PAMAfrica and the evolution of good clinical trials
This year, the World Health Organization published a new Guidance for best practices for clinical trials. Among its areas of focus, the guidance stresses the need for "good trials" to be collaborative and transparent, as well as to include populations that are underrepresented or historically excluded from the clinical trial setting, like pregnant and lactating women and children.
The PAMAfrica consortium set out to respond to this anticipated Guidance. The partnership aspired to demonstrate in practice a collaborative approach to conducting clinical trials with malaria-endemic countries, ensuring co-leadership and sharing of respective expertise between partners. To learn more about these aspirations and discuss the best practices and lessons learned from the PAMAfrica experience to this point, we sat down with the Principal Investigator of PAMAfrica’s CALINA study, Dr Bérenger Kaboré (CRUN, Burkina Faso) and Dr Helen Demarest, Senior Director, Clinical Operations (MMV, Switzerland).
Q: What were some of the practical challenges associated with conducting the CALINA trial (developing the first malaria treatment for babies under 5kg) and the importance of addressing the specific needs of this group to further the malaria elimination agenda?
Dr Kaboré: For a long time, many have assumed that children at this age were already well-protected from malaria by maternal immunity, or that when they presented with an illness, it was likely to be something other than malaria. Even community healthcare workers have traditionally neglected the extent of malaria in neonates. As such, beyond its main objective of developing a malaria treatment tailored to this specific group of patients, the CALINA study was an opportunity to raise awareness of the threat malaria poses to neonates and the need to protect them.
For example, when recruiting for the trial, many thought we would encounter problems identifying newborns under 5 kg with malaria, but this was not at all the case for children older than 1 month, although children younger than this were harder to identify. Indeed, this is a small group of patients, which has contributed to their underrepresentation in the clinical trials setting, but an important one nonetheless, and I’m both happy and proud to have been part of the success of this study.
Q: How have the goals of collaboration and transparency informed the design of the PAMAfrica partnership, and how has it supported necessary capacity while maximizing the use of resources and increasing efficiency?
Dr Demarest: At its core, PAMAfrica was envisaged as a partnership that would tap into the expertise, knowledge and experience of a range of global players to respond to unmet needs in malaria control and elimination. The goal was also to leverage the gains of one trial to the benefits of the others, by taking advantage of research capacity and infrastructure at the respective trial sites across the studies and helping to ensure their sustainability as centres of excellence.
Historically, clinical trials have occurred in isolation, and are ultimately one-off events used to generate data and guide treatment decisions, which does little in the way of maximizing the use of resources and increasing efficiency. For PAMAfrica, we wanted to nurture sustainable research environments – through targeted training and infrastructure investments – that could quickly, easily and efficiently design and manage new clinical trials in the future. PAMAfrica actively sought to invest in the sustainability of existing research capacity and ensure all studies in the portfolio were supported. The CALINA study focused on tiny babies but PAMAfrica also included trials for a new medicine to treat severe malaria and a next-generation combination for uncomplicated malaria. As such, having one capacity strengthening work package to benefit all three trials and the research teams involved in them has worked reasonably well, but of course, part of the process is identifying what worked well and how things could be improved moving forward.
Q: Having said that, what are some of the key takeaways from PAMAfrica in terms of best practices and lessons learned to improve partnerships of this nature in the future?
Dr Demarest: I think it’s been a learning experience for everyone involved. One area for improvement that comes to mind is that these partnerships can put more focus on building research and clinical trial capabilities to support the growth and promotion of the next generation of African scientific leaders through enabling opportunities of co-leadership with established Principal Investigators for experience and exposure, whilst benefiting from expert mentorship. Moreover, there should be a closer partnership between investigators and site team specialists, such as social scientists and trial sponsors, to appropriately input and align on delivering the best possible trial design and information for the community. The involvement of the social science experts in endemic countries, who are well-versed in local contexts, is crucial to informing trial protocols and bringing more transparency to the studies from the perspective of the communities in which they are recruiting, embodying the key theme of transparency in the Guidance.
Dr Kaboré: I had the opportunity to lead the CALINA study, which has allowed me to network with other young researchers involved in the PAMAfrica consortium. We also had the opportunity to engage in a variety of capacity building initiatives, like grant management, good clinical practices and research ethics. However, I think we can improve how we assess training needs by asking research staff and using their responses to inform our approach to capacity building. Moreover, since PAMAfrica researchers were spread across multiple sites, a train the trainer approach, where representatives convene for training workshops and then return to their respective sites to train other colleagues, can also be useful.
In terms of lessons learned, we cannot underestimate the importance of engaging with the local community, sharing results and ensuring information about the trials and their progress is accessible. Sharing results and keeping open lines of communication with the communities in which we work is of the utmost importance, both for the trials we are conducting now and the ones we will undertake in the future. It’s important to build trust and listen to voices from within the communities, and to do this, we need to be more transparent about our objectives and then come full circle once our studies generate results. Closing this loop by sharing updates on the CALINA study with the local community is something we plan to do in the near term.