Translational medicine policy issues in infectious disease.
ABSTRACT The European Academies Science Advisory Council has published a series of reports on infectious disease policy issues, analyzing priorities for building the science base as part of public health strategy. Among current challenges facing the European Union are the needs to tackle antibiotic resistance, promote vaccine innovation, prepare for the emergence of novel zoonoses, and integrate research approaches to human and animal health. The scientific community must help public policy-makers to address the organization, balance, and sustainability of research funding and infrastructure; encourage the creation of a more supportive regulatory environment for translational medicine; and evaluate new models for public-private partnership to facilitate innovation.
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ABSTRACT: Infectious diseases continue to pose major public health challenges in developed, as well as developing, countries. The European Academies Science Advisory Council aims to integrate multidisciplinary analyses to define priorities for European surveillance of new, growing, or potential threats from antimicrobial resistance, vector-borne disease, and pandemic influenza. There is a concomitant need to apply such knowledge toward the development of improved health care and robust policies. We discuss how translational medicine can bridge these global issues by helping to mobilize resources between academia, industry, health care services, and policy-makers.Science translational medicine 10/2011; 3(103):103cm30. · 10.76 Impact Factor
www.ScienceTranslationalMedicine.org 13 January 2010 Vol 2 Issue 14 14cm2 1
CREDIT: F. A. MURPHY/CENTERS FOR DISEASE CONTROL AND PREVENTION
Infectious diseases worldwide account for
about one-quarter of all deaths (1) (Fig.
1). In developed countries, an earlier op-
timism that most such diseases had been
conquered by improved surveillance and
public health measures is now seen to
have been misplaced. In Europe as else-
where, there are newly emerging threats to
confront (2): new infl uenza variants; new
microbes, especially those transmitted by
animals; resurgent infections like tuber-
culosis (TB); resistance to antimicrobial
drugs; and bioterrorism. Increasing migra-
tion and other eff ects of globalization com-
pound these challenges.
Communicable diseases have major
economic as well as health eff ects. In Eng-
land, for example, the direct economic
burden calculated from the cost of primary
care, hospital admission, and hospital-
acquired infection was estimated as up to
$15 billion annually (3). Th e net impact is
much greater when other ramifi cations are
included. Emerging zoonoses—infectious
diseases that can be transmitted to humans
from other animals—can be disruptive on
a global scale. For example, the cost of the
severe acute respiratory syndrome epidem-
ic (which occurred from 2002 to 2003 and
was caused by a virus that probably origi-
nated in bats), including the eff ect on trav-
el, tourism, economic growth, and fi nancial
markets, was estimated at $80 billion.
EASAC AND THE EU
In 2001, the national science academies of
the European Union (EU) Member States
formed the European Academies Science
Advisory Council (EASAC) to provide ex-
pert, independent science advice to those
who make policy in the European institu-
tions (Table 1). In a series of reports on
infectious diseases (4), EASAC identifi ed
EU priorities for building the science base
as an integral part of public health strategy.
In this Commentary, we draw on this accu-
mulating evidence to analyze policy issues
that aff ect multiple countries to improve
the translational medicine environment in
Europe and indicate where further reform
should be sought.
APPRECIATING THE IMPORTANCE OF
Th at diff erent policy-making functions
must be better coordinated at national and
EU levels to capitalize on the scientifi c evi-
dence base is a pervasive theme in EASAC
work. Th e challenge of antibiotic resistance
exemplifi es the problem: Historically, poli-
cy-makers’ use of evidence has been weak
and short-sighted, despite resistance ac-
counting for half of the deaths from health-
care-associated infections in some parts of
Europe (5). A recent Recommendation
from the EU Council (6), following Euro-
pean Commission proposals (7) to contain
antibiotic resistance by (i) strengthening
surveillance, (ii) standardizing infection-
control procedures, and (iii) improving
the awareness of the hospital workforce
and patients, typifi es the short-term eff orts
to make better use of research evidence
that is already available. Th e scientifi c
and medical communities together with
policy-makers must pursue an important
translational medicine agenda to measure
and contain the transmission of clinically
relevant pathogens and aim
to implement Europe-wide
accreditation programs for
hygiene standards, diagno-
sis, and prescribing.
tively immediate actions
are not enough. In the view
of EASAC, policy-makers
must also commit to a lon-
ger-term agenda to promote
science and innovation, in-
form coherent strategy, and
create new tools to detect,
monitor, prevent, and treat
medicine encompasses op-
portunities to understand
the behavior of both micro-
bial and human populations,
but requires better integra-
tion of research activities
and therapy development to
conceive new interventions
and use them in new ways—for example,
as diagnostic-therapeutic combinations in
Translational Medicine Policy Issues in
Robin Fears,1* Jos W.M. van der Meer,2 Volker ter Meulen3
Published 13 January 2010; Volume 2 Issue 14 14cm2
*Corresponding author. E-mail: email@example.com
1European Academies Science Advisory Council, The
Royal Society, London SW1Y 5AG, UK. 2Department
of General Internal Medicine, Radboud University
Nijmegen Medical Centre, and the Royal Netherlands
Academy of Arts and Sciences, Netherlands. 3President,
German Academy of Sciences Leopoldina, D-06019
Halle (Saale), Germany,and chairman of EASAC.
The European Academies Science Advisory Council has published a series of reports
on infectious disease policy issues, analyzing priorities for building the science base as
part of public health strategy. Among current challenges facing the European Union are
the needs to tackle antibiotic resistance, promote vaccine innovation, prepare for the
emergence of novel zoonoses, and integrate research approaches to human and animal
health. The scientifi c community must help public policy-makers to address the organi-
zation, balance, and sustainability of research funding and infrastructure; encourage the
creation of a more supportive regulatory environment for translational medicine; and
evaluate new models for public-private partnership to facilitate innovation.
Fig. 1. Death by infection. Viral and bacterial infections are
responsible for a large fraction of deaths worldwide. This dig-
itally-colorized negative-stained transmission electron micro-
graph shows several infl uenza A virions.
www.ScienceTranslationalMedicine.org 13 January 2010 Vol 2 Issue 14 14cm2 2
THE EXAMPLE OF VACCINES
EASAC reports (4) explored two European
gaps in translation: from basic science to
clinical studies and from clinical research
to routine application of new therapies in
health practice. Much more eff ort is needed
to link the advances in fundamental science
on pathogen characterization with clinical
infection research, product discovery, proof-
of-principle in early drug development, and
clinical scale-up. Merely improving linear
progression along the R&D continuum is
not enough; capitalizing on feedback from
outcomes in human research to inform pre-
clinical understanding, test hypotheses, and
steer the selection of novel disease targets
must also occur.
Th is complexity is exemplifi ed in EASAC’s
analysis of the policy issues for vaccine in-
novation. Although it is vitally important to
make the best use of vaccines already avail-
able, there are unmet vaccine development
needs in Europe, as elsewhere—for pandemic
infl uenza, established diseases (including TB,
human immunodefi ciency virus infection,
and respiratory syncytial virus infection),
other emerging diseases (for example, West
Nile virus infection), and antibiotic-resistant
pathogens. New opportunities are arriving:
Th e sequencing of bacterial and viral genom-
es has created the discipline of pathogenom-
ics, facilitating “reverse vaccinology” (8). In
this approach, scientists search for vaccine
targets by studying sequence information,
as well as the microorganisms themselves.
For example, European vaccine research on
mutating virulence genes produced a TB
strain potentially conferring greater protec-
tion and fewer side eff ects than the standard
bacillus Calmette-Guérin, or BCG, vaccine
(9). But funding agencies need to realize that
advances in genomics necessitate the simul-
taneous pursuit of an ambitious and diverse
research agenda in fundamental science—for
example, to understand the innate immune
system and the induction of T lymphocyte
responses, as well as to characterize patho-
gen functionality (particularly for growing
threats such as the fl aviviruses)—before a
new disease appears.
In short, vaccine R&D deserves a higher
priority. Th e use of improved research meth-
odologies must be matched by a receptiv-
ity at regulatory agencies for new types of
information. Preclinical work can suggest
biomarkers to serve as correlates of infection
and protection to help shorten the duration
of vaccine trials. But this process requires
iteration across basic and clinical research
to screen and validate sensitive and specifi c
markers, as it is oft en the clinical outcome
that informs preclinical routes to effi cacy
and safety indicators. Microbial challenge
studies—in which human volunteers are
deliberately infected with microorganisms—
provide another very specifi c example of
the value of feedback from human research.
Such studies continue to contribute to the
understanding of pathogenesis (for example,
for malaria) and the immune response and
may furnish proof-of-concept for an inter-
vention (10, 11).
POLICY CHALLENGES FOR A BROAD
Advances in basic science are beginning to
clarify key pathogen population functions
such as virulence and quorum sensing (dur-
ing which cells in a population coordinate
their behavior), and provide an information
resource for translation into novel diagnos-
tics and therapeutics, as well as vaccines. Ba-
sic bioscience will deliver further insight into
mechanisms of pathogenicity, interspecies
transmission of infection, and host adapta-
tion. Th ese fundamental advances and their
applications carry implications for health
services and the regulation of innovation.
For example, the narrow therapeutic speci-
fi city that is the likely consequence of viru-
lence inhibition mandates rapid and precise
diagnostic methods to direct therapy.
In addition to better integration of basic
and clinical studies, research funders and
practitioners need to attend to two other
germane matters. First, they must incorpo-
rate fi ndings from the social sciences. For
example, it is important to clarify the de-
terminants of antibiotic resistance in diff er-
ent settings and educate health profession-
als about these factors to improve rational
prescribing. Similarly, funders and practi-
tioners must clarify how to communicate
with the public about the benefi ts and risks
of vaccines to build public trust about vac-
cine use. Better socioeconomic assessment
of the impact of infections and health-care
interventions is also needed to raise the po-
litical visibility of these issues and inform
Second, funding agencies and research-
ers must integrate approaches to human and
animal health. Th e importance of coordinat-
ing research to foster “one health” is a con-
stant EASAC theme. Th is task is increasing-
ly necessary: About 75% of new infectious
diseases discovered in the last 10 years af-
fecting humans have originated in animals.
Research to contain the infl uenza pandemic
required coordinated work on several ani-
mal species as well as humans. Th e current
disconnect between the sectors amplifi es the
fragmentation between basic and applied
research and between national and interna-
tional policies that impedes the translation
of discovery into clinical advance. Th e steps
needed to achieve this better integration
pose problems for policy-makers because it
may be necessary to modify the entire or-
ganizational structure of infection research,
prevention, and response, perhaps by creat-
ing a national institute for infectious disease
Table 1. European institutions with responsibility for developing and applying policy associ-
ated with translational medicine. Activities at the EU level must also take into account the role
of national authorities to support research, deliver public health, and manage the approval and
availability of medical products.
European Commission Directorates-General for Research, Enterprise, and Public Health have
operational roles to support health-related research and its application.
The European Commission initiates law-making, develops policies, and
manages programs while respecting the principle of subsidiarity (in those
domains where the EU does not have exclusive competence to act).
European Agencies ECDC has roles to identify, assess, and communicate threats from infection.
EMEA has responsibility for EU-wide marketing authorization, comprising
assessment, supervision, and pharmacovigilance.
European Parliament Directly elected body of EU that can draft legislation and request the
executive to present proposals. Has codecision role in law-making with
Council of EU Composed of ministers from Member States and has codecision role with
Parliament. Can also set out general guidelines and political priorities for
the other institutions. Presidency of the council is held by each Member
State for 6 months in turn under a rotating system.
www.ScienceTranslationalMedicine.org 13 January 2010 Vol 2 Issue 14 14cm2 3
(12). At both national and European levels,
such changes require political will.
NEW WAYS TO BUILD TRANSLATIONAL
New infrastructure. EASAC proposed that
one way of integrating across disciplines
and across sectors would be to create mul-
tidisciplinary infectious disease centers of
excellence with areas of expertise designed
to span the sciences. For Europe, such cen-
ters should be networked to ensure research
capacity building in all Member States and
access to patients. In addition to providing
critical mass and interdisciplinarity, these
centers could help to remedy European
weaknesses that will otherwise hinder the
progress of translational medicine.
One current defi cit is in the provision
of training. By promoting education and
career development, new infrastructure
can become an important part of initiatives
such as the Clinical and Translational Sci-
ence Network (13). But the success of trans-
lational medicine does not depend only on
integrating diff erent skills and perspectives.
EASAC highlighted the problem of declin-
ing skills in traditional disciplines, such as
microbiology, immunology, and epidemiol-
ogy, that may compromise the performance
of the next generation of researchers. Other
disciplines, such as entomology, vector biol-
ogy, and microbial ecology, have also been
neglected yet are newly critical for transla-
tional medicine in terms of understanding
the increasing incidence and spread of in-
fections that are occurring as a result of cli-
mate change and other environmental pres-
sures (14, 15).
European capacity can also be augment-
ed by adding value to preexisting medical
microbiology infrastructure. In many Eu-
ropean hospitals, microbiology services are
poorly connected to research, teaching, and
training; microbiology laboratories also tend
to merge and be located remotely from hos-
pitals. European funding agency encourage-
ment of collaboration between universities
that harbor fundamental research groups
and hospital microbiology laboratories
would facilitate eff orts in pathogen function
elucidation, molecular epidemiology, target
discovery, improved screening assays, data
management, and modeling.
Another current weakness is the lack of
integrated database resources. TB research
exemplifi es the value to be gained by con-
structing an accessible and comprehensive
repository of well-characterized pathogen
strain isolates together with their genomic,
clinical, and epidemiological data to study
relationships between molecular variation
and clinical consequences (16) and, if also
including human samples, to study the in-
terplay between the bacterium and patient
(17). Th is knowledge platform could im-
prove drug susceptibility testing, enhance
the modeling of future drug-resistance sce-
narios, and act as a resource for developing
new interventions. To be eff ective, a database
must be international, requiring collabora-
tion between centers of excellence with the
European Centre for Disease Prevention
and Control (ECDC), the U.S. Centers for
Disease Control and Prevention, and other
resources worldwide. Such coordination
presents a challenge for global policy-mak-
ers for technical, institutional, and, perhaps,
ethical reasons (18).
New funding models. New funding
models should be created to facilitate mul-
tidisciplinary, long-term, costly infectious
disease research. Th e current EU system,
based on competition between individual
research groups and fragmented research
prioritization strategies, should be reformed
to incorporate the concept of Grand Chal-
lenges (19) whereby policy-makers identify
societal priorities and the research commu-
nity agrees on specifi c research goals for co-
ordinated, sustained inquiry.
New regulatory environment. Th e
Clinical Trials Directive was implemented by
the European Medicines Agency (EMEA) for
the European Commission in 2004 with the
objectives of improving research standards,
protecting patients, and enhancing the com-
petitiveness of large-scale medical trials.
However, the academic and smaller-com-
pany research communities are concerned
that the directive dramatically increased bu-
reaucracy and costs for researchers without
enhancing clinical safety or quality (20). Th e
inadvertent consequence of reducing the
number of academic researcher-initiated
trials in Europe is unfortunate; researchers
must inform policy-makers on the options
for proportionate trial regulation. Th ere are
also more general lessons to be learned—
that the academic community must be more
proactive in advising policy-makers earlier
in the legislative life cycle and, in turn, pol-
icy-makers should consult more widely if
they are to avert unintended consequences
New time scale in policy develop-
ment. Th e clinical and policy-making
communities now face an additional col-
lective challenge in accelerating the science
advisory processes. Th e current H1N1 in-
fl uenza outbreak provides a good example
of a situation in which information was
generated in real time to inform practical
decisions: to identify vulnerable popula-
tions, analyze available interventions, and
promote public awareness (21). Th is re-
sponse by the scientifi c community entailed
considerable laboratory, epidemiological,
and social science research; the policy chal-
lenge is to ensure that the lessons from this
episode are embedded in policy-making
more broadly and that suffi cient resources
are made available for researching other
threats, some unforeseen.
CONNECTING RESEARCH WITH
INNOVATION IN STRENGTHENED
Antibiotic and vaccine innovation comprise
lengthy, expensive, uncertain, and complex
processes. EASAC analysis substantiated
concerns expressed by many other advisory
groups in the United States and EU regard-
ing a declining pharmaceutical pipeline in
certain areas of infectious disease R&D, for
example, drugs targeting Gram-negative
bacteria. If increasing antibiotic resistance
portends a return to the pre-antibiotic era, it
would be diffi cult to overestimate the subse-
quent impact on modern medicine, depen-
dent on the surgery and other intensive hos-
pital care that becomes impossible without
eff ective infection prevention and control.
Th e nature of the current impediments
to innovation for both large pharmaceutical
and smaller biotechnology companies has
been discussed extensively in the EASAC
reports and elsewhere [for example, for an-
tibiotics (3, 22, 23) and for vaccines (24)],
and the need for innovative incentives to
encourage antibacterial R&D has become
a priority for the current Presidency of EU
Council. Although there are many issues
to face in encouraging innovation—for ex-
ample, in the regulation of marketing, pric-
ing, and reimbursement to counter industry
perceptions of the declining return on in-
vestment in this area—some optimism that
new approaches to risk-sharing in public-
private partnership will help drive R&D is
appropriate. Th e need to stimulate public-
private collaboration is a consistent theme
in EASAC work.
One recent advance is the Innovative
Medicines Initiative, a 2 billion euros part-
nership between the European Commission
and the pharmaceutical industry to sup-
www.ScienceTranslationalMedicine.org 13 January 2010 Vol 2 Issue 14 14cm2 4
port precompetitive research to tackle R&D
bottlenecks in safety, effi cacy, training, and
knowledge management. It is too soon to
judge if the partnerships will succeed, but it
is encouraging that the design of the initia-
tive takes account of criteria for success in
collaboration, identifi able from the work of
EASAC and industry commentators (25).
Th e factors deemed critical for success in-
clude substantial public funding, interna-
tional networking, early attention to conten-
tious ownership issues, and the involvement
of smaller companies.
Additional advances in shared approach-
es to safety evaluation will occur. Th e Seri-
ous Adverse Events Consortium recently
demonstrated (26) a markedly increased
risk of liver injury with the antibiotic fl u-
cloxacillin in patients carrying at least one
copy of the HLA-B*5701 allele. Subjects
and samples were recruited in the United
Kingdom in publicly funded research with
regulatory agency permission for access to
safety records. Th is model for investigating
adverse events merits wider adoption, for
example, in vaccine postmarketing surveil-
lance for which EASAC defi ned a responsi-
bility for EU Member States to develop mo-
lecular epidemiology networks for research
and product monitoring.
Individual companies can also collabo-
rate with academia aft er the precompetitive
research phase. However, as academic re-
searchers oft en have only a limited under-
standing of what industry needs in validated
drug targets, it is prudent not to overvalue
what such research can deliver in the absence
of industry advice. Consequently, although
there are roles for public research, notably in
target assay and validation and in medicinal
chemistry for the construction of more di-
verse chemical libraries [molecular scaff olds
(23)], to bridge the gap between academia
and industry, industry must also teach what
is needed for drug discovery research.
BUILDING MOMENTUM IN
TRANSLATIONAL SCIENCE AND POLICY
If the current shortcomings in infectious
disease research and innovation are to be
addressed, public policy-makers need to
reconsider the organization and balance of
research funding at national and EU levels.
Th is requires better sharing of those skills
compartmentalized within the tradition-
ally separate domains of academia, industry,
and government (27). We conclude by em-
phasizing two points. First, it is vital not to
neglect basic research; without this, trans-
lational medicine is impossible. Second,
although we focused on the EU, there are
opportunities for more coherence in policy-
making worldwide. Th e strategies for trans-
lational medicine have implications not only
for scientists but for many others, including
fi nance ministries, those concerned with
research governance, and the veterinary
sector. Such strategies will also aff ect inno-
vation and competitiveness, public health
infrastructure, and global development.
Th e scientifi c community must continue to
stimulate discussion of the policy options.
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Citation: R. Fears, J. W. M. van der Meer, V. ter Meulen, Transla-
tional medicine policy issues in infectious disease. Sci. Transl.
Med. 2, 14cm2 (2010).