Memorandum submitted by the Wellcome Trust
(SAGE 35)
INTRODUCTION
1. The Wellcome Trust is a global charity dedicated
to achieving extraordinary improvements in human and animal health.
We support the brightest minds in biomedical research and the
medical humanities. Our breadth of support includes public engagement,
education and the application of research to improve health. We
are independent of both political and commercial interests.
2. It is vital that policy makers and practitioners
can access robust scientific evidence to ensure appropriate preparation
and effective responses to public health emergencies. The Trust
therefore welcomes the Select Committee's inquiry on "Scientific
advice and evidence in emergencies".
3. Given the Trust's remit, our response is
focused on the 2009 H1N1 flu pandemic case study, and the importance
of research and scientific evidence in informing and strengthening
the public health response in an infectious disease outbreak.
Key issues that we discuss include:
— the importance of strategic co-ordination
between Government departments, public bodies, private bodies
and the research community to ensure a timely and rapid response
to the H1N1 pandemic;
— the need to address regulatory issues
to facilitate research that can inform policy during a pandemic
and infectious disease outbreak;
— the importance of international co-ordination
to enable effective preparedness and response to global diseases
such as the H1N1 pandemic; and
— the need to enhance pandemic preparedness,
by maintaining key skills and research programmes during the inter-pandemic
period.
4. Emerging and re-emerging infectious diseases,
such as influenza, carry an immense and growing global health
burden. It is important therefore to learn from the H1N1 pandemic
and continue to support research that will strengthen evidence-based
policies and healthcare practices.
STRATEGIC CO
-ORDINATION BETWEEN
GOVERNMENT DEPARTMENTS,
PUBLIC BODIES,
PRIVATE BODIES
AND RESEARCH COMMUNITY
5. The Department of Health played a central
role in co-ordinating the UK's response to the 2009 H1N1 pandemic,
by providing timely advice, co-ordinating with UK and international
partners and directly supporting research in the area.
6. The Health Protection Agency (HPA) also played
a pivotal role in the rapid co-ordination of the public health
management of the 2009 H1N1 flu pandemic. It conducted a number
of important virology and epidemiologic surveillance studies and
supported work for the vaccine studies (including facilitating
private-public partnership). Indeed, the regional H1N1 flu response
centres set up by the HPA in collaboration with the NHS during
the containment phase of the H1N1 pandemic, were recently recognised
by a Cabinet Office Innovation in Resilience Award at the Emergency
Planning Society Awards
7. It is crucial that these important functions
of the HPA, which enabled it to mount a rapid and effective public
health response to the H1N1 pandemic, are not lost under the Government's
proposed plans to disband HPA and transfer its functions to the
Secretary of State as part of the new Public Health Service.
8. It was also important that the research community
was able to respond quickly to the pandemic, working together
with Government to conduct new research to inform policy-making
and to provide valuable evidence about the effectiveness of potential
interventions. This was achieved in response to the 2009 H1N1
pandemic. The Wellcome Trust and other UK partners, including
the Medical Research Council (MRC) and Department of Health, rapidly
convened meetings of the clinical research community (in May 2009)
and the veterinary research community (in June 2009) to identify
and develop new or enhanced research responses to the pandemic.
In a short time-frame, the funders fast-tracked applications using
existing robust processes (which the Trust had previously used
in response to the Avian flu outbreak in 2005), to enable a rapid
initiation of key research projects. In addition, to circumvent
potential delays caused by recruitment issues, the funders also
agreed to be flexible in deploying skilled clinical and research
staff from other grants to the newly funded H1N1 pandemic research
projects.
9. Three UK studies were funded through this
fast-track process in 2009 following recommendations from the
two meetings:
— The Mechanism of Severe Acute Influenza
Consortium (MOSAIC) —Led by Peter Openshaw, a wide-ranging
multi-centre study of influenza pathogenesis in patients hospitalised
with severe H1N1 disease during the pandemic, funded by the MRC
and Wellcome Trust. This study built on the existing work of the
Centre for Respiratory Infection at Imperial College London to
study pathogenesis of respiratory viral diseases and to enhance
pandemic preparedness and response.
— FluWatch surveillance programme—Led
by Andrew Hayward, a large collaborative, community-based cohort
study of national households, examining epidemiology, severity,
treatment and vaccination strategies of influenza. Jointly funded
by the Wellcome Trust and MRC, it is the largest study of its
type. This programme builds on an existing study funded initially
by the MRC in 2006.
— The Combating Swine Influenza Initiative
(COSI) —Two inter-linked studies led by Ian Brown and
James Wood, to monitor and compare the evolution, transmission,
infection dynamics and immunopathology of H1N1 in pigs and humans
jointly funded by the BBSRC, DEFRA and Wellcome Trust.
10. These studies are still being conducted
in the post-pandemic period. The initial results are currently
being analysed and can be reported to the Select Committee in
due course, if it would be helpful. Community-based surveillance
programmes such as FluWatch are not only valuable for providing
crucial data on transmission patterns but can also serve as a
platform for large-scale public-health intervention studies (eg
hygiene measures and face masks). For example, preliminary analyses
in the FluWatch study indicate that frequent hand washing reduced
the risk of acquiring influenza infection, a finding that should
inform the advice given regarding risk reduction. The hospital-based
cohort is anticipated to provide invaluable data regarding the
viral and host factors associated with progression to severe influenza
and eventually lead to studies of new interventions that might
reduce the risks of complications and fatal outcomes. Furthermore,
a better understanding of the animal-human interface of zoonotic
influenza will help reduce the risks of zoonotic infections that
might lead to new influenza outbreaks, reduce transmission of
influenza between household members, and improve care of those
infected and help inform surveillance and reporting procedures.
11. Unfortunately, the MOSAIC and FluWatch studies
could not be completed in time to inform the response strategies
for the H1N1 pandemic due to regulatory hurdles (see below, paragraphs
12-15). However, the findings from all three studies will be invaluable
in informing the strategies and policies for the next influenza
pandemic and strengthen the UK's preparedness and capacity to
respond effectively to the next influenza pandemic and to seasonal
epidemics.
OBSTACLES TO
CONDUCTING RESEARCH
TO INFORM
POLICY DURING
THE PANDEMIC
12. While the research community and funders
were able to respond rapidly during the first wave of the pandemic,
both the MOSAIC and FluWatch studies were unable to roll-out their
studies in a timely manner during the autumn wave of the pandemic
due to unnecessary delays in gaining regulatory approval.
13. The MOSAIC group were delayed primarily
by the multiple and disparate NHS Research and Development (R&D)
approval processes at the various hospitals involved in the study.
In one instance it took eight months to secure R&D approval
from a participating hospital. Similarly, the FluWatch study was
delayed in rolling-out its large scale community study by the
R&D approval process for recruiting subjects through multiple
primary care sites, with applications taking over a month to be
approved. Consequently, the researchers (especially MOSAIC) missed
the peak in cases, which hampered recruitment of a sufficient
number of subjects.
14. In order to effectively respond to outbreaks
of infectious disease and pandemics such as the H1N1 pandemic,
it is crucial that there are appropriate mechanisms in place that
are capable of "fast-tracking" approvals to facilitate
research in the context of public health emergencies. We note
that, for the flu vaccine trials, it was possible to fast-track
approvals to allow these trials to progress in a timely manner.
15. There are increasing concerns that regulatory
burdens and unnecessary red tape are significantly delaying biomedical
research in the UK, and the Government has commissioned the Academy
of Medical Sciences (AMS) to undertake an independent review of
these issues to inform future policy. In our response[9]
to the AMS call for evidence we highlight concerns from researchers
that NHS R&D offices as the single biggest barrier to medical
research. There is an urgent need for R&D offices to be made
more efficient and harmonised, and for rationalisation of multiple
layers of approvals and bureaucracy. The proposals to introduce
a single research regulator provide a real opportunity to simplify
and streamline the approvals process. We strongly urge the Government
to ensure that any new governance framework facilitates research,
and includes appropriate mechanisms to enable a fast response
in a public health emergency situation.
16. At a Satellite workshop meeting at the Pacific
Health Summit 2010 hosted by the Wellcome Trust Influenza Research
team, researchers also suggested a system whereby there was ethics
pre-approval of projects and pre-positioning of generic protocols
at qualified sites as a way to reduce delays in the event of a
pandemic or novel outbreak. This would be worth exploring in more
detail. Establishing a network to study severe acute respiratory
infection was also suggested as a way forward to help overcome
regulatory hurdles. Such a network could also provide an established
research platform that could address relevant research questions
in the inter-pandemic period and be rapidly scaled up during a
future influenza pandemic (also see paragraphs 22-24 on preparedness).
17. In addition, FluWatch faced significant
delays recruiting appropriately qualified research staff, with
international expertise often crucial. We are concerned that the
current visa restrictions brought in early 2010 by the Labour
Government and the proposed restrictions on Tier One and Two visa
criteria would prevent or significantly delay the timely recruitment
of talented and highly skilled researchers from non-EU countries
that would be needed to carry out urgent research during a future
pandemic or infectious disease outbreak.
INTERNATIONAL CO
-ORDINATION AND
RESEARCH
18. Infectious diseases such as influenza are
global threats that the international community must work together
to address. An effective response requires a co-ordinated global
approach. With the H1N1 pandemic, this was effectively led by
the World Health Organisation (WHO), with local support from member
countries.
19. Effective communication and rapid sharing
of information, as achieved in the UK, are an integral part of
international co-ordination and key for an effective global response.
These key factors are particularly important in the complex and
challenging pandemic setting in which there is usually a limited
time-frame to mount an effective response.
20. On the research front, the Trust was an
active partner with WHO on the development of the WHO Public Health
Research Agenda for Influenza,[10]
on a range of influenza vaccine-related activities[11]
and on meetings related to clinical aspects and management of
pandemic H1N1 patients.[12]
A summary of the Trust's full range of activities can be found
at www.wellcome.ac.uk/influenza.
21. The South East Asia Infectious Disease Clinical
Research Network (SEAICRN) is an international and collaborative
partnership of hospitals and research institutions in Thailand,
Vietnam, Indonesia and Singapore, with technical and administrative
support provided by the Centre for Tropical Medicine, University
of Oxford. Formed in September 2005 and funded by the US National
Institutes of Health's National Institute of Allergy and Infectious
Diseases and the Wellcome Trust, SEAICRN focuses on clinical research
on human and avian influenza and other infectious diseases of
public health importance in the South East Asia region. The network
is key for preparedness, providing a clinical monitoring system
in a region where new infectious diseases can emerge and serving
as a clinical research platform to respond to new threats. Further
examples of some of the international influenza-related projects
funded by the Trust are provided below.
INFLUENZA-RELATED
RESEARCH IN
THE TRUST'S
MAJOR OVERSEAS
PROGRAMMES IN
AFRICA AND
ASIA
— Studies of severe pneumonia and respiratory
viruses at hospital and community level in Kenya (led by James
Nokes).
— Hospital-based surveillance for
influenza in an African population with a high burden of HIV,
malaria and malnutrition in Malawi (led by Rob Heyderman).
— A range of clinical research on serious
human, including H1N1, and avian influenza and other infectious
diseases of public health importance in the South East Asian region
(through the SEAICRN).
ENHANCING PANDEMIC
PREPAREDNESS AND
SEASONAL RESPONSE
22. While the H1N1 pandemic is now over, the
virus is still circulating and the long-term threat of a future
influenza pandemic remains high. In addition, the annual toll
of seasonal influenza outbreaks continues. The UK is already considered
to be one of the best prepared countries in the world for a new
pandemic, as recognised by WHO. The UK must maintain this status
as well as enhance its responses to seasonal influenza and other
respiratory illnesses.
23. Effective preparedness and response is dependent
on a number of essential factors, in particular:
— Having a surveillance system in place
to monitor changes in influenza virus activity and patterns in
people and animals nationally and globally on a year-round basis.
Continued support of national surveillance, which provides essential
data on virus strains and their sensitivity to antiviral drugs,
and of WHO's Global Influenza Surveillance Network is key.
— Ongoing support for the research platforms
and skill base of the type put in place during the H1N1 pandemic.
Having skilled staff, for example research nurses already on the
ground with the experience and knowledge, will enable ongoing
studies in the inter-pandemic period and a much more rapid research
response to new infectious disease events. This skills base will
facilitate the rapid scale-up and launch of clinical research
and acquisition of valuable data during the initial wave of a
new threat. Indeed, at the third scientific advisory group meeting
the European Centre for Disease Prevention and Control reported
that those European countries that did not have skilled and dedicated
staff already in place before the H1N1 pandemic were not able
to carry out any studies in response to the pandemic.
— Ongoing support for research projects.
Continued basic and applied research on zoonotic influenza viruses
and maintaining momentum of the research initiated during the
H1N1 pandemic is crucial to advance our understanding of the H1N1
virus (and other influenza viruses) and the disease. For example,
the H1N1 studies MOSAIC and FluWatch benefited from the influenza
virus sequencing "pipeline" at the Wellcome Trust Sanger
Institute set up in 2006 to sequence large numbers of influenza
viral genomes, to track the evolution of viruses, which is important
for not only monitoring virus with pandemic potential but also
in the development of vaccines in general. The state-of-the art
sequencing technology was used to rapidly analyse samples from
both studies.
24. Further research is needed to understand
the emergence, transmission, pathogenesis and control of influenza
caused by zoonotic viruses such as H1N1 at the global level. Many
of the research gaps identified during the H1N1 pandemic (some
examples are provided in Box 2 below) and on the WHO public health
research agenda for influenza remain to be addressed, and most
can be tackled during the inter-pandemic period. The UK is in
a prime position to capitalise on its strong research and skill
bases to address these research questions during the inter-pandemic
period. The lessons learned should serve the UK and global community
in formulating robust evidence-based policies and strategies for
better preparedness and response to future pandemics and other
infectious disease outbreaks.
EXAMPLES OF
KEY RESEARCH
GAPS FOR
INFLUENZA
— Communication and behavioural research:
further research is needed in order to develop more effective
and evidence-based health communication strategies and behavioural
interventions in response to future pandemic. For example, investigating
how to improve compliance with recommended public health measures
and examining why attitudes among professionals are crucial for
successful vaccine programmes.
— Clinical research: epidemiologic,
pathogenesis and intervention studies in the inter-pandemic period,
both in the community and in those hospitalised with more severe
illness. Such initiatives would serve to not only build this clinical
research capacity as a platform for response to new threats but
also to understand the impact of annual outbreaks of influenza
and other respiratory pathogens and test measures to mitigate
their impact through studies on patient management, particularly
those with severe illness.
— Modelling: mathematical modelling,
a current strength in the UK, can be used to help improve understanding
of the epidemiological factors and population processes shaping
infectious disease spread in human and animal populations (eg,
modelling influenza transmission and the impact of intervention
strategies such as closing schools and wearing masks).
— Surveillance and operational research
in households and at the human/animal interface to understand
viral evolution, risk factors for emergence of threat pathogens
and transmission to humans, and interventions to reduce transmission.
LOOKING TO
THE FUTURE—EFFECTIVE
PUBLIC HEALTH
RESPONSE IN
DISASTERS AND
EMERGENCIES
25. Emerging infectious diseases, such as influenza,
carry an immense and growing global health burden. It is important
therefore to learn from the H1N1 pandemic and continue to support
research that will strengthen evidence-based policies and healthcare
practices.
26. In the broader context, it is important
to note the growing number of emergencies which are triggered
by extreme weather events eg floods, storms and droughts, both
in the UK and particularly in low- and middle-income countries
(LMIC). The need for robust scientific evidence to inform the
response to such disasters is widely acknowledged by practitioners
and policy makers alike. Nevertheless research to strengthen the
public health response in such complex settings is challenging.
27. The Trust, as part of scoping work to identify
gaps and potential opportunities to strengthen the public health
response in disasters and humanitarian emergencies, held a "Frontiers
Meeting" in June 2010 bringing together NGOs, academics,
and representatives of multilateral agencies.
28. A number of common challenges and barriers
to undertaking research in the field immediately post-emergency
were identified. These included for example, the need for a robust
pre-agreed ethical framework to guide research in such situations;
improving the understanding and cooperation between practitioners
and between human and animal health experts; the need for improved
and timely evaluation of research studies and their findings;
and more rapid dissemination of research findings. Importantly,
all agreed on the need for a robust evidence base to inform policies
and the public health response in disaster settings.
29. We would happy to provide further details
about any of the issues raised in this response.
The Wellcome Trust
August 2010
9 http://www.wellcome.ac.uk/stellent/groups/corporatesite/@policy_communications/documents/web_document/WTX060175.PDF Back
10
http://www.who.int./csr/disease/influenza/2010_04_29_global_influenza_research_agenda_version_01_en.pdf Back
11
http://www.who.int/csr/disease/influenza/inforesources/en/index.html Back
12
http://www.who.int/csr/resources/publications/swineflu/clinical_managemnt_h1n1.pdf Back
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