Background
Clinical trials are research studies performed in people aimed at evaluating a medical, surgical, or behavioral intervention. They are the primary way that researchers find out if a new treatment, like a new drug or diet or medical device (for example, a pacemaker) is safe and effective in people (Vulcano, 2017). A clinical trial is often a clinical trial is used to learn if a new treatment is more effective and/or has less harmful side effects than the standard treatment (NIH, 2023).
Africa is home to 17% of the world’s population and carries 25% of the global disease burden (Hwenda et al., 2022). However, it contributes less than 3% of worldwide clinical trials conducted on the continent (Hwenda et al., 2022). Studies have shown that this is mainly due to limited clinical trial capacity, which is attributed to inadequate funding, poor research infrastructure, and a lack of trained personnel, including clinical trialists and laboratory researchers (Vischer, 2016). Furthermore, regulatory challenges, including ethical concerns, significantly hinder the implementation and expansion of clinical trials in Africa (Ndembi et al., 2024). Consequently, PTA practices are not as well established or widespread in Africa compared to other continents. Enhancing clinical trial application and review capabilities in African countries is crucial for revitalizing the continent's role in managing communicable and non-communicable diseases. It significantly improves PTA plans and practices among stakeholders and enhances the region’s preparedness for frequent pandemic onsets (Ogunleye et al., 2020).
Declaration of Helsinki, article 34 PTA states, “In advance of a clinical trial, sponsors, researchers, and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” (DoH, 2013). The Declaration of Helsinki has been revised; there is a recent version of 2024 (DoH, 2024). Therefore, PTA should be planned and documented in the study protocol. The execution plan should be reviewed and updated during the clinical trial. PTA has various aspects. First, it refers to providing knowledge and intervention, if any. Second, it refers to the potential beneficiaries, which could be research participants and/or the intended patient group in the community and/or country. Third, PTA provisions for research participants must be free of charge. PTA for the community and/or host country usually comes in the form of availability and accessibility of the medicinal product within a reasonable time. Access to an investigational intervention is justified by the principle of beneficence, “which requires researchers and sponsors to safeguard the health of participants when it is in their power to do so.” (CIOMS, 2016) It is also supported by the principle of distributive justice: participants, and by extension, the community or host country, assist researchers in generating valuable data, and, in return, researchers should ensure that participants receive the needed care to safeguard their health.
Even though the number of clinical trials in LMICs has increased dramatically (Van Roessel et al., 2019), most of the trials are funded, sponsored, or otherwise influenced by private or public entities from high-income countries. The lack of PTA introduces the risk of exploiting study participants in low- and middle-income countries who otherwise have limited access to healthcare (Singh et al., 2019). In this case, national ethics committees and the relevant drug regulation agencies must ensure PTA is in place. While there is limited practical experience on PTA in clinical trials in LMICs, the concept of benefit-sharing, which acts as the theoretical foundation of PTA, is firmly stipulated in different international ethical guidelines (Singh et al., 2019). The UNESCO Declaration on Bioethics and Human Rights, for example, highlights the duty of benefit-sharing pertaining to scientific and technological innovations, in particular with developing countries (Chirac & Torreele, 2006; UNESCO, 2009).
The Declaration of Helsinki requires the sharing of benefits in medical research with the vulnerable group (DoH, 2013), and the CIOMS International Ethical Guidelines require multi-stakeholder cooperation to make the studied intervention and the knowledge gained available to the population or community (CIOMS, 2016).
Hence, ethical guidelines are clear that PTA, in the form of concrete plans and procedures for benefit-sharing and access (may it be in the form of reasonable pricing of an approved indication in the host country, free medicinal product for research participants, the provision of knowledge to the relevant patient population and the community), must be intrinsic to clinical trial planning. Despite these ethical guidelines, the general status quo of PTA is not encouraging: the provision of PTA is “rather the exception than the rule” (Jimenez et al., 2019; Schippe, 2015).
In line with the above principles, this manuscript will explore PTA planning, type, and implementation on TB, Malaria, and NTDs clinical trials across Sub-Saharan African countries. For the purposes of this study, we define PTA arrangements or plans as preliminary discussions, commitments, and strategies developed before or during the trial to ensure post-trial access. It includes, but not limited to: (i)financial commitments for PTA, (ii) data and knowledge sharing plans, (iii) stakeholder and community engagement activities, including meetings with government agencies, regulators, or local organizations to discuss PTA expectations, (iv) informal and formal PTA discussions and commitments among sponsors, investigators, and health authorities, (v) addressing ethical review requirements related to PTA, (vi) collaboration between academic institutions and funding agencies to discuss PTA feasibility, (vii) negotiation of intellectual property (IP) rights or licensing agreements, where applicable, and (viii) inclusion of PTA considerations in trial protocols or informed consent documents.
We define PTA implementation as concrete actions after trial completion to ensure access to the tested interventions and/or knowledge. Examples include but are not limited to: (i) preferential pricing strategies for products in trial or host countries, (ii) conducting dissemination meetings with stakeholders, (iii) publishing results in open-access journals and popular literature to ensure knowledge sharing, (iv) securing regulatory approvals for the compassionate use of the intervention, (v) integration of the intervention into national health programs within a defined timeframe, (vi) technology transfer or capacity-building initiatives in the host country, (vii) distribution of educational materials, such as training guides or films, to relevant stakeholders, and (viii) post-implementation monitoring and/or evaluation to assess the uptake of impact of PTA efforts.
