Pharmacovigilance in developing countries

Abstract

Requires collaboration between stakeholders to develop novel models of funding

Efforts are increasing to ensure that resource poor countries, which bear almost 90% of the global disease burden, have access to effective medicines.¹ As a result, drug companies are facing increased pressure from governments, the World Health Organization, and patient lobby groups to remove legal and financial barriers to access.² However, although these campaigns are necessary and clearly laudable, they are not accompanied by the development or upscaling of processes for monitoring drug safety. Although many drugs have been extensively used and studied in developed countries (thus informing global practice), their safety profile cannot necessarily be generalised to developing countries, where the incidence, pattern, and severity of adverse reactions may differ markedly because of local environmental and genetic influences.³

After the thalidomide disaster in the 1960s, most Western countries developed national pharmacovigilance systems.⁴ These systems use spontaneous reporting or other pharmacoepidemiological methods to systematically collect and analyse adverse events associated with the use of drugs, identify signals or emerging problems, and communicate how to minimise or prevent harm. Although these processes are not perfect, as exemplified by recent problems,⁵ they do provide evidence that can be used to institute regulatory action to protect public health.

At the global level, the WHO programme for international drug monitoring at the Uppsala Monitoring Centre collates adverse drug reaction reports via the national pharmacovigilance centres of the 81 member countries (www.who-umc.org). However, currently only six sub-Saharan African countries (South Africa, Zimbabwe, Tanzania, Mozambique, Nigeria, and Ghana) are full members of the programme. In fact, less than 27% of lower middle income and low income economies have national pharmacovigilance systems registered with the WHO programme, compared with 96% of the high income countries in the Organisation for Economic Co-operation and Development. The main reasons for this are lack of resources, infrastructure, and expertise. Thus, although access to medicines is increasing in developing countries, there is a danger that their risk benefit profiles in indigenous populations will not be fully monitored and acted upon.

So what can be done to improve drug safety monitoring in developing countries? In the short term, we need to make better use of ongoing or planned studies. The ability to detect an adverse drug reaction depends on its frequency and the total number of people exposed to the drug.⁶ A logical approach would be to encourage collaboration between academic investigators, drug companies, and governments undertaking clinical studies to develop common adverse reaction reporting forms and to deposit the data into a single database.

Similar partnerships could also be established with organisers of public health and drug access campaigns and with regional surveillance systems, such as the East African network for monitoring antimalarial treatment⁷ and the network for assessing health and demography in developing countries.⁸ The operational advantages of this approach are that data can be obtained from a range of studies and that pre-existing manual and technical infrastructures can be used to acquire the data. This would provide demographically relevant data from large (and less homogeneous) populations in a structured and systematic fashion, and these data could then be used to identify warning signals.

Individual investigators would still own their data and publish results of their trials, but the pooling of data on adverse drug reactions would add value to ongoing studies. This has already happened on a small scale. For example, an increased risk of serious neurological reactions was identified in people taking ivermectin who were infected with Loa loa before treatment started.⁹ Such pooling of data needs to be increased and considered for all drug classes within a formulary.

What role should the drug industry have in promoting pharmacovigilance? The current model for drug development in resource poor settings depends on public-private partnerships, such as the Medicines for Malaria Venture. These partnerships should be encouraged to continue beyond the point of obtaining a drug licence to developing a proactive phase IV programme. Such a programme could be designed to show the effectiveness of the drug in a real world situation, and through this obtain safety data in much larger cohorts of patients. A few examples of this approach already exist in Africa,¹⁰ but these need to become the norm rather than the exception.

In the long term, every country should develop its own national pharmacovigilance system, which contributes to a global database such as that held by the Uppsala Monitoring Centre. This will need an extensive infrastructure, however, which would be costly. In a climate where health resources are limited, funding a pharmacovigilance system will come second to other competing priorities such as implementing a new vaccine programme. The funding model for pharmacovigilance activities in the United States recently advocated by the Institute of Medicine¹¹ is unlikely to work in developing countries if it increases drug costs, as this defeats the aim of increasing access to medicines. No easy answers are available, but WHO needs to lead a dialogue between the major stakeholders with the aim of developing a novel funding model that supports pharmacovigilance activities in developing countries. The lack of local expertise in pharmacovigilance could be tackled through developing exchange programmes with the major drug regulatory agencies and sharing of best practices.