Request for Letters of Intent (RFP 001) - April 2001
Competition Deadline: May 16, 2001

I. Introduction

Health Canada's Research Management and Dissemination Division (RMDD), situated within the Applied Research and Analysis Directorate of the Information, Analysis and Connectivity Branch, is pleased to announce the first Request for Letters of Intent (LOI) for Health Canada's Health Policy Research Program (HPRP).

The HPRP is intended to generate quality extramural policy-relevant research to meet the specific needs of Health Canada. In conjunction with in-house policy research, the HPRP will build the evidence base for decision-making on key policy issues of concern to Health Canada over the next two to five years. It will help bridge the gap between what is known and what is applied in policies and programs relevant to the department (and to other health policy makers).

The HPRP is a strategic, targeted contribution program. It will address corporate policy needs and concerns as identified through a departmental Policy Research Working Group, connected, as applicable, to national and international research endeavours.

The HPRP will fund research and related activities that directly support the department's policy and program functions through four components:

• research projects (original and secondary analyses as well as syntheses);
• Federal/Provincial/Territorial (F/P/T) health research partnerships;
• developmental projects (such as feasibility studies, assessment of pilot projects, development of policy research or knowledge transfer methodologies, or definition of the scope and parameters of a new policy research area); and
• policy-relevant workshops, seminars, conferences.

II. Important Information for Applicants

The RMDD has dedicated a $1.2 million envelope for this competition and expects to fund a total of approximately 6 to 8 projects across the two themes identified under the Scope section. Project duration is expected to be approximately 18 - 24 months.

This first Request for LOIs is focussed solely on primary research projects. Requests for LOIs or full proposals for other activities will follow.

III. Research and Policy Interface

The RMDD is committed to building a sustained collaboration between the research community and Health Canada's policy officials. As such, a key policy contact has been identified for each of the priority areas described in this document. This contact person will be responsible for ongoing substantive interaction with researchers to provide contextual guidance and advice to researcherson the policy interface at Health Canada.

We encourage all applicants to contact the policy official identified for consultation prior to and during the drafting of a Letter of Intent.

IV. Scope of Competition

LOIs are invited in one of the following policy relevant areas:

• Climate Change and Population Health;
• Assessment of Drug Effectiveness in the "Real World";

Specific policy questions are identified below.

Climate Change and Population Health

Michael Sharpe
Manager
Climate Change and Health Office
Safe Environments Programme
Healthy Environments and Consumer
Safety Branch
Health Canada
Tunney's Pasture, Rm 237, EHC Building
A.L. 0802D1
Ottawa/Ontario K1A 0L2
Telephone: (613) 954-0161
Fax:(613) 957-1886
E-mail: michael_sharpe@hc-sc.gc.ca

Paul Gully
A/Director General
Centre of Infectious Disease
Prevention and Control Population and Public
Health Branch
Health Canada
Tunney's Pasture, Rm 2391, LCDC Building
A. L. 0602C2
Ottawa/Ontario K1A 0L2 
Telephone: (613) 941-4339
Fax: (613) 946-5070
E-mail: paul_gully@hc-sc.gc.ca

It is now recognized that climate change, by altering weather patterns and by disturbing life-supporting systems and processes, will affect the health of human populations. The range of health effects will be diverse, often unpredictable in magnitude, and sometimes slow to emerge.

The projected health-related effects of climate change and the need for various adaptation strategies, such as expanded vigilance and medical services, health monitoring, environmental management, disaster preparedness and improved water and pollution control, could add to Canada's health care costs or necessitate changes in the structure of public health and health care activities. With research, planning and preparation, some projected impacts of climate change can be minimized while preparations for others can be undertaken.

Policy questions need to be addressed as an integral part of the decision-making process undertaken by governments and stakeholders. The proposed LOI should address one or more of the following policy questions:

• What are the possible consequences of climate change on the incidence of infectious and chronic diseases, migration patterns, and/or vulnerable population groups that will (have an) influence public health policy?
• How do we incorporate climate change considerations into the public policy risk management framework (notably risk identification, risk assessment, option development and consultation)?
• What are the best methods for assessing the impact of climate change on the need for a strengthened public health infrastructure?
• How can health and climate change considerations be integrated into a sustainable development framework and into interdepartmental and intergovernmental activities (ie: Environment Canada, Agriculture and Agri-food Canada and the Canadian Food Inspection Agency, Human Resources Development Canada, Indian and Northern Affairs).

Applicants are encouraged to consult Annex A for more information.

Assessment of Drug Effectiveness in the "Real World"

Policy Contact: Brad Buxton
Senior Policy Analyst
Active Surveillance, Research and Development
Product Utilization and Effectiveness Division
Marketed Health Products Directorate
Health Canada Room 1079D,
Brooke Claxton Building Tunney's Pasture
A.L. 0910D
Ottawa/ Ontario K1A 0K9
Telephone: (613) 948-6014 Fax: (613) 941-5258
Email: Brad_Buxton@hc-sc.gc.ca

With the exception of drugs dispensed for patients receiving hospital care, drugs are not coveredunder the Canada Health Act. Unlike hospital and medical care, which are publicly-financed, multiple payers are involved in the financing of prescribed drugs, including governments, private insurers and individual consumers. On September 11, 2000 Canada's First Ministers released a Communiqué on Health in which they reiterated their commitment to ensuring Canadians' access to new, cost-effective drugs.

Increased spending on drug products may be cost-effective within the health care system if drug products are effective and improved health outcomes and/or savings to the overall system are realized. However, expenditures on comparatively ineffective drug products may not contribute to improved outcomes and may threaten the sustainability of the health care system.

Health Canada is seeking proposals for a research project(s) that will identify policy options and methodologies leading to assessment of drug effectiveness in Canada. The research project(s) should address at least one of the following policy questions:

• How could information on drug effectiveness be used in establishing and revising formulary listings? As effectiveness information improves, what implications could this have for pharmaceutical policy development? For example: limiting access and second line approval for certain prescription drugs; and developing a common F/P/T drug review process.
  
  
• What are the strengths and weaknesses of existing analytical methods and sources of data for measuring drug effectiveness in the post-approval setting i.e. not in pre-Notice of Compliance clinical trials. How can these be improved to yield useful evidence for policy making? What changes to federal and provincial regulatory processes would be required?
  
  
• How is information on drug effectiveness currently communicated to policy makers, prescribers and consumers? How can this communication be improved to ensure evidence-based decision-making?
  
  
• Who/what types of organizations should be engaged to carry out effectiveness analyses?
  
  
• What type of criteria should be developed for Health Canada to: guide the process of engaging an organization to conduct analyses of drug effectiveness; and/or create a Canadian agency for pharmaceutical information assessment.

Applicants are encouraged to consult Annex B for more information.

V. Application and Review Processes

This is a two-phase application process:

• Letter of Intent
• Full Proposal

Letter of Intent

Researchers are invited to submit a Letter of Intent before 5:00 p.m. E.S.T.on May 16, 2001 in one of the priority areas identified in this document. The instructions for the preparation and submission of an LOI are provided in Annex C (Application Procedures) and ineligible activities are listed in Annex D.

The review process will consist of:

- screening within RMDD for eligibility; and
- review for policy relevance by Health Canada officials.

Through this process, Health Canada will provide input to applicants in the development of LOIs to facilitate the connection between research and policy/program development. Applicants will be advised of the outcome of the LOI review process and those whose LOIs were found to be relevant to the Department's policy needs will be invited to submit full proposals.

Full Proposal

Information on preparing and submitting a full application will be provided to the successful LOI applicants.

The review process will then consist of:

- review for eligibility;
- external peer review for policy priority and scientific quality; and
- approval by the Minister of Health (based on reviews and subject to availability of funds).

Health Canada will continue to provide input to applicants in the development of full proposals to further facilitate the connection between research and policy/program development.

** Please note that scientific and/or relevance review may also be applied to deliverables submitted upon completion of the research. **

VI. Inquiries

Inquiries should be directed to:

Information Officer
E-mail: rmddinfo@hc-sc.gc.ca
Telephone: (613) 954-8549
Fax: (613) 954-7363

ANNEX A

POLICY RESEARCH PRIORITIES:

CLIMATE CHANGE AND POPULATION HEALTH

Context:

It is now recognized that climate change, by altering weather patterns and by disturbing life-supporting systems and processes, will affect the health of human populations (InternationalPanel on Climate Change 2001). The range of health effects will be diverse, often unpredictable in magnitude, and sometimes slow to emerge.

Climate change includes global warming and a greater climate variability, i.e., a greater likelihood of extreme and unexpected weather and patterns. As some of the "greenhouse gases" also attack stratospheric ozone, there will also be higher UV radiation levels. These environmental changes can directly influence human health and well-being through physical stresses and weather disasters.

In addition, these changes profoundly affect the many interdependent plant and animal populations (ecosystems) which provide the natural "support services" on which human health and well-being depend. These population health risks have not yet been properly recognized by policy makers, and are not adequately covered and addressed by existing public policies and their associated risk assessment and risk management mechanisms. It will require the combined efforts of scientific researchers and of policy makers to meet the challenge of climate change.

To formulate new public policies or to amend existing ones in order to safeguard the health and well-being of people, scientific experts need to identify:

- Where and how the expected environmental changes will affect population health and well-being (refer to Research on Climate Change section below); and
- Possible protective and adaptive measures and their costs and benefits (refer to Climate Change Policy Implications section below).

1. Research on Climate Change

Due to the existence of regional climate variability across Canada, different population groups will likely differ in their vulnerability to climate extremes. A warming of 4-8^oC has been predicted in the south of Canada, with "little season to season change", from the Canadian Climate Centre General Circulation model, while a warming of 8-12^oC in winter and 0-6^oC in summer has been predicted for the north of Canada. The impacts of climate change will be distributed unevenly across sectors and regions and over time across generations. Some sectors may be at a greater disadvantage under a changed climate than others. There may also be political and social consequences as a result of climate changes occurring elsewhere, outside Canada.

The range of possible effects of climate change and variability in Canada could be clarified by considering some important population health determinants and population groups, as outlined below.

Infectious Diseases and Natural Toxins in Food and Water

A warmer climate and more extreme weather may reduce water and food quality and quantity through hot spells, droughts, storms, or floods, and in other ways. Extreme weather damages food crops, and may also lead to higher levels of microbes (e.g. E. coli, enteric viruses) and of harmful natural contaminants (e.g. algal and fungal toxins) in water and food. Water-borne diseases that have already infested American and Canadian watersheds include Giardia and Cryptosporidum, resulting in widespread human exposure. The changed climate might also favour the spread and population growth of existing or imported invertebrate and vertebrate vectors of infectious diseases (e.g. Dengue fever, Lyme disease, Hanta virus, West Nile Fever virus). Therefore, climate change and variability might increase the threat of zoonotic and other infectious diseases, and of illnesses due to increases of natural toxins in food and water.

Chronic Diseases

Cardiovascular and Respiratory Diseases: Climate change is expected to have some direct and indirect adverse impacts on human health. Direct impacts may include increase in heat exhaustion, heat cramps, heat rash and an increase in deaths related to heat stress. From 1965-1992, 183 Canadians died due to excessive heat. This number will likely increase with changes in climate, particularly in urbanized areas. Indirect effects include an increase in the incidence of cardiovascular disease and respiratory disorders. It is expected that short-term heat waves or periods of intense heat will have the most profound and direct effects on human health.

Skin Cancer and Cataracts: An increase in population exposure to UV radiation can be expected from the anticipated longer mild seasons with longer outdoor "warm-weather activity" periods for people who wear inadequate clothing, and who do not use adequate other protective measures.

Excessive exposure to UV radiation causes or contributes to skin cancer and cataract formation, and may also affect certain immune responses.

Chronic Diseases:

A warmer, sunnier climate may accelerate certain chemical reactions in the air which are responsible for the formation of smog (especially of ground-level ozone). A warmer atmosphere enriched with CO² can also greatly increase the production of pollen from allergenic plants. Warm, humid weather increases fungal growth and the level of fungal spores in the air. These climate related effects are known to contribute to asthma and other chronic pulmonary and cardiovascular diseases. Thus climate change and variability might increase the burden of chronic diseases in the Canadian population.

Increased Migration

Within Canada, some regions will be more affected than others. Thus climate change and variability could stimulate population shifts within Canada. Some densely populated developing countries will likely be far more severely affected by climate extremes and by coastal flooding than Canada. This might lead to an increase in calls for disaster relief, economic assistance and a large increase of "environmental refugees" leaving the most affected countries and seeking a better future in Canada. Thus, climate change and variability might bring about considerable and as yet unanticipated changes in the composition and distribution of the Canadian population, which might lead to certain social and economic stresses.

Vulnerable Population Groups in Canada

Past climate shifts and extremes have shown to be more vulnerable to environmental changes than others. They include those who rely directly on the productivity of natural or modified ecosystems (subsistence populations, farmers, fishers) and those who have the least physical resistance (the young, the elderly, the frail and the ill) and the least social and economic resources (the poor).

Other vulnerable people are those who take medications that affect their body's thermoregulatory ability. Due to the dependence of rural and subsistence populations on a consistent climate, and because of the urban "heat island effect" during the summer, as well as the social isolation and homelessness commonly seen in cities, the sensitivities and vulnerabilities of both rural and urban population groups in Canada to climate change and variability need to be clarified. For example, climate modeling and recent effects of a warmer climate seen in some parts of northern Canada indicate that change and variability may particularly affect northern populations, including First Nations and Inuit, especially those who rely on natural sources of food and income.

2. Climate Change Policy Implications

Public Policy Risk Management Framework

Existing public policies and policy implementation measures designed to improve the physical, mental, and socio-economic health and well-being of Canadians, to safeguard the environment or to promote sustainable development, do not adequately address the expected health and socio-economic impacts of climate change and variability. The Canadian Action Plan for Climate Change, including its research, mitigation, and adaptation components also does not adequately address human health concerns. Consequently, a federal draft policy framework for managing risks arising from climate change has not yet been formally adopted. There is a need for both research and policy development to clarify and manage the health and socio-economic implications of climate change and variability for Canada.

The projected health-related effects of climate change and the need for various adaptation strategies, such as expanded vigilance and medical services, health monitoring, environmental management, disaster preparedness and improved water and pollution control, could add to Canada's health care costs. With research, planning and preparation, some projected impacts of climate change can be minimized while preparations for others can be undertaken. Theconsideration of costs/benefits related to the health of Canadians is an important component in developing the federal government's strategy on climate change and needs to be an integral part of the decision-making process undertaken by governments and stakeholders.

The Impact of Climate Change on the Need for a Strengthened Public Health Infrastructure

Research on Climate Change and Population Health will aid in the development of a surveillance system to monitor the health effects related to climate change. For the year 1999, approximately 4 % of total emergency room visits were diagnosed as indirect chronic heat-related diseases;

60 % of these were attributed to cardiovascular diseases and 40% to respiratory diseases (Ottawa Hospital, Civic Campus, Emergency Patient Information System). Currently there is no reporting mechanism for chronic heat-related illnesses or deaths in the Canadian health care system. Therefore we can neither assess the extent nor the costs of these health effects nor predict future trends based on past experience.

Integration of Climate Change Considerations into a Sustainable Development Framework and Interdepartmental Activities

Health Canada's Sustainable Development Strategy 2000 focuses on several significant environmental, social/cultural and economic factors that impact the health and quality of life of Canadians. These issues include:

• Air quality - high costs, approximately $2.3 billion, associated with health care for respiratory diseases, caused by poor indoor and outdoor air quality; food safety and water quality.
• Significant changes which may arise in the pattern of agriculture, resulting in social, economic and health impacts and the need for mitigation.

According to the Sustainable Development Strategy (re: the physical environment), Health Canada's commitments, similar to those government-wide, are to address environmental issues of current or potential health impacts and to protect Canadians from environmental health hazards such as the risk of food-borne diseases, and health effects of climate change.

As a result of our changing climate, there is a growing need to estimate the magnitude of these changes, determine their environmental, social, and economic impacts and identify the most effective adaptation strategies to cope with the anticipated changes.

ANNEX B

Assessing the Effectiveness of Marketed Pharmaceutical Products in the "Real World"

Context

Expenditures on drug products account for a steadily increasing portion of total health spending, growing faster than any other component of health care. According to the Canadian Institute for Health Information, spending on drugs is expected to have reached $14.7 billion, representing 15.5% of total health care spending, following increases of 8.9% and 9.0% in 1999 and 2000. In 1998, total spending on prescribed drugs was an estimated $9.3 billion, an increase of 10.6% from 1997. Total spending on non-prescribed drugs, such as over-the-counter cold and headache remedies, was an estimated $3.1 billion in 1998, a 6.6% increase over 1997. Prescription drug expenditures are a function of demographics and the health status of the population, the availability and utilization of drug treatments, the utilization of newer more expensive drug treatments relative to existing drug treatments, and costs.

The terms efficacy and effectiveness are used interchangeably in the Canadian Food and Drugs Regulations. In practice, however, efficacy assessment has referred to the pre-market assessment of drug product and has been based on the information generated in controlled, clinical trials involving relatively few human subjects. In contrast, the term effectiveness has been used in relation to the relative performance of a drug product in comparison to other drug or non-drug treatment options. Unlike the controlled circumstances in which information is generated for pre-market assessment, there is relatively little information systematically collected in the post-approval phase of drug products' life-cycles. Consequently, it is difficult to generalize about the effectiveness of drug products and make evidence-based policy decisions about their on-going usefulness.

Formulary Listings

Drug products which have been licensed for sale in the Canadian marketplace may be listed as benefits on federal, provincial or territorial drug plan formularies. Listing is based primarily on therapeutic and cost advantages; some benefit programs may impose restrictions on the coverage of certain drugs, such as:

• Limited access - Ontario's Section 8 authorization process provides access to drug products, on a case-by-case basis, which are not normally covered as a benefit. In Saskatchewan, drug products not usually provided as benefits may be authorized on a case-by-case basis and provided as a benefit under Exception Drug Status.
• Second-line approval - many drug benefit formulary lists identify lower cost, standard courses of therapy. In order for an individual patient to obtain drug benefits for secondary or subsequently tiered products, it must be demonstrated by the clinician or pharmacist that other treatment options have been tried but either failed or were not effective.

Decisions are usually based on available measures of clinical trial outcomes, and models of effectiveness based on efficacy data. In order to assess the effectiveness and, ultimately, the cost-effectiveness of drug products, there is a need to improve the evidence base. Limited measures of the effectiveness of drug therapy in the real world is a serious concern to health care providers, consumers, regulators, and third-party payers. Health Canada is committed to improving post-approval surveillance of the effectiveness of drug products in Canada.

Who Conducts Drug Effectiveness Analyses?

A drug product is approved for sale in Canada based on demonstration of safety and efficacy in clinical trials. However clinical trials, in which a drug treatment is administered to a limited, select group of compliant patients who meet specific criteria, are not necessarily representative of the real world. The measures of safety and efficacy upon which market approval is based, may not reflect the effectiveness of a drug product within a real world setting.

Furthermore, given that most available information is based on proprietary data owned by the products' sponsors - either the patent holder or drug manufacturer - the issue of objectiveness of information on drug product effectiveness is often raised. Options for the development of objective information have been explored in Canada in the past. For example, in 1993 a recommendation was made to the Federal/Provincial/Territorial (F/P/T) deputy ministers of health to create a Canadian agency for pharmaceutical information assessment - a not-for-profit corporation with F/P/T funding. In the UK, the National Institute for Clinical Excellence has been established to research and make recommendations on appropriate therapy.

The First Ministers' Meeting resulted in a Communiqué on Health which commits to consideration "...of strategies which could include the creation of a common intergovernmental advisory process to assess drugs for potential inclusion in government drug plans."

Current Analytical Methods and Sources of Data Measuring Drug Effectiveness in the Post-approval Setting

Post-approval assessment of the effectiveness of drug therapy has been largely confined to passive reporting of adverse drug reactions, with little to no reporting on the effectiveness of drug therapy in achieving expected health outcomes. This is due to a variety of gaps in clinical management systems, regulatory requirements, consumer information and reporting systems.

To this end, Health Canada is seeking proposals for a research project(s) that will identify policy options and methodologies that would lead to assessment of drug effectiveness in Canada. The research project(s) would:

- Identify gaps in measuring drug effectiveness;
- Propose pilot projects to develop models for using measurements of drug effectiveness and suggest how these could be used in developing and revising formularies;
- Assess the feasibility of methodologies for measuring drug effectiveness;
- Consider standards for outcome measures, and linkages of databases; and
- Consider/recommend how this new information on drug effectiveness could be used by public/ private drug program benefit managers.

The proposed project(s) must reflect current policy initiatives being undertaken by Health Canada including but not limited to:

- Product licensing;
- Post-approval assessment strategy;
- Development of electronic health records;
- The National Health Surveillance project. Applicants should also review Health Canada's
- Post-Approval Assessment Strategy 1999-2003 and notes from the January 19, 2001 workshop on drug effectiveness (which will soon be available at the following website: www.hc-sc.gc.ca/hpb-dgps/therapeut/htmleng/ ).

ANNEX C

APPLICATION PROCEDURES

INSTRUCTIONS:

Content of each Letter of Intent (LOI) must not exceed three (3) pages (81/2x 11 inches). No appendices or attachments permitted. Print must be 1½ line spacing and be a font similar to Times Roman 12 pts. A one inch (1") margin must appear at the top, bottom, left and right sides of each page.

PART A - Provide the following information in this order:

Principal Investigator's name (one investigator only).
Full mailing address.
Telephone/fax/e-mail.
Name of institution which would administer the funds.
Title of project.
Policy research topic addressed.
Approximate total budget (and annual breakdown) and duration of research project.
List of all co-investigators with affiliations and role on the project.

PART B - Provide the following information in this order:

Proposed research objective(s) and /or research question(s).
Rationale showing how the proposed research objectives/questions will supply critical parts of the evidence base for addressing the policy questions. Study design and methodologies to be used.
Team Strengths (including the mix of team skills and ability to address the question(s) from a policy perspective and the linkages the team has developed and/or proposes to develop with Health Canada in the context of this project). Expected outcomes including the significance of the new knowledge that will be generated from the study and its ability to inform the specific priority question(s) identified in the April 2001 Request for Proposals.

Completed LOIs must be submitted to the Health Policy Research Program by:

Fax: (613) 954-7363
Mail: Health Policy Research Program
Research Management & Dissemination Division
Information, Analysis and Connectivity Branch
Health Canada, 15th Floor, Jeanne Mance Building
Tunney's Pasture / Ottawa, Ontario / KIA 0K9
Address Locator: 1915A
E-mail: rmddinfo@hc-sc.gc.ca

ANNEX D

INELIGIBLE ACTIVITIES

The Health Policy Research Program (HPRP) does not support projects that include any of the following activities:

Laboratory research including studies of bacteria, viruses, micro-organisms, etc., to understand the origin and/or progress of diseases, and laboratory drug tests;
Clinical research including:
studies that examine the development of a disease;
studies that test the efficacy of a treatment (drug or other therapy) on a sample of patients;
evaluations of clinical interventions;
Database development and/or maintenance (including stand-alone or descriptive surveys unless the latter are part of a variety of methods used to answer a specific policy research question);
Evaluations of local interventions and programs with limited generalizability to broader policy issues;
Payment of costs of program delivery;
Infrastructure costs;
Acquisition of capital equipment;
Professional development and/or curriculum development.