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

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Bringing antiretroviral drugs to children

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

The challenge

The Zambia National Health Research Policy of 2010 identified capacity building in ethical conduct of research as a key priority.

The body with overall responsibility for regulating clinical research in Zambia is the National Health Research Authority (NHRA). The NHRA includes a National Health Research Ethics Board (NHREB), which oversees research ethics committees and institutional review boards. However, these committees have limited expertise in ethics review, and the central regulatory bodies lack the full range of expertise necessary to build their capacity.  

The BUCARERZ project is enabling the NHRA to build its regulatory oversight capacities and systems, including those for ethics review of clinical research proposals. A research capacity needs assessment has been undertaken, as well as an audit of research ethics activities. These have been used to develop a national research ethics and regulatory capacity-building plan.

Through a ‘train the trainer’ model, 18 core staff from the NHRA, NHREB and the Zambia Medicines Regulatory Authority have taken part in training courses on various aspects of regulatory function across Africa, including Good Clinical Practice, Good Laboratory Practice and research ethics. Events are being organised to pass on this new knowledge to research ethics committee members, researchers and healthcare workers. NHRA staff will also undertake follow up of a selection of ongoing projects.

A new electronic platform, RHInnO Ethics, is being introduced for review of all proposals and research protocols.

Following the introduction of the new systems, the NHREB has begun to hold monthly meetings to improve efficiency and to manage an anticipated increase in applications. This has led to a significant reduction in the time taken to review proposals, from an average of 90 days to less than 30 days.

The NHREB has also launched regular interactions with research ethics committees, to discuss emerging ethical issues and to promote harmonisation in procedures. NHRA and NHREB members will also develop international contacts to network and share experience, with partners such as the African Medicines Harmonisation Programme.

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 BUCARERZ project is strengthening consideration of ethical issues in clinical research throughout the entire health research system in Zambia. As well as delivering measurable improvements in ethics review systems and practice, more generally it should also help to stimulate greater interest in clinical research across the country.

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