Important Dates

Table of Contents

• Description
• Objectives
• Eligibility
• Guidelines
• Performance Measurement
• Review Process and Evaluation
• How to Apply
• Contact Information
• Partner/Collaborator Description

Description

Medical imaging is one of the fastest growing fields in medicine. The development of innovative new imaging modalities, contrast agents, molecular probes and radiopharmaceuticals has significantly improved our ability to study biological structures and functions in health and disease, and continues to contribute to the evolution of medical care. In addition to routine X-rays, the most common imaging techniques in current clinical practice are: computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), and single photon emission computed tomography (SPECT). CT and MRI scanners, ultrasound units and gamma cameras are now an essential part of clinical practice. Positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) are also increasingly used in the management of patients with cancer and neurological disorders.

Imaging technologies that require the use of radiopharmaceuticals e.g. PET, SPECT, fall within the field of nuclear medicine. The practice of nuclear medicine is a small but essential sub-specialization within the field of medical imaging. It is estimated that about 1.5 million nuclear medicine procedures are performed annually in Canada. Over 80% of all nuclear medicine investigations involve radiopharmaceuticals labeled with Technetium-99m (99mTc) which are supplied by either large centralized radiopharmacies or small hospital-based manufacturing sites. 99mTc is obtained from Molybdenum-99 generators, produced in North America by one of two manufacturers: Covidien and Lantheus.

The world's supply of 99mTc is remarkably fragile, relying on the continued operation of just a handful of aging nuclear reactors. About 30-35% of the world's supply of Molybdenum-99 is made at the National Research Universal (NRU) nuclear reactor at Chalk River. The emergency closure of the NRU in 2007 led to a significant disruption in the supply of Molybdenum-99 and the cancellation of large numbers of medical procedures. Although the shutdown was for a relatively brief period, the crisis highlighted the fragility of the Molybdenum-99 supply chain.

Following the 2007 NRU shutdown, Health Canada established an Ad Hoc Group of Experts on Medical Isotopes to provide advice and strategies to the Minister of Health. Health Canada has continued to engage the Ad Hoc Group of Experts on the uses of, and alternatives to, medical isotopes in the health care system. Focusing on Health Canada's regulatory role, a regulatory working group was struck with members of the Ad Hoc Group, to enhance the regulatory approval process for alternative medical isotopes.

Since 2007, the emergency shutdown of the reactor in Petten, in the Netherlands, in 2008, further demonstrated the fragility of global supply... The recent closure of the NRU has now resulted in a major interruption in supply, leading to a serious situation in the health care system due to challenges accessing Technetium-labeled radiopharmaceuticals. The contingency measures implemented by the medical community and provincial health care systems are helping to maximize available supply of Tc-99m , but there is recognition that some diagnostic scans may have to be postponed. The issue will be magnified in 2010 when a number of other medical isotope reactors could likely be offline at, or near the same time, due to essential preventive maintenance schedules.

These continuing uncertainties in the supply of medical isotopes, especially 99mTc, have caused both the clinical and biomedical research communities to start looking for alternative ways to produce the 99mTc needed for vital clinical procedures and also to explore the potential of alternative medical isotopes to replace 99mTc as the radiopharmaceutical label in clinical practice.

In recent months, CIHR has been working closely with Health Canada, the Natural Sciences and Engineering Research Council (NSERC), other research agencies, research experts, and the Ad Hoc Group of Experts on Medical Isotopes (established by Health Canada following the closure of the NRU in late 2007) to plan a research strategy that will build on Canada's existing scientific and research expertise in medical imaging. Discussions have focused on the need to: evaluate the state of the science in medical imaging (nuclear and non-nuclear); identify areas where a targeted investment of funds might lead to advances in the field; and address the medical needs created by a potential reduction in access to Molybdenum-99.

As a first step, an invitational workshop has been planned for October 2009 that will lead to the development of a Request for Applications (RFA) in 2010. Because of the important role of medical imaging in the diagnosis and treatment of many different diseases and conditions, six of CIHR's thirteen Institutes have been involved in the planning and development of this strategic research initiative. They are: the Institute of Cancer Research (ICR), the Institute of Circulatory and Respiratory Health (ICRH), the Institute of Infection and Immunity (III), the Institute of Nutrition, Metabolism and Diabetes (INMD), the Institute of Neurosciences, Mental Health and Addiction (INMHA), and the Institute of Musculoskeletal Health and Arthritis (IMHA).

The research community in the natural sciences and engineering field has also been actively involved in planning this strategic research initiative. Most, if not all, of the imaging technologies currently used in nuclear medicine were first developed by chemists, physicists, and engineers. Canada is home to several internationally recognized research centres including TRIUMF, Canada's national laboratory for particle and nuclear physics; the Advanced Applied Physics Solutions (AAPS), a nationally designated Centre of Excellence (NCE) for Commercialization and research, established at TRIUMF; and the Canadian Institute for Photonic Innovations (CIPI), an NCE aimed at strengthening Canada's position at the forefront of photonics research and innovation in the 21st century. Several research chairs (Canada Research Chairs and NSERC Industrial Research Chairs) are currently established in Canadian universities with the objective of studying and developing new technologies to support, supplement and/or replace the current use of radiopharmaceuticals for medical imaging.

In 2008, a task force on alternatives for medical-isotope production was convened by TRIUMF, the University of British Columbia, and AAPS, with support from Natural Resources Canada and participation from many stakeholders including Health Canada. In its final report , the Task Force did not draw a conclusion about which technology is "better" as this was beyond its scope. Rather, the Task Force analyzed the case for, features of, and development path for photo-fission accelerator technology. The Task Force concluded that this technology has a sufficient number of attractive features that it warrants further attention by public and private enterprises.

Although the planning for the workshop and ensuing research initiative on medical imaging is continuing as scheduled, the recent emergency closure of the NRU has precipitated the need for more immediate action in addressing the anticipated short, medium and long-term global shortages of 99mTc and the impact this will have on patient care. As a result, NSERC and the six CIHR Institutes involved in planning the longer term initiative have come together to launch this current rapid response RFA.

Health Canada facilitated the development of guidelines by the ad-hoc Group of Medical Experts, based on the good work of Ontario, which identifies strategies to manage Tc-99m during a time of a shortage. The guidelines identify alternatives where available, and priority needs for Tc-99m where there are no alternatives.

The objective of this RFA is solely to provide the needed short-term impetus to speed the development of replacements for the PET and SPECT 99mTc – labeled, reactor-produced radiopharmaceuticals, especially those radiopharmaceuticals where no viable alternative currently exists in clinical applications. In addition, the RFA will support research on alternative means of 99mTc production that do not require the use of a nuclear reactor and that are likely to yield clinically useful Technetium – labeled radiopharmaceuticals within the two year granting period. It is expected that this RFA will lead to clinical trials applications and small scale clinical validation studies which compare the novel radiolabeled probes with those in current practice.

Due to the acute and potentially chronic shortage of 99mTc for essential medical procedures and the urgency of unmet health needs, the regular CIHR RFA application timelines have been significantly shortened to ensure disbursement of funds before the end of 2009.

Funds Available

CIHR's contribution to the amount available for this initiative is subject to availability of funds voted annually to CIHR by parliamentary appropriations, and the conditions that may be attached to them.

• The total amount available for this initiative is $6 million, with $3 million coming from CIHR and $ 3 million coming from NSERC. This amount may increase if additional funding partners decide to participate.
• No upper limit has been placed on the amount of funds available for individual projects but full budget itemization and justification will be required.
• Grants will be awarded for a period of up to 2 years.
• The equipment amount is awarded in year one.

Partner/Collaborator Participation

Objectives

The primary objective of this funding opportunity is to provide funds to accelerate the development of clinically useful alternatives to the ^99mTc radiopharmaceuticals that are currently produced using molybdenum generators derived from nuclear reactors. This objective includes alternative sources of Technetium production and alternative radionuclide labels for clinical radiopharmaceuticals. Projects that that can bring a new radiopharmaceutical to the clinic within a few months are strongly encouraged. At the same time, it is recognized that other alternatives exist that will need more time and significant funding to become clinically useful, hence the overall two year granting period of this RFA. Both types of application are invited in response to this RFA.

The specific objectives of this funding opportunity are:

• To advance research into alternative, non-reactor, means of producing clinically useful radionuclides of Technetium and to bring these methods to the clinic within the shortest time possible, and respecting the timeframe of the grant.
• To advance research into the development of alternate PET and SPECT radiopharmaceuticals that could replace those labeled with ^99mTc in certain imaging procedures and for which the radiolabel can be produced by means other than a nuclear reactor. Projects likely to achieve these goals within one year of receiving funded are strongly encouraged
• To support applications likely to lead to a clinically useful isotope or diagnostic tests in the shortest possible timeframe. Projects likely to deliver clinically useful results within one year of receiving funding are strongly encouraged.
• To fast track the production and testing of candidate radiolabelled tracers resulting in clinical studies to validate the new entity during, or by the end of, the two year granting period.

NOTE: Health Canada is working closely with the Expert Advisory Group to have the necessary accelerated regulatory requirements in place for clinical trials applications. Health Canada is, at all times, ready to provide both regulatory and clinical trial guidance to anyone applying to carry out such studies. Health Canada invites applicants to apply early and consult often to maximise the guidance provided. The regulations allow for a 30-day turnaround for each application, although Health Canada is aiming for a seven day target during the shortage. Information on the necessary documentation in support of a clinical trial application to Health Canada can be accessed through their website.

Relevant Research Areas:

Because this is a highly targeted RFA with the goal of rapidly producing alternatives to the nuclear reactor-produced 99mTc currently used in clinical investigations, the areas of research are limited to those areas where radiopharmaceuticals are in routine clinical use at the present time. The list below is derived from data from the Health Canada Regulatory Group and will form the basis of review of the clinical relevance of applications made in response to this RFA. The tests have been listed in order of perceived clinical need based on the current availability of alternate tests or radiopharmaceuticals. Additional candidates may be proposed if it can be demonstrated that they are likely to fulfill an identified clinical need and meet the timelines described in this RFA.

Specific Research Foci and Requirements

Applications that include alternate radiopharmaceuticals that are applicable to a broad range of clinical situations are encouraged. Applicants are requested to clearly state the potential relevance of their proposed research to the mandates of the supporting Institutes.

Considering the links between technologies and applications, multidisciplinary proposals that bring together health and natural sciences/engineering expertise are strongly encouraged in order to develop effective and efficient solutions. These teams can include international collaborators when appropriate.

Eligibility

Eligibility criteria for all CIHR research funding programs apply. The business office of the institution of an eligible Nominated Principal Applicant generally administers CIHR funds. Please refer to the Eligibility Requirements for CIHR Grants and Awards regarding the eligibility requirements for individuals and institutions.

Randomized Controlled Trials (RCTs) will be considered under this funding opportunity.

Specific Eligibility Requirements

Eligibility requirements specific to this funding opportunity include the following:

• Applicants must demonstrate that within their team they have the capability of developing and submitting a Clinical Trials Application and also that the team has the ability to conduct a proof of principle clinical trials.
• Research must begin within three months, or earlier, of the receipt of funds.

Guidelines

General CIHR Guidelines

This funding opportunity will follow the General Guidelines for Grant Programs. Applicants are encouraged to demonstrate the use of Gender and Sex-Based Analysis in applications.

Allowable Costs

Applicants should review the Use of Grant Funds section of the Tri-Agency (CIHR, NSERC and SSHRC) Financial Administration Guide for a complete listing and description of allowable costs and activities.

The full application must provide a detailed justification of all costs.

The following expenditures will be considered eligible for funding received through this funding opportunity:

• If animal toxicity studies are required to enable human use of novel radiopharmaceuticals the costs should be anticipated and included in the application with appropriate quotations from a GLP accredited laboratory.
• Costs related to the preparation of a clinical trials application to Health Canada e.g. to obtain licensing for a new product, or for a previously approved product for which a different clinical use is proposed
• Proof of Principle clinical trials to validate the comparative efficacy of a newly developed radiotracer

Conditions of Funding

All conditions specified in CIHR General Grants and Awards Policies shall apply to applications funded through this Funding opportunity. Conditions cover areas such as Applicant and Institutional Responsibilities, Ethics, Official languages policy, Access to Information and Privacy Acts, and Acknowledgement of CIHR's Support. Successful applicants will be informed of any special financial requirements prior to the release of funds or when they receive CIHR's Authorization for Funding (AFF) document.

In addition to CIHR/NSERC standard guidelines and requirements, the following special requirements shall apply:

• At the end of the first six months of funding and again at the end of the first year of funding, the Nominated Principal Investigator is required to submit a progress report indicating progress to date and a proposed timeline for the expected clinical applications of their research
• Within six months after the end of the grant's term, the Nominated Principal Investigator is required to submit a final performance report, summarizing the results and describing how the grant funds were used.
• Principal Investigators submitting clinical trials applications to Health Canada during, or following, the two year granting period are requested to inform the CIHR contact person identified on this RFA.

Access to Information Act and Privacy Act, and the Personal Information Protection and Electronic Documents Act (PIPEDA)

All personal information collected by CIHR about applicants is used to review applications, to recruit reviewers, to administer and monitor grants and awards, to compile statistics, and to promote and support health research in Canada. Consistent with these purposes, applicants should also expect that information collected by CIHR may be shared as described in Use and Disclosure of Personal Information Provided to CIHR for Peer Review.

CIHR as a federal entity is subject to the Access to Information Act and the Privacy Act, therefore the requirements of these two statutes will apply to all information located in CIHR's premises including, without limitation, cost-sharing agreements related to this Funding opportunity and all matters pertaining thereto.

While respecting the application of the Privacy Act to federal entities, all signing parties involved in a collaborative agreement will also be bound by the Personal Information Protection and Electronic Documents Act (PIPEDA). All personal information (as identified by the PIPEDA) collected, used or disclosed in the course of any commercial activity under collaborative agreements related to the Funding opportunity will be collected, used and disclosed in compliance with the PIPEDA.

CIHR Guidelines for Health Research Involving Aboriginal People

The CIHR Guidelines for Health Research Involving Aboriginal People came into effect as policy for CIHR-funded research on July 1, 2008. Applicants whose proposed research will involve Aboriginal People are strongly encouraged to familiarise themselves with these guidelines and in particular with the section "Application of the Guidelines," which outlines the situations in which these guidelines apply.

Policy on Access to Research Outputs

CIHR believes that greater access to research publications and data will promote the ability of researchers and knowledge users in Canada and abroad to use and build on the knowledge needed to address significant health challenges. Open access will promote accessibility to CIHR-funded research and will serve to increase the international visibility of Canadian research. As of January 1, 2008, CIHR grant recipients are reminded to adhere with the responsibilities outlined in the Policy on Access to Research Outputs. Under this policy, grant recipients must make every effort to ensure that research papers and bio-molecular data generated from CIHR funding are freely accessible online.

Communication Requirements

Grant recipients are required to acknowledge CIHR, its institutes and partners in any communication or publication related to the project. See CIHR General Grants and Awards Policies, Public Communication and Acknowledgement of CIHR's Support for details on CIHR's communication requirements. The contributing institutes/partners will be identified on the Authorization for Funding and decision letter.

Performance Measurement

CIHR is committed to demonstrating results to Canadians for the money invested in health research. Therefore, processes for monitoring progress and appropriate use of funds, as well as for performance measurement and program evaluation are in place. As a result, funding recipients must:

• contribute to the monitoring, review and evaluation of CIHR's programs, policies and processes by participating in evaluation studies, surveys, workshops, audits and providing data or reports as required for the purpose of collecting information to assess progress and results;
• encourage their associates, trainees and administration to participate in the monitoring, review and evaluation of CIHR's programs, policies and processes as required.

Review Process and Evaluation

Relevance Review

The CIHR Institute of Cancer Research, the Institute of Circulatory and Respiratory Health, the Institute of Infection and Immunity, the Institute of Musculoskeletal Health and Arthritis, the Institute of Neurosciences, Mental Health and Addiction, the Institute of Nutrition, Metabolism and Diabetes, and the Natural Sciences and Engineering Research Council of Canada will provide funding for applications that are relevant to (in alignment with) the objectives and research priority areas described in the Objectives section.

Prior to peer review, representatives from the funding partners mentioned in this RFA will have access to project titles and summaries to conduct relevance review.

The following criteria will be used in conducting the relevance review.

• Alignment with the objectives and relevant research areas as described under the Relevant Research Areas and Requirements section of this funding opportunity.
• Alignment with the relevant institute mandates and research priorities

Upon completion of peer review, the representatives from the funding partners mentioned in this RFA will receive the ranking list, merit scores (ratings) and recommendations on funding level and award term for the applications that fall in the fundable range and have been determined to be relevant to the specific research areas and objectives of the initiative.

Peer Review

A CIHR peer review committee will evaluate the full applications. The committee may be drawn from one of CIHR's pre-existing committees or may be created specifically for this funding opportunity. Committee members are selected based on suggestions from many sources including the institute(s) / portfolio(s) and partner(s), following CIHR's Policy on Conflict of Interest and Confidentiality in the context of Merit, Relevance and Peer Review (CCIP). For information on CIHR's peer review process in general, see the Understand Peer Review section of CIHR's website.

Evaluation Criteria

Peer review will be conducted in accordance with The CIHR Peer Review Process – Policies and Responsibilities of Grants Committee Members. Reviewers will use the following set of criteria for the evaluation of all CIHR grant applications:

1. Research Approach
2. Originality of the Proposal
3. Applicant(s)
4. Environment for the Research
5. Impact of the Research

A detailed elaboration of these criteria can be found in the Information for Peer Reviewers section of CIHR website.

To support the strategic objectives of this funding opportunity, the following factors will be considered in addition to the standard set of evaluation criteria:

• The applicability of the research to the table of identified clinical needs
• The likelihood of the proposed research resulting in a clinical trials application and clinical validation within one year or earlier, with a maximum of two years.
• The likelihood of the research leading to the clinical application of a previously licensed radiopharmaceutical in a novel way to improve patient outcome within the shortest feasible time frame with a maximum of two years following receipt of funds

How to Apply

Note: This funding opportunity requires the use of CIHR Web Forms to apply for funding.

• The application process for this funding opportunity is comprised of two steps: Registration and Application.
• To complete your Registration and Application, follow the instructions identified in the Operating Grants - Web Forms "Registration" Phase Instructions and the Operating Grants - Web Forms "Application" Phase Instructions.
• An overview of CIHR's application processes can be found under Apply for Funding.
• Reminder to applicants: Please ensure that your application is complete, includes all required signatures and submitted on time to CIHR. As of September 1, 2008, CIHR no longer assumes responsibility in following-up with applicants who submit an incomplete application. Incomplete or late applications will not be accepted into the competition.

Additional instructions that must be followed for this funding opportunity:

(Note: These additional instructions supersede all other policies or guidelines published by the Canadian Institutes of Health Research, including, but not limited to, the Grants and Awards Guide, the Memorandum of Understanding, etc.)

• In the Research Funding Program section of the Research Module, select "Strategic Initiative" and enter the title of this funding opportunity.

Send the completed registration and application packages by courier to:

RE: "Research/Operating Grants: Alternative Radiopharmaceuticals for Medical Imaging"
Canadian Institutes of Health Research
Room 97, 160 Elgin Street
Address locator: 4809A
Ottawa, Ontario K1A 0W9

Contact Information

For questions on CIHR funding guidelines, how to apply, and the peer review process contact:

Mary Fraser Valiquette
Program Delivery Officer
Canadian Institutes of Health Research
Telephone: 613-941-4394
Fax: 613-954-1800
Email: mary.fraservaliquette@cihr-irsc.gc.ca

For questions about this initiative and research objectives contact:

Judith Bray
Assistant Director
CIHR Institute of Cancer Research
Telephone: 613-954-7223
Fax: 613-954-1800
Email: judith.bray@cihr-irsc.gc.ca

Partner/Collaborator Description

Note: Additional partners/collaborators, including partners/collaborators from industry and the private sector are expected to join this funding initiative over the coming year.

Canadian Institutes of Health Research (CIHR)
CIHR is the Government of Canada's agency for health research. CIHR's mission is to create new scientific knowledge and to enable its translation into improved health, more effective health services and products, and a strengthened Canadian health-care system. Composed of 13 Institutes, CIHR provides leadership and support to nearly 12,000 health researchers and trainees across Canada.

CIHR – Institute of Cancer Research
ICR fosters research based on internationally accepted standards of excellence, which bear on preventing and treating cancer, and improving the health and quality of life of cancer patients. ICR is dedicated to supporting research that reduces the burden of cancer on individuals and families through prevention strategies, screening, diagnosis, effective treatment, psycho-social support systems, and palliation.

Partners

CIHR– Institute of Circulatory and Respiratory Health (ICRH)
ICRH supports research into causes, mechanisms, prevention, screening, diagnosis, treatment, support systems, and palliation for a wide range of conditions associated with the heart, lung, brain (stroke), blood, blood vessels, critical care and sleep.

CIHR – Institute of Infection and Immunity (III)
III supports research and helps to build research capacity in the areas of infectious disease and the body's immune system. Through the Institute's programs, researchers address a wide range of health concerns related to infection and immunity including disease mechanisms, disease prevention and treatment, and health promotion through public policy.

CIHR – Institute of Musculoskeletal Health and Arthritis (IMHA)
IMHA supports research to enhance active living, mobility and movement, and oral health; and addresses causes, prevention, screening, diagnosis, treatment, support systems, and palliation for a wide range of conditions related to bones, joints, muscles, connective tissue, skin and teeth.

CIHR – Institute of Neurosciences, Mental Health and Addiction (INMHA)
INMHA supports research to enhance mental health, neurological health, vision, hearing, and cognitive functioning and to reduce the burden of related disorders through prevention strategies, screening, diagnosis, treatment, support systems, and palliation.

CIHR – Institute of Nutrition, Metabolism and Diabetes (INMD)
INMD supports research to enhance health in relation to diet, digestion, excretion, and metabolism; and to address causes, prevention, screening, diagnosis, treatment, support systems, and palliation for a wide range of conditions and problems associated with hormone, digestive system, kidney, and liver function.

Natural Sciences and Engineering Research Council of Canada (NSERC)
NSERC's role is to make investments in people, discovery and innovation for the benefit of all Canadians. NSERC is the national instrument for making strategic investments in Canada's capability in science and technology. NSERC supports both basic university research through discovery grants and project research through partnerships among universities, governments and the private sector, as well as the advanced training of highly qualified people.