The role of stakeholder mapping and engagement in Mongolia during the implementation of the STREAM clinical trial for MDR-TB

Abstract

Background

Clinical trials evaluating new regimens for multidrug-resistant tuberculosis (MDR-TB) are typically conducted in multiple countries because global registration of new TB drugs requires evaluation in diverse populations. The complexity of multi-site trials makes implementation challenging, especially in lower-resource settings, where the burden of MDR-TB is highest. Stakeholder engagement can improve trial implementation and outcomes. Here, we describe the Mongolia site’s stakeholder engagement during STREAM, a phase III clinical trial evaluating novel treatment regimens for MDR-TB.

Main body

We assessed our stakeholder engagement against the PCORI rubric. Engagement at all phases of the trial aligned well with the PCORI engagement principles of reciprocal relationships; co-learning; building partnerships; and transparency, honesty, and trust. In the planning phase, we formed a key partnership with a civil society organization to co-lead the trial, undertook stakeholder mapping, and developed an overall engagement strategy. During trial implementation, we undertook activities aimed at ensuring feasibility of the study, improving recruitment, ensuring viability of the study, and ensuring authenticity/value of stakeholder engagement. Activities, which included continuous communication with the national TB program to ensure referral of potential trial participants, implementation of a comprehensive community engagement (CE) program, delivery in collaboration with partners of psychosocial support for trial participants, capacity-building and knowledge sharing, regular communications on trial developments and progress, and community advisory board (CAB) participation in CE assessment, contributed to achieving a 98% retention rate and the highest participant recruitment across all STREAM trial sites. In the dissemination phase, CAB members worked together with the site and sponsor to ensure strategies and materials were tailored to stakeholders’ needs, including participants; communities; frontline healthworkers; and national-level stakeholders. Stakeholder participation in research and in improving routine TB care in the country has been sustained since completion of the trial.

Conclusions

Significant and sustainable gains can be made through stakeholder collaboration. We recommend that trial sites in lower-resourced settings take an expansive view of relevant stakeholders when planning engagement; undertake capacity-building and knowledge sharing; plan for long-term sustainability of CE; design engagement around specific objectives; tailor and optimize communication strategies; and design stakeholder engagement to involve key policy makers.

Trial registration

ISRCTN78372190 - Registration date is October 14, 2010 (Stage 1) and ISRCTN18148631 - Registration date is February 10, 2016 (Stage 2). 

Background

The Evaluation of a Standardized Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis (STREAM) was a multi-site clinical trial to examine shortened regimens for multidrug-resistant tuberculosis (MDR-TB) [1]. It was the first phase III trial to test the efficacy and safety of bedaquiline, one of the newest MDR-TB drugs, within a shortened treatment regimen. STREAM enrolled more than 1000 participants over 8 years, at 15 sites in eight countries, including Mongolia, Ethiopia, India, Georgia, Moldova, South Africa, Uganda, and Vietnam [2].

Clinical trials evaluating new regimens for MDR-TB are typically conducted at multiple sites and countries, because it can be difficult to recruit a large enough cohort of patients at a single trial site [3], and because global registration of new TB drugs requires evaluation in appropriately diverse populations [4], the complexity of multi-site clinical trials makes implementation challenging in any setting, but even more so in lower-resource settings, where the burden of MDR-TB tends to be highest [5].

A recent systematic review identified several categories of challenges impeding clinical trial implementation in resource-limited settings [6], encompassing financial and human capacity constraints, ethical and regulatory system obstacles, lack of favorable research environment, operational barriers, and competing demands. Within the financial and human capacity constraints category, significant barriers include limited experience with clinical trials, especially regarding administrative and regulatory aspects [7, 8]. Ethical and regulatory system obstacles manifest as delays in regulatory approvals [6, 7, 9], heterogeneity in national regulatory structures [9, 10], under-resourced national regulatory institutions [7, 11], and complex national requirements related to drug procurement and importation [9, 10]. Research environments can be characterized by underdeveloped healthcare infrastructures at study sites [7, 9, 11]. Operational barriers include complex contracting issues [6, 9, 10], varying insurance standards [10], high turnover of qualified trial site staff [7, 8], distrust or suspicion of healthcare providers [7, 11], and local practices and beliefs impacting trial recruitment and participation [11]. Competing demands can add additional burdens of trial participant recruitment on already-stretched healthcare workers [6–8].

The Mongolian context

Mongolia, a large landlocked country in East Asia with a population of 3.4 million and a land area of approximately 1.5 million square kilometers, is one of the most sparsely populated countries globally. Since 2000, rapid urbanization has led to the expansion of Ger (yurt) areas on the outskirts of Ulaanbaatar (UB), the capital, creating densely populated peri-urban regions with limited public services access. Currently, about 1.4 million people reside in UB, with over one-third living in these expanding Ger areas [12]. Mongolia has the fourth highest tuberculosis (TB) burden in the WHO Western Pacific Region, with an estimated TB incidence of 452 per 100,000 population and 34 per 100,000 for multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) [13], predominantly affecting adult males aged 35–54 years. Approximately 70% of TB-affected households in Mongolia face catastrophic costs due to TB, rising to 85% for households affected by drug-resistant TB (DR-TB) [14].

The healthcare system in Mongolia is primarily government-managed, providing universal free care for TB. The National Center for Communicable Diseases (NCCD)—the STREAM trial site in Mongolia—is Mongolia’s tertiary level institution dedicated to prevention, control, and surveillance of infectious disease, including TB. It is located in UB and houses 200 of the 550 TB beds available nationwide and offers specialized TB care and services [15]. Additionally, 60 beds are allocated for MDR-TB patients nationwide, with TB dispensaries in UB and provinces delivering outpatient services and Directly Observed Treatment (DOT) for TB patients.

In 2018, the Mongolian government’s Science and Technology Fund allocated only 0.1% of the country’s gross domestic product to research and development. Observational studies constitute a significant portion of research in Mongolia, with STREAM being the first multi-site clinical trial in the country to evaluate an MDR-TB regimen, according to clinicaltrials.gov. Mongolia’s clinical trial infrastructure is less developed compared to countries with a more extensive history of clinical research. In Mongolia, a clinical trial typically requires approval from the Scientific Committee (SC) of the relevant research institutions to ensure scientific rigor. Additionally, approval from the Medical Ethics Monitoring Committee (EC) of the Ministry of Health (MoH) is necessary. The Medicine, Medical Devices Regulatory Agency of the MoH (since 2020) must also issue import permits for trial-related drugs/devices and export permits for biological samples sent for testing- responsibilities that were previously handled by the National Center for Health Development.

Stakeholder engagement rubrics

Stakeholder engagement models demonstrate that development and implementation of a comprehensive stakeholder engagement strategy can be an effective tool for improving the quality of research and addressing trial implementation challenges like those described above [16–26]. The potential benefits of engagement include ensuring that research questions and study measures reflect patient‐identified priorities [24], better recruitment and retention rates [27], improved research prioritization, better study design and data analysis, greater relevance, and uptake of research results [28, 29]. increased capacity of researchers and stakeholders, improved relationships between researchers and other stakeholders, better research processes, community empowerment, and increased buy-in for research results [30].

Models of stakeholder engagement have been operationalized into several practical rubrics/tools for use by researchers to guide stakeholder engagement. There are at least three widely applicable tools for health research—the Canadian Institute of Health Research (CIHR) Strategy for Patient Oriented Research Patient Engagement Framework, the National Institute for Health and Care Research (NIHR) Guidance on Co-producing a Research Project, and the Patient Centered Outcomes Research Institute (PCORI) Engagement Rubric for Applicants [28, 31–33]. By their terms, they apply to a wide spectrum of health research, across a range of study designs and without regard to disease or condition being studied.

The CIHR and NIHR tools cover strategies for engaging patients, whereas the PCORI Engagement Rubric applies to engagement with all stakeholders necessary to achieve patient-centered outcomes. None of the rubrics are prescriptive, stating instead that a principles-based approach more effectively enables researchers to adapt their approach to local circumstances. The principles underlying the guidance in each of these tools are set out below:

PCORI	CIHR	NIHR
• Reciprocal relationships • Co-learning • Partnerships • Transparency, honesty and trust	• Inclusiveness • Support • Mutual support • Co-building	• Sharing power • Including all perspectives and skills • Respecting and valuing the knowledge of all working on the research • Reciprocity • Building/maintaining relationships

Activities recommended by the PCORI tool are organized according to the stages of the research cycle—planning the study, implementing the study, and disseminating the results. The other tools are organized around principles, rather than research stages (although they often suggest activities at various stages of the research cycle) [28, 31–33].

We reviewed the CIHR, NIHR, and PCORI tools and concluded that the engagement activities undertaken as part of STREAM should be assessed using the PCORI tool. On a practical level, the tool’s clear delineation according to study stages mirrored how the study team had addressed stakeholder engagement in the trial. In addition, the tool’s explicit application to a wider range of stakeholders—in addition to patients—best-reflected the approach taken by the site, which concluded that engagement with a broad range of stakeholders would be necessary to achieve the aims of the trial, given the country’s relative inexperience with clinical research. The breadth of research reporting use of the PCORI tool to guide engagement was also a significant factor considered by the site [34–36].

Stakeholder engagement during implementation of STREAM trial

This commentary describes the site’s approach to stakeholder engagement according to the PCORI stakeholder engagement rubric [28, 33] during the three trial phases described by PCORI and elsewhere [28, 33, 37].

1. Identifying key stakeholder

A significant first step in planning an engagement strategy is to identify all stakeholders “who would need to be included in order for the project to be as successful as possible” ([33], p. 3). The site considered this to include all those who are interested in the research, have unique knowledge of the relevant topic, and have the power to make a difference (Table 1) [38]. In line with other researchers, it also concluded there would be interested stakeholders at each level of trial implementation (international, national and local) [28, 37–39].

Table 1.

Key stakeholders

Stakeholder	Role/importance
The Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM)	Funds Mongolia’s NTP; managed through the project coordinating unit (PCU)
World Health Organization (WHO) country office	Develops international evidence-based norms for MDR-TB and provides technical assistance to NTPs
Ministry of Health of Mongolia (MoH) a	Oversees health policy, programs and funding in Mongolia
National TB Program (NTP)	Manages provision of TB care in the country
Frontline health workers at district TB dispensaries	Provide decentralized TB care to patients in the capital city of Ulaanbaatar
National TB Reference Laboratory (NTRL)	Provides national TB diagnostics, including drug susceptibility testing; conducts quality assurance and oversees improvements to technical capacity of national TB laboratories
Directors/management of the National Center for Communicable Diseases	Senior managers of the NCCD
NCCD Scientific Committee	Reviews and approves scientific rigor and methodology of research protocols
Civil Society Organizations (CSOs)	Non-governmental organizations involved in TB research, care and advocacy
STREAM trial community advisory board (CAB)	Formed to serve as a bridge between community stakeholders and the site
People affected by MDR-TB	People with lived experience of MDR-TB

^aIncluding Department of Health Care and Services, Medical Ethics Monitoring Committee, Medicine, and Center for Health Development

A co-leadership arrangement for the trial was established between the trial site (NCCD) and the Mongolian Anti-Tuberculosis Coalition (MTC). Under the agreement, NCCD was responsible for managing clinical aspects of the trial and MTC agreed to oversee regulatory, administrative, and financial matters, as well as development of a support package for trial participants. Once this partnership was formed, a further stakeholder mapping exercise was carried out about 6 months prior to the date on which the site opened for recruitment (Site Initiation). The process identified 11 key stakeholders that were to be engaged across all phases of the trial (planning through to dissemination). A small number of additional stakeholders emerged during the trial and are described in the subsequent sections of the commentary.

• 2.Engagement during the planning/study initiation phase

Engagement during the planning phase extended over the 6 months preceding Site Initiation (Table 2). The PCORI stakeholder engagement rubric recommends engagement activities during this phase encompassing the following three aspects—development of research questions and outcomes to ensure relevance of the study to participant and stakeholder communities; defining participant characteristics to minimize risk that irrelevant inclusion/exclusion criteria are implemented; and designing the study to minimize disruptions to participants and other stakeholders to improve participant retention ([33], p. 5).

Table 2.

Stakeholder engagement during the initiation/planning phase for STREAM clinical trial

Stakeholder	Engagement activities/approach	Communications activities	Barriers addressed by engagement activities	Impact of engagement
The Global Fund to Fight AIDS, Tuberculosis and Malaria; WHO country office	Activities: Site met with the project coordinating unit (PCU) of GFATM and a WHO officer, jointly with NTP, to introduce the trial and to clarify sponsor’s responsibility for procuring interventional drugs Strategic insights: Meeting was important for ensuring continuity of international support for NTP and resource alignment. Helped ensure NTP and PCU incorporated trial’s expected drug procurement into GFATM’s procurement plans for the NTP	Timing: Five months prior to Site Initiation Mode: In-person meeting Frequency: Once Written materials used (if any): Introductory slides outlining the trial and associated implementation activities	Financial and human capacity constraints Lack of favorable research environment	GFATM support for Mongolian NTP (primarily funded by the GFATM) reinforced and continued
MoHa	Activities: Initial meeting with MoH to present the trial, introduce the site team, provide site-specific details and management of the trial at the site, and gather immediate feedback on the implementation of the trial. This meeting has also clarified details of information and documents required for import/export of samples, equipment and supplies Follow-on comms to better-define ethical and regulatory requirements for the trial, as well as to agree form and content of required agreements Site translated key trial documents from English to Mongolian for review by MoH Strategic insights: Engagement helped ensure MoH’s buy-in for the trial and facilitated site obtaining permission to export biological samples and import interventional drugs	Timing: Four months prior to Site Initiation Mode: Initial in-person meetings/follow on emails Frequency: Bi-weekly during the first month Written materials used (if any): Introductory slides outlining the trial and associated implementation activities	Ethical and regulatory system obstacles Lack of favorable research environment Operational barriers	High level of MoH buy-in for the trial Reduction of time to site opening Development of “work around” to allow export of microbiology samples to trial’s central laboratory in Belgium In principle permission to import trial drugs
NTP at the NCCD	Activities: Initial meeting with NTP manager to explain trial objectives and requirements, potential benefits to the NTP Follow on meeting with NTP managers to define a model of collaboration for the trial, including identification of suitable trial team members, identification and referral of participants to the trial, NTP support for DOT/patient management, etc. Meeting with MDR-TB clinicians to explain trial objectives and requirements, potential benefits to the NTP Site visit to National Reference TB lab, TB Pharmacy unit, and two MDR-TB wards to assess possible physical infrastructure improvements required for trial, approaches for integrating the trial activities and effective information flow and communications Strategic insights: Engagement led to adoption of a critical collaboration strategy with the NTP involving the sharing of scarce human resources by the trial and the NTP	Timing: Four to five months prior to Site Initiation Mode: In-person meetings/emails/phone Frequency: Five times Written materials used (if any): Trial summary	Financial and human capacity constraints Operational barriers Competing demands	High level of national buy-in for the trial Improved capacity of NTP staff to contribute to research Model developed for collaboration between NTP and future multi-site research studies High recruitment rate to the trial High retention rate for the trial, facilitated by NTP support for DOT/patient management Trial did not divert scarce human resources from NTP Good collaboration between government and non-government organizations
Frontline health workers at district TB dispensaries	Activities: Site, NTP leaders and sponsor met with TB dispensary coordinators and main clinicians responsible for patient management at 9 UB TB dispensaries to explain trial objectives and requirements, to discuss the trial’s potential benefits to participants and the NTP, and to obtain support for the trial from frontline health workers; followed by Q&A Site coordinator met with TB dispensary coordinators and main clinicians responsible for patient management at 9 UB TB dispensaries to understand patient referral mechanisms, DOT and patient management Site and district TB dispensaries defined roles/responsibilities related to all aspects of the trial Strategic insights: Engagement was important for providing TB dispensaries with clarity on trial processes and clearly defining roles/responsibilities of the site and TB dispensaries for the trial. Also helped strengthen communications between TB dispensaries and trial team	Timing: Four to five months prior to Site Initiation Mode: In-person meetings Frequency: Twice Written materials used (if any): Introductory slides outlining the trial and associated implementation activities	Financial and human capacity constraints Lack of favorable research environment Operational barriers Competing demands	High referral and recruitment rates to the trial High retention rate for the trial Reduced number of protocol deviations Improved capacity of frontline health workers to participate in clinical trials Trust and support built between the trial team and frontline health workers
NTRL	Activities: In-person initial meeting with NTRL to explain trial objectives and lab requirements, ensuring clarity on key tasks In-person technical meeting with the head of the NTRL addressed technical requirements of trial-specific procedures and regulatory requirements for sample exportation Site translated trial lab manual from English to Mongolian for review by NTRL senior staff Strategic insights:	Timing: Two to three months prior to Site Initiation Mode: In-person meetings/emails Frequency: Twice; follow up emails Written materials used (if any): Trial protocol	Financial and human capacity constraints Lack of favorable research environment Operational barriers	Trial lab assessments performed successfully as per protocol requirements Improved technical capacity of the NTRL and staff at NTRL Established successful model for future collaboration between national reference lab/programmatic lab and multi-site clinical research studies
NCCD directors/management	Activities: Meetings with NCCD General Director to provide an overview of the trial and its implementation, as well as discussion of trial team members Meeting with NCCD’s Deputy Directors and head of finance focused on legal agreements and financial matters Site translated key trial documents from English to Mongolian for review by directors/management of NCCD Strategic insights: Engagement was important for building high-level buy in and ensuring the trial was properly funded by Sponsor	Timing: Four to six months prior to Site Initiation Mode: In-person Frequency: Three times Written materials used (if any): Trial summary	Financial and human capacity constraints Competing demands	High-level buy-in for the trial at NCCD All required NCCD trial staff identified and in place in two months Clear time and effort allocations between trial and NTP activities for NCCD staff agreed and implemented
NCCD Scientific Committee (SC)	Activities: Initial in-person meeting with the SC scientific secretary held to gain a clear understanding of the SC’s application requirements Second in-person meeting with SC member in order to review the trial protocol and related documents, and address questions to ensure compliance with SC regulations Site translated key trial documents from English to Mongolian for review Strategic insights: Early engagement important so that any important concerns of SC could be identified and (if necessary) fed back to the Sponsor	Timing: Six months prior to Site Initiation Mode: In-person/phone/emails Frequency: Twice Written materials used (if any): Introductory slides outlining the trial and associated implementation activities	Lack of favorable research environment Operational barriers	High level of scientific buy-in for the trial Reduction of time to site opening
CSOs	Activities: Coordinated by MTC, site met with treatment support volunteers/community health workers from the Mongolian Anti-TB Association to gather valuable insights on how to best support MDR-TB patients Strategic insights: Engagement led to development of supplemental participant support package that contributed to better trial outcomes. Also gave site access to volunteers/community health workers, which helped to ensure treatment adherence.	Timing: Two months prior to and four months after Site Initiation Mode: In-person Frequency: Twice Written materials used (if any):	Operational barriers Competing demands	High retention rate for the trial, facilitated by CSO’s home DOT and psychosocial support for trial participant and their families CSO helped ensure participants attended trial specific follow-up visits and were referred for unscheduled visits, when necessary Model of collaboration between CSOs and study teams for future TB clinical research defined
CAB	n/a, not yet formed
People affected by MDR-TB	Activities: Site developed/completed a short survey (self-administered by Px; managed by senior nurses in twoTB wards) of 50+ MDR-TB patients to understand their experience of MDR-TB and identify their needs for support during treatment and follow up Strategic insights: Survey results provided crucial insights that helped to inform the development of a targeted patient support strategy for the trial	Timing: One month prior to Site Initiation Mode: In-person Frequency: Once Written materials used (if any): A summary outlining the purpose of the survey, a verbal consent script, and an anonymous, self-administered questionnaire	Operational barriers	Based on survey results, targeted patient support strategy developed and implemented, with the aim to improve recruitment and retention

^aIncluding Department of Health Care and Services, Medical Ethics Monitoring Committee, and Center for Health Development

The Mongolia site’s activities during the planning phase were focused on implementing the trial in a manner that would minimize disruptions to participants and other stakeholders. The main engagement activities were forming strategic partnerships, identifying the role(s) of key stakeholders in the research process, developing an engagement strategy, translation of key trial documents to Mongolian, face-to-face stakeholder meetings, follow on communications, identification of possible implementation barriers, development of stakeholder collaboration strategies, formative research relevant to trial implementation, and training/capacity building for key stakeholders. The site’s engagement did not encompass other recommended PCORI activities for this phase (i.e., identification of research questions/study outcomes and development of inclusion/exclusion criteria) [28, 33].

The site’s initial meetings with key stakeholders typically outlined an overview of the STREAM trial, what it aimed to achieve, its scientific and public health relevance in the Mongolian context, and the requirements to conduct the trial. These meetings enabled the site study team to understand and plan for each stakeholder’s requirements related to the trial, including with respect to regulatory and organizational approvals; stakeholder processes and timelines; possible required improvements to physical infrastructure required for the trial; and stakeholder funding/training needs. Initial meetings also helped to generate buy-in from key stakeholders.

Meetings with treatment support volunteers/community health workers and patient surveys conducted in the MDR-TB ward at the NCCD (unpublished, Tsog B.) helped identify challenges encountered by people affected by MDR-TB and informed the development, in partnership with MTC, of supplemental participant support aimed at improving retention and to enhance the overall patient experience during the trial.

Engaging with NCCD directors, the NTP (both centrally and at district-level TB dispensaries), and the NTRL prior to trial initiation influenced staffing strategies and helped identify physical infrastructure improvements required to implement the trial in accordance with the trial protocol and Good Clinical Practice/Laboratory Practice Guidelines. This increased buy-in for the trial (and therefore take-up of results) and helped ensure the trial did not disrupt routine operation of the NTP. Interactions with key stakeholders also permitted the core study staff to emphasize the longer-term benefits of the trial, including the positive impact on the country’s research capacity and on the quality of TB care and control; this helped to strengthen the overall research environment in the country.

Engagement with the PCU of the GFATM and the country officers from the WHO increased support for the trial and the NTP by the two international stakeholders that fund and provide technical assistance to the country’s NTP, respectively. In turn, this improved collaboration between the study team and the NTP. In addition, a decision was made for the trial to share NCCD’s NTP staff (rather than hire dedicated trial staff), providing additional training to NCCD NTP staff as required by the trial. This decision to integrate existing staffing for trial implementation, while clearly defining roles and time allocations between the NTP and the trial, was designed to improve recruitment rates, increase buy-in for the trial (and therefore take-up of results) and ensure the trial did not deplete already limited human resources. Moreover, having MTC as a co-leader of the trial gave the site access to TB-affected people and community-based actors.

Key challenges during this phase included limits on site input into trial design and inclusion/exclusion criteria as a result of trial design being centrally led by the Sponsor, financial issues caused by the long period of planning/preparation prior to Site Initiation, difficulty obtaining regulatory consents for export of microbiology samples to the trial’s central lab, and limited community-based engagement and input caused by the lack of a trial CAB. Significant activity was required to prepare for Site Initiation, but Sponsor funding was not in place until Site Initiation. This required MTC to contribute to the cost of planning activities from its own resources. Initial meetings with the MoH regarding export of microbiology samples indicated that it would be difficult for the site to obtain permission to export sputum isolates for analysis at the site’s central laboratory in Belgium, as required by the trial protocol. Following meetings with relevant regulatory authorities, an agreement in principle was reached for the regulator to permit export of inoculated samples instead of sputum isolates. This change required amendments to the trial protocol and laboratory manual, which contributed to delays in Site Initiation. The negative impact of failing to have a CAB in place during the planning phase was minimized through close collaboration with MTC and the pre-initiation survey of TB-affected people conducted by the site.

• 3.Engagement during the implementation phase

Consistent with the PCORI stakeholder engagement rubric, engagement activities during this phase focused on stakeholder support/participation in trial implementation, with the objectives of ensuring feasibility of the study for clinicians and trial participants, improving recruitment to the trial, ensuring viability of the study, and ensuring the authenticity and value of stakeholder engagement in the trial (Table 3) [28, 33]. Although not mentioned as an objective by PCORI, the site’s engagement activities also aimed to ensure learning from the trial was fed back to national stakeholders strengthen the research environment and programmatic TB care in the country. Engagement activities included:

• Continuous communication between the site and the NTP to facilitate identification and referral of all potential trial participants

• Development and implementation of a comprehensive community engagement (CE) program, including the creation of a community advisory board (CAB)

• Development and delivery by the site and CAB of a package of supplemental support for trial participants, guided by the site’s formative research with TB-affected people

• Capacity-building and knowledge sharing for key stakeholders

• Regular stakeholder updates on trial developments and progress

• CAB participation in assessing the trial’s CE program

Table 3.

Stakeholder engagement during the implementation phase for STREAM clinical trial

Stakeholders	Engagement activities/approach	Communication activities	Barriers addressed by activities	Impact of engagement
MoH ( Centre for Health Development )	Activities: Regular meetings with regulator (approximately once a month) to submit information and obtain import/export licenses, minimizing delays in trial operations Strategic insights: Proactive licensing coordination with the regulator was essential to ensure a stable supply of trial-related medications (preventing disruptions in patient treatment and study timelines) and timely export of samples for analysis	Timing: Continuing throughout implementation after Site initiation Mode: In-person Frequency: As needed (Approx. monthly) to ensure timely import of trial drugs, equipment and export of samples Written materials used (if any): N/A	Ethical and regulatory system obstacles Lack of favorable research environment Operational barriers	Improved understanding and faster response by regulators to trial requirements, resulting in more efficient import of trial supplies and export of specimens Trial avoided regulatory delays by providing complete/timely information to government agencies
SC and EC	Activities: Site met with SC and EC to explain major protocol amendments and significant PDs/SAEs Site provided SC and EC with information in the format requested—including translations, summary, table of amendments, rationale etc. Site and EC agreed on the form and format of reporting protocol deviations, Serious adverse events etc. Strategic insights: Providing committees with comprehensive overviews of major protocol amendments, SAEs, and other significant issues ensured committee members remained up to date and reduced delays.	Timing: In advance of major protocol amendments and other major events Mode: In-person/Follow on emails to ensure timely decision-making Frequency: Approx. eight in-person meetings Written materials used (if any): Typically, a summary table of changes to the protocol was necessary for protocol amendments. Sometimes PowerPoint presentations were prepared. Other information provided in the format requested by the committees	Lack of favorable research environment Operational barriers	Site, SC and EC managed protocol amendments in a timely manner – six major amendments managed during trial implementation Improved capacity of committee members to provide ethical oversight for future clinical trials of similar complexity
NTP/NTRL	Activities: Site provided continuous trial updates, including trial participants’ treatment experience, adherence and retention to stakeholders through in person meetings and updates in the Mongolian Journal of Infectious Research Diseases (MJIRD) Site team regularly provided training to NTP/NTRL staff covering basics of clinical trials, Good Laboratory and Pharmacy Practices, and community engagement experiences. Trial’s central laboratory in Belgium trained NTRL on trial-specific methods and assessments, as well as introduction of new methods, such as fluorescein diacetate for vital staining for detecting viability of acid-fast bacilli Strategic insights: Knowledge dissemination and capacity building were key to reciprocal relationships with the NTP and resulted in both immediate (weekly group email from the NTP on newly registered DR-TB patients that facilitated timely referral, screening and enrolment of trial participants) and long-term (invitation to support development of national plans, guidelines, funding proposals) positive outcomes.	Timing: Commencing approx. one month before Site Initiation and continuing throughout implementation Mode: In-person/email/publication Frequency: As needed Written materials used (if any): updates in the Mongolian Journal of Infectious Research Diseases (MJIRD); Site team leveraged the MJIRD News section to enhance trial transparency and stakeholder engagement by publishing several articles. These covered trial implementation, clinical, lab, pharmacy-specific aspects, and key updates, ensuring informed participation and reinforcing the trial’s credibility within the research and healthcare community.	Financial and human capacity constraints Operational barriers Competing demands	Close collaboration between trial team and NTP/NTRL resulted in (i) high referrals/recruitment; (ii) higher retention rate and (iii) improved data quality because of higher efficiency in managing trial procedures, and therefore better adherence to trial protocol. Importantly, successful engagement of these stakeholders resulted in high level buy-in for the trial, and contributions to programmatic planning and policymaking. NTRL capacitated by trial’s central laboratory on new laboratory methods
Frontline health workers	Activities: Site provided training and online support to health workers from family health centers and TB dispensaries and defined a model for collaboration with frontline health facilities. Strategic insights: Continuous engagement between clinical teams of the site and frontline health facilities ensured prompt resolution of queries that prevented delays or missed opportunities for enrolment, and reduced errors in patient follow-up management.	Timing: Two months after the Site initiation and continued monthly Mode: In-person Frequency: The site team conducted an initial meeting with district TB dispensary staff, followed by quarterly face-to-face supportive supervision. Written materials used (if any): Introductory slides outlining the trial and detailed implementation activities; trial treatment cards; and drug and injection logs (injection log was used during Stage 1 of the trial)	Financial and human capacity constraints Lack of favorable research environment Operational barriers Competing demands	Improved implementation efficiency by ensuring high recruitment/retention rates; and enhanced quality by ensuring adherence to treatment and follow-up. Contributed to sustainable strengthening of human resource capacity by equipping frontline health workers with trial experience that can be useful for future trials in Mongolia.
CSOs	Activities: Site formed a TB CAB comprising CSOs, reps from affected communities, trial participants, and staff with defined roles in specific areas of trial implementation: • Treatment management and adherence (DOT) support • Ongoing participant support through routine phone calls and periodic home visits, especially enhanced during the COVID-19 pandemic • Evaluation and refining of community engagement strategies. Strategic insights: Trial implementation that was inclusive of the CSOs/CAB was sensitive to participant needs and allowed for adherence to treatment and follow-up visits, and supportive home visits for care. Further, equipping CSOs with knowledge enhanced transparency and increased buy-in from the community for trial conduct.	Timing: Six months after the Site initiation of Stage 1 and continued during the Stage 2 trial implementation Mode: In-person/emails Frequency: An initial three-day meeting with the CSOs, followed by quarterly meetings and an annual general CAB meeting with all stakeholders. Written materials used (if any): Introductory slides outlining the trial and its implementation activities; trial progress presentations including CAB support for participants, as well as challenges and successes; and summary of CAB outreach efforts.	Lack of favorable research environment Operational barriers Competing demands	High retention rate for the trial, facilitated by CAB members’ support to patients and adjustments made by site team in response to participant feedback re: safety and well being Low loss to follow up/high adherence rate for the trial facilitated by CAB members’ support to patients Integration of CAB experiences (home and video DOT, joint patient and family member meetings) into the operations of the TB district dispensary Development of a model for community engagement/collaboration between trial teams and CSOs that can be used for future TB trials
People affected by MDR-TB	Activities: Site and CAB organized joint meetings between trial participants/their families, and trial staff to share ongoing updates, explain trial procedures and clarify support available to them. Site also facilitated engagement with people affected by MDR-TB by ensuring their representation in and contribution to the CAB. Strategic insights: Engaging trial participants, their families, and other people affected by MDR-TB was critical to fostering respect and transparency.	Timing: Four months after the SIV, engagement continued in alignment with trial enrollment to include newly enrolled patients and their families Mode: In-person Frequency: As needed Monthly food support and visit reminders. 26 joint meetings in total with trial participants/families. Written materials used (if any): N/A	Lack of favorable research environment Operational barriers	High recruitment/retention rates and increased buy-in for the trial facilitated by improved patient experience. Enhanced understanding, and reduced stigma of TB within communities. Development of a successful model for community engagement and collaboration.
Wider Community	Activities: Site and CAB participated in Television Health Programs to share information on STREAM, to increase awareness of TB and the trial, and to advocate for TB affected communities and key vulnerable populations CAB conducted outreach activities at a secondary school and in five khoroosλ across three districts of Ulaanbaatar, directly engaging with 400 people and enhancing local awareness of TB. Strategic insights: Diverse media engagement and ongoing community outreach to increase awareness of TB across multiple strata proved helpful to increasing acceptance of research and uptake of findings.	Timing: Following the availability of both the preliminary and the final results Mode: In-person/Media channels Frequency: As needed Five TB-related health and news channels segments and featured in radio news twice. Written materials used (if any): Trial information pamphlets and a trial summary page.	Lack of favorable research environment Operational barriers	Enhanced understanding and reduced stigma of TB in the community Higher acceptance of TB research

^λsymbol specifies the smallest administrative unit under the provinces

To improve trial recruitment, the NTP began providing the site with a weekly list of all newly registered DR-TB patients nationwide for consideration as potential participants in the trial. Additionally, site clinicians, who were also members of the MDR TB Concilium at the NCCD, were informed about potential trial participants hospitalized in two MDR TB wards at the NCCD. By using these existing processes, the site’s trial activities were incorporated into existing NTP activities, ensuring the trial was program-based rather than an externally imposed initiative. Continuous communication with TB dispensary staff also helped ensure appropriate referrals to the trial site.

Planning phase activities revealed participant’s supplemental support needs, which the site aimed to address in collaboration with key stakeholders during implementation. Survey respondents reported that lack of awareness about TB within families, communities, and workplaces caused discrimination. In response, the site organized 26 meetings for trial participants and their families, where the CAB facilitated discussions of the basics of TB, and the trial process and expectations. These meetings helped ensure the acceptability of the study and generated support for participants and their families during treatment. The site’s formative research also influenced the supplemental support made available to trial participants and how DOT was undertaken during the trial. CAB members delivered monthly food support to participants most in need. They also gave visit reminders, made routine phone calls, and completed periodic home visits, especially during the COVID-19 pandemic. In addition, the site covered participants’ transportation costs and provided medications to manage side effects, helping to minimize catastrophic costs. In addition to supplemental support, the site also implemented a number of changes to how directly observed treatment (DOT) was implemented in the country to reduce the burden of treatment for participants. Family members were trained as DOT providers; community health workers were trained to deliver medications to participants unable to attend the clinic; and arrangements were made for DOT to occur at the NCCD for participants who found it difficult to arrive at local TB dispensaries before they closed at 3:00 pm. The combined supplemental support available to participants, as well as adjustments to DOT, helped reduce the burden of the trial and the disease for participants and encouraged attendance at scheduled visits.

CE was a critical focus during this phase of the trial. After Site Initiation and with the site’s support, a CAB was established during a workshop facilitated by the sponsor. The CAB’s members included CSOs, people affected by TB, and site staff. Care was taken to ensure key community stakeholders were invited to join the CAB so that the CAB was both effective and viewed by the community as a legitimate bridge between them and the trial team. Initially, the CAB and the site established the CAB’s terms of reference and agreed a model of collaboration. With support from the Sponsor, the CAB then developed and implemented a CE program that included delivery of supplemental support for trial participants, community outreach, CAB capacity-building, cross-site learning with other STREAM CABs and participation in results dissemination. The CAB’s support to trial participants (see above) encouraged visit adherence. The CAB’s outreach work, which focused on raising community awareness about TB and TB research within communities, helped ensure community members remained aware of the trial as a possible treatment option and gave CAB members valuable experience. Through the CAB’s work, the study team also learned about community concerns and questions regarding STREAM, while the community remained updated about study progress. This mutual exchange of information positively influenced trial implementation and built community trust in both the trial and clinical research generally.

Clinical and scientific knowledge sharing by the site team with the NTP yielded significant benefits for both the trial and the NTP. The trial team trained NTP staff on new, shortened treatment regimens for MDR-TB based on their STREAM experience, in advance of introduction of shorter regimens by the NTP. The site also shared its experiences of treatment adherence and retention strategies at national seminars and high-level meetings so they could be considered as part of the national TB program. In addition, the trial team participated in the development of new programmatic guidelines, ensuring that the lessons learned from STREAM directly contributed to improving the national TB program. Similarly, as part of the trial, NTRL staff were trained on new diagnostic techniques and Good Laboratory Practices. This focus on continuous knowledge sharing gave Mongolian health sector stakeholders access to clinical and technical knowledge about some of the newest MDR-TB regimens and diagnostic techniques, which strengthened the relationship between the study, the NTP and the NTRL. In turn, the close collaboration between these stakeholders helped improve recruitment to the trial and coordination of patient management between the site and the NTP. The key stakeholders’ familiarity with the shorter/all-oral regimens evaluated in STREAM have also facilitated introduction of shorter, all-oral regimens by the NTP that occurred as the trial progressed.

During the implementation phase, the site regularly communicated trial progress and challenges to key stakeholders. The site hosted regular (usually bi-annually) in-person update meetings to share trial progress and challenges with key stakeholders, including the MoH, NTP, NCCD and district TB dispensary staff, regulatory authorities, PCU, and CSOs. Annual CAB meetings were also held to update CAB members and allow for feedback from the CAB regarding community issues/perceptions regarding the trial. In addition, two trial implementation reports (2014–2018 and 2019–2021) were submitted to the SC and EC, detailing site recruitment, retention, and the work of clinical, nursing, laboratory, pharmacy, data management, and CAB teams. These reports also addressed challenges such as specimen transportation and information flow improvements. The site’s commitment to transparent reporting helped to build and maintain trust between the site and key stakeholders.

The final engagement activity during this phase was site/CAB participation in an assessment of the trial’s CE program, focused on defining best practices, challenges, and lessons learned from the experience. The process took place in the months preceding site closure and entailed completion of a brief questionnaire by Stage 2 CABs at all STREAM sites. The results were reviewed and incorporated into a publication entitled “Community Engagement Lessons Learned: A community perspective,” which was produced by the Moldova CAB coordinator (with sponsor support) and distributed to all CABs. It is available on the Sponsor’s website.

Key challenges during this phase included establishing and maintaining participation in the STREAM CAB, the first CAB ever established in Mongolia. Identifying and encouraging community members/TB-affected people to participate in the CAB was difficult, given the ongoing stigma attached to TB. Challenges to sustaining the CAB included maintaining long-term participation of members and addressing CAB misunderstandings, the most common of which related to statistical concepts, inclusion/exclusion criteria and safety reporting. Many CAB members had no prior experience voicing opinions to healthcare workers as equals and questioned whether healthcare workers would really consider their input. Equally, healthcare workers had no experience working with a CAB and sometimes perceived the CAB’s involvement as criticism or a nuisance, rather than as constructive collaboration. Overcoming these mutual misconceptions required the CAB coordinator and site coordinator to continuously work together to build capacity of CAB members, to identify/create opportunities for authentic collaboration between the CAB and the study team, and to publicly highlight the value of CAB contributions to both the trial and routine TB care in the country.

• 4.Engagement during the dissemination phase

Activities during the dissemination phase took place for over 3-month period, starting about 3 months before availability of results and continuing for 4 months after. The PCORI stakeholder engagement rubric recommends engagement activities during this phase encompassing identification of partner organizations, planning dissemination efforts, participating in dissemination efforts, and use of non-traditional methods to get results into the hands of those who need them [28, 33]. In line with PCORI’s recommendations, the site’s dissemination activities were designed around the following objectives:

• Participants and families should be the primary beneficiaries of the knowledge of treatment outcomes, given their contribution to the trial

• Strategies/materials for CSOs and community stakeholders should focus on trial outcomes, the benefits of participation in research, and the role of communities in research

• Frontline health workers and the site team should be briefed on effectiveness and side effects of the investigational treatment and its potential impact on the NTP

• Strategies/materials for key national-level stakeholders, including the MoH and NTP, should provide the information necessary to make decisions about changes to policies and programmatic guidelines potentially arising from the results

About 3 months prior to availability of results, the sponsor began working with CABs and the site team to develop a dissemination strategy. The study team and the CAB gave input on the overall dissemination strategy to ensure it encompassed appropriate audiences, events, information, and materials (in light of the stakeholders’ goals for dissemination). The sponsor led preparation of communications materials geared to each audience (power point presentations, pamphlets, videos, etc.), seeking CAB and site input to ensure the materials presented results in a format and in a manner that was culturally relevant/appropriate and understandable for the relevant audience. The site also translated dissemination materials into the Mongolian language.

About 1 month after results became available, the site presented the results to key implementing stakeholders, including the MoH, the NTP, the NCCD, and the CAB at a trial closing meeting using a PowerPoint slide deck made available by the sponsor. Wider NCCD staff were informed over the next 2/3 months through smaller meetings and printed pamphlets, and the site team held a separate meeting for CAB members using less technical materials developed for community stakeholders. About 2 months after results became available, the study team presented the results to international donors, civil society, and other key stakeholders at a CSO-led forum. The results were more widely communicated to civil society by the CAB and the site through in-person and virtual meetings using shortened materials in the local language. Reporting back to these stakeholders was important to reinforce community collaboration. A meeting for trial participants and their families was hosted by the CAB and structured as a celebration—acknowledging the contributions of participants to the trial. Results were presented by the study team using a simplified PowerPoint deck, and participants were encouraged to ask questions. The site attempted to contact all participants that did not attend the celebration to individually convey the results. About 3 months after availability of the results, the CAB (with support from the study team) developed communications materials distributed via social media and national TV broadcasts publicizing the positive results of the trial, addressing TB stigma and fostering support for TB research in general. The sponsor also published the results in an international, peer-reviewed journal, including the Mongolia site team as authors.

Following dissemination of Stage 1 results (which occurred mid-way through Stage 2 of the trial), the sponsor surveyed site staff, CAB members and trial participants at all STREAM sites to understand whether the Stage 1 dissemination exercise was perceived to be useful, and whether it was effective to accurately convey the trial results in an accessible way (Table 4). Results of the survey were also shared with CAB members at an all-CAB meeting/workshop, where suggestions for improvements were solicited from CAB members. Conclusions from this evaluation were used to inform dissemination strategies and materials for Stage 2 of the trial. Key changes made to Stage 2 dissemination activities based on this evaluation were to accelerate dissemination to Stage 2 participants (who were among the last to receive results in Stage 1), improve clarity and relevance of dissemination materials for trial participants and community members by engaging a group of CAB members to work closely with the sponsor on the development of those materials, and offering Stage 2 participants the opportunity to speak one-on-one with study investigators after the celebratory event, in case they were not comfortable asking questions at the event.

Table 4.

Stakeholder engagement during the results dissemination phase for STREAM clinical trial

Stakeholder	Engagement activities/approach	Communication activities	Barriers addressed by engagement	Impact of engagement
Project coordinating unit, Country coordinating mechanism of GFATM and WHO country office	Activities: Attended CSO-led national forum “Civil Society leadership to end TB in Mongolia,” where study team presented results Strategic Insights: Engagement was important to ensure key donor organizations aware of excellent experience with shorter MDR-TB regimen assessed in the trial and operational achievements of trial team/NTP	Timing: Two months after results available Mode: In-person meeting Frequency: Once Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the study team	Financial and human capacity constraints Lack of favorable research environment	Strengthened donor support for NTP, in particular, during later transition to shorter treatment regimen in response to STREAM results
MoH	Activities: Attended a meeting with study team to gain deeper understanding of the findings and discuss key outcomes and their potential implications for national policies and programs. Attended trial closing event for implementing partners (where study team presented results and CAB member shared her lived experience with TB and the trial) to acknowledge contributions of participants to the trial and achievements of trial team. Attended national CSO-led forum where study team presented results. Strategic insights: Participation of MoH in these events was important to reinforce MoH’s institutional commitment to the trial/research and “ownership” of trial’s results, while publicly acknowledging the contributions of participants and the site team to strengthening TB research in the country	Timing: Beginning shortly after results available Mode: In-person meetings Frequency: Twice Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the study team	Lack of favorable research environment	Demonstrated buy-in of MoH for results Highlighted MoH’s support for research in the country and the achievements of the NCCD/NTP in implementing the trial Strengthened partnerships between MoH and implementing partners Helped reduce stigma of TB
NTP, NTRL of the NCCD	Activities: Attended trial closing event (see above) Strategic insights: Attendance at event was important to ensure NTP’s contributions to the trial were publicly acknowledged and they learned about the results their work helped to produce	Timing: One month after results available Mode: In-person meeting Frequency: Once Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the study team	Lack of favorable research environment	Public recognition of trial’s positive impact on research capacity in the country and contribution of NTP to producing important evidence for improving TB care Strengthened partnerships between implementing partners Strengthened environment of trust surrounding the trial
Frontline health workers at district TB dispensaries	Activities: Attended trial closing event (see above) Strategic insights: Attendance at event was important to ensure contributions of frontline health workers to the trial were publicly acknowledged and they learned about the results their work helped to produce	Timing: One month after results available Mode: In-person meeting Frequency: Once Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the study team	Lack of favorable research environment	Public recognition of trial’s positive impact on research capacity in the country and contribution of frontline health workers to producing important evidence for improving TB care Strengthened partnerships between implementing partners Strengthened environment of trust surrounding the trial
NCCD directors/management	Activities: Attended meeting with the study team where results presented before public dissemination events occurred	Timing: Shortly after results available (before public events) Mode: In-person meeting Frequency: Once Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the study team	Lack of favorable research environment	Strengthened environment of trust surrounding the trial
Wider NCCD staff (Other Infectious Diseases staff)	Trial results dissemination meeting at the NCCD Dissemination of the printed trial results booklets	Timing: Eight months after the last participant enrollment at the site Mode: In-person Frequency: One time Strategic insights: - Widespread dissemination of trial findings and institutional knowledge sharing ensuring that key stakeholders were informed about the study’s findings and implications for policy planning and TB control efforts	Financial and human capacity constraints Lack of favorable research environment	Strengthened trial site transparency Strengthened partnership and trust
SC and EC	Activities: Attended online and in-person results sharing meetings with the site	Timing: Following the release of results Mode: Online and in-person meetings Frequency: Once for each stakeholder Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the study team; key successes and challenges faced by the site	Lack of favorable research environment	Strengthened the transparency and ethical oversight Support the translation of evidence into policy or programmatic decisions Reinforced collaboration among researchers and regulatory bodies, improving coordination for future studies
CSOs	Activities: MTC organized and led a national forum in partnership with the site called “Civil Society leadership to end TB in Mongolia,” where study team presented results Strategic Insights: Decision to disseminate results through a CSO-led event for multiple stakeholders emphasized the important role of CSOs in research, as well as promoting knowledge exchange and encouraging participation in TB research Dissemination at CSO-led event was an opportunity for CSOs and site to work together, strengthening partnership	Timing: Two months after the last participant’s follow up at the site Mode: In-person meeting Frequency: Once Written materials used (if any): PowerPoint deck prepared by Sponsor and adapted/translated for the local audience by the CAB and study team	Lack of favorable research environment	Underscored positive role CSOs can play in the research cycle and programmatic TB care Strengthened partnerships between CSOs and health sector stakeholders
CAB	Activities: Shortly after results available, attended small meeting with study team where results were presented to CAB in advance of public events. Attended national CSO-led forum where study team presented results. Participated in evaluation of Stage 1 dissemination, providing feedback to improve Stage 2 dissemination. Some CAB members participated in small working group formed to develop the Stage 2 dissemination strategy/materials with the sponsor. Hosted dissemination event for patients and families, featuring celebrations, poetry reading and singing performances. Worked with study team to develop dissemination materials for communication to wider community. Strategic insights: CAB participation improved the dissemination process and materials, built capacity of CAB members and strengthened relationship of CAB with health sector.	Timing: Beginning three months before availability of results and ending four months after Mode: Virtual and In-person meetings Frequency: Each dissemination event occurred once for each Stage of STREAM. There were app. 5 meetings to develop the Stage 2 dissemination plan and materials. Written materials used (if any): Study team used PowerPoint deck to share results with CAB. CAB reviewed/revised draft dissemination materials aimed at patients and community members provided by sponsor. CAB developed social media and broadcast television materials with support of study team.	Lack of favorable research environment	Deepened CAB’s understanding of research concepts and communications. Built trust between CAB and study team, who worked together to implement the dissemination plan. Improved reach and impact of results of the trial by ensuring they were communicated using appropriate materials
Participantss and families	Activities: Attended celebratory meeting hosted by the CAB, where study team communicated results of the trial Some participants attended one-on-one meetings with the PI to discuss the trial/results Strategic insights: Succes of event improved through active outreach to participants, encouraging attendance at the event. Significant input of CAB members into dissemination materials helped ensure they were appropriate and relevant for participants and their families One-on-one sessions with PI provide an opportunity for participants to ask questions and strengthened participant trust in the trial process	Timing: One month after results available Mode: In-person Frequency: One time Written materials used (if any): PowerPoint deck for patients and community members developed by sponsor and CAB. “One-pager” summarizing results developed by sponsor and CAB.	Lack of favorable research environment	Improved patient experience and involvement Strengthened perception of trial transparency and built trust in research Improved family support for people with TB and helped reduce stigma Strengthened ownership of results of trial
Wider Community	Trial results were shared via CAB social media page Trial experience documentary was broadcasted by the National TV channels	Timing: Eight months after the last participant follow-up visit at the site Mode: In-person/online Frequency: One time Strategic insights: - Community-led information sharing and national media advocacy: Leveraging social media and TV broadcasts to enhance public awareness of TB research, trial implementation and its impact on TB care and policy	Lack of favorable research environment	Addressing TB stigma and discrimination Improved community engagement in research and acceptance of trial

The main challenges to dissemination included the complexity of trial-related concepts and language, which were difficult to translate into the Mongolian language. Stakeholders also had difficulty understanding complex concepts, given Mongolia’s limited experience with clinical trials. Calibrating the amount and detail of information appropriate for each stakeholder was also challenging; however, conclusions from the Stage 1 dissemination evaluation, as well as greater involvement of CAB members in preparations for Stage 2 dissemination, helped address these issues during Stage 2. Additionally, contacting all trial participants (some of whom had completed the trial years before) proved difficult for the site due to changes in participant contact details or lack of interest.

Conclusion

Stakeholder engagement and PCORI rubric

The STREAM clinical trial took a robust approach to stakeholder engagement designed to address the unique challenges of conducting a multi-site MDR-TB clinical trial in a lower-resourced setting. The site’s engagement strategy aligned well with the PCORI engagement principles—reciprocal relationships; co-learning; building partnerships; and transparency, honesty and trust. The core study team engaged in a comprehensive stakeholder mapping process to ensure key stakeholders were invited to participate in the trial. Regular meetings were held to address stakeholders’ concerns and align the trial’s objectives with national health priorities, fostering a sense of mutual benefit and creating reciprocal relationships. The trial facilitated co-learning through its focus on capacity-building and knowledge sharing for NTP staff, district TB dispensaries, the NTRL and the CAB. This focus not only enhanced the technical capacity of key stakeholders but also ensured the trial’s procedures were well-understood and effectively implemented. Building partnerships was a strategic focus throughout the trial. Early partnerships included the co-leader agreement with MTC and the site’s approach to sharing human resources with the NTP. Later in the trial, the site’s collaboration with the CAB improved support for trial participants and helped ensure dissemination was appropriately tailored to non-scientific audiences. Transparency was achieved through regular trial progress updates, broad-based dissemination of results, and honest information sharing with key stakeholders. This helped build trust in the trial and research more generally.

The trial incorporated most activities recommended by PCORI during each of the three phases of the trial. However, the site was unable to undertake PCORI-recommended activities related to the design of research questions and outcomes because study design was driven centrally by the sponsor, given the Sponsor’s need to ensure the trial design was acceptable to central regulators, including the US Food and Drug Administration. This centrally led design process, which is common for multi-site registrational trials, often limits trial site input during the planning phase, although it is possible for a committed Sponsor to seek input from trial sites and their stakeholders including existing CABs, on (among other things) secondary outcomes and inclusion/exclusion criteria.

Impact of stakeholder engagement and long-term sustainability

Engagement activities contributed to excellent trial results and had significant benefits for key stakeholders. Despite the country’s limited experience with multi-site MDR-TB clinical trials, key operational metrics indicate that the Mongolia trial site successfully implemented STREAM. The site recruited more than 160 participants across both stages of STREAM, making it the highest-recruiting site in the trial. The site successfully managed six protocol amendments, despite relatively undeveloped regulatory institutions; overcame significant regulatory restrictions on export of TB bacterial isolates to the trial’s central laboratory in Belgium; and consistently managed adverse events/safety reporting according to protocol and ethical requirements. The site’s participant retention rate was 98%.

The immediate benefits to key stakeholders of participating in the trial are discussed above. The longer-term impacts of the trial derive from equipping key stakeholders (often through partnerships developed during STREAM) to participate in future research and improved TB management in Mongolia. In 2024, following completion of STREAM, the site was selected to participate in the multi-center PRISM TB trial funded by USAID. It began planning for its participation using the same stakeholder engagement approach as it used in STREAM. It held two pre-initiation meetings with NCCD management and the NTP to introduce the trial, select the trial team, and discuss overall implementation, and met with the SC of the NCCD to facilitate ethical clearances. In March 2025, the site’s contract with USAID was terminated after the U.S. government terminated funding for USAID projects.

Since completion of STREAM, STREAM CAB members have contributed to the National TB Stigma Assessment (2023–2024) and Community Rights and Gender Assessment (2024–2025), consulting on methodologies and tools, and actively participating in data collection and monitoring. CAB members also contributed to focus group discussions in collaboration with the NTP and MTC as part of a multicenter study focused on developing patient-centered outcomes for clinical trials. In his role as a member of the Global TB CAB and the SMART4 TB Asia Pacific Regional CAB, the CAB coordinator has reviewed international clinical trial protocols for PRISM TB, SMILE TB, REACH TB, and RADIO TB. MTC, the Mongolian NGO that co-led the STREAM trial, has continued efforts to strengthen the regulatory infrastructure of the country, supporting the production of a Mongolian language version of the ICH-GCP rules and arranging ethics trainings with international experts for members of local ethics committees. The trial site coordinator is serving as a Scientific Committee member of both the National Center for Public Health (MOH) and the NCCD, participating in reviews of both locally and internationally initiated research studies.

STREAM stakeholders are also contributing to improving the NTP’s delivery of person-centered TB care, amplifying the impact of the trial’s training and partnership-building. A former STREAM trial participant is now employed by MTC and is leading TB Support Group meetings for NTP patients at a district TB dispensary. Since the trial’s end, two CAB members have been selected to serve as members of the GFATM Country Coordinating Mechanism. CAB members also helped to develop Mongolia’s first TB Community-led Monitoring (CLM) Strategy, and TB CLM has been integrated into the Mongolian National Strategic Plan 2025–2028 and the GFATM’s Grand Cycle 7 funding for Mongolia. The STREAM CAB coordinator and investigator remain actively involved in international, regional, and national TB advocacy, attending the UN Multistakeholder Hearing on TB, and the UN High-Level Meeting on TB, UHC and PPPR in September 2023.

Implications of STREAM stakeholder engagement for lower-resource settings

The following key lessons learned as part of STREAM may be helpful to researchers in other lower-resourced settings:

• Take an expansive view of relevant stakeholders: From the start, the site took an expansive view of relevant stakeholders through a careful stakeholder mapping exercise and committed to building stakeholder relationships before and throughout the research cycle. Actively engaging this wide range of community groups, healthcare actors, and policymakers can be an important factor for success across all phases of the research cycle.

• Undertake capacity-building and knowledge sharing: The site staff made significant investments to build stakeholder capacity on key topics related to clinical research and TB management. Enhancing understanding of a wide range of stakeholders—including local healthcare workers, researchers, TB-affected people and civil society organizations—helped embed knowledge gained during STREAM into the broader healthcare system. A similar approach should enable lower-resourced sites to leverage the benefits of participation in multi-site trials to improve local capacity for conducting future research more independently and with less external support. This may accelerate access for TB-affected people to newer, more effective treatments.

• Plan for long-term sustainability of community engagement: CE can be critical at all stages of the research cycle. However, CE (and CABs) tend to be funded on a trial-by-trial basis, making it more likely that CE funding and activities will lapse between trials. The site addressed this challenge by institutionalizing the CAB within MTC. By doing so, CE became and has remained a key focus for MTC, even after completion of the STREAM trial. This has allowed CAB members (including the CAB coordinator, and trial participant, who was hired by MTC after the trial) to continue participating in other research projects, such as the National TB Stigma and Discrimination Assessment and the Community, Rights, and Gender Assessment, which was conducted in partnership with the Human Rights Commission of Mongolia, the Gender Equality Committee of Mongolia, and NTP. In turn, this has further strengthened the network of community stakeholders.

• Design engagement around specific objectives: Achieving good recruitment, retention, and adherence rates is critical for most trials and STREAM engagement focused on these metrics by engaging with key stakeholders to improve identification of potential trial participants, reduce the burden of DOT for trial participants, food and transportation support to trial participants, and ensure the side effects of treatment were addressed by the trial. This type of results-based engagement should be useful for trial sites in other low-resource settings.

• Design stakeholder engagement to involve key policy makers: Continuous dialog with national health authorities and international organizations can help integrate trial findings into policy and practice, ensuring that successful interventions are scaled and sustained.

• Tailor and optimize communication strategies: Leveraging diverse communication channels, including national TV and social media, significantly improved public awareness. Future trials can further use digital platforms for timely updates, webinars, and ensure timely dissemination of research progress and findings.

Mongolia’s experience with stakeholder engagement underscores the gains that can be made when researchers, government agencies, civil society, TB-affected people, and other key stakeholders collaborate as partners for a common purpose.

Abbreviations

STREAM

Evaluation of a Standardized Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis

CAB

Community Advisory Board

CSO

Civil Society Organization

DOT

Directly Observed Treatment

EC

Medical Ethics Monitoring Committee

MDR-TB

Multidrug-resistant tuberculosis

MoH

Ministry of Health

NCCD

National Centre for Communicable Diseases

NTRL

National TB Reference Lab

NTP

National TB Program

PCORI

Patient Centered Outcomes Institute

SC

Scientific Committee

TB

Tuberculosis

UB

Ulaanbaatar

Authors’ contributions

BTs conceptualized the commentary and drafted the stakeholder engagement tables that formed its basis. BTs, EG, MG, and GB drafted various sections of the commentary. GM, ZKh, EB, ER, and NN gave feedback on the paper. GB provided the overall structure of the commentary. All authors read and approved the final manuscript.

Funding

STREAM Stage 1 was funded by The United States Agency for International Development (USAID) through the TREAT TB Cooperative Agreement No. GHN-A-00-08-00004, with additional support from the United Kingdom Medical Research Council (MRC) and the United Kingdom Department for International Development (DFID) under the MRC/DFID Concordat agreement. STREAM Stage 2 was funded by USAID and Janssen Pharmaceuticals, the maker of bedaquiline, with additional support from MRC and DFID. The contents are the responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government.

Data availability

There were no formal datasets generated and/or analyzed. The contents of this commentary are based on implementation experience of the trial site (NCCD), coordinating center (MRC-CTU), and sponsor (Vital Strategies).

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.