Canada's Research Response to SARS

Outcome and Impact Assessment of Research Coordinated by Canadian Institutes of Health Research on behalf of the Canadian SARS Research Consortium

SARS Outcome and Impact Working Group

  • Carol Richardson, Co-chair
  • Laura McAuley, Co-chair
  • Bey Benhamadi
  • Gwendoline Malo
  • Stephen Rimac
  • Julie Senécal
  • Bruno Théorêt

Report written by Michelle French, Scientific Communication

Table of Contents

Executive Summary

This report summarizes the findings of an outcome and impact assessment of research on severe acute respiratory syndrome (SARS) that was coordinated by the Canadian Institutes of Health Research (CIHR) on behalf of the Canadian SARS Research Consortium (CSRC) from 2003-2010. The analysis allows CIHR to account for investments in SARS research, improves future strategic initiatives and illustrates the impact of scientific research.

SARS is a new respiratory disease that emerged in China in November 2002. It rapidly spread to several countries and circulated until mid 2003. Approximately 10% of individuals infected with SARS died, but the rate varied with age and was highest (50%) in those over 65. Worldwide, 774 individuals died from SARS including 43 in Canada. In addition to this health burden, the SARS outbreak negatively affected the economies in several countries including Canada. Canada's GDP fell by $3-6 billion (US), and growth decreased by 1%.

Given that SARS was a new infectious disease, research was urgently needed to develop diagnostic tests, treatments and methods to prevent disease transmission. This was an opportunity for the CIHR Institute of Infection and Immunity to respond by bringing together partners, mobilizing the SARS research community and coordinating national and international research efforts. Research was supported via strategic requests for applications and by CIHR open competition grants and awards. Since 2003, over $6 million has been invested in SARS research with almost a third allocated in the 2003-04 fiscal year.

To assess the outcomes and impacts of this funding, information was gathered and analysed by members of the CIHR Impact Assessment and Data Analysis Units, Knowledge Translation Portfolio, CIHR Institute of Infection and Immunity, and CIHR Institute of Population and Public Health. Several data sources were used including researcher surveys and publication and funding databases. Responses to surveys were received from 24 of 32 researchers. For the analysis, five broad health impact categories were considered: advancing knowledge, building capacity, informing decisions, health and health systems impacts and economic impacts.

The assessment showed that the results generated by the funded researchers had an impact in all five categories. The greatest contribution was in advancing knowledge, but the research also led to improvements in health-care and health systems and informed policy decisions. Economic impacts included one spin-off company, three patent applications and the attraction of additional funding to create 30 jobs in Canada. A brief summary of the outcomes and impacts in each of these categories is provided below.

Advancing Knowledge

Breakthroughs were made in several areas including outbreak control, treatment, health policy and antivirals. The new information was disseminated in over 100 publications and via over 300 conference presentations. In general, SARS-related articles were published in higher quality journals and were cited more frequently than the researcher's other publications. An example of this quality is the "Paper of the Year Award" for 2006 that was awarded to Dr. François Jean for his description of a novel antiviral agent for SARS by the journal Biological Chemistry. Other advancements include:

  • A new treatment protocol for SARS using the antiviral interferon-alpha that has been adopted by the WHO;
  • Greater understanding of the biology of the SARS virus that will guide the development of new antiviral drugs; and
  • Discovery that the antiviral agent ribovarin caused adverse reactions in SARS patients and did not improve outcome.

Building Capacity

Over 80 trainees from undergraduates to post-doctoral fellows were supported by the SARS funding, and of these, nine individuals went on to secure their own funding in related areas. Also, collaborations among researchers were enabled. Examples of capacity building include:

  • Development of a biobank of serum from SARS patients and the establishment of ethics procedures and protocols so that researchers from around the world could access specimens;
  • Creation of a research network in Canada, Taiwan and Thailand for the study of emerging viral respiratory diseases; and
  • Generation of new epidemiological modelling tools that led to new contacts with caregivers and patients from participating hospitals. These contacts can be used for new studies to analyse the spread of infectious disease.

Informing Decision-Making

Key stakeholders, such as health-care practitioners, professional organizations, health system managers and other researchers, were both aware of and were influenced by the research findings. In several cases, stakeholders were also involved in the research projects themselves, thereby accelerating the uptake of research results. Examples of informing decision-making include:

  • Identification of ethical issues that arose during the SARS outbreak such as health-care worker obligations, priority setting, public health measures and global governance that formed the basis of the development of an ethical framework for pandemic influenza. The framework was adapted by WHO and was incorporated into the pandemic preparedness plans in Canada, the United States, New Zealand and Europe.
  • Discovery that psychological distress in health-care workers in SARS-affected hospitals was lower in those who felt well trained and supported. This has informed pandemic preparedness planning by WHO, Canada and Australia.

Health and Health Systems Impacts

SARS research led to advances in the prevention, diagnosis and treatment of SARS and other infectious diseases, as well as improvements in health systems. Some of these discoveries, such as evidence that masks of any type prevent the transmission of SARS, were made during the SARS outbreak and helped to reduce disease spread and improve treatment. Other breakthroughs will be useful if SARS were to return or in future infectious disease outbreaks. Examples of each include:

  • Development of improved methods to detect the SARS virus and other respiratory viruses;
  • Discovery of SARS vaccine candidates and development of a cross-Canada vaccine strategy; and
  • Discovery of novel interferon mimics that are stable in storage and could be used in the future to treat SARS or other viral infections.

Economic Impacts

SARS research had significant economic impacts, including new tools and products, patent applications, direct cost savings and a spin-off company. Investigators developed new methods to screen for novel antiviral agents, identified a number of lead compounds with antiviral activity, developed new epidemiological modelling tools, and established a new diagnostic technology that has attracted multinational investment and resulted in 30 permanent jobs in Canada. Examples include:

  • Development of a high-throughput screening assay that was subsequently used to identify novel antiviral agents targeting hepatitis C. The hepatitis C market is estimated to exceed $8 billion in 2012.
  • Discovery and patenting of novel interferon mimics that are anticipated to have broad application as an antiviral drug for the treatment of several types of infectious disease.
  • Development of mathematical models to accurately predict outbreak spread and the efficacy of interventions.

In summary, as a result of the knowledge created, Canada and the rest of the world are better able to respond to future outbreaks of SARS or other infectious diseases. The knowledge created has broad applications in areas such as preventing and mitigating transmission of other infectious diseases, improving the public health and health-care responses to disease outbreaks, and for the development of new antiviral drugs.

In addition to the outcomes and impacts of the knowledge gained through the SARS-funded research, the SARS outbreaks had a profound effect on Canada's health-care and public health systems and on research funding organizations. Deficiencies in Canada's public health system that were revealed during the SARS outbreak have subsequently been addressed through the establishment of the Public Health Agency of Canada and the Ontario Agency for Health Protection and Promotion.

The experience of helping to coordinate a research response and fund critical research during the SARS outbreak was the first trial for CIHR in taking a proactive role to prepare for and respond to an infectious disease outbreak. In 2006, with the threat of a possible influenza pandemic, CIHR established the Pandemic Preparedness Strategic Research Initiative (PPSRI) to build and maintain capacity in pandemic preparedness and influenza research. Strategic research priorities were developed, linkages between researchers and knowledge users were fostered and novel funding approaches were established so that funds for outbreak research were available in a timely fashion.

The global spread of a new pandemic strain of influenza in 2009 illustrates the wisdom of this approach, and once again reminds us of the continuing need for research capacity, coordination of efforts, and linkages to enhance communication between researchers and those who will use the research knowledge.

In conclusion, this outcome and impact assessment demonstrates that investments in research, both targeted and through open grant competitions, enabled the research community to play a critical role in responding to infectious disease outbreaks. Thus, CIHR is fulfilling its mandate to "support the creation of new knowledge and its translation into improved health for Canadians, more effective health services and products, and a strengthened Canadian health-care system".


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Overview

CIHR recently studied the outcomes and impacts of research on SARS that was supported by CIHR and partners through strategic initiatives, open competition grants and training programs. A modified version of the CIHR Impact Assessment Framework, published in 20071, was used to structure this assessment. The framework is currently comprised of five broad categories, namely, advancing knowledge, building capacity, informing decision-making, health and health system impacts and economic impacts.

Information was gathered and analysed by a working group with members from the CIHR Impact Assessment and Data Analysis Units, Knowledge Translation Portfolio, the CIHR Institute of Infection and Immunity, as well as the CIHR Institute of Population and Public Health (see Appendix 1).

The analysis allows CIHR to account for its investments in the SARS initiative and enhances its decision-making for future strategic initiatives. It also helps to inform interested parties about the impact of scientific research. The purpose of this report is to summarize the findings of the analysis.

Emergence of the SARS Health Crisis

SARS emerged in China in November 2002 as a new respiratory disease with substantial morbidity and mortality. Individuals infected with SARS developed a fever followed by respiratory symptoms such as a cough, shortness of breath, difficulty breathing and other flu-like symptoms. About 10 to 20% of those affected required mechanical ventilation. The overall mortality rate from SARS was approximately 10%, but the rate varied with age and was highest (50%) in those above 65 years of age. It is now known that SARS is caused by a coronavirus (SARS-related coronavirus) that originated in wild Chinese horseshoe bats2 and is transmitted between humans by close contact.

By the spring of 2003, SARS had spread to several countries, with local transmission occurring in Canada, Vietnam and Singapore and subsequently in Mongolia and the Philippines. The first Canadian cases arose in individuals who had recently returned from Hong Kong. Subsequent cases were traced to those who had contact with the original cases or to others who had travelled to infected areas.

The World Health Organization (WHO) estimates that between November 2002 and July 2003, there were 8096 probable cases of SARS and 774 deaths worldwide. These numbers included 251 probable cases and 43 deaths in Canada. The SARS outbreak also had significant adverse economic impacts particularly in Canada, China, Hong Kong and Singapore3. For example, Canada's GDP is estimated to have dropped by $3.2 to $6.4 billion (US), and growth fell by 1%. See Figure 1 for a summary of key events during the outbreak.

Figure 1: Key SARS-related events from February to July 2003

Figure 1: Key SARS-related events from February to July 2003


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Response by CIHR and Partners

One of the roles of CIHR is to respond to Canadian health challenges and opportunities with appropriate and timely research programs4. Given that SARS was a new infectious disease affecting Canadians, research was urgently needed to develop diagnostic tests, methods to combat disease spread and treatments for infected individuals. CIHR answered this challenge and responded to the SARS outbreak by:

  • helping to coordinate national and international research efforts;
  • developing partnerships to enhance SARS research funding; and
  • funding SARS research.

The urgent nature of the health crisis prompted CIHR to develop innovative approaches to ensure that research was funded in a timely manner. The CIHR Institute of Infection and Immunity launched its first request for proposals on April 10, 2003, only a few weeks after the first SARS cases appeared in Canada. In less than three weeks, proposals had been peer reviewed and four projects were funded5.

Coordinating Research Efforts

The CIHR Institute of Infection and Immunity played a leadership role in developing a cohesive research program by establishing the Canadian SARS Research Consortium in June 2003 (Table 1). The Consortium was dedicated to maximizing the impact of Canada's resources for SARS research by developing and sustaining a national research agenda. Members of the Consortium also partnered with CIHR to fund strategic SARS research. Appendix 2 provides information about the organizational structure of the Consortium. A detailed report on the Consortium and an evaluation of its activities are available.

Table 1: Canadian Research Consortium Member Organizations

  • Canadian Lung Association
  • Canadian Network for Vaccines and Immunotherapeutics of Cancer and Chronic Viral Diseases
  • CIHR
  • Fonds de la recherche en santé du Québec
  • GlaxoSmithKline Inc.
  • Health Canada
  • Michael Smith Foundation for Health Research
  • Ontario Research and Development Challenge Fund
  • Protein Engineering Network of Centres of Excellence
  • Sanofi Pasteur Limited

Developing a Strategic SARS Research Agenda

Strategic SARS research areas were identified and developed by CIHR and funding partners both during and after the SARS outbreaks. The identified strategic areas were: diagnostics, vaccine development, therapeutics, epidemiology and databases, and public health and community impact.

To support SARS research in these research areas, CIHR and its partners announced four strategic requests for applications between April 2003 and April 2005 (Figure 2). Table 2 shows the title of each request for applications and its research focus. Some SARS research was also supported through CIHR open competition grants and awards.

Figure 2: Timeline of SARS research funding

Figure 2: Timeline of SARS research funding

Table 2: SARS Strategic Requests for Applications

Title Focus of research
SARS I: Host Response to Severe Acute Respiratory Syndrome (SARS) To support research investigating the causes and consequences of severe acute respiratory syndrome.
SARS II: Public Health and Health Care System Preparedness and Response to Severe Acute Respiratory Syndrome (SARS): Evaluation and Lessons Learned To support research projects examining and analyzing the recent public health and health-care system response to the SARS outbreak in Canada in the context of the global epidemic. Special emphasis is placed on ways to ensure that evidence-based practice, and cost-effective outbreak management strategies are utilized to the maximum extent possible in future outbreaks of this kind.
SARS III: Severe Acute Respiratory Syndrome (SARS) Small Molecule Pilot Project Grants Initiative To support pilot project research in the area of SARS biology and identification of small molecule targets as antiviral agents.
SARS IV: SARS Patient Material Collection and Database Project To develop a SARS sample bank and registry in response to requests for blood from convalescent patients.

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Investment in SARS Research

The strategic investment in SARS research by CIHR and partners, along with CIHR open competition grants and training awards, amounted to a total investment of over $6.6 million from 2003-04 until 2009-10 (Figure 3). Almost a third of the total funding for SARS research was invested during the 2003-04 fiscal year, demonstrating the rapid nature of CIHR's response to the SARS outbreak. As Figure 3 shows, funding through the SARS I, SARS II and SARS IV grants provided the initial stimulus for SARS research in 2003-04 and 2004-05, while grants awarded via open competitions were the main source of funding from 2005-06 until the present. Appendix 3 provides more detailed information about the SARS grants that have been funded.

Figure 3: Annual Open and Strategic Fiscal Investments in SARS research, 2003-04 to 2009-10

Figure 3: Annual Open and Strategic Fiscal Investments in SARS research, 2003-04 to 2009-10

Overall, the research supported by CIHR and partners encompassed all of the CIHR's themes6. This distribution shows that responding to the challenges of the SARS outbreak involved the full spectrum of the health research sectors. The success of this approach is in itself an outcome that is worth mentioning.

Figure 4: Number of grants and awards by CIHR program theme

Figure 4: Number of grants and awards by CIHR program theme


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Framework Used to Assess the Impact of CIHR-funded SARS Research

The evaluation of the impact of the CIHR SARS initiative was structured around the CIHR impact assessment framework. The framework, partly built on the well-known and recognized "Payback Model"7, facilitates the identification of areas where specific initiatives can be evaluated. The framework consists of five broad categories of impacts (Table 3).

Table 3: CIHR framework for measuring impacts of health research

Category Description
Advancing Knowledge Discoveries/breakthroughs and contributions to the scientific literature
Building Capacity Development and enhancement of research skills in individuals and teams
Informing Decision-Making Impacts of research in the areas of science, public, clinical and managerial decision-making, practice and policy
Health & Health System Impacts Advances in prevention, diagnosis, treatment and palliation, as well as advances in the way the system functions
Economic Impacts Commercialization of discoveries, direct cost savings and human capital gains

This assessment is the second stage of a two-part evaluation of the CIHR SARS research initiative. The first stage was an analysis of the activities of the Canadian Research Consortium that was established during the SARS outbreak under the leadership of CIHR. The first-stage evaluation helped to direct subsequent strategic initiatives including the Pandemic Preparedness Strategic Research Initiative (PPSRI).

Impact Assessment Data Sources

Several sources of information were used in the analysis, including a survey of funded researchers, researchers' CVs, research summaries, searches of publication and funding databases and media reports, the CSRC report and the CSRC evaluation report. Funded researchers were identified through a search of the CIHR database8 using the keywords "severe acute respiratory syndrome" and "SARS". A total of 33 grants (32 nominated principal investigators) were identified.

The nominated principal investigator for each grant was contacted by CIHR and asked to submit data on the outcomes of their SARS research. Specifically they were asked to:

  • complete a web-based survey to acquire information about the outcomes of their project (Appendix 4);
  • prepare a lay summary of their research project and results (Appendix 5); and
  • submit an up-to-date CV with publications and sections related to SARS funding highlighted.

A total of 24 out of 32 researchers answered the survey, submitted a lay summary and CV, while two other researchers submitted the lay summary and CV alone. See Appendix 6 for the submitted lay summaries. End-of-grant reports were also available from 24 of the 32 researchers. Because complete data from only three quarters of the researchers was available for analysis, it is likely that the SARS research had a greater impact than reported here.

In addition to information provided by researchers, bibliometric data extracted from the Thomson Reuters' Web of Science database was obtained through a contract with the Observatoire des sciences et des technologies (OST) located at the Université du Québec à Montréal (UQAM). The search was conducted using the nominated principal investigators' names with no restriction on the topic of the articles. Articles published by the 32 researchers between 1998 and 2007 were analysed. This time frame was selected to allow for analysis of both pre- and post-SARS publication activity. Papers that were related to SARS were subsequently manually identified.


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Outcomes and Impacts of SARS Research

The SARS research advanced knowledge, built capacity, informed decision-making and formed the basis of improved health-care and health systems. The greatest contribution was in the area of advancing knowledge, but the research also had an economic impact resulting in, for example, three patent applications and one spin-off company. The following sections highlight the outcomes and impacts in more detail.

Advancing Knowledge

During and after the SARS outbreaks there was an urgent need for knowledge on which to base health-care decisions and to prepare for future SARS or another infectious disease outbreak. New information in fields such as basic science, clinical medicine and public health was generated by the funded researchers. The research breakthroughs included advancements in outbreak control, mathematical modeling of infectious disease outbreaks, outbreak/pandemic ethics, host response to SARS, antivirals and diagnostics. The new knowledge was disseminated through peer-reviewed publications and presentations made at conferences and workshops.

Some examples of breakthroughs include:

  • Drs. James Dennis and Eleanor Fish devised a new treatment protocol for SARS infection using the antiviral agent interferon-alpha. The WHO and Centers for Disease Control and Prevention (CDC) have adopted the protocol, which will be used should another outbreak of SARS occur.
  • Dr. François Jean developed a high-throughput screening assay that was used to discover a novel antiviral agent from a library of marine-based compounds. The agent has antiviral properties in cells infected with the SARS virus. These results were published in Biological Chemistry and received the journal's "Paper of the Year Award" for 2006.
  • Dr. Michael James determined the structure and catalytic mechanism of action of SARS peptidase, which is needed for maturation of the virus in infected cells. This discovery will allow for the design of new inhibitors of the SARS virus.
  • Dr. William Jai used a high-density peptide array technique to identify binding regions of human antibodies to components of the SARS virus. Sera from SARS patients can be applied to the arrays for identification of antibody-binding regions. The binding information can be used for the better designed diagnostics and therapeutic agents.
  • Dr. Chengsheng Zhang identified critical regions on a SARS viral surface protein that are needed for entry of the virus into cells, thereby, identifying new molecular targets for the development of novel therapeutic strategies and preventive vaccines for SARS.
  • Dr. Matthew Muller and his supervisor, Dr. Allison McGeer, discovered that treatment of SARS patients with high intravenous doses of the antiviral ribavarin caused novel adverse reactions, and furthermore, did not improve patient outcome. This knowledge will be valuable in planning treatment strategies for future SARS patients.
  • Dr. Therese Stukel determined that health officials took appropriate actions to control the spread of SARS and such measures can be used by policy makers and hospital administrators in future pandemics without jeopardizing essential care.

Analysis of the 67 SARS-related articles identified in the bibliometric database9 indicated that the researchers began publishing SARS-related articles in 2003 – the year that SARS emerged (Table 4). A similar proportion of primary articles and review articles related or unrelated to SARS were published by the researchers, although there was an increase in SARS-related review articles in comparison to SARS-related primary articles after 2006 (data not shown).

Table 4: Number of articles published by nominated principal investigators

Publication topic Year of publication
1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Total
SARS-related 0 0 0 0 0 7 10 18 17 15 67
Unrelated to SARS 71 90 105 94 78 111 81 131 113 121 965
Total 71 90 105 94 78 118 91 149 130 136 1032

More than half of all of the articles published appeared in clinical medicine journals and a further one third were published in biomedical research journals (Table 5), reflecting the expertise of the funded researchers. These trends were similar for SARS-related publications alone with the exception that a higher percentage of these publications were in journals in the field of health (SARS: 16.4% vs non-SARS: 7.9%). This reflects an increase in articles in the fields of public health, health policy and health services by researchers who might otherwise have published more often in biomedical research and clinical medicine journals.

Table 5: Research fields in which the researchers publisheda

Research field of journal Unrelated to SARS
(% total)		 SARS-related
(% of total)		 All
(% of total)
Biomedical research 33.4 31.3 33.2
Clinical medicine 52.8 49.3 52.5
Healthb 7.9 16.4 8.5
Otherc 5.9 3.0 5.8

a Includes publications from 1998 to 2007.
b Public Health, Health Policy & Services, Social Sciences and Biomedical, Geriatrics & Gerontology, Rehabilitation, and Nursing.
c Arts, Biology, Chemistry, Earth and Space, Engineering and Technology, Humanities Professional Fields, and Psychology.

The publications collected by OST were analysed to assess statistical differences in both the number of citations received and the impact factor of journals in which the SARS articles were published in comparison to the articles unrelated to SARS (see Appendix 7 for the results of the statistical analysis). When all of the SARS-related articles and all of the SARS-unrelated articles were compared, no significant differences were observed in the total number of citations received or in the quality (impact factor) of the journals in which the articles were published. However, when sub-analysis of the SARS-related and unrelated publications was performed in order to account for different citation practices, the SARS-related publications had a statistically significant greater number of citations (SARS: 3.3; non-SARS: 1.6; p = 0.00). Also, there was a significantly greater number of citations of the SARS-related articles in the first two years following publication, when adjusted for the average citations received by articles in the same subfield (SARS: 4.0; non-SARS: 1.7; p = 0.00). These results indicate that SARS-related articles were being cited significantly more often than those articles from the same authors that were unrelated to SARS.

Thus, an impact of SARS research funding was the production and advancement of important and useful knowledge. Also, funding for SARS research provided an opportunity for researchers to publish articles that were significantly more frequently cited than their other publications, demonstrating the scientific importance of the findings.


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Building Capacity

An objective of the SARS initiative was to build research capacity by training the next generation of researchers through both grants and training awards. Trainees at all academic levels, from undergraduates to post-doctoral fellows, were supported by the research grants (Table 6). In total, 78 trainees were supported, and of these, nine individuals went on to receive their own funding in the same area of research as a result of their association with the initial grants. In addition to this support, CIHR directly funded an additional five trainees engaged in SARS research through training awards (see Appendix 3 for successful applicants).

Table 6: Individuals trained under SARS research grantsa

Trainee type Number
Post-doctoral trainees 21
Doctoral students 19
Masters students 18
Undergraduate students 20

a Numbers based on survey responses of SARS-funded researchers (see Appendix 4 for survey questions).

Capacity to do research was enhanced through processes and procedures developed by Dr. Mark Loeb to make serum from SARS patients available to researchers around the world. Specifically, specimens were taken from health-care workers in Toronto who developed SARS and were stored at the Public Health Agency of Canada (PHAC) laboratories. Ethics procedures and a process whereby researchers could request specimens were implemented. The procedures can be used for the development of future biobanks. This is important because lack of access to clinical specimens often impedes research during infectious disease outbreaks.

Another way of developing capacity is by increasing the expertise available for research through collaborations. Two thirds of researchers (16/24) indicated that their projects involved national and/or international collaborations. These included collaborations with other researchers in Canada and in other countries and with representatives of biotechnology companies, multinational diagnostic companies and international organizations such as WHO and the Pan American Health Organization. Through collaboration and cooperation, funded researchers were able to attain their goals more efficiently, while the sharing of knowledge and expertise opened new avenues for research and development, accelerated the research process and helped to leverage more research funding.

The SARS initiative also provided an opportunity to increase capacity by developing new collaborations between researchers who received CIHR SARS funding, as witnessed through a number of jointly published articles. Fourteen of the 67 SARS-related articles identified in the bibliometric database included authors who were principal investigators on other SARS grants. As might be expected, some of these (four) were published by nominated principal investigators who were co-applicants on each other's grants. Eight of the 14 articles, however, were by nominated principal investigators who were not co-applicants on each other's grants. The remaining two of the 14 articles had both types of authors: co-applicants and non-co-applicants. Considering that the number of nominated principal investigators was limited to 32 researchers, this shows that more than a quarter of the researchers made connections that were developed and/or nurtured by the SARS-related funding and that these connections led to strong research linkages and to co-authorship of published articles.

Specific examples of capacity building include:

  • Dr. Michel Bergeron reported that his grant intensified collaboration with Dr. Guy Boivin at Laval University. The expertise that was developed was critical in obtaining other grants and research contracts.
  • Dr. Robert Anderson established a research network centered in Canada, Taiwan and Thailand in order to focus collective expertise on emerging viral respiratory diseases.
  • Dr. Babak Pourbohloul reported that his project to develop new epidemiological modelling tools resulted in the collection of a unique set of contact data within and between caregivers and patients from participating hospitals that can be used for new studies to analyze the spread of infections in hospital settings.
  • Dr. Danuta Skowronski and her colleagues established a cross-Canada scientific collaborative to develop the scientific and policy basis of a public health-driven SARS vaccine strategy.

Informing Decision-Making

Informing decision-making can take different forms including contributing to subsequent research; developing new research methods, theories, practices, products or tools; influencing public policies, health system services, health practice, program development; or changing the behaviour of individuals.

One way of informing decision-making is through publications and presentations. Researchers reported that their results were communicated to specialized audiences through publication of approximately 103 articles10 in scholarly journals (See Appendix 8 for the SARS-related articles published or in press that were listed in the researchers' CVs). Furthermore, a total of 343 presentations of results were made by the researchers at conferences and workshops.

As previously discussed, the researchers published more frequently than usual in clinical medicine journals, thereby, increasing the potential to inform decision-making at the clinical practice level. Also, their publications were cited significantly more often than their articles that were unrelated to SARS, when adjusted for the average number of citations received in the same subfield (see the "Advancing Knowledge" section of this report for details).

To enhance the impact of research on end-users, researchers can involve stakeholders at different stages of the research process. This ensures that the research is tailored to the needs of the decision-makers and their involvement improves the uptake of results by health-care practitioners and health system managers. Stakeholders were widely involved at different stages of the 24 research projects (Table 7). Not only were other researchers (non-grantees) involved in the research projects, but health-care practitioners and managers, professional organizations and federal and provincial governments were also engaged at different stages, culminating in the diffusion of results to a large portion of potential stakeholders.

Table 7: Involvement of stakeholders in supporting research and translating resultsa

Stakeholder Implementation of grant Interpretation of results Diffusion of results
Researchers (non-grantees) 7 8 11
Health-care practitioners 3 5 6
Professional organizations 2 3 6
Health system managers 2 3 4
Federal government 1 1 1
Provincial/Territorial governments 1 3 4
Municipal governments 0 0 0
Community groups 0 0 2
Voluntary health organizations/Charities 0 0 1
Industry/For profit sector 1 1 1
Media 0 0 2

a Number of projects for which stakeholders made contributions in creating and disseminating research results.


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Many individuals and organizations were perceived by the researchers to be aware of the findings, including other researchers, health-care practitioners, professional organizations, the media, health system managers and the federal and provincial governments, even though they were not directly involved in the research process. Also, an even greater number of stakeholders were perceived by the researchers to be interested in the research results, indicating that the diffusion of the research results to stakeholders may be continuing.

Table 8: Stakeholder interest in the research resultsa

Stakeholder Aware of findings Interested in findings
Researchers (non-grantees) 14 17
Health-care practitioners 10 15
Professional organizations 11 11
Health system managers 9 11
Federal government 5 11
Provincial/Territorial governments 6 10
Municipal governments 3 5
Patients 4 7
Community groups 3 8
Voluntary health organizations/Charities 2 4
Industry/For profit sector 7 11
Media 9 12

a Number of projects for which researchers reported stakeholders were aware of and/or interested in research findings.

Researchers also perceived that a large portion of potential stakeholders were influenced by their research results indicating that their results had already had an impact in the areas of science, public, clinical and managerial decision-making, practice and policy (Table 9).

Table 9: Uptake of research resultsa

Stakeholder Influenced by results
Researchers (non-grantees) 13
Health-care practitioners 8
Professional organizations 8
Health system managers 6
Federal government 4
Provincial/Territorial governments 5
Municipal governments 3
Patients 2
Community groups 3
Voluntary health organizations/Charities 3
Industry/For profit sector 3
Media 2

a Number of researchers who stated that the indicated stakeholders would be influenced by their research results.

Specific examples of how research results have informed decision-making include:

  • Dr. Robert Maunder, who studied the long-term psychological consequences of the SARS outbreak in Canadian health-care workers, found that workers in SARS-affected hospitals experienced higher levels of professional burnout and psychological distress following the SARS outbreaks. The distress was greater in health-care workers who felt isolated and was lower in those who felt well trained and supported. Dr. Maunder has widely communicated these findings, which have been incorporated into pandemic planning in Canada and Australia and at the WHO.
  • Dr. Ross Upshur identified ethical issues during the SARS outbreaks that they used to develop an ethical framework for pandemic influenza that addresses health-care worker obligations, priority setting, public health measures and global governance. The framework was adapted by the WHO in its guidance to member states and has been incorporated into pandemic plans in Canada, the United States, New Zealand and Europe.
  • Ms. Catherine Tansey with her supervisors Drs. Margaret Herridge and James Lavery have developed a new model for research ethics review during public emergencies that incorporates elements of special scrutiny and expedited, proportionate review. The new model will assist research ethics boards to improve the research approval process in times of outbreaks and pandemics.

Health and Health System Impacts

One immediate and direct impact of SARS research on the health system has been the realization that even though Canada had expertise and the know-how to prepare its health system for such a crisis, it should have been better prepared to deal with the outbreak.

SARS research has also led to advances in the prevention, diagnosis and treatment of SARS and other infectious diseases, as well as advances in health systems. One third of the researchers stated that health-care practitioners and professional organizations would be influenced by their research findings, and one quarter said that their findings would influence health systems managers in the event of a similar outbreak (Tables 8 and 9).

Other evidence for the impact of the research on health and health systems comes from analysis of the summaries of the research projects. At least 14 of the 24 summaries describe research results that have had or will have impacts on health and health systems.

Examples include:

  • During the SARS outbreak, the research conducted by Dr. Mark Loeb and collaborators led to improved methods to detect the SARS virus in patient samples, methods to predict which SARS patients would have poor outcomes, and to the conclusion that masks of any type significantly reduce the spread of SARS.
  • The research results from Drs. James Dennis and Eleanor Fish on the effectiveness of interferon-alpha in treating SARS formed the basis of subsequent research by Dr. Fish, who has identified interferon mimics. These mimics could be used in the future to treat several types of viral infection and which, unlike interferon, are stable when stored for long periods of time.
  • Dr. Stephen Hwang determined that despite a period of intense clinical service restrictions during the SARS outbreak, there was no significant change in population mortality rates compared with corresponding periods in previous years.
  • Drs. Michel Bergeron and Guy Boivin developed better diagnostic tools to detect the SARS coronavirus, along with other respiratory viruses.
  • Dr. Danuta Skowronski and her team identified several SARS vaccine candidates and developed vaccine evaluation capacity.

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Economic Impacts

A direct economic impact derived from the knowledge created and accumulated through SARS research is the cost savings related to experiencing a serious epidemic and having learned from it. In addition, while it can take longer for the economic impacts of research to be realized, there is evidence that the SARS research is, or will in the future, produce benefits in the areas of commercialization of discoveries, direct cost savings, and human capital gains. For example, ten researchers reported that their work led to new tools or products, three filed patent applications, three stated that their results led to direct cost savings and one has established a spin-off company (Table 10).

Table 10: Economic outcomes and impactsa

Outcome/Impact Yes May in future
New tools or products 10 5
New database/software 6 3
New patent 3 4
New product license 0 7
Marketing of a product 0 7
Spin-off company 1 3
Intellectual property claim 4 3
Direct cost savings 3 6

a Number of respondents who indicated that their research projects have had, or may in the future have, the indicated economic outcomes and impacts.

The Severe Acute Respiratory Syndrome (SARS) Small Molecule Pilot Project Grants Initiative (SARS III) projects have led to the development of new methods to screen for antiviral agents and to the discovery of a number of lead compounds with antiviral activity that could have both health and economic impacts. Examples include:

  • Dr. Eleanor Fish has designed and synthesized small compounds that behave as interferon mimics based on her research with Dr. James Dennis demonstrating the effectiveness of interferon-alpha for the treatment of SARS. These small compounds cost less to develop, manufacture and administer, and have a longer shelf-life in comparison to conventional interferons and other recombinant proteins. Dr. Fish has protected the intellectual property surrounding this approach and anticipates that an interferon mimetic will have broad application as an antiviral drug against many different viruses.
  • Dr. Jian Hui Wu has identified three anti-SARS agents and has developed an algorithm that can be used to rapidly evaluate the effect of the point mutations in the viral genome and for the design of novel chemical compounds against the mutants.
  • Dr. James Mahoney has developed a high-throughput method to screen for compounds that inhibit viral entry into host cells and used this approach to identify an anti-SARS agent.
  • The high-throughput screening assay that Dr. François Jean developed to identify a novel anti-SARS viral agent has subsequently been adapted and used in the discovery of novel protease inhibitors of the hepatitis C virus. It is estimated that 250,000 Canadians are currently infected with hepatitis C, which can lead to serious health effects including liver failure. Mirroring the remarkable transformation that protease inhibitors have had on the HIV market, by 2012 the hepatitis C market is anticipated to exceed $8 billion, and hepatitis C protease inhibitors will have applications in more than 20% of hepatitis C patients.

Other examples of research results that have had economic impact include:

  • Dr. Michel Bergeron reported that the expertise in diagnostics that he and colleagues developed during the sars outbreaks attracted the interest of multinational companies who invested in the technology, and have, along with additional funds from other grants, created 30 permanent jobs in canada. in addition, a new type of dna chip on plastic was invented that will have application in future diagnostic tools.
  • Dr. Babak Pourbohloul developed new risk assessment epidemiological modelling tools for containing disease spread in specific settings such as urban areas and hospitals nationwide. the model allows one to predict the fate of an outbreak and the efficacy of various interventions. the models are being developed further for influenza pandemic preparedness planning. being able to accurately predict outbreak spread will be essential in reducing not only the health burden, but also the economic burden, of infectious disease outbreaks by identifying the most cost-effective prevention strategies.

Researchers stated that their results often formed the basis of subsequent successful grant applications, thereby, helping to keep research, training and jobs in Canada. For example:

  • Dr. Michel Bergeron received a Genome Canada grant for further research on diagnostics.
  • Dr. Annalee Yassi and her colleagues received a grant from WorkSafeBC to support research to understand the determinants of an appropriate respiratory protection program. The group's results also led to a Pan American Health Organization (PAHO)-funded project focused on promoting healthy hospitals in Ecuador. The results also formed the basis of an international workshop promoting infection control for health-care workers in rural and remote areas and developing countries; spawned important initiatives across Vancouver Coastal Health, and led to further grants (from CIHR, Canadian Government Foreign Affairs and PAHO) to create innovative tools that have since been employed to promote occupational health and infection control across Latin America and the Caribbean.
  • Dr. François Jean received a CIHR grant to identify and develop a new class of anti-hepatitis C viral agents.

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Lessons Learned and Planning for the Future

The SARS outbreak had a major impact on Canada's health-care and public health systems and on research funding organizations, including CIHR. For example, deficiencies in the public health system were exposed particularly by the media during the SARS outbreak, prompting a review11, and the subsequent establishment of the Public Health Agency of Canada (PHAC) in 2004 and Ontario Agency for Health Protection and Promotion in 2007. These agencies will enhance Canada's ability to coordinate public health responses to future outbreaks and pandemics.

At the start of the SARS outbreak, CIHR had no mechanism in place to fund emergency research; the typical funding cycle from the launch of a request for applications to funding of peer-reviewed research projects was over a year. During the SARS outbreak, CIHR developed an expedited application and review process reducing this time to less than two months. More recently, CIHR developed new funding approaches to support the research community in its preparation for research to be performed during an infectious disease outbreak or pandemic. These novel approaches have ensured that funds for outbreak research were available in a timely fashion during the H1N1 influenza pandemic of 2009 and are recognizable and significant outcomes of the CIHR SARS research initiative.

The SARS outbreak also highlighted that a rapid research response to infectious disease outbreaks requires established researchers who have the expertise, infrastructure and tools to carry out essential studies. Thus, there is a continuing need to maintain research capacity. Also, to avoid duplication and speed the uptake of research results, it is critical to have pre-established linkages between researchers and those who will use the research knowledge. Public health organizations, health-care systems, researchers, governments, and other local, national and international organizations must be poised to act together.

This need for capacity, linkages and communication, and the threat of an impending influenza pandemic, directly spurred the development of the CIHR Institute of Infection and Immunity-led PPSRI in 2006. Through this initiative, strategic priorities in pandemic preparedness and influenza research have been identified, over 150 researchers have been supported or trained, research efforts are being coordinated and research is underway. As well, strong linkages have been established with PHAC. In 2009, PPSRI intensified its efforts in response to the global spread of a new pandemic strain of H1N1 influenza. Through the Initiative, research priorities have been refined through consultation, essential research projects have been funded and communication and linkages have been facilitated. The enhanced research capacity and pandemic readiness generated by PPSRI is a direct response to the challenges in mounting a research response to SARS during the outbreak.

Conclusion

The outcomes and impacts described in this report indicate that SARS research supported by strategic and open grants had a significant positive impact on research capacity, public policy, health-care and health systems, and the economy. High-quality articles advancing knowledge were published, researchers were trained and international linkages were fostered. New public health policies were established including an ethics framework for pandemic preparedness that was adopted by the WHO. The efficacy of interferon-alpha treatment for SARS was demonstrated and new guidelines for SARS treatment and prevention of transmission were established. New diagnostic methods were discovered and are now being used for the development of diagnostic tests for other viral diseases. Several candidate antiviral agents with broad efficacy and potential to be developed into therapeutic drugs have been identified. The research results have also stimulated further research in the areas of public health and pandemic preparedness.

The knowledge created by the SARS funding, together with new strategic CIHR initiatives that were driven by the SARS experience, have made Canada and the rest of the world better able to respond to infectious disease outbreaks. The research results have broad applications in areas such as preventing and mitigating transmission of infectious diseases, improving public health and health-care responses to outbreaks, and for the development of new antiviral drugs. Thus, CIHR is fulfilling its mandate to "support the creation of new knowledge and its translation into improved health for Canadians, more effective health services and products, and a strengthened Canadian health-care system".


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Notes

  1. A Framework to Measure the Impacts of Investments in Health Research
    by Alan Bernstein, Vern Hicks, Peggy Borbey, Terry Campbell, Laura McAuley and Ian D. Graham in Science, Technology and Innovation Indicators in a Changing World: Responding to Policy Needs, September 2007, ISBN 978-92-64-03966-7. The framework categories have undergone several iterations since 2007 based on consultation and discussion with stakeholders.
  2. Lau SKP, Woo PCY, Li KSM, Huang Y, Tsoi H-W, Wong BHL, Wong SSY, Leung S-Y, Chan K-H, Yuen K-Y. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc Natl Acad Sci U S A. 2005; 102:14040-14045.
  3. Keogh-Brown MR and Smith RD. The economic impact of SARS: How does the reality match the predictions? Health Policy 2008;88:110-120.
  4. CIHR Mission Statement, CIHR.
  5. Singh B. Innovation and challenges in funding rapid research responses to emerging infectious diseases: Lessons learned from the outbreak of severe acute respiratory syndrome. Can J Dis Med Microbiol 2004;15:167-170.
  6. The theme was identified by the researchers and validated by the SARS Outcomes and Impact Evaluation Working Group through analysis of research project summaries.
  7. Buxton MJ, Hanney S (1994) Assessing Payback from Department of Health Research and Development: Preliminary Report. Vol 1: The Main Report, HERG Research Report No 19.
  8. CIHR "Grants Applicants and Committee Records" - Information Bank # CIHR PPU 005
  9. The number of SARS-related papers published by the nominated principal investigators is actually higher than 67 because some papers were published after 2007, the cut-off date of the bibliometric study. Other papers, not accounted for in the collected data for the bibliometric study, were produced by associated principal investigators who did not list a nominated principal investigator as a co-author, and some were published under a group name. Others were published in non- refereed journals, or were not listed in the database.
  10. This list also includes some papers submitted to non-referred journals as well as 2008-09 published or in press publications.
  11. National Advisory Committee on SARS and Public Health. Lessons from SARS: Renewal of Public Health in Canada. 2003.