAMCD = FDATCHSP 
  TSPARAM = FDA Tech Spec 
  TSVAL = NASH Technical Specification Guidance v1.0 
 
5.1.14 RELREC Domain 
 
As discussed in previous sections, sponsors should use a RELREC domain to describe the 
relationship between records captured in separate domains together. A common use case for the 
RELREC domain is connecting AE and CM records. As it relates to this technical specification, 
the RELREC domain may connect the needle size captured in the BS domain with the biopsy 
slide measurements evaluated in the MI domain. Another example may be connecting the record 
of an MRI procedure in the PR domain with the results of that MRI in the ZI domain. Where 
relationships between records in different domains should be established, the RELREC domain 
should store those relationships.  
 
The full instructions for creating the RELREC domain, including the required variables, are 
located in the SDTM Implementation Guide. 
 
20 
  Contains Nonbinding Recommendations 
5.1.15 Other SDTM Considerations 
 
5.1.15.1  Gastroesophageal varices 
 
Subjects who progress to cirrhosis during the trial may undergo screening for gastroesophageal 
varices on esophagogastroduodenoscopy (EGD). Information on the EGD can be modeled in 
SDTM using the Procedures Domain (PR). The PR domain falls within the Interventions Class 
of domains and is intended to capture information on interventional activity that are to have 
diagnostic, preventive, therapeutic, or palliative effects. The name of the procedure, EGD, can be 
captured Reported Name of Procedure (PR.PRTRT).   
 
Currently, CDISC does not have any guidance on modeling the results of the EGD procedure 
related to varices (e.g., number of varices, size of varices, presence of red wale marks). Given 
that CDISC has a draft domain for Gastrointestinal System Findings (GI) that may be under 
development, the current recommendation is to model the results of the EGD procedure in the 
custom Imaging Results (ZI) domain that follows the structure of a CDISC findings domain. 
Occurrence of varices, red wale marks, and variceal bleeding can be modeled under using 
ZITESTCD and ZITEST Test Codes and Test Names. Sponsors may submit additional data 
points about the results of the endoscopy in the ZI domain.  
 
When gastroesophageal variceal hemorrhage is captured as an AE, it should be captured in the 
AE domain, with verbatim term indicating gastroesophageal variceal hemorrhage captured in the 
topic variable of AE.AETERM. The record in the AE domain should be linked to that of the ZI 
domain using the --LNKID variable, with relationships captured using the RELREC domain. 
 
5.1.15.2  All-cause mortality 
 
All-cause mortality or death is a component of several composite endpoints currently accepted 
by DHN to demonstrate clinical benefit in NASH clinical trials. If a subject dies during the 
study, information regarding the subjects death is tabulated in several SDTM domains including 
the Death Details (DD) domain, which should store all death information regardless of whether 
the death is related to the primary endpoint. Additional domains which should include death 
information are the Disposition (DS) domain that records the death as a disposition event, 
Adverse Events (AE), and Demographics (DM) to populate the Death Date (DTHDTC), and 
Death Flag (DTHFL) variables that are referenced within this domain. The records within the 
AE, DS, and DD domains should be linked using the --LNKID variable, with the relationship 
represented in the RELREC domain. Sponsors should consult CDISC Controlled Terminology as 
well as the SDTM Implementation Guide in using these domains. 
 
5.2 ADaM Data Sets 
 
This section contains three parts: Analysis Data Set Subject Level (ADSL), Occurrence Data 
Structure (OCCDS) data sets, and Basic Data Structure (BDS) data sets. At a minimum, sponsors 
should provide the data sets and variables listed throughout these sections. Sponsors can and 
21 
  Contains Nonbinding Recommendations 
should submit additional data sets and variables beyond what is listed below in accordance with 
the ADaM Implementation Guide (ADaMIG)25 and the FDA Data Standards Catalog.  
 
Sponsors should also include appropriate Sequence Number variables in their ADaM data sets 
for easy traceability back to the SDTM domains. Specific instructions are located in the ADaM 
Implementation Guide.  
 
5.2.1   Subject-Level Analysis Data Set (ADSL) 
 
The Subject-Level Analysis Data Set contains one record per subject and derives information 
from other data sets for analysis purposes. Sponsors should include all required variables in the 
ADSL, including basic demographic information, treatment variables, start and end date 
variables, study and treatment discontinuation variables, and treatment duration variables. The 
variables listed in Table 10 should also be included in the ADSL data set to allow FDA to 
conduct sub-group analyses.  
 
The baseline variables identified below should be used when those tests are collected and 
provided in the data submission. For example, if ELF score is not collected and reported, the 
ELFBL variable is not required for this data set. Sponsors may add additional flags to this data 
set as appropriate (e.g., special subject populations of interest for subgroup analyses or relevant 
concomitant medications).  
 
Table 10 provides a list of variables that should be included in the ADSL data set. The comments 
column contains recommended derivations for the baseline variables. Sponsors should include 
their derivations in the ADaM define.xml file. 
 
Table 10. ADSL Variables 
 
Variable Name  Variable Label  Type  Comments 
Baseline Vital Signs Characteristics Variables 
WEIGHTBL  Weight at Baseline (kg)  Num  VS.VSSTRESN where VSTEST = WEIGHT and VSBLFL = 
Y 
HEIGHTBL  Height at Baseline (cm)  Num  VS.VSSTRESN where VSTEST = HEIGHT and VSBLFL = Y 
BMIBL  Body Mass Index at  Num  VS.VSSTRESN where VSTEST = BMI and VSBLFL = Y 
Baseline (kg/m2) 
SYSBL  Systolic Blood Pressure  Num  VS.VSSTRESN where VSTEST = Systolic Blood Pressure and 
at Baseline (mmHg)  VSBLFL = Y 
DIABL  Diastolic Blood  Num  VS.VSSTRESN where VSTEST = Diastolic Blood Pressure and 
Pressure at Baseline  VSBLFL = Y 
(mmHg) 
HRBL  Heart Rate at Baseline  Num  VS.VSSTRESN where VSTEST = Heart Rate and VSBLFL = 
(beats/min)  Y 
 
25 Available https://www.cdisc.org/standards/foundational/adam/adamig-v1-1-release-package.  
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  Contains Nonbinding Recommendations 
Variable Name  Variable Label  Type  Comments 
RESPBL  Respiratory Rate at  Num  VS.VSSTRESN where VSTEST = Respiratory Rate and 
Baseline (breaths/min)  VSBLFL = Y 
WHBL  Waist to Hip Ratio at  Num  VS.VSSTRESN where VSTEST = Waist to Hip Ratio and 
Baseline  VSBLFL = Y 
Baseline Lab Characteristics 
ALTBL  Baseline ALT  Num  ADLB.AVAL where ADLB.PARAMCD = ALT and 
ADLB.DILIBLFL = Y 
ALTCAT  Baseline ALT Category  Text  Divide ADSL.ALTBL by LB.LBSTNRHI for the last pre-treatment 
record for ALT and set the category to one of the following: 
  If result is <=1: <= ULN 
  If result is >1 to <=3: > ULN to <=3x ULN 
  If result is >3 to <=5: >3x ULN to <=5x ULN 
  If result is >5: >5x ULN 
ALTCATN  Baseline ALT Category  Integer  Numeric Representation of ALTCAT. 1 = <=ULN, 2 = 
(N)  >ULN to <=3x ULN, 3 = >3x ULN to <=5x ULN, 4 = 
>5x ULN 
ASTBL  Baseline AST  Num  ADLB.AVAL where ADLB.PARAMCD = AST and 
ADLB.DILIBLFL = Y 
ASTCAT  Baseline AST Category  Text  Divide ADSL.ASTBL by LB.LBSTNRHI for the last pre-treatment 
record for AST and set the category to one of the following: 
  If result is <=1: <= ULN 
  If result is >1 to <=3: >ULN to <=3x ULN 
  If result is >3 to <=5: >3x ULN to <=5x ULN 
  If result is >5: >5x ULN 
ASTCATN  Baseline AST Category  Integer  Numeric Representation of ASTCAT. "1" = "<=ULN", "2" = 
(N)  ">ULN to <=3x ULN", "3" = ">3x ULN to <=5x ULN", 4 = 
>5x ULN 
ALPBL  Baseline ALP  Num  ADLB.AVAL where ADLB.PARAMCD = ALP and 
ADLB.DILIBLFL = Y 
ALPCAT  Baseline ALP Category  Text  Divide ADSL.ALPBL by LB.LBSTNRHI for the last pre-treatment 
record for ALP and set the category to one of the following: 
  If result is <=1: <= ULN 
  If result is >1 to <=2: > ULN to <=2x ULN 
  If result is >2: >2x ULN 
ALPCATN  Baseline ALP Category  Integer  Numeric Representation of ALPCAT. 1  = <=ULN, 2 = 
(N)  >ULN to <=2x ULN, 3 = >2x ULN 
TBILIBL  Baseline Total Bilirubin  Num  ADLB.AVAL where ADLB.PARAMCD = BILI and 
ADLB.DILIBLFL = Y 
TBILCAT  Baseline Tot. Bilirubin  Text  Set to <=ULN if ADSL.TBILIBL <= LBSTNRHI (for the last 
Category  pre-treatment record in SDTM.LB where LBTESTCD = BILI); 
else set to >ULN if ADSL.TBILIBL > LBSTNRHI 
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Variable Name  Variable Label  Type  Comments 
TBILCATN  Baseline Tot. Bilirubin  Integer  Numeric representation of ADSL.TBILCAT. 
Category (N)    1 = <=ULN, 2 = >ULN 
CBILIBL  Baseline Conjugated  Num  ADLB.AVAL where ADLB.PARAMCD = BILIDIR and 
Bilirubin  ADLB.DILIBLFL = Y 
CBILCAT  Baseline Conj.  Text  Set to <=ULN if ADSL.CBILIBL <= LBSTNRHI (for the last 
Bilirubin Category  pre-treatment record in SDTM.LB where LBTESTCD = 
BILDIR); else set to >ULN if ADSL.CBILIBL > LBSTNRHI 
CBILCATN  Baseline Conj.  Integer  Numeric representation of ADSL.CBILCAT.  
Bilirubin Category (N)  1 = <=ULN, 2 = >ULN 
CPKCAT  Baseline CPK Category  Text  Set to Normal if LB.LBSTRESN <= LB.LBSTNRHI for 
LB.LBTESTCD = CPK and LB.LBBLFL = Y; Set to HIGH 
if LB.LBSTRESN > LB.LBSTNRHI for LB.LBTESTCD = CPK 
and LB.LBBLFL = Y 
LDHCAT  Baseline LDH Category  Text  Set to Normal if LB.LBSTRESN <= LB.LBSTNRHI for 
LB.LBTESTCD = LDH and LB.LBBLFL = Y; Set to HIGH 
if LB.LBSTRESN > LB.LBSTNRHI for LB.LBTESTCD = LDH 
and LB.LBBLFL = Y 
PLATCAT  Baseline Platelets  Text  Set to Normal if LB.LBSTRESN >= LB.LBSTNRLO for 
Category  LB.LBTESTCD = PLAT and LB.LBBLFL = Y; Set to LOW 
if LB.LBSTRESN < LB.LBSTNRLO for LB.LBTESTCD = 
PLAT and LB.LBBLFL = Y 
EGFRBL  Baseline eGFR  Num  Baseline eGFR value 
EGFRCAT  Baseline eGFR  Text  Set to Normal if Baseline eGFR >= 90, Mild Renal Impairment 
Category  if 60 =< Baseline eGFR < 90, Moderate Renal Impairment if 30 
=< Baseline eGFR < 60 and Severe Renal Impairment if 30 > 
Baseline eGFR 
EGFRCATN  Baseline eGFR  Integer  Numeric representation of ADSL.EGFRCAT. 
Category (N)  1 if Normal, 2 if Mild Renal Impairment, 3 if Moderate 
Renal Impairment, 4 if Severe Renal Impairment 
Baseline Medical History Characteristics 
CHRONFL  Chronic Liver Disease  Char  Expected Values: Y or N 
Flag  Subjects with evidence of other causes of chronic liver disease at 
baseline should be flagged as Y. Else, N 
DIABFL  Diabetes Flag  Char  Expected values: Y or N 
Y if the subject is diabetic at baseline. Else, N. 
GALLFL  Gallstones Flag  Char  Expected values: Y or N 
Y if the subject has a history of gallstones at baseline. Else, N.  
PCOSFL  Polycystic ovary  Char  Expected values: Y or N 
syndrome Flag  Y if the subject has a history of Polycystic ovary syndrome at 
baseline. Else, N.  
Baseline Biopsy Characteristics 
FIBSCBL  Baseline Fibrosis Score  Char  MI.MIORRES where MIBLFL = Y, MITESTCD = FIBROSIS 
and MITSTDTL = NASH CRN FIBROSIS STAGE 
ISHAKBL  Baseline Modified  Num  MI.MORRES where MIBLFL = Y, MITESTCD = FIBROSIS 
ISHAK Score  and MITSTDTL = ISHAK FIBROSIS SCORE 
STEOBL  Baseline Steatosis  Integer  MI.MIORRES where MIBLFL = Y, MITESTCD = NAS and 
Score  MITSTDTL = Steatosis 
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Variable Name  Variable Label  Type  Comments 
HBALLBL  Baseline Hep.  Integer  MI.MIORRES where MIBLFL = Y, MITESTCD = NAS and 
Ballooning Score  MITSTDTL = Ballooning 
LOBINBL  Baseline Lobular  Integer  MI.MIORRES where MIBLFL = Y, MITESTCD = NAS and 
Inflammation Score  MITSTDTL = Lobular Inflammation 
PORTFL  Baseline Portal  Text  MI.MIORRES where MIBLFL = Y, MITESTCD = INFLAM 
Inflammation  and MITSTDTL = Portal Inflammation 
NASBL  Baseline NAS  Integer  Sum of ADSL.STEOBL, ADSL.HBALLBL, ADSL.LOBINFL 
NASCAT  Baseline NAS Category  Text  Set to NAS <6 if ADSL.NASBL<6; Set to NAS >=6 if 
ADSL.NASBL>=6 
NASCATN  Baseline NAS Category  Integer  Numeric representation of NASCAT. 1 = NAS <6, 2 = 
(N)  NAS >=6 
NASFIBFL  Overall Histological  Char  Expected Values: Y or N 
Diagnosis of NASH  If MI.MIORRES = Yes where MI.MITESTCD = NASHIND, 
with Fibrosis Flag  then Y. Else, N  
Non-Invasive Baseline Characteristics 
MELDBL  Baseline MELD Score  Num  RS.RSSTRESN when RS.RSBLFL = Y and RSTEST = 
MELD01-Score 
FIB4BL  Baseline FIB4  Float  Calculated using lab baseline values and age from Demographics 
as: Age (years) x AST (U/L)/[Platelet Count (x10^9/L) x 
ALT^(1/2) (U/L)] 
ELFBL  Baseline ELF  Float  MI.MIORRES where MIBLFL = Y, MITESTCD = Fibrosis 
and MITSTDTL = Enhanced Liver Fibrosis Score 
APRIBL  Baseline APRI  Float  LB.LBSTRESN where LB.LBBLFL = Y and LBTESTCD = 
APRI 
Concomitant Medications Characteristics 
LIPCAT  Lipid-Lowering Agents  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Category  Use, New Concomitant Use 
Any lipid-lowering agents, including statins 
STATCAT  Statins Category  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Use, New Concomitant Use 
Statins only 
ANHYPCAT  Antihypertensive  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Category  Use, New Concomitant Use 
Antihypertensive medications 
ANDIACAT  Antidiabetic  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Medications Category  Use, New Concomitant Use 
Any antidiabetic medications, including Thiazolidinediones 
TZDCAT  Thiazolidinediones  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Category  Use, New Concomitant Use 
Thiazolidinediones only 
VITECAT  Vitamin E Category  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Use, New Concomitant Use 
Vitamin E 
ANCPCAT  Anticoagulants and  Char  Expected values: No Concomitant Use, Prior and Concomitant 
Antiplatelets Category  Use, New Concomitant Use 
Anticoagulants and Antiplatelets 
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5.2.2   Occurrence Data Structure (OCCDS) Data Sets 
 
Occurrence Data Structure (OCCDS) Data Sets are used for the counting of subjects with a given 
record or term, and often includes a coding dictionary (e.g., MedDRA for adverse events, 
WHODrug for concomitant medications)). In creating ADaM OCCDS data sets, sponsors should 
follow the guidance specified by the ADaM Structure for Occurrence Data,26 including sections 
on dictionary coding and categorization variables, timing variables, and flag and indicator 
variables. 
 
5.2.2.1   Adverse Event Analysis Data Set (ADAE) 
 
Sponsors should include all records from SDTM.AE. If a sponsor uses the approach of recording 
multiple records in AE each time the event changes in severity, relationship, etc. then this should 
be noted in the metadata. Also note that the specification includes a flag variable that indicates 
which record had the worst severity grade for a given adverse event (MedDRA preferred term) 
when there are multiple occurrences (records) of the same adverse event for the same subject. 
Sponsors may select a grading scale of their choice, which should be pre-specified in the study 
protocol. In addition, sponsors should consult the FDA Data Standards Catalog for guidance on 
the appropriate MedDRA version to use.  
 
To aid evaluation of potential DILI, this specification also includes a Hepatic Injury Flag(s) to 
flag AEs occurring within defined grouped queries (e.g., Custom MedDRA Queries) and 
accompanying flags to identify the earliest record within each hepatic injury flag. Sponsors 
should discuss the exact derivations of the hepatic injury flags with the FDA. Any deviations 
from the specifications below should be clearly communicated to the review division.   
 
Table 11. ADAE Variables 
 
Variable Name  Variable Label  Type  Comments 
TRTEMFL  Treatment-Emergent  Char  Expected Values: Y or null 
Analysis Flag  A value of Y on a record should indicate a new or worsening AE 
after the first dose of investigational product. Metadata should be 
clear on the reference dates that are used to define the period during 
which an adverse event is considered treatment emergent.   
AOCCPIFL  1st Max Sev./Int.  Char  Expected Values: Y or null 
Occur Within PT  Character indicator for the first occurrence of the maximum 
Flag  severity/intensity within the subject and preferred term. 
HPxxFL  Hepatic Injury xx  Char  Expected values: Y or null 
Flag  Sponsors should create Hepatic Injury Flag(s) to capture specific 
preferred terms within the MedDRA hierarchy. Sponsors should 
consult FDA regarding how many flags are required and how exactly 
to derive each flag.  
HPFxxFL  First Hepatic Injury  Char  Expected values: Y or null 
xx Flag 
 
26 Available at https://www.cdisc.org/standards/foundational/adam/adamig-v1-1-release-package.  
26 
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Variable Name  Variable Label  Type  Comments 
Create one additional flag for each HPxxFL flag created and flag the 
earliest (min ASTDY) on treatment (ASTDY >= 1) for each subject 
and record that fits the criteria. Otherwise, null 
DILIFL  Potential DILI Event  Char  Expected values: Y or null 
Flag  Flag the following Adverse Events as Y: Fatigue, Nausea, 
Vomiting, Abdominal pain or tenderness, Fever, Rash, Pruritus, 
Jaundice/icterus, Altered mental status 
DILIPFL  Potential DILI Event  Char  Expected values: Y, N or null 
Flag (30-days prior)  Null for records where DILIFL is null. For records with DILIFL = 
Y: if the event occurs in the 30 days before a lab-identified DILI 
threshold met in the ADDILI data set, then Y. Else, N 
DILIAFL  Potential DILI Event  Char  Expected values: Y,N or null 
Flag (30-days after)  Null for records where DILIFL is null. For records identified with 
DILIFL = Y: if the event occurs in the 30 days after a lab-
identified DILI threshold met in the ADDILI data set, then Y. 
Else, N 
 
5.2.3   Basic Data Structure (BDS) Data Sets 
 
The following guidance should be used to create data sets that fall within the BDS structure (e.g., 
ADLB to display laboratory data). Specific guidelines are included for several BDS data sets. All 
BDS data sets should use the guidelines provided below, which have been written in accordance 
with the ADaM Implementation Guide.  
 
All BDS Data Sets should contain the identifier variables, record-level treatment and dose 
variables, and timing variables as specified in the ADaM Implementation Guide specifically the 
section as it relates to the ADaM Basic Data Structure (in ADaMIG v1.1, Section 3.3). 
 
5.2.3.1   Laboratory Analysis Data Set (ADLB) 
 
The following issues are considerations for the creation and content of the laboratory analysis 
data set. Sponsors should follow the ADaM Basic Data Structure (BDS) model when creating 
this data set. Visit windowing and/or inclusion of unscheduled visits should be included in this 
analysis data set (liver-related lab results should be included for all scheduled and unscheduled 
visits). When records are imputed or derived in any manner, the standard ADaM variable, 
DTYPE should be used. All tests and records included in the SDTM.LB domain should be 
carried into the ADLB data set, and sponsors should also include a derived parameter for the 
calculated R value. Sponsors should provide a clear derivation method for their calculation of the 
R value.  
 
It is acceptable for a sponsors ADLB data set to contain additional parameters beyond those 
noted above. Similarly, variables in addition to those described below may be included.    
 
CDER strongly encourages sponsors to identify the laboratory test units that will be reported in 
clinical trials that support applications for investigational new drugs and product registration. 
Although Systeme International (SI) units may be the standard reporting mechanism globally, 
dual reporting of a reasonable subset of laboratory tests in U.S. conventional units and SI units 
27 
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might be necessary to minimize conversion needs during review. Identification of units to be 
used for laboratory tests in clinical trials and solicitation of input from the review divisions 
should occur as early as possible in the development process. If conversion of units is performed, 
the sponsor should clearly indicate the units that the data was originally collected in. For more 
information on CDER/CBER current thinking on conventional units, please see the FDA Study 
Data Technical Conformance Guide available on the FDA Study Data Standards Resources 
webpage. FDA requests laboratory test results be presented in both SI units and US conventional 
units. 
 
The ADLB specifications listed below include four important variables for the analysis of drug-
induced liver injury: DILIBLFL, PEAKFL, REDUCEFL, and ONSETFL. These flags look for 
DILI records at their baseline, peak (maximum post-baseline), washout (50% reduction after 
reaching maximum post-baseline), and onset (first sign of potential DILI). There are many 
different ways to define the onset of liver injury; Sponsors should refer to the existing guidance 
for industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation (July 2009) and seek 
agreement with the FDA review division on how to specify the onset of DILI injury for their 
study.  
 
Table 12. ADLB Variables 
 
Variable Name  Variable Label  Type  Comments 
DILIFL  Drug-Induced  Char  Expected Value: Y or null 
Liver Injury Flag  This flag should have Y for the following records: 
  ALT, AST, ALP, GGT, Total Bilirubin, Direct Bilirubin, INR 
records 
AND 
  The evaluable record for each test at each visit. If more than 
one record is collected at each visit, a derived record should be 
created with DTYPE = AVERAGE. The average record 
should be flagged, and the individual records used to create the 
average record should not be flagged. Unscheduled visits may 
also be flagged as Y.  
Else, null 
ABLFL  Analysis Baseline  Char  Expected Value: Y or null 
Flag  Character indicator to identify the baseline record for each subject and 
parameter. Sponsors should confirm with the FDA review division on 
an appropriate definition for baseline. Examples may include flagging 
the last record prior to treatment or deriving a new baseline record as 
the average of all pre-treatment records for a given subject and 
parameter.  
DILIBLFL  DILI Baseline Flag  Char  Expected Value: Y or null 
For each subject and liver biochemistry parameter, flag the baseline 
record used for DILI analysis as Y. This flag is similar to ABLFL, 
however, in subjects with elevated transaminase levels at enrollment 
who show improvements in their transaminase levels and in essence, 
establish a new lower baseline during the trial, sponsors should use the 
new lower transaminase values in subsequent assessment for potential 
DILI (and subsequently using this flag to identify the record used in 
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Variable Name  Variable Label  Type  Comments 
baseline calculations for DILI analyses). Sponsors should seek review 
division agreement and provide clear guidance in their ADRG or 
define.xml file on derivations for alternate baseline calculations and 
provide a flag in the ADSL to indicate if any subjects have 
discrepancies between ABLFL and DILIBLFL for any liver 
biochemistry parameter.  
DTYPE  Derivation Type  Char  For the case where there are multiple observations and an average or a 
geometric mean will be used for the observation for the visit window in 
the analysis instead of a single selected real observation.  If this is the 
case, a new record should be created, and the records identified by 
having some values for these records in DTYPE variable. The possible 
value could be AVERAGE, or GEOMETRIC, or other meaningful 
values. This should be explained in the define file or SAP. 
R2ANRHI  Ratio to Analysis  Num  Ratio to the upper limit of the analysis range. Equal to AVAL / ANRHI.  
Range Upper Limit 
R2BASE  Ratio to Baseline  Num  Ratio to the baseline value. Equal to AVAL / BASE. If used for a given 
Value  PARAM, should be populated for all post-baseline records of that 
PARAM regardless of whether that record is used for analysis.  
ANL01FL  Analysis Record  Char  Expected Values: Y or null 
Flag 01  Flag the records to be used in analysis. If multiple records are recorded 
for a parameter at the same visit, use this flag to indicate which record 
should be used. Derived records (if it was appropriate to take an average 
of two records) may be flagged as Y. Sponsors should provide a clear 
derivation for how they choose to derive this flag.  
ANL02FL  Analysis Record  Char  Expected Values: Y or null 
Flag 02  Flag the maximum post-baseline record for each subject and parameter 
as Y 
ANL03FL  Analysis Record  Char  Expected Values: Y or null 
Flag 03  Flag the minimum post-baseline record for each subject and parameter 
as Y 
PEAKFL  DILI Peak Flag  Char  Expected Values: Y, N or null 
Null for all pre-treatment records and records where DILIFL = N. If 
ANL02FL = Y and DILIFL = Y, then Y. Otherwise, N 
REDUCEFL  DILI Reduction  Char  Expected Values: Y, N or null 
Flag  Null for all pre-treatment records and records where DILIFL = N. 
Flag the first record after PEAKFL for each subject and parameter in 
which AVAL is equal to or less than 50% of the value of AVAL where 
PEAKFL = Y 
ONSETFL  DILI Lab Onset  Char  Expected Values: Y or null 
Flag  Sponsors should discuss an appropriate definition of DILI onset with 
DHN. The agreed upon definition should be pre-specified in the study 
protocol. Based on the agreed upon definition, flag all DILI records as 
Y at a given visit when the onset trigger has been met.  
For example, if ONSET is determined as the first time a subjects ALT 
or AST value reaches >= 3x ULN with concurrent TB >= 2x ULN 
within 30 days of the ALT or AST elevation, when a subject does reach 
that threshold, all DILI records (ALT, AST, ALP, TB, DB, GGT) from 
that visit should be flagged as Y. 
LASTFL  Last Record Per  Char  Expected Values: Y or null 
Parameter Flag  Flag the last record (max ADY) for each subject and parameter. NOTE: 
this is not limited to last on-treatment record; this may include follow-
up records.  
 
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  Contains Nonbinding Recommendations 
5.2.3.2   Drug Induced Liver Injury Analysis Data Set (ADDILI) 
 
This custom data set will be used to analyze subjects for potential DILI. Sponsors should seek 
agreement with the FDA review division on the appropriate parameters to use for DILI 
assessments. This data set contains variables that seek a maximum value within xx days. 
Sponsors should discuss with the FDA the appropriate time window (e.g., 30 days) to use.  
 
For any subject meeting the sponsor-established criteria for potential DILI, two additional 
parameters should be created  one to provide the outcome and another to provide the action 
taken as a result of potential DILI.  
 
Sponsors may include additional parameters as they see fit and should consult with FDA if the 
review division requires other parameters specific for the review. Additionally, this data set 
includes a set of flag variables that identifies any procedure(s) and/or workups performed to 
evaluate a subject for potential DILI. These flag variables may be derived from the SDTM.PR 
(Procedures), SDTM.LB, or SDTM.MB domains (or other domains as determined by the 
sponsor).  
 
The ADDILI data set should include the basic demographic information, treatment variables, 
start and end date variables, and baseline lab characteristics variables from the ADSL data set.  
 
Table 13. ADDILI Variables 
 
Variable Name  Variable Label  Type  Comments 
PARAM  Parameter  Char  Expected values: Potential DILI and Outcome of Potential 
DILI, Action Taken from Potential DILI 
PARAMCD  Parameter Code  Char 
  For PARAM = Potential DILI: DILI 
  For PARAM = Outcome of Potential DILI  Outcome: 
OUTDILI 
  For PARAM = Action Taken from Potential DILI= 
ACNDILI 
AVAL  Analysis Value  Num  Expected Values: 1 or 0 
Note: The criteria below are example criteria for evaluation of 
DILI. Sponsors may consult the FDA for appropriate criteria 
for their study.  
 
Example 1: PARAMCD = DILI:  
  If ALTULNMX >= 3 and TBALTMX >= 2 and 
ALPALTMX < 2, then 1 OR 
  If ASTULNMX >= 3 and TBASTMX >= 2 and 
ALPASTMX < 2, then 1 
  Else 0 
Example 2: PARAMCD = DILI: 
  If ALPULNMX >= 2 and TBALPMX >= 2, then 1 
30 
  Contains Nonbinding Recommendations 
Variable Name  Variable Label  Type  Comments 
  Else 0 
AVALC  Analysis Value (C)  Char  If AVAL = 1, then Y; if AVAL = 0, then N 
For PARAMCD = OUTDILI 
  Expected values: FATAL, NOT RECOVERED/NOT 
RESOLVED. RECOVERED/RESOLVED, 
RECOVERED/RESOLVED WITH SEQUELAE, 
RECOVERING/RESOLVING, UNKNOWN 
For PARAMCD = ACNDILI: 
  Expected values: DOSE INCREASED, DOSE NOT 
CHANGED, DOSE RATE REDUCED, DOSE 
REDUCED, DRUG INTERRUPTED, DRUG 
WITHDRAWN, NOT APPLICABLE, UNKNOWN 
ALTULNMX  Post-Baseline Maximum  Num  For each subject, ADLB.R2ANRHI where ADLB.PEAKFL = 
Ratio ALT/ULN  Y and ADLB.PARAMCD = ALT 
ALTBLMX  Post-Baseline Maximum  Num  For each subject, ADLB.AVAL where ADLB.PEAKFL = Y 
Ratio ALT/BL  and ADLB.PARAMCD = ALT / ADLB.AVAL where 
ADLB.DILIBL = Y and ADLB.PARAMCD = ALT 
ASTULNMX  Post-Baseline Maximum  Num  For each subject, ADLB.R2ANRHI where ADLB.PEAKFL = 
Ratio AST/ULN  Y and ADLB.PARAMCD = AST 
ASTBLMX  Post-Baseline Maximum  Num  For each subject, ADLB.AVAL where ADLB.PEAKFL = Y 
Ratio AST/BL  and ADLB.PARAMCD = AST / ADLB.AVAL where 
ADLB.DILIBL = Y and ADLB.PARAMCD = AST 
ALPULNMX  Post-Baseline Maximum  Num  For each subject, ADLB.R2ANRHI where ADLB.PEAKFL = 
Ratio ALP/ULN  Y and ADLB.PARAMCD = ALP 
ALPBLMX  Post-Baseline Maximum  Num  For each subject, ADLB.AVAL where ADLB.PEAKFL = Y 
Ratio ALP/BL  and ADLB.PARAMCD = ALP / ADLB.AVAL where 
ADLB.DILIBL = Y and ADLB.PARAMCD = ALP 
TBALTMX  Post-Baseline Maximum  Num  For each subject, max value of ADLB.R2ANRHI where 
Ratio TB/ULN following  ADLB.PARAMCD = TB within xx days after post-baseline 
ALTULNMX  maximum ALT value.  
TBASTMX  Post-Baseline Maximum  Num  For each subject, max value of ADLB.R2ANRHI where 
Ratio TB/ULN following  ADLB.PARAMCD = TB within xx days after post-baseline 
ASTULNMX  maximum AST value.  
TBALPMX  Post-Baseline Maximum  Num  For each subject, max value of ADLB.R2ANRHI where 
Ratio TB/ULN following  ADLB.PARAMCD = TB within xx days after post-baseline 
ALPULNMX  maximum ALP value.  
ALPALTMX  Max ALP/ULN Ratio  Num  For each subject, max value of ADLB.R2ANRHI where 
after Max ALT/ULN  ADLB.PARAMCD = ALP within xx days after post-
Ratio  baseline maximum ALT value. 
ALPASTMX  Max ALP/ULN Ratio  Num  For each subject, max value of ADLB.R2ANRHI where 
after Max AST/ULN  ADLB.PARAMCD = ALP within xx days after post-
Ratio  baseline maximum AST value. 
RVAL  R Value  Num  ADLB.AVAL where ADLB.PARAMCD = R 
DILI Workup Flags 
ALCHFL  Alcohol Assessment Flag  Char  Expected Values: Y, N, or null 
If Alcohol information was collected and reported in the 
SDTM.SU domain as a result of potential DILI injury, then 
Y. If alcohol information was not collected as a result of 
potential DILI injury, then N. If unknown, null 
HEPFL  Hepatitis Serology Flag  Char  Expected Values: Y, N, or null 
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  Contains Nonbinding Recommendations 
Variable Name  Variable Label  Type  Comments 
If Hepatitis Serology information was collected and reported in 
the SDTM.MB domain as a result of potential DILI injury, 
then Y. If Hepatitis Serology information was not collected 
as a result of potential DILI injury, then N. If unknown, null 
AUTOIFL  Auto-Immune Serology  Char  Expected Values: Y, N, or null 
Flag  If Auto-Immune Serology information was collected and 
reported in the SDTM.LB domain as a result of potential DILI 
injury, then Y. If Auto-Immune Serology was not performed 
as a result of potential DILI injury, then N. If unknown, null 
ULTRAFL  Ultrasound Flag  Char  Expected Values: Y, N, or null 
If an ultrasound was performed and reported in the SDTM.PR 
as a result of potential DILI injury, then Y. If an ultrasound 
was not performed as a result of potential DILI injury, then 
N. If unknown, null 
CTFL  CT Scan Flag  Char  Expected Values: Y, N, or null 
If a CT scan was performed and reported in the SDTM.PR as a 
result of potential DILI injury, then Y. If a CT scan was not 
performed as a result of potential DILI injury, then N. If 
unknown, null 
MRIFL  MRI Flag  Char  Expected Values: Y, N, or null 
If an MRI was performed and reported in the SDTM.PR as a 
result of potential DILI injury, then Y. If an MRI was not 
performed as a result of potential DILI injury, then N. If 
unknown, null 
BIOPFL  Biopsy Flag  Char  Expected Values: Y, N, or null 
If a biopsy was conducted and reported in the SDTM.PR as a 
result of potential DILI injury, then Y. If a biopsy was not 
performed as a result of potential DILI injury, then N. If 
unknown, null 
ERCPFL  ERCP Flag  Char  Expected Values: Y, N, or null 
If an ERCP was performed and reported in the SDTM.PR as a 
result of potential DILI injury, then Y. If an ERCP was not 
performed as a result of potential DILI injury, then N. If 
unknown, null 
MRCPFL  MRCP Flag  Char  Expected Values: Y, N, or null 
If a MRCP was performed and reported in the SDTM.PR as a 
result of potential DILI injury, then Y. If a MRCP was not 
performed as a result of potential DILI injury, then N. If 
unknown, null 
LVTRNSFL  Liver Transplant Flag  Char  Expected Values: Y, N, or null 
If a liver transplant was performed and reported in the 
SDTM.PR as a result of potential DILI injury, then Y. If a 
liver transplant was not performed as a result of potential DILI 
injury, then N. If unknown, null 
OTHPRFL  Other Procedure Flag  Char  Expected Values: Y, N, or null 
If another procedure was performed as the result of potential 
DILI injury, then Y. If no other procedure was performed as 
the result of potential DILI injury, then N. If unknown, null 
 
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  Contains Nonbinding Recommendations 
5.2.3.3   Microscopic Findings Analysis Data Set (ADMI) 
 
The Microscopic Findings Analysis Data Set contains histological data used to support accepted 
efficacy determination in noncirrhotic NASH development programs. AVALC is the primary 
variable used to support the analysis. This data set should be derived primarily from the 
Microscopic Findings (SDTM.MI) data set and should contain additional parameters discussed 
with the FDA during the pre-NDA process to assess all histological endpoints. This data set 
follows the ADaM BDS.  
 
The ADMI data set should include the basic demographic information, treatment variables, start 
and end date variables, and baseline biopsy characteristics variables from the ADSL data set.  
 
Table 14. ADMI Variables 
 
Variable Name  Variable Label  Type  Comments 
Biopsy Parameter Information 
PARAM  Parameter  Text  The ADMI data set should contain all records from the SDTM.MI 
domain. In addition, the sponsor should create records with 
parameters to evaluate the histological endpoints, with results 
captured in the appropriate AVAL/AVALC variable.  
 
An example parameter may be: Improvement of Fibrosis Stage with 
No Worsening of NASH. In this case, sponsors should consider the 
results from the Fibrosis Stage and NASH score between the 
baseline and end of treatment biopsies.  
PARAMCD  Parameter Code  Text  Short Code for PARAM. Sponsors may choose an appropriate 
parameter code for the derived parameters that evaluate the 
histological endpoints.  
MITSTDTL  Microscopic  Text  MI.MITSTDTL 
Examination Detail 
PARCAT1  Parameter Category 1  Text  MI.MICAT for records coming from MI data set. For derived 
parameters evaluating histological endpoints, create an appropriate 
category (i.e., Primary histological endpoint, Secondary efficacy 
endpoint, etc.) 
Analysis Information 
AVAL  Analysis Value  Num  Transferred from either MI.MISTRESN or MI.MIORRES 
AVALC  Analysis Value I   Text  Transferred from MI.MISTRESC for character tests (i.e. Definite 
NASH) 
AVALCAT1  Analysis Category 1  Text  It may be appropriate to categorize results of certain tests. For 
example, the sponsor may decide it is important to separate Lobular 
Inflammation results of 0 and 1 from results greater than one. In that 
case, for records with PARAM = Lobular Inflammation, AVALCAT 
would take values of either Lobular Inflammation score 0 to 1 or 
Lobular Inflammation greater than 1. Additional variables may be 
created (AVALCAT2, AVALCAT3, etc.) as necessary.  
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Variable Name  Variable Label  Type  Comments 
Criteria Evaluation 
CRIT1  Analysis Criterion 1  Text  NOTE: This is an example of a criteria that may be used for analysis. 
Specific criterion to include in this data set should be discussed with 
the FDA, as this may change on a study-by-study basis. Should more 
than one criterion be required, used CRIT2/CRIT2FL, 
CRIT3/CRIT3FL, etc.  
Where PARAMCD is HCYTBALL, LOBINF, MODISHAK, 
NASHCRN, NASHHBLN, NLOBI, SAFACT, STEATOS 
indicates criteria of interest as Improvement of histological feature 
by at least 1 point/stage 
CRIT1FL  Criterion 1  Text  Set to Y if CRIT1 satisfied; else set to N 
Evaluation Result 
Flag 
Other Flags 
ABLFL  Analysis Baseline  Text  Set to Y for last non-missing record for each value of PARAMCD 
Flag  prior to TRTSDT 
ANL01FL  Analysis Record Flag  Text  Set to Y for the baseline record and the records closest to the 
01  target day within the visit target interval as defined by the study 
metadata.  
 
5.2.3.4   Non-Invasive Serum Biomarkers of Liver Fibrosis and NASH Analysis 
Data Set (ADRS) 
 
The Non-Invasive Serum Biomarkers of Liver Fibrosis and NASH Analysis Data Set contains 
information to support additional secondary efficacy endpoints based on non-invasive serum 
biomarkers of liver fibrosis and NASH (e.g., MELD, FIB-4, ELF, APRI). The MELD score 
should be provided for noncirrhotic NASH trials. Sponsors should consult with the FDA 
regarding additional tests that may be required for submission.  
 
AVAL is the primary variable used to support the analysis. This data set should be derived 
primarily from the Clinical Classifications and Disease Response (SDTM.RS) data set, though 
many of the tests are calculations based on measurements collected in the Laboratory 
(SDTM.LB) domain. This data set also contains flags based on the results of derived parameters 
in the ADMI data set. This data set follows the ADaM Basic Data Structure (BDS).  
 
The ADRS data set should include the basic demographic information, treatment variables, start 
and end date variables, baseline biopsy characteristics, and non-invasive baseline characteristics 
variables from the ADSL data set.  
 
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Table 15. ADRS Variables 
 
Variable Name  Variable Label  Type  Comments 
Parameter Information 
PARAM  Parameter  Text  The ADRS data set should contain all records from the 
SDTM.RS and SDTM.LB domains for the following example 
tests:  
  MELD Score 
  FIB-4 Score 
  ELF Score 
  APRI Score 
In addition, the sponsor should create records with parameters 
to evaluate the studys endpoints, with results captured in the 
appropriate AVAL/AVALC variable.  
An example parameter may be: MELD Score from Baseline 
=<12 to >15. In this case, sponsors should consider a subjects 
baseline MELD score and their maximum post-baseline record. 
If their baseline record was less than 12 and their maximum 
post-baseline record was greater than or equal to 15, AVALC 
would return a value of Y for this parameter. This is purely 
an example parameter  sponsors should create their own 
parameters in consultation with the FDA review division and 
the endpoints of their study.  
PARAMCD  Parameter Code  Text  Short Code for PARAM 
Analysis Information 
AVAL  Analysis Value  Num  Transferred from either LB.LBSTRESN or RS.RSSTRESN. 
For derived parameters that evaluate a specific endpoint, 1 if 
the endpoint criteria are met or 0 if the endpoint criteria are 
not met.  
AVALC  Analysis Value (C)   Text  Character value of AVAL. For derived parameters that 
evaluate a specific endpoint, AVALC is Y if the endpoint 
criteria are met. Otherwise, null.  
Biopsy Responder Flag(s) 
RESP01FL  First Primary Endpoint  Text  This flag is derived from the ADMI data set. For each derived 
Responder Flag  parameter in ADMI, create one flag (starting with RESP01FL, 
and then RESP02FL, RESP03FL, etc.) that take values of Y 
or N based on whether the subject meets the criteria of the 
derived parameter. For example, if a parameter in ADMI is 
Improvement of Fibrosis Stage with No Worsening of 
NASH and the subject met that criteria in ADMI (AVALC = 
Y), then set RESP01FL = Y. The specific parameter being 
evaluated should be listed in the comments for each parameter 
in define.xml.  
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Variable Name  Variable Label  Type  Comments 
Other Flags 
DTYPE  Derivation Type  Text  If multiple readings are taken at a given visit, create a new 
record if appropriate that takes the average measurements of 
the other records for that parameter at that visit. DTYPE in this 
case would take a value of AVERAGE.  
ABLFL  Analysis Baseline Flag  Text  Set to Y for last non-missing record for each value of 
PARAMCD prior to TRTSDT 
ANL01FL  Analysis Record Flag  Text  Flag records used for analysis. Note: This may differ from 
01  study-to-study, but one example definition may be: Flag 
baseline record and post-baseline records closest to the target 
day within the visit target interval listed in the study metadata.  
Criteria Evaluation 
CRIT1  Analysis Criterion 1  Text  Use this flag to support any derived parameters for this data 
set. For the example parameter listed under PARAM, the 
corresponding CRIT1 may take a value of MELD < 12 
where PARAM = MELD01-Score 
CRIT1FL  Criterion 1 Evaluation  Text  Set to Y if CRIT1 satisfied; else set to N 
Result Flag 
CRIT2  Analysis Criterion 2  Text  Use this flag to support any derived parameters for this data 
set. For the example parameter listed under PARAM, the 
corresponding CRIT1 may take a value of MELD > 15 
where PARAM = MELD01-Score 
CRIT2FL  Criterion 2 Evaluation  Text  Set to Y if CRIT1 satisfied; else set to N 
Result Flag 
 
5.2.4   Time-to-Event Analysis Data Set 
 
The Time to Event Analysis Data Set contains all records needed to support time-to-event 
analysis for noncirrhotic NASH endpoints and DILI. AVAL is the primary variable used to 
support the analysis. Sponsors should follow the ADaM Basic Data Structure for Time-to-Event 
Analyses27 when creating this data set. The description of the analysis parameter (PARAM) 
contains the unit of measurement where results are captured in AVAL.  
 
The time-to-event data set should include records for all subjects, including subjects who did not 
experience an event defined by PARAM. For a subject who did not experience a specific type of 
event, the subjects time to event is considered right-censored, where the value of AVAL 
represents the length of time between the starting point and the end of the observation period 
(e.g., the duration of the study for that subject). The numeric Censor (CNSR) variable is used to 
distinguish whether a subject experienced an event between the defined starting point and the 
end of the observation period. 
 
When supporting analyses as listed in the examples below, ADTTE may be sourced from 
ADAE, ADMI, ADDILI and ADSL (or elsewhere). Sponsors should consult FDA to determine 
 
27 https://www.cdisc.org/standards/foundational/adam/adamig-v1-1-release-package. 
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the appropriate parameters and their corresponding derivations to be collected and submitted in 
this data set.  
 
Sponsors should provide clear explanations in the ADaM define.xml for how AVAL is derived 
for each parameter. In some cases, such as Time to Death, it may look at ASTDY for one record. 
For other parameters where multiple records should be evaluated to determine if the subject has 
met the endpoint, the derivation for AVAL may be more complicated. For example, a Time to 
Peak Lab Washout for DILI parameter needs to consider both when the subjects labs peak as 
well as when those peaks reach a washout statein this case, sponsors could use values of 
ADY when ADLB.PEAKFL and ADLB.REDUCEFL = Y to calculate AVAL in ADTTE.  
 
Examples of applicable analyses to support safety and efficacy analyses may include: 
 
Table 16. Example Time to Event Parameters 
 
PARAMCD  PARAM28, 29  AVAL 
HPCIRRH  Time to Histological Progression to Cirrhosis (days) 
HEPDCE  Time to Hepatic Decompensation Event (days) 
ASCREQTR  Time to Ascites requiring treatment (days) 
Time to Hepatic Encephalopathy at least West Haven grade 2 
HEPENC 
or above requiring hospitalization (days) 
VARHEM  Time to Variceal hemorrhage requiring hospitalization (days)  Propose 
derivations for each 
Time to Other Clinical Decompensation Event (e.g.,  parameter 
OTHCDE 
Spontaneous Bacterial Peritonitis) (days) 
LVRTRNS  Time to Liver Transplant (days) 
DEATH  Time to Death (days) 
ONSETDIL  Time to Onset Potential DILI Injury (days) 
WASHOUT  Time to Peak Lab Washout for DILI (days) 
 
28 Per the ADaM Basic Data Structure for Time-to-Event Analyses, PARAM in the ADTTE may be longer than 40 
characters (maximum 200). See https://www.cdisc.org/standards/foundational/adam/adam-basic-data-structure-bds-
time-event-tte-analyses-v1-0. 
 
29 The examples listed below are measured in days. Sponsors should use their judgement in determining the 
appropriate unit of measurement.  
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APPENDIX 
 
Example ADLB and ADDILI Data Sets 
 
Consider the sample Laboratory Analysis Data Set (ADLB) and Drug-Induced Liver Injury Analysis Data Set (ADDILI) tables below 
for Subject ABC-123. This example only shows one subjects alanine aminotransferase (ALT) values; however, for the purposes of 
this example, assume the subjects aspartate aminotransferase (AST) and/or total bilirubin (TB) values indicate the subject is a 
potential drug-induced liver injury (DILI) candidate as identified by pre-established criteria between the sponsor and the U.S. Food 
and Drug Administration (FDA) (example criteria noted in the ADDILI section of this document). As a reminder, these criteria are 
sample criteria. Sponsors should consult with FDA to establish appropriate criteria to evaluate DILI. Below is a list of other 
considerations for this sample data set: 
 
  In this example, the subject has two pre-baseline lab readings. These lab reading are averaged to create a new baseline record 
for each parameter.  
 
  Onset DILI (ONSETFL = Y) is defined in this example as the first visit in which a subjects ALT > 3x ULN. This happens 
on Study Day 14 (assume ANRHI = 55.0). Sponsors may use their own definition for Onset DILI after consultation with the 
FDA review division.  
 
  Reduced Flag (REDUCEFL = Y) may only occur after a subject has reached their peak (PEAKFL = Y) for a given 
subject and parameter. 
 
  The example ADDILI data set only contains the variables pertinent to ALT; sponsors should follow the guidance provided in 
the ADDILI section of this document for the full list of variables to be provided. 
 
  For the example ADDILI data set, ALTULNMX is calculated as the maximum post-baseline ALT value divided by the upper 
limit of normal (197.0 / 55.0 = 3.58). ALTBLMX is calculated as the maximum post-baseline ALT value divided by the DILI 
baseline value (197.0 / 52.5 = 3.75).  
 
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Table A. Subset of Sample ADLB 
 
PARAMCD  AVAL  BASE  ADY  ABLFL  ANL02FL  ANL03FL  PEAKFL  REDUCEFL  ONSETFL  LASTFL 
ALT  51.0    -8               
ALT  54.0    1               
ALT  52.5      Y             
ALT  95.0  52.5  7        N  N     
ALT  197.0  52.5  14    Y    Y  N  Y   
ALT  191.0  52.5  21        N  N     
ALT  92.0  52.5  28        N  Y     
ALT  73.0  52.5  35      Y  N  N    Y 
 
Table B. Subset of Sample ADDILI 
 
PARAM  AVALC  ALTULNMX  ALTBLMX 
Potential DILI  Y  3.58  3.75 
Outcome of Potential DILI  RECOVERED/RESOLVED  3.58  3.75 
Action Taken from Potential DILI  DOSE REDUCED  3.58  3.75 
 
Example MI and SUPPMI Domains 
 
Consider the sample Microscopic Findings (MI) and Supplemental Microscopic Findings (SUPPMI) domains below for Subject ABC-
123. This subject has two biopsies, one at baseline and one at end of treatment, each with two Pathologists reviewing. Any disagreement 
between the histopathological assessment between the Pathologists results in an adjudication committee making a final determination 
(as shown with Microscopic Findings Test (MITEST) = FIBROSIS during the first biopsy). The data set should also include standard 
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variables such as STUDYID, DOMAIN, MIDTC, and MIDY as noted in the SDTM Implementation Guide.1 The sample below only 
contains a few measurements; sponsors should refer to the MI section of this document for the complete list of recommended and 
permissible parameters to be collected from the biopsy.  
 
This example domain uses MIREFID as the identifier for the slide being analyzed, but sponsors should use identifier variables 
available from the SDTMIG to label biopsies and slides cut from the biopsy. The linkage between the identifier variables should be 
made clear in the define.xml and/or Study Data Reviewers Guide (SDRG) files. Linkages between individual biopsies and/or slides 
and other domains such as Biospecimen Findings (BS) or Biospecimen Events (BE) should be connected via a RELREC domain.  
 
The SUPPMI domain shows the adequacy of the slides. The slide evaluated during the baseline biopsy was deemed adequate, and the 
end of treatment biopsy was deemed not adequate due to both a blurred image and cracked slide. As such, the MIACPTFL variable is 
null for the end of treatment biopsy as these records were not accepted for the analysis due to the inadequate slide.  
 
Table C. Subset of Sample MI Domain 
 
MIREFID  MITEST  MITSTDTL  MIORRES  MIACPTFL  MIEVAL  MIEVALID  VISIT 
SPEC001  NAFLD Activity Score  TOTAL SCORE  5    PATHOLOGIST  PATHOLOGIST 1  BASELINE 
SPEC001  Fibrosis  NASH CRN FIBROSIS STAGE  Moderate zone 3    PATHOLOGIST  PATHOLOGIST 1  BASELINE 
SPEC001  NAFLD Activity Score  TOTAL SCORE  5    PATHOLOGIST  PATHOLOGIST 2  BASELINE 
SPEC001  Fibrosis  NASH CRN FIBROSIS STAGE  Mild zone 3    PATHOLOGIST  PATHOLOGIST 2  BASELINE 
ADJUDICATION 
SPEC001  NAFLD Activity Score  TOTAL SCORE  5  Y  ADJUDICATOR  BASELINE 
COMMITTEE 
ADJUDICATION 
SPEC001  Fibrosis  NASH CRN FIBROSIS STAGE  Moderate zone 3  Y  ADJUDICATOR  BASELINE 
COMMITTEE 
END OF 
SPEC002  NAFLD Activity Score  TOTAL SCORE  5    PATHOLOGIST  PATHOLOGIST 1 
TREATMENT 
 
1 Available at https://www.cdisc.org/standards/foundational/sdtmig/sdtmig-v3-3.  
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MIREFID  MITEST  MITSTDTL  MIORRES  MIACPTFL  MIEVAL  MIEVALID  VISIT 
END OF 
SPEC002  Fibrosis  NASH CRN FIBROSIS STAGE  Mild zone 3    PATHOLOGIST  PATHOLOGIST 1 
TREATMENT 
END OF 
SPEC002  NAFLD Activity Score  TOTAL SCORE  5    PATHOLOGIST  PATHOLOGIST 2 
TREATMENT 
END OF 
SPEC002  Fibrosis  NASH CRN FIBROSIS STAGE  Mild zone 3    PATHOLOGIST  PATHOLOGIST 2 
TREATMENT 
 
Table D. Subset of Sample SUPPMI Domain 
 
IDVAR  IDVARVAL  QLABEL  QVAL 
MIREFID  SPEC001  Overall Image Quality   Adequate 
MIREFID  SPEC002  Overall Image Quality   Not Adequate 
MIREFID  SPEC002  Image Condition  MULTIPLE 
MIREFID  SPEC002  Image Condition 1  CRACKED SLIDE 
MIREFID  SPEC002  Image Condition 2  BLURRY IMAGE 
 
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