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 (ADaM), Version 2.1 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) For more information, see 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) For more information, see TLF Metadata.	Commonly provided as table shells. Can also include display-specific metadata (often as Microsoft Excel files) used by the analysis programs to generate the displays.
Analysis Results Metadata For more information, see Analysis Results Metadata.	Defined by the Analysis Data Model (ADaM), Version 2.1 document, Section 5.3. For more information, see Analysis Results Metadata.
Analysis Programs For more information, see 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.

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:

sample study library directory/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, see TLF 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:

sample study library directory/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 1.5, 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:

sample study library directory/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:

sample study library directory/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:

sample study library directory/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 program 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 program is located in this folder:

sample study library directory/cdisc-adam-2.1/sascstdemodata/programs/analyze_data.sas

In the sample driver program, 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                                                             
                                                                               
Creates an analysis result display from ADaM analysis data sets.               
                                                                               
The path to the code to create the display is provided either directly in the  
macro parameters or is derived from a metadata source. Examples of metadata    
sources are analysis results metadata or Tables, Listings, and Figures data    
definition metadata (TLFDDT) that 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 is %included below to generate an        
      analysis result (display).                                               
   2. Metadata provides the information necessary to generate an analysis      
      result (display). This metadata is in the form of the CDISC ADaM         
      analysis results metadata, supplemental Tables, Listings, and Figures    
      data definition metadata (TLFDDT), or both.                              
                                                                               
@macvar studyRootPath Root path to the sample source study                     
@macvar _cstCTDescription Description of controlled terminology packet         
@macvar _cstDebug Turns debugging on or off for the session                    
@macvar cstDefaultReportFormat Specifies the SAS ODS report destination        
@macvar _cstGRoot Root path of the Toolkit Global Library                      
@macvar _cstResultsDS Results data set                                         
@macvar _cstResultSeq Results: Unique invocation of check                      
@macvar _cstSASRefs Run-time SASReferences data set derived in process setup   
@macvar _cstSeqCnt Results: Sequence number within _cstResultSeq               
@macvar _cstSrcData Results: Source entity being evaluated                     
@macvar _cstStandard Name of a standard registered to Toolkit                  
@macvar _cstStandardVersion Version of the standard referenced in _cstStandard 
@macvar _cst_rc Task error status                                              
@macvar _CSTTLF_MASTERCODEPATH Dynamically derived code segment path from      
           TLF metadata.                                                       
@macvar workpath Path to the SAS session work library                          
                                                                               
@param _cstDisplaySrc - required - Where information comes from to generate    
           the result.                                                         
           Values:  Code | Metadata                                            
           Default: Metadata                                                   
@param _cstDisplayCode - conditional - Either a valid filename or the fully    
           qualified path to code that produces an analysis result. If         
           _cstDisplaySrc=Code, this parameter is used and is required. All of 
           the remaining parameters are ignored.                               
@param _cstUseAnalysisResults - conditional - The study-specific analysis      
           results metadata are used to provide report metadata.               
           If _cstDisplaySrc=Metadata, either this parameter or _cstUseTLFddt  
           must be set to Y. If both _cstUseAnalysisResults and _cstUseTLFddt  
           are set to Y, _cstUseAnalysisResults takes precedence.              
           Values:  N | Y                                                      
           Default: Y                                                          
@param _cstUseTLFddt - conditional - The study-specific mock table shell       
           metadata (known as Tables, Listings, and Figures data definition    
           metadata (TLFDDT)) are used to provide report metadata.             
           If _cstDisplaySrc=Metadata, either this parameter or                
           _cstUseAnalysisResults must be set to Y. If both                    
           _cstUseAnalysisResults and _cstUseTLFddt are set to Y,              
           _cstUseAnalysisResults takes precedence.                            
           Values:  N | Y                                                      
           Default: Y                                                          
@param _cstDisplayID - conditional - The ID of the display from the designated 
           metadata source. If _cstDisplaySrc=Metadata, this parameter is      
           required.                                                           
@param _cstDisplayPath - optional - A valid filename or the fully qualified    
           path to the generated display. If not provided, the 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 (ADaM), Version 2.1 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:

sample study library directory/cdisc-adam-2.1/sascstdemodata/metadata/analysis_results.sas7bdat