Virology Therapeutic Area
Data Standards
User Guide (VR-UG)
Prepared by the
CDISC Virology Team
Notes to Readers


This provisional user guide is based upon the forthcoming Version 1.4 of the CDISC Study Data
Tabulation Model and the CDISC Pharmacogenomic/Genetics Study Data Tabulation Model
Implementation Guide (SDTMIG-PGx), currently under development.
See Appendix C for Representations and Warranties, Limitations of Liability, and Disclaimers.
Revision History
Date
September 6, 2012
December 6, 2012
Version
1.0 Draft
1.0 Provisional
Summary of Changes
Released version for public comment.
Released version reflecting all changes and correction identified during
the comment period.
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
CDISC Virology User Guide (Version 1.0)
TABLE OF CONTENTS
1
INTRODUCTION ................................................................................................................................................1
1.1 PURPOSE .......................................................................................................................................................1
1.2 CDER GUIDANCE ON ANTIVIRAL PRODUCT DEVELOPMENT .........................................................1
1.3 RELATIONSHIP TO PRIOR DOCUMENTS................................................................................................ 2
1.4 ORGANIZATION OF THIS DOCUMENT ...................................................................................................2
1.5 DESIGN CONSIDERATIONS AND APPROACH .......................................................................................2
2
RELATIONSHIPS BETWEEN THE PHARMACOGENOMICS/GENETICS (PGX) AND
BIOSPECIMEN DOMAINS ............................................................................................................................... 4
2.1 RELATIONSHIPS BETWEEN MOLECULAR CONCEPTS .......................................................................6
3
VIRAL RESISTANCE FINDINGS (VR) ...........................................................................................................8
3.1 ASSUMPTIONS FOR VIRAL RESISTANCE TEST FINDINGS (VR) DOMAIN MODEL ..................... 11
3.2 EXAMPLES FOR VIRAL RESISTANCE TEST FINDINGS (VR) DOMAIN MODEL ........................... 11
4
PHARMACOGENOMICS FINDINGS (PF) ................................................................................................... 14
4.1 ASSUMPTIONS FOR PHARMACOGENOMICS TEST FINDINGS (PF) DOMAIN MODEL ................ 17
4.2 GENETIC VARIATION ASSUMPTIONS .................................................................................................. 17
4.3 EXPLANATORY NOTES ON SLC DATABASE GENETIC CODES ...................................................... 18
4.4 EXAMPLES FOR VIRAL GENETICS FINDINGS .................................................................................... 18
5
PHARMACOGENOMICS/GENETICS METHODS AND SUPPORTING INFORMATION (PG) ......... 26
5.1 ASSUMPTIONS FOR PHARMACOGENOMICS (PG) DOMAIN MODEL ............................................. 30
5.2 LIST OF IDENTIFIED COMMON SUPPQUALS ...................................................................................... 30
5.3 EXAMPLES OF TESTCDS FOR REFERENCING PUBLIC DATABASES ............................................. 31
5.4 PG EXAMPLES ............................................................................................................................................ 31
6
PGX BIOLOGICAL STATE (PB) .................................................................................................................... 33
6.1 ASSUMPTIONS FOR THE PGX BIOLOGICAL STATE (PB) DOMAIN MODEL ................................. 34
6.2 EXAMPLES FOR PGX BIOLOGICAL STATE (PB) DOMAIN MODEL................................................. 34
7
SUBJECT BIOLOGICAL STATE (SB) .......................................................................................................... 35
7.1 ASSUMPTIONS FOR THE SUBJECT BIOLOGICAL STATE MARKER (SB) DOMAIN MODEL ...... 36
7.2 EXAMPLES FOR SUBJECT BIOLOGICAL STATE MARKER (SB) DOMAIN MODEL ...................... 36
APPENDIX A – NEW AND DELETED DOMAINS AND VARIABLES ............................................................ 38
APPENDIX B – VIROLOGY CONCEPT MAPS .................................................................................................. 39
B.1 VIROLOGY RESISTANCE TESTING MAPS ............................................................................................ 39
B. 2 GENETIC TESTING .................................................................................................................................... 40
B. 3 BUILDING KNOWLEDGE OF VIRAL RESISTANCE MUTATION ...................................................... 42
B. 4 INFERRING VIRAL RESISTANCE FROM GENETIC MUTATION RESULTS .................................... 43
APPENDIX C – PARTICIPATING INDIVIDUALS AND ORGANIZATIONS ................................................ 44
APPENDIX D – REPRESENTATIONS AND WARRANTIES, LIMITATIONS OF LIABILITY, AND
DISCLAIMERS .................................................................................................................................................. 45
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LIST OF TABLES
VR.xpt, Pharmacogenomics Findings - one record per viral load observation per specimen collected, per test, per
date of test, per subject, tabulation. ............................................................................................................................... 8
PF.xpt, Pharmacogenomics Findings - one record per method/setup observation per specimen collected, per date of
test, per subject, Tabulation ......................................................................................................................................... 14
PG.xpt, Pharmacogenomics — Findings. One record per method/setup observation per specimen collected, per date
of test, per subject, Tabulation ..................................................................................................................................... 26
PB.xpt, Pharmacogenomics Biological State - Special Purpose Domain. One record per biomarker used in the study,
tabulation. .................................................................................................................................................................... 33
SB.xpt, Subject Biological State – Special-Purpose Domain. One record per subject per observed biological state in
the study, tabulation. .................................................................................................................................................... 35
LIST OF FIGURES
Figure 1: Biologic Specimen Natural Hierarchy ..........................................................................................................5
Figure 2: Relationships Between Molecular Concepts .................................................................................................7
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1
INTRODUCTION
1.1
PURPOSE
The purpose of this provisional Virology Therapeutic Data Standards Area User Guide (VR-UG) is to
provide guidance on the implementation of the Study Data Tabulation Model (SDTM) data standards for
virology data. This provisional virology user guide is designed to be used in concert with the SDTM model,
the SDTMIG-PGx (currently under development) and the SDTMIG. See paragraph four below and section
1.3 for more information.
This is the first attempt by CDISC to develop submission standards for virology-focused clinical trials, so it
is expected that there will be areas for further development. This user guide is dependent upon the
publication of Version 1.4 of the SDTM. Due to these reasons, the CDISC Virology Team is publishing
this supplement as provisional in order to allow time for completion of the new version of the SDTM and to
collect input from implementers.
The measurement of viral concentration is central to virology studies. The measurement of viral
concentration (i.e., viral load, a measure of disease burden) in specimens from subjects is handled via the
existing SDTM LB domain. This guide provides guidance on handling measurements of viral concentration
from in vitro resistance testing. Virology studies may also record viral genetic variations, and relate these to
changes in antiviral drug resistance and susceptibility. To this end, this VR-UG includes the following draft
domains:
1.
2.
3.
4.
5.
Viral Resistance (VR) - This new Findings domain is for data on viral resistance obtained by growing
a virus in culture in the presence of a drug and then quantifying the viral response to the drug.
Pharmacogenomics/Genetics Methods and Supporting Information (PG) - This updated Findings
domain describes new SDTM variables and stores information about the test methodology that collects
the set-up and quality control of the test. This contributes to the understanding of the test results
contained in the Pharmacogenomics Findings (PF) domain.
Pharmacogenomics Findings (PF) - This updated Findings domain includes new SDTM variables, and
is for the submission of results of genetic variations and gene expression.
PGx Biological State (PB) - This new Special-Purpose domain is a reference dataset that relates a set
of genetic variations to an inference about the medical meaning of the set of genetic variations.
Subject Biological State (SB) - This new Special-Purpose domain holds the medical statement from the
PB domain for individual subjects. Through the use of the PB and SB domain a mechanism is provided
to stay aligned with current medical knowledge.
A Pharmacogenomic/Genetics Study Data Tabulation Model Implementation Guide (SDTMIG-PGx) is
currently under development. This document will describe how to represent genetic data collected on
samples of DNA and RNA in SDTM-based format. The SDTMIG-PGx is envisioned to describe how to
accommodate genetic information from humans as well as from viruses, bacteria, and other
microorganisms including genetic variation and gene expression. Members of the user community are
encouraged to participate in the vetting of the SDTMIG-PGx standards.
1.2
CDER GUIDANCE ON ANTIVIRAL PRODUCT DEVELOPMENT
Implementers who intend to submit data to FDA are strongly encouraged to review current CDER guidance
documents related to the submission of antiviral drug resistance data, such as the CDER Draft Guidance on
Antiviral Product Development -Conducting and Submitting Virology Studies to the Agency – Guidance
for Submitting HCV Resistance Data (January 2012) and Guidance for Submitting HIV Resistance Data
(June 2012).
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1.3
RELATIONSHIP TO PRIOR DOCUMENTS
This document does not replace any of the standards defined in the current Study Data Tabulation Model
Implementation for Human Clinical Trials (SDTMIG) or other implementation guides to the SDTM. When
used for clinical trials data, this SDTM supplement should be implemented together with the current
version of the SDTMIG (available at http://www.cdisc.org/standards). The SDTMIG is based on the
general SDTM conceptual model for representing clinical study data that is submitted to regulatory
authorities and should be read prior to reading the VR-UG v.1.0. An understanding of both of these
documents is needed before attempting to understand this virology addendum.
1.4
ORGANIZATION OF THIS DOCUMENT
This document contains information on how to format tabulation data for the purpose of submission. While
the document is self-contained with respect to virology-specific information, the domains were designed to
work in concert with existing SDTM model constructs. This document has been organized into the
following sections:
 Section 1: Introduction - This section provides an orientation to this document.
 Section 2: Relationships Between the Pharmacogenomics/Genetics (PGx) and Biospecimen
Domains (BE, BS) - Provides an overview of the new domains and their relationship to each other as
well as to existing domains described in the SDTMIG.
 Section 3: Viral Resistance Findings (VR) - Describes the domain, assumptions and examples for
viral resitance findings
 Section 4: Pharmacogenomics Findings (PF) - Describes the PF domain and includes domain
models, assumptions, and examples.
 Section 5: Pharmacogenomics/Genetics Methods and Supporting Information (PG) - Describes
proposed new virology and updated PGx domains and assumptions for inclusion in a future SDTM
based implementation guide.
 Section 6: PGx Biological State (PB) - Describes the domain, assumptions, and examples for a
reference dataset of biomarkers.
 Section 7: Subject Biological State (SB) - Describes the domain, assumptions, and examples for
subject-level biomarker data.
 Appendices - Contains a table of new and deleted SDTM variables, a list of participating
organizations, and legal notices.
1.5
DESIGN CONSIDERATIONS AND APPROACH
The purpose of this section is to review the design approach and lessons learned by mapping complex PGx
and virology data. This section also serves to document issues encountered during the development process
and their respective resolutions.
1.
2.
3.
4.
5.
The initial approach was to represent genetic variation data by using the HUGO Nomenclature
(HGNC). An example HUGO representation of example a codon-level mutation is c.28CTC>ATC,
which means that at position 28 of the DNA sequence where the expected nucleotide sequence is
"CTC" the sequence "ATC" was observed.
During an early review, FDA reviewer participants asked that these data be parsed out into expected
nucleotide (CTC), position (28), and observed nucleotide (ATC).
An earlier design handled the position, expected nucleotide, observed nucleotide, and a number of
other test characteristics in separate rows. This design required variables to group rows together and
also resulted in very large files.
Given the challenges with the multi-row design, a different structure was proposed, and new variables
were added, so that the multiple results obtained for what was really a single test could be represented
in a single row.
The representation of codon changes and amino acid changes were considered to be separate results
and should be submitted as separate rows.
SPECIES and STRAIN were added to the domains to allow for the separation of genetic and genomic
data from pathogens, such as viruses (that are the subject of this user guide) from genetic data on their
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6.
7.
8.
human hosts (whose species and stain, if not human, would be submitted in the Demographics
domain).
It was suggested that SUBSTRAIN and CLADE be added to the domains. However, because of
ambiguous definitions and because the hierarchy used seems to differ, these potential additions were
deferred until a future version.
Representing viral resistance data in an SDTM-based domain model is a challenge. An initial attempt
was made to model these data in the Microbiology domains, but this approach was abandoned because
the current MB/MS domain structures are limited to resistance based on only one result. Virology data,
on the other hand, includes multiple results, and a net assessment that summarizes these results. The
use of the LB domain, which already includes examples of viral test data, was next considered but this
approach was felt to create too high a burden for creating test codes which would have included the
virus as part of the test name. After considering these alternatives, the team chose to create a Viral
Resistance (VR) domain that includes the species and strain variables, eliminating the need to maintain
pathogen-specific test names.
A draft SDTMIG-PGx document underwent public review in 2010. The need for new examples and
domains was identified to better document the PGx Biological State (PB) and Subject Biological State
(SB). These domains are included in draft form in this VR-UG and will be included SDTMIG-PGx
that is currently under development.
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2
RELATIONSHIPS BETWEEN THE
PHARMACOGENOMICS/GENETICS (PGX)
AND BIOSPECIMEN DOMAINS
The section explains the concepts and relationships between the two PGx domains (PG and PF) in this
guide and the three biospecimen domains (BE, BS, ES) that will be included in the forthcoming SDTMIGPGx. These domains support specimen re-sectioning (when a portion of a specimen is tested) or specimen
extraction (when a genetic sample such as RNA or DNA is extracted for genetic/genomic testing).
1. In the top left corner of Figure 1 is the Biospecimen Events (BE) domain that is used to capture the
date/time of important steps within the specimen handling process. Examples include the following:
- Date/time specimen was sent to a lab
- Date/time specimen was received by a lab
- Date/time and duration for flash freezing and/or thawing of the specimen
2. Next in line after BE is the Biospecimen Handling domain (BS) that contains the details regarding
biospecimen handling. Examples include specimen volume, flash-frozen temperature, preservative
type, preservative volume, stabilizing reagent, and stabilizing reagent volume.
3. The Extracted Sample (ES) domain stores information regarding materials extracted from sample such
as RNA or DNA from a blood or tissue sample. It may also contain information about resections
obtained from a biospecimen (e.g., RNA/DNA quantity extracted, genetic material extract, and PGx
specimen condition).
4. The results of PGx tests tend to be sensitive to the degree of adherence to the specimen handling and
test-setup processes specified in the test protocol. Therefore, additional quality control (QC)
observations are captured to document compliance to proper procedures. Knowledge of the setup
processes also contributes to improved understanding of the test results. Therefore, a two-domain
structure was developed, in which setup and QC observations are stored separately from test results.
The former are stored in the Pharmacogenomics/Genetics Methods and Supporting Information (PG)
domain (also described as the PG Setup and QC domain for brevity), while results are stored in the
Pharmacogenomics Findings (PF) domain. This separation allows PG set up and QC to appear once,
and be related to multiple pharmacogenomic findings. Examples include the following:
 For Gene Expression: Normalization Technique, RNA Integrity Number, A260/A230 ratio,
and A260/A280 ratio.
 For Genetic Variation (Genotype / SNP Probe): exons sequenced, sequence start, and
sequence length.
5. The PGx Findings (PF) domain contains the results of genetic variation and gene expression tests. For
genetic variation tests, test results may include portions of the genetic sequence and comparisons with
reference gene sequence.
6. Linking between these five domains is accomplished by means of SDTM identifiers (STUDYID,
LNKID, and REFID).
7. The PGx Biological State (PB) (Reported Medical Condition Associations) domain is a specialpurpose domain that documents known associations between observed variations and medical
conclusions (e.g., disease diagnosis, resistance of a virus to a particular drug).
8. The Subject Biological State (SB) (Subject Medical Condition Associations) domain applies
associations documented in PB to observed subject variation and mutation data in PF to document
medical conclusions for individual subjects.
There are many genetic tests that involve the comparison of subject data to a published database. Under
certain circumstances, a test may be re-evaluated against different versions of the published database. That
being the case, there is a need for additional linking is needed. To accomplish this, records in the PF
domain should use the LINKID to connect to the record in the PG domain that documents the reference
database used. Examples of this linking will be included in the forthcoming SDTMIG-PGx. The diagram
below describes the high-level hierarchy that links these domains starting with the biologic specimen.
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Figure 1: Biologic Specimen Natural Hierarchy
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2.1
RELATIONSHIPS BETWEEN MOLECULAR CONCEPTS
Figure 2 below shows an example of how the relationships from the collected specimen to the results can
be represented.
1.
2.
3.
4.
5.
The Biospecimen Handling domain (BS), which is described in the forthcoming SDTMIG-PGx,
contains information about the collected specimen. For example, this could be a collected tissue from a
normal or cancerous section of an organ. ABC-004 is the specimen identifier held in BSREFID. There
were no Biospecimen Events of interest in the example, so the BE domain is not included.
The Extracted Specimen domain (ES) (also described in the SDTMIG-PGx) shows the identifier
assigned to the genetic sample such as DNA once it is extracted. This domain would contain identifiers
for both the collected tissue sample and the extracted genetic sample.
Tests reported in the Pharmacogenomics Findings domain (PF) are linked to the specimen on which
they were run by means of the extracted specimen identifier (e.g. ABC-004-01), which is stored in
PFREFID, which is the same value in ESSPID.
The gene (in PFGENROI) is then associated with the amino acids that have been detected and
identified in rows containing a PFTESTCD value of AAOBS for the observed amino acid and
GENLOC for the position.
The amino acid can then be associated to the actual variation or mutation either represented as a codon
(with three nucleotides) or as individual nucleotides with their respective positions. PFRESCAT
qualifies the result in ORRES and STRESC (e.g., point mutation).
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Figure 2: Relationships Between Molecular Concepts
Relationships Among Molecular
Concepts in Virology Examples
BS.REFID
ABC-004
[Specimen]
1:M
Hierarchy is mostly one
to many except between
Amino Acids and
Codons
ES.SPID
ABC-004-01
[Genetic Material
Such as DNA]
1:M
PF.REFID
ABC-004-01
[DNA}
1:M
PF
GENTYP = GENE
GENROI = GENEID
[Gene]
1:M
PF
TESTCD = AA
[Amino Acid]
AA=I
GENLOC=71
PF
GENLOC
213
[Codon]
1:1
PFTESTCD=CDN
PFORRES= ATT
PFREFRES=GTT
PF
PFSPID
GENLOC=213
GENLOC=214
GENLOC=215
1:M
Nucleotide
TESTCD = NUC
ORRES =
A
ORRES =
A
ORRES =
T
RESCAT = “Point
Mutation”
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3
VIRAL RESISTANCE FINDINGS (VR)
VR.xpt, Pharmacogenomics Findings - one record per viral load observation per specimen collected, per test, per date of test, per subject, tabulation.
Variable Name
Variable Label
STUDYID
DOMAIN
Study Identifier
Domain Abbreviation
USUBJID
Controlled
Terms or
Format
Type
CDISC Notes
Core
Identifier
Identifier
Definition: Unique identifier for a study within the submission.
Definition: Two-character abbreviation for the domain most relevant to the
observation.
Req
Req
Unique Subject Identifier Char
Identifier
Definition: Unique subject identifier within the submission.
Req
VRSEQ
Sequence Number
Num
Identifier
Definition: Sequence number given to ensure uniqueness within a dataset for a
subject. Can be used to join related records.
Req
VRGRPID
Group ID
Char
Identifier
VRREFID
VRLNKID
VRASYID
VRTESTCD
Specimen ID
Link ID
Assay ID
Genomics Test Code
Char
Char
Char
Char
*
VRTEST
Char
*
Char
*
VRGENTYP
Pharmacogenomics Test
Description
Test Reference
Terminology Code
Test Reference
Terminology Name
Test Reference
Terminology Version
Gene Type
VRGENROI
Gene Region of Interest Char
VRSPCIES
Biological Classification Char
*
VRSTRAIN
Type of Strain
Char
*
VRCAT
Category for
Char
Pharmacogenomics Lab
Test
*
VRTSTRCD
VRTSTRNM
VRTSTRVR
Char
Char
Role
**VR
Char
Char
Char
Definition: Used to tie together a block of related records in a single domain to
support relationships within the domain and between domains.
Identifier
Definition: The identifier of the viral specimen being tested.
Identifier
Definition: Supports linking information across different domains
Identifier
Definition: A unique identifier for a test as maintained by a lab.
Topic
Definition: Short name for the test.
Examples: IC50T, IC50R
Synonym
Definition: The verbatim name used to obtain the measurement or finding.
Qualifier
Examples: IC50 result on treatment, IC50 fold change from baseline.
Result Qualifier Definition: The code of the result. For example; R is the code for Arginine and
C49488 is the code for Y.
Result Qualifier Definition: The name of the Reference Terminology for the result. For example;
CDISC, SNOMED, LOINC.
Result Qualifier Definition: The version number of the Reference Terminology, if required.
Perm
Result Qualifier Definition: Identifies the type of genetic region of interest, for example,
GENENAME, SECTOR, PROTEIN.
Record
Area within the DNA sequences.
Qualifier
Example: Protease (in the case of HIV), NS3/4A, NS5B (in the case of HCV).
Grouping
Definition: Biological classifications for an organism capable of breeding and
Qualifier
producing offspring. May also be used to designate organisms.
Example: HOMO SAPIENS, RAT, MOUSE, BACTERIUM, HCV, HIV
Grouping
Definition: A genetic variant or subtype of a micro-organism.
Qualifier
Examples: 1a, 1b.
Grouping
Definition: Used to categorize types of viral resistance tests.
Qualifier
Exp
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Perm
Perm
Perm
Req
Req
Perm
Perm
Perm
Exp
Perm
Perm
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Variable Name
VRSCAT
VRDRUG
Variable Label
Controlled
Terms or
Format
Type
Subcategory for
Char
Pharmacogenomics Lab
Test
Drug Name
Char
*
Role
Grouping
Qualifier
CDISC Notes
Core
Definition: A further categorization of the various test types based on particular Perm
characteristics of a test.
Record
Qualifier
Definition: the name of the drug for which resistance is based on genetic
biological markers.
Examples: Saquinavir, Indinavir
Result Qualifier Definition: Result of the measurement or finding as originally received or
collected.
Example: For this domain the results are generally numeric/char value as
provided by the laboratory.
Variable
Definition: Represents the unit of measure used by VRORRES if applicable.
Qualifier
Example: copies/5uL, LOG10 IU/mL
Exp
Result Qualifier Definition: Provides information such as the gene being tested for genotyping
tests as well as interpretations and other supporting information such as
insertions and deletions or intensity and P-Value for Array tests.
Example for CDNOBS:
AGC
Result Qualifier Definition: Used for continuous or numeric results or findings in standard
format; copied in numeric format from VRSTRESC. VRSTRESN should store
all numeric test results or findings.
Example for p-Value: 0.5391
Variable
Definition: Represents the unit of measure used by VRSTRESN.
Qualifier
Exp
Record
Qualifier
Definition: Used to indicate exam not done. Should be null if a result exists in
VRSTRESC.
Perm
Exp
VRORRES
Result or Finding in
Original Units
Char
VRORRESU
Original Units
Char
VRSTRESC
Character Result/Finding Char
in Std Format
VRSTRESN
Numeric Result/Finding Num
in Standard Units
VRSTRESU
Standard Units
Char
*
VRSTAT
Pharmacogenomics
Status
Char
(ND)
VRREASND
Reason Test Not Done
Char
Record
Qualifier
VRXFN
Raw Data File or LSID Char
Record
Qualifier
VRNAM
Vendor Name
Char
Record
Qualifier
Definition: Describes why a measurement or test was not performed such as
Perm
BROKEN EQUIPMENT, SUBJECT REFUSED, or SPECIMEN LOST. Used in
conjunction with VRSTAT when value is NOT DONE.
Definition: Direct reference identifier for Microarray or Genotypic data
Perm
contained in a separate file in its native format.
Life Sciences Identifier (LSID)
Definition: Name or identifier of the laboratory or biotech firm that provided the Perm
test results.
VRSPEC
Specimen Type
Char
Record
Qualifier
Definition: Defines the type of specimen used for a measurement.
Examples: TISSUE, SERUM, PLASMA, TUMOR, DNA, RNA
Perm
VRSPCCND
Specimen Condition
Char
Record
Qualifier
Definition: Free or standardized text describing the condition of the specimen.
Example: HEMOLYZED, ICTERIC, LIPEMIC, FRESH, FROZEN,
PARAFFIN-EMBEDDED etc.
Perm
(UNIT)
*
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Exp
Exp
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Variable Name
Variable Label
Controlled
Terms or
Format
Type
Role
CDISC Notes
Core
VRMETHOD
Method Code for Test
Char
*
Record
Qualifier
Definition: Special instructions for the execution of genomics or genetic testing. Req
Examples: PhenoSense GT
VRBLFL
Baseline Flag
Char
(NY)
Definition: Indicator used to identify a baseline value,
Perm
VRDRVFL
Derived Flag
Char
(NY)
Definition: Used to indicate a derived record.
Perm
VISITNUM
Visit Number
Num
Record
Qualifier
Record
Qualifier
Timing
Exp
VISIT
Visit Name
Char
Timing
VISITDY
Num
Timing
VRDTC
Planned Study Day of
Visit
Date/Time of Test
VRDY
Study Day of Test
Num
Timing
VRTPT
Planned Time Point
Name
Char
Timing
VRTPTNUM
Planned Time Point
Number
Elapsed Time from
Reference Point
Num
Timing
Definition:
1. Clinical encounter number.
2. Numeric version of VISIT, used for sorting.
Definition:
1.Protocol-defined description of clinical Encounter
2.May be used in addition to VISIT and VISITDY.
Definition: Planned study day of the visit based upon RFSTDTC in
Demographics.
Definition:
Date/time of specimen collection
Definition:
1. Study day of specimen collection, measured as integer days.
2. Algorithm for calculations must be relative to the sponsor-defined RFSTDTC
variable in Demographics. This formula should be consistent across the
submission.
Definition:
1.Text Description of time when specimen should be taken.
2. This may be represented as an elapsed time relative to a fixed reference point,
such as time of last dose. See VRTPTNUM and VRTPTREF.
Examples: Start, 5 min post.
Numerical version of VRTPT to aid in sorting.
Time Point Reference
Char
VRELTM
VRTPTREF
Char
Char
ISO 8601
ISO 8601
Timing
Timing
Timing
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Perm
Perm
Exp
Perm
Perm
Perm
Definition: Elapsed time (in ISO 8601) relative to a planned fixed reference
Perm
(VRTPTREF). This variable is useful where there are repetitive measures. Not a
clock time or a date time variable.
Examples: '-P15M' to represent the period of 15 minutes prior to the reference
point indicated by VRTPTREF, or 'P8H' to represent the period of 8 hours after
the reference point indicated by VRTPTREF.
Definition: Name of the fixed reference point referred to by VRELTM,
Perm
VRTPTNUM, and VRTPT.
Examples: PREVIOUS DOSE, PREVIOUS MEAL.
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CDISC Virology User Guide (Version 1.0)
Variable Name
VRRFTDTC
3.1
Type
Date/Time of Reference Char
Time Point
Controlled
Terms or
Role
Format
ISO 8601
Timing
CDISC Notes
Date/time of the reference time point, VRTPTREF.
Core
Perm
ASSUMPTIONS FOR VIRAL RESISTANCE TEST FINDINGS (VR) DOMAIN MODEL
1.
2.
3.
3.2
Variable Label
This domain is for data on viral resistance obtained by growing virus in culture in the presence of a drug and then quantifying virus (e.g. measuring
“viral load”). This is distinct from “viral load” measured on samples taken directly on a study subject to measure the status of the virus within the
subject that would be submitted in the LB domain. It is also distinct from genetic testing performed to detect viral variations and infer viral
resistance from variations; that data is stored in PF (see Example 4 in Section 4.6 of this supplement).
This domain is for clinical and pre-clinical use.
Viral resistance is determined by exposing the amplified virus in isolation (in vitro) to an anti-viral drug and then deriving from the raw viral load
values for each concentration the inhibitory concentrations (ICs) for various proportions of virus. For instance the IC50 is a concentration that limits
growth to 50% of what is seen for virus grown without drug. These inhibitory concentrations for a sample taken from a study subject may be
compared with inhibitory concentrations for a control strain of virus, usually a “wild type”, susceptible to the drug in question. The ratio of
inhibitory concentration for study subject virus and control virus is called a “fold increase.” All these measures may be considered in reaching an
overall assessment of the virus’s resistance to the drug.
EXAMPLES FOR VIRAL RESISTANCE TEST FINDINGS (VR) DOMAIN MODEL
Example 1: This HIV example shows that viral concentrations are measured after exposure to specified concentrations to determine levels of
susceptibility.. This example compares the subject’s specimen’s culture measurements to those of a control sample. A similar comparison could be made
to a baseline measurement for the subject.
In these examples, Rows 1-7 pertain to resistance to Drug A and Rows 8-14 pertain to resistance to Drug B.





Rows 1 and 8 show the response of the virus extracted from the subject based on drug concentrations expected to produce 50% inhibition of the
standard virus growth.
Rows 2 and 9 show a control viral sample response based on drug concentrations expected to produce 50% inhibition of the standard virus
growth.
Rows 3 and 10 show the fold change of the response of the virus extracted from the subject from control viral sample response based on drug
concentrations expected to produce 50% inhibition of the standard virus growth. This is the on-treatment result divided by the reference result.
Rows 4 and 11 show the response of the virus extracted from the subject based on drug concentrations expected to produce 95% inhibition of
the standard virus growth.
Rows 5 and 12 show a control viral sample response based on drug concentrations expected to produce 95% inhibition of the standard virus
growth.
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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CDISC Virology User Guide (Version 1.0)


Rows 6 and 13 show the fold change of the response of the virus extracted from the subject from control viral sample response based on drug
concentrations expected to produce 95% inhibition of the standard virus growth. This is the on-treatment result divided by the reference result.
Rows 7 and 14 show the net assessment (Reduced or Increased Susceptibility) based on the measurements.
Row
STUDYID
DOMAIN
USUBJID
VRSEQ
VRGRPID
VRREFID
VRGENTYP
VRGENROI
VRTESTCD
VRTEST
1
ABC-123
VR
R12345
1
1
16248
SECTOR
IC50T
IC50 Result on Treatment
2
ABC-123
VR
R12345
2
1
16248
SECTOR
IC50R
3
ABC-123
VR
R12345
3
1
16248
SECTOR
4
ABC-123
VR
R12345
4
1
16248
SECTOR
IC50 Reference Control
Result
IC50 Fold Change from
Reference
IC95 Result on Treatment
5
ABC-123
VR
R12345
5
1
16248
SECTOR
6
ABC-123
VR
R12345
6
1
16248
SECTOR
7
ABC-123
VR
R12345
7
1
16248
SECTOR
Nucleoside Reverse
Transcriptase
Nucleoside Reverse
Transcriptase
Nucleoside Reverse
Transcriptase
Nucleoside Reverse
Transcriptase
Nucleoside Reverse
Transcriptase
Nucleoside Reverse
Transcriptase
Nucleoside Reverse
Transcriptase
NETASSMT
IC95 Reference Control
Result
IC95 Fold Change from
Reference
Net Assessment
8
ABC-123
VR
R12345
8
2
16248
SECTOR
Protease
IC50T
IC50 Result on Treatment
9
ABC-123
VR
R12345
9
2
16248
SECTOR
Protease
IC50R
10
ABC-123
VR
R12345
10
2
16248
SECTOR
Protease
IC50FCR
11
ABC-123
VR
R12345
11
2
16248
SECTOR
Protease
IC95T
IC50 Reference Control
Result
IC50 Fold Change from
Reference
IC95 Result on Treatment
12
ABC-123
VR
R12345
12
2
16248
SECTOR
Protease
IC95R
13
ABC-123
VR
R12345
13
2
16248
SECTOR
Protease
IC95FCR
14
ABC-123
VR
R12345
14
2
16248
SECTOR
Protease
NETASSMT
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
IC50FCR
IC95T
IC95R
IC95FCR
IC95 Reference Control
Result
IC95 Fold Change from
Reference
Net Assessment
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Row
(cont)
1
2
3
4
5
6
7
VRSPCIES
VRSTRAIN
VRDRUG
VRORRES
HIV
HIV
HIV
HIV
HIV
HIV
HIV
1
1
1
1
1
1
1
Drug A
Drug A
Drug A
Drug A
Drug A
Drug A
Drug A
13.11
2.99603
4.37471
136.77
37.6061
3.6
Reduced Susceptibility
umol
umol
8
9
10
11
12
13
14
HIV
HIV
HIV
HIV
HIV
HIV
HIV
1
1
1
1
1
1
1
Drug B
Drug B
Drug B
Drug B
Drug B
Drug B
Drug B
7.97
1.71997
4.63569
28.54
11.9079
2.4
Reduced Susceptibility
umol
umol
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
VRORRESU
VRSTRESC
umol
umol
VRSTRESN
VRSTRESU
13.11
2.99603
4.37471
136.77
37.6061
3.6
umol
umol
7.97
1.71997
4.63569
28.54
11.9079
2.4
umol
umol
umol
umol
Reduced Susceptibility
umol
umol
umol
umol
Reduced Susceptibility
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CDISC Virology User Guide (Version 1.0)
4
PHARMACOGENOMICS FINDINGS (PF)
PF.xpt, Pharmacogenomics Findings - one record per method/setup observation per specimen collected, per date of test, per subject, Tabulation
Variable Name
Variable Label
STUDYID
DOMAIN
Study Identifier
Domain Abbreviation
USUBJID
PFSEQ
Controlled
Terms
or Format
Type
CDISC Notes
Core
Identifier
Identifier
Definition: Unique identifier for a study within the submission.
Definition: Two-character abbreviation for the domain most relevant to the
observation.
Req
Req
Unique Subject Identifier Char
Sequence Number
Num
Identifier
Identifier
Definition: Unique subject identifier within the submission.
Definition: Sequence number given to ensure uniqueness within a dataset for a
subject. Can be used to join related records.
Req
Req
PFGRPID
Group ID
Char
Identifier
Perm
PFREFID
PFLNKID
Specimen ID
Link ID
Char
Char
Identifier
Identifier
Definition: Used to tie together a block of related records in a single domain to
support relationships within the domain and between domains.
Definition: The identifier of the genetic specimen being tested.
Definition: Supports linking information across different domains.
PFASYID
PFRLOCID
Assay ID
Reference Result
Location
Genomics Test Code
Char
Char
Identifier
Identifier
PFTESTCD
Char
Char
Role
**PF
Char
*
PFTEST
Pharmacogenomics Test Char
Description
*
PFTSTRCD
*
PFGENLOC
Test Reference
Terminology Code
Test Reference
Terminology Name
Test Reference
Terminology Version
Genetic Region of
Interest Type
Genetic Region of
Interest
Genetic Location
PFSPCIES
Biological classification Char
PFTSTRNM
PFTSTRVR
PFGENTYP
PFGENROI
Char
Char
Char
Char
Char
Char
*
Perm
Perm
Definition: A unique identifier for a test as maintained by a lab.
Definition: Provides an external database identifier that can be used to locate the
documented reference sequence. Examples: dbSNP RS Number.
Topic
Definition: Short name for the test. Examples: AA, CHGTYP, CDNPOS,
CDNOBS, PATHTYP, POLYTYP, NINT1VAL, NINT2VAL, PVAL,
FOLDCHG, LOTINT, LOGERROR
Synonym
Definition: The verbatim name used to obtain the measurement or finding.
Qualifier
Examples: Amino Acid, Genetic Change Type, Codon Position, Observed
Codon, Pathological Type, Normalized Intensity Value 1, Normalized Intensity
Value 2, P Value, Fold Change, Log Intensity Type, Log Error.
Result Qualifier Definition: The code of the result. For example: LOINC code 48005-3 for amino
acid change.
Result Qualifier Definition: The name of the Reference Terminology for the result. Examples:
CDISC, SNOMED, LOINC.
Result Qualifier Definition: The version number of the Reference Terminology, if required.
Perm
Perm
Result Qualifier Definition: Identifies the type of genetic region of interest, for example,
GENENAME, SECTOR, PROTEIN.
Result Qualifier Definition: Area within the DNA sequences.
Example: Protease (in the case of HIV), NS3/4A, NS5B (in the case of HCV).
Result Qualifier Definition: Specifies a location within a sequence pertaining to the observed
results contained in PFORRES, PFSTRESC and PFSTRESN.
Grouping
Definition: Biological classifications for an organism capable of breeding and
Qualifier
producing offspring. May also be used to designate organisms.
Example: HOMO SAPIENS, RAT, MOUSE, BACTERIUM, HCV, HIV
Exp
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Req
Perm
Perm
Perm
Perm
Exp
Perm
Perm
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CDISC Virology User Guide (Version 1.0)
Variable Name
Variable Label
Controlled
Terms
or Format
Type
PFSTRAIN
Type of Strain
Char
*
PFCAT
Category for
Char
Pharmacogenomics Lab
Test
Subcategory for
Char
Pharmacogenomics Lab
Test
*
PFMUTYP
Mutation Type
Char
PFORRES
Result or Finding in
Original Units
Char
PFORRESU
Original Units
Char
PFSTRESC
Character Result/Finding Char
in Std Format
PFSTRESN
Numeric Result/Finding Num
in Standard Units
PFSTRESU
Standard Units
Char
*
PFRESRCD
Result Reference
Terminology Code
Char
*
PFRESRNM
Result Reference
Terminology Name
PFRESRVR
Result Reference
Terminology Version
PFSCAT
Role
CDISC Notes
Core
Grouping
Qualifier
Grouping
Qualifier
Definition: A genetic variant or subtype of a micro-organism.
Examples: 1a, 1b.
Definition: Used to categorize types of genetic/genomic tests.
Examples: MICRO ARRAY, EGFR MUTATION ANALYSIS.
*
Grouping
Qualifier
*
Grouping
Qualifier
Definition: A further categorization of the various test types based on particular Perm
characteristics of a test.
Examples: OBSERVED VALUE,
INTERPRETATION, PHENOTYPIC EXPRESSION
Definition: Indicates whether a mutation is inheritable or not.
Perm
Examples: GERMLINE
(UNIT)
Perm
Exp
Result Qualifier Definition: Result of the measurement or finding as originally received or
collected.
Example: Observed Nucleotide value: T.
Variable
Definition: Represents the unit of measure used by PFORRES if applicable.
Qualifier
Example: copies/5uL, LOG10 IU/ml
Exp
Perm
Result Qualifier Definition: Provides information such as the gene being tested for genotyping
Exp
tests as well as interpretations and other supporting information such as
insertions and deletions or intensity and P-Value for Array tests.
Example: Nucleotide change from reference sequence: A>T.
Result Qualifier Definition: Used for continuous or numeric results or findings in standard
Perm
format; copied in numeric format from PFSTRESC. PFSTRESN should store all
numeric test results or findings.
Example for P-Value: 0.5391
Variable
Definition: Represents the unit of measure used by PFSTRESN.
Perm
Qualifier
Result Qualifier Definition: The code of the result. For example: R is the code for Arginine and
C49488 is the code for Y.
Perm
Char
Result Qualifier Definition: The name of the Reference Terminology for the result. For example:
CDISC, SNOMED. LOINC
Perm
Char
Result Qualifier Definition: This is the code of the result. For example; R is the code for Arginine Perm
and C49488 is the code for Y.
PFREFRES
Reference Result Value Char
Result Qualifier Definition: Reference result used to determine variations based on the reference Perm
sequence.
PFRESCAT
Result Category
Char
Result Qualifier Definition: Identifies the type of result being reported.
Example: RESISTANCE VARIANT
Perm
PFSTAT
Test Status
Char
Record
Qualifier
Perm
(ND)
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Definition: Used to indicate exam not done. Should be null if a result exists in
PFSTRESC.
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CDISC Virology User Guide (Version 1.0)
Variable Name
Variable Label
Controlled
Terms
or Format
Type
Role
CDISC Notes
Core
PFREASND
Reason Test Not Done
Char
Record
Qualifier
PFXFN
Char
PFNAM
Raw Data File or Life
Science Identifier
Vendor Name
Record
Qualifier
Record
Qualifier
Definition: Describes why a measurement or test was not performed such as
Perm
BROKEN EQUIPMENT, SUBJECT REFUSED, or SPECIMEN LOST. Used in
conjunction with PFSTAT when value is NOT DONE.
Definition: Direct reference identifier for Microarray or Genotypic data
Perm
contained in a separate file in its native format.
Definition: Name or identifier of the laboratory or biotech firm who provides the Perm
test results.
PFSPEC
Specimen Type
Char
PFSPCCND
Specimen Condition
Char
Record
Qualifier
Record
Qualifier
Definition: Defines the type of specimen used for a measurement.
Examples: DNA, RNA
Definition: Free or standardized text describing the condition of the specimen.
Example: CONTAMINATED
PFMETHOD
Method Code for Test
Char
*
Record
Qualifier
Definition: Special instructions for the execution of genomics or genetic testing. Req
Examples: SNP PROBE, CLIP SEQUENCING, PYROSEQUENCING,
BICHROME GENE EXPRESSION CHIP).
PFBLFL
Baseline Flag
Char
(NY)
Record
Qualifier
Definition: Indicator used to identify a baseline value,
Perm
PFDRVFL
Derived Flag
Char
(NY)
Record
Qualifier
Definition: Used to indicate a derived record.
Perm
VISITNUM
Visit Number
Num
Timing
Definition:
1. Clinical encounter number.
2. Numeric version of VISIT, used for sorting.
Exp
VISIT
Visit Name
Char
Timing
Definition:
1. Protocol-defined description of clinical encounter
2. May be used in addition to VISITNUM and/or VISITDY
Perm
VISITDY
Planned Study Day of
Num
Visit
Date/Time of Specimen Char
Collection
Study Day of Specimen Num
Collection
Timing
Definition: Planned study day of the visit based upon RFSTDTC in
Perm
Demographics.
Definition:
Exp
Date/time of specimen collection
Definition:
Perm
1. Study day of specimen collection, measured as integer days.
2. Algorithm for calculations must be relative to the sponsor-defined RFSTDTC
variable in Demographics. This formula should be consistent across the
submission.
PFDTC
PFDY
Char
*
ISO 8601
Timing
Timing
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Perm
Perm
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CDISC Virology User Guide (Version 1.0)
Variable Name
Variable Label
Type
Controlled
Terms
or Format
Role
PFTPT
Planned Time Point
Name
Char
Timing
PFTPTNUM
Planned Time Point
Number
Elapsed Time from
Reference Point
Num
Timing
PFTPTREF
Time Point Reference
Char
PFRFTDTC
Date/Time of Reference Char
Time Point
PFELTM
4.1
ISO 8601
Timing
Timing
ISO 8601
Timing
Core
Definition: 1.Text Description of time when specimen should be taken.
Perm
2. This may be represented as an elapsed time relative to a fixed reference point,
such as time of last dose. See PFTPTNUM and PFTPTREF.
Examples: Start, 5 min post.
Definition: Numerical version of PFTPT to aid in sorting.
Perm
Definition: Elapsed time (in ISO 8601) relative to a planned fixed reference
Perm
(PFTPTREF). This variable is useful where there are repetitive measures. Not a
clock time or a date time variable.
Examples: '-P15M' to represent the period of 15 minutes prior to the reference
point indicated by PFTPTREF, or 'P8H' to represent the period of 8 hours after
the reference point indicated by PFTPTREF.
Definition: Name of the fixed reference point referred to by PFELTM,
Perm
PFTPTNUM, and PFTPT.
Examples: PREVIOUS DOSE, PREVIOUS MEAL.
Definition: Date/time of the reference time point, PFTPTREF.
Perm
ASSUMPTIONS FOR PHARMACOGENOMICS TEST FINDINGS (PF) DOMAIN MODEL
1.
2.
3.
4.
5.
6.
7.
8.
4.2
Char
CDISC Notes
PF captures results for genetic variation and gene expression.
This domain is for clinical and pre-clinical use, and for tests on a study subject or an infectious microbe.
PFASYID is used to distinguish between records for the same genetic test performed using different assays. The combination of PFNAM,
PFASYID, and REFID will be needed to obtain the full set of genomic data produced and sent by the lab for a specific test.
PFMETHOD lists techniques for the execution of genomics or genetic testing.
Only the p-value calculation performed by the lab and sent to the sponsor should be included in PF.
External terminology variables, (e.g., PFRESCD, PFRESRNM, PFRESRVR), will have examples in the forthcoming SDTMIG-PGx.
For viral findings, mutation type (PFMUTYP) should always be set to “GERMLINE”.
PFCAT is used to designate the technology used, (e.g., GENETIC VARIATION, GENE EXPRESSION).
GENETIC VARIATION ASSUMPTIONS
1.
2.
3.
PFTESTCD generally specifies what the test assessed, such as nucleic acid, amino acid, or codon.
PFSCAT is used to categorize the tests, for example, AMINO ACID, MUTATION, or IDENTIFIER.
PFASYID provides a mechanism to identify results as belonging to a common set. When a genetic test is performed on an individual subject using
multiple assays, the combination of vendor name and PFASYID will support linking between the PF domains and the full set of genomic data
produced and sent by the lab. This can facilitate delivering additional information to regulatory agencies, if needed.
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
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CDISC Virology User Guide (Version 1.0)
4.
5.
4.3
PFORRES and PFSTRESC are used to store genetic and amino acid variants as well as interpretations and other supporting information such as
insertions and deletions or intensity and p-values for array tests. If no standardization is being done, both variables will have identical content.
When results indicate a mixture of genetic results, as when two strains of a virus such as HIV are present in a sample, all the results present should
be concatenated using slashes. For example, “C/T” indicates that at that nucleotide position, the virus has both cysteine and tyrosine present,
indicating a multi-strain infection.
EXPLANATORY NOTES ON SLC DATABASE GENETIC CODES
The following information is provided for those not familiar with genetic nomenclature. Codons are made up of three nucleotides. A nucleotide may
have one of the following values: A (adenosine), G (guanosine), T (thymidine), or C (cytidine). Amino acids are encoded by the nucleotides. It is the
preferred convention to use a single-letter code (SLC) to identify an amino acid. This link, http://www.cbs.dtu.dk/courses/27619/codon.html, provides
the mapping between the single-letter amino acid code and its full text name, which correlates to the codon values.
4.4
EXAMPLES FOR VIRAL GENETICS FINDINGS
Example 1: Only amino acid observations are being reported. In this example, the change type is a substitution.
Row 1: The DNA came from a sample taken from the study subject at Visit 1. The test assesses the observed amino acid in the genetic region shown in
PFGENROI at the location given by PFGENLOC, performed by the vendor (PFNAM) using a particular method (PFMETHOD). The result is an amino
acid, represented by the standard one-letter code. The record also shows a reference result (the amino acid at the same location in the reference
sequence) in PFREFRES, and provides a classification of the result, based on the comparison of the observed result to the reference result, in
PFRESCAT.
Row
1
STUDYID
DOMAIN
USUBJID
PFSEQ
PFREFID
PFGENTYP
PFGENROI
PFTESTCD
PFTEST
PFSPCIES
PFSTRAIN
PFCAT
PFSCAT
P70815101
PF
P7081-510101201
1
ABC-001
PROTEIN
NS5B
AA
Amino
Acid
HCV
1a
GENETIC
VARIATION
AMINO
ACID
PFRESCAT
Point
Mutation
PFNAM
Acme
Genetics
PFSPEC
DNA
VISITNUM
1
VISIT
Baseline
Row
(cont)
1
PFORRES
R
PFGENLOC
65
PFREFRES
Q
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
PFMETHOD
CLIP
SEQUENCING
PFBLFL
Y
VISITDY
1
VFDTC
2003-03-27
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CDISC Virology User Guide (Version 1.0)
Example 2: This example contains both an amino acid observation and the underlying nucleic acid sequence (codon). The variant identified in these
records is a deletion.
Row 1 shows the amino acid observed at a particular location in the genetic region NS5B71 and its reference result. This record is marked as derived,
since the amino acid is derived from the observed codon via the standard look-up table.
Row 2 reports the nucleic acid sequence for the associated codon and its reference result and classifies the comparison between the result and the
reference result as a DELETION.
Row
2
PFGENTYP
PFTESTCD
AA
PFTEST
Amino
Acid
PFSPCIES
HCV
PFSTRAIN
1b
PFCAT
PROTEIN
PFGENROI
NS5B
2
ABC-003
PROTEIN
NS5B
CDN
Codon
HCV
1b
GENETIC
VARIATION
PFMETHOD
CLIP
SEQUENCING
PFBLFL
Y
VISITNUM
1
VISIT
Baseline
VISITDY
1
PFDTC
20030327
CLIP
SEQUENCING
Y
1
Baseline
1
20030327
P70815101
PF
PFORRES
I
PFSTRESC
I
PFGENLOC
71
PFREFRES
V
PFRESCAT
PFNAM
Acme
Genetics
PFSPEC
DNA
ATT
ATT
213
GTT
DELETION
Acme
Genetics
DNA
2
Row
(cont)
1
PFREFID
ABC-003
DOMAIN
PF
1
USUBJID
P7081510106891
P7081510106891
PFSEQ
1
STUDYID
P70815101
GENETIC
VARIATION
PFSCAT
AMINO ACID
NUCELOTIDE
Example 3: The example below focuses on how variations would be reported at the nucleotide level. Note that the change type record was not shown,
but would be recorded just as shown in previous examples. There is one record for which the observed nucleotide is different from the reference result.
The nucleic acid at this position is missing, so the change type (PFRESCAT) is "DELETION". Nucleotide-level reporting is suggested only for special
circumstances such as frame shifts since it tends to greatly increase the size of the data files. Codon-level reporting (as in the previous two examples)
will result in a significant 66% saving of space.
Row 1 shows the deletion of a nucleotide at a particular position. This absence of a nucleotide at this position is represented as the result “NONE”.
Rows 2-9 show adjacent nucleotide positions, which are unchanged.
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
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December 6, 2012
CDISC Virology User Guide (Version 1.0)
Row
1
STUDYID
P70815101
DOMAIN
PF
2
P70815101
PF
3
P70815101
PF
4
P70815101
PF
5
P70815101
PF
6
P70815101
PF
7
P70815101
PF
8
P70815101
PF
9
P70815101
PF
USUBJID
P341510106345
P341510106345
P341510106345
P341510106345
P341510106345S
P341510106345
P341510106345
P341510106345
P341510106345
PFSEQ
1
PFREFID
ABC-004
PFGENTYP
PROTEIN
PFGENROI
NS5B
PFTESTCD
NUC
PFTEST
Nucleotide
PFASYID
D391395001
PFSPCIES
HCV
PFSTRAIN
1a
PFCAT
GENETIC
VARIATION
PFSCAT
NUCLEOTIDE
2
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
3
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
4
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
5
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
6
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
7
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
8
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
9
ABC-004
PROTEIN
NS5B
NUC
Nucleotide
D391395001
HCV
1a
GENETIC
VARIATION
NUCLEOTIDE
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Page 20
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Row
(cont)
1
PFORRES
NONE
PFSTRESC
NONE
2
T
T
3
C
4
PFSTRESN
PFGENLOC
213
PFREFRES
A
PFRESCAT
DELETION
PFNAM
Acme
Genetics
PFSPEC
DNA
PFMETHOD
DIRECT SEQUENCING
PFBLFL
Y
214
Acme
Genetics
DNA
DIRECT SEQUENCING
Y
C
215
Acme
Genetics
DNA
DIRECT SEQUENCING
Y
A
A
216
Acme
Genetics
DNA
DIRECT SEQUENCING
Y
5
A
A
217
Acme
Genetics
DNA
DIRECT
SEQUENCING
Y
6
G
G
218
Acme
Genetics
DNA
DIRECT SEQUENCING
Y
7
A
A
219
DNA
DIRECT SEQUENCING
Y
8
G
G
220
Acme
Genetics
Acme
Genetics
DNA
DIRECT
SEQUENCING
Y
9
T
T
221
Acme
Genetics
DNA
DIRECT SEQUENCING
Y
Example 4: This is an example of viral genetic testing undertaken to determine drug resistance. Records come in pairs, one record for the observed
codon and one for the amino acid coded by the observed codon. This distinction is made in PFSCAT. All records are for the same sample of RNA from
a strain 1a of HIV.
Rows 1 and 2: These results show a variation in the Protease region of the virus. The change in the codon shown in Row 2 is classified as a point
mutation. The change in amino acid is classified as a resistance mutation (PFRESCAT).
Rows 3-26: Illustrate the representation of other variants in a similar manner.
Row
1
2
3
STUDYID
STDY505357
STDY505357
DOMAIN
PF
USUBJID
521298
PFSEQ
1
PFGRPID
1
PFREFID
D391395
PFGENTYP
SECTOR
PFGENROI
Protease
PFTESTCD
AA
PF
521298
2
1
D391395
SECTOR
Protease
CDN
STDY505357
PF
521298
3
2
D391395
SECTOR
Protease
AA
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
PFTEST
Amino
Acid
Codon
PFSPCIES
HIV
PFSTRAIN
1a
HIV
1a
Amino
Acid
HIV
1a
PFCAT
GENETIC
VARIATION
GENETIC
VARIATION
GENETIC
VARIATION
PFSCAT
AMINO ACID
NUCLEOTIDE
AMINO ACID
Page 21
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Row
4
STUDYID
STDY505357
DOMAIN
PF
USUBJID
521298
PFSEQ
4
PFGRPID
2
PFREFID
D391395
PFGENTYP
SECTOR
PFGENROI
Protease
PFTESTCD
CDN
PFTEST
Codon
PFSPCIES
HIV
PFSTRAIN
1a
PFCAT
GENETIC
VARIATION
PFSCAT
NUCLEOTIDE
5
STDY505357
STDY505357
PF
521298
5
3
D391395
SECTOR
Protease
AA
HIV
1a
521298
6
3
D391395
SECTOR
Protease
CDN
HIV
1a
GENETIC
VARIATION
GENETIC
VARIATION
AMINO ACID
PF
Amino
Acid
Codon
STDY505357
STDY505357
PF
521298
7
4
D391395
SECTOR
Protease
AA
HIV
1a
PF
521298
8
4
D391395
SECTOR
Protease
CDN
Amino
Acid
Codon
HIV
1a
9
STDY505357
PF
521298
9
5
D391395
SECTOR
Reverse
Transcriptase
AA
Amino
Acid
HIV
1a
GENETIC
VARIATION
AMINO ACID
10
STDY505357
PF
521298
10
5
D391395
SECTOR
Reverse
Transcriptase
CDN
Codon
HIV
1a
GENETIC
VARIATION
NUCLEOTIDE
11
STDY505357
PF
521298
11
6
D391395
SECTOR
Reverse
Transcriptase
AA
Amino
Acid
HIV
1a
GENETIC
VARIATION
AMINO ACID
12
STDY505357
PF
521298
12
6
D391395
SECTOR
Reverse
Transcriptase
CDN
Codon
HIV
1a
GENETIC
VARIATION
NUCLEOTIDE
13
STDY505357
PF
521298
13
7
D391395
SECTOR
Reverse
Transcriptase
AA
Amino
Acid
HIV
1a
GENETIC
VARIATION
AMINO ACID
14
STDY505357
PF
521298
14
7
D391395
SECTOR
Reverse
Transcriptase
CDN
Codon
HIV
1a
GENETIC
VARIATION
NUCLEOTIDE
15
STDY505357
PF
521298
15
8
D391395
SECTOR
Reverse
Transcriptase
AA
Amino
Acid
HIV
1a
GENETIC
VARIATION
AMINO ACID
16
STDY505357
PF
521298
16
8
D391395
SECTOR
Reverse
Transcriptase
CDN
Codon
HIV
1a
GENETIC
VARIATION
NUCLEOTIDE
17
STDY505357
STDY505357
PF
521298
17
9
D391395
SECTOR
Protease
AA
HIV
1a
521298
18
9
D391395
SECTOR
Protease
CDN
HIV
1a
GENETIC
VARIATION
GENETIC
VARIATION
AMINO ACID
PF
Amino
Acid
Codon
STDY505357
PF
521298
19
10
D391395
SECTOR
Protease
AA
Amino
Acid
HIV
1a
6
7
8
18
19
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
GENETIC
VARIATION
GENETIC
VARIATION
GENETIC
VARIATION
NUCLEOTIDE
AMINO ACID
NUCLEOTIDE
NUCLEOTIDE
AMINO ACID
Page 22
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Row
20
STUDYID
STDY505357
DOMAIN
PF
USUBJID
521298
PFSEQ
20
PFGRPID
10
PFREFID
D391395
PFGENTYP
SECTOR
PFGENROI
Protease
PFTESTCD
CDN
PFTEST
Codon
PFSPCIES
HIV
PFSTRAIN
1a
PFCAT
GENETIC
VARIATION
PFSCAT
NUCLEOTIDE
21
STDY505357
STDY505357
PF
521298
21
11
D391395
SECTOR
Protease
AA
HIV
1a
521298
22
11
D391395
SECTOR
Protease
CDN
HIV
1a
GENETIC
VARIATION
GENETIC
VARIATION
AMINO ACID
PF
Amino
Acid
Codon
STDY505357
STDY505357
PF
521298
23
12
D391395
SECTOR
Protease
AA
HIV
1a
PF
521298
24
12
D391395
SECTOR
Protease
CDN
Amino
Acid
Codon
HIV
1a
STDY505357
STDY505357
PF
521298
25
13
D391395
SECTOR
Protease
AA
HIV
1a
PF
521298
26
13
D391395
SECTOR
Protease
CDN
Amino
Acid
Codon
HIV
1a
22
23
24
25
26
GENETIC
VARIATION
GENETIC
VARIATION
GENETIC
VARIATION
GENETIC
VARIATION
Row
(cont)
1
PFORRES
PFSTRESC
PFGENLOC
PFREFRES
PFRESCAT
PFNAM
PFSPEC
PFMETHOD
PFBLFL
I
I
10
L
Resistance Mutation
DNA
ATC
ATC
28
CTC
Point Mutation
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
2
Acme
Genetics
Acme
Genetics
3
G
G
17
G
Silent Mutation
DNA
GGG
GGG
49
GGR
Duplication
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
4
Acme
Genetics
Acme
Genetics
5
I
I
13
V
Polymorphism
DNA
ATA
ATA
37
GTA
Point Variation
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
6
Acme
Genetics
Acme
Genetics
7
L
L
33
I
Unexpected Mutation
DNA
TTA
TTA
97
ATA
Point Mutation
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
8
Acme
Genetics
Acme
Genetics
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
DNA
DNA
DNA
DNA
NUCLEOTIDE
AMINO ACID
NUCLEOTIDE
AMINO ACID
NUCLEOTIDE
PFDRVFL
Y
Y
Y
Y
Page 23
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Row
(cont)
9
PFORRES
PFSTRESC
PFGENLOC
PFREFRES
PFRESCAT
PFNAM
PFSPEC
PFMETHOD
PFBLFL
M
M
41
L
Resistance Mutation
Acme
Genetics
DNA
CLIP
SEQUENCING
Y
10
ATG
ATG
121
TTA
Point Mutation
Acme
Genetics
DNA
CLIP
SEQUENCING
Y
11
V
V
90
V
Silent Mutation
DNA
GTT
GTT
268
GTY
Deletion
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
12
Acme
Genetics
Acme
Genetics
13
I
I
135
V
Polymorphism
Acme
Genetics
DNA
CLIP
SEQUENCING
Y
14
ATA
ATA
103
GTA
Point Variation
Acme
Genetics
DNA
CLIP
SEQUENCING
Y
15
K
K
70
E
Unexpected Mutation
Acme
Genetics
DNA
CLIP
SEQUENCING
Y
16
AAA
AAA
208
AGA
Point Mutation
Acme
Genetics
DNA
CLIP
SEQUENCING
Y
17
G
G
48
V
Unexpected Mutation
DNA
GGG
GGG
142
GTG
Point Mutation
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
18
Acme
Genetics
Acme
Genetics
19
K
K
20
K/R
Unexpected Mutation
DNA
AAG
AAG
58
ARG
Point Mutation
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
20
Acme
Genetics
Acme
Genetics
21
M
M
36
I
Unexpected Mutation
DNA
106
106
106
ATA
Point Mutation
CLIP
SEQUENCING
CLIP
SEQUENCING
Y
22
Acme
Genetics
Acme
Genetics
23
A
A
71
V
Unexpected Mutation
DNA
GCT
GCT
211
GTT
Point Mutation
CLIP
SEQUENCING
CLIP
Y
24
Acme
Genetics
Acme
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
DNA
DNA
DNA
DNA
DNA
PFDRVFL
Y
Y
Y
Y
Y
Page 24
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Row
(cont)
PFORRES
PFSTRESC
PFGENLOC
PFREFRES
PFRESCAT
PFNAM
PFSPEC
Genetics
25
V
V
82
T/S
Unexpected Mutation
26
GCT
GCT
244
GTT
Point Mutation
PFMETHOD
PFBLFL
PFDRVFL
SEQUENCING
Acme
Genetics
Acme
Genetics
DNA
CLIP
SEQUENCING
CLIP
SEQUENCING
DNA
Y
Y
The PB domain that would accompany this findings example can be found in Example 1 of the PB domain.
Example 5:
The example shows typical results for genetic variation tests. The Findings data structure was extended to accommodate genetic concepts. It now
supports genetic region of interest (PFGENROI), its type (PFGENTYP), the reference result (PFREFRES), and genetic location (PFGENLOC). Rows 1
and 2 both show the use of the HUGO nomenclature in the PFSTRESC variable. The reference sequence can be represented in the PG domain as a row
with a test code of GENBNKID. The result variable in PG reported the NIH Genetic Sequence Database (GenBank) accession number associated with
the reference sequence being used. The XFN variable may contain a pointer to a file containing the entire reference sequence. This example also shows
the use of the new terminology variables (PFTSTRCD, PFTSTRNM, PFTSTRVR) to link the tests to an external dictionary such as LOINC.
Row 1-2 shows that at nucleotide at position 2155 a genetic change occurred where a G was changed to an A.
It also shows that a change occurred from the amino acid Glycine (Gly) at location 719 to Serine. Since the amino acid change is not directly observed
but derived from the variation, the derived flag is set to "Y" if the sponsor is performing the interpretation.
Row
1
STUDYID
ABC-01234
DOMAIN
PF
2
ABC-01234
Pf
USUBJID
17C0154
PFSEQ
1
PFREFID
8250863
1
8250863
PFASYID
X421395001
X421395001
PFTESTCD
AA
CDN
PFTEST
Amino
Acid
Codon
PFTSTRCD
48005-3
PFTSTRNM
LOINC
PFTSTRVR
2.40
48004-6
LOINC
2.40
Row
(cont)
1
PFGENTYP
SECTOR
PFGENROI
Protease
PFGENLOC
13
PFSPCIES
HCV
2
SECTOR
Protease
2155
HCV
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
PFCAT
GENETIC
VARIATION
GENETIC
VARIATION
PFORRES
S
PFSTRESC
C.13G>S
PFREFRES
G
AGC
C.2155GGC>AGC
GGC
PFRESCAT
Disease
Mutation
Point
Mutation
PFNAM
Biotech
ABC
Biotech
ABC
PFSPEC
DNA
DNA
Page 25
December 6, 2012
CDISC Virology User Guide (Version 1.0)
5
PHARMACOGENOMICS/GENETICS METHODS AND
SUPPORTING INFORMATION (PG)
PG.xpt, Pharmacogenomics — Findings. One record per method/setup observation per specimen collected, per date of test, per subject, Tabulation
Variable Name
Variable Label
STUDYID
DOMAIN
Study Identifier
Domain Abbreviation
USUBJID
Controlled
Terms or
Format
Type
Char
Char
Role
CDISC Notes
Core
Identifier
Identifier
Definition: Unique identifier for a study within a submission.
Req
Definition: Two-character abbreviation for the domain most relevant to the Req
observation.
Unique Subject Identifier Char
Identifier
Definition: Unique subject identifier within a submission.
Req
PGSEQ
Sequence Number
Num
Identifier
Definition: Sequence number given to ensure uniqueness of records for a
subject within a dataset. Can be used to join related records.
Req
PGGRPID
Group ID
Char
Identifier
Definition: Used to tie together a block of related records in a single domain Perm
to support relationships within the domain and between domains.
Example: For PGx we have decided that a simple numbering convention
works quite well (e.g. 1, 2, 3, etc.)
PGREFID
Specimen ID
Char
Identifier
Definition: The identifier of the genetic specimen being tested.
Example: Specimen ID.
Perm
PGSPID
PGLNKID
Sponsor ID
Link ID
Char
Char
Identifier
Identifier
Definition: Optional sponsor-defined reference number.
Definition: Supports linking information across different domains.
Perm
Perm
PGASYID
Assay ID
Char
Identifier
Definition: A unique identifier for a test as maintained by a lab.
Exp
PGTESTCD
Pharmacogenomics Test
Code
Char
Definition: Short name for the test or measurement described in PGTEST.
Examples:
QTYEXT represents the DNA or RNA Quantity Extracted.
ACTSEQ for Active Sequence
NORMMETH for Normalization Technique
DIAG for Diagnosis
DNAPUR for DNA Purity
LBLCMPND for Label Compound
EXON for Exon with Change
EXONSEQ for Exons Sequenced
Req
**PG
*
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Topic
Page 26
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Variable Name
Variable Label
Controlled
Terms or
Format
Type
PGTEST
Pharmacogenomics Test
Description
Char
*
PGTSTRCD
Char
*
Char
*
PGGENROI
Test Reference
Terminology Code
Test Reference
Terminology Name
Test Reference
Terminology Version
Genetic Region of Interest
Type
Genetic Region of Interest
PGSPCIES
Biological classification
Char
*
PGSTRAIN
Strain
Char
*
PGCAT
Category for
Pharmacogenomics Test
Char
*
PGSCAT
Reference Subcategory for Char
Pharmacogenomics Test
*
PGORRES
Result or Finding in
Original Units
Char
PGORRESU
Original Units
Char
PGSTRESC
Character Result/Finding Char
in Std Format
PGSTRESN
Numeric Result/Finding in Num
Standard Units
PGSTRESU
Standard Units
PGTSTRNM
PGTSTRVR
PGGENTYP
Char
Char
CDISC Notes
Core
Synonym
Qualifier
Definition: Verbatim name of the test or examination used to obtain the
measurement or finding.
Example: Quantity Extracted
Result Qualifier Definition: The code of the test.
Example: 48019-4 is the code for Genetic Change Type using LOINC.
Result Qualifier Definition: The name of the Reference Terminology for the test.
Example: CDISC, SNOMED, LOINC.
Result Qualifier Definition: The version number of the Reference Terminology, if required.
Req
Definition: Identifies the type of genetic region of interest, for example,
GENENAME, SECTOR, PROTEIN.
Definition: Area within the DNA sequences.
Result Qualifier Example: Protease (in the case of HIV), NS3/4A, NS5B (in the case of
HCV).
Grouping Definition: Biological classifications for an organism capable of breeding
Qualifier
and producing offspring.
Examples: HOMO SAPIENS, RAT, MOUSE, STAPHYLOCCCUS
AUREUS, HCV
Grouping Definition: A genetic variant or subtype of a micro-organism.
Qualifier
Example: 1a for HCV
Grouping Definition: Used to categorize types of genetic/genomic tests.
Qualifier
Examples: GENETIC VARIATION, GENE EXPRESSION.
Exp
Result Qualifier
Char
Char
Role
(UNIT)
*
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Grouping
Qualifier
Definition: A further categorization of the various test types based on
particular characteristics of a test.
Examples: INTERPRETATION, SETUP, and QC.
Result Qualifier Definition: Result of the measurement or finding as originally received or
collected.
Example for Exons Sequenced: 13-21
Variable
Definition: Represents the unit of measure used by PGORRESU if
Qualifier
applicable.
Example: copies/5ul, LOG10 IU/ml
Result Qualifier Definition: An expression of the genetic change recorded in PGORRES in
standard nomenclature such HUGO.
Result Qualifier Definition: Used for continuous or numeric results or findings in standard
format; copied in numeric format from PGSTRESC. PGSTRESN should
store all numeric test results or findings.
Example: Exon that is exhibiting the variant: 18
Variable
Definition: Represents the unit of measure used by STRESN if applicable.
Qualifier
Example: copies/5ul
Perm
Exp
Exp
Exp
Perm
Perm
Exp
Perm
Exp
Perm
a Exp
Perm
Perm
Page 27
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Variable Name
Variable Label
Controlled
Terms or
Format
Type
PGRESRCD
Result Reference
Terminology Code
Char
PGRESRNM
Result Reference
Terminology Name
PGRESRVR
*
Role
CDISC Notes
Core
Result Qualifier Definition: The code of the result. For example: R is the code for Arginine
and C49488 is the code for Y.
Exp
Char
Result Qualifier Definition: The name of the Reference Terminology for the result. For
example; CDISC, SNOMED, LOINC
Exp
Result Reference
Terminology Version
Char
Result Qualifier Definition: The version number of the Reference Terminology, if applicable.
Example: LOINC 2.38.
Exp
PGSTAT
Completion Status
Char
PGREASND
Reason Test Not Done
Char
PGXFN
Raw Data File or LSID
Char
Record
Qualifier
Definition: Direct reference identifier for a raw Microarray or Genotypic data Perm
file.
PGNAM
Vendor Name
Char
Record
Qualifier
Definition: Name or identifier of the laboratory or biotech firm who provides Perm
the test results.
PGSPEC
Specimen Type
Char
Specimen Condition
Char
PGMETHOD
Method of Test or
Examination
Char
VISITNUM
Visit Number
Num
Timing
VISIT
Visit Name
Char
Timing
Definition: Defines the type of specimen used for a measurement.
Examples: TISSUE, SERUM, PLASMA, TUMOR, DNA, RNA
Definition: Free or standardized text describing the condition of the
specimen.
Example: HEMOLYZED, ICTERIC, LIPEMIC, FRESH, FROZEN,
PARAFFIN-EMBEDDED.
Definition: Special instructions for the execution of genomics or genetic
testing.
Examples: SNP PROBE, LASER MICRODISSECTION, POPULATION,
CLIP SEQUENCING, DIRECT SEQUENCING, PYROSEQUENCING,
REAGENT, GENE chip such as AGILENT or AFFYMETRIX.
Definition:
1. Clinical encounter number.
2. Numeric version of VISIT, used for sorting.
Definition:
1. Protocol-defined description of clinical encounter
2. May be used in addition to VISITNUM and/or VISITDY
Perm
PGSPCCND
Record
Qualifier
Record
Qualifier
VISITDY
Planned Study Day of
Visit
Num
Timing
Definition: Planned study day of the visit based upon RFSTDTC in
Demographics.
Perm
**ND
*
*
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Result Qualifier Definition: Used to indicate exam not done. Should be null if a result exists Perm
in PGORRES.
Record
Definition: Describes why a measurement or test was not performed.
Perm
Qualifier
Examples: BROKEN EQUIPMENT, SUBJECT REFUSED, SPECIMEN
LOST AND AMPLIFYING PROBLEM.
Record
Qualifier
Perm
Req
Exp
Perm
Page 28
December 6, 2012
CDISC Virology User Guide (Version 1.0)
Variable Name
PGDTC
Variable Label
Char
Controlled
Terms or
Format
ISO 8601
Role
CDISC Notes
Core
Timing
Definition: Date and time of specimen collection.
Exp
Num
Timing
Perm
PGTPT
Planned Time Point Name Char
Timing
PGTPTNUM
Planned Time Point
Number
Num
Timing
Definition:
1. Study day of specimen collection, measured as integer days.
2. Algorithm for calculations must be relative to the sponsor-defined
RFSTDTC variable in Demographics. This formula should be consistent
across the submission.
Definition:
1. Text Description of time when specimen should be taken.
2. This may be represented as an elapsed time relative to a fixed reference
point, such as time of last dose. See PGTPTNUM and PGTPTREF.
Examples: Start, 5 min post.
Definition: Numerical version of PGTPT to aid in sorting.
PGELTM
Elapsed Time from
Reference Point
Char
PGTPTREF
Time Point Reference
Char
PGRFTDTC
Date/Time of Reference
Time Point
Char
PGDY
Date/Time of Specimen
Collection
Study Day of Specimen
Collection
Type
ISO 8601
Timing
Timing
ISO 8601
Timing
Perm
Perm
Definition: Elapsed time (in ISO 8601) relative to a planned fixed reference Perm
(PGTPTREF). This variable is useful where there are repetitive measures.
Not a clock time or a date time variable.
Examples: '-P15M' to represent the period of 15 minutes prior to the
reference point indicated by PGTPTREF, or 'P8H' to represent the period of
8 hours after the reference point indicated by PGTPTREF.
Definition: Name of the fixed reference point referred to by PGELTM,
Perm
PGTPTNUM, and PGTPT.
Examples: PREVIOUS DOSE, PREVIOUS MEAL.
Date/time of the reference time point, PGTPTREF.
Perm
* Indicates variable may be subject to controlled terminology
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
Provisional
Page 29
December 6, 2012
CDISC Virology User Guide (Version 1.0)
5.1
ASSUMPTIONS FOR PHARMACOGENOMICS (PG) DOMAIN MODEL
1.
2.
3.
4.
5.
6.
7.
8.
5.2
PG will capture information about the test methodology that contributes to the understanding of the test results contained in the PF domain. These
are methods that are used for test setup or quality control.
This domain is for both clinical and pre-clinical use and for tests on both study subjects and infectious microbes.
This domain contains the following new variables: PGTSTRCD, PGPSTRNM, PGPSTRDE, PGRESRCD, PGRESRNM, and PGRESRVR. These
are needed to link to external terminology such as LOINC. Examples for use of these variables will be included in the forthcoming SDTMIG-PGx
document.
Additional data elements that are specific to Pharmacogenomics Findings will be supported via the use of Supplemental Qualifiers. Examples of
typical data that might be submitted via a SUPPPG dataset include those listed in the table below.
PGREFID should contain an identifier for the DNA or RNA extraction sample.
PGREASND is used in conjunction with PGSTAT when value is NOT DONE.
PGTESTCD and PGTEST should not include gene codes. Whether collecting the complete detail for a variation or mutation or a subset, the test
code GENEID will be used to collect the gene of interest in the results variable. DISC plans to use test codes that correspond to LOINC codes.
When using the pharmacogenomics domains for viral test reporting, the identification of the virus requires the virus name be placed in the
PGSPCIES field and if available, the strain, type or subtype is placed in PGSTRAIN field.
LIST OF IDENTIFIED COMMON SUPPQUALS
QNAM
GNANLDTC
QLABEL
Gene Analysis Date and Time
COMMENTS
Can be used to indicate when genetic/genomic data was re-evaluated against the public database(s).
RPANLDTC
Reported Gene Analysis Date and Time
Used to reference date/time results were reported back to the sponsor.
ACCESNO
ACCESSION NUMBER
The accession number is obtained from the lab for a lab test. Accession numbers can be useful in cases where
the FDA requests more information for a particular test. The accession number helps locate information in the
public databases.
Note: DO NOT confuse this with Assay ID which is an identifier assigned to the work order at the lab.
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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5.3
EXAMPLES OF TESTCDS FOR REFERENCING PUBLIC DATABASES
The following examples show how reference databases can be identified using the PGTEST and PGTESTCD fields.
PGTESTCD
PGTEST
COMMENTS
XREFDB
Reference Database
Identifies the public database used to identify variants and mutations.
HGNCID
HUGO ID
HUGO Gene Nomenclature Committee Database Reference. For example, the HGNCID for the EGFR gene
is HGNC: 3326
PROTDB
HUMAN PROTEIN DATABASE
Database Reference
GENBNKID
Gen Bank ID of Reference
Gene Bank Identification of Reference
5.4
PG EXAMPLES
Example 1:
This example shows genotypic data collected about the exons that were sequenced, the associated gene name, the sequence position, and length.
Row 1 specifies the gene name related to the results in the PF domain.
Row 2 identifies the GenBank identifier for the Reference Sequence.
Row 3 identifies the exons that were sequenced during the test.
Row 4 points to additional documentation related to the conduct of the genetic tests whose results will be reported in the PF domain.
Rows 5-6 show the quality control information for the starting position and length of the gene sequence used in the test SEQSTART and SEQLTH.
Row
1
2
3
4
5
6
STUDYID
ABC01234
ABC01234
DOMAIN
PG
USUBJID
17C0154
PGSEQ
1
PGGRPID
1
PGREFID
5493283
PGTESTCD
GENEID
PG
17C0154
2
1
5493283
GENBNKID
ABC01234
ABC01234
PG
17C0154
3
1
5493283
EXONSEQ
PG
17C0154
4
1
5493283
REFERENC
ABC01234
ABC01234
PG
17C0154
5
1
5493283
SEQSTART
PG
17C0154
6
1
5493283
SEQLTH
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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PGTEST
Gene
Identifier
Gen Bank
ID of
Reference
PGASYID
1
PGGENTYP
GENE
PGGENROI
EGFR
PGCAT
IDENTIFIER
1
GENE
EGFR
IDENTIFIER
Exons
Sequenced
Submission
Reference
Document
1
GENE
EGFR
VARIANT
1
GENE
EGFR
VARIANT
Sequence
Start
Sequence
Length
1
GENE
EGFR
VARIANT
1
GENE
EGFR
VARIANT
PGNAM
Biotech
ABC
Biotech
ABC
Biotech
ABC
Biotech
ABC
Biotech
ABC
Biotech
ABC
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Row
1
EGFR
PGORESS
EGFR
PGSTRESC
PGSPEC
Tumor
2
NM_005228.3
NM_005228.3
Tumor
3
13-21
13-21
DNA
4
5.23.445.1.4.165008.1.8:86175
5.23.445.1.4.165008.1.8:86175
5
1
1
1
DNA
6
5616
5616
5616
DNA
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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PGSTRESN
PGMETHOD
MASSIVELY PARALLEL
SEQUENCING
MASSIVELY PARALLEL
SEQUENCING
MASSIVELY PARALLEL
SEQUENCING
MASSIVELY PARALLEL
SEQUENCING
MASSIVELY PARALLEL
SEQUENCING
MASSIVELY PARALLEL
SEQUENCING
PGDTC
2012-1023T10:06
2012-1023T10:06
2012-1023T10:06
2012-1023T10:06
2012-1023T10:06
2012-1023T10:06
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6
PGX BIOLOGICAL STATE (PB)
PB.xpt, Pharmacogenomics Biological State - Special Purpose Domain. One record per biomarker used in the study, tabulation.
Variable Name
Variable Label
BRIDG
Mapping Type
ISO 21090
Datatype Controlled Terms or
Format
STUDYID
DOMAIN
Study Identifier
Domain Abbreviation
Char
Char
PBSEQ
Sequence Number
Num
PBMRKRID
Biological State
Identifier
Char
PBGENTYP
Genetic Region of
Interest Type
Genetic Region of
Interest
Char
PBSPCIES
Biological
classification
Char
*
PBSTRAIN
Type of Strain
Char
*
PBDRUG
Drug Name
Char
PBDIAG
Diagnosis
Char
PBMRKR
Biological Marker
Char
PBGENROI
**PS
Identifier
Identifier
CDISC Notes
Core
Definition: Unique identifier for a study.
Definition: Two-character abbreviation for the domain.
Req
Req
Identifier
*
Char
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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Role
*
Definition: Sequence number given to ensure uniqueness Req
within a dataset for a subject. Can be used to join related
records.
Identifier Definition: Uniquely identifies an individual or group of Req
biological markers that have medical significance in the
study.
Record
Definition: Identifies the type of genetic region of interest, Exp
Qualifier for example, GENENAME, SECTOR, PROTEIN.
Record
Definition: Area within the DNA sequences.
Perm
Qualifier Example: Protease (in the case of HIV), NS3/4A, NS5B
(in the case of HCV).
Grouping Definition: Biological classifications for an organism
Perm
Qualifier capable of breeding and producing offspring. May also be
used to designate organisms.
Examples: HOMO SAPIENS, RAT, MOUSE,
BACTERIUM, HCV, HIV
Grouping Definition: A genetic variant or subtype of a microPerm
Qualifier organism.
Examples: 1a, 1b.
Record
Definition: the name of the drug for which resistance is Exp
Qualifier based on genetic biological markers.
Examples: Saquinavir, Indinavir
Record
Definition: Disease diagnosis based on detected genetic
Exp
Qualifier biological markers.
Example: Adenocarcinoma.
Record
Definition: Identifies a biological marker that is part of the Exp
Qualifier group identified by PBMRKID.
Examples: G48V, L10I
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Variable Name
PBSTMT
6.1
Medical Statement
BRIDG
Mapping Type
ISO 21090
Datatype Controlled Terms or
Format
Char
*
Role
Record
Qualifier
CDISC Notes
Core
Definition: Represents a medical conclusion such as
confirmation of a diagnosis or resistance to a particular
medication based on genetic biological markers.
Example: RESISTANCE (when PBDRUG is populated),
POSITIVE (when PBDIAG is populated)
Exp
ASSUMPTIONS FOR THE PGX BIOLOGICAL STATE (PB) DOMAIN MODEL
1.
2.
3.
4.
6.2
Variable Label
The Pharmacogenomic Biological State domain is a special-purpose reference dataset (i.e., independent of data about study subjects) that relates a
set of genetic variations to an inference about the medical meaning of that set of genetic variations (i.e., a Medical Statement).
The medical statement in PBSTMT may document the implications of these variations for use of a drug, (in PBDRUG) or for the diagnosis of a
medical condition (in PBDIAG).
In some cases, a medical statement may be inferred from the presence of a single genetic variant, but more often all genetic variations in a set must
be present for an inference to be drawn. The PB domain is structured with one record for each variant contained in the set. PBMRKR identifies the
genetic variation. It is recommended that standard nomenclature be used to identify the genetic variations.
PBMRKRID is used to group genetic variation records which belong to a set and which form the basis for medical statement inference. It is
recommended that the value in PBMRKID be formed from the short names of the genetic variations that make up the set, separated with a plus (+)
symbol. This uniquely identifies each set of genetic variations and is also intelligible to reviewers.
EXAMPLES FOR PGX BIOLOGICAL STATE (PB) DOMAIN MODEL
Example 1:
This example shows two sets of genetic variations with associated inferences about a drug.
Row 1 shows a single genetic variant (set of one) whose presence infers resistance to Saquinavir.
Rows 2-6 shows the individual genetic variations in a group of genetic variations, which, if all are presence, infers resistance to Indinavir.
ROW STUDYID
DOMAIN PBSEQ
PBMRKRID
1
STDY-505357 PB
1
G48V
2
STDY-505357
L101+K20R+M361+
PB
2
A71+V82T
3
STDY-505357
L101+K20R+M361+
PB
3
A71+V82T
4
STDY-505357
L101+K20R+M361+
PB
4
A71+V82T
5
STDY-505357
L101+K20R+M361+
PB
5
A71+V82T
6
STDY-505357
L101+K20R+M361+
PB
6
A71+V82T
PBGENROI PBGENTYP PBSPCIES PBSTRAIN PBDRUG
Protease
SECTOR
HIV
1a
Saquinavir
Protease
SECTOR
HIV
1a
lndinavir
Protease
SECTOR
HIV
1a
lndinavir
Protease
SECTOR
HIV
1a
lndinavir
Protease
SECTOR
HIV
1a
lndinavir
Protease
SECTOR
HIV
1a
lndinavir
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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PBMRKR
G48V
PBSTMT
RESISTANCE
L10I
RESISTANCE
K20R
RESISTANCE
M361
RESISTANCE
A71V
RESISTANCE
V82T
RESISTANCE
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7
SUBJECT BIOLOGICAL STATE (SB)
SB.xpt, Subject Biological State – Special-Purpose Domain. One record per subject per observed biological state in the study, tabulation.
Variable Name
Variable Label
Type
STUDYID
Study Identifier
Char
DOMAIN
Domain Abbreviation
Char
USUBJID
Controlled
Terms or
Format
Role
CDISC Notes
Core
Identifier
Definition: Unique identifier for a study.
Req
Identifier
Definition: Two-character abbreviation for the domain.
Req
Unique Subject Identifier Char
Identifier
Definition: Unique subject identifier within the submission.
Req
SBSEQ
Sequence Number
Num
Identifier
Definition: Sequence number given to ensure uniqueness within a dataset for a
subject. Can be used to join related records.
Req
SBGRPID
Group ID
Char
Identifier
Used to tie together a block of related records in a single domain for a subject
Perm
SBREFID
Specimen ID
Char
Identifier
Definition: The identifier of the genetic or viral specimen being tested.
Perm
SBMRKRID
Biological Marker
Identifier
Char
Identifier
Definition: Uniquely identifies an individual or a group of biological markers that
has medical significance in the study.
Req
SBGENTYP
Genetic Region of
Interest Type
Record
Qualifier
Definition: Identifies the type of genetic region of interest.
Examples: GENENAME, SECTOR, PROTEIN.
Exp
SBGENROI
Genetic Region of
Interest
Char
Record
Qualifier
Definition: Area within the DNA sequences.
Example: A genotype or subtype of a microorganism.
Perm
SBSPCIES
Biological Classification
Char
*
Grouping
Qualifier
Perm
SBSTRAIN
Type of Strain
Char
*
Grouping
Qualifier
Definition: Biological classifications for an organism capable of breeding and
producing offspring. May also be used to designate organisms.
Examples: HOMO SAPIENS, RAT, MOUSE, BACTERIUM, HCV, HIV
Definition: A genetic variant or subtype of a microorganism.
Examples: 1a, 1b.
SBNAM
Vendor Name
Char
Visit Number
Num
VISIT
Visit Name
Char
Timing
VISITDY
Planned Study Day of
Visit
Num
Timing
Definition: Name or identifier of the laboratory or biotech firm who provides the
test results.
Definition:
1. Clinical encounter number.
2. Numeric version of VISIT, used for sorting.
Definition:
1.Protocol-defined description of clinical Encounter
2.May be used in addition to VISIT and VISITDY.
Definition: Planned study day of the visit based upon RFSTDTC in
Demographics.
Perm
VISITNUM
Record
Qualifier
Timing
SB
*
Char
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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Perm
Exp
Perm
Perm
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Variable Name
SBDTC
Variable Label
Date/Time of Test
Type
Char
Controlled
Role
Terms or
Format
ISO 8601 Timing
CDISC Notes
Core
Definition:
Date/time of specimen collection
Exp
7.1
ASSUMPTIONS FOR THE SUBJECT BIOLOGICAL STATE MARKER (SB) DOMAIN MODEL
1.
5.
The SB domain provides the linkage between a subject's observed genomic or virological findings and medical statements defined within the PB
domain. Thus, based on one or more subject findings, a statement about a subject's clinical state, or about the response of a subject's virus to a treatment
is made.
SBMRKRID should match a value of PBMRKRID in the PB domain.
In order to access medical statement pertaining to a subject, link via --MRKRID the SB and PB domains (PBSTMT).
The PBMRKR variable is used to identify the members (biological markers) that belong to the group identified by PBMRKRID in the PB domain.
These are then linked via SBMRKRID-PBMRKRID to the SB domain.
The medical statement is about either a drug (PBDRUG) or a medical condition (PBDIAG) as designated in the PB domain.
7.2
EXAMPLES FOR SUBJECT BIOLOGICAL STATE MARKER (SB) DOMAIN MODEL
2.
3.
4.
Example 1:
This example below shows how to associate markers to a subject in order to communicate the presence of a particular biological state.
Row 1 shows an example of one biological marker (G48V) being in the group and related back to a subject.
Row 2 shows an example of multiple biological markers (L101, K20R, M361, A71, and V82T) that must be present before a virus can be said to have
resistance to Indinavir.
STUDYID
STDY505357
STDY505357
DOMAIN
SB
USUBJID
521298
SB
521298
SBSEQ
1
SBGRPID
1
2
1
VISITNUM
1
VISIT
BASELINE
VISITDY
-1
SBDTC
3/1/2010
1
BASELINE
-1
3/1/2010
SBREFID
D391395
G48V
SBGENTYP
Sector
SBGENROI
Protease
SPSPCIES
HIV
SBSTRAIN
1a
SBNAME
BIOTECHA
D391395
L101+K20R+M361+A71+V82T
Sector
Protease
HIV
1a
BIOTECHA
© 2012 Clinical Data Interchange Standards Consortium, Inc. All rights reserved
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SBMRKRID
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APPENDICES
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Appendix A – New and Deleted Domains and Variables
In order to develop this virology supplement to the SDTM, new SDTM domains and variables were created to
complement the SDTM and SDTMIG.
Classification
Major
Type
Deletion
Domain(s)
PG/PF
Major
Major
Addition
Addition
BS, BE, ES
PG, PF, PB, SB
Major
Addition
VR
Major
Addition to
Findings
PG, PF
Major
Addition to
Identifiers
Addition to
Findings
Addition to
Findings
PG, PF
Addition to
Identifiers
Addition to
Findings
Addition to
Findings
Addition to
Findings
Addition to
Findings
Addition to
Findings
PG, PF
Major
Major
Major
Major
Major
Major
Major
Major
PG, PF, SB, PB
Description
The LOINC variable will be deleted in the next version of the
SDTM. New terminology variable will provide more
functionality will take its place.
New domains for specimen collection and handling.
New domains for OMICS data (e.g., gene expression, genetic
variation). Future releases will include cytogenetics.
New domain to store viral resistance data collecting during
viral load testing.
--TSTRCD, --TSTRNM, --TSTRVR
Terminology variables that support the content in TEST and
TESTCD.
--ASYID for Assay ID – a unique identifier for a test
maintained by the lab.
--SPCIES and --STRAIN – use to describe the organism whose
DNA/RNA is undergoing testing.
--RESRCD, --RESRNM, --RESRVR
Terminology variables that support the encoding of the test
results.
--LNKID used to support the linking of results between
domains.
--DRUG, --INDIC, --MRKR, --STMT, --DIAG to support
documenting the PGx biological markers being used.
--GENROI, --GENTYP, --GENLOC
PB, SB
--MRKRID is a biomarker identifier.
PF
--RLOCID is a public database entry identifier.
PF
--MUTYP can be used to designate somatic or germline.
PG, PF
PG, PF
PB
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Appendix B – Virology Concept Maps
This section includes initial concept maps for viral drug resistance testing, viral genetic variation testing, and
inference of drug resistance from genetic variations results. The VR concept map shows viral resistance testing to
produce inhibitory concentration results (IC50, IC95), and results derived from inhibitory concentration results. The
genetic testing diagram shows the mapping of date into the PG and PF domains. The combination of viral resistance
and genetic testing to develop knowledge of genetic variations that cause viral resistance is mapped to the PB
domain. Inferred viral resistance from genetic testing results is shown mapped to the SB domain. Note that specimen
collection includes extraction of part of a specimen to create a different kind of specimen. Figure 1 below shows the
color codes used in the maps that follow.
Figure 1 - Color Codes
B. 1 Virology Resistance Testing Maps
Details of specimen handling may be stored in biospecimen domains being developed as part of the SDTMIG-PGx
document. Figure 2 shows inhibitory concentration results (IC50, IC95) stored in the VR domain.
Figure 2 – Inhibitory Concentration Results
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Figure 3 shows derivation of ‘fold increase” results (comparisons between two inhibitory concentration results).
Shows the net assessment based on all the “fold increase” results. Note: Comparisons to baseline are not always part
of the net assessment,
Figure 3 – From Inhibitory Concentrations to New Assessment of Resistance
B. 2 Genetic Testing
Figure 4 for genetic testing shows original specimen collection and processing of a specimen to produce a viral
DNA specimen not shown. The map also includes set-up parameters and QC testing results (at the far left in the
diagram) stored in PG. Genetic results are mapped to the PF domain.
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Figure 4: Genetic Testing of Virus
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B. 3 Building Knowledge of Viral Resistance Mutation
Viral samples undergo both viral resistance and genetic mutation testing. Results of these tests are compiled, and
from them knowledge of what genetic variations confer resistance to what drugs can be determined. These sets of
variations that confer resistance to a particular drug are stored in the PB domain.
Figure 5: Combining Viral Resistance and Viral Mutation Knowledge
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B. 4 Inferring Viral Resistance from Genetic Mutation Results
Once it is known which sets of genetic variations confer resistance to a drug, a sample need not be tested for viral
resistance directly. Genetic testing shows what genetic variations a virus has. A virus’s genetic variations can be
compared to reference data in the PB domain to infer its resistance to drugs. Inferred resistance is stored in the SB
domain.
Figure 6: Viral Drug Resistance Inferred from Variations
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Appendix C – Participating Individuals and Organizations
Leadership Team
Carol Vaughn
Chuck Cooper
Diane Wold
Doris Li
Fatima Elnigoumi
Fred Wood
Helena Sviglin
James Sullivan
Jenise Gillespie-Pederson
Joy Li
Joyce Hernandez
Patricia Wesolowski
Patrick Harrington
Phil Pochon
Rhonda Facile
Rich Nagel
Sharon Wang
Ward Lemaire
Wayne Kubick
Organization Affiliation
Sanofi-Aventis
FDA, CDER Data Standards Program
GSK
IMCLONE
FDA, CDER Data Standards Program
Octagon Research Solutions
FDA, Center for Drug Evaluation and Research
(CDER)
Vertex
FDA, CDER Data Standards Program
FDA, Center for Drug Evaluation and Research
(CDER)
Merck (Project Leader)
Vertex
FDA, Center for Drug Evaluation and Research
(CDER)
Covance (Project Co-Leader)
CDISC (Project Co-Leader)
Liaison Technologies
Genentech
J&J
CDISC
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Appendix D – Representations and Warranties, Limitations of Liability, and Disclaimers
CDISC Patent Disclaimers
It is possible that implementation of and compliance with this standard may require use of subject matter covered by
patent rights. By publication of this standard, no position is taken with respect to the existence or validity of any
claim or of any patent rights in connection therewith. CDISC, including the CDISC Board of Directors, shall not be
responsible for identifying patent claims for which a license may be required in order to implement this standard or
for conducting inquiries into the legal validity or scope of those patents or patent claims that are brought to its
attention.
Representations and Warranties
Each Participant in the development of this standard shall be deemed to represent, warrant, and covenant, at the time
of a Contribution by such Participant (or by its Representative), that to the best of its knowledge and ability: (a) it
holds or has the right to grant all relevant licenses to any of its Contributions in all jurisdictions or territories in
which it holds relevant intellectual property rights; (b) there are no limits to the Participant¹s ability to make the
grants, acknowledgments, and agreements herein; and (c) the Contribution does not subject any Contribution, Draft
Standard, Final Standard, or implementations thereof, in whole or in part, to licensing obligations with additional
restrictions or requirements inconsistent with those set forth in this Policy, or that would require any such
Contribution, Final Standard, or implementation, in whole or in part, to be either: (i) disclosed or distributed in
source code form; (ii) licensed for the purpose of making derivative works (other than as set forth in Section 4.2 of
the CDISC Intellectual Property Policy (³the Policy²)); or (iii) distributed at no charge, except as set forth in Sections
3, 5.1, and 4.2 of the Policy. If a Participant has knowledge that a Contribution made by any Participant or any other
party may subject any Contribution, Draft Standard, Final Standard, or implementation, in whole or in part, to one or
more of the licensing obligations listed in Section 9.3, such Participant shall give prompt notice of the same to the
CDISC President who shall promptly notify all Participants.
No Other Warranties/Disclaimers. ALL PARTICIPANTS ACKNOWLEDGE THAT, EXCEPT AS PROVIDED
UNDER SECTION 9.3 OF THE CDISC INTELLECTUAL PROPERTY POLICY, ALL DRAFT STANDARDS
AND FINAL STANDARDS, AND ALL CONTRIBUTIONS TO FINAL STANDARDS AND DRAFT
STANDARDS, ARE PROVIDED ³AS IS² WITH NO WARRANTIES WHATSOEVER, WHETHER EXPRESS,
IMPLIED, STATUTORY, OR OTHERWISE, AND THE PARTICIPANTS, REPRESENTATIVES, THE CDISC
PRESIDENT, THE CDISC BOARD OF DIRECTORS, AND CDISC EXPRESSLY DISCLAIM ANY
WARRANTY OF MERCHANTABILITY, NONINFRINGEMENT, FITNESS FOR ANY PARTICULAR OR
INTENDED PURPOSE, OR ANY OTHER WARRANTY OTHERWISE ARISING OUT OF ANY PROPOSAL,
FINAL STANDARDS OR DRAFT STANDARDS, OR CONTRIBUTION.
Limitation of Liability
IN NO EVENT WILL CDISC OR ANY OF ITS CONSTITUENT PARTS (INCLUDING, BUT NOT LIMITED
TO, THE CDISC BOARD OF DIRECTORS, THE CDISC PRESIDENT, CDISC STAFF, AND CDISC
MEMBERS) BE LIABLE TO ANY OTHER PERSON OR ENTITY FOR ANY LOSS OF PROFITS, LOSS OF
USE, DIRECT, INDIRECT, INCIDENTAL, CONSEQUENTIAL, OR SPECIAL DAMAGES, WHETHER
UNDER CONTRACT, TORT, WARRANTY, OR OTHERWISE, ARISING IN ANY WAY OUT OF THIS
POLICY OR ANY RELATED AGREEMENT, WHETHER OR NOT SUCH PARTY HAD ADVANCE NOTICE
OF THE POSSIBILITY OF SUCH DAMAGES.
Note: The CDISC Intellectual Property Policy can be found at:
http://www.cdisc.org/about/bylaws_pdfs/CDISCIPPolicy-FINAL.pdf
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