Strengthening and expanding capacities in clinical trials: advancing pandemic prevention, preparedness and response in Africa

Despite its sizeable human population, pathogen diversity and unique disease profiles, Africa is under-represented in global clinical research, with less than 3% of worldwide clinical trials conducted on the continent¹. As a result of this under-representation, global health entities often do not have data on the efficacy of their products in Africa¹. The gap is primarily due to insufficient clinical trial capacity attributable to a multitude of factors, including limited funding, inadequate research infrastructure, and a scarcity of trained personnel, including clinical trialists and laboratory researchers. Moreover, regulatory hurdles, including ethical concerns, pose significant challenges to implementing and scaling up the conduct of clinical trials in Africa. Several African countries’ regulatory landscapes are less adapted to embrace new scientific developments, leading to delays, increased potential for ethical dumping, and increased costs in initiating studies. Ethical concerns, particularly those relating to the conduct of trials in populations with limited access to healthcare, further complicate the situation, necessitating robust frameworks to ensure the protection of participants. Furthermore, operational challenges such as the inability to use technologies and digital methods, socio-cultural issues limiting acceptance, enrolment, and adherence of patients in clinical trials, and political instability and armed conflicts in some parts of the region affect the operationalization of clinical trials in Africa. However, without routine clinical trials conducted on the continent, African populations are deprived of access to cutting-edge diagnostics, therapeutics, and vaccines that could address specific health needs in consideration of uniquely African factors such as genetic makeup.

Many initiatives aim to address some of these challenges one of which is the European & Developing Countries Clinical Trials Partnership (EDCTP). Abdool Karim and Sikazwe also outlined the ongoing endeavors in Africa to build upon Pasteur’s legacy, which is crucial for enhancing pandemic preparedness and ensuring timely access to vaccines through high-quality clinical research². However, the launch of the Consortium for COVID-19 Vaccine Clinical Trials (CONCVACT) by the African Union filled a critical gap. CONCVACT aimed to bolster the continent’s capacity for conducting pivotal research and ensuring vaccine accessibility (Fig. 1)³.

This map provides a visual representation of the geographical distribution of the 21 research centers affiliated with the CONCVACT Network across Africa. Black pins: Indicate the locations of individual research centers. Green pin: Marks the ___location of the CONCVACT Network itself.

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CONCVACT was established in July 2020 through funding from Skoll Foundation with the aim of establishing 24 ready-to-go fully operational clinical trial sites in 12 African countries for COVID-19 vaccine trials. It partnered with vaccine manufacturer, Sanofi Pasteur, to support a continent-wide clinical trial of a vaccine that was subsequently licensed. CONCVACT brought together several of the continent’s leading experts in clinical trials to provide scientific advice and guidance on the continental response to COVID-19. Results from the clinical trial investigating the safety and immunogenicity of the booster showed neutralizing antibodies increased 9- to 43-fold regardless of the primary vaccine received (AstraZeneca, Johnson & Johnson, Moderna, BioNTech/ Pfizer) and for all age groups tested.

The continent also has a clinical trial ecosystem that comprises of the Pan-African Clinical Trials Registry (PACTR), which fosters transparency and supports the visibility of clinical research conducted in Africa^4,5; and the Clinical Trial Community (CTC) Platform (https://www.ctc.africa/map) that enables engagement among key stakeholders, enhancing efficiency and enabling robust collaboration. The platform provides a simple interface to link clinical trial sponsors with clinical trial sites with the desired expertise, facilities, staffing, laboratory capacity, and target populations for testing new products. Future additional features will profile clinical research service providers. There is also the European Union-funded project that will establish the Clinical Trials Community Africa Network (CTCAN) to foster collaboration among crucial clinical research stakeholders, pharmaceutical partners and other African international counterparts. The project’s primary goal is to improve coordination and sustainability in clinical research through network alignment, raising awareness about available facilities, streamlining regulatory processes and promoting knowledge sharing across regions⁶. The Coalition for Epidemic Preparedness Innovations (CEPI) is another initiative contributing to human resource development in Africa, focusing on rapid vaccine development and deployment within 100 days of a pandemic threat⁷. A strategic approach of the CEPI is to strengthen clinical trial capacity in Africa to respond to emerging health threats swiftly. In addition, the African Medicines Agency (AMA) was established to harmonize regulatory standards and foster an environment conducive to high-quality research in Africa⁸. This effort at building a unified clinical trial ecosystem for Africa that balances rigorous science, ethical requirements, and urgent public health responses can enhance its capacity for clinical trials, thereby playing a pivotal role in global health research and pandemic prevention preparedness and response (PPPR).

Capacity building to conduct clinical trials within Africa is a strategic imperative to address health challenges, ensure population wellbeing and promote economic growth. It transcends the immediate need for pandemic prevention preparedness and response. It is fundamental to achieving health sovereignty and ensuring equitable access to global health innovations.

Strengthening clinical trial capacity requires building physical facilities and a supportive ecosystem that includes competent clinical trialists, stringent regulatory agencies and ethical review boards, data management systems, and community engagement mechanisms. These elements are essential for conducting scientifically robust, ethically sound, and socially acceptable trials⁹. The Africa Centers for Disease Control and Prevention (Africa CDC) report on optimizing efficiency and impact in the African clinical trials ecosystem outlined several enablers that need to be addressed¹⁰. These include harmonizing research regulatory policies and procedures among African countries to facilitate faster and more efficient clinical trial approvals. Human resource development is another critical aspect that needs to be addressed. Initiatives to train and retain clinical researchers and healthcare professionals in Africa are vital for sustaining research activities and fostering innovation from within the continent. Strategies for resource development include running traditional educational programs, hosting mentorship programs well adapted to the continent’s needs, and providing career development opportunities that can mitigate the brain drain from Africa. Strengthening community engagement practices is also needed to ensure that clinical trials are conducted in ways that respect and involve local populations and address their health concerns and priorities¹⁰. Furthermore, developing regional and continental networks for clinical trials to share best practices, resources, and knowledge is crucial. It requires a collaborative approach, involving governments, research funding agencies, pharmaceutical companies, regulatory agencies, communities, and research institutions. These networks can enhance collaboration and enable the rapid scale-up of clinical trials in response to health emergencies.

Figure 2 illustrates a strategic framework for the regional consolidation of Research and Development (R&D) centers proposed by the Africa CDC. It aims at enhancing infrastructure capacity and expertise across a defined portion of the R&D value chain. This framework is supported by a Coordinating Platform, which facilitates integration and synergy among the R&D centers within the region¹¹. In this model, each R&D center contributes its specialized knowledge and infrastructure, collectively forming a robust network that addresses diverse research and development needs. The regional focus not only enhances the overall capacity but also ensures that expertise is distributed and accessible, promoting equitable growth and development. The Coordinating Platform acts as a nexus, harmonizing efforts and optimizing collaboration across the R&D value chain.

R&D Centers will regionally consolidate infrastructure, capacity and expertise across a given portion of the R&D value chain supported by a Coordinating Platform.

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The diagram underscores the pivotal role of R&D centers in fostering innovation and driving progress in various sectors. By consolidating these centers regionally, the framework leverages localized strengths and capabilities, ensuring a more efficient and effective utilization of resources. This consolidated approach is designed to streamline processes, reduce redundancies, and foster a collaborative environment that accelerates innovation. By aligning infrastructure and expertise with regional strengths, the framework aims to maximize the impact of R&D efforts, ultimately contributing to advancements in technology and industry on a broader scale.

The response to the COVID-19 pandemic highlighted the need and potential for rapid scientific advancement and capacity building within the African research community; researchers on the continent made significant contributions to monitoring and responding to the unprecedented global health challenge. One opportunity for further capacity building lies in leveraging the growing digital health infrastructure to streamline clinical trials. Digital technologies can facilitate remote monitoring, participant recruitment, and data management, thereby enhancing the efficiency and reach of clinical studies across the continent.

The Africa CDC and the World Health Organization’s Africa Infodemic Response Alliance (AIRA) are initiatives that have been instrumental in coordinating efforts to respond to pandemics across the continent¹². Leveraging the opportunities these initiatives create could further support the development of clinical trial capacity for PPPR by strengthening infrastructure development and program coordination to develop centralized data collection and management systems, streamline information sharing and improve real-time data analysis for clinical trials. In addition, the fostered collaboration can enhance knowledge exchange and facilitate multi-center clinical trials with engaged global research organizations, pharmaceutical companies and networks established by Africa CDC and AIRA to bring international expertise and funding to African clinical trials, ensuring alignment with global research priorities and standards. The patnership can also enhance efficient allocate resources across regions based on needs assessments thereby ensuring equitable support for clinical trial activities.

Sustained capacity-building efforts facilitated by a consortium of donors and partners, including EDCTP, the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), the U.S. National Institutes of Health (NIH), the Welcome Trust, and the Bill & Melinda Gates Foundation (BMGF), can strengthen clinical trial capacity for improved pandemic preparedness, prevention, and response in Africa. This collaborative approach underscores the importance of international cooperation and investment in developing a resilient healthcare infrastructure capable of conducting clinical research to inform the response to future health crises. It also highlights the need for indigenous funding by African philanthropists and governments that signed the Abuja declaration two decades ago, committing to a minimum of 15% of their annual budget for the health sector, including research. This will contribute to the sustainability of the African clinical trial consortium and decolonizing Global Health. However, the implementation of this commitment by governments has not reached the desired level.

Africa’s diverse genetic and epidemiological landscape presents a unique opportunity for conducting clinical trials that can offer insights into disease mechanisms and treatment responses in Africa that are globally relevant. The Human Heredity and Health in Africa (H3Africa) initiative is a continental asset in this respect. The establishment of biobanks is a step towards harnessing this genetic diversity, providing valuable resources for research into genetics, infectious diseases, and non-communicable diseases. Leveraging Africa’s growing biobanking infrastructure can also enhance the continent’s readiness to participate in vaccine development and other diagnostic and therapeutic research critical for pandemic response.

Investing in local manufacturing capabilities for vaccines, diagnostics and therapeutics represents a forward-looking pathway to enhance Africa’s self-sufficiency in critical medical supplies. Initiatives like the African Union’s Partnerships for African Vaccine Manufacturing (PAVM) aim to increase local vaccine production to meet 60% of the continent’s vaccine needs by horizon 2040, signalling a significant shift towards healthcare independence¹¹. One of the bold programs of PAVM is to expand the capacity for vaccine research and development (R&D) across the continent. Organizations involved in vaccine R&D include research institutes, biotechnology companies, government organizations and Clinical Research Organizations (CROs) that bring together the infrastructure, capacity, and expertise across a particular area of the R&D value chain as depicted in Fig. 2. Such ecosystem is needed for a well-coordinated response mechanism to pandemics.

The Pandemic Treaty represents a significant step towards establishing a comprehensive framework that ensures preparedness and responsiveness to future pandemics. An integral part of this treaty encompasses the establishment of regional R&D centers, each supported by a Coordinating Platform that ensures acess to funding requirements, and support for the governance structures essential to operationalize these centers. Thi would enhance global health security through effective pandemic preparedness and response. Such support can facilitate access of each center must be equipped with state-of-the-art laboratories, data centers, and communication facilities to enable the seamless execution of research activities, data analysis, and information dissemination. The coordinating platform should also support the staffing at these centers with highly qualified professionals, including researchers, epidemiologists, data scientists, and support personnel; and continuous professional development of the staff to keep the workforce adept at handling evolving challenges. High quality staff can also be accessible through establishing robust collaboration frameworks with academic institutions, private sector entities, and international organizations to facilitate knowledge exchange and resource sharing. Such a system can strengthens the region’ defense against health threats and also fosters a collaborative, innovation-driven environment that can drive significant advancements in public health.

To secure funding for the research site, the coordinating platform shall work through the African Union with member states to enure they contribute a percentage of their Gross Domestic Product (GDP) towards the funding of these centers. The coordinating platform manage this centralized fund. In addition, the ecosytem shall leverage on investments from private sector companies, especially those in the pharmaceutical and biotechnology industries, to provide additional financial support. In return, these companies can benefit from the research outputs and innovations. Grants from international health organizations, non-governmental organizations, and philanthropic foundations can also supplement funding. Transparent reporting and accountability mechanisms would be in place to ensure the effective use of these funds.

Capacity and capability centers (CCCs) will connect educational institutions with industry to enhance educational programs and create internships and on-the-job development programs. Educational institution participants could include universities as well as other post-high school options such as vocational schools or trade schools (where relevant). Industry players will include both manufacturing facilities and R&D institutions.

The central Coordinating Platform proposed to oversee the activities of the regional R&D centers is the Africa CDC. This platform will be responsible for setting research priorities, allocating resources, and monitoring progress. It will also facilitate communication and collaboration among the centers. The Platform shall have an independent advisory board comprising experts from various fields, including public health, epidemiology, and bioethics, to provide strategic guidance and ensure that the centers adhere to the highest standards of scientific integrity and ethical conduct. Africa CDC is geared to change the historical paradigm wherein academic and industry sponsors have often conducted trials in Africa without adequate local involvement in decision-making processes. This coordinating framework focuses on empowering African scientists to lead clinical research, promote local investment in research conduct and trial capacity building, and enure equitable agreements with collaborators. By building this collective trial capacity, Africa can position itself as a robust and reliable partner in global clinical research.

Each center shall be required to comply with international regulations and standards to continue to receive support from the Africa CDC. In addition, they each would be required to engage with local communities and stakeholders in decision-making processes to ensure that the benefits of research primarily target research hot communities and the benefits of research are shared equitably. Regular audits and evaluations shall be conducted by the Africa CDC to ensure compliance and to identify areas for improvement.

Once the collective trial capacity is established, it becomes a core asset to attract sponsors and collaborators, and forming strategic alliances with international research organizations and pharmaceutical companies who are able to see the benefits of conducting trials within an African-led framework through demonstrated competence and reliability of local scientists and institutions. To, however, ensure equitable and sustainable research practices, pre-negotiated agreements on data ownership and future benefit sharing will be etablished. This would include clearly defined and agreed upon data ownership rights to ensure that African scientists and institutions retain control over the data generated from trials conducted in Africa; clauses in agreements that mandate the transfer of technology to local institutions, enabling them to develop and produce interventions locally; and ensuring that the outcomes of the research lead to affordable and equitable access to the developed products for African populations. These agreements will protect the interests of African scientists and ensure that the benefits of research are shared equitably.

Currently, the R&D centers were established based on critical criteria including access to skilled individuals, existing R&D initiatives and infrastructure, stringent National Regulatory Authority (NRA) and a supportive environment with government contributions. These centers will foster the strengthening of R&D assets and infrastructure across the continent, such as by building up research institutes within academic organizations and strengthening review and approval boards. In addition to R&D centers, a continental R&D coordinating platform can be set up to orchestrate R&D across the continent. This will help to guide continental R&D vaccine priorities and strategy, support information sharing and collaboration across regions and countries, develop partnerships with both local and international organizations and connect knowledge enablers across the continent, bring together scientists and expertise across the continent to share progress and learning regularly, promote the scale-up of critical infrastructure and networks including local animal research facilities and CROs. As we envision the pandemic agreement, which calls for geographically diversified and sustainable production of countermeasures, the proposed coordination mechanism is a critically important strengthening mechanism for the R&D centers that Africa CDC hopes to pilot over the next five years prior to scaling up it R&D program¹¹.

As we look towards the future, the lessons learned from the COVID-19 pandemic and previous health crises highlighting the need for local solutions must inform a proactive approach to building resilient systems to support the conduct of robust, ethical, and impactful clinical trials in Africa. This will enable the continent to participate actively as part of the global scientific community, which will significantly contribute to providing unique insights and innovations for responding to diseases and health threats.

The imperative for strengthening a sustainable clinical trials ecosystem in Africa extends beyond the need to respond to pandemics or manage current health crises. It requires a deliberate continental strategy, long-term plan, sustainable funding, and strong coordination to strengthen clinical trial infrastructure, enhance regulatory frameworks, and invest in digital health technologies and local manufacturing capabilities. The ongoing efforts at building the clinical trial ecosystem on the continent must be scaled up through concerted efforts by African governments, African philanthropists and international partners, grounded in equity, respect, and mutual benefit principles. North-South collaborations are being built on mutually respectful partnerships for combined benefits emanating from co-creation. As clinical trial capacities are established and expanded in Africa, the continent’s needs should be prioritized as there is a need to foster equity in terms of accessing clinical trial data and sharing benefits emanating through clinical trials. This needs to be accompanied by the transfer of technologies and skills to local African collaborators and scientists. Investing in building Africa’s clinical trial ecosystem will facilitate the gradual move to inclusive, innovative, and responsive health outcomes that can adequately support pandemic response on the continent and contribute to the global health response. This strategic investment in Africa’s future will pay dividends for pandemic preparedness and the broader quest for a healthier, more equitable world.