Imagine a world where deadly diseases like tuberculosis ravage communities, claiming over a million lives annually, and yet, the path to finding effective vaccines hinges on something as fundamental as getting people to sign up for clinical trials. That's the stark reality we're tackling in low- and middle-income countries (LMICs), where vaccine research isn't just a scientific endeavor—it's a lifeline. But here's where it gets controversial: Are we truly empowering these communities, or are we merely tapping into their desperation? Stick around as we dive into the unique challenges and successes of participant recruitment in these trials, and you might just rethink what 'collaboration' really means.
Participant Recruitment in LMIC Clinical Trials
By Alemnew Dagnew, Head of Vaccine Development at the Gates Medical Research Institute (Gates MRI)
Conducting clinical trials for potential vaccines in low- and middle-income countries (LMICs) differs significantly from similar efforts in the United States and Europe. One standout distinction lies in how participants are recruited, a process shaped by the local context and urgency.
The heavy load of infectious diseases in LMICs creates a heightened sense of immediacy and importance for vaccine studies. Take tuberculosis (TB), for instance—the deadliest contagious illness globally, responsible for more than 1.2 million deaths in 2023 alone. That same year saw around 10.8 million people fall ill with the disease, and in many LMICs, individuals often have personal connections to someone who's battled TB, like a family member or neighbor undergoing treatment. This personal link acts as a powerful motivator, driving people to join TB vaccine trials with genuine enthusiasm.
At the Gates Medical Research Institute, where we focus on tackling worldwide health crises like TB and malaria, we're driven by the pressing needs of these communities. But we approach our work with deep respect, ensuring that every step honors their involvement. Recruitment for these trials involves extensive community collaboration to clarify the goals of each study and demonstrate how both the community as a whole and its members can actively shape and support the research.
Why Participant Recruitment Is Crucial for Clinical Trial Success
Even though TB is the world's top infectious killer, it boasts just one vaccine—BCG—which has been in use for over 100 years. While BCG shields young children from severe forms of TB, such as meningitis, it provides scant protection against pulmonary TB in teens and adults, the group that bears the greatest disease burden and serves as the primary transmitters of the illness.
At Gates MRI, we're pioneering the M72 vaccine to combat pulmonary TB in adolescents and adults. Our most extensive trial so far is the M72 Phase 3 study, unfolding across 54 sites in Indonesia, Kenya, Malawi, South Africa, and Zambia. To supercharge our recruitment and hit our goal of 20,000 participants 11 months early, we adhered to three guiding principles:
First, Scout Ahead to Pinpoint Disease Hotspots
TB predominantly impacts residents of low- and middle-income nations, so it makes sense to run large-scale Phase 3 trials where the disease is most rampant. Yet, executing such ambitious studies in these environments isn't straightforward. To wrap up a trial of this scale in a practical timeframe, you require a substantial participant pool—and that demands numerous, well-equipped sites. This is where a smart epidemiological investigation proves invaluable. It enables us to set up sites proactively and pinpoint TB hotspots before the main trial begins.
Before launching the M72 trial, we carried out a comprehensive epidemiology study spanning 14 nations and 45 locations, which guided our recruitment tactics. We gathered samples from volunteers and tested them for TB infection and disease, mirroring the processes of the actual trial. By cross-referencing this data with insights from national TB initiatives, we mapped out hotspots effectively.
Spotting these hotspots was essential for the M72 trial's success, as our analysis hinges on events—specifically, accruing 110 lab-confirmed cases of pulmonary TB to evaluate the vaccine's effectiveness. This threshold of 110 was chosen as the statistically sound number needed to draw reliable conclusions about the vaccine's impact. However, if the trial areas have a low TB incidence, reaching those 110 cases could drag on indefinitely. By focusing on high-burden regions, we can expedite the evaluation, wrapping up the study much faster. And this is the part most people miss: In a low-burden area, a trial might never reach its endpoint, potentially wasting resources and leaving communities underserved—does that make these 'convenient' choices ethically tricky?
Second, Foster Trust via Genuine Community Involvement
Community outreach has evolved beyond simple participant sign-ups; it's now about cultivating enduring partnerships and nurturing a sense of shared stewardship in the research. Communities are increasingly taking active roles in shaping study designs and recruitment methods.
For the M72 study—and the epidemiology work that preceded it—we kicked things off by consulting a global community advisory board. Members of this board possess deep knowledge of TB and research, engage with community or civil society groups, spread information through networks, and drive action at local, national, regional, or global levels. We shared the full program details, absorbed their input, and refined our approach accordingly.
At the trial sites, teams work diligently to forge bonds with locals by integrating leaders, advisory panels, and health workers from day one. Community advisory boards (CABs) are pivotal here. Most of our sites have local CABs—akin to the global ones but tailored to the area—and some tap into other established engagement channels. This setup guarantees that community concerns are not only heard but promptly addressed. But here's where it gets controversial: Could this level of involvement sometimes blur the lines between researchers and participants, raising questions about who truly controls the narrative? Is it empowering, or just another form of influence?
Third, Strengthen and Enhance Local Collaborations and Skills
When selecting trial locations, we prioritize teamwork with on-the-ground healthcare providers, like TB clinics, to more precisely target and connect with high-risk communities. To illustrate, the pre-trial epidemiology study for M72 ensured that vital infrastructure—such as labs for sample testing and logistics for shipping to central facilities—was ready and optimized. It also tested intake procedures, revealing areas for enhancement and offering sites real-world practice with the upcoming Phase 3 trial protocols.
In essence, clinical trials thrive on interconnectedness. Recruitment isn't a one-off task; it's the foundation for ongoing community alliances that endure through the trial's duration and beyond.
About The Author:
Alemnew Dagnew, MD, MSc, MPH, serves as the head of vaccines & biologics development at the Gates Medical Research Institute (Gates MRI, located at https://www.gatesmri.org/). He oversees the clinical advancement of the M72 tuberculosis vaccine, which aims to alleviate a scourge that disproportionately harms marginalized groups and presents formidable global health hurdles, alongside other initiatives combating major public health threats. Dagnew has been instrumental in securing vaccine approvals and managing international trials scrutinized by bodies like the South African Health Products Regulatory Authority, African Vaccine Regulatory Forum, U.S. FDA, European Medicines Agency, and Health Canada.
What do you think? Is prioritizing high-burden areas in trials a pragmatic necessity, or does it risk exploiting vulnerable communities? And how do we balance respect with urgency in global health research? Share your views in the comments—do you agree with these approaches, or do they challenge your perspective on ethical science?
