Our friend and colleague Dawn Edgerton is back to provide us with more information on changing data standards and FDA submissions. Thank you Dawn for sharing your knowledge and expertise!

Will your Study Data Meet FDA’s Technical Requirements for Submissions?

Ensuring Conformance to CDISC Data Standards

In my last article, I outlined the components of the submission package for each type of data (non-­clinical, clinical, and analysis). In this article, we will address the question “How do I know if my data will meet the technical specifications set forth by the FDA?” Fortunately, there is a tool that gives you much of this answer.

The one I am most familiar with and is used by many CROs is called Pinnacle21 (Pinnacle21). It is formerly known as OpenCDISC. The Pinnacle21 Validator can be used to check conformance to CDISC SDTM, SEND, ADaM, and Define.xml standards. It also executes the FDA published business rules for submission data.

There is a free version of this tool that anyone can download. I have it. It has an easy to use drop-and-run type interface. The free version is called Pinnacle21 Community. The FDA implements the pricier version called Pinnacle21 Enterprise under the name “DataFit”. Pinnacle21 Enterprise is also the version many CROs will have. (Note to sponsors: When you select your CRO, ask if they use Pinnacle21 to validate the conformance of their datasets and define.xml files.)

After running your datasets or define.xml through Pinnacle21, the software will generate a report of errors, warnings, and a listing of issues grouped by dataset. Here is an example of an error.

Domain Variable Value Message
AE AESER Y No qualifiers set to “Y”, when AE is serious.

 

This error comes up when the variable AESER (Serious Event) in the AE (Adverse Events) dataset (or domain in CDISC-speak) is set to Y (Yes) , but none of the various seriousness indication variables such as AESCAN are set to Y (Yes). It is an error because when the AESER is ‘Y’, then at least one of seriousness criteria variables is expected to have value ‘Y’ (Involves Cancer (AESCAN), Congenital Anomaly or Birth Defect (AESCONG), Persist or Significant Disability/Incapacity (AESDISAB), Results in Death (AESDTH), Requires or Prolongs Hospitalization (AESHOSP), Is Life Threatening (AESLIFE), or Other Medically Important Serious Event (AESMIE)).

Here is an example of a warning.

Domain Variable Value Message
CM Variable, Excess CMENRF,1 Variable is too long for actual data.

 

This record tells you that the variable CMENRF (end of medication relative to the sponsor defined reference period) in the CM (Concomitant Medications) SDTM domain is too long for the actual data it holds. Defining the variable with an unnecessarily long length is a waste of space.

When is the best time to have run your datasets and define.xml in Pinnacle21? The Pinnacle21 Validator can – and should – be run more than once. In fact, you can run the validator as soon as you have data. No need to wait. Run it early, definitely before database lock, and often to address issues when they are easiest to solve. You will also want to run Pinnacle21 again after database lock to and update the Reviewer’s Guides with any issues that cannot be remedied and why.

Next up will be a short discussion on the Study Data Standardization Plan. You will learn when it should be submitted to the FDA and how to fill out the information. Until then…

Dawn M. Edgerton, MBA, RAC

edgertondataconsulting