2. © CDISC 2015 2 CDISC UK Network TC 24 th September 2015 Speakers: Paul Houston, (CDISC Head of European Operations) Jenny Griffiths (Roche Products Ltd) Will Stevens (University of Oxford) Gavin Winpenny (Roche Products Ltd)

3. © CDISC 2015 Agenda Feedback from Face to face meeting in June  General feedback from F2F meeting  Future TC topic suggestions  CDASH / Standards Governance + Controlled Terminology  SDTM  Regulatory Submissions  Presentation by Gavin Winpenny on future of ADaM standards AOB

4. © CDISC 2015 General Feedback from F2F meeting Face to face meeting hosted by Oracle in Reading 60 delegates from wide range of companies 16 survey responses All found topics relevant All agreed panel session good way of asking questions to the speakers All found breakout sessions efficient way to discuss topics in more depth All enjoyed the venue and found the lunch / tea breaks acceptable

5. © CDISC 2015 Feedback from F2F meeting Future topics asked for More on CDASH and benefits of adoption. Include overall "End to End" review of how all of the separate components fit together to form one solution. This would be helpful as most of the people where seemed only to have knowledge of the area of CDISC that directly affects them. Controlled Terminology More ADaM presentations as usage seems to be growing.

6. © CDISC 2015 Questions escalated to CDISC and network professionals Spreadsheet to be updated continuously and issues escalated through E3C and amalgamated with other CDSIC User groups/networks Will be made Available on the portal

7. © CDISC 2015 Feedback from F2F meeting CDASH breakout session feedback General points: Challenge with governing standards - protocol not being consistent, getting the correct people to review the eCRF and for it to be targeted review Discussion on Davy’s presentation re. eCRF compliance tool CDASH version was discussed and version 2.0 is being worked on; Feedback from CDISC: The CDASH Model & CDASH IG v2 will be reviewed by SRC prior to public review at the November 16 SRC meeting

8. © CDISC 2015 Feedback from F2F meeting Controlled terminology session feedback SDTM CT general points  it is not always backward compatible  requires better versioning]  Better explanation when term / value is removed CDASH terminology is limited to a small number of domains as shown in the list below: CM, EG, EX, SU, DA and VS, so less codelists than SDTM CDASH terminology in most instances is subset of SDTM terminology and more generic

9. © CDISC 2015 Feedback from F2F meeting SDTM breakout session feedback Gold members now have access to CDISC SHARE (since 10 Sept 2015). See updated list of member benefits: http://www.cdisc.org/membership-benefits-and-options

10. © CDISC 2015 Feedback from F2F meeting SDTM breakout session feedback More implementation examples, based on real-world trials. IG should contain guidance for the kinds of problems faced in practice.  Is there any prospect of producing a comprehensive dummy trial exemplifying CDISC standards, based on a real trial design?  There was a CDISC/FDA pilot in 2008-2009, SDTM datasets were created and a submission package was made for four studies. The final report was never published, but some information about it is available here: http://tinyurl.com/o5pre73 http://www.cdisc.org/eu-interchange-presentations-2010http://www.cdisc.org/eu-interchange-presentations-2010 (Session 4) http://support.sas.com/resources/papers/proceedings09/171-2009.pdf

11. © CDISC 2015 Feedback from F2F meeting SDTM breakout session feedback Any CDISC plans for a model for event adjudication? Adjudication is mentioned in sections 3.2.1 and 1.7 of the cardiovascular TAUG V1 (dated Oct 2014): http://www.cdisc.org/system/files/members/standard/PDF/TAUG-CV_v1.pdf Section 1.8: it will be addressed in a future CDISC publication. Some interchange presentations related to adjudication: http://www.slideshare.net/SimoneSuriano/disc-europe-interchange-56-may-2015-basel- ch-clinical-endpoint-adjudication-could-a-dedicated-cdisc-standard-improve-quality http://www.cdisc.org/system/files/all/generic/application/pdf/4_session_5c_barrie_nelso n_tom_guinter_2013_11_cdisc_interchange_presentation_adjudication___nelson__gui nter.pdf

12. © CDISC 2015 Feedback from F2F meeting Regulatory Submissions breakout session How to select the version required for a Submission?  Certain TAs require a later version of the standard, but the FDA is not yet accepting SDTM 3.2. Suggestion is to keep a close eye on the catalog on the for industry page and interim contact CDER Dataset XML? Strong business case for change: 8 characters for variable name, 40 for label and an overall limit of 200 chars limitations be removed using dataset XML.  The suggestion from the CDER team members at that time was that CDER have more work to do before deciding whether to support it. Perhaps a phase 2 pilot.

13. © CDISC 2015 Feedback from F2F meeting Regulatory Submissions breakout session EcTD – would SEND ever be included in eCTD?  SEND would fit well (Mike Harwood)  Contacted ICH and FDA colleagues For listings are the regulators going to use SDTM, ADaM?  Can we remove tables? Do we have to send listings for EMA?  These are not requested by EMA, but are required for FDA.

14. © CDISC 2015 Feedback from F2F meeting Regulatory Submissions breakout session Do we need a standard for the audit trail? In Europe they want access to trial data and audit information.  ODM can take audit this information, this could be a potential standard When to standardize data? Do you standardize data for submission at the beginning consistently or when the trial gets called for submission?  As required by your business. There comes a point when it makes sense to realize your investment by converting lots of legacy data for cross trial analysis. Submitting programs for ADaM data sets?  Not clear

15. © CDISC 2015 Feedback from F2F meeting

16. © CDISC 2015 Feedback from F2F meeting The future of ADaM standards? Disclaimer: The views expressed here are a personal viewpoint and summation of the discussion at the CDISC UK User Group meeting in June 2014. These views expressed are not representative of BDLS (my previous employer) or Roche (my current employer). Gavin Winpenny, Manager, Statistical Programming and Analysis at Roche

17. © CDISC 2015 Feedback from F2F meeting The future of ADaM standards? How far can we go in Standardizing ADaM datasets and TFLs as an industry? 1.Do we want to? 2.Safety data – what is the situation? 3.Efficacy data – what is the situation? 4.Barriers / Drivers to Success?

18. © CDISC 2015 Feedback from F2F meeting The Future of ADaM standards? Standardizing ADaM datasets and TFLs as an industry - Do we want to? General consensus - ‘Yes, it is worth doing so, but real difficulties in doing so’. The building blocks are in place, the uptake is there, but as yet, no common ‘this is how we do...’.

19. © CDISC 2015 Feedback from F2F meeting The Future of ADaM standards? Safety Data Standard Datasets + TFLs Improved Quality / Reduced Cost Standardizing ADaM datasets and TFLs as an industry – Safety Data, what is the situation? For Safety Data and Analysis there could/should be far more agreement on what are the standards for datasets and for TFLs. The benefits could be: reduced costs, improved quality common understanding

20. © CDISC 2015 Feedback from F2F meeting The Future of ADaM standards? Efficacy Data TA Standards – shared scientific understanding Unique Analysis – Exploration and Scientific challenge Efficacy is far more complicated, but could build on the TA standards from SDTM and ADaM. Core sets of TA analyses could be defined across companies. Unique analyses would still be required, but would have a ‘standards’ framework to reference for TA. Standardizing ADaM datasets and TFLs as an industry – Efficacy Data, what is the situation?

21. © CDISC 2015 Standardizing ADaM datasets and TFLs as an industry – Barriers/Drivers to Success - Technology? Feedback from F2F meeting The Future of ADaM standards? Barrier to Success: Many companies are heavily invested in existing technology, corporate standards and reports. Driver to Success: Move conversation from ‘we like our tables to look like this’ to ‘this is how we as an industry build datasets, and the summary tables that go with them look the same’. Differences should not be about cosmetics, but clinical information.

22. © CDISC 2015 Standardizing ADaM datasets and TFLs as an industry – Barriers/Drivers to Success – Political Debate? Feedback from F2F meeting The Future of ADaM standards? Barrier to Success: Getting companies to agree what is ‘standard’ and who decides is a challenge. Driver to Success: Part of the purpose of organizations such as CDISC and PhUSE is to achieve agreement and consensus across the industry. This should be an area for future exploration.

23. © CDISC 2015 Standardizing ADaM datasets and TFLs as an industry – Barriers/Drivers to Success – Communication and Trust? Feedback from F2F meeting The Future of ADaM standards? Driver to Success: Development and usage of standards is ultimately enlightened self- interest. No company has the perfect solution - improving standards benefits individual companies and the industry as a whole. Barrier to Success: Companies may see their solutions as part of the competitive advantage they have in reduction of time for analysis and getting their drug through submission.

24. © CDISC 2015 Standardizing ADaM datasets and TFLs as an industry – Barriers/Drivers to Success – Enforcement of standards? Feedback from F2F meeting The Future of ADaM standards? Driver to Success: Development of expert working groups along the model of SDTM TAUG; Buy-in of companies to work across TAs with key stakeholders; Regulatory Requirement - need definitive statement of requirement from regulatory agency to create the commitment. Barrier to Success: ADaM is a framework of rules by which to build datasets. If it becomes more prescriptive, who is to decide?

25. © CDISC 2015 Feedback from F2F meeting The Future of ADaM standards? Enterprise- level commercial platforms scientific knowledge- sharing collaboration budget constraints Ever increasing amounts of data Increasing regulatory focus on standards Standardize ADaM + TFLs.

26. © CDISC 2015 Feedback from F2F meeting The Future of ADaM standards?

27. © CDISC 2015 AOB Next TC meeting will be on 24 th November Topics TBC

28. © CDISC 2015