Ethics statement

Ethical approval for the parent LeDoxy Trial was obtained from the National Health Research Ethics Committee of the Tanzania Medical Research Coordinating Committee, with certificate number NIMR/HQ/R.8a/Vol. IX/2693. Clinical trial approval was granted by the Tanzania Medicines and Medical Devices Authority, under certificate number TFDA0017/CTR/0020/3.

As the study included adolescent participants aged 14–17 years, formal written informed consent was obtained from all participants aged 18 years and above. For participants under 18 years of age, written informed assent was obtained from the adolescent, alongside written informed consent from a parent or legal guardian.

For participants who could not read or write, the information sheet and consent form were read aloud in the presence of an impartial witness. Consent was documented using the participant’s thumbprint, countersigned by the witness.

Study design and paper classification

This paper is a structured implementation and experiential analysis documenting the processes, challenges, and lessons learned from establishing and operationalizing the LeDoxy clinical trial platform in a resource-limited setting in Tanzania. It does not report clinical efficacy or safety outcomes of the LeDoxy Trial, which are published elsewhere. Rather, it focuses on the operational, infrastructural, regulatory, and human resource dimensions involved in setting up and managing a complex interventional clinical trial in a previously under-researched region.

Accordingly, this work does not follow a hypothesis-driven or comparative study design. Instead, it adopts a retrospective, descriptive analytical approach grounded in systematic documentation, triangulation of implementation records, and reflective synthesis of experiences generated during trial preparation, execution, and close-out.

Relationship to the parent LeDoxy Trial

The LeDoxy Trial was a multinational, double-blind, randomized, placebo-controlled clinical trial evaluating doxycycline for the management of filarial lymphedema, conducted between 2018 and 2021 in Tanzania’s Lindi and Pwani regions. While the parent trial generated clinical and laboratory data subject to formal statistical analysis, the present paper draws exclusively on non-clinical implementation data and operational experiences associated with establishing and running the trial platform. No participant-level clinical outcome data were analyzed for this manuscript.

Data sources

Multiple sources of information generated throughout the lifecycle of the LeDoxy Trial were systematically reviewed and synthesized to inform this analysis. These sources included site readiness and feasibility assessment reports; laboratory accreditation and quality improvement documentation, including records from the Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA); and training-related materials such as training plans, curricula, attendance registers, and post-training evaluation reports. Regulatory and ethics correspondence with national oversight authorities was also reviewed, alongside monitoring and supervision reports from both remote and on-site visits. Additional sources comprised trial management records documenting staffing arrangements, logistics, and infrastructure upgrades, as well as community engagement records, including summaries of stakeholder meetings and reports from community health worker (CHW) activities. Oversight documentation maintained by the National Institute for Medical Research (NIMR) in its role as trial sponsor was also included. All materials were generated as part of routine trial governance, quality assurance, and regulatory compliance processes and did not involve the collection of new primary data for the purposes of this manuscript.

Perspective and analytical lens

The analysis reflects the collective perspectives of the trial sponsor, site leadership, and core implementation team. Authors involved in trial sponsorship, coordination, laboratory oversight, regulatory management, and field implementation contributed to the synthesis of lessons learned. These perspectives reflect operational roles held during trial preparation, implementation, monitoring, and close-out. To reduce reliance on individual recollection, experiential insights derived from documented implementation processes were cross-checked against contemporaneous written records wherever available. The analytical lens was informed by established principles of clinical trial implementation, health systems strengthening, and research capacity building in low- and middle-income country contexts.

Analytical process

A structured thematic synthesis approach was employed to analyze the implementation experiences documented during the LeDoxy Trial, drawing exclusively on implementation documentation rather than primary interview or focus group data. The analysis began with an initial mapping of key implementation domains aligned with the major phases of the trial, including site preparation, participant recruitment, trial execution, monitoring, and sustainability planning. Recurrent challenges, enabling factors, and mitigation strategies were then systematically identified from the reviewed documentation. These observations were subsequently organized into thematic domains encompassing governance and sponsorship, human resource management, laboratory and infrastructure development, regulatory processes, community engagement, participant recruitment and retention, and adaptive responses to external disruptions, including the COVID-19 pandemic. The thematic framework was iteratively refined through internal discussion among the authors to ensure coherence, internal consistency, and alignment with the available documentary evidence. The final thematic structure informed the organization and presentation of the Results and Implementation section.

Ensuring analytical rigor and trustworthiness

Several measures were employed to enhance the credibility and trustworthiness of the analysis. Triangulation was undertaken across multiple documentary sources and stakeholder perspectives to ensure consistency and completeness of the observations reported. Wherever possible, contemporaneous trial records were prioritized over retrospective recollection to minimize recall bias. Key claims and interpretations were cross-validated against monitoring and supervision reports, training documentation, and laboratory accreditation records. Throughout the analysis, a clear distinction was maintained between empirically observed implementation outcomes and the authors’ interpretive reflections on those experiences. In addition, the non-comparative and descriptive nature of the analysis was explicitly acknowledged, ensuring that findings are presented as observational and experience-based rather than inferential. These measures were selected to enhance rigor within a descriptive, non-comparative implementation analysis rather than to support inferential or hypothesis-driven claims.

Recruiting clinical trial research teams

In LMICs, clinical trial staff often face the challenge of balancing dual responsibilities providing routine healthcare services and managing research activities. This dual focus can create tensions that may impact either the quality of patient care or the integrity of the clinical trial [11]. To mitigate this risk, it was essential to negotiate adequate time allocation and resource management with healthcare facility authorities prior to the commencement of the trial. This step was crucial to ensure that research activities did not interfere with ongoing patient care.

A key component of recruitment was identifying and training personnel capable of assuming leadership roles, as well as cultivating a strong research culture at the trial sites. To achieve this, we established clear selection criteria based on specific qualifications and experience levels, as outlined in NIMR staff regulations, ensuring alignment with the expertise required for each role. This approach not only ensured that the research team comprised individuals with the necessary skills and commitment to conduct the trial effectively, but also guaranteed that project staff remained eligible for future research and employment opportunities at NIMR after the study’s conclusion.

The recruitment strategy focused on including both researchers and study team members from the local health facilities and communities where the trial would be conducted as shown in Fig 1. By setting clear criteria for staff qualifications, we aimed to build a team that not only met the technical requirements of the trial but also integrated well with the local healthcare system. This approach not only facilitated the recruitment of competent staff but also garnered the support of local authorities and healthcare teams, fostering a sense of ownership and commitment to the trial’s success.

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Fig 1. Organizational structure of the LeDoxy Trial showing formal reporting and supervisory relationships across leadership, coordination, functional teams, and field implementation levels.

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Moreover, comprehensive training programs combining theoretical and practical components were implemented to equip the recruited staff with the necessary skills and knowledge. The theoretical component covered fundamental principles of clinical research, Good Clinical Practice (GCP) guidelines, and the specific protocol requirements of the LeDoxy trial. Practical training included hands-on sessions in patient assessment, data collection procedures, laboratory techniques specific to filarial diagnostics, and adverse event monitoring. This training encompassed not only the technical aspects of clinical research but also the cultural and contextual nuances of working in a resource-limited setting. Emphasizing the importance of building a scientific and research-oriented culture, the training aimed to align the staff’s efforts with the trial’s objectives while maintaining a high standard of patient care.

Therefore, effective recruitment and training of clinical trial staff in LMICs involves careful planning and negotiation to balance research and service responsibilities. By setting minimum requirements for qualifications and investing in comprehensive training, we were able to build a capable and committed team, essential for the successful implementation of the trial.

Study site selection and preparedness

Selecting and preparing study sites for clinical trials in resource-limited settings involves a series of strategic steps to ensure compliance with international standards and local requirements. A critical component of this process is the development of a standard clinical trial checklist, which outlines the essential criteria and operational requirements for trial sites. This checklist serves as a guide for identifying and preparing facilities that can effectively support the trial’s needs.

In our study, significant challenges arose in locating laboratory facilities that were enrolled in an accreditation program, a crucial requirement for ensuring the quality and reliability of trial data. Since 2015, government health facilities in Tanzania have participated in the WHO AFRO program, which employs the Stepwise Laboratory Improvement Process Towards Accreditation (SLIPTA) to enhance laboratory quality across the African region. This program uses a 5-star rating system to evaluate facilities. Higher star ratings reflect improved adherence to good laboratory practices, biosafety, documentation, and quality management systems [12].

At the start of the TAKeOFF project, the Sokoine Regional Referral Hospital laboratory in Lindi had an SLIPTA rating of 2 stars. Through a deliberate capacity-building strategy, the project facilitated its upgrade to 4 stars and eventual full accreditation by the Southern African Development Community Accreditation Services (SADCAS). This improvement was achieved through a combination of targeted staff training on GCLP, infrastructure upgrades that included the provision of centrifuges, deep freezers (-20°C and -80°C), and liquid nitrogen tanks, as well as the establishment of internal quality management systems aligned with ISO standards. Regular supportive supervision and mentorship were provided to reinforce adherence to standardized operating procedures and continuous quality improvement practices. These interventions significantly enhanced the laboratory’s readiness to support the trial.

To meet the GCP standards required for the trial, it was necessary to select facilities with a star rating of at least 3 under the WHO AFRO SLIPTA accreditation program. The study team identified Sokoine Hospital, a regional referral hospital in Lindi, as the primary site for clinical, laboratory, and pharmacy functions. The Lindi region was chosen due to its high burden of lymphatic filariasis, lack of prior clinical research infrastructure, and its strategic importance for expanding health services in southern Tanzania. However, given that the Lindi region had limited options for qualified health facilities, it was essential to establish a backup plan. Consequently, St. Benedict Ndanda Hospital, located in the neighboring Mtwara region, approximately 104 kilometers away, was designated as the secondary laboratory site to ensure continuity and mitigate potential disruptions at the primary location. The selection was based on the fact that the hospital was equipped with a backup generator, adequate freezer space, and a comparable star rating to the Sokoine Hospital.

The process of preparing these sites for the trial was comprehensive and time-consuming. It involved rigorous assessments to ensure that the facilities met the necessary standards for clinical research. Monitoring was conducted biweekly using a hybrid model that combined remote oversight with periodic on-site visits. Quality control measures included standardized data validation checks and adherence to ISO-accredited protocols for laboratory testing. Preparation activities encompassed infrastructure upgrades, staff training, and the implementation of robust quality control systems. The entire site readiness process spanned approximately 12 months, reflecting the complexity and meticulous planning needed to establish a robust and compliant trial environment.

By achieving this level of accreditation, the Lindi site now meets essential international standards and is positioned to support future clinical trials. This progress represents a significant step toward decentralizing clinical research in Tanzania and enhancing research equity by establishing sustainable capacity in historically underserved regions.

Sponsor responsibilities in the global South

Historically, clinical trials conducted in sub-Saharan Africa have predominantly been led by research partners and sponsors from the global North. This pattern has led to a landscape where research priorities, methodologies, and funding decisions are often driven by external entities, potentially creating disparities in how research is conducted and utilized within the region. The reliance on international sponsors has sometimes resulted in a lack of local ownership and capacity-building opportunities within the host countries.

In this context, sponsorship refers to the regulatory and operational oversight role as defined by ICH-GCP guidelines, distinct from funding. While the German Federal Ministry of Education and Research (BMBF) provided financial support, NIMR assumed sponsor responsibilities including: [list specific responsibilities]. This represents a shift from traditional models where external institutions fulfill both funding and sponsor roles.

However, the TAKeOff Consortium has pioneered a transformative approach by empowering Southern partners to take on the role of sponsor. This shift has been particularly significant in the context of the filarial clinical trial, where NIMR in Tanzania assumed the role of sponsor for the study. This development marked a critical departure from traditional practices and represented a milestone in the evolution of research sponsorship in the region.

Assuming the sponsor role, NIMR was required to demonstrate significant administrative and operational capabilities. It involved overseeing the study’s design, implementation, and compliance with both international and local regulations. This responsibility included ensuring that all aspects of the trial adhered to GCP standards, managing budgets, coordinating with research sites, and maintaining high standards of ethical conduct throughout the study.

The success of NIMR in this role underscores the Institute’s growing expertise and capacity in managing complex clinical trials. This trial underscores the importance of empowering local research institutions to lead clinical trials, fostering sustainability, and reducing dependence on external actors in LMICs. It highlights the potential for local institutions in the Global South to not only participate in but also lead clinical research efforts. By taking on the sponsor role, NIMR has not only contributed to the advancement of medical research in Tanzania but has also paved the way for other Southern institutions to assume similar responsibilities in future trials.

This shift towards local sponsorship has several key benefits. It fosters a greater sense of ownership and accountability among local research teams, enhances the sustainability of research initiatives, and builds long-term research infrastructure within the region. Furthermore, it supports the development of local expertise, which is essential for addressing health challenges specific to the region.

The successful execution of the sponsor role by NIMR serves as a valuable model for other institutions in the Global South. It demonstrates that local entities can effectively manage and lead clinical trials, provided they have the appropriate support and resources. The importance of building clinical trial capacity in Africa is increasingly recognized as critical for addressing health challenges and improving pandemic preparedness. As highlighted by Ndembi in 2024 [13], less than 3% of global clinical trials are conducted in Africa, largely due to insufficient infrastructure, limited funding, and regulatory barriers. Initiatives such as the Consortium for COVID-19 Vaccine Clinical Trials (CONCVACT) and the Pan-African Clinical Trials Registry (PACTR) have demonstrated the potential of regional collaboration and capacity-building efforts in overcoming these challenges [13]. Similarly, the LeDoxy Trial underscores the necessity of strengthening local research institutions, promoting ownership, and fostering sustainability in clinical research. These efforts not only enhance health systems but also position African institutions to make effective contributions to global health research and innovation. This approach strengthens the local research ecosystem, fosters regional self-reliance and contributes to more equitable and impactful research outcomes.

Ultimately, the TAKeOff Consortium’s decision to empower Southern partners as sponsors represents a significant advancement in clinical research. It exemplifies how local institutions can successfully undertake leadership roles in research, driving forward the development of medical knowledge and improving health outcomes within their own regions while advancing global equity.

Sustainability and long-term capacity building

Recognizing the importance of sustainable research infrastructure beyond the trial period, several mechanisms were established to ensure long-term maintenance and continued research capacity. A formal memorandum of understanding was developed with the regional health authorities, transferring ownership of key equipment (centrifuge, freezers, and temperature monitoring devices) to the health facilities upon completion of the trial. This arrangement ensured that the upgraded infrastructure would continue to benefit the local healthcare system and support future research initiatives.

To address ongoing maintenance challenges, local technical staff were trained in equipment operation and basic maintenance procedures during the trial period. Additionally, service contracts were established with regional equipment suppliers to provide continued technical support for critical equipment including the -80°C freezers and laboratory instruments. The enhanced internet connectivity installed during the trial was maintained through partnerships with local telecommunications providers, enabling continued data management capabilities in subsequent research activities.

The laboratory upgrades, which contributed to the facility’s advancement from a 2-star to 4-star rating, were designed with sustainability in mind. The accreditation processes and quality management systems implemented during the trial were integrated into the facility’s standard operating procedures, ensuring continued compliance with international standards. Regular follow-up assessments were scheduled to monitor the maintenance of these standards and provide additional support as needed. However, sustained adherence to quality standards in resource-limited settings requires ongoing financial support, technical mentorship, and institutional commitment that extends well beyond individual trial periods.

These sustainability measures enabled the Lindi research site to transition from LeDoxy trial implementation to early post-trial interventional research activity. In 2025, the site commenced a TAKeOFF Consortium–led interventional study evaluating doxycycline and moxidectin plus albendazole under a test-and-treat strategy for lymphatic filariasis elimination in Tanzania. The study, led by NIMR in collaboration with the Ministry of Health, was ongoing at the time of manuscript submission and builds directly on laboratory, clinical, and human resource capacities established during the LeDoxy Trial.

Impact on laboratory standards

A noteworthy achievement was the substantial improvement in the laboratory’s rating. The laboratory at Sokoine Regional Referral Hospital, previously rated 2 stars, achieved a remarkable 4-star rating within 12 months following targeted infrastructure upgrades and comprehensive staff training. Additionally, the laboratory initiated the process of obtaining ISO 15189:2012 accreditation from the Southern African Development Community Accreditation Services (SADCAS), further demonstrating its commitment to excellence in clinical research. These improvements not only enhanced the laboratory’s operational quality but also contributed to the trial’s overall success, which included a 92% participant retention rate resulting from tailored follow-up strategies and robust community engagement efforts.

These infrastructure improvements were instrumental in establishing a robust research platform. They not only ensured compliance with the required standards but also laid a strong foundation for future research endeavors. By enhancing both physical infrastructure and operational capabilities, the study sites were better equipped to conduct high-quality research, contributing to the overall success of the trial.

Human resource development and training

To ensure the successful implementation of the trial, a comprehensive and integrated human resource development and training program was implemented for healthcare professionals and research staff involved in the LeDoxy Trial. The program was designed to equip personnel with the clinical, research, and managerial competencies required to deliver high-quality patient care while ensuring rigorous adherence to clinical trial standards. Fig 2 illustrates the Capacity Building Framework implemented during the trial, highlighting the interconnected training components and their alignment with the trial’s objectives.

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Fig 2. Capacity building framework for the LeDoxy Trial.

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The LeDoxy Trial placed strong emphasis on capacity building through targeted training of healthcare professionals and research personnel across multiple competency domains. One key focus area was the clinical management of lymphatic filariasis (LF), where participants received specialized instruction on morbidity management, hygiene assessment, acute dermatolymphangioadenitis (ADL) attack prevention, disability mitigation, and patient-centered hygiene education. This component aimed to strengthen both clinical knowledge and practical skills, enabling frontline providers to deliver consistent evidence-based care for LF-related health outcomes in the community.

In parallel, a structured protocol and clinical research training programme was delivered to prepare staff for participation in a regulated clinical trial environment. The program was delivered by both local and international facilitators, covering essential aspects of clinical research conduct, including study procedures, data collection, and ethical considerations. Given that many participants were new to formal clinical research, special attention was given to the principles of GCP and Good Laboratory Practice (GLP). Informed consent procedures were addressed in detail, ensuring that all team members clearly understood their responsibilities to uphold ethical standards and safeguard participant rights throughout the trial.

As part of the morbidity management training, hygiene training kits were distributed to patients with lymphoedema to support the practical application of hygiene-based care. Hygiene training kits were provided to patients with lymphedema, containing essential items such as buckets, basins, medicated soap, towels, soap dishes, antifungal creams, and antibiotic creams. These kits were intended to facilitate daily hygiene practices essential for managing lymphedema and preventing complications.

Overall, a total of seventy-three healthcare workers from the study implementation areas participated in the training program alongside twenty staff members from NIMR in its role as study sponsor. This inclusive approach ensured that both site-level implementers and sponsor representatives were equipped with a shared understanding of clinical care standards, research procedures and trial governance requirements.

The integrated training programme was instrumental in developing a competent and motivated team capable of supporting both clinical service delivery and high-quality research implementation. Beyond enabling the smooth execution of the LeDoxy Trial, these investments contributed to strengthening local human resource capacity and laid the foundation for sustainable research and clinical practice improvements within the participating regions.

Stakeholder engagement

Prior to initiating the trial, strategic efforts were undertaken to engage regional and district health authorities in Lindi, Tanzania. Recognizing the importance of local buy-in, the LeDoxy trial team implemented a comprehensive stakeholder and community engagement strategy to ensure acceptance, address concerns, and foster trust and collaboration throughout the study period.

The engagement process began with consultative meetings involving regional and district health leadership, which helped contextualize the trial within local health priorities and established critical partnerships. This was followed by a social mobilization strategy designed to inform communities about the trial’s purpose, procedures, and ethical safeguards. Multiple communication channels were utilized including community meetings, printed materials, and local radio segments to ensure broad awareness and understanding.

A key component of the strategy was the integration of a rumor monitoring and response mechanism within the existing health system. This enabled the trial team to identify emerging concerns in real-time and take appropriate corrective action. CHWs, who played a central role in this process, engaged directly with households and local groups to provide accurate information and respond to questions. These interactions also helped surface common misconceptions, such as confusion around eligibility criteria or trial procedures, which were then addressed through targeted follow-up and small-group dialogue sessions.

Additional stakeholder meetings with caregivers, elected leaders, healthcare providers, and opinion leaders served as platforms for transparent communication and feedback. Across these engagements, particular emphasis was placed on the scientific, ethical, and medical standards guiding the trial, reinforcing community confidence in the research process.

Stakeholder engagement remained a continuous process throughout the trial. Annual stakeholder meetings provided regular updates and incorporated feedback from key partners. Participation in the National NTDs Dissemination Forum, jointly organized by the NIMR and the National NTD Program, enabled broader dialogue with policymakers, researchers, and community representatives.

This multi-level engagement approach ensured the successful integration of the trial into the local health system and contributed to a positive perception of the research activities. By fostering open communication, prioritizing responsiveness, and embedding trusted community structures into the engagement process, the LeDoxy trial secured essential community support and helped strengthen local readiness for future research efforts. Fig 3 outlines the Stakeholder and Community Engagement Activities and Communication Channels.

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Fig 3. Stakeholder and community engagement activities and communication channels.

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Recruiting and consenting participants

Informed consent is a fundamental process in clinical trials, ensuring that potential participants are fully aware of the study’s nature, objectives, procedures, potential risks and benefits, and any alternative treatment options available [14,15]. The effective recruitment and retention of study participants are critical to the success of clinical trials, as they can significantly impact the timeline and costs of the study [16,17]. To address these challenges, the LeDoxy trial employed a strategic approach to participant recruitment and retention.

To streamline and expedite participant enrollment, the study team developed a targeted, participant-focused recruitment plan. This strategy aimed to effectively engage potential participants while proactively addressing barriers to participation, including misconceptions and logistical constraints. Central to this effort was the involvement of CHWs, who played a pivotal role throughout the recruitment process. Their deep familiarity with local residents and established relationships within the community positioned them as trusted intermediaries, enhancing the credibility and acceptability of the trial. The critical role of community-directed distributors in NTD control has been well documented across sub-Saharan Africa, with millions of community health workers contributing to the successful delivery of interventions for neglected tropical diseases including lymphatic filariasis over more than two decades [18].

Participants were more receptive to being approached by CHWs, who were viewed as reliable and familiar figures. Working closely with the site clinical team, CHWs engaged directly with community members to explain the study’s purpose, procedures, and potential benefits. This collaborative outreach not only supported efficient participant recruitment but also contributed to building community trust and reinforcing transparency throughout the trial process.

During the informed consent process, potential participants were provided with comprehensive information about the study. This included clear explanations of the study’s objectives, procedures, potential risks and benefits, as well as available alternative treatments. The process was designed to ensure that participants could make fully informed decisions regarding their involvement. Open and ongoing communication between the research team and participants was a key component of the consent strategy. The research team prioritized accessibility and transparency, ensuring that participants could consult with study staff and receive support whenever they had questions or concerns. This approach helped reinforce participants’ confidence and trust in the research process, upholding ethical standards throughout the study.

Participant retention and follow-up

To minimize dropout rates and loss to follow-up, the study team implemented a structured retention plan that emphasized consistent communication and participant support throughout the trial. Regular contact with participants was maintained to ensure they remained informed, engaged, and connected to the research team. CHWs played a central role in supporting retention efforts. Beyond their initial involvement in recruitment, CHWs maintained regular engagement with participants by offering continued support, including hygiene education and the distribution of antimicrobial and antifungal creams for the management of lymphedema. Their ongoing presence helped foster trust and promote adherence to the study protocol. An important operational insight gained during the study was the need to consider the local economic and occupational context. Many community members were involved in seasonal farming and fishing activities, which significantly influenced their availability. By understanding and adapting to these seasonal patterns, the study team was able to optimize the timing of follow-up visits and reduce the risk of missed appointments or participant attrition.

By leveraging the expertise and relationships of CHWs, maintaining open communication, and tailoring recruitment and retention strategies to the local context, the LeDoxy trial effectively managed participant recruitment and retention. This approach not only facilitated the successful execution of the study but also built strong community support and trust, contributing to the overall success of the trial.

Impact of the COVID-19 pandemic on trial implementation

The onset of the COVID-19 pandemic during the recruitment phase of the LeDoxy trial introduced significant challenges to the health sector, profoundly disrupting research activities and impacting every aspect of trial implementation, from regulatory approvals to participant engagement.

The pandemic coincided with the trial’s early stages, overwhelming regulatory authorities with a surge of COVID-19-related clinical trial applications, which delayed approvals for ongoing trials, such as LeDoxy. The study team mitigated this through sustained dialogue with regulatory and ethics bodies, adapting to revised guidelines and public health protocols. Heightened concerns about COVID-19 transmission among participants and staff prompted the implementation of stringent infection control measures, including minimizing in-person interactions, mandating personal protective equipment, and implementing safety-focused procedures. Travel restrictions further complicated planned monitoring, leading to the adoption of remote monitoring via video conferencing tools (e.g., iPads, laptops, smartphones), enabling real-time oversight with an external monitor in Kenya. Global supply chain disruptions also delayed essential material deliveries, necessitating flexible timeline adjustments and innovative logistics planning.

Despite these obstacles, the LeDoxy trial demonstrated resilience by integrating pandemic response into its operations. In alignment with Tanzanian government directives, the team contributed to the national COVID-19 effort by developing and distributing tailored information, education, and communication (IEC) materials, enhancing community awareness and trust in both research and public health systems. This dual focus on trial continuity and public health support underscored the importance of adaptability, leveraging existing engagement infrastructure (e.g., community health workers) to maintain a 92% retention rate. The experience strengthened the trial’s protocols, fostering innovation, regulatory collaboration, and technological integration, and provided valuable lessons for conducting resilient clinical trials in low-resource settings during future public health crises.