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PEDIATRICS Volume 137 , number 2 , February 2016 :e 20153611
The recent Ebola epidemic exposed critical knowledge gaps about the
disease and its impact on different populations, particularly children,
which hindered the public health and medical response. For instance,
unanswered questions remain about the natural history of Ebola virus
disease in young children and its transmissibility in breast milk. Other
emerging infectious diseases, such as Middle East Respiratory Syndrome
(MERS), remind us that there will always be another pathogen lurking
around the corner. Public health emergencies (PHEs) resulting from
natural disasters are increasing in ferocity and frequency.1 How can we
ensure that we address our current knowledge gaps to better prepare for
future disasters?
Awareness of the need to integrate scientific research into PHE response
is growing,2 but the discussion of research involving children has been
limited. Although several efforts have addressed the unique physical
and socio-emotional needs of children in PHEs,3,4 pediatric research
during PHEs has been lacking, resulting in significant knowledge gaps for
children compared to adults. Conducting research, especially in children,
without interfering with the PHE response is challenging. The present
article discusses the importance of including children in PHE research
and proposes components of a robust infrastructure that need to be in
place to facilitate this research.
BARRIERS TO INCLUDING CHILDREN IN PHE RESEARCH
Including children in PHE research presents special challenges,
including issues with recruitment, informed consent, and enrollment.3,5
Institutional review boards (IRBs) have more stringent requirements
for inclusion of children in research than for adults.6 A life course
perspective is needed to study the impact of PHEs in children at different
developmental stages. The use of medical countermeasures such as
vaccines and antimicrobial agents for prophylaxis and treatment of
children often requires extrapolation from adult studies and must
consider weight-based dosing and different formulations and routes
of administration. Despite these complexities, these challenges can be
addressed with advanced planning and need not hamper a rapid, effective
PHE response.
Planning for Research on Children During Public Health EmergenciesLaura J. Faherty, MD, MPH,a,b Sonja A. Rasmussen, MD, MS,c Nicole Lurie, MD, MSPHd
PEDIATRICS PERSPECTIVES
aRobert Wood Johnson Foundation Clinical Scholars Program,
University of Pennsylvania, Philadelphia, Pennsylvania; bLeonard Davis
Institute of Health Economics, University of Pennsylvania, Philadelphia,
Pennsylvania; cCenter for Surveillance, Epidemiology and Laboratory
Services, Centers for Disease Control and Prevention, Atlanta, Georgia;
and dOffi ce of the Assistant Secretary for Preparedness and Response,
Department of Health and Human Services, Washington, DC
Dr Faherty refi ned the conceptualization of the Perspective,
drafted the initial manuscript, and revised subsequent drafts;
Dr Rasmussen conceptualized the Perspective, outlined an
initial organization of the manuscript, and reviewed and
revised subsequent drafts; and Dr Lurie conceptualized the
Perspective and reviewed and revised the manuscript. All
authors approved the fi nal manuscript as submitted.
The fi ndings and conclusions in this report are those of
the authors and do not necessarily represent the offi cial
positions of the Centers for Disease Control and Prevention or
the Department of Health and Human Services.
DOI: 10.1542/peds.2015-3611
Accepted for publication Oct 28, 2015
Address correspondence to Laura J. Faherty, MD, MPH,
Blockley Hall, 13th Floor, Room 1310, 423 Guardian Dr,
Philadelphia, PA 19104. E-mail: lajohns@mail.med.upenn.edu
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-
4275).
Copyright © 2016 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they
have no fi nancial relationships relevant to this article to
disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors have
indicated they have no potential confl icts of interest to
disclose.
To cite: Faherty LJ, Rasmussen SA, Lurie N. Planning for
Research on Children During Public Health Emergencies.
Pediatrics. 2016;137(2):e20153611
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FAHERTY et al
THE RISKS AND BENEFITS OF INCLUDING CHILDREN IN PHE RESEARCH
All research must weigh risks and
benefits, and an acceptable risk/
benefit ratio for research in children
is significantly different from that in
adults.6 In the United States, research
on specific PHE countermeasures or
interventions using child subjects
is typically only conducted before
a PHE if the research presents "no
more than minimal risk," because
riskier research is justified only if
there is the prospect of direct benefit
to the child or the need for the
research study is clearly of critical
importance.7 In contrast, emergent
situations might shift the risk/benefit
ratio, making research that would be
unethical in a nonemergent situation
acceptable, even ethically imperative,
during a PHE.5
Understanding the continuum of
potential risks and benefits of PHE
research is critical to planning for
research involving children (Fig 1).
At one end of the continuum are
observational studies that may not
confer direct benefits to the child
but are noninvasive or minimally
invasive. These studies present fewer
ethical challenges because they pose
minimal risk, answer important
questions, and produce generalizable
knowledge. For example, longitudinal
cohorts of children were followed
after Hurricane Katrina; the
tornadoes in Joplin, Missouri, and
Tuscaloosa, Alabama; and the
Deepwater Horizon oil spill. Before
the Deepwater Horizon disaster, we
had failed to learn about the health
effects on children from the nearly
two dozen oil spills in the United
States in recent decades because the
necessary research infrastructure
was lacking.
Toward the other end of the
continuum are studies involving
novel interventions that may
present greater than minimal risk.
They might offer direct benefit
for the exposed child by reducing
immediate or later morbidity and
mortality, and they could indirectly
benefit children affected by future
events by producing generalizable
knowledge about a previously
untested countermeasure. For
instance, because Anthrax Vaccine
Adsorbed is not approved for
pediatric use, pre-event studies are
only possible with age de-escalation
protocols, which test the product
in progressively younger cohorts
as safety is established.8 However,
after an intentional release of
anthrax spores, the potentially
lifesaving benefit of the off-label
use of this countermeasure might
outweigh the risk of adverse effects
in children. Similarly, it would have
been unethical to study the Ebola
monoclonal antibody ZMapp (Mapp
Biopharmaceutical, Inc, San Diego,
CA) in healthy children before the
West African outbreak; however,
during the PHE, the Liberian
government and the National
Institute of Allergy and Infectious
Diseases enrolled children with
Ebola virus disease in a clinical trial
of this countermeasure.9 Invasive
interventional studies at the far end
of the ethical complexity continuum
might be possible only when the
risk/benefit ratio has shifted during
a PHE.
INFRASTRUCTURE TO SUPPORT PEDIATRIC-FOCUSED RESEARCH DURING PHES
Developing the required
infrastructure to conduct pediatric-
focused research during PHEs
requires several interrelated efforts.
The first effort is the articulation
of a cohesive research agenda for
use during disasters. This agenda
should be developed in the pre-
event period and be generic yet
flexible enough to be adapted “just
in time” for a variety of PHEs. It
should identify and prioritize key
research questions that could arise
during PHEs. By identifying these
questions in advance, the agenda
should guide data collection efforts,
including collection of baseline data
immediately after a PHE. Given that
children grow and develop, baseline
data on mental and physical health
are even more important for the
pediatric population than for adults,
and these data must be collected in
an ethical and community-engaged
way. The National Institute of
Environmental Health Sciences’
Disaster Research Response Web
site provides examples of pediatric-
relevant instruments for this purpose
(http:// dr2. nlm. nih. gov/ ).
Input from experts in disaster-
related pediatric research, such as
pediatricians, psychologists, public
health planners, bioethicists, and
federal subject matter experts, is
critical to developing this agenda.
Ideally, these experts would
meet regularly before a PHE to
develop prepositioned generic, yet
customizable, research agendas
that incorporate the perspectives of
parents, educators, and child care
professionals. Postevent refining
of the generic research agenda is
imperative. As an example of this
strategy, the Institute of Medicine
convened a meeting of stakeholders
to review existing knowledge
regarding Ebola virus disease and
set research priorities related to
environmental transmission and
personal protective equipment
(report available at http:// www.
nap. edu/ catalog/ 19004/ research-
priorities- to- inform- public- health-
and- medical- practice- for- ebola-
virus- disease).
Another critical component is
the development of a network of
pediatric “research responders” who
could rapidly execute the research
agenda after a PHE. These research
responders should be available to
quickly mobilize, select questions
from the research agenda to address,
amend and activate precleared
protocols, assemble pretrained
research teams, and initiate data
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PEDIATRICS Volume 137 , number 2 , February 2016
collection and analyses as soon as
possible during a PHE.
The development of both generic
and scenario-specific prepositioned
research protocols specific to the
needs of children and quickly
deployable during a PHE are needed
to successfully execute the research
agenda. One of the few existing
examples is the International Severe
Acute Respiratory and Emerging
Infection Consortium–World
Health Organization’s Clinical
Characterization Protocol for severe
infections with emerging pathogens,
which can be adapted to patients
of all ages (https:// isaric. tghn. org/
protocols/ clinical- characterization-
protocol/ ).
Such protocols can be used to
build another component of PHE-
related research infrastructure:
generic minimum data sets. In
the adult arena, the United States
Critical Illness and Injury Trials
Group's Program for Emergency
Preparedness network is charged
with developing processes for
rapid data collection to create a
minimum data set during PHEs,
real-time analysis of clinical data,
and timely dissemination of results.
This network could be adapted
to include children. An existing
3
FIGURE 1A continuum of risks and benefi ts and examples of knowledge gaps for pediatric-specifi c research in PHEs.
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FAHERTY et al
pediatric network that could be
leveraged and expanded to rapidly
collect, analyze, and disseminate
pediatric-specific data in a PHE is
the Pediatric Acute Lung Injury and
Sepsis Investigators network of >78
PICUs throughout North America
(www. palisi. org), which facilitated
multicenter trials during the 2009-
2010 influenza pandemic. To glean
important clinical information about
the unique pediatric impact of PHEs,
generalizable information could be
gained from pooling the experiences
and patient numbers from many
facilities, as well as including a
longitudinal component, to create
data sets for analysis during and after
a PHE.
Rapid review by an IRB, particularly
for multisite studies, is needed for
PHE-related research. Revisions to
the Federal Policy for the Protection
of Human Subjects (“Common
Rule”) were proposed in August
2015 (http:// www. hhs. gov/ ohrp/
humansubjects/ regulations/
nprmhome. html). If approved, these
revisions may allow a single IRB
review for multicenter studies and
are anticipated to simplify aspects of
the IRB process. In addition, any US
academic institution can designate
the nascent Public Health Emergency
Research Review Board, housed
within the National Institutes of
Health, as its IRB of record. IRBs must
be prepared to recognize the shifted
risk/benefit ratio during a PHE and
to consider the particular legal,
ethical, and scientific ramifications
of involving children in PHE-related
research before an event.
Lastly, the issue of funding this
infrastructure is complex and
situation-dependent. Fortunately,
multiple sources of funding exist. The
National Science Foundation provides
rapid research grants after PHEs. In
addition to the National Institutes
of Health, other nongovernmental
organizations, and philanthropies
may also provide support, depending
on the circumstance.
CONCLUSIONS
We describe the risks and benefits
of research involving children
during PHEs and the key
components of a pediatric-focused
research infrastructure. Not all
PHE-related research in children is
created equal, and certain PHEs alter
the risk/benefit ratio for postevent
investigations that become both
ethically permissible and ethically
imperative if untested medical
countermeasures are used to save
children’s lives. Although these
postevent studies must not interfere
with the response itself, we owe
it to the youngest members of our
communities to learn from each
event, to fill in our critical
knowledge gaps, and to do so
through ethically sound research
during PHEs.
ACKNOWLEDGMENTS
The authors thank Georgina
Peacock, MD, MPH, and Stephanie
Griese, MD, MPH, of the Centers for
Disease Control and Prevention,
and Diane DiEuliis, PhD, of the
Office of the Assistant Secretary for
Preparedness and Response, for
helpful discussions.
ABBREVIATIONS
IRB: institutional review board
PHE: public health emergency
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DOI: 10.1542/peds.2015-3611 originally published online January 4, 2016; 2016;137;Pediatrics
Laura J. Faherty, Sonja A. Rasmussen and Nicole LuriePlanning for Research on Children During Public Health Emergencies
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