1. Clinical Trials Ontario Making Ontario a preferred location for global clinical trials, while maintaining the highest ethical standards Susan Marlin, President and CEO LEXPERT Life Cycle of Pharmaceuticals Conference November 4, 2014

2. ABOUT CLINICAL TRIALS ONTARIO  Clinical Trials Ontario is an independent not-for-profit organization  Established with seed funding from the Province of Ontario– $4.5 million over 4 years in response to:  Significant decline in clinical research in Ontario – pharma investment  2009: $550m | 2010: $500m | 2011: $438m | 2012: $368m  Recognition of Ontario’s strengths (e.g. excellent research capacity, high quality data) and areas to improve (e.g.speed, cost)  Mandate for CTO – support a streamlined approach to conducting multi-centre clinical trials in Ontario while ensuring the highest ethical standards for patient safety

3. Streamlining REB and other CT Admin processes Improving Participant Recruitment and Retention Promoting Ontario and Attracting Investments Corporate Projects Operations & Governance Engagement of the Clinical Trials Community in Ontario

4. CTO Streamlined Research Ethics Review System The CTO System is expected to provide significant benefits to sponsors, investigators, institutions and REBs conducting multi-centre clinical research by harmonizing processes and reducing time and effort required to initiate research across multiple sites in Ontario.  Supports a single REB in providing research ethics review and oversight to multiple research sites  Can be used for any multi-site clinical research, i.e. industry sponsored or investigator initiated  Ensures that all REB reviews done through the CTO system are conducted by high- quality REBS that have achieved Qualification status  Investigators/applicants will use the same interface and REB application forms, irrespective of which REB is providing oversight; Consistency in submission requirements  Two primary components: 1.CTO REB Qualification Program 2.CTO Stream - web-based information technology system that will enable research ethics reviews, document management and communication across multiple REBs and institutions

5. CTO REB QUALIFICATION PROGRAM  Provides an external review and qualification of REBs in Ontario planning to participate in the CTO Streamlined Ethics Review System.  Qualification Manual and process based on the Toronto Academic Health Sciences Network (TAHSN) REB Qualification Manual with amendments:  Qualification Checklist/Standard  Based on applicable ethics review regulations, policies etc. including the CGSB; has undergone two external expert reviews  Qualification Review Team  includes an experienced auditor and 1-2 members of the REB community – an experienced Chair/Vice-Chair and an experienced REB Operational expert  REB community members participating in reviews drawn from the CTO “College of Reviewers”  Qualification Review Outcome  review identifies findings; once findings addressed “CTO Qualification” status issued  remains in effect for 3 years, with brief annual updates

6. CTO REB QUALIFICATION PROGRAM - STATUS  College of Reviewers:  5 REB Chairs & 4 Operational Experts Recruited  REB Qualification Status:  2 Qualified REBs  2 REBs in process; 2 REBs scheduled for review  4 additional requests expected by end of 2014  REB Preparation for Qualification  REB SOPs in place; N2/CAREB available now  SOPs and procedures checked against the CTO REB qualification checklist (in the manual at www.ctontario.ca)www.ctontario.ca  Complete questionnaire and schedule visit  SOPs reviewed prior to on-site visit; 2-day on site visit - includes interviews with REB Office team and REB Chairs/Vice-Chairs  REB Chair/Operational lead invited to join CTO Res Ethics Review Governance Committee

7. CTO STREAMLINED ETHICS REVIEW SYSTEM  Based on ‘delegated board of record model’; a qualified REB is delegated by participating institutions the responsibility to provide ethical oversight for a clinical research study conducted across multiple institutions – “one study, one REB”  Infrastructure includes web-based e-REB system “ CTO Stream”, policies and procedures, tools and education  All applications for Research Ethics Review through the CTO system will go through the CTO Stream application; all investigators and REBs will have the same interface  CTO Stream based on Infonetica system, with multiple customizations  Design/customization complete and undergoing UAT  Pilot(s) this fall:  Industry sponsored study  Investigator led study

8. Delegated Board of Record Model REB application submitted by any registered investigator/site, i.e. “Provincial Applicant” CTO assigns Board of Record (any Qualified REB in Ontario) and advances application Board of Record reviews application and resolves any issues with applicant Once issues are resolved Board of Record approves study Site adopts approved Informed Consent Form. Submits site application focused on site specific information Site application advances to Board of Record Board of Record reviews application (usually expedited) and resolves any issues with site applicant Step 1 Applying for a New Multi-Centre Clinical Trial Step 2 Adding New Investigators / Research Sites Initial Application Process Participating sites are notified and given access to REB materials in CTO system Board of Record issues approval for site to participate

9. Documentation submitted by “Provincial Applicant” Board of Record reviews submission and resolves issues with provincial applicant Once issues are resolved, approval or acknowledgement is issued by Board of Record and sent simultaneously to all approved participating sites Board of Record reviews submission and resolves issues with research site Approval or acknowledgement issued by Board of Record New overall (study-level) event, e.g. amendment, Data Safety Monitoring Board report, safety update New site level event, e.g. continuing (annual) review, local Serious Adverse Event, protocol deviation Documentation submitted by research site Delegated Board of Record Model Continuing Oversight and Approval

10. ASSIGNING THE BOARD OF RECORD Industry Sponsored/Led Studies:  CTO will look first at matching the study area to REB expertise  If more than one qualified REB with expertise, will assign REB based on balancing workload of CTO studies amongst REBs Investigator Led Studies:  Preference will be to assigning to the ‘home’ REB of the lead investigator; REB likely to have the expertise, and some desire expressed in the community for having more institutional support for Investigator led studies  If ‘home’ REB not possible, CTO will look to match REB expertise  If more than one qualified REB with expertise, will assign REB based on balancing workload of CTO studies amongst REBs

11. CLINICAL TRIAL AGREEMENTS Canada Cdn Clinical Trials Coordinating capacity – working with select industry partners to advance model clinical trials contract for academic sites across Canada Ontario CTO has developed a model CTA for Ontario, starting with the draft national model and incorporating input from across Ontario institutions Will be attempting to implement this with trials that go through the CTO system for ethics review Predicted challenges Industry cannot get approval from ‘global’ Industry has already negotiated a ‘template’ with individual sites Others? Solutions???

12. PATIENT AND PUBLIC ENGAGEMENT Phase I: October 2014-March 2015  Communications: Provide/link to Clinical Trial Resources for patients/public  Information gathering:  Participant/non-participant survey  Outreach to CT professionals (surveys, focus groups, consultation)  Potential public survey  Supporting/enhancing Clinical Trials Conduct  Promoting discussions re: privacy/ethics issues relating to CTs – e.g. recruiting, identifiers, accessing databases, linking data, future research; focus ½ workshop at CTO conference  Engaging public/patients in model consent form development, design/development of any patient/public engagement programs, policy development when appropriate Phase II: April 2015-May 2016 - activities based on ‘learnings’ from phase I

13. CTO CONFERENCE 2015  Scheduled for March 4-5, 2015 – Hilton, Toronto; agenda/speakers under development  Theme: What’s Next for Clinical Research in Ontario and Canada  Plenary - Day 1  Introductory Remarks:  Bob Bell, Deputy Minister, MOHLTC  Four sessions 1.Building a global system for excellence in clinical research  Keynote: Greg Koski, Co-Founder & President ACRES; former Director OHRP & Investigator/Physician, Harvard  Building a Global System for Excellence in Clinical Research base don values of Integrity, Inclusiveness, Innovation and Implementation 2.Developments in the CT Environment 3.The Investigative Site Perspective 4.Participant Engagement  Targeted Workshops – Day 2 1.Ethical and Privacy Issues in Clinical Research 2.CTO Streamlined Ethics Review System

14. CONTACT INFORMATION Website: www.ctontario.cawww.ctontario.ca E-mail: susan.marlin @ctontario.casusan.marlin @ctontario.ca @clinicaltrialON linkedin.com/company/clinical-trials-ontario Clinical Trials Ontario 661 University Avenue, Suite 460 MaRS Centre, West Tower Toronto, Ontario Canada M5G 1M1 Tel / 416.276.1381