Applying CIHR's Research Excellence Framework – Best Practices for Clinical Trials

As Canada's national funder of health research, CIHR intends that publicly funded clinical trials must meet the highest standards of both scientific excellence and impactful research excellence – standards that prioritize inclusive, transparent, and collaborative science at all stages of discovery and mobilization.

This document is being published as a companion piece to CIHR's broader Research Excellence Framework, and reflects comments received through an online consultation, ongoing partner and stakeholder engagement, and international best practices, including draft guidance from the World Health Organization, concepts articulated by the Good Clinical Trials Collaborative, and relevant ICH guidances.

As CIHR's approach to research excellence may evolve as part of ongoing dialogue with national and international partners as well as the Canadian health research community, the application of this framework to CIHR-funded clinical trials will also continue to evolve.

It should be noted that the best practices recommendations in this document remain voluntary at this time. However, it is CIHR's intention that some or all of these elements will become requirements in future clinical trials funding opportunities.

We welcome your feedback. Comments should be provided to clinicaltrials-essaiscliniques@cihr-irsc.gc.ca  

We thank all those involved in the clinical trials ecosystem for their continued support for excellent clinical trials.

Existing Mandatory Requirements for Clinical Trials

CIHR and tri-agency policies that apply to clinical trials are listed on the CIHR Funding policies web page. Notably, compliance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS2) 2022 is a requirement of funding, and all clinical trials funded by CIHR must be registered and results disclosed. See the policy guide for full requirements.

Existing requirements for applications containing randomized controlled trials will continue to be applied, as relevant.

Research Excellence Components and Clinical Trials Recommendations

In alignment with the key components of CIHR's Research Excellence Framework, we recommend the following best practices for clinical trials.

Ethics: Excellent research must meet international standards of ethics.

As indicated above, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS2) 2022 is a key guidance for ethical conduct of clinical trials.

Equity, Diversity, and Inclusion (EDI): Research is excellent when it is inclusive, equitable, diverse, anti-racist, anti-ableist, and anti-colonial in approach and impact. Excellent research reflects the diversity of scientific talent in Canada, empowers participation of communities historically marginalized and disadvantaged in health research (including but not limited to women, Francophone researchers, Indigenous Peoples and organizations, persons with disabilities, and Black and other communities marginalized by race), and supports inclusion across the lifespan for research involving humans. Within this component, it should be especially noted that the right to conduct research in the official language of one's choice, which is protected through the Official Languages Act, is a key pillar of inclusion.

Recommendations

Guided by TCPS2, Chapter 4: Fairness and equity in research participation, the following should be addressed in trial planning:

Inclusion of populations: Clinical trial plans should include a clear and well-documented rationale for the exclusion of any participant populations, including pregnant people, infants and children, and older adults. Such an approach would support broad inclusion of clinical trial participants and ensure that research results are applicable to trial participants and relevant populations.

Equity, diversity, inclusion and accessibility: Clinical trial plans should address how diverse populations will inform, develop, implement, and participate in the study, and how results will be analyzed, interpreted, and communicated in ways that are equitable, accessible, relevant, and useful to a diversity of populations.

Diversity in data: Published results from CIHR-funded clinical trials should describe the participant populations (e.g., by sex, race/ethnicity, or other relevant characteristics), and where statistically valid, should report results disaggregated by subgroups.

Indigenous Knowledge: Guided by a spirit of reconciliation and co-existence, research must prioritize requirements of First Nations, Inuit and Métis communities and must respect the self-determination of Indigenous Peoples. This involves building trust, respect, and relationships with communities; recognizing Indigenous knowledge systems; learning and understanding culture; co-producing research to ensure research questions and approaches are shaped by community priorities and remain in the community; presenting findings using accessible and community-centric approaches; and respecting Indigenous data sovereignty.

Recommendations

TCPS2 (2022) Chapter 9 provides guidance on ethical conduct of research involving First Nations, Inuit, and Métis people in Canada.

For all research by and with First Nations, Inuit, and Métis communities, applications must respect and integrate meaningful and culturally safe practices, plans and activities, as well as Indigenous rights, self-determination and governance, relevant Indigenous community policies on research data management such as the First Nations Principles of OCAP®1 (Ownership, Control, Access and Possession) and the CARE Principles for Indigenous Data Governance.

Patient-Oriented Research: Excellent research includes meaningful engagement of patients, people with lived and living experience, and other knowledge users as partners throughout the entire research process. This approach helps to ensure questions and results are relevant and enhance the integration of findings into the health care system and clinical practice, with the goal of improving patient experiences and outcomes.

Recommendations

Patients and knowledge users should be involved and engaged throughout all stages of clinical trial development and implementation, including in the identification of research questions, research processes, proposed interventions/treatment, and outcome measures.

Clinical trial processes should be designed with the research participant involved and in mind, for example, through

Knowledge Mobilization: Excellent research employs tailored approaches for optimizing the impact of agency-funded research. Excellent research involves co-designing research priorities and questions with knowledge users, and/or mobilizing findings via a broad range of accessible and equitable formats to inform health-related decisions by policy makers, practitioners, patients, and communities.

Recommendations

Consistent with CIHR's approaches to knowledge mobilization and the concept of learning health systems, the intent of knowledge mobilization is to accelerate the availability of high-quality evidence and research data for translation into policy, practice and/or clinical guidelines, where appropriate for the phase and intent of the clinical trial. Knowledge mobilization strategies should be developed in the context of patients (or people with lived experience) and knowledge user engagement and should take into consideration the need for evidence and research data inclusive of specific underserved populations.

Open Science: Excellent research incorporates open science practices that enable timely access and sharing of research findings, data, and other outputs, in order to maximize the use and impact of agency-funded research.

Recommendations

FAIR principles: As described in the Tri-Agency Research Data Management Policy, research data management is a necessary part of research excellence. CIHR supports the FAIR (Findable, Accessible, Interoperable, and Reusable) guiding principles for research data management and stewardship.

Secondary use of data: Publicly funded research should support the greatest public good through the effective use of data, increased efficiency and the reduction of research waste. CIHR encourages researchers to consider other potential uses of data collected during clinical trials, to seek ethics advice on best practices and where possible, to plan for rigorous secondary use of data in their informed consent and data management processes. [see article 3.13 of the TCPS2 (2022) regarding broad consent that applies to all research, including clinical trials].

Protocol transparency: In addition to CIHR's existing policy on clinical trial registration and disclosure, early disclosure of clinical trial protocols in open access registries is also encouraged.

Scientific Rigour: Excellent research must use robust research designs that minimize bias across methodologies, analysis, interpretation, and transparent reporting of results.

Recommendations

Need for the clinical trial and anticipated impact: In addition to existing application requirements for rigorous and intersectional clinical trial design and appropriate and valid methods of determining statistical power, plans for trials should be supported both by a literature review that demonstrates the need for the trial, as well as a search of clinical trial databases to ensure that the proposed trial expands, complements or adds to ongoing research efforts, where applicable, and that it only reproduces existing work when that is the intended research aim. Applications should provide documentation of prioritization of the research question and clearly describe the anticipated impact of the trial on informing healthcare decisions at the individual, population, practice, or policy level.

Standardized approaches to improve comparability: Standardized outcomes to be measured and reported for clinical trials which involve patients (or people with lived experience of the condition of interest) in their development (for examples, visit COMET Initiative), can improve the comparability of trials and their results, and should be used when they exist for the condition being studied. Additionally, templated, or standardized protocols or checklists for clinical trial protocols (such as SPIRIT) should be used to support the development of comprehensive trial protocols.

Training, Mentorship and Sponsorship: CIHR recognizes the importance of training, mentorship, and sponsorship in creating and supporting the diversity of talent needed to conduct excellent research. This includes valuing efforts to address gaps in training and support across all career stages, transitions, and paths, and to build capacity amongst groups currently underrepresented in the health research ecosystem.

Recommendations

CIHR encourages each research team to include early career researchers as meaningful contributors to the clinical trial leadership, and to provide opportunities for trainees to be involved in clinical trial development and implementation. Diverse research teams and equitable, accessible, and inclusive workplaces that support integrated learning and development will support the overall clinical research ecosystem.

Efficient Clinical Trials

While the CIHR Research Excellence Framework does not directly address research process efficiencies, inefficient processes which delay the initiation of clinical trials have been repeatedly raised as issues of concern.

Recommendations

Research ethics review processes: Duplicative research ethics board (REB) reviews have been identified as a significant barrier to the efficient launch of multi-site clinical trials. For multi-site clinical trials, using a board of record or streamlined research ethics board process where available in the jurisdictions in which the trial will be performed is strongly recommended [noting Indigenous-specific ethics considerations as described in Article 9.9 of the TCPS2 (2022), as well as Chapter 8, which allows and strongly encourages harmonization and streamlining the ethics review processes and offers examples of alternative REB review models].

Contracting processes: Lengthy contracting processes, both between institutions and between institutions and suppliers have also been identified as a significant cause of clinical trial delays. Adopting streamlined institutional contracting processes, such as master clinical trial agreement templates, and continuous improvement in administrative practices, is strongly recommended.

CIHR will explore the possibility of mandating streamlined administrative processes and/or meeting defined timelines in order to be eligible for CIHR clinical trials funding in the future.

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