Clinical Trials Ontario Streamlined Research Ethics Review System Susan Marlin President and CEO CAREB NATIONAL MEETING 2015

ABOUT CLINICAL TRIALS ONTARIO  Clinical Trials Ontario is an independent not-for-profit organization  Established by the Province of Ontario in response to:  Significant decline in clinical research in Ontario  Recognition of:  research strengths (e.g. excellent research capacity, high quality data)  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  First priority – implementing a streamlined research ethics review system

CTO STREAM LAUNCHED: MARCH 4, 2015 New streamlined system for research ethics review launched in Ontario Press release posted on ctontario.ca  386 page views from Canada, UK, Japan, United States, Germany, India, Australia and Hong Kong. Stakeholder Pick-up  Life Sciences Ontario  Ontario SPOR SUPPORT Unit  CAHO Catalyst  CAREB  MEDEC

The System

CTO STREAMLINED RESEARCH ETHICS REVIEW SYSTEM  Supports a single REB in providing research ethics review and oversight to multiple research sites; relies on a “REB of Record Model”  REB oversight responsibilities delegated by participating institutions to the REB of Record  Can be used for any multi-site clinical research, i.e. industry sponsored or investigator initiated  Currently can accept multi-site clinical trials; in future multi-site health research will be accepted as well  Primary components:  CTO REB Qualification Program  CTO Stream: Web-based Research Ethics Review System  The Three P’s: Policies, Procedures & Paperwork

CTO REB QUALIFICATION PROGRAM  Provides REBs planning to participate in the CTO Streamlined Research Ethics Review System with an external review of their governance, membership, operations and review procedures.  Based on the Toronto Academic Health Sciences Network (TAHSN) qualification process.  REBs are reviewed against a transparent standard, the CTO REB Qualification Checklist, that is informed by the applicable regulations, policies and guidelines. REB Qualification Manual available at  CTO REB Qualification checklist aligned with the N2/CAREB REB SOPS.  Each full visit is conducted by a Qualification Team composed of:  Auditor with specific training relating to review of REBs  CTO Program Coordinator  Two experienced members from the research ethics community (e.g., REB Chair/Vice-Chair and REB Director/ Manager/ Coordinator) selected from the CTO College of Reviewers.

CTO REB QUALIFICATION PROGRAM  REB SOPs reviewed prior to on-site visit; on site interviews with REB Chair(s) & operations team and review of facilities and documentation.  Report issued following visit; all items (200+) must be addressed before “Qualification” status issued.  Qualification status remains in effect for 3 years with submission of annual updates.  8 REBs are CTO Qualified in Ontario; 2 in process; several others preparing;  Lessons learned:  Different ways to be compliant; documentation is key  Common issues/questions/concerns:  quorum, incidental findings, appeals, finding and maintaining REB members (e.g. law, community); staying on top of emerging issues and education  REB Council to be convened soon (goal: 10 REBs qualified); composed of REB Chairs and REB Operation Leads from each qualified REB.

CTO STREAM  Standalone web-based electronic platform:  Enables research ethics review, document management, and communication between multiple institutions and multiple REBs  Uses common application forms standardized for all types of clinical trials  Built on Infonetica platform  CTO Stream is built using the latest technology and is continuously being improved based on community feedback  Supports the latest version of the most popular browsers (Internet Explorer, Google Chrome, Firefox, Opera and Safari)  Supports all mobile platforms and tablets (Apple, Android and Blackberry)  Supports any file type for uploads (i.e., word documents, excel documents, pdfs and text files)  Built using smart questions and smart forms  Uses electronic signatures for all applications  User friendly easy to use environment with 24 hour support provided by CTO and Infonetica  Launched March 4, 2015 at the CTO Conference; studies going through system

Using the CTO Streamlined Research Ethics Review System

INSTITUTIONAL RESPONSIBILITIES Per TCPS2  Accountable for the research carried out in its own jurisdiction or under its auspices.  Responsible for the ethical acceptability and ethical conduct of research undertaken within its jurisdiction or under its auspices.  Establish or appoint REB(s) to review their research; can be an REB external to the institution; can establish/appoint one or more.  Grants the REB the mandate to review the ethical acceptability of research on behalf of the institution, including approving, rejecting, proposing modifications to, or terminating any proposed or ongoing research involving humans. (TCPS2 Article 6).  Delegation of research ethics review responsibilities to another REB requires a formal agreement. The REB is responsible for research ethics oversight, and protecting the rights, safety, and well-being of research participants (GCP and CGSB)

CTO PARTICIPATION AGREEMENT  Between CTO and Participating Institutions (e.g. academic hospital, community hospital, university)  Sets out CTO’s and the Participating Institution’s respective rights and obligations  Participating Institutions can serve as:  REB Host Institution: Institution has established an REB that is qualified (or to be qualified) by CTO and will serve as an REB of Record for multi-site clinical/health research  Recruiting Site: Investigators working under the auspices of the Institution will recruit participants to studies approved through the CTO System  Both  Includes as Schedule E the REB of Record Study Agreement, executed on a study-by-study basis  Parties to the agreement: REB Host Institution of the REB of Record, Institution of the Recruiting Site, and the Principal Investigator at the Recruiting Site.  Template agreement formally delegates REB review and oversight responsibilities to the REB of Record and must be executed prior to the start of the study at each Recruiting Site.

ASSIGNING THE REB 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

REB REVIEW FEES – INDUSTRY SPONSORED TRIALS  Industry Sponsor  Charged $3000 for each of the 1st 5 participating sites; $2000 for each of the next 5 and $1500 for each additional site after 10; $500 for the 4th and subsequent major amendments  REB of Record Institution  Receives $5000 for the initial review and $250 for each participating site after 2; $500 for the 4 th and subsequent major amendment  Recruiting Site Institution  Receives $500 per CTO trial they participate in, if they have an internal REB or support an institutional REB – allocated to support REB activities

JOINING THE CTO SYSTEM  Learn about the CTO System: CTO website, webinars, manuals + customized visits, presentations, webinars etc.  Understand and implement what policy, governance, procedural changes etc. need to implemented to use the system; all non-ethics local requirements for study initiation will need to be met  If your institutions intends to be a REB Host institution and is not qualified, prepare for REB Qualification (N2/CAREB SOPs)  Review and sign the CTO Participation Agreement  Customized training provided: REBs, investigators, institutional representatives

REB OF RECORD MODEL Initial Application Process REB application submitted by any registered investigator/site, i.e. “Provincial Applicant” CTO assigns REB of Record (any Qualified REB in Ontario) and advances application REB of Record reviews application and resolves any issues with applicant Once issues are resolved REB of Record approves study Recruiting Institution signs REB of Record Agreement, delegating ethics review and oversight to REB of Record; Local PI adopts approved consent form and submits site application focused on site specific information Site application advances to REB of Record REB of Record Host Institution signs REB of Record Agreement and REB 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 Sites wishing to participate are notified and given access to REB materials in CTO system REB of Record issues approval for site to participate

Continuing Oversight and Approval Documentation submitted by “Provincial Applicant” REB of Record reviews submission and resolves issues with provincial applicant Once issues are resolved, approval or acknowledgement is issued by REB of Record and sent simultaneously to all approved participating sites REB of Record reviews submission and resolves issues with research site Approval or acknowledgement issued by REB 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 REB OF RECORD MODEL

Building the System

LEARNING FROM WHAT HAS BEEN DONE Programs/Systems/Expert Papers etc. reviewed  Other programs for streamlining/harmonization – provincial, international  E-REB systems, locally and internationally  TAHSN REB System RFP  TAHSN REB Qualification Manual  AAHRPP accreditation process  Processes/policies etc. from multiple REBs  OCREB’s “Everything”, in detail  CIHR External Advisory Committee on Streamlining Health Research Ethics Review (SHRER)  Forms from multiple REBs  Consents from multiple REBs, groups etc.  CAREB guidance – e.g. SAEs  N2/CAREB REB SOPs

LEARNING FROM THOSE WHO DO IT

BUILDING TOGETHER  External Committees/Groups  REB Streamlining Working Group  Legal and Liabilities Working Group  IT and Metrics Working Group  Research Ethics Review Advisory Group  College of reviewers  Technical/Operations Committee  E-REB RFP Evaluation Committee  E-Forms Working Group (Clinical Trials)  Model Clinical Trials Agreement  Participant Engagement Advisory Group  Industry Advisory Group  CTO Participation Agreement Advisory Group  E-Forms Working Group (non-clinical trials) __________________________________________ Total = 109 Volunteers  Community Experts Hired PT/Seconded: 9  CTO In-house Team: 7

CTO 2015 CLINICAL TRIALS CONFERENCE

“TO DO LIST” Streamlined Research Ethics Review System  Initiate the CTO REB Council  Support multi-centre health research (non clinical trials)  Implement CTO Registry & Reporting capabilities  Develop template consent form (clinical trials)  Explore opportunities for provincial collaborations  Develop and offer CTO Stream for local REB review Other Streamlining Measures  Clinical Trial Agreements  Determine other opportunities for streamlining/efficiencies Participant/Public Engagement  Landscape review: Determine programs/areas where CTO can add value  Public / Participant surveys – partner with BCCRIN  Engage with health charities & patient advocacy groups  Develop participant & public facing materials for the website  Engage participant & public in program development where appropriate (e.g. sample consent forms)

CONTACT INFORMATION Website: @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 /