Streamlining the Regulatory Submission Process: Understanding Integrated Analysis Data Approaches in Pharmaceutical and Biotechnology
The Pharmaceutical and biotechnology industries are working hard to get their products to market as quickly and efficiently as possible. In order to achieve this, they must follow regulatory guidelines and standards set by regulatory agencies like the FDA. To streamline this process, industry groups like CDISC and PHUSE have been working on standardizing the data and documentation submitted by companies for regulatory review.
In 2016, the FDA mandated that companies adopt the CDISC data format for individual studies for NDA, ANDA, and BLA submissions. While this format has helped with consistency in the presentation of data for individual studies, there was a lack of standardization for presenting integrated analysis data, which is a combination of multiple studies.
As companies plan for regulatory submissions, they must compile appropriate studies to support their submission and then standardize and integrate the data. This process can be challenging as the data may come from multiple sources in multiple formats, and there may be a need for recoding and harmonizing to incorporate data exchange and terminology standards.
To address this challenge, the PHUSE ODS Working Group has developed an Integrated Analysis Data Reviewer’s Guide (iADRG) template. This template was created by incorporating information from the Analysis Data Reviewer’s Guide (ADRG) and gathering input from regulatory agencies such as the FDA and PMDA. The iADRG provides additional context for integrated analysis datasets received as part of a regulatory submission, and is intended to describe the analysis data submitted for integrated data summaries (e.g. ISS, ISE, etc.).
To help companies better understand the different approaches available to them, the Working Group has considered the following four integration methods:
- ADaM -> integrated ADaM: This is a common approach where individual study ADaM datasets are combined to form integrated analysis datasets.
- ADaM +/- Legacy ADaM -> integrated ADaM: In this approach, individual study ADaM datasets are combined with legacy ADaM datasets that are no longer accepted by regulatory agencies. The legacy ADaM data is up-versioned to the latest dictionary versions and the ADaM version accepted by the agency.
- ADaM +/- Legacy ADaM +/- Legacy analysis -> integrated ADaM: In this approach, study ADaM datasets are combined with legacy ADaM and analysis datasets from individual studies. Both legacy datasets are converted to ADaM format and harmonized to meet regulatory agency requirements.
- Integrated SDTM -> integrated ADaM: This approach is not conventional but is still being used by some sponsors. Integrated SDTM is transformed into integrated ADaM for use in integrated analysis.
The iADRG covers several key aspects of integration including the sources of data, integration methods, and information affecting integrated datasets. The template assumes that the analysis datasets adhere to the ADaM standard, and includes a Legacy Data Conversion Plan and Report appendix in case a sponsor has converted any non-standard source data.
The significant elements of the iADRG include:
- Source Data Used for Integrated Analysis Dataset Creation
- Traceability Flow Diagram
- Description of Protocols Used in the Integrated Dataset
- Integrated Analysis Strategy and Design in Relation to Analysis Concepts
- Analysis Considerations Related to Integrated Analysis Datasets
- Integrated Analysis Data Creation and Processing Issues
- Integrated Analysis Datasets Descriptions
- Data Conformance Summary
- Submission of Programs
In conclusion, the integration approaches outlined above are key considerations for companies preparing for regulatory submissions. The Integrated Analysis Data Reviewer’s Guide (iADRG) provides a comprehensive guide for presenting integrated analysis data in a standardized manner that meets regulatory agency requirements. Companies must understand the different approaches available to them and choose the one that best fits their needs to streamline their regulatory submission process.
