Health Canada – Clinical Trials Regulatory Modernisation Initiative

The current clinical trial regulatory framework has served Canada well by upholding high standards and patient safety. A modernised clinical trials regulatory framework is needed in light of:

  • ongoing and accelerated technology advances
  • the development of new types of promising health products
  • the arrival of new clinical trial types and designs
The clinical trials regulatory modernisation initiative

The modernisation of clinical trial regulations is one of the 5 key pillars of the Government of Canada’s Regulatory Innovation Agenda for health products. It is an important goal for the federal government and will benefit people living in Canada. Key aspects of the clinical trial regulatory modernisation initiative include:

  • Agile life cycle: introduces a single authorisation for trials involving multiple product types. It also offers greater agility in the oversight of clinical trials over their life cycle.
  • Risk-based approach: provides proportional oversight of clinical trials based on the known safety information and relative risk of the product(s) involved in a trial.
  • Terms and conditions: give Health Canada the ability to apply (case-by-case) terms and conditions to a clinical trial at any point of the trial to better manage significant risk and uncertainties related to clinical trials.
  • Decentralised trials: provide opportunities for patients and clinicians who are not connected to major health institutions and/or cannot relocate to a clinical site due to disabilities, family, work, social challenges or other factors, to participate in clinical trials.
  • Service provider oversight: gives Health Canada direct authority and oversight over service providers (such as contract research organisations).
  • Transparency: better informs and educates people on clinical trials by providing them with solid and accurate information.

As stated in the Forward Regulatory Plan for 2021-2023, Health Canada is committed to modernising the clinical trials framework with the intention to:

  • introduce a coherent risk-based approach
  • offer greater flexibility in the safe development of innovative therapies
  • authorise clinical trials for non-compliant foods for a special dietary purpose
  • streamline processes to achieve greater efficiency and clarity
  • align with international best practices on matters related to oversight and public access to information

A modernised regulatory framework for clinical trials in Canada should support the adoption of promising novel safe and effective health care therapies. It should also support innovations that can improve people’s health. With this initiative, Health Canada wants to ensure that people have access to the information they need to make informed decisions about their health.

The consultation and webinars

As part of the modernisation initiative, Health Canada consulted stakeholders across Canada in the spring and summer 2021. Stakeholders came from various sectors, including academics and research institutes, industries, patient advocacy groups, health care practitioners and health care organisations. Their feedback is being used to inform the development of the proposed policy and regulatory framework. Eight interactive webinar sessions were held to engage stakeholders on the Clinical Trials Regulatory Modernisation Initiative.

Feedback from stakeholders

Overall, most stakeholders support the modernisation initiative. Approximately 75%* of the respondents said that the modernisation proposals would facilitate and encourage innovative clinical trials in Canada if certain conditions were met. including, for example:

  • regulatory alignment with other major regulators (such as the U.S. and European Union)
  • predictable regulations and application requirements
  • reasonable review timelines to reduce burden for sponsors and attract trials to Canada

A snapshot of the feedback is provided below:

  • The agile life cycle approach – Most respondents favoured a more agile life cycle approach to regulating clinical trials (for example, such an approach would create a more favourable environment for conducting master protocols and adaptive trials).The modernised framework would enable and support novel and innovative types of clinical trials in Canada.
  • Patient safety – Respondents agreed that helping participants to access innovative clinical trials is important while ensuring participant safety. Some emphasized that the innovative nature of the trial should not supersede the safety of the trial.
  • International alignment – Industry respondents said that the proposed changes are aligned better with international clinical study practice requirements. Harmonisation, collaboration and alignment across global regulators are valued, certainly for complex and innovative clinical trials. Biologic and radiopharmaceutical drugs stakeholders suggested that Health Canada accepts or considers foreign clinical trial authorisations to decrease submission burdens.
  • Research ethics boards and Health Canada alignment – Industry respondents also said it’s important to ensure that research ethics boards and Health Canada are better aligned in their processes. Further clarification of their respective roles would also ensure efficiency. Sponsors should be able to submit their trials for review to both a research ethics board and Health Canada at the same time.
  • Other suggestions and concerns to consider included the following:
    • establish an effective and collaborative framework to partner with sponsors to develop innovative trial designs
    • implement a process to seek pre-submission advice from all pertinent review divisions on matters such as study design, statistical methods and novel endpoints
    • introducing a clearly defined mechanism for post-trial access to investigational products.
  • Some industry and patient group respondents were concerned the new regulatory framework may create significant administrative barriers (for example, monitoring safety while the trial is ongoing). They felt these proposed requirements should be further clarified. Others viewed those tools and requirements as beneficial to better ensure the safe conduct of trials in Canada.
  • Single authorisation for multiple products – A modernised regulatory framework would make single authorisation possible for clinical trials involving:
    • combination products (such as a product that combines a drug component and a medical device component) and/or
    • multiple products of different product lines (such as drugs, natural health products and medical devices)
  • Efficiency and reducing burdens – A modernised regulatory framework would significantly increase efficiencies for the application, amendment and authorisation processes for clinical trials involving multiple health products. This would further streamline Health Canada’s interactions with the sponsor throughout the trial.Most respondents said the more streamlined approach would reduce the burden on sponsors for trials that involve multiple products. Currently, these fall under different regulations. The proposed approach would facilitate the conduct of more complex trial types in Canada
  • Good clinical practice – Most respondents indicated that they did not anticipate issues adhering to GCP across product lines. However, some respondents from the medical devices industry suggested lighter regulatory requirements for trials involving in vitro diagnostic devices
  • Risk-based approach – The proposed risk-based approach for clinical trials would stratify different levels of regulatory requirements based on the known safety information and relative risk of the product(s) involved in a trial. Most respondents said this approach would be more efficient without adversely affecting patient safety. It would also facilitate the conduct of clinical trial research in Canada by reducing the administrative burden for lower-risk trials.
  • Clearly defining risk categories and process – Industry respondents asked for more clearly defined, detailed and articulated risk categories (for example, in a guidance document). They requested greater evidence as to why certain trials fall under each risk categorisation. They also asked for examples of the different trial requirements and criteria used to distinguish between risk categories.
  • Predictable and consistent regulatory requirements – Industry respondents also said that efficiencies are best realised when regulatory requirements are predictable and consistent.
  • Well-defined parameters – Most respondents supported this approach and some emphasised the importance of having well-defined parameters for using terms and conditions to ensure they are applied in a predictable manner. 
  • Research ethics boards and Health Canada alignment – Some industry respondents said the responsibilities of Health Canada and research ethics boards should be clarified. Where possible, they should also be harmonised to avoid redundancies and potential contradictions.
  • Decentralised clinical trials
    • Most respondents supported the proposed approach to facilitate the use of decentralised clinical trials (DCTs) in Canada. This is an important initiative, as over 30% of the population lives outside medium-sized and large urban areas.
    • Respondents agreed that DCTs are more equitable. They provide an opportunity for patients and clinicians who are not connected to major health institutions and/or cannot relocate to a clinical site due to disabilities, family, work, social challenges or other factors.
    • Respondents also said that additional details and clarity are needed to better define DCTs in Canada.
    • Industry respondents said that further clarification is needed on the technological requirements for data collection and other types of technologies that may be used to support DCTS (for example, requirements for e-signatures and digital identity). They also said that documented informed consent requires clear interpretation to ensure it incorporates remote and virtual consent formats.
    • Some industry respondents favoured a hybrid approach for decentralised trials (a combination of site and virtual/remote options).
  • Service provider oversight – Proposed amendments to the regulations would give Health Canada direct authority and oversight over service providers (for example, contract research organisations (CROs), site management organisations (SMOs)). This would enable it to address non-compliance or deficiencies in the conduct of clinical trials, which could affect participant safety and data integrity. From the sponsors’ perspective, respondents supported the proposal, stating it would help clarify expectations between sponsors and service providers involved in a clinical trial. It would also increase the quality of outsourced activities since service providers would be accountable for their actions (for instance, improve adherence to regulatory requirements).
  • Transparency – Most respondents saw value in a new transparency policy and/or regulations for registering trials and reporting results. Support was strongest from the academic community (73%) compared with industry (54%).
  • Public disclosure of results – Most respondents from industry and academic research institutes (73%) report their results in international registries. Many commented on the value of results reporting.
  • Challenges with reporting results – Of the 27% of respondents who said they do not report their results in international registries, about half say it’s not their role or responsibility. These were contract research organisations (CROs) working with both industry and academic sponsors. Most said this is the sponsor’s responsibility.
  • Off-label use trials of licensed devices – Health Canada is exploring the possibility of reducing the requirements for clinical trials studying off-label use of medical devices licensed in Canada. Patient safety remains a priority. Most responses supported reduced regulatory requirements for off-label use trials of licensed medical devices, as these products have known safety profiles.
  • Notifications and amendments – As part of the regulatory modernisation initiative, Health Canada is proposing to allow amendments to clinical trial applications to be made without requiring the sponsor to submit a new application. Most respondents supported the 3 pathways proposed for clinical trial amendments (significant changes, notifiable changes and non-significant changes). Industry stakeholders highlighted the importance of a simple and streamlined online system with predictable timelines that’s easy to navigate. They also requested further guidance on the assessment of changes as significant or non-significant.
  • Investigator-initiated trials – The current Medical Devices Regulations permit only manufacturers and importers of medical devices to apply for clinical trial authorisation. The Clinical Trial Modernisation framework would expand who can file an application to include independent investigators in addition to manufacturers and importers. Some stakeholders indicated that these trials may help to generate new clinical data. In all cases, stakeholders emphasized that patient safety and clinical trial integrity should remain priorities.
Next steps

The feedback received during the consultation process will help Health Canada refine the policy and develop regulations to modernise the clinical trials framework. It will continue to engage stakeholders and subject matter experts as this initiative progresses.

Source: Health Canada