Author:

Abstract:

Clinical trials are more and more delocalized to low- and middle-income countries (LMICs), either for reasons of external validity (to test new interventions in various epidemiological settings), or for convenience reasons (lower costs, easier review and easier availability of subjects), or for global health reasons (to address the local health needs). But the weakness of regulatory supervision in many LMICs makes trials’ participants more likely to be exposed to exploitative practices -just like it limits the capacity to assure the quality of pharmaceutical products and exposes people to the risk of poor-quality medicines. Clinical trials include commercial trials, sponsored by a pharmaceutical company and aimed at developing new medical products, and non-commercial trials, sponsored by a non-commercial entity and which can provide answers to highly relevant research questions not addressed by commercial research. All clinical trials must comply with adequate ethical and methodological standards, to provide public assurance that the rights, safety and well-being of trial subjects are protected, and that trial data are credible. The international Good Clinical Practices (GCP) codes of the World Health Organization (WHO) and of the International Conference of Harmonization (ICH) are intended to set such globally applicable standards. They guide and orient most national legislators, and also the policies of most funding agencies. They were issued in 1995 and 1996, respectively. No update is planned for the WHO GCP, while a process of partial update of the ICH GCP is ongoing. So, to date both codes reflect the situation of more than twenty years ago, when trials were mainly conducted in Western contexts by commercial sponsors, and they do not take into account the contextual and cultural specificities in the new research environments, nor the challenges met by non-commercial research consortia. This situation leaves North-South collaborative research groups, as well as commercial research groups working in LMICs, without adapted guidance, and may result in poor protection of subjects and communities in LMICs. There is an urgent need to advocate for a revision of the international GCP codes, but such advocacy should be supported by an assessment of their current gaps. Thus, the primary objective of this doctoral research is to identify gaps of the international GCP codes in light of the new scenarios of globalized clinical research, with focus on sub-Saharan Africa, and to formulate recommendations for their improvement. The secondary objective is to compare the challenges related to clinical research standards versus the challenges related to the standards for quality of medicines in resource-limited settings. Our methodology is articulated around three elements. First, we assessed the adequacy of the GCP definition of a trial’s “sponsor”, by means of an original analysis of how “sponsor” is defined by various organizations that play a role in defining clinical research standards. Second, we assessed the adequacy of the GCP approach for non-commercial trials in LMICs, by means of eleven specific studies and/or viewpoints. Third, we assessed the North-South gap in quality-assured medicines, in a series of six viewpoints and letters. Even if we could not cover all the issues that are at the same time especially challenging in LMICs and insufficiently addressed by GCP, our analysis confirmed that the current international GCP codes lack adequate consideration for many challenges met by non-commercial clinical research groups in LMICs, such as the definition of sponsor; the relation between non-commercial sponsors and external funding agencies; the trial policy insurance; the trial monitoring; the clinical trial laboratories; the double ethical review in externally-sponsored trials; the definition of vulnerability; the informed consent process; the role and perspective of the communities; the role of qualitative research in clinical trials; the notions of benefit sharing and of impact of research; and the quality of investigational products. We also noted that some other important challenges are related to the poor awareness of some sponsors and/or funding agencies of GCP/GCLP requirements; to a too dogmatic approach to GCP training and implementation; and to a gap between the field and regulators. We translated our findings into 16 recommendations, which could help triggering a process of “holistic” revision of the international GCP codes, i.e. a revision serving the interests of science, patients and communities globally. This revision should not lower the standards for academic research, for LMICs or for a specific region (i.e. we are not advocating for a specific “African GCP”), but rather design adequate rules and procedures that remain strongly rooted in ethics; are sensitive to different cultural and social perspectives; take into account trials- and context-related challenges; and prioritize substantive over administrative requirements. Adequate and inclusive representation of researchers, sponsors, regulators and ethical reviewers from LMICs, as well as of Northern and Southern non-commercial researchers and sponsors, should be ensured in the revision process, for (a) overcoming the current divide between the regulatory policies and guidelines on the one side, and the concrete field challenges on the other side, and (b) making the international GCP codes at the same time “global”, “context-centered” and “patient-centered”.