The Canadian Traumatic Brain Injury Research Consortium: Epitomizing Collaborative Research in Canada

Abstract

Traumatic brain injury (TBI) is the leading cause of death in the first half of life and a chronic disability for Canadians of all ages. Despite the recognized importance of TBI, there is no integrated national strategy for research and best practices in Canada. We therefore created the Canadian TBI Research Consortium (CTRC) to build an ideal model of collaboration between Canadian TBI researchers. Our objectives were to: (1) Create a collaborative Canadian research network, (2) improve patient survival, functional outcome, and health through sustainable and scalable evidence-based practice implementation, (3) strengthen the healthcare system for patients with TBI, (4) provide international leadership and collaboration in TBI research, (5) build stronger links with patients and their representatives to help set the research agenda, and to participate in analysis of its impacts, and (6) support current researchers and prepare the next generation of leaders in TBI research. Building on the highly successful 30-year history of the Canadian Critical Care Trials Group, we developed a highly collaborative research group that integrates the multi-disciplinary network of TBI researchers in Canada. The CTRC conducts multi-center clinically relevant practice changing research. Our research is developed around investigator-led project-based research using a programmatic approach and multiple methodologies. Through strong and sustainable career development and mentorship programs, we train and develop the next generation of TBI researchers. Our group is composed of more than 100 Canadian researchers from coast to coast, most of them funded by the Canadian Institutes of Health Research and other granting agencies. In conclusion, the CTRC prioritizes investigator-led TBI research and broadens the research agenda by integrating researchers from different disciplines in the field of TBI research to optimize delivery of care and improve the health of Canadians with TBI. Our goals are being accomplished across the whole continuum of care by conducting clinically relevant and practice-changing research.

Introduction

Traumatic brain injury (TBI) is a leading cause of acquired disability and death in children, adolescents, and young adults.^1

–5 It accounts for approximately 150,000 annual emergency room visits and hospital admissions, and approximately 500,000 people are living with a TBI-related disability in Canada (based on estimates generated from United States and European data).⁴ The 2014 National Population Health Study of Neurological Conditions documented the direct and indirect costs of hospitalized TBI in Canada and reported that next to Alzheimer disease and other dementias, TBI is the second highest neurological condition necessitating health care. In recent years, TBI has become the condition with which the highest number of Canadians have to live. It has numerous causes, the most common being from falls, sports-related injury, and motor-vehicle collisions.^4,6 Survivors are at risk for cognitive, behavioral, and/or motor disabilities^7,8 requiring rehabilitation services.⁹ While the range of outcomes is broad and difficult to predict,^10,11 the long-term burden for many patients and their families is overwhelming.^12
–14

Despite the magnitude of the socioeconomic and healthcare problem posed by TBI, clinical research in the field has not been as extensive as in other fields of medicine such as oncology, cardiology, or respirology, to name a few. Advances in basic science have failed to translate into successful clinical research, and most clinical applied research initiatives conducted over the last decades were single center, of low impact, and thus have a limited ability to change practices and improve care. More so, the field is fragmented, because concussion researchers typically work separately from researchers working on more severe brain injuries, acute care researchers have limited contact with rehabilitation researchers and vice versa. Basic science researchers working with animal models have limited collaboration with researchers in clinical applied research, and often have limited access to biobanks and clinical data.

Current management is highly variable, and most interventions used at the bedside are based on limited evidence.¹⁵ More importantly, death and long-term outcomes vary across centers.^15,16 Many people living with TBI have long-term symptoms, physical or mental health problems yet, early after injury, we are unable to determine prognosis to help with level of care decisions for the most severely injured patients, and to plan rehabilitation or tailor support services. Finally, because the research agenda for major health conditions is often driven to develop for-profit interventions, it limits the spectrum of new discoveries, and several interventions used at the bedside are still poorly studied and of unknown efficacy.

We felt an urgent need to coordinate research initiatives and bring Canadian TBI researchers together to lead national and international projects with the overarching goal to change practices and improve outcomes for persons with TBI. We believed that an open, inclusive, collegial, and collaborative consortium for investigator-led research was needed to accelerate high impact research and knowledge translation.

The Canadian Traumatic Brain Injury Research Consortium

We named our group the Canadian TBI Research Consortium (CTRC) and modeled it after two Canadian consortia with a long history of collaborative interdisciplinary work; the Canadian Critical Care Trials Group (CCCTG), a collaborative clinical applied research network in critical care medicine, and the Canadian Critical Care Translational Biology Group (CCCTBG), the basic science and translational biology research group that is partnered with the CCCTG. The CCCTG, which was formed in 1989, is the oldest critical care research group in the world and has served as an exemplary model for the development of multiple Canadian and international pediatric and adult critical care, emergency medicine, and anesthesia research consortia.^17,18 Funding for the CTRC was awarded in January 2016 by the Canadian Institutes of Health Research (CIHR) and our first face-to-face scientific meeting was held in June of that year. We hold two face-to-face scientific meetings per year where we propose, critically appraise, and plan investigator-led collaborative multi-center research.

What is our vision and what are our objectives?

Based on a combined 30 years of experience participating in and helping lead the CCCTG and CCCTBG, the inaugural co-chairs of the CTRC, Dr. Jamie Hutchison and Dr. Alexis Turgeon, along with the members of the executive committee, scientific members, and trainees, created and endorsed a vision and mandate for our group. Our Vision: To create and sustain a collaborative, integrated, and impactful consortium for the Canadian TBI research community and to elevate Canadian research in TBI to a new level.

Our objectives are: (1) To create a consortium infrastructure that demonstrably facilitates linkages, communication, and knowledge translation among Canadian TBI researchers to align our efforts with the research priorities of victims of TBI, their caregivers, and their communities; (2) to support research projects that integrate national TBI research and align them with and/or lead international research. It is worth noting that CTRC includes the full spectrum of TBI severity, from the most mild (including concussion) to the most severe injuries, and the full age range of victims—infants, toddlers, children, adolescents, adults and the elderly. Efforts to ensure a good representation of research conducted across the spectrum of severity, age, and neurodevelopment will be a priority for the future directions of the CTRC.

How is the CTRC structured?

We built the CTRC with two main components—a coordination and a research one. The coordination component provides structure and administration to help organize our collaborative group. This includes oversight and organizational structure for face-to-face meetings, teleconferences, networking, and communication. Our scientific meetings are held twice a year, in January and June, with two days of scientific presentations by the researchers and one day dedicated for scientific presentations by trainees with researchers attending. We developed a logo and a public website (http://www.ctrc-ccrt.ca/). We have organized and implemented education, mentoring, and career planning for trainees and early-career investigators. Our education committee organizes a trainee day where trainees present their research and receive critical appraisal from both trainee peers and CTRC researchers, and where researchers present personal experience and pearls for mentoring and career planning. We formed a CTRC Grants and Manuscripts Peer Review Committee that organizes and implements internal peer review of manuscripts and grant proposals before submission on behalf of the CTRC. Our peer review committee also reviews applications for CTRC internal award grants, such as those for projects, graduate and post-doctoral awards, and travel awards.

Our research component helps support research programs by providing methods expertise to CTRC members leading multi-center national and international investigator-initiated programs. Our goal is to do research that will have a high impact in the scientific community, but more importantly for the patient, by improving care and the quality of life of victims of TBI and their families/caregivers. We created four platforms to support the investigator-led research programs of the members, including knowledge synthesis, data sharing, pilot projects (seed funding), and training and career development. Our platforms provide training through webinars, expertise, and mentorship to members to help them to develop their projects/programs of research.

The CTRC executive committee is composed of the two CTRC co-chairs (Dr. Jamie Hutchison and Dr. Alexis Turgeon), two executive managers, three regional committee members, and a representative of the TBI community. We have purposely fostered an open collegial environment inviting researchers, trainees, and research personnel to join the CTRC from any scientific discipline as long as their research is focused on TBI (Fig. 1). The CTRC members therefore have diverse backgrounds including basic science, translational biology, evaluative science, clinical applied research, and knowledge translation, and we also include patient/family representatives. Currently, more than 100 members form the CTRC and close to 50 trainees are also involved in our activities. We move from bench to bedside and study humans across the TBI severity spectrum. We also study TBI across their continuum of care including community, pre-hospital, acute hospital, and long-term rehabilitation.

FIG. 1.

Structure of the Canadian Ttaumatic Brain Injury Research Consortium (CTRC).

How do our scientific meetings work?

The organization and structure of our face-to-face scientific meetings are key to our success. Before the meeting, deadlines are forwarded to the members via email. Scheduling of presentations are then requested by members including the title of the project/program of research and the time required for the presentation. A structured abstract and questions for the group, to facilitate the discussion, must be submitted in advance of the meeting, and the abstracts are then shared with each member before the meeting. At the meeting, the presentations are encouraged to be about new projects/programs that are multi-center (i.e., national or international in scope). The spirit of the CTRC is to work together as a team to conduct collaborative impactful research, so if a researcher wants to answer a specific research question, it should be done as part of a comprehensive program of research involving several projects.

Following each presentation and discussion and feedback from the group, the project or program of research is considered a CTRC project or program (i.e., The CTRC is considered an “investigator” on the project or program). The project or program may need to be modified before going forward, and the principal investigators must follow the comments received from the group to develop the next steps. The CTRC members interested in helping or collaborating as part of the leadership of a specific research project or within the program of research presented are encouraged to do so according to their expertise, or to simply collaborate as a participating site when the project is ready. We encourage collaboration and expect members to involve other members that are interested in helping out as co-investigators and/or collaborators. Research projects have started with multiple collaborators and sites for both basic science and clinical applied research. Presentations, key discussion points, and those interested in leading and collaborating are documented in the minutes of the meetings.

What is our approach to a research question?

The CTRC promotes a programmatic approach to research. This approach starts with a research question that must be of interest for both the principal investigator/member of the CTRC who will be leading the program of research and the CTRC members. The question is brought forward at one of our face-to-face scientific meetings along with a plan for answering it. As opposed to other collaborative research groups, the research agenda of the CTRC is driven by its membership and what is of interest for them, and not by the executive committee or the leaders.

When first presented, a program of research may be completely at its beginning or may follow some background work already conducted by the research team. However, the common denominator is that, for each research question and program of research, the necessary steps (background projects) must be planned and performed before a large-scale multi-center study or trial can be submitted for funding and conducted (Fig. 2). This programmatic approach has been used successfully by other groups and has led to major practice changing programs of research—namely, in critical care medicine at large.^17,19

FIG. 2.

Programmatic approach to research in traumatic brain injury (TBI) within the Canadian TBI Research Consortium (CTRC). Multiple methods, from bench to bedside, are used to answer a research question. Ultimately, the investigator conducts a multi-center observational study or randomized controlled trial to definitively answer the question. Knowledge translation experts within the CTRC will help accelerate the application of this new knowledge to improve patient care.

This approach involves several steps starting with a systematic review of the current evidence on the question of interest, to appraise the level of evidence and the gap in knowledge. It is then followed by the different necessary steps (projects) that may be different for each program of research, but are often about ensuring the relevance of the question. These steps may help address whether there is a biological rationale, whether it really is an issue and whether the problem is real, if the community is interested in this question, and if it is feasible to perform the planned large-scale multi-center study or trial. For doing so, clinical and evaluative research methodologies may be required. The researcher may use knowledge synthesis, qualitative research, quantitative research using large databases and/or clinical trial methodology. For collaborative basic science or translational biology research projects, the researchers may share certain laboratory methods, research platforms, or core technologies (e.g., for genomics and proteomics). Certain investigator-led research programs are encouraged to include both basic science and clinical research components.

The CTRC members interested in the research topic and with the necessary methodological expertise will thus be approached to be involved in these different projects and the expertise from the methodological platforms of the CTRC will be sought. As part of a project/program, a knowledge translation plan (project) is developed with the help of our members with knowledge translation methods expertise to ensure the rapid uptake of the findings. A key principle of the programmatic and collaborative approach is that if multiple CTRC members are interested in a similar research question, they must work together in partnership in a sole program of research that will have a broader scope than one study typically planned in a single institution. The development and conduction of a program of research from its inception to successful funding for the different steps through to the completion of a large-scale practice-changing study must thus be planned and executed over many years. Some examples of CTRC research projects or programs are shown in Table 1.

Table 1.

Examples of Canadian Traumatic Brain Injury Research Consortium Research Projects or Research Programs

Studies or programs	Principal investigators	Focus
The effect of individually tailored subsymptoms threshold exercise prescription in adolescents with physiological post-concussion disorder	Carolyn Emery	A multi-institutional randomized controlled trial evaluating whether an exercise program improves the rate of recovery from a concussion in adolescents
SiMPly Rehab: Seeing-Moving-Playing: Early Rehabilitation utilizing visual and vestibular technology following traumatic brain injury	Isabelle Gagnon	Multi-center cohort study to test the use of novel technologies to stimulate recovery in children following TBI
A national biobank and database for patients with traumatic brain injury (TBI) (CanTBI)	Jamie Hutchison	Multi-center cohort study and biobank to discover molecular and neuroimaging biomarkers across the age and TBI severity spectrum
HEMOTION Trial	Alexis Turgeon	International multi-center randomized controlled trial of liberal versus restrictive transfusion thresholds in critically ill adults with moderate and severe TBI
	Dean Fergusson
	Francois Lauzier
TBI-Prognosis Multicentre prospective study	Alexis Turgeon	Multi-center cohort study to develop a prognostic model in critically ill adults with severe TBI based on clinical data, molecular biomarkers, and neuroimaging
Detection and Validation of Fluid-Based Biomarkers in TBI Using Ultra Sensitive Simoa Technology	Cheryl Wellington	Use of an ultrasensitive technology for detection of brain molecular biomarkers for diagnosis and prognosis using a multi-center biobank

What do we expect from members?

We developed terms of reference to define what is expected of CTRC members. Once a project and/or program is endorsed by the CTRC members, it becomes a CTRC project/program and must be recognized as such when presenting the project/program in the future. Principal investigators are expected to present an update of progress at each meeting and present questions to lead discussions. The discussion and helpful advice from experienced researchers are extremely important to help overcome obstacles and ensure the success of each CTRC research project/program. These inputs help improve the quality of the projects/programs and increase the chance of successful funding by peer-review granting agencies.

Any grant application submitted to a peer review granting agency of a project/program endorsed by the CTRC must first be submitted, in advance of the grant deadline, to the CTRC Grants and Manuscripts Review Committee. Following internal peer review (open review by members) and satisfactory revision of the grant application, if so requested, formal support of the CTRC is given for submitting the grant proposal. Any manuscript submitted from a CTRC project/program must also be submitted on behalf of the CTRC and should include collaborators/co-investigators meeting authorship criteria. Manuscripts must also undergo an internal peer-review process before being submitted for publication.

Members are expected to attend the face-to-face meetings and to participate in the discussion to help develop the projects/programs of colleagues. The rationale for these expectations are: (1) that we document our successful grant applications and publications as metrics of our collaborative productivity; (2) that the spirit of CTRC researchers and patients is both collaborative and respectful of intellectual property; (3) that these expectations help ensure our trust and accountability to each other and to our funders, and; (4) that they help to build credibility to ensure sustainability and future funding for infrastructure and for hypothesis-driven scientific research.

Conclusions

We created the CTRC based on the successful approach developed by other collaborative research groups.^17,18,20 Over the last two years, we grouped together most TBI researchers in Canada from basic science to translational, clinical applied and evaluative research, from the acute to the rehabilitation phases of care and from the whole disease severity in both pediatric and adult populations. Our membership is growing, and our mentorship role to trainees and early career researchers in the field is very appreciated by the research community. With more than 100 current members from coast to coast representing most academic institutions in Canada and close to 35 different programs of research, some already funded by national granting agencies, we have reached the goal we set for ourselves.

The success of the CTRC belongs in the collaborative spirit surrounding our meetings, the respect of each other's work, and the collegiality that has developed over time. Importantly, it also requires our members and colleagues to help others develop their ideas by providing methodological expertise or giving access to and sharing data. Such collaboration and sharing of expertise is key to developing research that will have an impact on patients' care by ensuring the appropriate scope and feasibility. Another incredibly important collaborative function of the CTRC is the enrollment of participants and collection of data across multiple study sites in CTRC projects.

In summary, the CTRC is the first collaborative research group in TBI research within which projects and programs of research that are investigator-led are developed in a collaborative fashion. Our group develops research that is not driven by a commercial agenda, is independent of industry partners and funding, and CTRC members are involved in the funding of the venue for our scientific meetings. These principles help ensure that the work developed by the group has optimal relevance to the scientific TBI community and is free of biases and conflicts of interest.

Footnotes

Acknowledgments

We would like to thank the Canadian Institutes of Health Research (CIHR) and the Ontario Neurotrauma Foundation (ONF) for funding the CTRC. We want to thank Dr. Anthony Philips and Dr. Elizabeth Theriault, from the Institute of Neuroscience Mental Health and Addiction (INMHA) of the Canadian Institutes of Health Research (CIHR), for helping in envisioning the organization of the network of Canadian TBI researchers. Dr. Gagnon is supported by a clinical investigator award from the Fonds de Recherche du Québec – Santé (FRQS). Dr. Turgeon holds a Canada Research Chair in Critical Care Neurology and Trauma.

Author Disclosure Statement

No competing financial interests exist.

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