INT J TUBERC LUNG DIS 8(5):683–686
© 2004 IUATLD
Overcoming ethical barriers to childhood tuberculosis
research in developing countries
B. J. Sina,* E. Molyneux†
* Division of Training and Research, Fogarty International Center, National Institutes of Health, Bethesda, Maryland,
USA; † Department of Paediatrics, Malawi College of Medicine, Blantyre, Malawi
In 2002, an international Workshop on Tuberculosis in
Children was held to determine priority areas for basic,
clinical and programmatic research to improve paediat-
ric TB practice. During the workshop, issues related to
the ethical treatment of children as research subjects,
particularly in resource-poor settings, were identified as
major constraints to the goal of expanding paediatric
TB research. Based on participation in the workshop
discussions, this article proposes concrete activities that
can begin to address the ethical barriers. The time and
costs associated with creating collaborative scientific
and ethical research projects between high and low-
income countries should be supported in grants for pae-
WHO CAN GIVE CONSENT for an orphan to par-
ticipate in a trial of new anti-tuberculosis drugs?
How do researchers resolve contradictory recom-
mendations from the ethics review committees in
industrialised country and collaborating developing
country institutions? Should the best known stan-
dard care or locally feasible, affordable or available
treatment be provided to participants in the control
arm of a clinical trial? What benefits of a successful
trial should be promised to the families and commu-
nities of children participating in the study? Many
ethical questions face clinicians and researchers
conducting clinical studies of paediatric tuberculo-
sis in low-income countries, especially when institu-
tional ethical review committees from the high-
income country institutions are unfamiliar with the
culture and clinical milieu in which the study is to
be undertaken.
In October 2002, an international Workshop on
Tuberculosis in Children was convened by the Inter-
national Union Against Tuberculosis and Lung Disease,
the International Pediatric Association, the US Centers
of Disease Control and Prevention, the US National
Institutes of Health (NIH) and the World Health
Correspondence to: Barbara J Sina, Division of Training and Research, Fogarty International Center, National Institutes of
Health, Building 31 Room B2C29, Bethesda, MD 20892, USA. Tel: (1) 301-402-9467. Fax: (1) 301-402-0779. e-mail:
sinab@mail.nih.gov
CHILDHOOD TB
SUMMARY
diatric TB research studies in developing countries. Pae-
diatric TB researchers in developing countries should be
given opportunities to participate in international pro-
grammes that develop bioethics expertise. Relevant case
studies of paediatric research in developing countries can
assist ethical review committees in industrialised countries
in understanding the special issues related to paediatric
research in resource-limited settings. Paediatricians in
developing countries need to be included in childhood
TB research studies and ethical review committees.
K E Y W O R D S : bioethics; developing countries; paediat-
ric research
Organization (WHO) for expert scientists and clini-
cians to determine priorities for research. There was
discussion about the special ethical considerations
required for children to participate as research subjects.
Children are considered to be a vulnerable research
population because they lack both the legal capac-
ity to consent to participation, and, particularly the
younger ones, the capability to sufficiently compre-
hend the purpose, risks, benefits and alternatives to
participating in a study. These constraints exist for
paediatric research anywhere, but are further compli-
cated by socio-economic tensions and cultural sensi-
tivities in developing countries. The wide spectrum
of difficult ethical questions posed by the conduct of
clinical research in developing countries and recom-
mendations to protect research participants in these
settings have recently been examined in depth by sev-
eral internationally recognised organisations,1,2 and
will not be reviewed here. Nor will we review the
broad debates regarding children as research sub-
jects.3,4 In this paper we suggest how issues related to
the ethical concerns of doctors involved in paediatric
tuberculosis research in developing countries may be
better understood and addressed.
684 The International Journal of Tuberculosis and Lung Disease
COLLABORATION BETWEEN RESEARCHERS
IN INDUSTRIALISED AND
DEVELOPING COUNTRIES
Increasingly, and justifiably, doctors and scientists
from developing countries are becoming equal partners
in health research conducted with foreign researchers
at their institutions. There are growing expectations
for community collaboration in local research modelled
on environmental and occupational health studies and
voiced by patient advocacy groups. Intellectual part-
nership and shared responsibility will better hone
research studies to the needs of participants in devel-
oping countries. Equitable collaboration in determin-
ing the ethical content of research was recently recog-
nised to be as important as scientific partnership for
conducting the best clinical studies in developing coun-
tries.1,2 However, the sources of funding for such col-
laborative research are largely from wealthy countries
with advanced technical and research capabilities.
This creates disparate pressures on the scientific goals
and ethical review processes of the collaborators and
their institutions. The time and costs associated with
creating the collaborative scientific and ethical content
of research projects are usually not specifically sup-
ported by research grants. We therefore recommend
that initial collaborative research and ethical planning
phases be supported in grants for clinical research
studies in developing countries, to enhance the oppor-
tunities for shared equitable scientific and ethical
decision making between collaborators.
INCREASING INTERNATIONAL
BIOETHICS EXPERTISE
We recommend that international bioethics expertise
should be increased among paediatric health researchers
and ethical review committees in both industrialised
and developing countries. This would promote inter-
nationally acceptable ethical review processes and
enhance the ability to engage in equitable collabora-
tive research in developing countries. Several activi-
ties are underway to increase the capacity for inter-
national bioethics expertise. The Fogarty International
Center (FIC) at the US NIH supports collaborative
research and research training grants for US and
developing country scientists. The FIC currently sup-
ports 14 international bioethics training programmes
worldwide to increase research bioethics expertise
and build sustainable bioethics capacity in developing
country institutions.5 The WHO provides publica-
tions in several languages on ‘Operational Guidelines
for Ethics Committees that Review Biomedical Re-
search’6 and ‘Guidelines for Good Clinical Practice
(GCP) for Trials of Pharmaceutical Products’.7 The
WHO is supporting an initiative to evaluate the per-
formance of health research systems in developing
countries; this includes ethical practices and recom-
mending new approaches. The FIC, along with the
Wellcome Trust, the UK Medical Research Council,
the Pan-American Health Organization, the WHO
and the Institut Pasteur support an annual Global
Forum on Bioethics in Research that focuses on the
perspectives and issues of particular interest to devel-
oping country researchers.8–10
INCREASING THE INTERNATIONAL
BIOETHICS KNOWLEDGE BASE
The ethical review process often places the researcher
in the centre of debate over international ethical stan-
dards and processes. A call for the development of
international ethical standards for conducting clinical
trials was made during the debate about the ethical
issues associated with conducting clinical trials of
antiretroviral drugs to prevent mother-to-child trans-
mission of HIV/AIDS in developing countries.11,12
However, recent revisions of international guidelines
diverge on several substantive issues.13–15 Various
national laws, regulations, guidelines and standards
related to ethics in research disagree on language and
justifications, represent different goals and constituen-
cies, and have different claims to authority. Researchers
seeking ethical approval of research protocols and
those on ethical review panels judging these protocols
must struggle to apply this tangle of national and
international ethics rules to the practical aspects of
conducting a clinical research study. This is further
complicated by most international grant-giving agency
requirements for grantees to obtain approval from
the ethics review committees of both their own insti-
tution and the collaborating institution. The two eth-
ical review panels frequently differ in opinion, and
there is no official process to resolve the differences.
To ease this burden, we recommend that funding be
provided to collect and disseminate to ethical review
committee members and researchers case studies de-
scribing how to successfully design clinical research
protocols and resolve ethical issues for selected pae-
diatric infectious disease research studies in develop-
ing countries.
INCREASING THE DEVELOPING COUNTRY
PAEDIATRICIAN’S ROLE IN RESEARCH
AND RESEARCH ETHICS
The question should perhaps be posed more fre-
quently—is it ethical NOT to perform a research study?
The question may be posed for a specific paediatric
participant in a tuberculosis study. For instance, is it
better to not test an orphan with chronic chest infec-
tions for HIV infection without a legal guardian
present to give consent? The child may not be treated
for lymphocytic interstitial pneumonia or given pro-
phylactic anti-tuberculosis drugs or cotrimoxazole.
Or the question may be posed for tuberculosis research

in general. Is it better not to test anti-tuberculosis
drugs and vaccines in children due to the potential
risks and additional barriers in the ethical process?
Despite the amount of attention given to consent
forms, confidential data collection and research pro-
tocol approvals, these play a relatively minor role in
the actual protection of young participants in paedi-
atric tuberculosis research. Protection stems from the
trust and respect established between participants
and researchers. Paediatricians are qualified to under-
stand the specific needs related to the protection of
young research participants. Local paediatricians are
sensitive to socio-economic and cultural factors con-
cerning the health of their patients, and are experi-
enced in dealing with these influences in resource-
poor settings. We therefore recommend that more
paediatricians based in developing countries should
be involved as researchers and ethical reviewers of
research for the benefit of children in their countries.
It is up to all partners in tuberculosis research to pave
the way for critically needed ethical childhood tuber-
culosis research.
Acknowledgements
We thank Dr Naomi Bock, Division of TB Elimination, National
Center for HIV, STD and TB Prevention, Centers for Disease Con-
trol and Prevention, Atlanta, GA, for key points and references con-
tributed to this paper.
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RÉSUMÉ
tées devraient être soutenus par des subventions pour les
études de recherche en matière de TB infantile dans les
pays en développement. Les chercheurs en matière de
TB infantile dans les pays en développement devraient se
voir offrir l’occasion de participer à des programmes
internationaux qui développent l’expertise en bioéthique.
Des études de cas significatives en matière de recherche
pédiatrique dans les pays en développement peuvent
aider les comités critiques d’éthique dans les pays en
développement à comprendre les problèmes particuliers
liés à la recherche pédiatrique dans les contextes à res-
sources limitées. Les pédiatres des pays en développe-
ment doivent être intégrés dans les études de recherche
de TB infantile et dans les comités critiques éthiques.
686 The International Journal of Tuberculosis and Lung Disease
En el año 2002 se realizó un taller internacional sobre la
Tuberculosis (TB) Infantil, con el objeto de determinar
las áreas prioritarias en materia de investigación básica,
clínica y programática y mejorar así la práctica con
respecto a la TB infantil. Durante el desarrollo del taller,
los problemas relativos a la ética de los tratamientos de
los niños utilizados como sujetos de investigación fueron
considerados como una dificultad importante para la
extensión de la investigación en TB infantil, en particu-
lar en los contextos con escasos recursos económicos. En
base a las distintas participaciones a las discusiones del
taller, los autores proponen actividades concretas que
pueden empezar a enfrentar las barreras éticas. El
tiempo y los costos asociados a la creación de proyectos
de investigación ética y científica en colaboración entre
RESUMEN
países ricos en recursos y aquéllos con recursos limita-
dos, deberían ser apoyados por subvenciones para los
estudios de investigación en TB infantil en los países en
desarrollo. Debiera darse la oportunidad a los investiga-
dores en TB infantil de los países en desarrollo, para
participar en programas internacionales que permiten
adquirir una experiencia en bioética. Los estudios de
casos de la investigación pediátrica en países en desar-
rollo pueden ayudar a las comisiones de revisión ética de
los países desarrollados, en el sentido de comprender
mejor los problemas específicos planteados por la inves-
tigación pediátrica en los contextos con recursos limita-
dos. Los pediatras de los países en desarrollo necesitan
ser incluidos en los estudios de investigación en TB
infantil y en las comisiones de revisión ética.