Language selection

Government of Canada / Gouvernement du Canada

Search

Draft guidance on decentralized clinical trials

On this page

Purpose

This guidance outlines regulatory considerations for conducting decentralized clinical trials in Canada. These considerations are supported by Part C, Division 5 of the Food and Drug Regulations (regulations) and the International Council for Harmonization Guideline for Good Clinical Practice (ICH E6).

In decentralized clinical trials, some or all trial-related activities are conducted at locations other than traditional trial centres with the help of digital health technologies and virtual methods. Decentralized elements can help reduce the travel burden for participants and also make clinical trials more accessible and diverse.

Health Canada is currently modernizing how clinical trials are regulated. This modernization initiative is intended to better accommodate new trial types and designs.

Learn more about the clinical trials modernization initiative.

This guidance is an interim measure to support decentralized clinical trials under Part C, Division 5 of the regulations. Once the modernized regulatory framework is in force, we will update this guidance to reflect the new regulations.

Scope and application

This guidance applies to any party involved in conducting clinical trials in humans in Canada. This includes:

This guidance concerns the following clinical trials involving drugs that are conducted in humans in Canada:

This guidance does not apply to:

The considerations listed in this guidance apply specifically to decentralized clinical trial activities. For a complete understanding of regulatory requirements for clinical trials, consult:

Policy statements

Decentralized clinical trials consist of visits and activities that are conducted outside of traditional clinical trial centres, bringing research closer to participants. They can:

They also allow researchers and other health care providers in remote areas to better connect to and participate in pan-Canadian research efforts, without requiring them to be co-located geographically.

Planning and conducting a decentralized clinical trial may involve other considerations, but the regulatory requirements are the same as any other clinical trial.

As part of their clinical trial applications (CTA), sponsors must demonstrate in documentation that the inclusion of decentralized elements or activities are not against the best interest of participants.

Sponsors must also demonstrate that:

Sponsors must identify the decentralization-related risks and manage those risks according to the regulations and ICH E6 guidelines. Managing the risks requires well-coordinated trial monitoring and oversight by all parties involved in conducting the clinical trial. Risk mitigation strategies can be built into various aspects of the trial, such as protocol design, contractual agreements and the informed consent process. They can also be outlined in other trial-related documentation that defines and records the roles and responsibilities of everyone involved in the trial.

Decentralized clinical trials should:

Decentralization can involve a qualified investigator (QI) at a main location of a clinical trial site, who delegates trial-related activities to personnel or third parties in other physical locations. Regardless of geography, all locations where trial-related activities occur under the supervision of a QI are considered part of a single clinical trial site. A “clinical trial site” refers collectively to the main location and other locations.

Background

Decentralized elements may involve using validated digital health technologies and community-based health care resources, such as:

Decentralized clinical trials also make it possible for community-based health care professionals to participate in research activities. Partnering with a traditional clinical trial site could also help them gain access to more clinical trials and potentially beneficial novel treatments.

Decentralization is very important for clinical trials that face challenges with recruiting sufficiently large, geographically and culturally diverse participant group, such as rare disease trials. It can also improve the ability to recruit and retain a more representative participant group, which can lead to stronger and more general evidence or results.

Conducting geographically dispersed trial activities under a single clinical trial site can also reduce logistical or administrative burdens associated with operating multiple sites or coordinating participant visits across several locations.

Decentralized clinical trials can reduce the need for participants to travel to a traditional clinical trial site, allowing for more efficient participation. And for those who cannot travel due to family, work, geography or circumstance, a decentralized option means they can connect to research efforts and have access to novel treatments.

Design considerations for decentralized clinical trials

Sponsors may use several strategies to:

For example, in a large cohort or a national trial, sponsors could establish multiple clinical trial sites under a single clinical trial application (a multi-site trial). Each clinical trial site would require its own CTSI form. Table 1 lists things to consider when designing a decentralized clinical trial.

Table 1: Design items to consider for decentralized clinical trials
Consideration Single-site with decentralized elements Multi-site
Trial suitability Suited for investigational products with an established safety profile or where complex initial assessments can be done centrally with follow-ups at home Suited for complex trials, those needing large cohorts or where in-person site-specific interactions are required
QI oversight Single QI is responsible for overseeing and monitoring trial activities at all locations A separate QI is responsible for each of the clinical trial sites, including any decentralized elements associated with that site
Operational model Main location, with remote activities at other locations to facilitate trial activities Distributed operations across multiple independent sites, under a single study protocol
Administrative burden related to REBs Approval only needed from the REB related to the main location REB approval is required for each of the clinical trial sites

Interprovincial considerations

Decentralized elements that cross provincial jurisdictions may introduce additional considerations related to applicable provincial regulations

May allow individual sites to adapt to:

  • local applicable provincial laws and regulations
  • institutional capacity and requirements

May add complexity to the coordination of a single study protocol

Patient reach

Broad geographic reach, up to a point

Participant-centric by reducing travel burden

Broad geographic reach due to having sites in different areas

Multi-site trials

For multi-site trials, there must be a QI for each clinical trial site. The QI must maintain their own delegation log and documentation to demonstrate compliance with Division 5 of the regulations and the applicable GCP requirements. For a large sample size or pan-Canadian clinical trial, a multi-site design may help overcome provincial or territorial legislative requirements for sharing participant data or around institutional REB approvals.

QIs and sponsors may also use decentralized elements in multi-site trials to reduce participant burden and involve local health care networks (taking into account their capacity to participate). When decentralizing activities in a multi-site trial, sponsors should ensure that trial-related activities delegated from each QI’s main location are within the scope of that site’s REB approval and supervized by the site-specific QI.

Research ethics boards

As per the regulations, each clinical trial site must receive REB approval before a trial can begin at that site.

By decentralizing trial-related activities to trial-related personnel or other third parties in other locations, sponsors and QIs can conduct REB-approved trial activities across a wider geographic area. While Health Canada doesn’t require additional REB approvals, sponsors may need to obtain additional approvals, permissions or meet community-specific requirements to gain access to specific locations or populations.

For multi-site trials where Health Canada requires each clinical trial site to obtain a REB approval, sponsors should consider using streamlined REB review systems.

Find information on multi-jurisdictional research under the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans.

In some cases, an institution may allow its REB to rely on an external REB’s review to decide if a study is ethically acceptable. This may be especially true if the REBs are recognized members of a streamlined ethics review network or have formalized cross-institutional agreements.

Several initiatives and organizations have facilitated more streamlined ethics review systems in Canada:

Considerations for coordinating decentralized clinical trials

When decentralizing activities from the QI’s main location to other locations, sponsors should minimize the risk to participants and safeguard the integrity and security of trial data.

QIs may delegate trial activities to individuals or organizations located outside their main location. These delegated activities can range from highly specialized trial-related procedures requiring specific equipment or assessments to non-trial-specific activities such as routine blood work or imaging.

When deciding to decentralize trial activities, QIs and sponsors should consider:

Digital health technologies should be validated for their intended use and demonstrate compliance with ICH E6, for example, by:

Agreements (or contracts) can help all parties who conduct trial activities know their roles, responsibilities and liabilities. They can also help protect the safety of trial participants.

Written agreements should clearly set out:

Agreements that are clearly written and set out the division of responsibilities can help trial personnel, service providers and local health care providers comply with applicable laws, regulations and professional standards.

Records of agreements (paper or electronic) must be available or accessible from the main location (associated with the QI) of the clinical trial site. They may be reviewed during an inspection to ensure that all:

As per subsection C.05.012(4) of the regulations, records of contractual agreements must be maintained for 15 years.

Submitting a clinical trial application

A CTA is not required for clinical trials involving marketed drugs where the investigation is to be conducted within the parameters of the notice of compliance (NOC) or drug information number (DIN) (phase IV trials).

As part of their CTA, sponsors must provide information to show that the:

Sponsors must also attest that the trial will be conducted according to good clinical practices (GCP).

Depending on the decentralized activities within the proposed trial, sponsors should describe in their CTA:

Conducting a clinical trial with decentralized elements

As per Division 5 of the regulations, including sections C.05.010 to C.05.015, sponsors and investigators must adhere to GCP to ensure that investigational drugs are used properly in a clinical trial. This includes meeting requirements on:

Sections C.05.010 to C.05.015

Health Canada inspects clinical trials to assess adherence to GCP, according to the following guidance:

Find more information in the section on inspections.

Sponsor’s obligations

Sponsors should consult other relevant policy and guidance documents, such as:

In general, sponsors are responsible for coordination, logistics, maintaining records of personnel and activities, and reporting SUSARs, among other activities. Sponsors must also ensure that the clinical trial and the drug comply with the approved protocol and applicable laws and regulatory requirements. This includes provincial or territorial statutes on informed consent, privacy and health records management.

Sponsors must implement a quality system consisting of documented procedures (for example, standard operating procedures or SOPs, protocol procedures) to ensure quality of every stage of the trial process and at all sites. Such a system should comply with the regulations and ICH E6.

Decentralization of clinical trial activities across third parties and locations could complicate oversight and monitoring of trial activities. Sponsors should develop and implement robust, comprehensive plans (or written procedures) for the decentralized elements to help them:

Where a trial involves several physical locations, sponsors should ensure the informed consent process is carried out in a way that mitigates risks to participants and maintains appropriate records of participant consent.

When identifying trial-related personnel or other third parties involved in trial activities, sponsors should take appropriate measures to ensure that:

Investigator responsibilities

QIs may delegate specific trial-related activities to qualified trial personnel or other third parties, including local health care providers and contracted service providers. QIs are responsible for:

When delegating trial-related activities to trial personnel or other third parties, QIs must ensure that:

Training and qualification

A range of trial-related activities may be delegated, and could include:

Sponsors and QIs should document the specific training required for the activity to be conducted by delegated personnel. Training requirements should be flexible to minimize unnecessary burden for participating health care providers while ensuring that delegated activities are conducted safely and according to the protocol.

In general, training should be relevant to the study-related duties and include the relevant sections of trial protocol for which the person is responsible to carry out. If applicable, training should also be provided on relevant supporting guidance, including, for example, ICH E6.

For example:

Oversight and delegation log

QIs must oversee delegated activities throughout the trial. Accordingly, they should implement procedures to:

QIs must maintain a delegation log, available at the main location of the clinical trial site (associated with the QI). The delegation log must clearly identify all persons to whom study-specific responsibilities have been delegated.

The delegation log should also:

Trial-related documentation (for example, supervision plans) should distinguish between activities requiring delegation and training, and those that fall within routine clinical practice.

QIs do not need to include the following procedures in the delegation log. However, they should take appropriate measures to ensure that the individuals involved are qualified and that their planned involvement is clearly outlined in trial-related documentation:

For these types of procedures, Health Canada recognizes that, within reason, documentation on the qualifications of all third-parties may not be readily available to the QI.

For more information on delegation logs and training for clinical research, consult:

The delegation log and other relevant documentation to manage delegated activities must be available at the main location of a clinical trial site and may be requested by Health Canada during an inspection. Note that this documentation includes any established contracts or agreements between the sponsor and other third parties, institutions or locations outlining specific roles, responsibilities, liabilities and indemnities.

Informed consent process

Sponsors must inform participants of the risks and anticipated benefits of participating in the trial. Informed consent must comply with the applicable laws and regulations governing consent:

For decentralized clinical trials, the informed consent process may involve the QI (or delegated persons) at a main location and participants at other physical locations.

If applicable, trial-related documentation should support:

Sponsors and QIs should establish a process for how informed consent will be obtained according to ICH E6 requirements. The process should give potential participants information on the following:

Virtual meeting platforms and electronic signatures may make the informed consent process more efficient for those who live in remote areas. However, sponsors should be careful not to create a disadvantage for those who do not have access to or prefer not to use virtual platforms. Doing so may introduce ethical considerations related to fairness and equity.

Consider:

Virtual platforms and digital technologies bring concerns about privacy, confidentiality and trust, as well as the need to verify the accuracy of information provided by generative models (artificial intelligence). Such technologies must be validated for their intended use and could require additional security measures to protect participants’ personal information and safety.

During an inspection, Health Canada will verify that:

Clinical trial inspections

Health Canada monitors clinical trials through inspections to ensure that clinical trials are being conducted according to legal and regulatory requirements. During an inspection, inspectors assess that clinical trial activities comply with regulatory requirements, applicable standards and the approved protocol.

In decentralized clinical trials, the main location of the clinical trial site (associated with the QI) is the main point of contact for an inspection. Health Canada inspectors may ask sponsors and QIs to provide documents demonstrating adequate coordination, oversight and monitoring of delegated parties and the protection of participant safety.

Health Canada may inspect other physical locations where study-specific activities take place. We identify these locations based on the risk associated with the types of delegated activities being conducted there. Proper documentation at the main location can help inform whether there is a need to inspect any other decentralized location associated with that site.

In general, routine or ad hoc procedures that don’t involve protocol-specific elements and are performed in settings such as a medical imaging clinic or hospital emergency department are not subject to inspection.

Sponsors should consider the inspection process from the outset when designing a decentralized clinical trial, especially around planning trial activities in participants’ homes. For example, Health Canada may need to enter a home if the clinical trial activity occurring there poses a hazard to a participant. Recognizing that an inspection in a home may invade a participant’s privacy, sponsors should ensure that trial-specific procedures are conducted in appropriate settings according to the risk or hazard posed to participants. If it’s expected that study-related procedures will take place in a participant’s home, the participant must be told that an inspection may take place as part of the informed consent process.

For virtually conducted activities involving other locations, all related information and records must be accessible for inspection from the main trial location.

For an investigational drug that requires specific storage conditions, Health Canada inspectors may request documentation so they can assess if the drug was stored appropriately when being transported to remote locations. This may mean ensuring that shipping containers and configurations offer the required conditions (for example, 2°C to 8°C, keep frozen, prevent from freezing) for the maximum expected transport time.

Page details

2025-12-23