Evolving Requirements For Posting Clinical Trial ...

1 Oladayo Oyelola, PhD, SC (ASCP)Director, Clinical Trial Information DisclosureDaiichi Sankyo Pharma DevelopmentEdison, NJ 08837 Evolving Requirements For Posting Clinical Trial Information on the EudraCT and the EU Portal: Potential Impact on DemandCBI Clinical Data Disclosure and TransparencyPhiladelphia, PA. 18 & 19 January 20172 DisclaimerThe opinions expressed in this presentation are my own,and not that of Daiichi Sankyo presentation is for informational purposes are no representations or warranties expressed or implied.

2 With respect to the usefulness or sufficiencyof the presentation for the purposes ofclinical Trial information EudraCT and EU Portal Requirements 3 Presentation Outline Background and Timelines of Clinical Trial Information Disclosure Overview of US and EU Clinical Trial Disclosure Regulations and Requirements EMA Regulation (EU) No. 536/2014 New EU Portal and Database EudraCT (US) Data ElementsEvolving EudraCT and EU Portal Requirements 4 Clinical Trial Disclosure Background & TimelinesEvolving EudraCT and EU Portal Requirements 1988/1997US HOPE Act / Launched in US2004/2005 ICMJE Trial registration requirement for publication consideration.

3 EFPIA/IFPMA/JPMA/PhRMA Joint Position regional and national disclosure laws2008 -2010EU Directives on Trial disclosuresJapan: MHLWN otification #415 Joint Position revisedJoint Position of Clinical Trial Results in Scientific LiteratureOther national disclosure disclosure of results notification process during informed consent (in effect 2012)US TEST Act introduced to expand Requirements (not enacted)2013 WMA s Declaration of Helsinki Revised article 26 Alltrials Campaign LaunchedPhRMA / EFPIA s principles for responsible data sharingEU Ombudsman s petition for access to research data2014 NIH proposals to enhance transparency of Clinical Trial resultsTransCelerate recommendation on non promotional Lay SummariesEMA New Clinical Trial Regulation Policy 0070 2015 IOM issues report on sharing Clinical Trial dataEMA Policy 0070 in effectWHO position Statement on ethics of publication and data sharingGood Pharma

4 Scorecard initiative2016 EMA Policy 0070 Final GuidanceTransCelerate MRCT white paper on return of results to Clinical Trial participants (input from EMA / FDA) ICMJE data sharing proposal for publicationOpen Knowledge: Online database of Clinical trialsUS White House Cancer Moonshot InitiativeModified from TransCelerate BIOPHARMA INC2017?5US Public Law 110-85: FDAAA/Final Rule (2007/2016)Scope:Registration of Clinical trials for Drugs & Medical devices Applicable to all Phase II to IV trials (Phase I trials are optional)

5 Registry site launched in 1999 Sponsors or PI submit information on registration system managed by the NIH Registration within 21 days of subject enrollment Standard statement on registration required in informed Consent forms Study results data interface activated in 2007 Results submission within 12 months of primary / study completion date Delayed submission may be approved, if certify seeking initial approval (new product license) or new use or new indicationProtocol registration & study results Posting on Registration certification, Form 3674 for US IND submissions FDA Compliance Program Guidance Manual -"Registration of Studies on "(Section D of Chapter 48) Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting Oct 2016 Evolving EudraCT and EU Portal Requirements 6EU Trial Disclosure/RegistrationEU Article 57(2) of Regulation (EC)

6 No 726/2004 Applies to adult trials within EU and third countries, if part of Paediatric Investigation Plan (PIP) Applicable to Phase II to IV trials + Phase I, if part of a PIPA rticle 41(2) of Regulation (EC) No 1901/2006 Applies to paediatrics trials within EU and third countries, if part of PIP Applicable to Phase I to IV trialsNew EMA Regulation(EU) No. 536/2014 Scope the same Art 41 and 52 -interventional Clinical trials of medicinal products A new single EU portal and database planned to support: One application dossier for each Clinical Trial and/or modifications Coordinated approach to Clinical Trial authorization and supervision Transparency of Clinical Trial authorization, conduct and resultsStudy Protocol information registration site launched in March 2011 EMA extracts and registers protocol information in EudraCT As submitted in the Clinical Trial Application (CTA)

7 Form before enrolment Direct disclosure on EU-CTR at the time of Clinical Trial authorisationEvolving EudraCT and EU Portal Requirements 7EU Clinical Trial Disclosure Regulations Study Results data and information site launched in October 2013 Scope covers all studies conducted in the EU or 3rd country, if part of PIP Studies in the EudraCT database from 2004 to date Compliance effective date is 21 July 2014 Paediatric study results disclosure within 6 months of study completion LSLV Adults study results disclosure within 12 months of study completion LSLV Results of studies ending after date will be required as indicated above Results of studies that ended before July 2014, to be completed within 24 months Study data entry by Sponsor, Marketing Authorisation Holder.

8 Or PIP addressee Applicable to all medicinal products -licensed/marketed and those in developmentDisclosure on EU- Clinical Trial Register EudraCT and EU Portal Requirements 8 Overview of EMA Policy -0070 The new policy will exist alongside the current access to documents policy The policy applies prospectively, it will not apply to legacy data submitted prior to the implementation of the policy Policy scope: Clinical data submitted on/after the implementation date in relation to EU centralized procedure (CP) and article 58 applications (WHO).

9 Does not apply to Clinical data submitted for non-CP products. Clinical data: Clinical reports and individual patient data (IPD) Clinical reports: CTD Modules Clinical overview; synopses, ISS, ISE and 5 CSR plus appendices (Protocols), (CRF) & (SAP) The policy is effective 1 January 2015 implementation in 2 phasesoPhase 1: Publication of Clinical reports in effectoPhase 2: Review of various aspects in relation to IPD Policy 0070 implementation updates:oUsers survey June 2015 oPublic consultation on procedural guidance -October 2015 Evolving EudraCT and EU Portal Requirements 9 EMA Regulation (EU) No.

10 536/2014* Single EU portal and database to support: One application dossier for each Clinical Trial or modifications Coordinated approach to Clinical Trial authorisation and supervision Transparency of Clinical Trial authorisation, conduct and results One Clinical Trial application form and supporting dossier to cover: One or more Member States, and all regulatory and ethics assessment Public registration of the Trial and its subsequent updates, including the necessary elements of international registration at WHO ICTRP portal Providing the Trial design elements to support subsequent entry and publication of the summary of resultsEvolving EudraCT and EU Portal Requirements *Slides 9 -16: from Marcal A, EMA: EU Portal : a Gate way to Simplified Clinical Research 17 Oct Regulation (EU) No.