3 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.
4 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.
5 Analysis Datasets and Tables, Listings, Graphs (TLGs) VAD ModuleReporting moduleIn: SDTMv data setsOut: Analysis dataIn: Analysis data setsOut: Standard TLGsSDTMADaMTLGsprocessAnalysis Datasets sometimes called VADs Value Added Datasets
6 Differences between SDTM and ADaM Designed for communication of scientific results of the trialContains collected and derived data as per analysis planMay use variables from multiple SDTM domains and other ADaM datasetsRedundancy is needed for easy analysis and may contain variables for supportive purposesNumeric variables are often needed for analysisDates are numeric to allow calculationHeavily reliant on descriptive metadataSDTMDesigned to store trial data as collectedNo redundancyDesigned for data transfer and InteroperabilityFew derived variablesStandard domains for each type of subject areaPredominantly character variablesDates are ISO8601 character strings
7 Going from SDTM to ADaM example of “composite endpoint”
8 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.
9 Where is it described: Core ADaM Standard Documents Analysis Data Model v2.1Analysis Data Model Implementation Guide v1.0Analysis Data Model Data Structure for Adverse Event Analysis v1.0The ADaM Basic Data Structure (BDS) for Time-to-Event Analyses v1.0ADaM Examples FinalADaM Validation Checks v1.2……..Plus Appendix referencesAnalysis Data Model vBasic principles and standards for metadata to apply to all analysis datasetsIntroduction to the Basic Data Structure (BDS) and Subject Level analysis dataset (ADSL)Descriptive metadata (specs) examplesAnalysis Data Model Implementation Guide vDefinition and standards for Basic Data Structure (BDS) and Subject Level Analysis dataset (ADSL)Standard implementation of analysis issuesStandard variable names and labelsADaM Examples Document 2011Illustrates ADaM concepts and principlesIt does NOT implement or advocate new rules or standardsAnalysis Data Model Data Structure for Adverse Event Analysis v1.02012 Dataset structure specifically for AE dataThe ADaM Basic Data Structure (BDS) for Time-to-Event Analyses v1.02012 How to use the BDS for TTE dataADaM Validation Checks vADaM Validation Checks in pdf and excel format
10 ADaM Dataset Classes ADSL (Subject Level Analysis Data) one record per subjectthe only required dataset in a CDISC-based submissionallows simple merging with other datasetsBDS (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 recordedOther future planned additional datasets : eg General Occurrences: Medications, Medical History.
11 ADSL & BDSGo to implementation guide for list of variables.
14 ADaM “Metadata” as described in the docs is: Analysis Dataset Metadata – description of datasetAnalysis 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.
15 ADaM Metadata Analysis Dataset Metadata Dataset name (e.g. ADEFF)Dataset Description (e.g. Primary Efficacy analysis dataset)Location – filepath where the dataset is storedStructure (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
17 ADaM Metadata Analysis Variable Metadata Variable Name and Dataset NameLabelTypeCodelist /Controlled terminologySource or derivationCore (Req Cond Perm)CDISC NotesAnalysis variable metadata describes each variable in the dataset.
19 ADaM Metadata Analysis Parameter-Value Level Metadata Part of Analysis Variable Metadata for VADs with BDS structureParameter 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.
20 Example of metadata for param codes – value level metadata
21 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.
22 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 analysisThese 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”
26 Summary of ADaM contents ADSL dataset structureBDS dataset structure (with BDS TTE and Lab section)ADAE dataset structureDescriptive metadata – for datasets, parameters (value level metadata) and results (Table, Listings, Graphs (TLG)) metadata.Validation checksDo we have to bear in mind direct links between SDTM model and ADaM model (eg ADSL, ADAE)………………scoping discussion