Table 1.

Core Elements in the Translation of Evidence to Action.

Core Elements	Selected Examples of Recent Progress	Way Forward
Agenda Setting and Normative Guidance
Establishing Research and Development Priorities: Identifying the greatest need for novel approaches, tools, and regimens to improve care	WHO Roadmap towards ending TB in children and adolescents WHO Pediatric Anti-TB Drug Optimization (PADO-TB) ➢Stop TB Partnership Child and Adolescent TB Working Group establish pediatric formulations as a priority	Establish more public–private partnerships to accelerate action on identified priorities
Policy and Guideline Development: Synthesizing latest evidence, identifying priority interventions, establishing reference standards and benchmarks	WHO Consolidated guidelines on TB. Module 5 Management of TB in children and adolescents National TB Guidelines ➢2010 WHO Rapid Advice: Treatment of TB in Children; 2014 Guidance for national TB programs on the management of TB in children ✓2017 WHO Guidelines for the treatment of drug-susceptible TB and patient care establishes person-centered care as a priority for NTPs ✓CaP-TB and DETECT projects inform 2022 WHO child and adolescent TB guidelines	Adapt global guidance to national context through coordination with MOH, technical, and funding partners
Establishing Implementation Priorities: Establishing program priorities for implementation	National TB Strategic Plans and budgets Global Fund to Fight AIDS, TB and Malaria (GFATM) prioritizes children under 5 for TB funding proposals (2020) ➢NTPs work with the WHO, STP Global Drug Facility (GDF), TB Alliance to prioritize child-friendly FDCs ➢Unitaid and donor organizations from several nations catalyze creation of STEP-TB ✓Uganda NTLP incorporated decentralized care into successive National Strategic Plans (2015–2025) and funding proposals to GFATM	Include child and adolescent TB interventions in NSP, costed budgets, and funding proposals Donors prioritize child and adolescent TB in requests for proposals
Operational and Implementation Guidance: Developing tools, algorithms, job aids, training materials, and other practical guidance required for implementation	The WHO operational handbook accompanying guidelines STP Child and Adolescent TB Working Group (CAWG) develop budgeting tools to improve costing of child and adolescent TB interventions WHO releases Best practices in child and adolescent tuberculosis care (2018) Implementation guidance for use of non-sputum specimens for diagnosis of TB among children ➢The WHO releases Technical Briefing Note: Technical step process to switch to new pediatric TB formulations; TB Alliance and others offer technical support for regulatory and training needs ✓Uganda NTLP adapts approach, training, and tools for expanded scale up beyond pilot districts	Build upon the WHO Operational Handbook implementation guidance to offer context-specific tools and adaptations
Innovation Inception and Delivery
Pre-Clinical Development and Clinical Trials: Trials establishing safety, efficacy, non-inferiority of novel treatment regimens or diagnostic techniques	TAG Pipeline Report TB Alliance: New Pathways for Childhood TB Treatment Clinical trial networks (e.g., IMPAACT4TB, TBTC, DOLPHIN KIDS) ➢Macleods develops water-soluble FDC of RHZ and RH ➢Macleods with Baylor and Stellenbosch Universities and TB Alliance conduct trials of the new FDC	Increase investment for TB R&D in accordance with UNHLM targets Develop pre-clinical dosing models in children and include children in parallel with adults to speed access to new tools
Regulatory Approval: International and national	➢TB Alliance and partners work with the WHO to achieve pre-qualification and listing on the EMLc and provide technical support to NTPs for regulatory approval	Prioritize review for pre-qualification of pediatric formulations
Market Shaping and Consolidated Procurement: Quantifying market for therapeutics, diagnostics, commodities; consolidated procurement with negotiated prices	STP/Global Drug Facility WHO PADO ➢STP/GDF work with TB Alliance and MacLeods to bulk procure product upon agreement with NTPs for forecasted needs; WHO Technical Brief provides forecasting advice	Expand pooled procurement Incentivize manufacturers of pediatric TB medications through improved stakeholder coordination Streamline regulatory approvals Increase consumer education on guidelines
Program Implementation and Continuous Quality Improvement
Surveillance and Data for Decision Making: Routine recording and reporting of indicators paired with routine use of data and experience to improve performance by targeting gaps and developing solutions	Making sense of TB data (Zimbabwe) TB Situation Room (Zambia) Clinic-Lab Interface for Continuous Quality Improvement (CDC CLICQ!) ➢NTP and TB Alliance monitor proportion of patients receiving new FDC in early rollout; adverse event and discontinuation monitored over time ✓Uganda NTLP monitored expansion of decentralized care approach through routine surveillance in 10 expansion districts	Ensure appropriate fine age disaggregation at all levels to assess performance across age groups
Training TB Program Staff and Health Care Workers: Providing routine training to all health cadres and volunteers involved in delivery of health services	The WHO TB knowledge-sharing platform TB-Speed Project Extension for Community Healthcare Outcomes (ECHO) ➢Health care workers and caregivers trained on administration of new FDC ✓Catalyzing Innovations for Pediatric TB (CaP-TB) and Decentralize TB services and Engage Communities to Transform lives of Children with TB (DETECT TB) projects emphasize training at the primary care level	Develop capacity building strategies that emphasizes skill transfer at the lowest levels of health system
Supportive Supervision and Mentorship: Providing oversight against performance targets and mentorship for skill development	TB Situation Room (Zambia) ✓CaP-TB and DETECT TB provided on-site supervision and mentorship to sustain skill development	Integrate routine mentorship to improve performance at lowest levels of health system
Operational Research and Program Adaptation: Adapting evidence-based innovations to a specific context through implementation and evaluation	Clinical trial and operational research consortia (IMPAACT4TB, CaP-TB, TB-Speed) STP TB REACH ➢Louder than TB Campaign in Kenya adapts the use of formulation to Kenyan context; IEC materials developed for community ➢Evaluation of FDC palatability and patient preference within SHINE trial documents room for improvement ✓Both Cap-TB and DETECT projects were pilots to adapt recommended approaches to different contexts for the purpose of enabling sustainable scale up	Align with agreed-upon implementation priorities from NTP and agenda-setting bodies and seek collaboration with COP for accelerating scale up of effective demonstrations
Communities of Practice (COP): Platforms for sharing best practices and lessons learned in implementation among peers; may provide expert consultation for donor and multilateral institutions	CAWG and national Child and Adolescent TB Technical Working Groups Sentinel Project Union Child and Adolescent TB Center of Excellence ➢TB Alliance developed a platform for sharing information, lessons learned, and other updates with NTP and program staff in interested countries ✓CaP-TB shares best practices across platform of engaged countries	Develop framework for joint responsibility across COPs for agreed-upon priorities Develop training materials on child and adolescent TB aligned with guidelines and the WHO TB knowledge-sharing platform
Platforms for Building Political Will
Civil Society and Community Engagement: Raising awareness among general and affected populations, providing input into service delivery and program priorities, and providing support to affected communities	WHO Civil Society Taskforce WHO ENGAGE-TB Approach: Operational Guidance STP Challenge Facility for Civil Society (CFCS) Global Coalition of TB Activists ➢Kenya’s Louder than TB Campaign engaged civil society and survivors of TB to raise awareness of the new formulation in the community	Engage with existing platforms to provide input and direction to national and local TB programs Mobilize resources for community action through existing donor programs
Building Political Will: Raising awareness of the burden of TB among political, opinion, and thought leaders to build political will and investment	WHO End TB Strategy UNHLM Political Declaration and 2020 UN Secretary-General progress report Annual WHO Global Tuberculosis Reports Global TB Caucus Rome Action Plan on Pediatric HIV and TB Dedicated funding for TB prevention and care, from major donors such as the Bill and Melinda Gates Foundation, CDC, the Global Fund, Unitaid and the United States Agency for International Development (USAID) as well as bilateral donors, philanthropists and others ➢TB Alliance and partners worked with policymakers at all levels to raise awareness of the need of new FDC	Continue to build political will for addressing child and adolescent TB Monitor progress against commitments and targets

➢ Indicates an action taken in development, delivery, adaptation, and scale up of pediatric formulation of drug-susceptible TB; ✓ Indicates an action taken in development, delivery, adaptation, and scale up of decentralized models of care, including in Uganda.