Prepare now for adoption of ADaM standard

What’s on the horizon: mandatory FDA PDUFA V

Per PDUFA V Commitment, FDA shall issue final guidance on the standards and format of electronic submission of drug marketing application by end of 2014. All new original NDA and BLA submissions, supplements and amendments are required to follow the final guidance by end of 2016. All original commercial INDs and amendments are required to follow the guidance.

What is the CDISC ADaM Standard?

The CDISC Analysis Data Model (ADaM) standard provides data and metadata models along with examples of how to use analysis datasets to generate statistical results for regulatory submissions. The key principle of ADaM standard is to “facilitate clear and unambiguous communication of analysis data creation and analysis result generation and provide a level of traceability of each step of data operations.”

FDA supports ADaM standard as important part of standard for electronic data submission. FDA references the ADaM 2.1 and the ADaM-IG V1.0 documents on its Study Data Standards Resources website as one of the “Study Data Standards in Current Use.”

Current Industry ADaM adoption

The BioPharma industry has been slow to adopt ADaM standards. A survey of FDA Statistical Reviewers showed that only about 40% of submissions in 2012 contained ADaM based analysis datasets. Clearly, the industry need to ramp up our adoption of ADaM data standards in the coming year to meet the coming FDA mandate.

The Challenge of ADaM adoption

Why have BioPharma companies not adopted ADaM standards sooner? Surely we all want to do everything we can to get our clinical trials through approval. Surely unambiguous communication and increased traceability should facilitate that.

Ironically, one of the reasons the industry has not embraced these standards is ambiguity! For one thing, CDISC ADaM data standards are still evolving. The current implementation guides do not provide specific instruction on how certain analysis data should be represented to support efficient statistical analysis.

This has basically left BioPharma companies on their own to interpret the standards and to implement internal frameworks to meet them.

Companies that have already or are currently adopting ADaM standards have one thing in common. They have worked diligently. develop comprehensive, yet flexible, analysis data standards and put in place a framework for continued analysis data standardization internally

Criteria for ADaM adoption To be ADaM compliant, analysis datasets must meet the following conditions.

• Adhere to the CDISC ADaM basic principles of 1) having full and meaningful metadata, 2) being analysis ready, 3) supporting traceability.
• Include a compliant Subject Level Analysis Dataset (ADSL)
• Capture analysis dataset metadata in the format of define.xml
• Include compliant Adverse Event Analysis Dataset (ADAE) and other occurrence datasets by extension.
• Use Basic Data Structure (BDS) where possible
• Pass the current OpenCDISC ADaM compliance checks [link to these should go here]

How can you implement ADaM at your company? Internal ADaM standards development – preliminary “best practices”

1. Establish a dedicated team responsible for all aspects of ADaM standards development and implementation.
2. Support your ADaM team in developing company-specific ADaM standards.

Issues for your ADaM team to address:

• Identify common process/design issues that arise during your internal ADaM implementation and develop standard (company-specific) solutions
• Identify and develop macro/tools
• Create ADaM data definition tables templates and controlled terminology
• Contribute and review ADaM implementation guides and supporting documentation (e.g., rich examples)
• Review project-level ADaM specifications
• Provide expertise and advice for addressing implementation questions

The design of analysis data sets is typically based on the scientific and medical objectives of the clinical trial. Therefore your primary goal is to create standards that can be uses for all clinical trials sponsored by your company. Adapt the above guidelines as appropriate for your company’s business.

We hope this has been helpful. 2014 is right around the corner. If you have questions, please don’t hesitate to contact Princeton Pharmatech