EXCELERATOR

The Blueprint Translational Research Group was established in 2016 at the Ottawa Hospital Research Institute, in collaboration with the Ottawa Methods Centre. Co-led by Dr. Dean Fergusson and Dr. Manoj Lalu, with the operational leads Mohamad Sobh and Josh Montroy, Blueprint developed an innovative model called the Excelerator program to enhance and enable efficient clinical translation through rigorous methods and approaches. In 2019, Blueprint partnered with the Faculty of Medicine at uOttawa to extend the Excelerator program to its faculty to help rapidly develop promising therapies from bench to early-phase trials.

The Excelerator method targets several issues that contribute to failed translation when pre-clinical and early phase clinical trial protocols are developed. Given the broad array of complex issues that prevent efficient bench-to-bedside translation, it is clear that a traditional single-investigator driven approach is simply inadequate to address these challenges. Instead, the Excelerator is a collaborative “team-science” model that leverages various expertise.

Excelerator model MS

First, we conduct systematic reviews to objectively appraise available preclinical data and early phase clinical data. This allows us to assess safety, efficacy, and identify knowledge gaps. In addition, our reviews have been well received by regulatory agencies (i.e. Health Canada) that are highly concerned about safety when initiating ‘first-in-human’ and early phase clinical trials.

Second, we use ‘implementation diagnostics’ to identify barriers and facilitators to patient and clinician participation in clinical trials. These interview and survey studies (Dr. Justin Presseau) have helped us optimize eligibility criteria, specifics of interventions, and outcomes to be assessed in order to make early phase trials more palatable to these stakeholders. This helps avoid issues with patient recruitment, as 80% of clinical trials fail to accrue sufficient patients in their target time.

Third, we perform early economic evaluation of therapies (Dr. Kednapa Thavorn) to estimate the maximum cost at which they can be brought to market and still be considered cost-effective. Economic implications for novel therapies are often overlooked by investigators, and this delays commercialization and reimbursement processes necessary for clinical adoption.

Fourth, we “test” various planned eligibility criteria using available databases (e.g. The Ottawa Hospital Datawarehouse). These retrospective cohort studies ensure that inclusion/exclusion criteria for an early phase trial remain feasible and a sufficient number of eligible patients could be recruited.

Last, we provide consultation for regulatory requirements, GMP, GLP (Dr. Michael Jamieson, The Ottawa Hospital Biotherapeutics Manufacturing Centre), as well as help with developing clinical trial protocols in order to test and validate the studied therapy.

By addressing many of these issues a priori with a set of focused studies, we can help researchers and clinical investigators delivering optimized clinical trial protocols with the best possible chance of success.

Contacts

Projects that benefited from EXCELERATOR program:

Knowledge Synthesis: Systematic Reviews and Meta-Analyses

There are many types of knowledge synthesis methods, but in the context of the BLUEPRINT group, we are primarily focused on systematic reviews with/without meta-analyses.

Systematic Reviews and Meta-Analyses:

We are working towards reporting guidelines for systematic reviews. Members of our group and collaborators contributed to the recent update for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. We are now developing reporting guidelines for systematic reviews of preclinical/basic science studies using in vivo animal models.

Patient Engagement

Simply put, patient engagement in research can be described as “research being carried out ‘with’ or ‘by’ [patients/ caregivers/ the public] rather that ‘to’, ‘about’ or ‘for’ them” (INVOLVE).

The core concept behind patient engagement is that patients and caregivers are the ultimate end-users of the healthcare innovations, thus they should have a voice to help guide research to develop and evaluate these Past/ongoing projects focused on or including patient engagement:

Preclinical/Basic Science Studies

Preclinical/basic science research informs our fundamental understanding of human physiology and pathophysiology.

Preclinical Multicenter Studies

Preclinical multicenter trials can be defined as collaborative research formally conducted at multiple centers using a shared protocol and analysis. The use of the multicenter study design has been advocated as a solution to both the ‘replication’ crisis in preclinical research and the failure to translate innovative findings from laboratories to patients.

Completed and ongoing project working towards Canada’s first preclinical multicenter studies:

Lung Injury and Sepsis

Despite decades of research, supportive therapy remains to be the mainstay treatment as there is currently no effective specific therapy for either condition. Our lab focuses on studying potential new therapies to treat sepsis and ARDS including mesenchymal stem cells and their paracrine factors (e.g. extracellular vesicles). Watch this space for ongoing work as it is published!