“
test the safety and efficacy of this new formulation in young children

”

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Clinical trials are critical for ensuring the safety of new drugs (and safe new use of existing drugs). However, clinical trials can never be big enough to detect rare but significant side effects. Therefore, systems are needed to monitor adverse reactions to new drugs after they have been introduced (pharmacovigilance).

In addition, patients are at risk from harm from poor quality and counterfeit medications. This issue is of particular concern in Africa, which accounts for more than 40% of global reports of substandard and fake medical products.

Strong national regulatory agencies are required to ensure participant safety through clinical trials and after licensing, as well as to combat counterfeit medications. However, national regulatory agencies often lack the resources and expertise to perform these functions effectively.

The EAPI project was established to strengthen pharmacovigilance systems in Kenya. EAPI is a partnership between the Pharmacy and Poisons Board – the national regulatory agency in Kenya – and the University of Nairobi. Jointly, the two bodies have been designated a Regional Centre of Regulatory Excellence for Pharmacovigilance by the African Union Development Agency.

Drug regulatory agencies in sub-Saharan Africa have limited budgets and face shortages of appropriately trained staff. Academics can fill gaps but require practical training to fulfill a role as part-time drug evaluators.

The EAPI project therefore developed e-learning material to support a master’s in pharmacovigilance and a pharmacoepidemiology programme at the University of Nairobi, open to pharmacists in Kenya and beyond. A total of 14 modules were converted for online use, opening up much wider access to high-quality materials. The project also developed short courses to build the skills of national ethical committees and regulatory agencies in pharmacovigilance and other key areas.

The University of Nairobi has also helped the Pharmacy and Poisons Board to develop an innovative coding system to facilitate ‘track and tracing’ of pharmaceutical products, with integrated pharmacovigilance reporting. Following piloting, the new system could have a major impact on how the Board operates.

Through its website and other activities, the EAPI project is also raising awareness among stakeholders, including the general public, of the importance of pharmacovigilance.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The EAPI project has established a mechanism for enhancing the capabilities of Kenya’s national regulatory agency across all stages of clinical evaluation, including ‘phase IV’ pharmacovigilance. Its virtual training tools could potentially also help to develop capacity across other countries in East Africa.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact