Clinical Trials In Africa Research Articles

Lessons from enriching Tanzania’s clinical research ethics clinical trials oversight and pharmacovigilance through the ASCEND project

Engaging in clinical trials in Africa not only enhances researchers' comprehension of local health concerns but also plays a crucial role in tackling global health challenges. In Tanzania, there has been a surge of clinical research for the past 10 years indicating a need to improve ethical and clinical trial regulatory capacity. Several initiatives to address the clinical trial regulatory and ethics challenges have been done. Lessons from such initiatives are important to inform evidence-based decision-making for sustainability. The ASCEND project with the theme of “Moving Tanzania’s Clinical Research Ethics and Medicines Regulatory Capacity to the Next Level: Fostering Medicine Quality, Safety and Good Clinical Practice (GCP) on Clinical Trials” was implemented in Tanzania Mainland and Zanzibar from November 2020 to December 2023. A thorough review of the project implementation reports and on deliverables was conducted to identify the lessons learned. Inductive content analysis was used to analyze the information. A total of seven lessons were deduced from the reviewed documents. These include capacity building through training on clinical trials review and approval process, research ethics and GCP inspection which cannot be overlooked; engaging the community in reporting adverse drug events is worth considering; digitalization of electronic systems enhances clinical trial control and creates a dynamic regulatory ecosystem; compliance to requirements for clinical trials conduct is enhanced by training of early and mid-career researchers; networking and broad stakeholders’ engagement and participation in ethics and regulations governing clinical trials is a cornerstone for strengthening collaboration between researchers and regulators; the need for electronic systems for monitoring and evaluation of the project is inevitable and the need for adhering to project timelines is crucial for successful implementation of the project. Sustainability is the take-home message from the ASCEND project and should inform stakeholders for future improvement. Continuous investment and advancement in research ethics and regulatory oversight across Africa should be prioritized.

Breaking the barriers for conducting clinical trials in Africa: A need for higher commitment and collaborations

Breaking the barriers for conducting clinical trials in Africa: A need for higher commitment and collaborations

Analyse des limites du partenariat France–Afrique en recherche biomédicale à travers les données de la bibliométrie et des essais cliniques

France is the fifth largest contributor to official development assistance, with 7% of its aid directed towards health and 39% towards African countries. Databases now make it possible to address the quantitative impacts of this policy. This study analyzes biology and health publications co-authored by France, African countries, and major countries between 2012 and 2021, as well as joint clinical trials. The results reveal that France remains focused on infectious diseases, but is slowly declining in output volume, now ranked fourth and overtaken by Germany and other European countries that have diversified their cooperation in other areas. France maintains bilateral relations with African regions with which it has historical ties, while collaborations with other regions occur within the framework of international networks. Clinical trials in Africa remain low relative to the population, and the observed growth, which has doubled in 10 years. They come primarily from Egypt, a country which has been able to diversify beyond infectious diseases. This is not the case for France: the 63 interventional trials sponsored by France in Africa are limited to infectious diseases and epidemiology. This study suggests the need for a rebalancing of public development assistance to support research, with a focus on strengthening bilateral aid, supporting sectors such as chronic diseases, and evaluating partnerships to enable excellence in research and expertise.

Cancer Research in sub-Saharan Africa: Progress in closing the gap

Cancer presents an escalating challenge in Sub-Saharan Africa (SSA), necessitating strategic interventions grounded in regionally relevant evidence-based medicine. Informed decision-making is critical to formulate effective strategies for cancer prevention, diagnosis, funding, and treatment within the SSA population. The aim of this study is to highlight ongoing clinical trials in SSA, emphasizing the continuous initiatives aimed at filling existing knowledge gaps. Further, the study seeks to assess whether SSA is progressing or stagnating in the global landscape of cancer research. A comprehensive review of research papers and online registries on clinical trials was executed, focusing on English-language journal articles retrieved from the PubMed database. Additionally, a quantitative, web-based, retrospective review was conducted on registered cancer studies in SSA over the past decade (2000-2023) from ClinicalTrials.gov and the Pan African Clinical Trials Registry (PACTR) databases. The review resulted in the inclusion of 71 articles from PubMed, alongside 104 and 140 clinical trials from ClinicalTrials.gov and PACTR databases, respectively. Aggregate findings from PubMed and clinical trial databases revealed that East Africa is the predominant contributor (37%) to cancer clinical trials, whereas Central Africa exhibited the lowest contribution (4%). Notably, PubMed indicated a predominant focus on cervical cancer in clinical trials. Between 2000 and 2015, less than 4% of global cancer clinical trials listed on ClinicalTrials.gov were performed in SSA; in subsequent years, there was an observable increase in the percentage of total trials performed in SSA. Analyses of funding sources revealed that 45% and 32% of clinical trials in SSA were supported by the United States and the United Kingdom, respectively. In the last two decades, the formation of entities like the African Consortium for Cancer Clinical Trials, spearheaded by BIO Ventures for Global Health in partnership with African ministries of health, cancer hospitals, private industry, research institutions, and global oncology experts, contributed to increasing the effective implementation of multicenter clinical trials in Africa. Noteworthy instances, such as the Burkitt's lymphoma and HypoAfrica studies, serve as examples of the results arising from these collaborative initiatives, reflecting substantial progress within SSA’s cancer research landscape.

Responsive Sensory Evaluation to Develop Flexible Taste-Masked Paediatric Primaquine Tablets against Malaria for Low-Resource Settings.

Primaquine is an important antimalarial drug for malaria transmission blocking and radical cure, but it is not currently available in child-friendly formulations in appropriate doses. Adult-strength tablets are often crushed and dissolved in water to obtain the required dose, which exposes the drug's bitter taste. As part of the developing paediatric primaquine (DPP) project, this study adopted a responsive sensory pharmaceutics approach by integrating real-time formulation development and pre-clinical taste assessment to develop palatable, flavour-infused primaquine tablets. A design of experiment (DoE) approach was used to screen different taste-masking agents and excipient blends with trained, expert sensory assessors, with quinine hydrochloride as a model bitter tastant. The taste-masking efficacy of selected prototype formulation blends was validated with naïve assessors using the highest 15 mg primaquine dose. The mean bitterness intensity rating, measured on a discrete 11-point scale, was halved from 7.04 for the unflavoured control to 2.74-3.70 for the formulation blends. Sucralose had the biggest impact on bitterness suppression and improving palatability. Two different flavouring systems have been developed, and their acceptability in paediatric patients will be assessed as part of upcoming validation field clinical trials in Africa.

An ethics of anthropology-informed community engagement with COVID-19 clinical trials in Africa.

The COVID‐19 pandemic has reinforced the critical role of ethics and community engagement in designing and conducting clinical research during infectious disease outbreaks where no vaccine or treatment already exists. In reviewing current practices across Africa, we distinguish between three distinct roles for community engagement in clinical research that are often conflated: 1) the importance of community engagement for identifying and honouring cultural sensitivities; 2) the importance of recognising the socio‐political context in which the research is proposed; and 3) the importance of understanding what is in the interest of communities recruited to research according to their own views and values. By making these distinctions, we show that current practice of clinical research could draw on anthropology in ways which are sometimes unnecessary to solicit local cultural values, overlook the importance of socio‐political contexts and wider societal structures within which it works, potentially serving to reinforce unjust political or social regimes, and threaten to cast doubt on the trustworthiness of the research. We argue that more discerning anthropological engagement as well as wider collaboration with other social scientists and those working in the humanities is urgently needed to improve the ethics of current biomedical and pharmaceutical research practice in Africa.

Action for Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials-Is Africa the Answer? Report From a Satellite Session of the Accelerating Anti-Cancer Agent Development and Validation Workshop.

Patients of African ancestry are not well-represented in cancer clinical trials despite bearing a disproportionate share of mortality both in United States and Africa. We describe key stakeholder perspectives and priorities related to bringing early-stage cancer clinical trials to Africa and outline essential action steps. Increasing Diversity, Market Access, and Capacity in Oncology Registration Trials—Is Africa the Answer? satellite session was organized at 2021 Accelerating Anti-Cancer Agent Development and Validation Workshop. Panelists included representatives of African Organization for Research and Training in Cancer, Uganda Cancer Institute, Uganda Women's Cancer Support Organization, BIO Ventures for Global Health, Bill & Melinda Gates Foundation, the US Food and Drug Administration, Nigeria's National Agency for Food and Drug Administration and Control, Bayer, and Genentech, with moderators from ASCO and American Cancer Society. Key discussion themes and resulting action steps were agreed upon by all participants. Panelists agreed that increasing diversity in cancer clinical trials by including African patients is key to ensuring novel drugs are safe and effective across populations. They underscored the importance of equity in clinical trial access for patients in Africa. Panelists discussed their values related to access and barriers to opening clinical trials in Africa and described innovative solutions from their work aimed at overcoming these obstacles. Multisectoral collaboration efforts that allow leveraging of limited resources and result in sustainable capacity building and mutually beneficial long-term partnerships were discussed as key to outlined action steps. The panel discussion resulted in valuable insights about key stakeholder values and priorities related to bringing early-stage clinical trials to Africa, as well as specific actions for each stakeholder group.

Strengthening laboratory capacity for HIV vaccine clinical trials and epidemiological studies in Eastern and Southern Africa

Background: Conducting successful HIV vaccine clinical trials in resource-limited settings is hampered by lack of adequate laboratory capacity at trial sites, poor infrastructure, lack of well-trained technical personnel, and inadequate laboratory quality management Systems. We describe our approach to establishing sustainable laboratory capacity for clinical trials in Africa. Methods: IAVI identified 9 CRCs where a capacity building program that supports immunology and clinical testing was established. Information from the 9 CRCs was collected retrospectively and compiled in Microsoft excel for descriptive statistics. Mapping was done in Quantum Geographic information system. Results: Newly built and refurbished laboratories have been equipped with the required testing laboratory equipment. All CRC laboratories (n=10, 100%) received Good Clinical Laboratory Practice (GCLP) accreditation between 2004 and 2016, and accreditation maintained annually. A total of 89 audits were done between 2005-2019. KAVI and KEMRI had the highest number of audits (n=11, 12.4%). IAVI successfully trained a total of 1811 individual, of which (n=1130, 62.7%) trained on GCLP, (n=330, 18.3%) Quality Management Systems, (n=311, 17,2%) laboratory techniques and (n=32,1.8%) between 2004 and 2021. All the 13 Assays were registered in either College of American pathologist (CAP) or Royal college of pathologists of Australasia (RCPA) for Proficiency testing. Conclusion: The establishment of GCLP accredited laboratories and well-trained personnel has created centers of excellence and it has enabled them to attract independent competitive research funding. The GCLP accreditation and standardized testing procedures ensured reliable and accurate data, especially important for multi-country and multi-center studies.

A Review Assessing Participants’ Understanding of Informed Consent for Clinical Trials in Africa

Background: Informed consent provides detailed information to the participants to make informed voluntary and rational decision to participate in a study. It is a communication tool between investigator and the subject to ensure that high research ethical standards are followed. This review paper assessed the level of participants’ understanding of the information given to them by researchers during the clinical research. Methods: A review approach was used to achieve the study objective. Results: The findings showed that the level of comprehension varied from study to study. There was a good comprehension in four domains; purpose, voluntariness, benefits and right to withdraw. Poor comprehensions were mostly in risks, side effects, and blinding. Higher level of education, repeated assessments of comprehension, time spent by the researcher explaining and clarifying the information influenced the comprehension. Conclusion: The study findings point out that comprehension to informed consent is still a challenge that needs to be addressed during the field study. Once the consent is given it becomes a distant memory for most of the participants. This implies that proper tools and cut off points to determine participants’ comprehension need to be developed for standard assessment of such.

Cancer Clinical Trials in Africa-An Untapped Opportunity: Recommendations From AORTIC 2019 Conference Special Interest Group in Clinical Trials.

Cancer is now a formidable health care burden in sub-Saharan Africa (SSA) due to lifestyle westernization and longer life expectancy. The exponential increase in cancer incidence coupled with high mortality rate is not comparable with that seen in westernized countries. To address global cancer disparity, globalization of cancer clinical trials to involve sub-Saharan Africa can serve as a platform where innovative targeted therapies can be made available to patients in the environ. In the 2019 African Organization for Research and Training in Cancer (AORTIC) conference held at Maputo, Mozambique, a group of clinical trialists spanning across multiple continents highlighted the opportunities in Africa for the conduct of cancer clinical trials. The secondary purpose of the meeting was to address the belief that Africa was incapable of conducting interventional cancer trials but showed the in-continent strengths, such as available capacities, trained local clinical trialists with clinical trial experiences, clinical trial consortia, local capabilities, mapping out logistics, ethical consideration, political will, real-time benefits of clinical trials to clinical practice, and future directions for trials.

Evaluation of Critical Quality Attributes of a Pentavalent (A, C, Y, W, X) Meningococcal Conjugate Vaccine for Global Use.

Towards achieving the goal of eliminating epidemic outbreaks of meningococcal disease in the African meningitis belt, a pentavalent glycoconjugate vaccine (NmCV-5) has been developed to protect against Neisseria meningitidis serogroups A, C, Y, W and X. MenA and X polysaccharides are conjugated to tetanus toxoid (TT) while MenC, Y and W polysaccharides are conjugated to recombinant cross reactive material 197 (rCRM197), a non-toxic genetic variant of diphtheria toxin. This study describes quality control testing performed by the manufacturer, Serum Institute of India Private Limited (SIIPL), and the independent control laboratory of the U.K. (NIBSC) on seven clinical lots of the vaccine to ensure its potency, purity, safety and consistency of its manufacturing. In addition to monitoring upstream-manufactured components, samples of drug substance, final drug product and stability samples were evaluated. This paper focuses on the comparison of the vaccine’s critical quality attributes and reviews key indicators of its stability and immunogenicity. Comparable results were obtained by the two laboratories demonstrating sufficient levels of polysaccharide O-acetylation, consistency in size of the bulk conjugate molecules, integrity of the conjugated saccharides in the drug substance and drug product, and acceptable endotoxin content in the final drug product. The freeze-dried vaccine in 5-dose vials was stable based on molecular sizing and free saccharide assays. Lot-to-lot manufacturing consistency was also demonstrated in preclinical studies for polysaccharide-specific IgG and complement-dependent serum bactericidal activity for each serogroup. This study demonstrates the high quality and stability of NmCV-5, which is now undergoing Phase 3 clinical trials in Africa and India.

Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?

Safety and efficacy of rituximab in Malawi: a case for multicentre oncology clinical trials in Africa?

Oncology Clinical Trials in Africa: Partnering for Quality.

Oncology clinical trials are requisite for testing the safety and effectiveness of promising treatments and deciphering new knowledge into concrete benefits for patients. They present opportunities to innovate promising, novel cancer remedies. A dearth of local evidence to guide cancer treatment in Africans is creating an increased interest in oncology clinical trials to improve patient care. This is primarily because of limitations in pathology, surgery, medical oncology, radiation, and palliation that are leading to worse cancer outcomes on the continent.Investment in oversight of Human Research Ethics committees and Medicines Regulatory Authorities in Africa has improved the potential for many countries to host clinical trials. However, the distribution of cancer trials remains poor across the continent, resulting in inadequate treatment options for patients with cancer.There are some initiatives aimed at developing research capacity to host trials in Africa. However, there is now a need to establish strategic partnerships whose aim should be to achieve harmonized, accredited Clinical Trials Units capable of running trials to meet Good Clinical Practice standards. This article discusses what has been achieved and proposes a model for quality oversight of Clinical Trials Units in Africa.

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4.

BackgroundClinical laboratory reference intervals (RIs) are essential for diagnosing and managing patients in routine clinical care as well as establishing eligibility criteria and defining adverse events in clinical trials, but may vary by age, gender, genetics, nutrition and geographic location. It is, therefore, critical to establish region-specific reference values in order to inform clinical decision-making.MethodsWe analyzed data from a prospective observational HIV incidence cohort study in Kombewa, Kenya. Study participants were healthy males and females, aged 18–35 years, without HIV. Median and 95% reference values (2.5th percentile to 97.5th percentile) were calculated for laboratory parameters including hematology, chemistry studies, and CD4 T cell count. Standard Deviation Ratios (SDR) and Bias Ratios (BR) are presented as measures of effect magnitude. Findings were compared with those from the United States and other Kenyan studies.ResultsA total of 299 participants were analyzed with a median age of 24 years (interquartile range: 21–28). Ratio of males to females was 0.9:1. Hemoglobin range (2.5th—97.5th percentiles) was 12.0–17.9 g/dL and 9.5–15.3 g/dL in men and women respectively. In the cohort, MCV range was 59-95fL, WBC 3.7–9.2×103/μL, and platelet 154–401×103/μL. Chemistry values were higher in males; the creatinine RI was 59–103 μmol/L in males vs. 46–76 μmol/L in females (BRUL>.3); and the alanine transferase range was 8.8–45.3 U/L in males vs. 7.5–36.8 U/L in females (SDR>.3). The overall CD4 T cell count RI was 491–1381 cells/μL. Some parameters including hemoglobin, neutrophil, creatinine and ALT varied with that from prior studies in Kenya and the US.ConclusionThis study not only provides clinical reference intervals for a population in Kisumu County but also highlights the variations in comparable settings, accentuating the requirement for region-specific reference values to improve patient care, scientific validity, and quality of clinical trials in Africa.

Why is there a paucity of clinical trials in Africa?

SummaryDisproportionately few clinical trials are undertaken on the African continent, in part due to lingering neocolonial attitudes in the Global North which keep research activity primarily in developing countries, while being skeptical of the abilities of those in the Global South to undertake organized clinical studies. In the era of the COVID-19 pandemic, applicable research and clinical trials should be undertaken in relevant populations in order to extrapolate to a population level. This is all the more important in Africa, which has a rich genetic diversity. We suggest that a lack of organized research ethics committees across the continent and a deficiency of appropriate training are responsible in part for the reluctance of clinical trial organizers in the developed countries of the Global North to engage with medical leadership in Africa. We consider ways of alleviating this problem, including suggesting a pan-continental surveillance of ethics committee agendas and of training, either through the auspices of the African Union or the World Health Organization. In addition, medical leadership in African nations must be encouraged to take ownership of their medical ethics agendas to facilitate decent international clinical trial participation for the good of the continent as a whole.

In the COVID-19 era, let's keep an eye on clinical trials in Africa.

In the COVID-19 era, let's keep an eye on clinical trials in Africa.

Challenges of HIV Lymphoma Clinical Trials in Africa: Lessons From the AIDS Malignancy Consortium 068 Study.

The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.

Landscape of Oncology Clinical Trials in Africa

PURPOSEThe burden of cancer in Africa is of significant concern for several reasons, including that incidence of cancer in Africa continues to rise while Africa is also dealing with communicable diseases. To combat cancer in Africa, oncology clinical trials are needed to develop innovative interventions for cancer prevention, screening, diagnosis, treatment, and survivorship. Unfortunately, there is a paucity of clinical trials in Africa and it is difficult for African clinicians to get information on open oncology clinical trials and impossible for African patients with cancer to access this information. The primary objective of this study was to identify open oncology clinical trials in Africa.METHODSThis project was part of a large-scale study to develop an African Virtual Platform for Oncology Clinical Trials Registry. The study was a quantitative, web-based, retrospective review of clinical trials registries.RESULTSA total of 109 open oncology clinical trials were identified. Most of the trials were in Egypt, South Africa, Algeria, and Kenya. The top cancer types for oncology clinical trials in Africa were breast, cervical, and lung cancers. The top sponsor of oncology clinical trials in Africa was academic institutions, especially institutions in the United States.CONCLUSIONThe paucity of clinical trials in Africa will continue to magnify the global disparities of cancer in the African population. Clinical trials are needed to ensure therapeutic interventions are safe and effective in the African population. In the era of personalized and precision health, it no longer suffices to assume that drugs developed in North America, Europe, or Asia will be effective in the African population.

Historical Perspectives on Ethical and Regulatory Aspects of Human Participants Research: Implications for Oncology Clinical Trials in Africa.

Clinical trials research involving human participants has led to numerous medical advances. Historically, however, clinical trials research was the source of major concerns for the safety and welfare of the human participants taking part in these studies. The ethical principles of autonomy, beneficence, and justice came about in response to medical atrocities, and regulations were ultimately put in place to protect the rights and welfare of human participants and to maintain the public trust in the research enterprise. Today, clinical trials are one of the most heavily regulated practices in the world, and yet still not all people are provided the same oversights and protections, with improprieties disproportionately affecting poor-resource nations and vulnerable populations. As Africa approaches the post–communicable disease era, cancer is set to take the lead as the most burdensome disease, making the need for oncology clinical trials in Africa greater than ever before. Africa represents a heterogeneous market with 55 countries, most with their own National Regulatory Agency (NRA) and each with varying levels of regulatory maturity. This diversity creates a highly complex regulatory environment and causes challenges when bringing drugs to market. There is a large need for harmonization and increased collaboration between the African nations’ NRAs. In addition, many African countries need to be better equipped to handle research ethics committees and/or learn how to rely on neighboring countries with more established ethics committees. Well-run clinical trials offer solutions to national health care problems, and all people deserve equal access to their benefits.

Partnerships and Collaborations: The Right Alliances for Clinical Trials in Africa.

Africa attracts < 1% of all trials conducted around the world. The implication is that proof of safety and efficacy in Africans is lacking for a lot of new therapies. The sizeable proportion of approximately 20% of the global population that Africa represents largely does not have empiric data to support use of new therapies in a population with a distinct genetic and racial profile. Beyond the imperative of evidence-based interventions, Africans carry a disproportionately heavy burden of certain diseases, including prostate cancer, sickle cell anemia, and malaria. It therefore provides opportunity for efficient recruitment of participants for trials for such diseases. However, this advantage has not convinced sponsors to carry out clinical trials in Africa. India and China each have roughly the same population size as Africa, but each presents just one regulatory jurisdiction for clinical trials. Africa has 54 countries, and a sponsor would theoretically need to file 54 different applications to cover the entire continent. Collaboration and partnership among all stakeholders in the clinical trial ecosystem will reduce the burden on sponsors and make Africa competitive as a destination for clinical trials. Collaboration among national regulatory agencies will enable Africa to be treated as one regulatory jurisdiction and reduce administrative burden. Sites and researchers can partner to improve quality, attain necessary certifications, and increase overall efficiency. Central to all of these are clinical research organizations that can coordinate and work across borders to make clinical trial projects seamless. Ultimately, patients will benefit as quality of clinical practice improves and access to new therapies is enhanced.