Methodological and ethical challenges in sponsorship of non-commercial North-South collaborative research

Globalization has a heavy impact on the North-South divide in access to health: Southern populations often lack regular access to quality essential medicines and are exposed to risks due to poor practices in medical care and research. In the field of clinical trials, new elements emerged over the last decade:
- A tendency to “delocalize” trials to resource-poor settings, either due to the need to test new interventions in different epidemiological settings and populations, or to “convenience reasons” such as lower costs, easier ethical and regulatory review, and easy availability of subjects;
- An increase of North-South collaborative trials carried out by non commercial actors (academia, NGOs, international organizations etc.) in resource-poor settings, prompted by the urgent need to address public health problems of these populations. The availability of new funding mechanisms today allows non-commercial research groups to design and carry out complex multi-country trials, especially in the field of HIV-AIDS, malaria and tuberculosis.
Nonetheless, the enforcement of appropriate standards for clinical research, inspired by the ethical principles agreed in the Nuremberg Code, Belmont Report and Helsinki Declaration, and set in the Good Clinical Practices of the World Health Organization and of the International Conference of Harmonization (ICH), lags behind in many low and middle-income countries. In addition, the major GCP Guidelines that guide and orient national legislators were issued respectively in 1995 (WHO) and 1996 (ICH), and to our knowledge no revision process has been started yet. Thus, they reflect the situation of almost twenty years ago, when multicentre clinical trials were mainly conducted in Western contexts by commercial sponsors, and do not take into account the role currently played by non commercial sponsors, neither the challenges met by these new actors in international research. Such challenges, examples of which are summarized in Table I, have been described in many papers and guidance documents. A few stringent regulatory authorities (SRAs) have started processes to ensure that double standard is avoided when trials are conducted in third countries, but such procedures may only be enforced for trials included in marketing authorisation applications submitted to such SRAs. In addition, their efficacy may be loosened by contradictory provisions (i.e., the US FDA formally discontinued in 2008 its reliance on the Declaration of Helsinki for foreign trials supporting domestic applications).