Have you heard the FDA will require electronic submissions that use CDISC standardized study data? In my work at Certara, I’ve noticed there’s a lot of confusion, and even significant apprehension, surrounding this issue. To combat the misconceptions about what these regulations will mean for drug developers, I’ve compiled a list of common questions (and answers) designed to clarify what CDISC standards are, and why you should care about them.
What exactly IS the FDA mandate?
The FDASIA (FDA Safety & Innovation Act of 2012) Statute on Authorized Required Electronic Submissions states that:
“…no earlier than 24 months after final guidance issued after public notice [certain] submissions shall be submitted in such electronic format as specified by the Secretary in such guidance.”
The draft guidance was published last spring. Thus, if the final guidance is published next year as expected, all studies that start in 2017 or later will be required to submit their data to the FDA in an electronic format that uses CDISC data standards.
Who is CDISC and what are their data standards?
The Clinical Data Interchange Standards Consortium (CDISC®) is an international, non-profit organization that has established standards to support the acquisition, exchange, submission and archive of preclinical and clinical research data. CDISC aims to make drug development more efficient by developing data standards that are easily interpreted and understood by regulatory reviewers. Former FDA Commissioner Lester M. Crawford was quoted as saying:
“The importance of a standard for the exchange of clinical trial data cannot be overstated. FDA reviewers spend far too much valuable time simply reorganizing large amounts of data submitted in varying formats. Having the data presented in a standard structure will improve FDA’s ability to evaluate the data and help speed new discoveries to the public.”
Satisfying regulatory requirements is an obvious reason to be concerned about CDISC data standards. Moreover, having data in a common standard makes it easier and faster for pharmaceutical companies and CROs to collaborate on projects. While it is possible to collect and analyze drug development data in non-CDISC formats and then convert them to CDISC formats for submission, my experience is that customers benefit from getting their data into CDISC formats as soon as possible.
How is CDISC data organized?
Some of the CDISC data standards that my customers use most frequently include the clinical study data standard, SDTM (Study Data Tabulation Model), and the preclinical data standard, SEND (Standard for Exchange of Nonclinical Data).
CDISC data is organized into domains. Some of the relevant domains for PK analysis include:
- DM- demographic information
- EX- exposure information
- PC- pharmacokinetic concentration data
- VS- vital signs
- PP- pharmacokinetic parameters
How does Certara’s Phoenix Connect support the FDA mandate?
To better serve customers’ needs, the newest version of Phoenix Connect will provide improved support for SDTM and SEND. Converting domain datasets from SDTM or SEND into a worksheet that can be analyzed with Phoenix WinNonlin is a critical, and often cumbersome, task. Phoenix Connect 1.4 will provide a new CDISC Data Preparation Object that creates analysis-ready worksheets from an imported set of CDISC domains with little or no additional user input.
The CDISC Data Preparation Object will merge data from domains (PC, EX, DM, and others) to create an analysis-ready worksheet. Phoenix WinNonlin will then use the resulting worksheet for NCA (non-compartmental analysis) to calculate pharmacokinetic parameters which can be exported into the PP domain. RELREC records will be generated to show which PC records were used to calculate which PP data. Because the data preparation object is part of the project workflow, the whole process – data preparation, analysis, and output generation – can be re-executed when new data are available or re-used in a Phoenix template.
Want to learn more about the FDA’s requirements for standardized study data?
This is a very high level view of some aspects of the CDISC data standards, and there is much more to this complicated and pressing topic. I think it’s important to get as much information as possible before jumping to action. Last spring, I attended the Computational Science Symposium at PhUSE (the Pharmaceutical Users Software Exchange) and heard Dr. Ron Fitzmartin of the FDA present a great summary regarding the FDA mandate. Check out his presentation, “FDA Standards Strategy: Where Are We and Where Are We Going”!