Download special report ethical issues in medical research

Developing World Bioethics ISSN 1471-8731 (print); 1471-8847 (online)
doi:10.1111/j.1471-8847.2008.00229.x
SPECIAL REPORT
ETHICAL ISSUES IN MEDICAL RESEARCH IN THE DEVELOPING WORLD:
A REPORT ON A MEETING ORGANISED BY FONDATION MÉRIEUX
CHRISTOPHE PERREY, DOUGLAS WASSENAAR, SHAWN GILCHRIST AND
BERNARD IVANOFF
Keywords
developing world,
clinical trials,
investigators,
informed consent,
pharmaceutical,
practice guidelines,
ethics
ABSTRACT
This paper reports on a multidisciplinary meeting held to discuss ethical
issues in medical research in the developing world. Many studies, including
clinical trials, are conducted in developing countries with a high burden of
disease. Conditions under which this research is conducted vary because
of differences in culture, public health, political, legal and social contexts
specific to these countries. Research practices, including standards of care
for participants, may vary as a result. It is therefore not surprising that ethical
issues emerge. This meeting sought to identify and discuss these issues
from the perspectives of the many actors in such research, including community representatives, with a view to finding ethical and pragmatic solutions
to these issues. Dialogue between these actors was also promoted, with a
view to identifying the need to develop such dialogue in future.
Drawing from the experiences of the speakers, the colloquium attempted
to outline some answers to several key questions characterising the field
today. Experiences related to epidemiologic research, vaccine trials, drug
trials, diagnostic tests and to some fundamental ethical issues in health
research. Speakers were from different countries, disciplines and professions. The meeting provided a forum for consultation and debate between
different ethics actors. Both encouraging findings and challenges emerged.
INTRODUCTION
More and more clinical trials are performed in developing countries where populations suffer from a high
burden of disease. Various factors affect the conditions
under which this research is conducted, such as differences in culture, local standards of care and public health,
as well as differences in the political, legal and social
environment specific to the host country. Under these
circumstances, it is not surprising that ethical issues
emerge.
The objective of the meeting organised by the Mérieux
Foundation1 in April 2006 was to share information and
debate questions relevant to ethics of research in developing countries, and to foster dialogue between a range
of disciplines, institutions (public and private) and
1
Fondation Mérieux was set up in 1967 by Doctor Charles Mérieux in
memory of his father, Marcel Mérieux, a pupil of Louis Pasteur and
founder of the Mérieux Institute in 1897. It is now an independent
foundation which works to serve the interests of public health, especially by combating infectious disease in developing countries.
Address for correspondence: Christophe Perrey, 131 Boulevard du Général Koenig, Neuilly sur Seine 92200, France. [email protected]
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd., 9600 Garsington Road, Oxford OX4 2DQ, UK and 350 Main Street, Malden, MA 02148, USA.
2
Christophe Perrey, Douglas Wassenaar, Shawn Gilchrist and Bernard Ivanoff
geographical areas on ethical issues related to clinical
trials. This article presents a summary of the different
issues that were tackled.
After briefly describing some differences in conducting
clinical research in developed and developing countries,
several challenges faced in the South were identified and
solutions proposed. Speakers subsequently examined
the roles of various key actors (clinicians, philosophers,
social scientists, patients’ associations, etc.). Issues
related to ethics committees in developing countries were
then discussed (composition, role, legal status, etc.), as
was the role of international organizations (governmental
or other) in fostering a competent ethical review process.
Finally, the role of lawyers and media professionals in
upholding ethical standards was discussed.
To address the different challenges that the ethics of
research raises, a multidisciplinary approach is essential.
To narrow the gap between current practices and the
ideal, actors from different fields need to collectively
review the issues and propose new approaches to better
align universal principles with particular values. The
world must face the challenge of ‘crossbred ethics’ and
find a means to articulate the different requirements of
various cultures in a harmonious way, while avoiding the
dangers of uniformity and of ethical relativism.2 There is
also a responsibility to support ongoing innovation in
therapy and prevention and ensure the best possible protection against abuses. As one speaker stated: ‘The most
profoundly unethical course is to do nothing to prevent
or alleviate such suffering.’ Therefore, the ethics of
research has to evolve with the growing complexity of the
research enterprise.
However, differences do exist, even if varied in number
and degree.4 These differences, of varying importance,
give rise to several difficulties, depending on the country
and the type of research undertaken (epidemiology, diagnostics development, new drug or vaccine development,
etc). In addition, there may be a perception by some that
the countries of the South constitute ‘guinea-pig populations’ for those of the North.
Several major challenges related to conducting
research in developing countries were raised.
ETHICS AND FIELD RESEARCH IN
DEVELOPING COUNTRIES
The principle of ‘equity’ should be scrupulously
respected. It would be unethical to test a vaccine or drug
There are similarities in conducting clinical research in
developed and developing countries. In both environments, a clinical trial always takes place in a network
made up of different actors. The decision to participate in
a trial does not result from a perfect understanding of the
delivered information or from a perfect rational evaluation of the benefit/risk balance.3 It corresponds to an
overall wish to be better taken care of.
d’Engagement dans des Essais Vaccinaux Contre le VIH. Psychologie
Française 1997; 42: 291–300; R. Jenkins, L. Temoshok & K. Virochsiri.
Incentives and Disincentives to Participate in Prophylactic HIV Vaccine
Research. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 9: 36–42;
P. Amiel & A. Fagot-Largeault (dir). 2000. Enquête sur les Pratiques
et Conceptions de l’Information et du Recueil du Consentement dans
l’Expérimentation sur l’être Humain. Paris. Convention MIRE, n°15–97.
4
Some factors may distinguish developing from developed countries:
scarcity of research skills, poor quality of infrastructure (e.g. hospitals,
laboratory facilities, communications networks), limited legislative constraints, paucity of experience in biomedicine, low levels of income,
limited availability of resources for scientists, differing human rights
environments (statutory and operational), differing perception of diseases, weaknesses of the health care system, lower regulatory stringency
of the research environment (leading to temptation to operate at a lower
costs with less ethical consideration in a less constrained environment),
limited availability of epidemiological data, relative weaknesses of some
research ethics committees and lack of enabling legislation.
2
R. Macklin, ed. 2004. Double Standards in Medical Research in Developing Countries. Cape Town: Cambridge University Press.
3
F.J. Ayd. Motivations and Rewards for Volunteering to be an Experimental Subject. Clin Pharmacol Ther 1971; 13: 771–778; A. Giami & C.
Lavigne. Motivations et Représentations Chez les Volontaires Engagés
dans des Essais Vaccinaux Contre le VIH (Phase 1). Psychologie
Française 1996; 41: 173–188; A.Giami & C. Lavigne. Refus
A lack of reliable epidemiological data for a
given disease
This often requires an additional study to predetermine
the real incidence of the disease and the justifiability of
specific proposed research studies, especially clinical
trials in order to ensure that such trials are clinically
relevant to the health needs of the host country.
Limited involvement of researchers from the
South in the conceptualization of research
The type of research to be conducted will depend on the
purpose: for example, to guide public health policy, to
support a file for licensure of a new drug or vaccine, etc.
Therefore, developing countries (host countries) need to
be involved, from the start, in the conceptualization of
the research to maximise the relevance of studies conducted and ensure the building of local capacity to
conduct and direct health research.
Achieving equitable sharing of risks
and benefits
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
Ethical Issues in Medical Research in the Developing World
in a country that would not derive a subsequent benefit.
Moreover, there is an obligation during the trial to facilitate access to care, and treatment should be of a globally
acceptable effective standard or at least a significant
improvement over what is locally available. Post trial
access to eventual products should be discussed in
advance of trials and preferential agreements should be
negotiated by partners to ensure access to effective products arising out of clinical research.
Strengthening capacity and transferring
knowledge
Field research can be an opportunity to strengthen local
technical capabilities. In this regard, as many of the investigations as possible should be conducted locally.
Capacity building should also include the following:
establishing or strengthening scientific capacity and infrastructure, training scientists in research ethics,5 ethical
review committees, and health-related education of the
communities from which participants are drawn.
Respecting the right to privacy/confidentiality
and good research practices
Restricted access to data is justified by a study subject’s
right to autonomy and because personal harm may ensue
if the data were disclosed.
Community participation and informed
consent
There was unanimous agreement on the absolute need to
obtain individual informed consent except in specified
unusual circumstances (e.g. mental disorder, incapacity,
etc.). Informed consent should, however, not be reduced
to the simple gathering of a signature. Instead, consent
may be a complex process with multiple stages, depending on the complexity of the research and the related risks
and benefits involved. Adequate informed consent should
usually involve the following: (1) Obtaining the assent of
local leader. As suggested in the Council of International
Organanisations of Medical Sciences (CIOMS),6 local or
5
D.R. Vasgird. Prevention over Cure: The Administrative Rationale
for Education in the Responsible Conduct of Research. Acad Med 2007;
82: 835–837.
6
Council for International Organizations of Medical Sciences
(CIOMS). 2002. International Ethical Guidelines for Biomedical
Research Involving Human Subjects. Geneva: CIOMS. Available at:
http://www.cioms.ch/frame_guidelines_nov_2002.htm [Accessed 12 Dec
2007].
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
3
traditional leaders may need to be consulted in order to
obtain courteous access to the community in question in
certain developing country contexts.7 Although this is not
a substitute for informed consent, this dimension may be
problematic if the leader refuses, or if the leader makes
stipulations that are unworkable or unethical. Community participation is an alternate operationalisation of
this process;8 (2) Providing information in the language of
the recipient and at a reading level appropriate to the
recipient’s reading level; (3) Ensuring understanding of the
information. Several recent studies have examined different ways of determining whether information is understood.9 Informed refusals may be an index of a sound
consent process; (4) Ensuring that the decision is taken
freely and voluntarily. To date there has been relatively
little research exploring the voluntariness component of
consent, probably because it is more difficult to conceptualise and study empirically than understanding.10
However, at the very least, there should be no undue
inducement to participate. Coercion, which is probably
very rare in research,11 should also not be present. Those
approached for research should also be allowed time to
discuss enrolment with their relatives before consenting
to research, particularly in relation to risks and benefits;
and (5) Reporting the agreement. (Signature or videotape.) The signature provides a legal record of consent
but its importance may be overemphasised in developed
countries. For oral cultures, it can be substituted by other
7
P.O. Tindana, N. Kass & P. Akweongo. The Informed Consent
Process in a Rural African Setting: A Case Study of the KassenaNankana District of Northern Ghana. IRB 2006; 28: 1–6; R. Upshur,
J.V. Lavery & P.O. Tindana. Taking Tissue Seriously Means Taking
Community Seriously. BMC Med Ethics 2007; 8: 11; C. Weijer, G.
Goldsand & E.J. Emanuel. Protecting Communities in Research:
Current Guidelines and Limits of Extrapolation. Nat Genet 1999; 23:
275–80.
8
E. Emanuel et al. What Makes Clinical Research in Developing
Countries Ethical? The Benchmarks of Ethical Research. J Infect Dis
2004; 189: 930–937; D.P. Diallo et al. Community Permission for
Medical Research in Developing Countries. Clin Infect Dis 2005; 41:
255–259.
9
G. Lindegger et al. Beyond the Checklist: Assessing Understanding
for HIV Vaccine Trial Participation in South Africa. AIDS 2006; 43:
560–566; A. Leach, S. Hilton & B.M. Greenwood. An Evaluation of the
Informed Consent Procedure Used during a Trial of Haemophilus
Influenzae Type B Conjugate Vaccine Undertaken in the Gambia, West
Africa. Soc Sci Med 1999; 48: 139–48; D.W. Fitzgerald et al. Comprehension during Informed Consent in a Less-developed Country. Lancet
2002; 360: 1301–1302; J. Sugarman. Empirical Research on Informed
Consent: An Annotated Bibliography. Hasting Center Rep 1999; 29(1):
S1–S42.
10
N.W. Barsdorf & D.R. Wassenaar. Racial Differences in Public Perceptions of Voluntariness of Medical Research Participants in South
Africa. Soc Sci Med 2005; 60: 1087–1098.
11
J.S. Hawkins & E.J. Emanuel. Clarifying Concerns about Coercion.
Hastings Center Rep 2005; 35(5): 16–19.
4
Christophe Perrey, Douglas Wassenaar, Shawn Gilchrist and Bernard Ivanoff
forms of validation (for example by videotape, through
participants’ advocates, or independent witnesses),
ideally negotiated in advance by preparatory social
science fieldwork. Developed country sponsors and ethics
committees may require signed consent to minimise
liability or rejection by regulatory bodies.
Using placebo or comparative treatment
From a universal ethical perspective, the same rules for
field trial design should apply everywhere to prevent
exploitation of developing country populations.
However, from a pragmatic and contextual ethical perspective, medical and economic inequalities may justify
differences in the design and methods of trials. The ‘gold
standard’ of clinical trials is the randomised, doubleblinded, placebo-controlled trial. In fact, Guideline 11 of
CIOMS allows for placebo or ‘no treatment’ under
certain conditions.12 Another issue is whether the ‘best
attainable’ treatments should be used in the host country
at the time of the trial or simply a known effective treatment. There was agreement that it was desirable to offer
comparator treatments that were better than those locally
available and that ‘locally available’ was an unacceptable
comparator if no effective treatment was available in the
local public health sector.
Meeting obligations in the post-trial period
Several obligations lie with the sponsor (or government
of host country): (1) the storage of samples and data; (2)
the dissemination of the results to participants, stakeholders (local, national and international e.g. the World
Health Organization (WHO)), regulatory authorities,
and scientific and public health communities; (3) the
availability of new drugs or vaccines after the trial. There
was consensus that this question must be settled by pretrial agreement – it may constitute a precondition. Complexities involve determining who should be responsible
for funding and providing such treatment. These details
should ideally be negotiated in advance of the study;13 (4)
the maintenance of the site and surveillance – it is the
responsibility of local stakeholders to maintain the activity of the trial site by utilising the acquired capacity and
attracting other projects; and (5) there should also be
ongoing respect for the confidentiality of the personal
12
Council for International Organizations of Medical Sciences, op. cit.
note 6, Guideline 11.
13
T. Tucker & C.M. Slack. Not If, But How? Caring for HIV-1 Vaccine
Trial Participants in South Africa. Lancet 2003; 36: 995.
records, and, in the case of socially sensitive research, the
identity of the community should be concealed.
Following the above points, discussion turned to other
partners who should ideally be included in field research,
especially in the developing country context.
Patient organizations
With the emergence of AIDS, patient groups play an
increasingly important role in the ethical scrutiny of
health research. For example, in France the coalition
of AIDS patient organizations work on the issues of
research and treatment (TRT-514). They closely review
study protocols and may sometimes ensure that patient
representatives are included in review committees. Other
initiatives could involve technical support for nongovernmental organizarions (NGOs) in developing countries,
training (North/South and South/South), networking,
advocacy for access to care, support for the creation of
local patient associations, and alliances of researchers,
politicians, patient organizations and trial participants.
Such organisations promote education, legal and ethical
analysis, and policy development related to AIDS. They
produce quality of information for patients, provide
advice on negotiations for participation in a research
project, and organise the training of civil society actors
on ethics of research. They have played a role in the
denunciation of nonethical research, for example, the
Tenofovir trial in sex workers.15
Social scientists
The major contribution to biomedicine by researchers in
the social sciences is to objectively demonstrate, through
field studies, the gap between the desirable and the actual
conduct of research. Various roles include the following:
(1) Prior to biomedical studies: contributions to the debate
on relativism and universalism of ethics,16 evaluation of
14
TRT-5 (Therapeutic Research and Treatment group).
J.A. Singh & E.J. Mills The Abandoned Trials of Pre-exposure Prophylaxis for HIV: What Went Wrong? PLoS Med 2005; 2(9): e234. They
analyzed the study protocol and found out that no female condoms
were going to be made available to study participants. No access to care
was planned if participants were screened out (being already HIV+) or
became infected during the trial. The informed consent was only available in English and difficult to understand for Cameroonian women.
Access to the study drug after the trial was not planned if the study
results were positive.
16
R. Massé. L’Anthropologie au Défi de l’Éthique. Anthropologie et
Sociétés 2000; 24(2): 5–11.
15
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
Ethical Issues in Medical Research in the Developing World
the role of ethics committees,17 analysis of the different
decision-making processes, identification of local authority structures and consent procedures,18 documentation
of local ethics and traditional values and beliefs, classification of risk categories (e.g. ethnic groups in epidemiological surveys) while avoiding labeling; (2) During
biomedical studies: reviews of the conduct of clinical
research, examination of specific issues such as informed
consent (e.g. assessment of community participatory
processes and structures, decision-making processes,
understanding of information, etc), observance of
confidentiality, etc; and (3) For post-biomedical studies:
evaluation to improve communication of certain results
to individuals (e.g. in the event of seropositivity) and
communities, evaluation of such processes to improve
presentation of study results to participants and lay
public.
Philosophers
Moral philosophy informs many questions related to the
ethics of research. Philosophers contribute to the formulation and justification of ‘principles’ that can guide
conduct for issues arising from biomedicine, and, in particular, from research on human beings.19 The basis of
good and evil is not entirely independent of sociocultural
context. Philosophers can contribute to the development
of local and national ethics and can advise on alignment,
or not, with other ethical frameworks. In addition to
contributing theory, philosophers can contribute to
decision-making within ethics committees or international bodies for the establishment of guidelines.
ETHICS COMMITEES IN DEVELOPING
COUNTRIES
Several studies of the existence and resources of ethics
committees in developing countries, like those undertaken in Africa by Networking for Ethics in Biomedical
Research in Africa (NEBRA), the WHO/Joint United
Nations Programme on HIV and AIDS (UNAIDS)
African AIDS Vaccine Programme (AAVP),22 or in
South America by the Bioethics unit of the Pan American
Health Organization (PAHO), reveal that there are great
disparities between and within countries.23 These inconsistencies relate to the existence or absence of the committees themselves, their guiding documents, their
personnel and procedures, their physical resources and
status, legally and institutionally, and their workloads
per meeting. The findings of these studies highlight the
need for individualised or regional capacity building
efforts. Several other needs of ethics committees were
identified in discussion, including:
•
Historians
Historians can provide a historical dimension that can
help to elucidate the gap between ‘the seductive vice of
utopia’ and ‘the stringent call of reality’.20 There is no
doubt that case studies can be very informative. The
responsibilities of historians could also be ‘to remind the
academic community, political body and industrial partners of unfulfilled promises.’21
17
Many questions can be addressed, such as the existence of such a
committee, their independence, their material and intellectual capacity,
training, procedures, legal status, etc.
18
C. Molyneux et al. Community Voices on the Notion and Practice of
Informed Consent for Biomedical Research. Soc Sci Med 2005; 61:
443–454.
19
L.A. Eckenweiler & F.G. Cohn, eds. 2007. The Ethics of Bioethics:
Mapping the Moral Landscape. Baltimore, MA: Johns Hopkins.
20
A.M. Moulin. Extracts from the meeting’s conclusive remarks.
21
Ibid.
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
5
•
Training for ethics committee members. Many institutions in the North provide training workshops in
developing countries. But their real long-term impact
has limited value for several reasons: (1) the acquisition of the needed theoretical tools for an ethical
evaluation of research requires more than a ready-touse tool kit, (2) the best theoretical knowledge cannot
be applied if the basic material conditions for the functioning of ethics committees are not ensured, (3)
repeated workshops may be attended by a select group
of individuals who receive repeated training and who
do not go on to train their colleagues. However, for
many ethics actors, these workshops are their only
exposure to bioethics and therefore do serve a useful
purpose, particularly if tailored to specific audiences
or types of trials.
Definition of the mandate of ethics committees. Their
primary function is the protection of study participants. Should they evaluate both ethical and scientific
aspects of a study? Positions differ on this subject. For
some, what is not scientific cannot be ethical, and a
simultaneous two-pronged evaluation is essential.24
However, available scientific expertise is limited and
the same individuals who develop the studies are often
22
See C. Milford, D.R. Wassenaar & C.M. Slack. Perceived Capacity
of Selected African Research Ethics Committees to Review HIV
Vaccine Trial Protocols. IRB 2006; 28(2): 1–9.
23
N. Kass et al. The Structure and Function of Research Ethics Committees In Africa: A Case Study. PLoS Med 2007; 4(1): e03.
24
E. Emanuel. Ending Concerns about Undue Inducement. J Law Med
Ethics 2004; 32: 100–105.
6
Christophe Perrey, Douglas Wassenaar, Shawn Gilchrist and Bernard Ivanoff
called upon to evaluate them from a scientific perspective. A minority view holds that ethics committees
must be confined to ethical review, and other organizations made responsible for the scientific review.
• The composition of ethics committees. Consensus
emerged on the need for multidisciplinary and multisectarian representation. But there was little agreement on the ideal profile for membership. Ideally, the
committee should include clinicians, lawyers, social
scientists (e.g. sociologists, psychologists, anthropologists), patient groups (to limit ideological conflicts), as
well as persons external to the reference institution.
Philosophers, ethicists, economists, representatives of
political or religious groups, and nurses should also be
sought.
• Funding of ethics committees. This raises issues related
to the conditions of existence, and to independence
from the sponsors.25 Generally, the sponsors of studies
should pay an administration fee to the host institution of the ethics committees. These financial contributions primarily cover the ethics committee’s
operating expenses (logistics, etc.). Moreover, true
independence is not readily achievable because ethics
committees are accountable to their home institutions
and to their communities. Committees must, however,
avoid conflicts of interest (e.g. by excluding persons
with financial interests in the institution that sponsors
the trial). Attention was drawn to the CIOMS26 and
Nuffield Council on Bioethics27 documents in which
developed country sponsors should provide funds for
ethics review capacity along with scientific funding.
Funding of ethics committees in Africa was reported
as inadequate in many cases.28
• Reference texts. In the best of cases these are guidelines published by national or international institutions, established procedures for referring and
analysing processing cases, rules describing the ethics
committees functioning and reports of sessions.
However, the multiplicity of available texts may create
confusion in some instances. Milford et al. found that
few chairs and members of research ethics committees
25
E. Bekelman, Y. Li & C.G. Gross. Scope and Impact of Financial
Conflicts of Interest in Biomedical Research: A Systematic Review.
JAMA 2003; 289: 454–465.
26
Council for International Organizations of Medical Sciences, op. cit.
note 6.
27
Nuffield Council on Bioethics. 2002. The Ethics of Research Related
to Healthcare in Developing Countries. London: Nuffield Council on
Bioethics.
28
C. Milford., D.R. Wassenaar & C.M. Slack. Perceived Capacity of
Selected African Research Ethics Committees to Review HIV Vaccine
Trial Protocols. IRB 2006; 28(2): 1–9.
were aware of applicable national laws relating to
health research and research ethics.29
To address the needs of ethics committees, several institutional actors must be mobilised:
•
•
NGOs (e.g. Foro Latinoamericana de Comités de
Ética en la Investigación en Salud (FLACEIS)) may
motivate development in the field of ethics when the
actions of the state are insufficient, without substituting for the state. They allow for (1) the establishment
of a network between countries of the same continent,
(2) sharing of experiences, (3) action on both pragmatic and theoretical levels, and (4) building bridges
between ethics committee members, regulatory agencies, researchers and the sponsors. Their principal
challenge is that many research ethics committees
(RECs) lack legitimacy. However, members with
standing and alliances with key institutions (like
WHO) can help to overcome this.
International institutions like the European Union,
WHO, United Nations Educational, Scientific and
Cultural Organization (UNESCO), World Medical
Association (WMA), CIOMS, or foundations associated with research structures (e.g. Fogarty/NIH) may
provide advice, regulatory frameworks and organise
or sponsor training to foster ethics committees. For
example, some agencies (like the WHO/UNAIDS
AAVP) are supporting law reform to enhance participant protections and to give RECs more legitimacy.
In spite of the extensive divide between the ideal and
current epidemic realities, it remains possible to bring
about concrete improvements in participant protections though efforts to contribute to developing institutional and individual research ethics capacity. Some
such efforts were discussed and are mentioned below.
ROLE OF INTERNATIONAL
INSTITTUTIONS IN FOSTERING
AN ETHICAL REVIEW PROCESS
Several international institutions have contributed to the
development of ethical review processes: the Council on
Health Research for Development (COHRED), WMA,
CIOMS, the European and Developing Countries Clinical Trials Partnership (EDCTP), the Wellcome Trust, the
United States National Institutes of Health (NIH)
Fogarty International Center, and the Council of
Europe.
29
Ibid.
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
Ethical Issues in Medical Research in the Developing World
Several possible actions and associated issues
were identified
The first action is the coordination and centralization of
work related to research ethics, as well as the organization of dialogue between researchers from the South and
North. Since 2000, one major international forum for
bioethics debate has been provided by the Global Bioethics Forum, supported by various research institutions
(NIH, WHO, Wellcome Trust, Institut National de la
Santé et de la Recherche Médicale (INSERM), NIH/
Fogarty, Medical Research Council (MRC) (UK & SA)).
COHRED has recently been appointed as the secretariat
of the Global Bioethics Forum to ensure continuity
between meetings, sustain focussed debates and generate
useful ethical outputs, thereby promoting increased and
sustained North and South participation in discussions,
and giving more consideration to ethics in ethics versus
science debates.
The second action is the development of guidance and
standards for framing international research. The specific
roles of the WMA and CIOMS, respectively, in fostering
an ethical review process were presented.
The WMA essentially exerts its role in the ethics of
research by producing policy development and review.
Many researchers declare in their publications that their
work was conducted in strict compliance with the Declaration of Helsinki,30 which is also used by various ethics
committees in countries of the South. The WMA also
plays a role in capacity building31 and ethics education.32
CIOMS is a ‘forum to consider and prepare advice on
contentious issues in health and research ethics.’33 It is an
international nonprofit organisation, established in 1949
by UNESCO and WHO. It focuses on aspects of research
in developing countries. Special consideration is given
to sociocultural, religious, and community aspects, the
national legal and administrative context, the quality
of care and the particular health needs of countries.
7
Particular attention is also paid to the ethical justification
of research (meeting a country’s needs, translation of
research into policy and practice, etc.), procedures for
evaluation of ethics (ethical and scientific review, multicentre trials, etc), choice of control groups, and additional actions (strengthening capacity building in the field
of ethics, provision of health care given during and
beyond the trial period).
The Council of Europe also plays an important
role. This intergovernmental organization (regrouping
46 countries) carries out a normative function within
the European Union (EU) by defining fundamental
principles, seeking a balance between scientific/medical
progress and human protection, and by helping EU countries to implement those principles. The major text is the
Convention for the Protection of Human Rights and
Dignity of the Human Being with regard to the Application
of Biology and Medicine: Convention on Human Rights
and Biomedicine34 (Oviédo) with an additional protocol
on biomedical research, and a recommendation on
research on biological material of human origin (2005).35
This text reflects European consensus and takes into
account the international dimension of research.
In light of the proliferation of national and international guidelines, harmonisation appears unlikely in the
short term, and some questioned the desirability of
harmonisation.
The third possible action is the funding of a long-term
partnership between Europe and developing countries to
promote clinical trials through the EDCTP for investigations in tuberculosis, HIV/AIDS and malaria.36 Clinical
trials in developing countries should not be undertaken
without also promoting the development of the requisite
capacity to evaluate the ethical dimension (Nuffield
Council of Bioethics Report). Establishing and sustaining
such ethical review processes is part of EDCTP activities, which are operationalised through inviting grant
30
World Medical Association (WMA). 1964. Declaration of Helsinki.
As amended by the WMA 52nd General Assembly, Edinburgh, Scotland, 2000. Ferney-Voltaire: WMA. Available at: http://www.wma.net/
e/policy/b3.htm [Accessed 3 Dec 2007].
31
They are associated with the Networking for Ethics in Biomedical
Research in Africa (NEBRA) project and to two European and Developing Countries Clinical Trials Partnership (EDCTP) proposals.
32
They produce the WMA Medical Ethics Manual, write articles and
organise conferences.
33
CIOMS includes over 100 international/national biomedical science
organizations/bodies. This institution produced the International
Ethical Guidelines For Biomedical Research Involving Human Subjects –
first published in 1982, and revised in 1993, with the latest revised
version being published in 2002: See Council for International Organizations of Medical Sciences op. cit. note 6.
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
34
Council of Europe. 1997. Convention for the Protection of Human
Rights and Dignity of the Human Being with regard to the Application of
Biology and Medicine: Convention on Human Rights and Biomedicine.
Strasbourg: Council of Europe. Available at: http://conventions.coe.int/
treaty/en/Treaties/Html/164.htm [Accessed 21 Dec 2007].
35
Council of Europe. 2005. Additional Protocol to the Convention on
Human Rights and Biomedicine, Concerning Biomedical Research. Strasbourg: Council of Europe. Available at: http://conventions.coe.int/
treaty/en/Treaties/Html/195.htm. [Accessed 21 Dec 2007].
36
The different scopes covered by this programme are: (1) the integration of European national programmes, (2) North-South partnerships
to conduct clinical trials in Africa, (3) capacity building in developing
countries, and (4) South-South network.
8
Christophe Perrey, Douglas Wassenaar, Shawn Gilchrist and Bernard Ivanoff
applications for general capacity building, general initiatives37 and partnerships with other structures.38
The fourth field is the strengthening of local capacities
in the field of ethics. WHO has a department of Ethics,
Trade Human Rights and Health Law which is engaged
in ethics research and capacity strengthening in all
WHO’s regions. It works with countries to strengthen the
ethical review process of health research, to develop
capacity building, to offer technical assessment for
standard-setting and regulatory issues, and to promote
networking to facilitate access to information, experience
exchanges and public debates. The US NIH Fogarty
International Center has taken the lead in funding several
large research ethics training initiatives in developed and
developing countries, aimed at building sustainable training capacity and centers of excellence for scholarship and
policy development in the North and South as required.
The EU has begun to offer limited funding to develop
international capacity in research ethics.
ROLE OF THE MEDIA IN MAINTAINING
ETHICAL STANDARDS
The denunciation of studies on ethical grounds can seriously damage the reputation of researchers, sponsors, or
investigators. Because of the ease of worldwide dissemination of information, the media have become real actors
in regulation of international research. The example of
Tenofovir in Cameroon demonstrates the impact of the
mainstream print media working with patient groups.
Yet, the mainstream press does not function with the
same logic as the scientific press. It focuses more on
scoops and sensational events to the detriment of rigorous analysis. Training in bioethics of research would be
very beneficial to journalists and allow for better understanding and reportage of key aspects of clinical trials.
Research ethics training for scientific editors may also
play an important role as they determine what gets published. Publications are central to the evaluation and validation of any research and researcher. Editors’ level
of involvement can be both general and specific. Editors
can exert pressure on the pharmaceutical industry, or
sponsors, to adhere to a high level of ethical standard
37
By supporting (1) networking with other national ethics committees
at a regional level, (2) online literature and websites on ethics and
clinical access, and (3) funding participants to the 6th Global Forum in
Bioethics Research.
38
World Health Organisation/Special Programme for Research and
Training in Tropical Diseases Strategic Initiative for Developing
Capacity in Ethical Review, Networking for Biomedical Research in
Africa and others.
through the ‘International Committee Of Medical Journals Editors’ (Vancouver group) that published guidance
for those who want to publish. Similarly, the Committee
of Publishing Editors (COPE) checks research submitted
for publication for conformity to the Helsinki Declaration. The Lancet has also a ‘protocol service’ which
allows researchers to submit protocols for review before
studies are started. Ethical considerations can thus be
identified and addressed in the early stages of the research
process.
Editors are responsible for what they publish. The peer
review process, already in debate,39 could be further
undermined in the event of failure in this field. Without
replacing scientific and ethical review prior to studies,
editorial boards should also consider the ethical dimensions of studies they are considering for publication.
Taking into consideration the very low number of studies
that are rejected for publication on ethical grounds, the
above arguments may appear theoretical. In this regard,
some argue a difference between intent and practice.
Editors and scientists alike should strive for publications
reflecting the highest possible ethical and scientific
standards.40
CONCLUSION
The past 25 years have seen a large increase in clinical
trials in developing countries, and, encouragingly, there
are increasing rates of publication, training, guidance
documents and workshops on the associated ethical
issues. Many sponsors now systematically integrate
ethical requirements into the development of research
protocols and long-term projects (e.g. the South African
AIDS Vaccine Initiative (SAAVI) sponsored HIV/AIDS
Vaccines Ethics Group (HAVEG) in South Africa).
Ethics committees in developing countries have specific
capacity needs that should be carefully assessed and met,
and various initiatives have taken some important steps
in this regard. With the support of countries from the
North, patient groups are further developing in the
South. Patient advocacy groups and other professionals,
such as philosophers, historians and social scientists, are
also active in contributing to the ethical conduct of clinical trials. Some developing countries have given legal
status to RECs and have developed supporting guidelines
and policies. Lastly, recent experiences highlight the
39
40
A. Mulligan. Is Peer Review in Crisis? Oral Oncol 2005; 41: 135–141.
Vasgird, op. cit. note 5.
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
Ethical Issues in Medical Research in the Developing World
role of the media as whistle-blower, generating political
attention. However, progress still needs to be made in
dealing with ethics in research and promoting deep interdisciplinarity. The meeting provided the opportunity for
exchange between different actors in the ever-evolving
field of research ethics. Coordinated international efforts
must continue to ensure that science that serves the developing and developed worlds also promotes respect for
human dignity
Acknowledgements
This meeting was made possible by an unrestricted educational grant
from Sanofi-Pasteur.
Christophe Perrey, PharmD, PhD in Social Anthropology, is a
researcher associated with the Groupe de Travail en Éthique et Philosophie des Sciences (GTEPS) at the Collège de France in Paris and is also
an expert in ethics for the European Commission. For this institution,
he reviews submitted studies and has also participated in the Networking for Ethics on Biomedical Research in Africa (NEBRA) project
© 2008 The Authors. Journal compilation © 2008 Blackwell Publishing Ltd.
9
aimed at evaluating the needs of the ethics committees in Africa.
Douglas Wassenaar is director of the South African Research Ethics
Training Initiative (SARETI) and is Director of the WHO/UNAIDS
African Aids Vaccine Programme working group on Ethics, Law, and
Human Rights, both based at the School of Psychology, University of
KwaZulu-Natal, Pietermaritzburg, South Africa, where he is Associate
Professor of Psychology. Shawn Gilchrist, MD, MSc in International
Health in the Tropics, and Diploma in Tropical Medicine and Hygiene
from the London School of Hygiene and Tropical Medicine is the
Director of Public Affairs at Sanofi Pasteur. He is responsible for relationships with international organizations and UN agencies and represents his company in professional associations. He is currently the
International Federation of Pharmaceutical Manufacturers Associtation (IFPMA) vaccine industry representative on the GAVI Working
group. Dr Gilchrist has a deep interest, and longstanding experience, in
international health, primarily in west and central Africa. Bernard
Ivanoff, PharmD, PhD, is a scientist educated in France, including at
the Institut Pasteur, Paris, with a specialization in microbiology and
immunology. He has a long experience in bacterial vaccines, particularly in enteric vaccines development. Dr Ivanoff spent six years in
Africa as a General Director of a medical research centre and is working
as Scientific Director of Fondation Mérieux. He has retired from his
work at WHO.