Participant Recruitment In LMIC Clinical Trials
By Alemnew Dagnew, head of vaccine development, Gates Medical Research Institute (Gates MRI)
There are many differences between conducting clinical trials for potential vaccines in low- and middle-income countries (LMICs) and in the United States and Europe. One of the more prominent differences is recruitment.
Due to the high burden of infectious diseases in LMICs, there is a greater perceived urgency and relevance for vaccine trials. For example, tuberculosis (TB) is the most lethal infectious disease in the world, killing more than 1.2 million people in 2023. An estimated 10.8 million people fell ill with TB that year, and, often in LMICs, people personally know a family member or community member who has been treated for TB. This strongly motivates their participation in TB vaccine trials.
In our work at the Gates Medical Research Institute addressing global health threats, especially TB and malaria, we are responding to the urgency that the community faces, but we must also be respectful as we proceed. Participant recruitment for clinical trials, therefore, entails significant work with communities to make sure they understand the aims of each trial and how they — the communities as well as the community members — can contribute to these research efforts.
Participant Recruitment Underpins Clinical Trial Success
Despite being the world’s deadliest infectious disease, TB still has only one vaccine — BCG — which has been used for over a century. While BCG helps protect young children from severe TB forms like meningitis, it offers little to no protection against pulmonary TB in adolescents and adults, for whom the burden of pulmonary TB is the highest and who are also the main source of disease transmission.
At Gates MRI, we are developing the M72 vaccine with the aim of helping to prevent pulmonary TB in adolescents and adults. Our largest clinical trial to date is the M72 Phase 3 clinical trial. This clinical trial is being conducted at 54 clinical trial sites in Indonesia, Kenya, Malawi, South Africa, and Zambia. We have followed three broad themes to bolster our participant recruitment efforts for this clinical trial, helping us reach our recruitment target of 20,000 participants 11 months ahead of schedule:
Advance Work In Identifying Hotspots
TB primarily affects people living in low- and middle-income countries, so naturally, you have to conduct your Phase 3 study in the regions where the disease burden is highest. But running large efficacy trials in those settings isn’t easy. To complete a study of this magnitude within a reasonable time frame, you need a large sample size — and to enroll that many participants, you need a large number of well-prepared clinical sites. That’s where an epidemiologic study came into play. It allowed us to prepare sites and identify TB hotspots in advance of the Phase 3 study.
In advance of the M72 trial launch, we conducted a thorough epidemiology study across 14 countries and 45 sites that informed our participant recruitment strategies. We collected samples from recruited participants and evaluated them for infection with the TB bacteria and TB disease, as we need to do for the actual trial. The results, when correlated with data from other sources such as the national TB program, helped to identify TB hotspots.
Identifying these hotspots is critical for the success of the M72 trial, where our analysis is event-triggered, meaning that we will run the analysis of the experimental vaccine’s efficacy when we accrue 110 laboratory confirmed pulmonary TB cases. This number, 110, was determined to be the statistically relevant threshold we could use to reach a conclusion on the efficacy of the experimental vaccine. This statistical approach meant, however, if the communities hosting the trial sites have a low burden of TB, then it will take too long to reach the events needed to trigger the analysis. Conducting the study in a high burden setting allows us to complete the evaluation of the experimental vaccine in a much shorter period of time.
Build Trust Through Community Engagement
Community outreach is no longer just about recruiting participants — it’s about building long-term relationships and fostering shared ownership of the research. There is increasing involvement of the community in research, where community members are actively involved in study design and recruitment strategies.
For the M72 study, and the epidemiology study that informed it, first we began discussions with a global community advisory board whose members have a knowledge of TB and medical research, actively participate in community or civil society networks, can disseminate information through these networks, and bring about local, national, regional, and/or global action on issues. We presented the entire program to them, listened to their feedback, and made adjustments to the strategy.
The clinical trial sites also work hard to establish strong relationships with communities by involving local leaders, advisory boards, and health workers from the outset. Community advisory boards (CABs) are critical to this principle. In our trials, most trial sites have their own CABs — which are similar to the global boards but with a more local scope — and some also utilize other locally established community engagement mechanisms. In this way, we ensure that all issues raised by the community are heard and responded to appropriately.
Leverage And Improve Local Partnerships And Expertise
As we determine trial sites, we emphasize collaboration with local healthcare providers — such as TB clinics — to identify and reach high TB burden communities (TB hotspots) more effectively. In this light, the epidemiology study we conducted in advance of the M72 trial allowed us to make sure that the necessary infrastructure and support services, like sample processing and shipping to the central laboratory, are in place to handle the work. The epidemiology study provided an opportunity to see if the intake procedures worked well and to determine where they could be improved. Overall, the study offered a valuable opportunity for sites to gain practical hands-on experience with the clinical trial procedures of the upcoming M72 Phase 3 trial.
In conclusion, clinical trials do not operate in a vacuum. Participant recruitment is often the gateway to a collaboration with the community that lasts throughout the life cycle of the clinical trial and afterward.
About The Author:
Alemnew Dagnew, MD, MSc, MPH, is head of vaccines & biologics development at the Gates Medical Research Institute (Gates MRI), where he leads the clinical development of the M72 tuberculosis vaccine — addressing a disease that disproportionately affects underserved populations and poses major global health challenges — along with other programs targeting diseases of significant public health importance. Dagnew has played a key role in vaccine licensure and the conduct of international clinical trials reviewed by regulatory authorities such as the South African Health Products Regulatory Authority, African Vaccine Regulatory Forum, U.S. FDA, European Medicines Agency, and Health Canada.