Quick tour of CDISC’s ADaM standard

FDA/PHuSE ADaM Kick off Meeting

Location in the CDISC Standards ADaM is the last standard in the food chain when it comes to presenting the results of a clinical trial for revision by the authorities.

Clinical trial data and information flow Going back to basics, a protocol is written with the plans for the trial and from that some sort of Statistical Analysis Plan is written to define how the results from the patients will be presented in order to prove safety and efficacy of the drug. Data is collected from the patients and stored in a system called SDTM. The SDTM data is taken and processed into other datasets called Analysis Datasets which summarise and calculate results. These Analysis datasets are then used to create reports here called Analysis results.

Analysis Datasets and Tables, Listings, Graphs (TLGs) VAD Module Reporting module In: SDTMv data sets Out: Analysis data In: Analysis data sets Out: Standard TLGs SDTM ADaM TLGs process Analysis Datasets sometimes called VADs Value Added Datasets

Differences between SDTM and ADaM Designed for communication of scientific results of the trial Contains collected and derived data as per analysis plan May use variables from multiple SDTM domains and other ADaM datasets Redundancy is needed for easy analysis and may contain variables for supportive purposes Numeric variables are often needed for analysis Dates are numeric to allow calculation Heavily reliant on descriptive metadata SDTM Designed to store trial data as collected No redundancy Designed for data transfer and Interoperability Few derived variables Standard domains for each type of subject area Predominantly character variables Dates are ISO8601 character strings

Going from SDTM to ADaM example of “composite endpoint”

ADaM is designed to standardise the way that analysis results are stored and thus presented to authorities. It is predominantly designed for statistical analyses to reduce and eliminate any processing required by the reviewer.

Where is it described: Core ADaM Standard Documents www.cdisc.org/adam Analysis Data Model v2.1 Analysis Data Model Implementation Guide v1.0 Analysis Data Model Data Structure for Adverse Event Analysis v1.0 The ADaM Basic Data Structure (BDS) for Time-to-Event Analyses v1.0 ADaM Examples Final ADaM Validation Checks v1.2 ……..Plus Appendix references Analysis Data Model v2.1 2009 Basic principles and standards for metadata to apply to all analysis datasets Introduction to the Basic Data Structure (BDS) and Subject Level analysis dataset (ADSL) Descriptive metadata (specs) examples Analysis Data Model Implementation Guide v1.0 2009 Definition and standards for Basic Data Structure (BDS) and Subject Level Analysis dataset (ADSL) Standard implementation of analysis issues Standard variable names and labels ADaM Examples Document 2011 Illustrates ADaM concepts and principles It does NOT implement or advocate new rules or standards Analysis Data Model Data Structure for Adverse Event Analysis v1.0 2012 Dataset structure specifically for AE data The ADaM Basic Data Structure (BDS) for Time-to-Event Analyses v1.0 2012 How to use the BDS for TTE data ADaM Validation Checks v1.2 2012 ADaM Validation Checks in pdf and excel format

ADaM Dataset Classes ADSL (Subject Level Analysis Data) one record per subject the only required dataset in a CDISC-based submission allows simple merging with other datasets BDS (Basic Data Structure) – one or more records per subject, per analysis parameter per analysis timepoint (Also used for time to event analyses and LABs. ADAE (Adverse Events) one row per subject per adverse event recorded Other future planned additional datasets : eg General Occurrences: Medications, Medical History.

ADSL & BDS Go to implementation guide for list of variables.

BDS example

ADaM RA VAD

ADaM “Metadata” as described in the docs is: Analysis Dataset Metadata – description of dataset Analysis Variable Metadata (dataset structures) Analysis Parameter Value-Level Metadata – specs/derivations used to create analysis values (paramcds) Analysis Results Metadata – derivations and statistical procedures used for a report.

ADaM Metadata Analysis Dataset Metadata Dataset name (e.g. ADEFF) Dataset Description (e.g. Primary Efficacy analysis dataset) Location – filepath where the dataset is stored Structure (e.g. one observation per subject per visit) Class (e.g. “ADSL” , “BDS” or OTHER) Key variables (e.g. USUBJID, AVISIT, PARAMCD) Documentation (e.g. Descriptions of source data, processing steps or references to external documents like Protocol, DAP) These can be included as separate files and hyperlinked

ADaM Metadata Analysis Dataset Metadata

ADaM Metadata Analysis Variable Metadata Variable Name and Dataset Name Label Type Codelist /Controlled terminology Source or derivation Core (Req Cond Perm) CDISC Notes Analysis variable metadata describes each variable in the dataset.

ADaM Metadata Analysis Variable Metadata

ADaM Metadata Analysis Parameter-Value Level Metadata Part of Analysis Variable Metadata for VADs with BDS structure Parameter Identifier for different values of PARAM/PARAMCD contains specifications for how the parameters are derived. In a BDS analysis dataset, the variable PARAM contains a unique description for every analysis parameter included in that dataset. The variable PARAMCD contains the short name of the analysis parameter in PARAM, with a one-to-one mapping between the two variables.

Example of metadata for param codes – value level metadata

Descriptive metadata representation… …………The display presentation of the metadata should be determined between the sponsor and the recipient. The example is only intended to illustrate content and not appearance.

ADaM Metadata Analysis Results Metadata Allows reviewers to link from an analysis result to important information describing the analysis such as the reason for performing the analysis, and the dataset and selection criteria used to generate the analysis These metadata provide traceability from a result used in a statistical display to the data in the analysis datasets. Analysis results metadata are not required. However, best practice is that they be provided to assist the reviewer by identifying the critical analyses, providing links between results, documentation, and datasets, and documenting the analyses performed. These metadata provide traceability from a result used in a statistical display to the data in the analysis datasets. Analysis results metadata are not required. However, best practice is that they be provided to assist the reviewer by identifying the critical analyses, providing links between results, documentation, and datasets, and documenting the analyses performed. For further details see ADaM 2.1 Section 5.3 “ Analysis Results Metadata”

ADaM Metadata Analysis Results Metadata

Validation Checks

Special AE dataset structure

Summary of ADaM contents ADSL dataset structure BDS dataset structure (with BDS TTE and Lab section) ADAE dataset structure Descriptive metadata – for datasets, parameters (value level metadata) and results (Table, Listings, Graphs (TLG)) metadata. Validation checks Do we have to bear in mind direct links between SDTM model and ADaM model (eg ADSL, ADAE) ………………scoping discussion