CDISC Submission Standards

StudySAS Blog

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 CDISC – Clinical Data Interchange Standards
Consortium

The mission of CDISC is to develop and support

global, platform-independent data standards that
enable information system interoperability to
improve medical research and related areas of
healthcare.

• SDTM – Study Data Tabulation Model

• FDA – Food and Drug Administration
• FDA desires SDTM data.
Future: require SDTM
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 July 2003, the FDA announced that the Study Data Tabulation Model
(SDTM) developed by CDISC would be the standard format for
sponsors of human drug clinical trials when submitting data to the FDA.

ODM (Operational Data Model),

LAB (Laboratory Data Model),
SDS (Submission Data Model),
ADaM (Analysis Dataset Model) which are under development by
CDISC are all XML based.

ODM- addresses data used during trials and analyses

LAB - describes ECG and other laboratory data standards
SDS - emphasizes data flow from database to regulatory submission
ADaM- defines safety domains and efficacy variables to facilitate
statistical analysis.

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 WHY STANDARDS?
65% - 75% submission information is associated with
safety data. A big volume of listings (e.g. for CRT
dataset and patient profile, etc.) is always included
even in electronic submissions.

Only 30% of programming time is used to generate

statistical results with SAS®, and the rest of
programming time to familiarize data structure,
check data accuracy, and tabulate/list raw data and
statistical results into certain formats.

This non-statistical programming time

because of CDISC’s uniform data structure, its useful
functions.

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 What is SDTM: Study Data Tabulation
Model
This model describes the
contents and structure of
SDTM
data collected during a
Animals clinical trial
Humans
(SEND) The purpose is to provide
(SDTMIG)
regulatory authority reviewers
(FDA) a clear description of
the structure, attributes and
contents of each dataset and
variables submitted as part of
a product application

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 Before SDTM
• Domains = Yes
• Standard Domain Names = No
• Standard Variables = No
• Standard Variable Names = No
Result
• Reviewers had to familiarize themselves with unique domain names,
variables and variable names used in an application - TIME CONSUMING
• Pooling, joining datasets awkward, difficult
• Good portion of review time spent “cleaning up the data”
• Inefficient, error-prone
After SDTM
• Domains = Yes
• Standard Domain Names = Yes
• Standard Variables = Yes
• Standard Variable Names = Yes
Result
•Standard Domain Names = Easy to Find Data
• Standard Variables/Variable Names = Immediate Familiarity with the Data
• Consistency
• Minimal learning curve
• TIME EFFICIENT

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Fundamentals of SDTM -
Domains
 Domain: Collection of observations with common topic
 Case Report Form ---- SDTM domain---- Dataset
– A domain may collect data from more than one CRF
form
– Generally each domain is represented by a dataset
 Each domain has a unique two-character domain name (e.g., AE, CM, VS)
 Variables in domain begin with the domain prefix: (e.g., VSTESTCD)
 Domain structure: vertical
 Two categories of domains:
– CDISC Standard Domains (spelled out in detail in the
Implementation Guide).
– Custom Domains
• Based on one of the General Observation Classes (findings, events,
interventions)
• Basic variables are outlined in the SDTM

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 Special
Interventions Events Findings
Purpose

Conmeds AE ECG Ques’aire Demog

Exposure Disposition Incl/Excl SubjChar Comments

SubjElements
SubstUse MedHx Labs Vitals v3.1.2
SubjVisits
Deviations
v3.1.2
v3.1.2 PhysExam DrugAcct
SUPPQUAL
Clinical PK Conc PK Param
Events v3.1.2 v3.1.2 RELREC
v3.1.2
SDTM = Study Data Tabulation Model
Micro MB Micro MS Trial Design
v3.1.2 v3.1.2 (5 Tables)
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SDTM General Observation
Classes
Interventions class captures investigational, therapeutic and other treatments
that are administered to the subject (with some actual or expected physiological
effect) either as specified by the study protocol (e.g., “exposure”), coincident
with the study assessment period (e.g., “concomitant medications”), or self-
administered by the subject (such as alcohol, tobacco, or caffeine)
Events class captures planned protocol milestones such as randomization and
study completion (“disposition”), and occurrences, conditions or incidents
independent of planned study evaluations occurring during the trial (e.g.,
“adverse events”) or prior to the trial (e.g., “medical history”)
Findings class captures the observations resulting from planned evaluations to
address specific tests or questions such as laboratory tests, histopathology, ECG
testing, and questions listed on questionnaires. Most findings are measurements,
tests, assessments, or examinations performed on a subject in the clinical trial

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SDTM Basics - Special-Purpose
Datasets
Not Classified as Interventions, Events, or Findings
They Have Special Rules
– Demographics (DM)
– Comments (CO): free text comments
– Trial domains: to describe the design of a trial
– RELREC dataset: represent the relationship between
datasets and records
– SUPPQUAL: used for data items not included in the
SDTM standard

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 Fundamentals of SDTM - Variables
• CDISC categorizes variables as being
– Required: variables need to be in the domains
• Their values cannot be null
– Expected: variables need to be in the domain
• Some values may be null
– Permissible: variables included in the domain as
needed
• CDISC categorizes variables into five roles
– Identifier: identify the study, subject no., the
sequence number
– Topic: specify the focus of the observation
(such as the name of the lab test)
– Timing: describe the timing of the observation
(Visit, Start/End date, Days, Time Points,
Duration)
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 Fundamentals of SDTM - Variables
• Variables Attributes
– Variable Name: limited to 8-chars
– Variable Label: <=40 chars
– Variable Type: mainly characters
– Variable Length: <=200 chars

• Date/time format
– ISO 8601 is a text string YYYY-MM-DDT hh:mm:ss (not
a SAS format)
– Has ability to handle incomplete date
– Example: December 15, 2003 13:14:17 ----- 2003-12-
15T13:14:17
December 15, 2003 ------------------ 2003-12-
15

• Controlled Terms or Format

– Controlled terminology or text should be used instead
of, or in addition to arbitrary number codes (No SAS
format!!)
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 Example

“Subject 9201 had mild fatigue starting on Day 3.”

Topic Variable = adverse event = fatigue

Identifier Variable = subject ID = subject 9201
Timing Variable = start date = Day 3
Qualifier Variable = severity = mild
Observation Record

Grouping Synonym Result Variable Record

Topic Identifier Timing Qualifier
Qualifier Qualifier Qualifier Qualifier

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 Basic Concepts in CDISC/SDTM
Variable Roles
Grouping qualifiers
are used to group together a collection of observations within the same domain.
Topic variables
– Examples include --CAT, --SCAT, --GRPID, --SPEC, --LOT, and --NAM. The latter three
which specify the focus of the observation (such
grouping qualifiers can be used to tie a set of observations to a common source (i.e.,
as the name of a lab test), and vary according to specimen, drug lot, or laboratory name, respectively)
the type of observation.
Synonym Qualifiers
specify an alternative name for a particular variable in
Identifier variables an observation.
which identify the study, the subject (individual – Examples include --MODIFY and --DECOD, which are equivalent terms for a --TRT or
human or animal) involved in the study, the --TERM topic variable,
domain, and the sequence number of the and --LOINC which is an equivalent term for
record. a --TEST and --TESTCD.
Result Qualifiers
describe the specific results associated with the topic variable for a finding. It is the answer to
Timing variables the question raised by the topic variable. Depending on the type of result (numeric or character)
which describe the timing of an observation different variables are being used. Includes variables for both original (as supplied values) and
(such as start date and end date). for standardised values (for uniformity).
– Examples include --ORRES,
--STRESC, and --STRESN.
Variable Qualifiers
are used to further modify or describe a specific variable within an observation and is only
meaningful in the context of the variable they qualify.
– Examples include --ORRESU, --ORNHI, and --ORNLO, all of which are variable
qualifiers of --ORRES: and --DOSU, --DOSFRM, and --DOSFRQ, all of which are
variable qualifiers of --DOSE.
– Indictors where the results falls with respect to reference range
Record Qualifiers
define additional attributes of the observation record as a whole (rather than describing a
particular variable within a record).
– Examples include --REASND, AESLIFE, and all other SAE flag variables in the AE
domain; and
--BLFL, --POS and --LOC.

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SDTM Mapping examples
 1:1 mapping
 Date of birth on a CRF page → Column “BRTHDTC” in SDTM DM table (horizontal)

 Sex on a CRF page → Column “SEX” in SDTM DM table (horizontal)

 Weight and Height on a CRF page → Weight and Height in the column “VSORRES” of the SDTM VS table (vertical)

 1:N mapping
 Visit date on one CRF page → Visit date in many SDTM tables

 M:1 mapping
 Date of FU visit on a CRF page - Date of baseline Visit on another CRF page → Study day in SDTM

 DIRECT: a CDM variable is copied directly to a domain variable without any changes other than assigning the CDISC standard
label.

 RENAME: only the variable name and label may change but the contents remain the same.

 STANDARDIZE: mapping reported values to standard units or standard terminology

 REFORMAT: the actual value being represented does not change, only the format in which is stored changes, such as
converting a SAS date to an ISO8601 format character string.

 COMBINING: directly combining two or more CDM variables to form a single SDTM variable.

 SPLITTING: a CDM variable is divided into two or more SDTM variables.

 DERIVATION: creating a domain variable based on a computation, algorithm, series of logic rules or decoding using one or
more CDM variables.

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StudySAS Blog
Implementation
Challenges
1. CDISC Variable Names
All dataset column names must follow the standards
in the SDTM.
Example:
• Sponsor uses a variable named AEBGDT for the
beginning of an adverse event.
• SDTM variable name is AESTDTC.
• The sponsor must rename the variable.

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2. Fitting Data into the Findings Observation Class (1)

• Some datasets may be structured to facilitate analysis or the

use of code lists (e.g., one record per subject per visit), and will
require transformation to conform to the structure of the
Findings model (one record per measurement).

• Existing denormalized datasets could still be used and

submitted as analysis datasets after columns are renamed

2. Fitting Data into the Findings Observation Class (2)

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