Requests for Proposals and Opportunity Highlights

Note: The request for application process has been suspended until further notice.

Background

As part of Health Canada's strategy to address the issue of medical marijuana, in 1999, the Department (Health Canada) created the Medical Marijuana Research Program (MMRP). The establishment of the Program recognized the need for research into marijuana and associated cannabinoids to determine the safety and efficacy of these compounds in the management of symptoms in patients unresponsive to usual treatment modalities. The Program was originally anticipated to contribute $7.5 M to research over five years.

Marijuana is not approved as a therapeutic product in any country and there have been few clinical trials on the use of marijuana for medical purposes. The existing knowledge with respect to the use of marijuana for medical purposes has been assessed by several health and governmental organizations in various countries as well as by the World Health Organization (WHO). According to reports from these organizations, evidence of the potential therapeutic efficacy of smoked marijuana is heavily anecdotal and while there are reports of the therapeutic value of smoked marijuana, scientific studies supporting the safety and efficacy of marijuana for therapeutic claims are inconclusive. The general consensus of international reports is that additional research is needed.

Marijuana has been claimed to relieve symptoms associated with the followingmedical conditions:

1. Nausea and vomiting: For the relief of nausea and vomiting associated with cancer and AIDS therapies
2. Wasting syndrome: To stimulate appetite and produce weight gain in AIDS and cancer patients
3. Multiple sclerosis, spinal cord injury or disease: For the relief of muscle pain and spasms
4. Epilepsy: To help reduce the frequency of epileptic seizures
5. Glaucoma: To lower intra ocular pressure
6. Chronic and severe pain due to several medical conditions

Program Strategy

The ultimate objective of this Program is to investigate clinical treatment of patients unresponsive to usual treatment modalities with smoked and non-smoked marijuana and cannabinoids. It is envisioned that through this Program a better understanding of the safety and efficacy of using marijuana to control these symptoms will be forthcoming.

During the first two years of the Program, 1999-2001, research focussing on the use of smoked marijuana was solicited. Marijuana's potential as a medicine is undermined if patients must inhale harmful smoke (Institute of Medicine report,1999) [see end of this document for reference to this report and to some other background material]. Nevertheless, the investigation of the safety and efficacy of smoked marijuana continues to be a focus of this Program. The reasons for this are that there presently is a perception that smoked herbal marijuana is effective for the treatment of some disease symptoms and smoked marijuana is currently used by patients in Canada for symptomatic relief under special conditions. Health Canada is interested in the evaluation of this use.

Research involving a much broader scope of investigations will now be considered under the program. Projects involving non-smoked marijuana and cannabinoids will now also be considered. In order to foster the development of routes of administration as alternatives to smoking, research projects investigating dosage forms that eliminate the inhalation of harmful smoke will now be considered eligible for funding. The need for research on the development of alternative delivery systems will be balanced by the Program's need for practical solutions to delivery issues within a short time frame. Only projects that will involve the administration of a drug to humans in a dosage form will be eligible. The Program will not fund projects involving toxicological or other studies required for approval of clinical studies using these products. For projects investigating new dosage forms, those involving clinical safety and efficacy will be given priority. However, projects investigating only the pharmacokinetics of new dosage forms will also be considered.

Health Canada is also developing a new initiative with CIHR that will focus on the conduct of open label clinical trials with marijuana. Further details regarding this initiative will be posted on the CIHR website as soon as they are available.

The expansion of the scope of Health Canada's research program with marijuana is expected to generate interest from a wider segment of Canada's research community. Funding priority will continue to be accorded clinical trials investigating the efficacy of marijuana and cannabinoids. Open label clinical trials will be the next priority followed by all other clinical trials consistent with this Program strategy.

Governance

Health Canada and CIHR are pleased to combine some of their expertise in a partnership to facilitate this research. This will ensure that the research conducted supports the development of health policy to address the medical use of marijuana and cannabinoids and that the research is scientifically sound. More detailed information on the roles and responsibilities of Health Canada and CIHR and Program processes is given below under Program Delivery.

Program Delivery

The Program will be delivered through activities conducted by both Health Canada and CIHR according to a partnership which will combine the expertise and resources of both organizations. Health Canada will contribute the funds, define policy needs and ensure that the research conducted supports the development of health policy to address the medical use of marijuana and cannabinoids. Health Canada will also ensure that research conducted under the MMRP complies with the provisions of the Food and Drugs Act and its Regulations and the Controlled Drugs and Substances Act and its Regulations. CIHR will ensure that the research is scientifically sound, and manage communications with investigators and the conduct of approved research projects.

Eligibility

The intent of CIHR is to fund the best health research in Canada. CIHR will, therefore, allow as many qualified health researchers in the country as possible to compete for its grants and will accept applications from Principal Applicants from various communities and sectors including researchers, scholars and health professionals. Further details on funding requirements are available on the CIHR website. Proposals requesting funding for multi-year projects with terms up to the end of the Program may be submitted.

Review of Proposed Research

Consistent with the responsibilities of Health Canada and CIHR described above, both organizations will review the proposed research. In order to assess the relevance of the proposed research to policy needs and hence the eligibility of applications, a summary of the research proposal must be sent to Health Canada for preliminary review. Acceptance of the proposal by Health Canada will result in a call for a complete project proposal for assessment through the CIHR process.

The initial step in the CIHR application process involves registration. This step requires the submission of limited information comprised of selected pages from the CIHR application modules. Health Canada will accept the registration information for an initial review of the proposal's relevance. If the information contained in the "summary of the research proposal" is insufficient for this review, applicants will be contacted for further information. The registration for this initiative must be received by both Health Canada and CIHR offices 60 days prior to the deadlines for full applications. Further details on submission dates are given below. CIHR will advise candidates as to the eligibility of their proposal for this initiative 30 days before the deadlines for full applications. Those whose projects are deemed eligible will be invited to submit to CIHR offices full applications according to the guidelines and requirements of CIHR.

Health Canada Review

Health Canada will review the summaries of the research proposals and will consider the following eligible for funding:

• clinical studies on either the safety or efficacy or both of smoked or unsmoked marijuana, or
• clinical studies involving the development of a dosage form that will eliminate the need to smoke marijuana and involving the administration to humans of a drug derived from marijuana.

CIHR Review

Proposals will be evaluated on scientific excellence. Applications will be submitted to the appropriate CIHR peer review committee(s) for scientific evaluation. The criteria used for review of applications include:

• for clinical trials, the likelihood that the study will increase our understanding of the clinical effects of marijuana and/or cannabinoids or will provide alternative mechanisms to administer marijuana and/or cannabinoids;
• the appropriateness and adequacy of the experimental approach and methodology proposed to carry out the study:
• the qualifications and research experience of investigators; and
• the availability of resources and facilities necessary to perform the research.

Regulatory Considerations

In Canada, the importation and use of marijuana for therapeutic purposes is regulated under the Controlled Drugs and Substances Act (CDSA), the Narcotic Control Regulations (NCR) and the Food and Drugs Act (F&DA) and the Food and Drug Regulations (F&DR). The CDSA and its regulations provide a framework for the control of the import, export, distribution and use of controlled drugs and substances. The F&DA and its regulations provide a framework to ensure that all therapeutic drugs available to Canadians are safe, effective and of high quality. To undertake research on marijuana, the current regulatory controls must be satisfied. Marijuana derived from other than legal sources may not be used in this Program.

Applicants are reminded that before initiating a clinical study under this Program, they must be authorized by the Therapeutic Products Directorate (TPD) of Health Canada. New regulations pertaining to the conduct of clinical studies were made on June 17, 2001. These regulations ensure that the design and conduct of studies are in keeping with national and international standards and that patients are not exposed to undue risk. There is a 30-day default period, to allow for the review of a Clinical Trial Application (CTA), before a trial may be started. The default status of this review process means that the TPD, on behalf of the Minister, must indicate that the submission is not satisfactory within a 30 day period. For further information on the requirements related to CTA approval, investigators may wish to consult the Health Canada website. The new regulations are also available on this website.

All research involving human subjects conducted under the sponsorship of CIHR is required to be approved by a research ethics board (REB). At the present time, prior approval by an REB is not necessary for CTA approval. It is required, however, that REB approval be obtained before the study is initiated.

Preparation of a Clinical Trial Application

The proper preparation of a CTA is essential to ensure that all of the concerns anticipated during the review of the information during the regulatory process are adequately addressed. Where the investigators developing a proposal do not have experience in the preparation of CTA, Health Canada will consider funding, on a limited basis, the acquisition of this expertise by the applicant through a contract. This funding would be in addition to that needed to conduct the research. Before a commitment is made to this additional funding, the research application must have been evaluated and deemed by CIHR to be fundable under the MMRP. Health Canada will also consider requests for limited funding assistance for other aspects of activities under this program.

Source of Marijuana

Applicants should assume that a licit source of research grade marijuana will be accessible through Health Canada. In December, 2000 a contract was awarded to a Canadian company, Prairie Plant Systems Inc. of Saskatoon for the cultivation of Canada's supply of marijuana for research purposes. Marijuana and placebo produced under this contract will be available for all Health Canada research initiatives investigating the use of marijuana for medical purposes. Applications are required to indicate the intended dose, the THC content of the material, and the total amount needed for the study. The cost of marijuana will be determined by Health Canada and added to the budget submitted for funding by the applicant.

Health Canada will collect the information necessary to satisfy the Chemistry and Manufacturing portion of the CTA where the marijuana is used as received and is not processed further. Investigators contemplating the development of proposals are encouraged to contact the Manager, Evaluation and Research Coordination Division, early in the project to discuss their needs and the availability of material. This will allow Health Canada to adjust production to satisfy researchers needs and to generate the information necessary for inclusion in the Chemistry and Manufacturing portion of the CTA. It can be anticipated that several months may be required to prepare the materials for the study and to generate sufficient analytical data on the available materials for inclusion in the Chemistry and Manufacturing portion of a CTA.

Funding

The general guidelines for CIHR research funding programs will be followed. For further details, please refer to CIHR's Grants and Awards Guide on CIHR's website.

Research Projects/Operating Grants, including Randomized Controlled Trials: As there are no set amounts for individual projects, the total number of projects funded under this partnership will depend on the size of the approved grant(s). Funding will be based on the priorities described above. The final decision on funding will be made by Health Canada.

Applications

Applications under this program will be managed according to normal procedures used by CIHR for requests for funding. CIHR issues a call for proposals twice per year for operating grants, and four times per year for randomized controlled trials. For the purposes of this program, CIHR defines a Randomized Controlled Trial as a study involving humans where at least two interventions in health care (possibly including placebo or standard care) are compared using random allocation, statistical methodologies and blinding techniques. Applications for dose finding studies, safety and efficacy studies and other non-randomized controlled studies must be made through the CIHR Operating Grants Program.

Candidates must apply using CIHR's application process and specified forms. Please refer to CIHR's Grants and Awards Guide on CIHR's website: www.cihr.ca for further information and to download the appropriate application modules. The initial step in the CIHR application process involves registration. This step requires the submission of limited information comprised of selected pages from the CIHR application modules. Health Canada will accept the registration information for an initial review of the proposal's relevance. If the information contained in the "summary of the research proposal" is insufficient for this review applicants will be contacted for further information. In order to allow for the review of the proposal's relevance under this program, this registration information must be submitted to Health Canada and CIHR 60 days prior to the deadline for full applications. Deadlines for full applications for Operating Grants are September 15 and March 1 of each year. Deadlines for full applications for Randomized Controlled Trials are September 1, November 1, February 15 and April 1 of each year.

Those candidates whose projects are deemed eligible must submit to CIHR offices full applications according to the guidelines and requirements of the program they are applying to, either CIHR Operating Grants or CIHR Randomized Controlled Trials, by the above-mentioned dates. In addition, candidates are also required to submit directly to Health Canada further information concerning the drug material that will be used in the study. This information must include the specifics of the study including: the amount of marijuana (in grams or kilograms), required for the study; the amount required per subject; the number of subjects; the duration of the study; storage location(s); and any other details which will help Health Canada ensure successful applicants can meet regulatory requirements.

Please send the Health Canada copy of the registration information and the additional detailed information in confidence to:

Manager
Evaluation and Research Coordination Section Division
Office of Controlled Substances
Healthy Environments & Consumer Safety Branch
Health Canada A.L. 3503B
Ottawa ON K1A 1B9

Please send the CIHR information to:

Canadian Institutes of Health Research
410 Laurier Avenue W., 9th Floor
Address Locator 4209A
Ottawa ON K1A 0W9

Communications

Recipients of all awards will be requested to submit annual progress reports to CIHR and acknowledge the Health Canada/CIHR Medical Marijuana Research Program as a source of support in publication(s) and presentation(s) of their research findings. Recipients will be also be requested to notify Health Canada prior to any scientific publication(s) and presentation(s) of their research findings.

For further information concerning the Medical Marijuana Research Program, please contact:

Dr. Suzanne Desjardins
Manager
Evaluation and Research Coordination Division
Office of Controlled Substances
Healthy Environments & Consumer Safety Branch
tel: (613) 946-4223
email: suzanne_desjardins@hc-sc.gc.ca

Isabell Schmid
Deputy Director, Research Translation Program
Randomized Controlled Trials Unit,
Canadian Institutes of Health Research
tel: (613) 941-4438
email: ischmid@cihr-irsc.gc.ca

Some Background Material

• US Institute of Medicine (IOM), report entitled Marijuana and Medicine: Assessing the Science Base, published by the National Academy Press, Washington, DC, 1999.
• National Institutes of Health. Medical Marijuana. Workshop Proceedings: February 19-20, 1997. Bethesda MD, USA.
• World Health Organization. Cannabis: a health perspective and research agenda. Publication no. who/msa/psa/97.4, 1997
• Health Council of the Netherlands: Standing Committee on Medicine."Marijuana as medicine." , December 3, 1996, publication no. 1996/21E.
• British Medical Association. Therapeutic uses of cannabis. Amsterdam: Harwood Academic Publishers, 1997.
• The Report of the UK House of Lords, Select Committee on Science and Technology, Session 1997-98, Cannabis: the scientific and medical evidence. 9th Report, HL Paper 151, November 1998.