Sample Reporting Methodology

Overview

The primary purpose of the CDISC ADaM standard is to build analysis data sets that support analysis and reporting of clinical research. This purpose, in turn, supports the greater goal of submitting clinical research results to regulatory authorities. These regulatory authorities determine the efficacy and safety of a medical device or product.

The Analysis Data Model, Version 2.1, ADaM Document provides specifications for the structure and content of analysis data sets, and a suggested metadata format for documenting the analysis results generated. Analysis results metadata describe the major attributes of a specified analysis result found in a clinical study report or submission. Analysis results metadata support traceability from an analysis result used in a statistical display to the data in the analysis data sets.

The SAS Clinical Standards Toolkit representation of the ADaM standard includes a sample implementation of an analysis reporting methodology.

Note: This methodology is for illustrative purposes only. Each organization has its own set of processes and workflows that support the generation of a clinical study report or submission. The sample reporting methodology provided with the SAS Clinical Standards Toolkit is intended to be representative of similar industry reporting methodologies. The intent is not to provide a definitive reporting methodology, but to illustrate the interaction of reporting components through the adoption of the ADaM standard.

Key clinical trial reporting components are described in this table.

Key Clinical Trial Reporting Components

Reporting Component	Comments
Clinical Protocol, Statistical Analysis Plan	Used to identify and define data to be collected, analysis methods and algorithms to be used, and efficacy endpoints and safety measures that determine report output.
Source Data	Source data for analysis data sets, often SDTM. Traceability back to source data is a key ADaM requirement.
Source Metadata	Metadata about the source data.
Controlled Terminology	Set of allowable terms used in any source or analysis data set. For CDISC, NCI EVS serves as the primary source of terms.
Analysis Data Sets	ADaM data sets, typically including the ADSL data set and any number of BDS data sets (for example, ADAE and ADLB) required to support analyses.
Analysis Data Set Metadata	Metadata about the analysis data sets.
Analysis Results (Tables, Listings, and Figures)*	The set of statistical displays (for example, text, tabular, or graphical presentation of results) or inferential statements (such as p-values or estimates of treatment effect).
TLF Metadata (to include table shells)*	Commonly provided as table shells, which provide templates for the statistical displays. Can also include display-specific metadata (often as Microsoft Excel files) used by the analysis programs to generate the displays.
Analysis Results Metadata*	Defined by the Analysis Data Model, Version 2.1, ADaM Document, Section 5.3. For more information, see Analysis Results Metadata.
Analysis Programs*	Programming code that uses the analysis data sets (and, optionally, TLF metadata) to create the analysis results.
Submission Package (for example, eCTD)	The structured submission used to package data, metadata, code, and results in a standard form to facilitate review.
Define.xml	A metadata format that documents each tabulation (SDTM) or analysis (ADaM) data set, ancillary documents, and controlled terminology for a study or submission.
CSR/ISS/ISE	The focus of each ADaM implementation. Most commonly a Clinical Study Report (CSR) for a single clinical study. Can be an Integrated Summary of Safety (ISS) or Integrated Summary of Efficacy (ISE) across multiple clinical studies.

*Component that is discussed later in this section.

The majority of the files supporting the ADaM sample reporting methodology provided with the SAS Clinical Standards Toolkit are located in the ADaM analysis folder:

!sasroot/../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/analysis

Here is an illustration of the ADaM analysis folder hierarchy:

SAS Clinical Standards Toolkit ADaM Analysis Folder Hierarchy

Here are noteworthy folders:

The code folder contains the code to create each statistical display. This corresponds to the Analysis Results component described in Key Clinical Trial Reporting Components.
The data folder contains the display-specific metadata noted in the TLF Metadata component of Key Clinical Trial Reporting Components.
The documents folder contains table shells for the TLF Metadata component. For more information about table shells, seeTLF Metadata.
The results folder contains several sample statistical displays, which correspond to the Analysis Results component.

TLF Metadata

A common industry reporting strategy is to create table shells (templates) which specify the output for each statistical display. The SAS Clinical Standards Toolkit provides sample table shells in this file:

!sasroot/../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/analysis/documents/Mock_tables_shells.pdf

One of these displays, a table reporting patient demographics (Table 14.2.01), follows:

SAS Clinical Standards Toolkit Sample Table Shell

The elements of each table shell (for example, titles, footnotes, headings, column and row labels, cell formatting, and so on) are sometimes captured in a metadata format, often in Microsoft Excel files. The usual intent is to create reporting macros that can generate analysis reports based on this metadata, so that changes in metadata are all that is required to modify and rerun any report.

For the SAS Clinical Standards Toolkit 1.4, sample metadata is included that illustrates the use of such metadata within the ADaM reporting environment.

Note: The sample metadata provided does not represent a full implementation. All metadata fields used in the report examples are not provided.

Supplemental metadata is provided in this file:

!sasroot/../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/metadata/tlfddt.xml

To interpret this metadata, a sample SAS XML map file (tlfddt.map) is provided in the same folder. SAS data sets, representing this XML metadata, are provided in the library of SAS files located in this folder:

!sasroot/../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/analysis/data

The following figures provide examples of some of the metadata available in the source XML file. This metadata has been extracted into SAS data sets.

Sample TLF Metadata: Tlf_index

Sample TLF Metadata: Tlf_master

Sample TLF Metadata: Tlf_titles

Row 1 of the Tlf_master data set describes a centered landscape table and shows where the generating code can be found. The title for that table is provided in the Tlf_titles file. These tables correspond to the table shell titles specified in SAS Clinical Standards Toolkit Sample Table Shell.

Analysis Programs

The analysis program to generate sample Table 14.2.01 is located in this folder:

!sasroot/../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/analysis/code

Two versions are provided:

Table_14.2.01.sas uses the TLF metadata described previously.
Table_14.2.01_nomd.sas does not rely on TLF metadata to generate the report output.

As noted above, these sample analysis programs do not fully use the sample TLF metadata provided with the SAS Clinical Standards Toolkit. The basic coding strategy adopted with each SAS Clinical Standards Toolkit sample analysis program is to build each section (one or more row combinations) and to concatenate these sections into a single input file used by PROC REPORT.

A sample driver module is provided to perform the process setup, to define (or reference) the sasreferences data set, to perform any required report setup, and to call the generic ADaM reporting macro adam_createdisplay(). This sample driver module is located in this folder:

!sasroot/../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/programs/analyze_data.sas

In the sample driver module, a call is made to adam_createdisplay() for each analysis report to be produced:

%adam_createdisplay (displaysrc=Metadata,useanalysisresults=N,usetlfddt=Y,
displayid=%str(Table_14.2.01));

To automate this process of creating all analysis reports for a study, it would be necessary to cycle through any available metadata (such as that described in Sample TLF Metadata: Tlf_master) to construct multiple calls to the adam_createdisplay macro. The adam_createdisplay macro header provides an overview of the macro functionality and a summary of the defined macro parameters:

adam_createdisplay

Generate an analysis result from ADaM analysis data sets

The basic function of this code module is to create an analysis result display. The path to
the code to create the display is provided either directly in the macro parameters or is
derived from a metadata source such as the analysis results metadata or Tables, Listings
and Figures data definition metadata (TLFDDT) you maintain and reference in the SASReferences
data set.

Two primary paths (parameter settings) are supported:
(1) A code source is specified. A fully qualified path is required. The expectation is
that this module will be %included below to generate an analysis result (display).
(2) Metadata is to be used to provide the information necessary to generate an analysis
result (display). This metadata will be in the form of the CDISC-ADaM Analysis Results metadata,
supplemental Tables, Listings and Figures data definition metadata (TLFDDT), or both.

@param displaysrc - Where will information come from to generate result? Values: Code |
Metadata (default). Required.
@param displaycode - Either a valid filename or the fully qualified path to code to produce an
analysis result. Required and used only if displaysrc=Code. All of the remaining parameters
below are ignored.
@param useanalysisresults - Should the study-specific analysis results metadata be used to
provide report metadata? Values: N | Y (default). Either this parameter or usetlfddt must
be set to Y if displaysrc=Metadata. If both the useanalysisresults and usetlfddt parameters
are set to Y, useanalysisresults will take precedence.
@param usetlfddt - Should the study-specific mock tables shells metadata (known here as Tables,
Listings and Figures data definition metadata (TLFDDT)) be used to provide report metadata?
Values: N | Y (default). Either this parameter or useanalysisresults must be set to Y if
displaysrc=Metadata. If both the useanalysisresults and usetlfddt parameters are set to Y,
useanalysisresults will take precedence.
@param displayid - The ID of the display from the designated metadata source. Required if
displaysrc=Metadata.
@param displaypath - Either a valid filename or the fully qualified path to the generated
display. Optional. If not provided, code looks in SASReferences for type=report.

The SAS Clinical Standards Toolkit ADaM reporting methodology uses a report.properties file to specify the default report format. By default, the property (and global macro variable) _cstDefaultReportFormat is set to PDF. Submitting the analyze_data.sas driver module produces the specified statistical displays and generates a process results data set. Here is a sample results data set:

Sample Results Data Set Generated by the analyze_data.sas Driver Module

Analysis Results (Tables, Listings, and Figures)

Each generated statistical display should correspond to a table shell, as described in the TLF Metadata section. (See SAS Clinical Standards Toolkit Sample Table Shell.)

For example, the Summary of Demographic and Baseline Characteristics provided in Table 14.2.01 is shown in this figure:

Sample Analysis Report: Table 14.2.01

Analysis Results Metadata

The Analysis Data Model, Version 2.1, ADaM Document provides specifications for capturing analysis results. As a result, traceability back to the contributing source data is possible. Analysis Results Metadata identifies the columns to be included in the analysis results data set. All analysis results metadata for the two statistical displays provided with the SAS Clinical Standards Toolkit is shown in this figure:

Analysis Results Metadata

The analysis results data set is located at:

!sasroot/.../SASClinicalStandardsToolkitADaM21/1.4/sample/cdisc-adam-2.1/sascstdemodata/metadata/analysis_results.sas7bdat