Keynote
I thank the organizers for the invitation. The meeting comes at a
unique time when there are efforts to strengthen capacity for both
research-related activities and regulation of the research. Also, it
comes at a time when there is unprecedented interest by various
stakeholders in research linkages in Botswana. We at the Botswana
Harvard Partnership certainly welcome all newcomers and hope that their
efforts in Botswana and regionally shall drive research activities to a
higher level, resulting in scientific research and new innovations
actively contributing towards the diversification of the economy and
development in Botswana. The conference also comes at the time when the
School of Medicine is in its formative stages, so students, staff, and
community members shall benefit from the outcome of deliberations. If
the first two days of the conference are any indication, I can only hope
that my presentation shall add value to the addresses that have preceded
mine. I refer to the very pertinent key issues addressed in Archbishop
Tutus opening keynote address on Human Illness and the Experience of
Vulnerability, and the various contributions of other speakers and
presenters.
Advances in scientific research and development have largely been
vested in the developed countries. There is no doubt that science drives
economic growth and development. The phenomenal growth and discovery of
new information technologies is an indication of how that aspect has
contributed to economic growth in some countries. Countries that have
prioritized science, such as Japan, have leapfrogged over others in
various indices of development.
The topic at hand is Globalization and the Diplomacy of Science.
My definition of globalization in science is as follows: It is the
process of increasing the connectivity and interdependence of the
world's scientific community in areas of research and scientific
development. This definition has implications for the development of the
physical and human infrastructure for scientific activities. It also
implies homogeneity, benchmarking, uniformity of scientific processes,
competencies and activities. Globalization in science, for me, is the
trans-frontier ability to harness scientific and technological advances
for the promotion of peace and sustainable development for the benefit
of all countries individually and collectively!
Embedded in my utopian definition of the globalization of science
is a moral and ethical obligation we have to ensure diplomacy, the
equitable distribution of research and development opportunities, and of
uniformity in scientific investment and resource allocation to ensure
standardization of the physical and human infrastructure for scientific
research and development. There are challenges to that definition, which
is why I believe the organizers added the aspect of diplomacy ... Hence,
Globalization and the Diplomacy of Science.
Coming from an HIV/AIDS background, I have chosen to use the
HIV/AIDS challenge as a case study to underpin various perspectives that
relate to the topic at hand. Why? Because HIV/AIDS has catalyzed an
unprecedented interest in global health. In turn, global health has been
driven by the worldwide threat of new emerging diseases and different
paradigms of the spread of diseases, such as severe acute respiratory
syndrome (SARS), swine flu (HIN1), tuberculosis (TB) and malaria.
HIV/AIDS and these emergent diseases have triggered new challenges for
research and have stimulated collaborative approaches to address the
problems they pose.
These disease-focused universal problems have encouraged decision
makers in academic institutions--including those in the USA, Europe, and
Japan--to prioritize and deploy resources for global health programs.
These resources include investment in research, such as HIV research, to
yield cost-effective and timely endpoints; this work needs to be located
in high incidence geographic areas.
Vertical programs, such as the President's Emergency Plan for
AIDS Relief (PEPFAR), contribute to infrastructural developments mainly
for HIV/AIDS, but also increasingly offer concessions to
holistic/integrated approaches to disease management, including
operational research/strategic information. In addition, we are
increasing multi-site and network trials, thus enhancing the training of
research personnel.
This plethora of interest in global health is not without cost, as
the targeted countries where research and programming is to be
undertaken seek certain reciprocities, including: 1) upgrading and
strengthening of local infrastructure and capacity development, such as
skills transfer; 2) in-country institution and local IRB demands for
in-country research, also known as the necessary ransom (an example of
some of the demands includes provision of study interventions beyond the
research period); 3) improvement of science, technology, and local
standards of care, and thus an increase in ethical obligations and
challenges for research and study equipoise; 4) prioritization of
resource allocation in regards to the conflict between care and
research; 5) a research agenda based on local public health priorities
and local participation in concept development and research design; and
6) local investigator involvement in the entire research process to be
undertaken in the developing countries.
All the above posturing in the globalization process for research
science and development demands a new form of diplomacy and
understanding based on mutual respect and the recognition of each
other's potential, role, and strengths. Clearly, research,
development and science cannot, and should not, take place in an
environment where the roles of the various stakeholders have not been
clearly defined. There has to be a local principal investigator (PI),
for example, when a multi-site network trial is to be undertaken. This
person understands the relevant local cultural, environmental, and
practical nuances that will impact the conduct of that research. The
local PI would ensure that the application for the research meets local
ethical and regulatory requirements prior to implementation. Research is
not a franchise and should be contextualized to the local environment.
There are certain specific issues that are important to address in
the context of Globalization and the Diplomacy of Science, once more
using HIV/AIDS as a case study.
Resources
Most scientific resources for HIV/AIDS research and development
have been and largely remain in the developed world. Until recently,
investments in HIV/AIDS research were largely based on the scientific
agenda for developed countries and research funding largely targeting
developed world issues. Ninety percent of the budget for HIV/AIDS has
been based on the B subtype of the virus, whereas 90% of the persons
affected--70% of whom are in Sub-Saharan Africa--have contracted the C
subtype. HIV vaccine design, investigational new drug (IND) research,
and for that matter behavioural interventions, have been based on
studies in the developed world.
While in certain areas such as drug efficacy, this approach has not
had any negative impact, in some aspects such as HIV vaccines, there
have been definite ramifications, including the failed Merck HIV vaccine
trials. In this case, since the vaccine had adenovirus as the vector,
there seemingly was an increased risk for HIV acquisition for the
enrolled recipients who had high titres of adenovirus antibodies. This
example demonstrates that research studies have to be undertaken in the
environment where the intervention is to take place, including in the
sub-population that shall be provided with the intervention. Very often
these studies are undertaken as pilot projects, so they may not be
instituted in an environment that is conducive enough to maximize
testing of the concept and design. Notwithstanding benchmarking and
standardization of research and scientific resources, researchers need
to consider the applicability of the research design, irrespective of
where the research and development (R&D) is to be undertaken.
Funding and Mechanisms of Funding
Funding has been obtained largely through competitive grant
applications. This system has favoured investigators who have grant
writing skills and proven research track records, and is a disincentive
to upcoming scientists to apply for and receive money. Sources of
funding have also been limited, with most being offered by the
governments from developed countries and institutions such as the
National Institutes of Health (NIH), the Bill and Melinda Gates
Foundation, Wellcome Trust, and pharmaceutical companies. This situation
has emanated from the high cost of conducting research, making it
prohibitive for developing country governments and institutions to
allocate money. For example, the cost of conducting an HIV Vaccine
Trials Network Phase I study (HVTN protocol 048) in Botswana in
2003-2005 that enrolled 14 participants was $1 million per year for the
three years it took to complete this research. It would have been
impossible for the BHP to secure such funding from the Ministry of
Health Botswana. Globalization has, however, resulted in new funding
opportunities offered by new sources such as PEPFAR, the Global Fund,
and the European and Developing Countries Clinical Trials Partnerships
(EDCTP) program. These funding sources have provided opportunities for
new projects on HIV/AIDS in the developing countries.
Regulation and Legal Framework for Research and Development
As new resources and stakeholders have been attracted to developing
countries for research and development, the regulatory framework for
research has in some instances been found to be inadequate, and the
capacities of the local ethics institutions have been overwhelmed by the
volume of research and the complexities of the research process. IRBs
have worked tirelessly to fulfill their mandate, very often with scarce
resources. At this point, I wish to personally acknowledge and commend
their dedication and commitment towards their work. The need to
strengthen those institutions cannot be overemphasized. I believe, in a
transparent and coordinated way, that there should be a globalized
IRB-capacity strengthening process and mechanism, in much the same way
as we undertake multi-site trials in an ethical manner that would not be
deemed to be influencing the review process. The independence and
autonomy of the IRB should also be protected and the scope of its work
should be, in my opinion, of a scientific nature removed from political
influences.
Community Issues
To avoid exploitation, it is essential to ensure a fair
distribution of the benefits of research to the communities where such
research is being undertaken. It is also important to avoid the
displacing local medical staff from pressing community clinical care
needs and to focus only on research, and to ensure that disruption to
services where research is being undertaken is minimized. There is a
fine balance between the need for healthcare providers to balance their
participation in research with their role as healthcare providers. All
research and development must ultimately take into account the ethical
hazards that may be part of the social, economic, and political
landscape of the community.
Specimen Banks, Sample Storage, and Shipping
Very often as part of research activities either to validate or
confirm a finding, one needs storage of samples and specimens in the
event that a particular endpoint necessitates testing primary samples.
It may also be important to store specimens for future usage in the
event that a new technique becomes available for retesting, or to group
specimens due to rare occurrence of endpoints. Storage is expensive and
requires reliable quality management (QM) systems, including stable
sources of power and backup methods. Shipping samples to international
labs is necessary for the standardization of multi-site trials, analysis
using techniques that are not available locally, and for long-term
storage under specific conditions that cannot be maintained locally.
That said, genuine skills transfer and capacity building should in no
way be sacrificed.
While this shipping may result in delays and conflicts with
capacity building, it should be undertaken for the above reasons. The
conditions for storage and shipping need to be clarified, with clearly
defined policies and consent by protocols. Ultimately, there must be
resourcing and the establishment of local specimen repositories.
Principal Investigators, Capacity Building, and Mentoring
This issue was discussed at this conference along with the
challenges associated with the brain drain. It is essential to invest in
and develop research infrastructure for the retention of scientists in
developing nations and to foster ethos for research and development. It
is also important to develop structures that protect research time for
promising government or private employees, and to develop expectations
that local researchers should lead and publish some aspects of their
studies.
Access and Delivery of New Therapeutics
There are moral arguments for participants and communities of
R&D to access products of research and INDs undertaken in their
communities. This is based on their altruism and moral ethical
obligation to do so.
Complexities of Care
HIV and most science projects are not easily simplified into
vertical programs. There is a need for expansion of diagnostic and
therapeutic capacity. Future trials are likely to bring about increasing
laboratory complexity such as phenotypic testing and propriety issues,
human leukocyte antigen (HLA) typing such as HLA*B5701, (a type of HIV
that is slow to replicate), and co-receptor tropism such as Trofile,
which measures the growth of HIV in response to different environments.
There is an obvious need to reach out diplomatically to new partners in
new fields.
Data Management
A study is only as good as the data it generates. Information
technologies currently drive development, and concerted efforts to
develop that infrastructure in the developing countries shall enhance
and foster the Globalization of Science. Currently there are few
bio-statisticians, programmers, and data analysts in developing nations.
Intellectual Property
There are cries to accept the intellectual property (IP) rights of
scientists in developed countries and to develop systems and processes
to protect those rights. This right to IP can come to fruition if local
scientists are given the same opportunities to test their concepts and
to lead and take part in network trials.
Recommendations
I would like to end by giving a few recommendations:
1. For globalization to occur, we need a Marshal Plan for Science
to facilitate human and infrastructural development that elevates
research and development infrastructure standards in developing nations
to those practiced in developed countries--i.e., we must have
institutions equivalent to the Massachusetts Institute for Technology
(MIT) in Botswana--not only in Boston. We thus must have the financial
resources to support local scientists, equipment, and reagents, and if
not locally then regionally. In parallel, capacity building initiatives
need to be strengthened to ensure demonstrable capacity to undertake the
most complicated scientific research and development locally.
2. We need a harmonized approach to regulation in the same spirit
as the International Conference on Harmonization. This could include the
institution of a regional and international IRB for broader scientific
perspectives and local IRBs for local cultural ethical reviews of
concepts.
3. While endorsing network research like the Aids Clinical Trial
Group (ACTG), the International Maternal Pediatric Adolescent AIDS
Clinical Trials (IMPAACT),and the HIV Vaccine Trials Network (HVTN), we
should foster increased individually focused network capacitated
research and training similar to the European & Developing Countries
Clinical Trials Partnership (EDCTP), with a prescription for
North-South, South-South collaboration.
Conclusion
In concluding, I wish to point out that, despite the aforementioned
conflicts, I believe there has been demonstrable capacity for some local
research and development, and that this capacity can be strengthened by
the globalization of science. The current network multi-site model,
although not perfect, is the basis for hope.
I will end now with a few words from Dr. Gerald T. Keusch, Director
of the Fogarty International Center:
I thank you, ladies and gentlemen.
Editorial Note
The following is the text of the closing keynote address presented
on the afternoon of Wednesday, December 9, 2009. Three responses
followed.
Author's Note
The opinions presented in this text are those of the author and do
not reflect the official policy or positions of the Botswana Harvard
Partnership (BHP).
Joseph Makhema, MBChB, FRCP
Director, Botswana Harvard Partnership
Gaborone, Botswana
The future of science in developing countries requires investments
in information technology, the creation of a culture of research
ethics, and investments in modern science.