Cannabis research licence: Additional information to conduct non-therapeutic research on cannabis

On this page

• Pre-application meetings
• Study personnel
• Additional considerations for Category 1 studies
• Ethical requirements
• Informed consent
• Cannabis research and evidence dossier
• Good Clinical Practice principles
• Notification of study commencement
• Summary report on all adverse reactions
• Actions related to a cannabis-related issue
• Retention of samples
• Potential terms and conditions

Pre-application meetings

You can request a pre-application meeting with Health Canada to discuss non-therapeutic research on cannabis (NTRC) for your proposed study prior to submitting a research licence application. Topics of discussion may include:

• requesting guidance on study risk category as it applies to your proposed NTRC study and the associated application requirements
• requesting guidance on which framework your study could fit (for example, a clinical trial under the Food and Drug Regulations or NTRC under the Cannabis Regulations)
• identifying possible problems or issues before the research licence application for NTRC is submitted
• providing an opportunity for you to discuss details of your research licence application with Health Canada and obtain feedback regarding areas of concern
• increasing the quality of information submitted
• providing the Controlled Substances and Cannabis Branch the opportunity to plan for the submission of the application

Important: Having a pre-application meeting doesn't constitute or guarantee future approval of your research licence application.

Submitting a pre-application meeting request

A pre-application meeting request needs to be made at least 30 calendar days prior to the proposed meeting date. It needs to include the following information:

• The purpose of the meeting
• Information on the proposed study (for example, study objective, design, methods, cannabis, or participants)
• The risk category of the proposed study, if known
• A list of questions you want to ask at the meeting
• A list of attendees and their emails
• Three possible meeting dates, and whether an afternoon or morning meeting is being requested. Meeting durations are typically 30 minutes to 1 hour.
• The projected submission date of the research licence application

A request can be submitted to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca using the subject line "NTRC – Pre-Application Meeting Request".

Health Canada will evaluate your pre-application meeting request and determine whether a meeting is necessary. A meeting may not be granted if your questions can be directly addressed in writing.

Preparing for a pre-application meeting

If Health Canada agrees that a pre-application meeting is necessary to discuss your proposed study, you'll be issued a pre-application meeting number (NTRC-PRE-XXXX). This pre-application meeting number needs to be included in the subject line of all future pre-application meeting correspondences sent to Health Canada and in your Application form to authorize activities in relation to NTRC.

To guide the conversation during the pre-application meeting, Health Canada will ask you to send presentation slides no later than 15 calendar days before the meeting. This presentation should not exceed 10 minutes to ensure the meeting duration doesn't exceed the allocated time.

You should submit your presentation to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca using the subject line "NTRC-PRE-XXXX – Pre-application meeting: Presentation".

After a pre-application meeting

Following your pre-application meeting, you should provide Health Canada with the meeting minutes. They should be provided no later than 15 calendar days after the meeting date.

You should submit your meeting minutes to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca using the subject line "NTRC`-PRE-XXXX – Pre-application meeting: Meeting minutes".

The meeting minutes should also be uploaded in the CTLS with your research licence application for NTRC.

Study personnel

While not necessarily required, having study personnel with specific and suitable qualifications is recommended to properly design and conduct your NTRC study. The study personnel may include a principal investigator (PI), a qualified professional (QP) and/or a health care practitioner (HCP), depending on the procedures and interventions to be performed during your study.

Principal investigator

A PI may oversee the conduct of your NTRC study at the study site(s). The PI may be the same individual as the licence holder or the responsible person.

The PI would be an individual who:

• possesses the appropriate combination of education, training, knowledge, and experience to conduct research with human participants relevant to the study protocol submitted
• is responsible for preparing, designing, conducting, and administering all aspects of the study protocol
• has sufficient knowledge of the provisions of the Cannabis Act and its Regulations that apply to NTRC

Qualified professional

A QP may perform tasks or interventions during your NTRC study that are relevant to their knowledge, experience, and training.

Examples of tasks that may be performed by a QP include:

• collecting biological specimens
• operating medical instruments or imaging (for example, CAT scan, x-rays, MRI scans, ultrasound)

Health care practitioner

An HCP may be required during your NTRC study to perform any interventions and procedures that would normally be performed by an HCP.

An HCP is an individual who meets both following criteria:

• is lawfully entitled under the law of a province or territory to provide health services in the place in which the services are provided by that person, this may include a medical doctor, a nurse practitioner, a nurse, a dentist, and a pharmacist
• possesses sufficient knowledge, experience, and training to properly and safely perform tasks required by that individual as outlined in the study protocol

The HCP would only complete tasks within the scope of their profession, as dictated by their respective College.

Examples of tasks that may be performed by an HCP include:

• screening and monitoring of participants taking health products (including prescribed medications, over-the-counter medications and natural health products) for the treatment or prevention of a pre-exiting medical problem that isn't worsening in extent or severity (such as a stable health problem)
• interpreting medical imaging (for example, CAT scans, x-rays, MRI scans, ultrasound scans)

Additional considerations for Category 1 studies

As described in the Cannabis licensing application: Research licence, Category 1 studies can only evaluate the organoleptic properties (such as taste, sight, smell or touch) of cannabis or the chemesthetic or sensory-emotive responses to cannabis.

To limit the non-organoleptic effects of cannabis in Category 1 studies, Health Canada recommends that licence holders authorized to conduct activities in relation to NTRC under Category 1 limit participants' cannabis consumption by asking them:

• for topical application: to wash off the topical after application
• for inhalation: to not inhale deeply or hold their breath upon inhalation
• for ingestion: to spit out the cannabis and rinse their mouth after taste testing

Ethical requirements

If you're conducting a Category 1 NTRC study, you need to have an ethical framework in place to address any ethical considerations that may pertain to your study. There is an attestation in the Application form relating to the need for an ethical framework for Category 1 studies.

Ethical considerations may include but aren't limited to:

• informed consent
• the use of the research findings
• any possible conflicts of interest
• the safety and welfare of study participants
• the rights, privacy, and confidentiality of study participants

It's recommended to consider the ethical principles and guidelines below in developing your ethical framework.

Ethical principles and guidelines

Studies with human participants must be conducted under the ethical principles and guidelines articulated in the Declaration of Helsinki. In Canada, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS-2) serves as a leading guidance for the ethical conduct of studies with humans. As per Article 1.1 of the TCPS-2, the ethical conduct of studies with humans requires consideration of three core ethical principles:

• justice
• respect for persons
• concern for welfare

The TCPS-2 provides guidance on topics including but not limited to:

• the informed consent process (Chapter 3)
• fairness and equity (Chapter 4)
• privacy and confidentiality (Chapter 5)
• governance of research ethics review (Chapter 6)
• conflicts of interest (Chapter 7)

Consideration for all of these is required to implement and practice the core principles of the TCPS-2. For further information about the TCPS-2, the CORE online training platform offers a 4-hour self-paced tutorial.

The ethical principles and considerations described in the TCPS-2 and the Declaration of Helsinki form the foundation on which researchers develop processes related to:

• the evaluation and continuous monitoring of risk
• the receipt of free, informed and autonomous consent from participants
• the protection and safeguarding of participant data (for example, through study blinding and anonymity in the dissemination of data)

Assessment of ethical considerations

If you're conducting a Category 2 or 3 NTRC study, as a condition of your licence, you may be required to obtain approval from a Research ethics board (REB), Institutional review board (IRB) or Independent ethics committee (IEC) and to submit a letter or certificate of approval to Health Canada prior to starting your study.

REBs, IRBs and IECs are often responsible for assessing ethical considerations related to the conduct of studies with humans. An REB is an independent committee composed of members with medical and non-medical expertise, such as physicians, statisticians, and community advocates. IRBs and IECs may be considered equivalent to REBs.

REBs review information such as:

• the study protocol
• the proposed study period
• the study's sources of funding
• the recruitment and consent process
• the privacy, confidentiality, record keeping, conflict(s) of interest
• the qualifications of the individuals involved in the conduct of a study
• any other aspects that might affect the rights, safety, or well-being of study participants

REBs are also often responsible for monitoring ongoing studies and reviewing any unanticipated adverse reactions that may occur during the conduct of the study. Studies involving humans are also subject to continuing ethics review by the REB throughout the lifecycle of the study.

To maintain valid REB approval, you may be required to:

• submit annual progress reports or end of study reports
• report any unanticipated safety issues including adverse reactions
• seek approval for any amendments to the approved study protocol

Submitting a letter or certificate of REB, IRB or ERC approval

You need to submit your letter or certificate of approval prior to starting your study to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca with the subject line "Proof of REB/IRB/IEC Approval, Licence Holder Name, Research Licence #". The body of the email needs to include the:

• protocol title and protocol number of the study;
• complete REB, IRB or IEC contact information (full name and address, name of the REB, IRB or IEC chair and contact information);
• date of approval; and,
• a statement informing Health Canada if a licence change will be submitted.

Informed consent

International and provincial rules require researchers to obtain informed consent from research participants. You may need, as a condition of a licence, to obtain documented (such as written or electronic) informed consent from participants. Only applicants conducting a Category 3 study are required to submit the Informed consent form (ICF) at the time of application. For more information, consult the Cannabis licensing application: Research licence.

What is informed consent?

Informed consent is a process by which a potential participant voluntarily confirms their willingness to participate in a particular study, after having been informed of all aspects of the study that are relevant to their decision to participate and after having had the opportunity to ask any questions.

Information to share with the potential participants includes:

• the known and potential risks to their health arising from participating in the NTRC study
• all other aspects of the NTRC study that are necessary for the potential participants to make an informed decision to participate in the study

The informed consent process is an ongoing process. If there are any changes during the conduct of the study that may influence the initial consent process, they should be communicated to participants and additional consent should be obtained.

Informed consent is documented by means of a written or electronic signed and dated ICF.

Guidance on informed consent

The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS-2) and the International Council for Harmonisation E6: Guideline for Good Clinical Practice (ICH E6) provide guidance on the informed consent process and contents of the ICF. The ICH E6 is the international standard for studies with human participants, including their:

• design
• conduct
• analysis
• auditing
• reporting
• recording
• monitoring
• performance

Complying with this standard provides public assurance that the rights, safety, and well-being of study participants are protected, and that study data are credible.

Health Canada implemented the ICH E6 guidance in April 2019, endorsing the principles of Good Clinical Practice (GCP) to ensure the protection of human participants and reliability of study results. As such, you should ensure that your ICF includes all applicable information from the sections on informed consent in the ICH E6.

As described in the TCPS-2, you're responsible for ensuring that all applicable legal requirements with respect to consent are met. For example, requiring participant medical records may carry additional obligations for consent.

In preparing, obtaining, and documenting informed consent, you should follow:

• the applicable sections on informed consent described in the ICH E6
• chapter 3 of TCPS-2: The consent process
• any other applicable laws governing informed consent

Developing an informed consent form

When developing your ICF, you can either use an available ICF template or develop your own. Most Canadian academic institutions and research institutes have their own ICF template. Health Canada and the Public Health Agency of Canada also provide an ICF template.

You should be mindful of the following guidelines when developing your ICF:

• The ICF and any additional documents for participants need to be presented on institutional or corporate letterhead
• The level of language used needs to generally correspond to grade 6-8 reading levels
• The informed consent form needs to be provided in a language that the participant is comfortable with and can read and understand
• The language used in the ICF and associated forms cannot be coercive, needs to be written in plain language, and be as non-technical, practical and understandable to the participants as possible

An ICF must include information on:

• the purpose and objective(s) of the study, the study design, and procedures
• all risks that may occur as a result of participating in the study, even if minimal or remote. A statement should be included if there may be unforeseeable or unknown risks, such as uncertainties due to gaps in safety or toxicological data for certain substances.
• benefits
  • it should be mentioned in this section that participation in an NTRC study doesn't provide any individual-level benefit to the participants as these studies aren't meant to study any therapeutic effects.
  • benefits may include those directed to society at large, such as increasing knowledge on cannabis and its effects, informing public health, safety, education, and policy, or furthering research and development of cannabis products
• cost and compensation for participating, and compensation or treatment in the event of injury
• how privacy and confidentiality will be maintained
• how and for how long the data or samples will be retained and any potential future uses of that data or samples, if applicable
• how results will be reported
• contacts available to participants for any questions they may have related to the research study, their rights and what to do in case of an adverse event or if they have any complaints
• withdrawing from the study

The signature page must include statements that:

• providing consent isn't a waiver of the participant's legal rights
• researchers or licence holders cannot be released from liability for negligence or other fault(s)

However, the signature page must not include:

• a statement that an REB has approved the study, since this may appear to offer a guarantee of safety
• a refusal signature line as it's considered coercive and inappropriate; if a potential participant chooses not to participate, they will simply not sign

Documentation provided to participants

Upon providing consent and throughout the conduct of the study, participants should receive a copy of:

• the completed and signed ICF
• any other informational documents provided to them
• if any changes occur during a participant's participation in the study, or any additional information becomes available that may impact the ICF, a copy of the amended documents and newly signed ICF

If e-consent is used as part of the informed consent process, participants should receive an electronic copy of the ICF.

Cannabis research and evidence dossier

As described in the Cannabis licensing application: Research licence, if you're applying for a research licence to conduct NTRC and your proposed study falls under Category 2 or 3, you need to provide Health Canada with additional information and evidence supporting the safety of the cannabis you wish to include in your study. This information is provided through the Cannabis research and evidence dossier (CRED).

The CRED:

• outlines the safety profile of the cannabis to be used in an NTRC study
• provides research personnel involved in the conduct of your study with the necessary information to assist their understanding of key features of the study protocol, including:
  • safety monitoring procedures
  • the duration and mode(s) of consumption
  • the amount(s) of cannabis to be administered and at what frequency

You should present the CRED in a concise, simple, objective, balanced and non-promotional manner. This enables the personnel involved to make their own unbiased assessment of the risks and considerations of the study.

Evidence requirements for the Cannabis research evidence dossier

The primary source of evidence for the CRED is Health Canada's Information for Health Care Professionals: Cannabis and the cannabinoids (IHCP), a peer-reviewed publication with information on cannabis and cannabinoids, such as:

• dosage
• warnings
• chemistry
• toxicology
• precautions
• pharmacology
• adverse effects

As the IHCP isn't updated at the same pace as the rapidly evolving evidence for cannabis, it's your responsibility to provide additional relevant and more recent evidence to supplement or complement the information provided in the IHCP.

From highest to lowest weight of evidence, the types of supporting evidence you may want to include are:

1. Systematic reviews and meta-analyses of clinical trials
2. Clinical trials
3. Unpublished proprietary safety studies in humans
4. Evidence of a positive decision from another jurisdiction with similar regulatory requirements
5. Other peer-reviewed or unpublished evidence in humans, such as:
   • Detailed narrative reviews which cite detailed primary evidence
   • Observational and real-world evidence studies containing safety data
   • Unpublished summary studies with detailed primary evidence focusing on safety assessment
   • Surveys on cannabis similar or identical to the cannabis to be used
   • Published case reports and case series of adverse reactions with cannabis
6. Pre-clinical animal studies
7. Relevant adverse reaction data from sources such as the licence holder's adverse reaction data or complaints from the Canada vigilance adverse reaction online database
8. Other relevant data (such as volume of sales) for legally available cannabis products

Good Clinical Practice principles

Depending on the risk category of your study, you may need, as a condition of your licence, to follow certain principles for Good Clinical Practice (GCP) listed in listed in the ICH E6 guidance.

The following GCP principles may apply to your NTRC study:

1. Research with humans should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki
2. Research with humans should be designed and conducted in ways that ensure the rights, safety, and well-being of participants
3. Informed consent is a requirement for the ethical conduct of research with humans. Participation should be voluntary and based on a consent process that ensures participants are well-informed
4. Research with humans should be scientifically sound for its intended purpose and based on robust and current scientific knowledge and approaches
5. Research with humans should be designed and conducted by qualified individuals.
6. Systems with procedures that assure the quality of every aspect of the study should be implemented
7. Study processes, measures and approaches should be proportionate to the risks to participants and to the reliability of study results
8. Research studies should be described in a clear, concise, and operationally feasible protocol
9. Research studies should generate reliable results, and all study information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification
10. Roles, tasks, and responsibilities in research studies should be clear and documented appropriately

Notification of study commencement

You need to notify Health Canada of your NTRC study commencement date within 30 calendar days from when your study begins. The commencement date is defined as the date on which your study is ready to enroll participants. If there are multiple sites, the commencement date should be specified for each site.

You need to submit your notification to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca with the subject line "Notification of study commencement, Licence Holder Name, Research Licence #". The body of the email needs to include the:

• protocol title
• risk category
• site address(es)
• date(s) of study commencement for each site (YYYY-MM-DD)
• licence change request (CHG #) associated with the initial NTRC research application (for institution-wide research licence holders only).

Summary report of all adverse reactions

If your Category 3 study is considered to have higher risks than other Category 3 studies, you may need, as a condition of your licence, to submit to Health Canada a summary report of all recorded adverse reactions (AR), both serious and non-serious ARs, that occurred during the conduct of your NTRC study. An example of a higher-risk Category 3 study would be a study using vape cartridges that contain a substance where injury could occur based on a risk assessment or information from other jurisdictions.

This summary report needs to be submitted within 70 business days of study completion (such as when the last participant completes the "end of study" visit as defined in the protocol). For multi-year studies, you may be asked to submit to Health Canada, within 70 business days of each yearly anniversary following study initiation, an interim summary report of all recorded ARs that would include all serious and non-serious ARs that occurred during the preceding 12 months.

Health Canada is currently developing detailed guidance to assist research licence holders authorized to conduct NTRC studies in meeting their adverse reaction reporting requirements under section 248.2 of the Cannabis Regulations. Any questions about reporting of adverse reactions to cannabis that occur during an NTRC study can be directed to the Office of Cannabis Science and Surveillance at cannabis_oss-cannabis_bss@hc-sc.gc.ca.

Submitting a summary report

You need to submit your summary report and interim summary report, if applicable, of all adverse reactions to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca. The subject line should be either:

• For the summary report: "NTRC Summary report of adverse reactions for Licence Holder Name, Research Licence #"
• For the interim summary report, if applicable: "NTRC Interim summary report Licence Holder Name, Research Licence #"

For institution-wide research licence holders, the body of the email should include the licence change request (CHG #) associated with the initial NTRC research application.

Actions related to a cannabis-related issue

If you're conducting a Category 2 or 3 study, you need to notify Health Canada within three business days of becoming aware of a cannabis-related issue that may expose or have exposed participants who have been or will be administered the cannabis to a serious or temporary adverse health consequence.

Submitting a cannabis-related issue

You need to submit cannabis-related issue notifications to sp-licensing-cannabis-licences-sp@hc-sc.gc.ca with the subject line "NTRC Cannabis-related issue, Licence Holder Name., Research LIC #". The body of the email needs to include:

• the protocol title
• the affected lot(s) or batch(es) of cannabis (if applicable)
• if the cannabis has been administered to participants, the number of unit(s) or amount of each lot or batch that was administered, and the number of units or amount of each lot or batch that was consumed by each participant
• the date of the recall, if applicable
• the date they became aware of the cannabis-related issue
• a description of the cannabis-related issue
• the actions they have taken or plant to take in response to the issue.

Retention of samples

If you're conducting a Category 2 or 3 study, you may need, as a condition of your licence, to retain a sample of each lot or batch of cannabis distributed to participants for at least six months after the last administration of that lot or batch of cannabis to participants. The samples retained would have to be stored under conditions that maintain their quality and be of sufficient quantity for applicable testing as specified in Parts 5 and 6 of the Cannabis Regulations.

Potential terms and conditions

Under certain circumstances, research licences to conduct activities related to NTRC may be subject to terms and conditions. Potential terms and conditions that licence holders may see upon issuance of their research licence may be related to:

• retaining samples
• obtaining informed consent
• following certain principles of GCP
• submitting a summary report of all adverse reactions
• taking actions related to an issue related to cannabis used in the NTRC study
• obtaining approval from an REB, IRB or IEC and submitting a letter or certificate of approval to Health Canada prior to starting the NTRC study

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