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02 CDISC UK Network Is It Possible To Make A Global Submission

The webinar discusses the challenges of making a global CDISC submission due to differing regulatory requirements from the FDA and PMDA. It emphasizes the need for careful planning, adherence to guidelines, and the necessity of creating separate submission packages for each agency. Ultimately, the conclusion is that a unified global submission is not feasible due to these discrepancies.

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sdp.1888
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15 views21 pages

02 CDISC UK Network Is It Possible To Make A Global Submission

The webinar discusses the challenges of making a global CDISC submission due to differing regulatory requirements from the FDA and PMDA. It emphasizes the need for careful planning, adherence to guidelines, and the necessity of creating separate submission packages for each agency. Ultimately, the conclusion is that a unified global submission is not feasible due to these discrepancies.

Uploaded by

sdp.1888
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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Is it possible

to make a
global CDISC
submission?
By Marianne Caramés,
Novo Nordisk A/S
CDISC UK Network Webinar 31 October 2018 2

Agenda

• Preparing for the submission


• Planning your trial
• Guidelines, conformance checks, submission deliverables and
challenges
• Recommendations
• Conclusion
CDISC UK Network Webinar 31 October 2018 3

Agenda

• Preparing for the submission


• Planning your trial
• Guidelines, conformance checks, submission deliverables and
challenges
• Recommendations
• Conclusion
CDISC UK Network Webinar 31 October 2018 4

Preparing for the submission

• When do you have to comply with the CDISC requirements for your
submission?
• FDA requires all trials with start date after 16-Dec-2016 to be in CDISC
format
• PMDA requires that all submissions submitted after 01-Apr-2020 are in
CDISC format

• Differences in planning documents and timing:


• FDA requires the sponsors to fill in the Study Data Standardisation Plan at
the time of the first IND and no later than end-of-phase II
• PMDA requires the sponsors to fill in the Appendix 8 (’Consultation on data
format of submission of electronic study data’) before the first e-data
consultation
CDISC UK Network Webinar 31 October 2018 5

Agenda

• Preparing for the submission


• Planning your trial
• Guidelines, conformance checks, submission deliverables and
challenges
• Recommendations
• Conclusion
CDISC UK Network Webinar 31 October 2018 6

Planning your trial

• Plan you trial with the future submission in mind


• Check the Data Standards Catalogue from both FDA and PMDA for
supported versions of SDTM, ADaM and controlled terminologies
CDISC UK Network Webinar 31 October 2018 7

Choosing SDTM and ADaM versions

• You may want to use the newest standards, but make sure to choose
a set which is supported by both FDA and PMDA

Sources: FDA Data Standards Catalogue v. 4.10 (Oct 24, 2017)


Data Standards Catalogue (2017-03-03)
CDISC UK Network Webinar 31 October 2018 8

Choosing versions of controlled terminologies

• For controlled terminology versions it is a little more difficult to


choose

Sources: FDA Data Standards Catalogue v. 4.10 (Oct 24, 2017)


Data Standards Catalogue (2017-03-03)
CDISC UK Network Webinar 31 October 2018 9

Can we use the same data model?

• Both FDA and PMDA require submission data


in CDISC format

• Both agencies require the CDISC SDTM data


model

• The CDISC organisation has detailed the


implementation of the data model in the IG
CDISC UK Network Webinar 31 October 2018 10

Agenda

• Preparing for the submission


• Planning your trial
• Guidelines, conformance checks, submission deliverables and
challenges
• Recommendations
• Conclusion
CDISC UK Network Webinar 31 October 2018 11

Technical Conformance Guides and FAQs

• The data submission must also comply with


the Technical Conformance Guide and
recommendations in the FAQ document
(PMDA only)

• The Technical Conformance Guides and FAQ


instructions are not binding, but sponsors
are expected to be compliant
CDISC UK Network Webinar 31 October 2018 12

Contradicting guidance from agencies

• Example: PP domain in SDTM:


• Novo Nordisk has taken the position, that the PP data are derived data,
and hence belong in ADaM
• FDA accepted the Novo Nordisk approach
• The PMDA FAQ states that PP data should be included in the SDTM
database regardless of whether it is derived
• Novo Nordisk will bring the question to an e-data consultation

Sources: FAQs on Electronic Study Data Submission (Excerpt)


CDISC UK Network Webinar 31 October 2018 13

Contradictions in guides
• Sometimes the Technical Conformance Guides and the SDTMIG are
not aligned

• Example: description of ARM for screening failure subjects


SDTMIG 3.2:

FDA Technical Conformance Guide v. 4.1:

Sources: SDTMIG 3.2


Study Data Technical Conformance Guide. 4.1 (Mar 2018)
CDISC UK Network Webinar 31 October 2018 14

Conformance checks – finding you way

• FDA and PMDA each have a set of conformance checks for checking:
• SDTM datasets and conformance to the SDTM model
• ADaM datasets and conformance to the ADaM model
• Define.xml structure

• FDA and PMDA have different severity categories for checks


• FDA : Error, Warning, Note
• PMDA: Rejection criteria, Error, Warning

• Some SDTM checks overlap, but also each agency has additional data model checks
• FDA has 12 additional checks
• PMDA has 23 additional checks
• 111 checks differ in severity
• 2 checks differ in content
• 2 checks target different domains

Sources: JPMA(Japan Pharmaceutical Manufacturers Association):


Analysis of differences in FDA/PMDA Validation Rules
SDTM Validation Rules, Pinnacle21:
https://www.pinnacle21.com/validation-rules/sdtm
CDISC UK Network Webinar 31 October 2018 15

Submission deliverables

• The two agencies require different submission deliverables:


• Study Data Reviewer’s Guide:
FDA Name: cSDRG filename: csdrg.pdf
PMDA Name: SDRG filename : study-data-reviewersguide.pdf

• Analysis Data Reviewer’s Guide:


FDA Name: ADRG filename: adrg.pdf
PMDA Name: ADRG filename: analysis-data-reviewers-guide.pdf

• PMDA requires extra documents for the submission:


• Attachment 4: dataset definition document for PK analysis, population analysis,
physiologically based pharmacokinetic model analysis
• Attachment 5: detailing procedures for running programs for population analysis

Sources: FDA: Study Data Technical Conformance Guide. 4.1 (Mar 2018)
PMDA: Revision of Technical Conformance Guide on Electronic Study Data Submissions (August 24, 2016)
CDISC UK Network Webinar 31 October 2018 16

Agenda

• Preparing for the submission


• Planning your trial
• Guidelines, conformance checks, submission deliverables and
challenges
• Recommendations
• Conclusion
CDISC UK Network Webinar 31 October 2018 17

Recommendations
• Plan your trial using the latest versions of SDTM, ADaM and controlled terminologies supported
by both agencies

• When requirements differ with respect to the domains and variables follow the guidance in this
order of priority:
• Guidance from CDISC Implementation Guides
• Binding agency guidance
• Non-binding agency guidance
• Lastly always talk to your reviewers

• P21 conformance checks:


• Use the latest version
• Run both the FDA and PMDA checking rules and update the (c)SDRG/ADRG accordingly
• Remember to check the define.xml also

• Due to the differences in requirements for the submission deliverables, you will probably need
to implement different packages for each agency
CDISC UK Network Webinar 31 October 2018 18

Agenda

• Preparing for the submission


• Planning your trial
• Guidelines, conformance checks, submission deliverables and
challenges
• Recommendations
• Conclusion
CDISC UK Network Webinar 31 October 2018 19

Question: Is it possible to make a global CDISC submission?

• The answer must be ‘No’, since the differences in regulatory


requirements with respect to implementation and submission
deliverables will require that two different packages are created

• As a sponsor you could wish for


• more alignment between the agencies
• that the guidance in technical conformance guides and FAQs were
implemented in the CDISC Implementation Guides to clear away the
inconsistencies
CDISC UK Network Webinar 31 October 2018 20

Thank you for your attention !


CDISC UK Network Webinar 31 October 2018 21

Presenter

Marianne Caramés
Principal Programming Specialist
Biostatistics Anchor

Novo Nordisk A/S

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