Around the Globe: Africa
Drug Development and Clinical Research in Africa
Part 2: African Clinical Trials, Good Clinical Practice, and Diversity: Practical Challenges and Considerations
Lisa Ursella Collins
Innomas Clinical Research
Leslie Sam
Leslie Sam and Associates
Jayesh Pandit
Patient Safety Advocate, Kenya
Helen Ndagije
Uganda National Drug Authority
Wangui Mathenge
International Society of Pharmacovigilance Africa Chapter

oth experienced and aspiring research professionals with an interest in participating in more global drug development and clinical research activities are keen to see an increase in the contribution of African countries to global research programs and in the increased arsenal of interventions that could potentially increase treatment options for their patients.

“There is a longstanding need to have more representation from Africa within the processes of global drug development, and this need has become even more evident in light of emerging diseases and their novel treatments,” explains Kenyan pharmacovigilance and patient safety advocate Jayesh Pandit. “Although the number of trials in Africa has been on an increase, there remain very few phase 1 and 2 trials. Africa typically remains a recipient of ‘medicines’ rather than ‘innovative, game-changing molecules.’ Early involvement of Africa, I believe, will give a more balanced and wholesome representation in global data. Similarly, there is an urgent need to have more post-approval safety-related data coming from Africa. There is little African-generated data within global databases, and hence our unique responses to novel medicines and biologicals, and consequently our safety-related risks and our risk management systems, may not be up to date.”

Helen Ndagije of the Uganda National Drug Authority summarizes the challenges that African countries face when trying to engage in global clinical trials:

  • Limited involvement in trial protocol development: Africa mostly implements completed (finalized) research protocols, which do not easily accommodate site-specific implementation.
  • Lack of data ownership and limited infrastructural capacity to support data handling.
  • Reliance on data with no specific mechanisms for evaluating processes and methods that generated the data.
  • Some sponsors provide limited safety and efficacy information under the guise of proprietary protection.
  • Disproportionate underrepresentation of Ugandan scientists in protocol development and publications authorship.
  • Limited laboratory capacity for sample testing.
  • Language barriers and time zone differences for multisite trials.
  • Extrapolating Western health systems to African health systems when reviewing global clinical trial applications.
  • Lack of easily accessible, post-COVID information from regulators beyond Africa.

“The very nature of trying to attract a global clinical trial to consider a site in Kenya or any other African country as a clinical trial study site in the development of new-generation or cutting-edge drugs so as to have a rich and diverse study group in the clinical trials has been an uphill task,” concurs Wangui Mathenge of the International Society of Pharmacovigilance Africa Chapter. “This could be due to a number of reasons: poor return on investment from the sponsor’s/investor’s perspective, which could be based on the fact that Africa is perceived to have ‘poor purchasing power’ when it comes to purchasing drugs; inadequate legal and/or regulatory frameworks for data protection and/or intellectual property protection, from both the patient’s perspective and the manufacturer’s perspective; and a very diverse and unharmonized drug regulatory framework in and across Africa, making the process of participating in a global clinical trial much harder.”

Thinking Outside the Box, Intentionally Shifting Mindsets

Investigators, research staff and site identification and training, supply chain, appropriate documentation, protocol deviations, patient consent, and access to equipment and materials are just some areas of research that continue to present global challenges when conducting clinical trials, including in Africa.

Due to the lack of participation of African countries in clinical research on the world stage, sponsors looking to conduct research in Africa may need to invest in long-term support to provide training and other resources since it’s likely that many clinical sites in Africa will be “research naïve.” This is not a unique or unreasonable expectation. Trial sponsors in the growing rare-disease field often find themselves investing in naïve sites out of sheer necessity because patients with rare diseases are typically under the care of physicians without industry research experience, located in research-naïve facilities. There is a corresponding and increasing need in the US to identify, train, and invest (long term) in naïve sites as experienced sites not only become saturated but are insufficient in number to keep up with increasing clinical trial demand. Can the approaches used to identify, train, and build long-term relationships with US sites in New Orleans, Louisiana, be replicated at sites in Kigali, Rwanda?

There are other areas where innovation and new ways of thinking have been implemented. ICH GCP, for example, is designed to operate in a culture based on Western lifestyles and cultural constructs but has been implemented in other regions, including in Africa. Implementing it globally comes with certain challenges. For example, in cultures where it is commonplace for a grandmother or grandfather to serve as primary caregiver for a child their entire life but who may not be a blood relative of the child, or may not have legal guardianship paperwork for the child, how do we arrange the consent of the child to participate in a study? There are other examples where ICH GCP principles may not account for a region’s social norms and may require review or revision to maintain the same level of patient safety, rights, and well-being, and yet account for different cultural environments.

But the challenges within the diversity of the 55 African countries are not monolithic. A research team in rural Mozambique will face unique challenges compared to a team executing a study out of a hospital group with numerous locations in metropolitan Lagos, Nigeria. The drug developer’s job is to provide proactive solutions to challenges, make informed decisions, and adapt to the local environment.

Diversity, Equity, and Inclusion

Industry has recently shifted its focus toward diversity, equity, and inclusion (DE&I) in clinical trials. Conversations regarding the heterogeneity of clinical and genetic data have been amplified. In April 2022, the FDA issued a guidance document to provide recommendations “to sponsors developing medical products on the approach for developing a Race and Ethnicity Diversity Plan … to enroll representative numbers of participants from underrepresented racial and ethnic populations in the United States.” Though the focus of the guidance is the US, this has amplified conversations about health equity globally and steered attention toward Africa.

Does this further open Africa up to the risks (and benefits) of being included in trials to meet enrollment targets? For sponsors truly committed to global health equity, this era may be the catalyst to focus research on Africa and advance the understanding that data from Africa could contribute genetic and clinical information that potentially benefits not only the 1.4 billion people in Africa but those of African descent located across the diaspora as well as other populations.

As the US shifts towards more actively including “African-American” patients in clinical trials, similarities in factors that impact their enrollment are mirrored on the African continent: Mistrust, lack of community and cultural understanding, and historical abuses have also been seen across African countries. From the Tuskegee Study to Henrietta Lacks’ cells to the 1996 Trovan study conducted in northern Nigeria, to misuse of DNA from nearly 2100 genomes of Ugandan people, lack of trust in clinical research and drug development among Africans and those of African descent across the diaspora is a genuine barrier to enrollment.

A significant risk to the conduct of African clinical trials that meet global standards is that African populations are often looked upon as needing to be “saved” and are approached with an attitude of charity. The sentiment that the research being conducted in a rural setting, for example, has the potential to save many lives, or is of interest for the greater good, and therefore outweighs upholding the principles of GCP, leads to the question: Are the participants in studies conducted by such researchers aware that they are part of a clinical trial and what this means? How often are samples and data being used to benefit or satisfy the curiosities of the West without the knowledge or consent of research participants?

The paucity of clinical trials across the continent also leads to unawareness, or inadequate application, of global trial standards by research-naïve professionals who have only experienced research in the setting of their own country. Conversations with researchers in different African countries confirm their being approached by sponsors to conduct studies in pregnant women or to investigate oncology investigational products at higher doses than used in countries outside Africa. These practices create the distrust that Africans across the continent and diaspora have towards clinical research. They also highlight the need for researchers with global experience, from across the continent and around the world, to disseminate their knowledge of global standards to support the growth of clinical trials and drug development across Africa, and the need for sponsor companies to be strictly regulated as they conduct clinical trials in African countries.

These attitudes towards research conducted across Africa are detrimental to the protection of the safety, rights, and well-being of African populations and are sometimes expressed by medical doctors who do not distinguish between a medical practitioner and a research professional. Illiterate and poor populations are some of the most vulnerable; however, illiterate and poor does not equate to unintelligent or unworthy of dignity, and we would do well to remember that the population of Africa includes millions of literate children and adults, with an average literacy rate of 67%.

The authors thank Ian Mugisa, Joyce Batera, Marvin Buleera, Keneth Mugisa, Diana Nakitto, and Sharon Kiggundu from the Uganda National Drug Authority for their contributions to this article.