Regulatory Requirement for Electronic Data Submission in Standard Format (CDISC)
04 Apr 2018
Submitting a dossier to the US Food and Drug Administration (FDA) using Clinical Data Interchange Standards Consortium (CDISC) data standards has become the norm in the industry in recent years. CDISC standard has been strongly encouraged by the major regulatory bodies (USFDA and PMDA, Japan) to expedite the review process. Additionally, it can also help sponsors to bring the drug to the market in a shorter duration.
Way back in July 2004, FDA Commissioner Lester M. Crawford announced the desire of the FDA to receive data in a standard CDISC (SDTM) format, he said “FDA reviewers spend 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.”
That was a very welcome message and encouraged many pharmaceutical and service provider companies to become more interested in CDISC standards; however, it hardly produced a sudden adoption of CDISC data standards among all the sponsors. Later, in 2013, FDA published a new statement on Study Data Standards for Regulatory Submissions, which reiterated that FDA was firmly committed to implement CDISC data standards, which would be required ‘in the near future’.
Regulatory agency requirements
In December 2014, the FDA finalized guidance documents that make submission of electronic data mandatory for IND, NDA and ANDA related submissions, and also require the data to be in the standard format (i.e. CDISC) that the FDA can process, review and archive. By the end of 2016, both the FDA and PMDA will require CDISC standards for all CDER and CBER related submissions. Submissions that do not comply with the CDISC requirements, after that timeframe, could potentially receive a Refusal to File (RTF) from the agency.
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What exactly is the FDA mandate?
The FDA Safety and Innovation Act of 2012, statute on authorized required electronic submissions states that – “Beginning 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 final guidance was published in December 2014. Thus, all studies that start in the year 2017 or later will be required to submit their data to the FDA in an electronic format i.e. CDISC.
In September 2013, the Japanese regulatory agency PMDA established a task force for ‘Advanced Review and Consultation with Electronic Data’. On April 1, 2014, the task force was changed to ‘Advanced Review with Electronic Data Promotion Group’ as an official department of PMDA. Later, on November 18, 2015, PMDA announced SDTM submission rules, which shows that PMDA is also keen on accepting only CDISC SDTM data in the near future.
Thus, for any human intervention trial, CDISC (SDTM) is going to be the preferred data format. CDISC (SDTM) data are organized into different datasets called domains. Even for simple BA/BE studies where data collection is very limited, we can generate required SDTM domains for regulatory submission. Some of the common relevant domains for BA/BE analysis are –
- Demographic Information – DM
- Exposure Information – EX
- Vital Signs – VS
- Pharmacokinetic Concentration – PC
- Pharmacokinetic Parameters – PP
CDISC data standards can bring more than just savings in time and money
- Cross functional communication among project teams and partners can be hassle free
- Easier transfer of clinical data between partners and regulatory
- Data acquisitions (using CDASH) are less frightening with standard data structure
- Regulatory can review an application faster because of common standards
- Ability to combine data for cross-projects safety reviews
Lambda offers CDISC implementation and legacy data conversion services
Our team at Lambda has developed a standard conversion approach that helps us to provide high quality, on-time deliverables. At Lambda, we have standard CDISC conversion SOP, and experience across different therapeutic areas. We have developed oncology specific SDTM domains (TR, TU), converted legacy pharmacokinetics data (PC, PP) and even worked with patient reported outcome data (i.e. HAQ, SF36).
If there is a need to convert a single project’s data for regulatory submission or to implement CDISC standards across multiple trials, Lambda Therapeutic Research has the experience and expertise in the following activities –
- CDASH compliant CRF design
- SDTM CRF annotations
- SDTM, ADaM mapping specifications
- SDTM, ADaM programming and validation