Clinical trials are needed to address this disproportionately high burden of communicable (e.g.; HIV/AIDS, tuberculosis, and malaria) and non-communicable diseases (e.g., diabetes) in developing countries, for identification of efficient and effective new diagnostic and treatment modalities.

According to Shamley et al, ( 2007)¹ “Research in Africa, is regarded as a ‘luxury’, rather than a necessity and accounts for 2% of world research, yet the region accounts for 25% of the global disease burden and 15% of the world’s population. It is noteworthy that despite clear evidence that; Clinical trial activities and development of more effective and less toxic therapies have led to significant improvements in morbidity and mortality from cancer in HICs, that Africa, with its growing cancer burden, remain, drastically under-represented in cancer clinical trials. In real terms, the figures are quite appalling, as we see that Africa which contributes up to 17.9% to world population, only participates in 1.4% of, ‘The Total Global Clinical Trial Volume”.²

This gross under-representation in ‘Global Clinical Trials’ and research activities contribute to sustained health inequities in LMIC countries, especially Africa, with attendant consequences of; Limited Progress in Understanding the African Genome, & Slow Healthcare System Development.³

The COVID19 pandemic has further highlighted the gap in access to African sites for vaccine trials, and a clear mandate for ‘African Clinical Trial Consortium-ACTC’s proffered solution for increasing Africa’s participation in Global Clinical Trials. In order to exploit the opportunities thrown up by Africa’s increased Oncology/other NCD’s Disease Burden & gap noted with the present pandemic, ACTC is providing  an Internationally-acceptable ‘Quality Management Echo-System⁴ (ACTC-QMeS), for strategic development; of well-coordinated, harmonized, Multi-therapeutic ‘Clinical Trial Units’/sites in the African region, capable of running trials to GCP standards, and of databases for existing ‘GCP-ready Clinical Trial Units’, in Africa,. These units would be an asset to these countries, in future endemics and pandemics.

Despite the pressure & current growth in the requirement for clinical trials to be run in populations other than those of High-Income Countries (HIC), & for compliance with ensuring diversity in ‘Trial Participant’s demographics’ (which is an NIH Charge), the reality we have at hand, in Africa, is that; The Clinical Trial Sector Is Still Plagued by The Following Challenges & Barriers;

Basically, 5 Systems drive the Barriers for conducting clinical trials;

These are, in total, 5 SYSTEMS cementing the circumstance of few high-quality clinical trials in Africa

• Lack of confidence in the ‘Clinical Trial Quality Management Systems’ by all relevant stakeholders (This System constitutes ‘The Focus’ of ACTC efforts)
• Underdeveloped and highly diverse local health care systems
• Unharmonized, Sparse Commitment, and partly unstable political and economic systems
• Lack of incentives for the healthcare market participants
• Stereotyped ‘Lack of trust’ of the African population

These systems can be summarized to be; financial and human capacity barriers, ethical and regulatory system obstacles, inadequate research environment, operational barriers, & competing demands.

Exemplary reasons underscoring these 5 systems include.

• Poor human capacity, limited research community and infrastructure, limited experience, and expertise
• Lack of resources, equipment, technology, or skilled workforce
• Lack of funding and budgetary commitment, lack of harmonized regulation and registries in some countries
• Local market demand for medical solutions might not ensure profitability
• Non-existent/un-funded ethical review boards, lack of media communications to provide full context, Sensational journalism by uninformed African Media

Ethical challenges, identified as draw backs to the success of any prospective clinical trial in the Nigeria, based on experiences garnered from the ‘Nigeria HIV-BMD’ study, include; infrastructural deficits, unavailability of cutting edge technology for advanced studies, lack of interest on the part of funders to support clinical trials that are designed to address local health problems in countries with poor market economy, inadequate capacity to conduct clinical trials and adequacy of the consenting process.(SAM & GERD)

Further elaborating on the barriers, some studies, documented:

• That site governance of trials and the necessary infrastructure in Africa are low and, where they exist, the standard is variable. 
• That Current QMS for CTUs in Africa, remain poorly implemented and ineffective, ultimately leading to a lack of confidence in the system and a low number of trials
• lack of consolidated research teams and commitment
• lack of reliable internet access and staff skilled in research. 
• limited learning opportunities (which negatively affect human resources), 
• lack of recognition and career options, 
• lack of experience, poor planning and problems with trial management. 

Two key issues, which were mirrored in a feedback received from the delegate workshops during the 2019, Africa Clinical Trial Consortium -ACTC Summit, in Cape town, were:

• The importance of planning phase of clinical trials, which includes budget feasibility, clear project ideas, realistic deadlines, understanding trial processes, contextual adaptation and involvement of site staff in planning de novo.
• Site Organization, described as staff turnover, employment conditions, career pathing, delegation and workload and governance, was the Second, and important proviso 

Generally, it was noted that, though Lack of interest by clinical investigators was not a barrier, lack of resources was highly significant. 

Proffered solutions

These Challenges & Barriers are not dissuading but rather, became the drivers that challenged ACTC to rise up & offer the creative/innovative/& credible solution of ACTC-Quality Management Echo-System (ACTC-QMeS), capable of instilling confidence, in Industry & other CT Sponsors, quickly, efficiently and sustainably, for the future.

ACTC is thus Building Stakeholder Confidence and Site Capacity⁵, by leveraging some opportunities to proffer solutions to these Challenges & Barriers! 

Harmonization of standards for clinical trial sites definitely portends significant promise in improving clinical trials. The template of this ‘Harmonization of Standards’ could be leveraged to accommodate formation of a ‘Site Accreditation System’ globally. 

Accreditation processes are designed to ensure optimal performance at all levels of trial implementation. To circumvent the problem of Clinical Trials Units (CTUs) with variable standards, Europe created criteria for accreditation of sites and, more recently, the USA produced a document detailing the harmonization and accreditation of all research units including trial sites (AAHRPP).

Conclusion

It is instructive that, the NIH restructured Clinical trials definition to include ‘behavioral outcomes’, January of 2015. This defines, its current definition, which reads:  “A research study in which one or more human participants are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes”^6. Thus, the area of Implementation Science & Investigator initiated Clinical Trials become ‘Low Hanging Fruits’ for Africa to quickly develop it’s capacities and position itself for inclusion in Global Clinical Trial Industry⁷.

Beyond the rigorous assessment of natural medicines, other anticipated benefits of ACTC include the expansion of Africa’s cost-effective clinical capabilities to meet global standards, acceleration of clinical trial timelines in Africa, incorporation of a translational research mentality into Africa’s research institutions, and additional definition and institutionalization of the continent’s regulatory systems.(check Graaf & Okoye)⁸

REFERENCES

1. Shamley, D.R., Srinanaganathan, R., Weatherall, R., Oskrochi, R., Watson, M., Ostlere, S., et al. (2007) Changes in shoulder muscle size and activity following treatment for breast cancer. Breast Cancer Research and Treatment, 106, 19-27.
   
   
2. Pivotal Clinical Trials for New Molecular Entity Drugs and Biologics Approved by FDA From 2010 to 2012, American Journal of Therapeutics: November/December 2015 - Volume 22 - Issue 6 - p 435-455 doi: 10.1097/MJT.0000000000000177
   
   
3. Dube MP,  Qian  D,  Edmondson-Melancon  H, Sattler  FR, Goodwin  D,  Martinez C,  Williams  V, Johnson  D,  Buchanan    Prospective,  intensive study  of  metabolic  changes associated  with  48 weeks  of  amprenavir-based  antiretroviral therapy. Clin Infect Dis 2002; 35:475–81
   
   
4. ERG, 2016. Eastern Research Group, Inc. Quality Assurance Project Plan for ECHO Website. September 2016.
   
   
5. World Health Organization. International Clinical Trials Registry Platform. March 2, 2014.
   
   
6. Africans begin to take the reins of research into their own genomes by Elizabeth Pennisi; Feb. 4, 2021 , 2:15 PM
   
   
7. Clinical Research Resource HUB, ClinicalTrials.gov: Definition of a Clinical Trial: Last revised: 05/14/
   
   
8. Food fortification. In de Jong N, Adam SGM, de Groot LCPGM, de Graaf Variability of micronutrient content in enriched dairy and fruit products. International Journal of Food Science and Nutrition. 1993;51:247-257. Tyndall JA, Okoye V, Elumelu F, Dahiru A, Pariya HB