Addressing a Public Health Priority: First Canadian Research Agenda on Influenza Prevention, Control and Management

15 November 2006

Volume 32

Number 22

On 31 August and 1 September, 2005, over 70 Canadian and international vaccine experts, policy-makers and researchers gathered in Ottawa to participate in the Influenza Research Priorities Workshop. The event was sponsored and organized by the Public Health Agency of Canada (PHAC) and the Canadian Institutes of Health Research (CIHR) Institute of Infection and Immunity in collaboration with the Canadian Association for Immunization Research and Evaluation.

Participants were given the task of developing the first Canadian research agenda on influenza in order to provide Canada with a comprehensive means to direct and coordinate research on influenza prevention and control. In addition to yielding a priority driven research agenda, the workshop format allowed organizers to test a priority-setting methodology that can be applied in identifying future vaccine research priorities.

Methods

Although a workshop approach is often used in contexts involving diverse stakeholders in order to reach consensus on a given question, the 2-day event was a first attempt to involve the influenza research community in establishing research priorities and identifying the requisite infrastructure and capacity to carry them out.

A multidisciplinary planning committee guided the workshop design and the selection of participants. To identify Canadian influenza researchers, organizers searched databases of national funding agencies and scrutinized scientific publications and individual Web sites. Participants came from academia, funding agencies, industry, public health and international bodies such as the World Health Organization (WHO), the US National Institute of Allergy and Infectious Disease and the US National Vaccine Program Office. They represented quite varied disciplines, such as animal infections, clinical trials, economics, epidemiology, ethics, immunology, infectious disease, mathematical modelling, molecular biology, pharmaceutical science, public health, social sciences and virology.

The workshop agenda consisted of plenary sessions to provide an overview of the current knowledge of influenza, break-out sessions that focused on specific areas for influenza research from a multidisciplinary perspective and a final plenary session to cluster research priorities into 10 priority areas.

The opening plenary session provided participants with an overview of Canadian and international knowledge of influenza. Topics covered the following areas: communicability, pathogenesis, epidemiology and the immune response to influenza infection in humans; current Canadian public health programs and strategies for the prevention and control of annual and pandemic influenza; available and new anti-influenza drugs and identified gaps in current knowledge; strengths of and opportunities for Canadian vaccine programs; recent and current influenza research in Canada; global influenza research strategies and activities, presented by the WHO representative; and US influenza research strategies and activities, presented by the US National Vaccine Program Office representative.

Six break-out sessions were held over the 2 days. Two nationally recognized experts chaired each session, and participants represented a deliberate mix of knowledge and expertise. Sessions opened with a brief overview of knowledge gaps followed by a brainstorming period to elaborate on the gaps. The Chairs urged each group to reach consensus on three to five key research priorities and to identify related infrastructure and capacity gaps. A five-point Likert relevancy scale was used to assess research priorities in terms of urgency for public health, uniqueness to Canada, feasibility, impact on decreasing the burden of disease and potential for rapid knowledge translation. Participants were instructed to articulate research priorities to a level suitable for Requests for Applications rather than for specific projects.

Day One breakout sessions covered (1) the challenges that influenza poses in the community, with a focus on research pertaining to disease risk and impact assessment, as well as prevention and control strategies in the community other than immunization; (2) challenges in health care settings, including diagnosis, patient treatment and management (other than antiviral drugs), infection control, ambulatory care, health care system interventions, clinical trials and other clinical research capacity; and (3) challenges to basic and applied science with emphasis on rapid diagnostics, animal models, virulence factors, correlates of protection and transmissibility of animal influenza viruses.

Day Two focused on (1) optimizing influenza vaccines through consideration of opportunities for novel vaccine development, increasing vaccine immunogenicity and effectiveness, use of adjuvants and other dose-sparing strategies, finding improved correlates of protection and broader cross-protection against circulating viruses; (2) optimizing vaccination programs, for instance, by assessing program strategies and effectiveness, the disease impact of vaccination programs, vaccine safety, the economic impact, ethical issues, communications and public opinion research; and (3) optimizing the use of antiviral and other therapeutic drugs for influenza, with a focus on novel therapeutics, the effectiveness of antivirals for treatment and prophylaxis, drug safety, drug resistance, economic impact, ethical issues, communications and public opinion research.

Results

Participants in the break-out sessions identified 20 research questions and 16 corresponding infrastructure/capacity gaps. During the closing plenary session, research questions were clustered into the 10 following research priority areas:

• Influenza virus characterization and ecology: studies on the basic science (virology, immunology, biology) of influenza viruses and the ecological relation between animal and human viruses; and more information concerning influenza subtypes to determine the nature and extent of animal reservoirs and the factors involved in viral modification and acquisition of virulence.

• Influenza virus transmission: enhanced understanding of the influenza virus shedding patterns of infected persons and the means of transmission to susceptible contacts.

• Public health preventive measures: better understanding of the effectiveness and safety of current public health interventions aimed at preventing infection in both the community and institutions, and of populations' reactions to influenza and influenza control measures.

• Improving rapid diagnostic test availability: research aimed at expanding the use of highly accurate and rapid diagnostic tests to guide the use of antiviral agents and improve assessments of disease burden and vaccine effectiveness.

• Clinical management of influenza patients: understanding the most effective ways to clinically manage and treat influenza patients, particularly the most ill.

• Development and optimal use of antiviral drugs: research aimed at the development and use of antivirals in the treatment of individuals with influenza and in the prevention of infection, including studies of novel approaches with existing antiviral medications and research aimed at the development and evaluation of new antiviral agents.

• Surge capacity of the health care system: research to ensure that the health care system is ready to respond quickly and effectively to increased demand brought on by pandemic and inter-pandemic influenza.

• More effective and acceptable influenza vaccines: more effective vaccines, using adjuvants and non-injection methods, must be developed using new technologies that trigger the immune system more readily and produce longer lasting protection and cross-protection.

• Immunization programs: differing vaccination programs across Canada provide a significant opportunity to evaluate various vaccination strategies to control influenza. Population- based data on the uptake, effectiveness and safety of influenza immunization is needed.

• Preparation for a pandemic vaccine: challenges involved in the preparation, testing and evaluation of a vaccine in the context of a pandemic are expected. Canada will be responsible for evaluating the pandemic vaccine produced by its domestic manufacturer.

Conclusions

In achieving consensus on 10 research priority areas of Canadian researchers and funding agencies, the Influenza Research Priorities Workshop, including its priority-setting methodology, proved to be a success. In addition to identifying national research priorities that will inform pandemic and inter-pandemic influenza prevention and control strategies, the Research Agenda is a valuable resource to guide investments and enable partners to mobilize around specific areas of research. PHAC and CIHR have used the recommendations from this meeting to inform research investment by the federal government. In May 2006, the federal government announced $1 billion for pandemic initiatives and, of this, more than $21.5 million will go to fund research activities. CIHR recently issued a Request for Applications relating to pandemic influenza preparedness, based on the results of the workshop.

The workshop process had some limitations, principally a lack of time to describe infrastructure gaps in detail and a tendency for participants to articulate research priorities in broader terms than would have been ideal. While participants appreciated the novel opportunity to meet other experts from a range of disciplines, the workshop was too brief to refine the priorities in the 10 research areas, encourage the development of new collaborations or begin planning specific proposals. Future priority-setting workshops would ideally allow more time for researchers to interact. Identifying new funding opportunities to pursue the identified priorities is always a challenge. In addition to federal funding considerations, other funding opportunities would ideally be identified shortly after such a consultation.

Planning Committee

Co-Chairs

David Scheifele
Director, Vaccine Evaluation Centre
Chair, Canadian Association for Immunization Research and Evaluation
British Columbia Children's Hospital

Theresa Tam
Associate Director
Immunization and Respiratory Infections Division
Public Health Agency of Canada

Members

Gordean Bjornson
Administrative Chair
Canadian Association for Immunization Research and Evaluation
Vaccine Evaluation Centre

Tim Booth
Director, Viral Diseases Division
Public Health Agency of Canada
National Laboratory for Viral Diagnostics

Michelle Gagnon
Assistant Director
Partnerships and Knowledge Translation
Institute of Health Services and Policy Research
Canadian Institutes of Health Research

Karen Grimsrud
Deputy Provincial Health Officer
Alberta Health and Wellness
Provincial Health Office

Greg Hammond
Director of Public Health
Public Health Branch
Manitoba Health

Mark Loeb
Associate Professor, McMaster University
Departments of Pathology and Molecular Medicine and Clinical
Epidemiology and Biostatistics
Michael G. De Groote Centre for Learning

Lisa Paddle
A/Head, Immunization Research
Immunization and Respiratory Infections Division
Public Health Agency of Canada

Carol Richardson
Manager, Programs and Evaluation
Institute of Infection and Immunity
Canadian Institutes of Health Research

Bhagirath Singh
Scientific Director
Institute of Infection and Immunity
Canadian Institutes of Health Research

Susan Tamblyn
Public Health Consultant

Secretariat

Laura Amos
Project Officer
Immunization and Respiratory Infections Division
Public Health Agency of Canada