Table 1.

Research questions relevant to each gap in the TB care cascade.

Research questions	Potential research approaches	Relevance
Gap 1: Case-finding
Which populations do not have access to TB services?	• Analysis of data from national demographic and health surveys • Local exercises mapping the geographic distribution of notified patients in relation to the availability of TB services	• May help to identify locations where TB services need to be expanded to ensure access to high-risk populations • May identify populations that would benefit from novel community-based strategies such as use of health extension workers for TB screening
Why do some individuals with active TB in the population not seek care or delay seeking care?	• Interviews with individuals diagnosed with TB in prevalence surveys who have not sought care • Interviews with individuals with symptoms concerning for TB in the community who have not sought care • Interviews with TB patients who had substantial delay in seeking care	• May help guide targeting of public education strategies via radio, television, or social media • May help identify the types of individuals who should be prioritized in community active case-finding activities
Why do some healthcare providers (HCPs) not refer individuals for TB testing?	• Questionnaires using clinical vignettes to assess HCP knowledge • Standardized patient studies to assess actual HCP behavior • Qualitative research to understand HCPs’ clinical decision-making	• May help identify types of HCPs who lack necessary knowledge or provide suboptimal care with regard to TB evaluation and testing • Standardized patient and knowledge assessments provide approaches for testing the benefits of interventions aimed at modifying behavior, including education of HCPs, use of incentives, and provision of support through public-private initiatives • Understanding HCPs clinical decision-making may facilitate educational strategies targeted at shifting their behavior
How can case detection rates of active case-finding (ACF) initiatives be increased?	• ACF trials focusing on high-risk groups, such as household contacts, people living with HIV (PLHIV), or individuals with silica exposure • ACF trials using identification of geographic TB hotspots to facilitate spatial targeting of case-finding approaches	• May help identify the most efficient approaches for focusing ACF initiatives to increase the case detection and therefore the number of individuals entering the TB care cascade
Gap 2: Diagnosis
Which patients disproportionately do not get diagnosed with TB?	• Cross-sectional studies using exit interviews with structured or qualitative data collection to identify patients presenting to different health system levels who have not been tested for TB despite having symptoms • Cohort studies to understand which patients are not being appropriately tested	• May help to identify whether certain groups are being disproportionately missed
Why do some patients not get appropriately diagnosed with TB, despite getting evaluated and tested?	• Patient pathways analyses to understand where TB tests are available in relation to patient care-seeking • Cohort studies to understand risk factors for patient attrition during the TB diagnostic workup • Qualitative research to understand barriers in the TB evaluation process	• May help identify types of health facilities where World Health Organization (WHO)-approved TB tests are not accessible or feasible to implement, requiring a triage and referral mechanism • May help to identify patient characteristics that predict attrition during TB evaluation to facilitate development of targeted interventions • May help to identify health system barriers that need to be addressed to facilitate completion of the TB diagnostic process or whether the appropriate diagnostic algorithms are being used
How do we improve diagnosis of TB test-negative (i.e., smear-negative, Xpert-negative) TB patients?	• Cohort studies to understand patient attrition during the TB diagnostic workup, with a specific focus on TB diagnostic test-negative patients • Qualitative research to understand barriers in the TB evaluation process	• May facilitate approaches for simplifying algorithms for the diagnostic workup of test-negative TB to reduce patient attrition
Gap 3: Linkage to care
Why do some diagnosed TB patients experience pretreatment loss to follow-up (PTLFU)?	• Cohort studies to understand patient attrition during linkage to care • Qualitative research to understand challenges in the process of linkage to care	• May help to identify patient characteristics that predict PTLFU • May help to identify health system barriers contributing to PTLFU • May inform development of technology- and human-resource-based interventions to improve linkage to care
Gap 4: Retention on therapy and medication adherence
Why do some patients experience suboptimal TB treatment outcomes or medication non-adherence?	• Cohort studies to understand patient attrition during TB treatment or non-adherence to medications • Qualitative research to understand barriers to completing TB treatment or adhering to medications	• May help to identify patient characteristics that predict suboptimal treatment outcomes or medication non-adherence • May help to identify health system barriers contributing to suboptimal treatment outcomes or medication non-adherence • May inform development of technology- and human-resource-based interventions to TB treatment outcomes and medication adherence
Gap 5: Post-treatment TB recurrence-free survival
Why do some TB patients experience post-treatment disease recurrence or death after finishing treatment?	• Cohort studies to understand post-treatment TB recurrence or mortality • Studies assessing post-treatment disability, mental health, pulmonary function, and emerging chronic diseases	• May help to identify patient characteristics that predict post-treatment disease recurrence and mortality • May help to inform the development of approaches to post-treatment care for TB patients that would aim to achieve early identification of disease recurrence while facilitating treatment of post-TB sequelae, such as chronic lung disease