The DECIDE-TB Trial; Validation of Treatment Decision Algorithms for Childhood Tuberculosis

The Decide-TB trial is a pragmatic cluster-randomized study utilizing a stepped wedge design to provide scientific evidence on a comprehensive TDA-based approach for TB screening, diagnosis, and treatment in children under 15 years at low healthcare levels in Zambia and Mozambique.

The trial's primary objective is to evaluate the effectiveness, feasibility, implementation, acceptability, costs, cost-effectiveness, and adoption of a TDA-based approach for childhood TB screening, diagnosis, and treatment decision-making under programmatic conditions at District Hospitals (DH) and Primary Health Centres (PHC) levels in these countries.

There are five specific objectives corresponding to the trial's research components:

1. To assess the effectiveness of the comprehensive TDA-based approach in increasing TB case detection in children as compared to the Standard of Care (SOC), and in providing good quality TB diagnosis and treatment decision (diagnostic accuracy and reliability of treatment decision for TB and shorter treatment). 2. To describe the implementation and the feasibility of using the comprehensive TDA-based approach, including associated digital tools, and to identify contextual determinants influencing implementation and contribute to improved implementation/adaptations throughout intervention delivery. 3. To assess preferences, acceptability, and perceived feasibility of using the comprehensive TDA-based approach, including associated digital tools, among end-users, beneficiaries, and key stakeholders. 4. To assess the costs from the health system and the beneficiary (parents/caregivers of children) perspective, the cost-effectiveness of using the comprehensive TDA-based approach, including associated digital tools, and the budget impact of scaling up the intervention. 5. To assess the factors and stakeholders that support or constrain the adoption of the comprehensive TDA-based approach as health policy at district level.

The intervention will be implemented as a programmatic pilot, following the National TB Programs' decision in Mozambique and Zambia to adopt a TDA-based approach in line with World Health Organisation's (WHO) conditional recommendations. Additionally, both the standard of care and the intervention will be implemented in a non-randomized district to document diagnostic accuracy throughout the trial. The Decide-TB trial is a hybrid effectiveness-implementation trial (type 2), assessing both the clinical intervention's effectiveness and the feasibility and utility of the implementation strategy.

Diagnostic accuracy of both the standard of care and the intervention will be evaluated in an additional district, which will transition to the intervention phase alongside the last district selected per the stepped wedge design. Aggregated data will be retrospectively collected over 12 months from all participating districts and health facilities.

The Decide-TB trial endpoints include effectiveness, acceptability, implementation, health economics, and health policy. Effectiveness endpoints include the proportion of children who started TB treatment, the time it takes to make a treatment decision, and the consistency of TDA results with final treatment decisions, among other factors. Acceptability endpoints consider user preferences and local social value, whereas implementation endpoints evaluate the practicality, fidelity, contextual aspects, and sustainability of the TDA-based method. Health economics endpoints include cost assessments, cost-effectiveness, and budget impact of scaling up the TDA-based approach vs the standard of care, while health policy endpoints look at key stakeholders' roles, practices, and policy translation processes.

• Effectiveness endpoints: Children treated for TB among those with presumptive TB [Срок оценки: Throughout the study, an average of 24 months]
• Effectiveness endpoints: TB treatment proportion in high-risk pediatric groups [Срок оценки: Throughout the study, an average of 24 months]
• Effectiveness endpoints: Microbiologically confirmed TB cases [Срок оценки: Throughout the study, an average of 24 months]
• Effectiveness endpoints: Time to TDA assessment completion [Срок оценки: From the start of intervention to the end of the project, an average of 21 months]
• Effectiveness endpoints: Concordance of TDA results and TB treatment decisions [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: Missed and over-diagnosed TB cases [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: Concordance of TB severity evaluation and treatment regimen decision [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: False positive and negative TB severity assessments [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: Non-severe TB cases initiated on shorter treatment [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: TB treatment outcomes stratified by severity and regimen duration. [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: Deaths averted [Срок оценки: From the start of intervention to the end of the intervention, an average of 21 months]
• Effectiveness endpoints: Child TB among all diagnosed TB cases, including adults [Срок оценки: Throughout the study, an average of 24 months]