CDISC ADaM 2.1

Purpose

The Analysis Data Model (ADaM) specifies the fundamental principles and standards to follow when creating analysis data sets and associated metadata. ADam supports efficient generation, replication, and review of analysis results. The design of analysis data sets is generally driven by the scientific and medical objectives of the clinical trial. A fundamental principle is that the structure and content of the analysis data sets must support clear, unambiguous communication of the scientific and statistical aspects of the clinical trial.

The purpose of ADaM is to provide a framework that enables analysis of the data. At the same time, ADaM enables reviewers and other recipients of the data to have a clear understanding of the data’s lineage from collection to analysis to results. Whereas ADaM is optimized to support data derivation and analysis, CDISC Study Data Tabulation Model (SDTM) is optimized to support data tabulation.

Release Date

CDISC ADaM Analysis Data Model, Final Version 2.1, December 17, 2009

The ADaM Basic Data Structure for Time-to-Event Analyses, Version 1.0, May 8, 2012

Analysis Data Model (ADaM) Data Structure for Adverse Event Analysis, Version 1.0, May 10, 2012

Regulatory Basis

(Source: Submission of Data in CDISC Format to CBER, http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/ucm209137.htm, page updated: October 18, 2013)

Effective December 15, 2010, SDTM and ADaM are being accepted for CBER IND, NDA, and BLA submissions.

(Source: Study Data Specifications, Version 1.5.1, January 4, 2010)

“Prior to submission, sponsors should contact the appropriate center’s reviewing division to determine the division’s analysis dataset needs. CDISC/ADaM standards for analysis datasets (www.cdisc.org/adam) may be used if acceptable to the review division.”

(Source: CDER Common Data Standards Issues Document, Version 1.1/December 2011, http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM254113.pdf)

“In determining how to create ADaM analysis datasets for submission to CDER, sponsors should refer to three documents: the Analysis Data Model and the ADaM Implementation Guide (www.CDISC.org), and the FDA Study Data Specifications Document (http://www.fda.gov/downloads/ForIndustry/DataStandards/StudyDataStandards/UCM199599.pdf). Close adherence to the ADaM Implementation Guide is expected and any specific questions that result from attempts to adhere to these documents should be discussed with the review division.”

CDISC ADaM 2.1 Reference Standard

Section 2.1 of the Analysis Data Model Implementation Guide provides the fundamental principles of the CDISC ADaM model.

Analysis data sets and associated metadata must clearly and unambiguously communicate the content and source of the data sets supporting the statistical analyses performed in a clinical study.
Analysis data sets and associated metadata must provide traceability to enable an understanding of where an analysis value came from.
Analysis data sets must be readily usable with commonly available software tools.
Analysis data sets must be associated with metadata to facilitate clear and unambiguous communication. Ideally, the metadata is machine-readable.
Analysis data sets should have a structure and content that enable statistical analyses to be performed with minimal programming. Such data sets are described as analysis-ready.

Implementation of the CDISC ADaM 2.1 reference standard in the SAS Clinical Standards Toolkit supports each of these principles.

The number and structure of analysis data sets are highly dependent on the type of study, the study objectives as defined in the statistical analysis plan, and discussions with the reviewing authority. ADaM data sets incorporate derived and collected data that permit analysis with little or no additional programming. Data can be from various SDTM domains, other ADaM data sets, or any combination thereof.

The CDISC ADaM 2.1 reference standard currently supports these analysis data set structures:

The subject-level analysis data set (ADSL) provides descriptive information about subjects, such as study disposition, demographic, and baseline characteristics. The ADSL is the primary source for subject-level variables included in other analysis data sets, such as population flags and treatment variables. There is only one ADSL per study, and the ADSL and its related metadata are required in each CDISC-based submission of data from a clinical trial, even if no other analysis data sets are submitted.
The ADaM Basic Data Structure (BDS) is used for the majority of ADaM data sets, regardless of the therapeutic area or type of analysis. Each BDS data set contains one or more records per subject and analysis parameter. The structure of some BDS data sets might include an analysis time point. A record in a BDS analysis data set can represent an observed, derived, or imputed value required for analysis. Each BDS data set contains a core set of variables that describe the analysis parameter and the value being analyzed. A data value can be derived from any source file, including any combination of SDTM and ADaM data sets. The Time-to-Event analysis data set is an example implementation of the BDS structure.
The Adverse Event analysis data set (ADAE) structure is built on the nomenclature of the CDISC SDTM Implementation Guides for collected data. The ADAE data set adds attributes, variables, and data structures that are required for statistical analyses. The primary SDTM source domain for the ADAE data set is AE, with the corresponding SUPPAE. Additional variables can be added from the ADaM ADSL data set. The ADAE data set is required when SDTM AE is not sufficient to support all adverse event analyses. The ADAE structure for the standard adverse event safety data set has at least one record per each AE recorded in the SDTM AE domain.

Metadata for the ADSL, BDS, and ADAE data sets is defined in the SAS Clinical Standards Toolkit reference_tables data set in the standard metadata folder.

The Analysis Data Model identifies four types of metadata that are captured and supported by the SAS Clinical Standards Toolkit.

ADaM Metadata Types and SAS Clinical Standards Toolkit Locations
ADaM Metadata Type	SAS Clinical Standards Toolkit Location
Analysis data set metadata	global standards library reference_tables.sas7bdat
Analysis variable metadata	global standards library reference_columns.sas7bdat
Analysis parameter-value-level metadata	global standards library valuemetadata.sas7bdat template sample library metadata source_values.sas7bdat example
Analysis results metadata	global standards library analysis_results.sas7bdat template sample library metadata analysis_results.sas7bdat example

Version 1.0 of the Analysis Data Model Implementation Guide (ADaMIG) defines a common set of ADSL and BDS columns that can be used as templates for ADaM analysis data sets. This set of ADSL and BDS columns has been supplemented with Version 1.0 of the Analysis Data Model (ADaM) Data Structure for Adverse Event Analysis. Metadata for the 290 columns in the SAS representation of ADSL, BDS, and ADAE is defined in the SAS Clinical Standards Toolkit reference_columns data set in the standard metadata folder. Empty ADSL, BDS, and ADAE data sets containing these columns can be derived from the SAS Clinical Standards Toolkit global standards library using the utility macro %CST_CREATETABLESFORDATASTANDARD.

The SAS Clinical Standards Toolkit CDISC ADaM reference standard also provides metadata and code to validate the structure and content of the ADaM analysis data sets.

To enable validation, supplemental files supporting ADaM validation processes include these SAS Clinical Standards Toolkit global standards library files:

The Validation Master data set in the validation/control folder contains the superset of checks validating the structure and content of each analysis data set. These checks are based on versions 1.1 and 1.2 of the CDISC ADaM Validation Checks as prepared by the CDISC ADaM team, as well as selected checks that are unique to the SAS Clinical Standards Toolkit.
The Messages data set in the messages folder provides error messaging for all Validation Master checks.
SAS code in the macros folder provides code that is specific to ADaM that augments code that is provided in the primary SAS Clinical Standards Toolkit autocall library (!sasroot/cstframework/sasmacro).

These supplemental files, in whole or in part, define the SAS Clinical Standards Toolkit CDISC ADaM reference standard.