Integrating Analysis Result Metadata (ARM) in Existing Define.xml: A Simple Method for Enhancing Clinical Trial Data Integrity
Introduction
Clinical trials are crucial in the development of new drugs and therapies. The regulatory authorities review the data from these trials before approving the drugs for use in patients. The review process involves examining the statistical analyses and datasets used in the trials. In order to streamline the review process, regulatory authorities require that the results of the trials be submitted in a standardized format called the define.xml. Analysis Result Metadata (ARM) adds significant value to a regulatory submission. It provides agency reviewers with a means to trace results back to their source documents, such as key pieces of SAS programs used for analysis, datasets, data selection criteria, and even specific pages in a statistical analysis plan. However, the define.xml for many completed studies does not have ARM included due to earlier technical constraints. This article presents a method for integrating ARM in existing define.xml version 2.0.
The Need for ARM in Define.xml
Define.xml is a standard format for submitting clinical trial data to regulatory authorities. It is an XML file that contains metadata describing the data used in the trial, such as the datasets, variables, and statistical analyses. Define.xml provides a standard way for regulatory authorities to access and review the data submitted by sponsors. ARM adds another layer of metadata to define.xml, providing a link between the results in the define.xml and the source documents used to generate them. ARM includes information such as the data selection criteria used for statistical analysis, the SAS programs used for generating the results, and the specific pages in the statistical analysis plan where the results were derived from. By including ARM in define.xml, regulatory authorities can trace the results back to their source documents, ensuring the integrity and accuracy of the data submitted.
Challenges in Including ARM in Define.xml
Despite the benefits of including ARM in define.xml, many completed studies do not have ARM included due to technical constraints at the time of study completion. Furthermore, the latest version of Pinnacle 21 (P21), a popular software tool used for generating define.xml files, does not have the capability to generate define.xml with the feature of ARM. This creates a challenge for sponsors who want to include ARM in existing define.xml files for future submissions. Fortunately, a simple method has been developed to address this issue.
Method for Integrating ARM in Existing Define.xml
The method for integrating ARM in existing define.xml involves two steps: (1) collecting the necessary information for ARM in an Excel spreadsheet, and (2) using a macro to convert the collected information to ASCII text in valid xml syntax and adding them to proper locations in existing define.xml. The Excel spreadsheet is designed to collect information such as the data selection criteria, the SAS programs used for generating the results, and the specific pages in the statistical analysis plan where the results were derived from. The macro then converts this information to ASCII text in valid xml syntax and adds it to the appropriate locations in the existing define.xml. The resulting define.xml file includes all the necessary ARM features and passes P21 define.xml schema validation, making it ready for submission to regulatory authorities.
Conclusion
Integrating ARM in existing define.xml files is an important step in ensuring the accuracy and integrity of clinical trial data submitted to regulatory authorities. Despite the technical constraints that prevented the inclusion of ARM in earlier define.xml files, a simple method has been developed to add ARM to existing define.xml files. The method involves collecting the necessary information in an Excel spreadsheet and using a macro to convert the collected information to valid xml syntax and add it to the appropriate locations in the define.xml file. This method has been shown to be effective in creating define.xml files that include all the necessary ARM features and pass P21 define.xml schema validation.
