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P21 Validation Engine Improvements

This is the fourth in a series of posts where we answer questions from our recent webinar. Below, we’ve summarized the regulatory expectations and our top insights.

Not Submitted Annotations

For any information that is on the CRF but not mapped to SDTM, annotate the page and/or field with "NOT SUBMITTED."

(Originally published on October 6, 2020. Last Updated on October 30, 2020)

Effective October 1st, 2020, China’s NMPA will accept CDISC submissions. To support this initiative, Pinnacle 21 has released a new Chinese-language validation engine, available now in both Enterprise and Community. This engine supports datasets with Chinese-encoded characters and displays rule messages and descriptions in Chinese translation.

Regulatory Expectations

These Data Standards Catalogs from the FDA and PMDA show the valid ADaM-IG versions for your submission’s date.

• FDA currently accepts ADaM-IG 1.0 and ADaM-IG 1.1.
  • Note: ADaM-IG 1.0 is only accepted for studies that began prior to the dates below. If your study started on or after these dates, then you can no longer use ADaM-IG 1.0 to submit that study.
    • 03/15/2019 for NDAs, ANDAs, and certain BLAs
    • 03/15/2020 for certain INDs
• PMDA currently accepts ADaM-IG 1.0 only. Note: Unlike the FDA, the PMDA does not grant exceptions for issues in the Reject category.

Versions and Revisions

You need to annotate and submit only the unique forms from the final version of the CRF, provided that they cover all the collected data. Combine all unique pages, e.g., those for clinical data and central review data, into a single acrf.pdf. Here are some example scenarios:

• If Version 1 had pages not used to collect data, and Version 2 removed those pages, then submit only Version 2.
• If Version 1 had pages used to collect data, but Version 2 removed those pages, then submit both versions.

Intro to ADaM Conformance

ADaM data are required by the FDA and PMDA, and accepted by China’s NMPA. Agencies often begin reviews with ADaM data validation, which helps them understand the analyses performed and reproduce results.

This is the first in a series of posts where we answer questions from our recent webinar, Exploring Common CDISC ADaM Conformance Findings. In this post, we focus on implementation recommendations.

In the regulatory review process, it's critical to have analysis data that comply with the CDISC ADaM standard. Both the FDA and PMDA require ADaM data, and as they begin reviews, they start with ADaM data validation. ADaM data help these agencies understand the analyses performed and reproduce the results for further validation.

In this webinar, Trevor Mankus covers the more commonly occurring validation rules and some potential reasons why they fired.

In August 2020, we released our new Pinnacle 21 validation engine “FDA (1907.2)” for preparing study data for FDA submissions. It includes the validation rules currently used by FDA’s DataFit, the agency’s implementation of Pinnacle 21 Enterprise.

The previous, outdated version of the validation rules is represented by our “FDA Legacy (1903.1)” engine. It will be available for the next few months until our next release. This window allows you to finalize your ongoing submission preparations.

Tables of Contents and Bookmarks

A table of contents with hyperlinks to bookmarked pages is seen in CDISC's sample aCRF (avaliable in the Define-XML v2.0 download). Both the Metadata Submission Guidelines (MSG) from CDISC and the PDF specifications from the FDA require aCRFs to have hyperlinks to bookmarked pages. The PDF specifications also require a table of contents.

Intro to aCRF Formatting

"How should I best format the annotations on my CRFs?" We get that a lot. The requirements may feel murky. Users often mimic CDISC’s sample aCRF (in the Define-XML v2.0 download). But even then, you might lack confidence on the specific formatting details, and wonder how to fit your content into the usable space.