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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

To provide a nurturing environment for clinical research, countries need effective and efficient regulatory and ethics review structures that safeguard the interests of participants in research and also minimise any unnecessary obstacles to clinical research. Effective pharmacovigilance systems to detect and investigate possible adverse reactions to new interventions are a critical aspect of these oversight mechanisms.

As national regulatory landscapes can be complex, effective coordination across stakeholders is also important. In Tanzania, key bodies include the National Institute of Medical Research (NIMR), the Tanzania Medicine and Medical Devices Authority (TMDA) and the National Health Research Ethics Committee.

The SMERT project has focused on developing the technical competence of those involved in ethics review, the efficiency and coordination of administrative processes, and strengthening pharmacovigilance systems for clinical research in Tanzania.

It initially set out to identify the development needs of all stakeholders to inform future activities. The needs assessment covered the National Health Research Ethics Committee and 13 institutional review boards. A bioethics curriculum has been developed at Kilimanjaro Christian Medical University College for all postgraduate medical and biological sciences students, and has been taken up by two other universities in Tanzania. It incorporates several emerging areas of ethical interest, including research during public health emergencies and use of stem cell technologies. A staff member of the National Health Research Ethics Committee was supported to undertake master’s training in bioethics, helping to build national bioethics capacity.

A short ethics training course has been developed and completed by 87 members of institutional review boards; it is being refined and will be made available as a free online resource. Following training of researchers and ethics committee members, the median time of approval of research protocols was reduced from 120 to 32 days.

In addition, an electronic system has been developed to enable the electronic submission and review of proposals and to deliver feedback to applicants. To improve efficiencies, the NIMR and TMDA have begun to undertake joint monitoring visits. In addition, to enhance pharmacovigilance, an electronic system has also been introduced for reporting of adverse events during clinical trials, and a system for reporting adverse events of licensed medicines has been advanced, leading to a tripling in the numbers of adverse events reported.

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 SMERT project has achieved major improvements in the efficiency and coordination of ethics review activities in Tanzania, leading to measurable changes in performance. The project’s activities have fed into the East African Health Research Commission’s work on harmonisation of research ethics review and, with the SMERT project’s support, the TMDA hosted a forum for East Africa’s national medicines regulatory bodies – a first step towards the development of a common set of high-quality standards across the region.

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