CTO 2014 CLINICAL TRIALS CONFERENCE February 27, 2014

Transcription

1 CTO 2014 CLINICAL TRIALS CONFERENCE February 27, 2014

2 CONTENTS INTRODUCTION EVOLVING CHALLENGES AND OPPORTUNITIES FOR CLINICAL TRIALS Experts Discuss Fundamental Issues Driving Challenges and Opportunities in Clinical Trials DEVELOPMENTS IN THE NATIONAL AND PROVINCIAL ENVIRONMENT Seven Essential Updates on the Clinical Trials Environment in Canada and Ontario STREAMLINING RESEARCH ETHICS REVIEWS Challenges and Opportunities CLINICAL TRIALS PARTICIPANT ENGAGEMENT AND RETENTION This is About People : Insights Into Participant Engagement and Retention ACKNOWLEDGEMENTS GLOSSARY OF ACRONYMS CONFERENCE DIGEST CREDITS Editor: Sean Power Design and Layout: Thomas Boldt Photos: Warren Toda Photography Project Management: Manal Siddiqui Slides: Replicated with permission

3 INTRODUCTION Clinical research is a major contributor to medical discoveries being made in Ontario and in Canada. Successful trials lead to new drugs, devices and procedures that can improve treatment, enhance quality of life, reduce health care costs and generate more investment in health research. Clinical Trials Ontario (CTO) is an independent not-for-profit corporation supported by the Government of Ontario through the Ministry of Research and Innovation. Our mandate is to provide the life sciences industry with a streamlined approach to conducting multi-centre clinical trials in Ontario while ensuring the highest ethical standards for participant safety. Core to the development of CTO programming is our understanding that, first, clinical trials are important to advancing our health and our economic well-being in Ontario; and second, that our clinical research and research ethics communities, both public and private, do the actual work the design, conduct, ethical oversight, and quality management of clinical trials. Our focus at CTO is in understanding how we can best support you in accomplishing your goals. This Conference Digest is in response to the overwhelming interest we received from our community in the content presented at the CTO 2014 Clinical Trials Conference. It is intended to highlight key discussions and themes emerging from the conference in order to extend its reach beyond the day-long event. We hope that it will inform and continue conversations already taking place in the clinical research community. If you would like to send feedback, please write to us at info@ctontario.ca. We look forward to hearing from you! Conference at a Glance CTO Clinical Trials Conference 2014 Attendee Breakdown Other / Unspecified 5% Professional Service Provider 6% Patient Advocacy Group / Health Charities 7% Conference Attendees Speakers Association 4% Institutions (Hospitals, Universities, Research Institutes, etc) 28% On February 27, 2014, CTO hosted its first annual Clinical Trials Conference in Toronto, which brought together over 200 members of the clinical research community to advance discussions relevant to improving the clinical trials environment in Ontario and in Canada. 14% Government / NFP 16% Research Ethics Board / Office 20% Industry 1 CLINICAL TRIALS CONFERENCE DIGEST 2014

4 EVOLVING CHALLENGES AND OPPORTUNITIES FOR CLINICAL TRIALS Experts Discuss Fundamental Issues Driving Challenges and Opportunities in Clinical Trials At the CTO 2014 Clinical Trials Conference, four experts on global clinical trials activity discussed the evolving challenges and opportunities for clinical trials. The panel, moderated by Paul Lucas, President and Chair of Life Sciences Ontario and former President of GlaxoSmithKline Canada, consisted of representatives from companies involved in participant outreach, drug development, and device development: Nita Arora, Regional Head of Affiliate Management, North America, Hoffmann-La Roche; Neil Maresky, Vice President of Scientific Affairs, AstraZeneca Canada; James Wilson, President of Brancorth Medical Inc. and member of the CTO board of directors; and, Keynote speaker Ken Getz, Director of Sponsored Research Programs, Tufts Center for the Study of Drug Development and Chairman and Founder of The Center for Information and Study on Clinical Research Participation (CISCRP). According to Mr. Getz, throughout the 1990s, procurement and cost containment were primary strategies for improving productivity. Containing costs through procurement led to vertical integration during the 2000s, which provided drug and device development companies with the opportunity to downsize and consolidate. Since 2010 and moving forward into the future, according to Mr. Getz, cost pressures will continue as companies focus on integrated outsourcing. Now we re moving to an environment where integration is everything, says Mr. Getz. Primary Strategies Driving Development Productivity & Performance Source: Ken Getz Future Operating Changes Alliances Technologies Project Management Procurement / Cost-containment M&As Private/Public Partnerships Transactional Outsourcing Rapid Screening Combinatorial Chemistry EDC and IVRS The cost of development per new molecular entity (NME) has grown from $2.2 billion in 2003 to $5.1 billion in 2013 according to PricewaterhouseCoopers. Dr. Maresky agrees that rising costs pose a challenge to conducting clinical trials. Globalization Downsizing and Consolidation M&As In-Licensing and Joint Ventures FSP Outsourcing -Omics eclinical Trial Solutions (e.g., CTMS) Globalization Downsizing and Consolidation Variable and Virtual Staffing M&As, In-Licensing, JVs Open R&D Alliances Private-public alliances Precompetitive Integrated Outsourcing Platform Technologies Companion Diagnostics Integrated Real-world Data Social Media and mhealth 2 CLINICAL TRIALS CONFERENCE DIGEST 2014

5 The Rising Cost per NME In Billions USD Data: Price Waterhouse Coopers Source: Ken Getz Three fundamental root causes are driving the high price for clinical trials, according to Mr. Getz: 1. Complex, infeasible protocol designs; 2. A fragmented site landscape; and, 3. Poor public and patient outreach and education. These issues are occurring in parallel with the trend of increasing drug development duration. Increasing Drug Development Durations Mean Approval Time Mean Clinical Time Cycle Time in Years from IND Approval to NDA Approval Data: Tufts, CSDD Source: Ken Getz CLINICAL TRIALS CONFERENCE DIGEST

6 Study enrollment cycle times, which refers to the length of time required to reach target enrollment, are likewise growing. This is happening as sites increase the planned study duration in order to reach the target enrollment. Global Investigative Site Performance Regional Differences Percentage Randomizing at Least One Patient Per Trial Overall 89% Source: Ken Getz Percentage Eventually Meeting Enrollment Target Per Trial 85% Ms. Arora suggests that the continued decision to sponsor clinical trials in places such as Latin America has been driven more by speed of patient recruitment than cost, as these emerging countries are no longer as inexpensive as previously thought. Asia Pacific Europe North America Latin America Rest of World Site Setting Differences 91% 92% 87% 80% 94% 108% 72% 98% 104% 56% Analysis of regional differences in site performance for enrollment indicates that Asia Pacific and Latin America outperform North America when it comes to the percentage of sites meeting enrollment targets per trial. Independent Physicians 91% 96% University/Hospital/Gov. Clinics 87% 73% Innovation in the process of conducting clinical trials has to match the innovation in the actual drug discovery. The transformation that we are looking at is the innovative way that we engage with patients in North America as we ask them to consider participating in clinical trials, says Ms. Arora. Doubling Actual Study Enrollment Cycle Times Source: Ken Getz Promoting clinical research to the public, as well as reaching out to patients and participants, is a fundamental challenge for the clinical trials sector, making it difficult to recruit participants, according to Mr. Getz Screen to Completion Rates Overall 56% Increase in Planned Study Duration to Reach Target Enrollment 94% For example, research out of Tufts shows that, of nearly 16,000 sites participating in 153 global Phase II and III clinical trials, 11 per cent failed to enroll a single patient and another 37 per cent under-enrolled. Cardiovascular CNS Endocrine/Metabolic Oncology Respiratory 59% 61% 41% 78% 59% 99% 116% 113% 71% 95% Mr. Wilson suggests that sites might be able to improve recruitment and retention by following up with trial participants. This observation is in line with research by CISCRP, which, in 2013, found that 93 per cent of study volunteers never learn about the results of their clinical trials. 4 CLINICAL TRIALS CONFERENCE DIGEST 2014

7 We cannot afford to have anybody who relies on clinical trials to have second doubts about it, says Dr. Hofstein. The same study by CISCRP revealed that the public supports the general purpose of clinical research but that mistrust of the pharmaceutical industry remains a barrier to participant recruitment. Raphael Hofstein, President and CEO of MaRS Innovation and member of the CTO board of directors, who introduced Mr. Getz and Mr. Lucas, alludes to this issue of trust. We cannot afford to have anybody who relies on clinical trials to have second doubts about it, says Dr. Hofstein. Site Performance N = 15,965 sites participating in 153 global Phase II and III Clinical Trials Data: Tufts CSDD, 2011 Source: Ken Getz Meet Enrollment Targets 39% Under Enroll 37% Well Exceed Enrollment Targets 13% Fail to Enroll a Single Patient 11% A failure to engage health providers is a root cause for this lack of trust, according to Mr. Getz. The public perceives medical professionals as honest but less than 15 per cent of trial volunteers report that they learned about clinical trials from their primary/specialty care physician. The medical professionals who patients trust, then, are not the people recommending participation in health research. We have to change the way we provide information to the patient, as well as those people that they trust to help them make important decisions, says Ms. Arora. The panel is generally optimistic about the prospects for Canada to capitalize on opportunities in clinical trials. Ms. Arora suggests that drug development companies would accept higher costs that come with conducting trials in Canada, but only as long as we deliver and deliver consistently on our commitments. Failure to Engage Health Providers Perceived Honesty / Integrity Rated by Public as High/Very High Data: Gallup Survey, 2010 Source: Ken Getz Less than 15% of volunteers report that 81% they learned about clinical trials from their primary/specialty care physician 71% (Centerwatch, 2007) 66% Greater disparities among minority patients given low physician involvement Less than half of physicians refer patients to clinical trials with a typical referral rate of <1% of community 26% served (Centerwatch, 2007) Medical Doctors Pharmacists Nurses Auto Mechanics 87% of physicians who have conducted clinical research in the past report regularly referring their patients 5 CLINICAL TRIALS CONFERENCE DIGEST 2014

8 Dr. Maresky looks at the complexity of the development pipeline in terms of proteins, large and small molecules, diagnostics, and other forms of specialized entities, as an additional opportunity. Take that quality and reliability message, says Dr. Maresky, overlaid with messaging about portfolio complexity, to our global organizations. Mr. Wilson believes that Canada can leverage its strengths to address challenges facing its clinical research community. Canada is a good, collaborative environment to get things done, says Mr. Wilson. The panel s sentiment is that Canadian clinical trials have a reputation for being reliable and of high quality. Focusing on these traits will empower researchers in Canada to advance health discoveries that improve patient care by attracting investment from global companies who need reliable, high quality research. 6 CLINICAL TRIALS CONFERENCE DIGEST 2014

9 DEVELOPMENTS IN THE NATIONAL AND PROVINCIAL ENVIRONMENT Seven Essential Updates on the Clinical Trials Environment in Canada and Ontario The CTO 2014 Clinical Trials Conference offered an opportunity for representatives from organizations and associations across Canada and Ontario to provide the community with updates on developments in the clinical trials sector. The national and Ontario updates reflect coordinated and collaborative efforts in the clinical research community, working toward the same goal of realizing efficiency gains in the system through streamlining and harmonizing activities. Achieving the objectives within this goal such as increasing the speed of clinical trial start up times, reducing duplication of efforts, and eliminating administrative redundancies both Canada s reputation for quality is, I think, unparalleled, says Jared Rhines, Vice President of Scientific and Strategic Affairs at Rx&D. in Ontario and across Canada, will advance the development of much-needed treatments and medical devices in our health care system. 1 Canada s Research-Based Pharmaceutical Companies (Rx&D) has seen significant progress in developing the Canadian Clinical Trials Asset Map. Canada s reputation for quality is, I think, unparalleled, says Jared Rhines, Vice President of Scientific and Strategic Affairs at Rx&D. Nevertheless, North America (including Canada) has seen a 31 per cent decline in patient recruitment between 2004 and This fact, among others, provides the impetus behind the Canadian Clinical Trials Asset Map (CCTAM), a web-based living, easily searchable, interactive database of Canadian clinical research capabilities. The CCTAM promotes Canadian researchers and sites nationally and internationally. Global Patient Recruitment by Region 2004 Data: 2012 CMR Factbook -31% 49% 34% North America -13% 15% 13% Europe (core) Source: Jared Rhines 75% 4% 7% Latin America 9% 333% 39% Europe (other) 267% 11% 3% SE Asia & W Pacific 2010 In-region % Change 267% 11% 3% ME & Africa 7 CLINICAL TRIALS CONFERENCE DIGEST 2014

10 Rx&D member companies are in the process of contributing data to populate the database while data from existing asset maps are currently being extracted. According to Mr. Rhines, several Rx&D member companies have already begun the process. Once complete, the CCTAM will be a comprehensive one-stop tool for both local and global entities considering Canada as a site for clinical research. Developing this database, or catalogue, of Canadian based research organizations and their capabilities, will improve capacity for both academia and industry to conduct clinical studies in Canada. 2 The newly-merged Association of Canadian Academic Healthcare Organizations / Canadian Healthcare Association (ACAHO-CHA) aims to put the needs and preferences of each province at the centre of a model Clinical Trials Agreement. The Clinical Trials Action Plan which came out of the Clinical Trial Summit in 2011 hosted by Rx&D, the Canadian Institutes of Health Research (CIHR), and ACAHO calls for the streamlining of processes in order to position Canada as a premier country for industry led clinical trials. One component of the Clinical Trials Action Plan is the development of a model Clinical Trials Agreement (mcta). The mcta is a standard clinical trial template agreement that can help to streamline the negotiation process between sponsors and sites in an effort to improve clinical trial start up times. According to Tina Saryeddine, Assistant Vice-President of Research and Policy Analysis at ACAHO-CHA, a pilot program revealed that the best way to streamline the negotiation process 8 CLINICAL TRIALS CONFERENCE DIGEST 2014

11 would be to allow for flexibility at the provincial level. After conducting the pilot, ACAHO-CHA reconciled advanced versions of the mcta from Quebec and British Columbia. The reconciled version was then circulated to all ACAHO members for feedback. Sixteen institutions in Ontario contributed to the initial feedback with a goal of developing a single Ontario response, coordinated by Clinical Trials Ontario, along with the Ontario Council of University Research (OCUR) and the Council of Academic Hospitals of Ontario (CAHO). The draft Ontario response to the mcta was then circulated with consensus changes to Ontario institutions for final comment before it was submitted to ACAHO-CHA. By tailoring the mcta to specific provincial needs, ACAHO-CHA and its partners aim to improve business operations through reducing costs associated with contract negotiations, and to improve the quality and speed of clinical trial start up times. 3 The Strategy for Patient-Oriented Research (SPOR) Streamlining Health Research Ethics Review (SHRER) Committee has made progress towards greater harmonization and standardization among research ethics boards (REBs). In order to streamline, says Sharon Freitag, Director of the Research Ethics Office at St. Michael s Hospital, we really need to focus on what our core business is, do it, and do it well. Ms. Freitag and her team on the SHRER Committee aim to consolidate the existing knowledge about barriers to streamlining the research ethics review system and to recommend steps to improve the process. 9 CLINICAL TRIALS CONFERENCE DIGEST 2014

12 The SHRER Committee has offered a number of recommendations to improve the research ethics review process. Highlights are listed below: Establish a national strategic leadership forum on greater harmonization and standardization for REBs; Develop a system for evaluations and qualifications of REBs and Human Research Protection Programs (HRPP); Develop a common template for an REB clinical trial application form and adult consent form; and, Establish a national repository of resources to facilitate streamlining. These resources might include a database of REBs, forms, and policies, among others. These recommendations will help to bring down barriers to streamlining efforts. They will also foster a common understanding of how to improve the process. Doing so will eliminate administrative redundancies, thereby enabling clinical research to be conducted more efficiently. 4 Developments in the clinical trials environment amplify the need for collaboration among stakeholders through initiatives such as the Network of Networks (N2) and the Canadian Cancer Clinical Trial Network (3CTN). The Network of Networks (N2) is a national alliance of clinical research stakeholders with common interests. One of its goals is to bridge regional and provincial initiatives. The Canadian Cancer Clinical Trial Network (3CTN) is a new 10 CLINICAL TRIALS CONFERENCE DIGEST 2014

13 Highest Network Priorities Working Group Objective Activity Timeline Business Practices Performance - Initiation 3CTN tools for streamlining trial initiation, feasibility and workload assessments Immediate Disseminate ISCT recommendations Short term Standard of care costing initiative Long term Best Clinical Performance, Quality - N2 SOPs or equivalent at all sites Immediate Trial Practices Regulatory Compliance Information Technology Biospecimens & Imaging Research Priorities Lay Representation cancer initiative to enable an increase in the clinical research capacity of Canadian cancer centres to effectively conduct cancer clinical trials sponsored by academic institutions or cooperative clinical trials groups that will address questions of greatest importance to Canadians and the Canadian health care system. Performance - Ethics Performance, Quality Performance, Quality Impact, Sustainability Impact, Sustainability Source: Karen Arts Relevance of N2, Now More Than Ever Education & training required by HC and TCPS 3CTN will collaborate with existing ethics streamlining initiatives 3CTN will assist with EDGE system roll-out SPOs for biospecimen and imaging Checklist for equipment and resources for biospecimen handling at sites Training and certification of staff by CTRNet Imaging activities will be developed in first 2 years Economic and patient impact of clinical trials on health care system Innovation in clinical trials methods Lay representation throughout 3CTN Develop framework and role description Collaborate with Canadian Cancer Action Network Rising costs of development & pressure on R&D budgets, more complex research and regulatory environment, competitive environment, loss of opportunity, more education, support and resources needed Examples of Common Issues Common Solutions: N2 Rising cost and deficits Patient recruitment issues Inefficient processes Lengthy delays to start up trials Lack of metrics Lack of formal uniform, nationwide standards and research best practices HC findings: inadequate processes and systems, education and SOPs Inadequate research support from government and institutions Silos; we are special phenomenon Source: Karen Arts Immediate Short term Immediate Immediate Immediate Short term Short term Long term Long term Immediate Immediate Immediate Network, one voice Patient recruitment strategy, portal and materials Harmonize, educate, streamline, leverage (contracts, budgets, tools, ethics, recruitment, etc) Metrics initiative SOPs, education, quality HRP program Quality initiatives Collaborate with others Initiative to streamline clinical trials, ACAHO, CAREB, CTRNet, Provincial groups, etc. 11 CLINICAL TRIALS CONFERENCE DIGEST 2014

14 The relevance of N2 is becoming more and more apparent, says Karen Arts, Chair of the Board of N2 and Director at 3CTN. N2 is working on solutions to common issues faced by Canada s clinical research community. 3CTN s priorities offer a road map for improving the conduct of academic clinical trials in oncology. By carrying out their respective activities on a national level, N2 and 3CTN are addressing duplication of efforts and gaps across the country so that more efficient processes may be developed. 5 The Canadian Association for Independent Clinical Research (CAICR) suggests that it is critical to align all stakeholders in order to improve the clinical trials environment. Jack Corman, President of the Canadian Association for Independent Clinical Research (CAICR), an association that represents the independent clinical research community, and President of IRB Services, an independent research ethics review board, suggests that aligning all stakeholders, including the private sector, is necessary for improving the clinical trials environment in Canada. Through effective collaboration, Mr. Corman says, we can only get better at moving the ball downfield than any of us could do on our own. Two case studies particularly exemplify the benefits of bridging the gap between institutional and private clinical research, according to Mr. Corman. 12 CLINICAL TRIALS CONFERENCE DIGEST 2014

15 Through effective collaboration, Mr. Corman says, we can only get better at moving the ball downfield than any of us could do on our own. One example, the JUPITER Trial a study involving 18,000 patients that was conducted by the private sector used a single private ethics review for 83 Canadian community cardiology sites in multiple provinces to allow for a two- to three-day turnaround for investigator approval. The multi-year study required four amendments. Each amendment experienced similar turnaround times for approvals. the clinical research environment in Canada. Therefore, says Mr. Corman, aligning and involving all stakeholders will help to ensure that Canada and Ontario improves the clinical research environment, captures global market share of clinical trial activity, and attracts investment to the province and the country. 6 Clinical Trials Ontario (CTO) is making progress on its efforts to streamline the research ethics review system in the province. Susan Marlin, President and CEO of CTO, says that a strategic objective of CTO is to develop and support a streamlined ethics review system in Ontario. The streamlined ethics review system will be composed of two primary components: A second example showcased a story about a private clinical investigator network, Trial Management Group (TMG), which assumed a research project in Canada after a global contract research organization (CRO) could not meet the required timeline. The success of the first study with TMG led to a second study that involved collaboration with the Centre Hospitalier Universitaire de Québec (CHUQ), an academic centre in Québec. In total, the research involved 35 sites between two studies: 265 subjects were screened resulting in 162 randomized subjects. The single private ethics review and approval process enabled a two-week turnaround time or better for each study. Mr. Corman says that the private sector conducts more than 60 per cent of clinical trials activity in Canada and so is a critical stakeholder group. He explains that both institutional and private clinical research groups have an interest in advancing 1. A process to review and qualify REBs; and, 2. The implementation of a delegated board of record model. Streamlining REB & other CT admin processes Promoting Ontario & attracting investments Corporate Projects Operations & Governance Improving participant recruitment and retention Engagement of Clinical Trials Community in Ontario 13 CLINICAL TRIALS CONFERENCE DIGEST 2014

16 The delegated board of record model supports any CTO Qualified REB in conducting an ethics review of multi-centre research on behalf of multiple research sites across the province. In November 2013, CTO conducted a pilot phase with the Ontario Cancer Research Ethics Board (OCREB), which became the first Qualified REB. Taking lessons learned from the pilot, CTO plans to incorporate expert reviews of the qualification checklist, post the REB Qualification Manual for public consultation, qualify up to 20 REBs next year, and continue to revise and refine the program. Conference attendee Richard Sugarman, Chair of OCREB, describes CTO s efforts as a great beginning for figuring out how to work with this conundrum, for balancing speed, quality, and efficiency. CTO remains committed to attracting clinical trial investments to Ontario and is conducting ongoing industry outreach, developing a registry and asset map in partnership with other organizations, and creating a metrics and evaluation program. Meanwhile, it is also developing collaborations to determine how CTO can best add value to recruitment and retention efforts in Ontario. CTO s programming around streamlining the research ethics review system seems to appeal to industry, observes Dr. Sugarman. Involving all stakeholders, including industry, is essential for making Ontario a preferred location for clinical trials. 14 CLINICAL TRIALS CONFERENCE DIGEST 2014

17 7 Liability insurance for research is changing with developments in the clinical trials environment. As industry sponsored clinical trials activity has declined, the liability insurance landscape has changed for research institutions. Frank Naus, Director of Research Administration at Hamilton Health Sciences Corporation (HHSC), explains the changes. According to Mr. Naus, research has been conducted at HHSC for several years and the organization typically relied on the pharmaceutical sponsor s liability coverage to insure the institution for clinical trial work. Three options are available to research institutions in light of the trend of declining industry-sponsored clinical research, according to Mr. Naus: No insurance, which is not realistic today, he adds; Self insurance; and, Captive insurance. One of the challenges facing research insurance companies is the degree of variation between research institutions. The risk profile if you re running clinical trials is very difficult to generalize, says Mr. Naus. For this reason, he suggests, research institutions should explore captive insurance. Captive insurance, which allows organizations to compartmentalize the organization s risk exposure so that one cell does not put other cells at risk, provides tailored coverage for research institutions. Some of the benefits of captive insurance range from improved risk management and risk financing to Research Insurance Corporation Source: Frank Naus Cell #1 HHS internal smoothing of deductibles, to name a few. The captive model is more flexible and addresses inefficiencies, says Mr. Naus. It offers higher flexibility when taking all aspects into account such as legal costs and the profitability of winning or losing a lawsuit. Research Insurance Corporation Cell #2 Cell #3 Cell #4 Cell #5 Reinsurance Program: Applicable to all segregated or individual cells Reinsurance is in excess of the risk retained in each cell Each cell is autonomous and shares costs with other cells and core captives; each cell benefits from its own experience. All cells benefit from group buying power with respect to insurance. By addressing these inefficiencies in liability coverage, research institutions can reduce the cost of conducting trials. 15 CLINICAL TRIALS CONFERENCE DIGEST 2014

18 STREAMLINING RESEARCH ETHICS REVIEW Challenges and Opportunities A Perspective from a Principal Investigator My interest is in time-sensitive, life-saving interventions, says Laurie Morrison, Professor and Clinician Scientist, Division of Emergency Medicine, Department of Medicine, University of Toronto and Li Ka Shing Knowledge Institute, St. Michael s Hospital. At the CTO 2014 Clinical Trials Conference, Dr. Morrison spoke about the challenges of being a primary investigator. Dr. Morrison s research interests span from cardiac arrest, life-threatening trauma, pre-hospital and transport medicine to resuscitation research and emergency health care delivery. Her story brought to life why it is so important to streamline the research ethics review process. The system is so arduous to get through, she says. This is because multiple reviews create redundancies and duplication of efforts. For example, when initiating a clinical trial, companies and investigators face multiple forms, processes, and standards that serve the same purpose. These complexities result in inconsistent turnaround times, higher costs, and delays. By streamlining the process for 16 CLINICAL TRIALS CONFERENCE DIGEST 2014

19 conducting multiple reviews, the clinical research community can simplify the system while achieving the same objectives. As an investigator within the Resuscitation Outcomes Consortium, Dr. Morrison has been funded by the US National Institute of Health, Canadian Institutes of Health Research and Heart and Stroke Canada. In Dr. Morrison s view, clinical research needs to be nimble. It s better for us. It s better for the patients. And, it s much, much better for science, she says. In Canada, we re good at listening to the REB [research ethics board]. But that doesn t mean it always goes smoothly, says Dr. Morrison. In Dr. Morrison s view, clinical research needs to be nimble. It s better for us. It s better for the patients. And, it s much, much better for science, she says. For her, the impetus for streamlining the research ethics review system comes chiefly from the urgency associated with emergency medicine research. Preparing for a Streamlined Ethics Review System One of the lessons learned from the streamlining initiative in the UK, according to Janet Manzo, Executive Director of the Ontario Cancer Research Ethics Board (OCREB), is that their initial efforts focused too much on implementing an online ethics review system, while ignoring the change management activities required to ensure that the people and the processes were ready for the new model of ethics review. The UK also noted that they had underestimated how embedded investigators were with their local research ethics boards (REBs) and how challenging it is for one REB to develop trust in another REB. In a survey of patients about the single REB model, the response was mixed. Some felt protected by their hospital REBs while others thought local (hospital) REBs were not independent enough. Likewise, the Clinical Trials Transformative Initiative (CTTI) project to advance the use of central Institutional Review Boards (IRBs) in the USA learned about barriers to ethics streamlining efforts. They stress the importance of delineating the responsibilities of each party, of clearly defining the expectations, of developing solid communication plans, and of employing change management techniques. OCREB s own experience in centralizing oncology ethics reviews in Ontario produced insights similar to those in the UK and USA. Ms. Manzo agrees that the conflation of institutional responsibilities with the ethics review responsibilities of the REB is probably the biggest hurdle to overcome. The reliance on an external REB requires the creation of new processes for institutional reviews, which historically have been allocated to the local REB. One of the key lessons learned from all of the ethics streamlining initiatives is that the research ethics board (REB) is only one 17 CLINICAL TRIALS CONFERENCE DIGEST 2014

20 component of human research protection, says Ms. Manzo. The REB, the institution and the researcher all have responsibilities in ensuring the ethical conduct of research and all parties must be engaged and accountable in order for CTO to be successful. Ms. Manzo also stresses that it is impossible to underestimate the communication efforts required for the success of such an initiative. She puts it this way in one of her slides: Communication with researchers and teams; Communication with the institution; Communication with sponsors/contract research organizations; and, Communication. Communication. Communication. OCREB was the first REB in Ontario to be qualified under CTO s REB Qualification Program. Ms. Manzo notes that many challenges and opportunities lie ahead; however, she recognizes the importance of the initiative and notes that having incorporated many of the national activities into its development, CTO provides Ontario with a leadership role in streamlining clinical trials, says Ms. Manzo. This is really an opportunity to leverage our expertise, says Sharon Freitag, Director of the Research Ethics Office at St. This is really an opportunity to leverage our expertise, says Sharon Freitag, Director of the Research Ethics Office at St. Michael s Hospital. It is important that clinicians are a part of the research, says Dr. Coughlin. In the community hospitals, to maintain that culture [of research], it s important. Michael s Hospital. According to Jack Holland, Oncology REB Review Panel Chair, University Health Network, The barriers are the ones that are human in nature. Fellow panelists Keitha McMurray, Director of the Human Research Protections Program at Sunnybrook Health Sciences Centre, David Mazer, Chair of the Research Ethics Board at St. Michael s Hospital, and Michael Coughlin, Chair of the Tri-Hospital Research Ethics Board, suggest that the clinical trials community can overcome these challenges with active involvement from all stakeholders. It is important that clinicians are a part of the research, says Dr. Coughlin. In the community hospitals, to maintain that culture [of research], it s important. Susan Marlin, President and CEO of CTO, explains that efforts to eliminate barriers have, in part, shaped the development of the REB Qualification Program and the delegated board of record model. Together, these two initiatives provide REBs with a common standard to facilitate trust between participating REBs. 18 CLINICAL TRIALS CONFERENCE DIGEST 2014

21 My feeling, optimistically, is that this is going to work, adds Dr. Holland. Institutions need to trust other boards to produce a review of the same quality, says Ms. Marlin. This trust is integral to the success of a streamlined system for research ethics reviews of multi-centre trials. My feeling, optimistically, is that this is going to work, adds Dr. Holland. The CTO REB Qualification Process: A Look Under the Hood A presentation delivered by Anita Sengar, Research Ethics Board Operations Manager, University Health Network, offers an overview of the CTO REB Qualification Program. As Ms. Sengar explains, members of the CTO REB Streamlining Working Group reviewed several models for assessing the quality of REBs and recommended that the Toronto Academic Health Sciences Network (TAHSN) REB Qualification Manual be used as a starting point for a qualification program. Reviewed by external experts, the CTO REB Qualification Manual is built on the work done by TAHSN and is informed by the Canadian General Standards Board (CGSB), the second edition of Tri-Council Policy Statement: Ethical Conduct for Research 19 CLINICAL TRIALS CONFERENCE DIGEST 2014

22 Involving Humans (TCPS2), Health Canada, the International Conference on Harmonization of Technical Requirements for the Registration of Pharmaceuticals for Human Use Guidance E6-Good Clinical Practice (ICH-GCP), and Food and Drug Administration regulations and policies. The CTO Qualification Review Team consists of a College of Reviewers. The College of Reviewers includes an auditor, REB Chair, REB Operations Personnel, and a CTO representative. Qualification Program in what was a collaborative and collegial pilot program, according to Ms. Sengar. Next steps include further refinement of the qualification checklist, which provides a standard for qualifying REBs, based on expert reviews. CTO will also upload the manual for community feedback and is currently recruiting REBs to undergo the CTO REB Qualification Program. The [Research Ethics Review] advisory group felt that this approach was a good one that allowed for cross-pollination of knowledge from across Ontario, says Ms. Sengar. OCREB volunteered to be the first to go through the CTO REB 20 CLINICAL TRIALS CONFERENCE DIGEST 2014

23 CLINICAL TRIALS PARTICIPANT ENGAGEMENT AND RETENTION This is About People : Insights Into Participant Engagement and Retention The Trial Centric Process Source: Ken Getz Hear of the study Respond & take prescreener AWARENESS Contact Investigator RECRUIT Make Appointment Consent Randomize CONVERSION Attend Appointment RETAIN Exit Trial In his keynote address, Ken Getz, Director, Sponsored Research Programs and Associate Professor, CSDD, Tufts University School of Medicine, Founder and Board Chair, The Center for Information and Study on Clinical Research Participation (CISCRP), identifies the lack of public and participant outreach and engagement as one of the root causes behind some of the challenges facing the clinical research community. Mr. Getz explains the differences between a trial centric process for recruitment and retention and a patient centric one. trials focuses on patient-driven research agendas, funding, and participation. It s not about bringing patients to trials, says Mr. Getz. It s about bringing trials to patients. According to Mr. Getz, a patient centric process uses a wide variety of channels including social and digital media to educate, Worsening Patient Enrollment Rates N = 3,534 phase II-IV protocols Data: Tufts CSDD Source: Ken Getz According to Mr. Getz, the traditional trial centric process focuses on meeting trial enrollment targets. It does not respond to negative portrayals of clinical research. It also relies on ineffective and misaligned messages. 73% 59% 57% 67% 49% 43% 49% Mr. Getz goes on to explain that, despite significant efforts with a trial centric process, patient enrollment rates are worsening. 29% 25% By contrast, a patient centric process for conducting clinical Screened to Randomized Randomized to Completed Screened to Completed 21 CLINICAL TRIALS CONFERENCE DIGEST 2014

24 reach, and engage study volunteers. It crowdsources input into program planning and protocol design. It shares findings with health care providers and disseminates trial results to study volunteers. In other words, a patient centric process educates, informs, and empowers patients to understand what it means to be an active participant. I think there s a real lack of awareness of how rigorous [clinical trials] are, says Linda Bennett, Executive Director of the Canadian Rheumatology Research Consortium. We need to address the public s lack of trust in the research eco-system. James Lavery, Research Scientist at the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael s Hospital, Associate Professor, Dalla Lana School of Public Health and Joint Centre for Bioethics, University of Toronto, highlights the importance of community engagement in research ethics. Community engagement is about relationships, says Dr. Lavery, whose research in global health examines community engagement. Dr. Lavery says that engagement accomplishes three ethical goals: minimizing risk and balancing effect, demonstrating respect, and enhancing legitimacy of the findings among the interested community. According to Dr. Lavery, when researchers engage communities they learn about how research may affect the community s interests. This learning enables the researchers to acknowledge 22 CLINICAL TRIALS CONFERENCE DIGEST 2014

25 Public and Patients Engaging the Research Enterprise General Education Ongoing messages positioning participation and the Enterprise Development Planning & Fundraising Collaboration with patients and patient communities those interests, be responsive to them, and therefore protect them. By learning, acknowledging, responding, and protecting interests, researchers achieve the three ethical goals outlined above. Study Design Solicited input into design and flexibility from patients and patient communities Supported by, and coordinated with, enabled investigative sites Built on a foundation of engaged stakeholders including health care professionals and health educators Karen Arts, Director of Business Development, High Impact Clinical Trials Program, Ontario Institute for Cancer Research (OICR), Chair of the Board of Network of Networks (N2), and Director at the Canadian Cancer Clinical Trial Network (3CTN), highlights the benefit of involving lay representatives in clinical trials beyond the role of the participant. OICR, for example, involves lay representation in protocol review committees. Recruitment & Retention Awareness and encouragement from patient communities Monitor & Analyze Data Patient membership on DSMBs Regulatory Review & Approval Patient participation on advisory committees and postmarket surveillance initiatives Disseminate & Communicate Results Distribution and ongoing discussion through patients and patient communities Source: Ken Getz Education Ambassadors Interaction at community centers, the media, classrooms Community engagement is about relationships, says Dr. Lavery, whose research in global health examines community engagement. Another example is a model put forth by the Canadian Institutes of Health Research s Strategy for Patient-Oriented Research in which patients might provide input on identifying health research priorities. They would participate in the design and undertaking of research projects in order to improve the patient experience as well as health outcomes. Ms. Arts emphasizes that to ensure lay representation is meaningful for both the health care provider and the lay representative, it is critical to define the role of lay representatives. To assist, 3CTN has assembled a working group on lay representation with a plan to offer recommendations for a number of issues: How best to achieve meaningful lay representation; A conceptual framework to assist with achieving meaningful lay representation; and, Support, training, and education with a toolkit of best practices, tools, processes, and systems for lay representation. Since participants live with their health condition daily, it is crucial to put the patient at the centre. Dawn Richards, presenting as a person living with rheumatoid arthritis, focuses on the need for patient-driven, national arthritis advocacy and education. Dr. Richards volunteers as the Vice President of the Canadian Arthritis Patient Alliance (CAPA) and is an Arthritis Consumer Experts Advisory Board Member. Those affected by the decision must be involved in making the decision, says Dr. Richards. The first expert in arthritis is the 23 CLINICAL TRIALS CONFERENCE DIGEST 2014

26 person living with arthritis. CAPA advocates that people with arthritis have both the right and responsibility to help form policy about health care and research decisions related to their health and quality of life. For CAPA, this right and responsibility entails creating and producing information about their condition, leading organizations involved in arthritis care, translating messages into lay language to help raise clinical research literacy, and disseminating information to patients and the public. The person living with the condition, then, becomes a bridge between health researchers and the public. This bridge can help engage the arthritis community and encourage their participation in clinical research. Community engagement is about engaging the physicians, too, Dr. Lavery adds. Those enrolling physicians are stakeholders. From his perspective, physicians in the community likewise bridge the gap between researchers and the public. Ms. Bennett says that public education is a key component of the solution; we must raise awareness of the value of research to our collective health and help the public to better understand how we safeguard participant well being and research integrity. 24 CLINICAL TRIALS CONFERENCE DIGEST 2014

27 CIHR Strategy for Patient-Oriented Research (SPOR) Source: Karen Arts Improved patient experience with health system and health outcomes Patients influence and accelerate decision making and uptake of new practices Research is conducted in areas patients value Researchers understand the value of patient involvement and patients understand the value of research CTO is exploring how key elements from the CTO 2014 Clinical Trials Conference might come together to form a framework to better engage the public in research. CTO is seeking perspectives from a variety of constituencies including patients, health charities, researchers, sponsors, and academic institutions. These perspectives will help to determine whether there exists a specific role for CTO in improving public engagement and participant outreach. Provide input on identifying health research priorities Participate in the design and undertaking of research projects Patients Pulling together the ideas put forth by the afternoon panel, Ms. Bennett suggested these might form the basics of a framework to engage the public in research. If we begin by creating national resources to support shared needs and then establish a forum of community groups that engage patients directly, we can develop the tools and processes to gather and share specific information that is relevant at a community or individual level. The main message from Ms. Bennett s presentation, though, is that we need input from the patients in order to successfully engage their communities. If we could cultivate, support and utilize patient advisors and ambassadors as partners in research, this might be an important step toward more meaningful engagement at the broader community level. 25 CLINICAL TRIALS CONFERENCE DIGEST 2014

28 ACKNOWLEDGEMENTS Clinical Trials Ontario would like to thank all attendees, speakers, panel moderators, session moderators, CTO board members, and everyone involved in the production of the CTO 2014 Clinical Trials Conference. We would like to thank a number of individuals in particular: Linda Bennett, Executive Director, Canadian Rheumatology Research Consortium Jack Corman, President, IRB Services; President, CAICR Michael Coughlin, Chair, Tri-Hospital Research Ethics Board Sharon Freitag, Director, Research Ethics Office, St. Michael s Hospital; Chair, SHRER Committee Session Moderators Raphael Hofstein, President and CEO, MaRS Innovation; CTO Board Member Clive Ward-Able, Executive Director, R&D, Amgen; CTO Board Member Raphael Saginur, Chair, Research Ethics Board, Ottawa Hospital; CTO Board Member Michael Wood, Director, Office of Research & Innovation, North York General Hospital; CTO Board Member Kenneth A. Getz, Director, Sponsored Research Programs, Tufts Center for the Study of Drug Development; Chairman and Founder, The Center for Information and Study on Clinical Research Participation Jack Holland, Chair, Oncology REB Review Panel, University Health Network James V. Lavery, Research Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael s Hospital; Associate Professor, Dalla Lana School of Public Health and Joint Centre for Bioethics, University of Toronto Speakers and Panel Moderators Karen Arts, Director of Business Development, High Impact Clinical Trials Program, Ontario Institute for Cancer Research (OICR); Board Chair, N2; Director of External Initiatives, 3CTN Paul Lucas, President and Chair, Life Sciences Ontario Janet Manzo, Executive Director, Ontario Cancer Research Ethics Board (OCREB) Nita Arora, Regional Head, Affiliate Management, North America Hoffmann La Roche Neil Maresky, Vice President, Scientific Affairs, AstraZeneca Canada 26 CLINICAL TRIALS CONFERENCE DIGEST 2014

29 Susan Marlin, President and CEO, Clinical Trials Ontario David Mazer, Chair, Research Ethics Board, St. Michael s Hospital; Vice-Chair, Department of Anesthesia, University of Toronto Keitha McMurray, Director, Human Research Protections Program, Sunnybrook Health Sciences Centre Laurie Morrison, Professor and Clinician Scientist, Division of Emergency Medicine, Department of Medicine, University of Toronto and Li Ka Shing Knowledge Institute, St. Michael s Hospital Frank Naus, Director of Research Administration, Hamilton Health Sciences Corporation Jared Rhines, Vice President, Scientific and Strategic Affairs, Rx&D Dawn Richards, Vice-President, Canadian Arthritis Patient Alliance Tina Saryeddine, Assistant Vice President Research & Policy Analysis, ACAHO-CHA Anita Sengar, Research Ethics Review Board Operations Manager, University Health Network James Wilson, President, Brancorth Medical Inc.; CTO Board Member 27 CLINICAL TRIALS CONFERENCE DIGEST 2014