Background: Digital adherence technologies (DATs) with associated differentiated care are potential tools to improve tuberculosis (TB) treatment outcomes and reduce associated costs for both patients and healthcare providers. However, the balance between epidemiological and economic benefits remains unclear. Here, we used data from the ASCENT trial to estimate the potential long-term epidemiological and economic impact of DAT interventions in Ethiopia. Methods: We developed a compartmental transmission model for TB, calibrated to Ethiopia and parameterised with patient and provider costs. We compared the epidemiological and economic impact of two DAT interventions, a digital pillbox and medication labels, to the current standard of care, assuming each was introduced at scale in 2023. We projected long-term TB incidence, mortality and costs to 2035 and conducted a threshold analysis to identify the maximum possible epidemiological impact of a DAT intervention by assuming 100% treatment completion for patients on DAT. Findings: We estimated small and uncertain epidemiological benefits of the pillbox intervention compared with the standard of care in Ethiopia, with a difference of −0.4% (95% uncertainty interval (UI) −1.1%; +2.0%) incident TB episodes and −0.7% (95% UI −2.2%; +3.6%) TB deaths. However, our analysis also found large total provider and patient cost savings (US$163 (95% UI US$118; US$211) and US$3 (95%UI: US$1; US$5), respectively, over 2023–2035), translating to a 50.2% (95% UI 35.9%; 65.2%) reduction in total cost of treatment. Results were similar for the medication label intervention. The maximum possible epidemiological impact a theoretical DAT intervention could achieve over the same timescale would be a 3% (95% UI 1.4%; 5.5%) reduction in incident TB and an 8.2% (95% UI 4.4%; 12.8%) reduction in TB deaths. Interpretation: DAT interventions, while showing limited epidemiological impact, could substantially reduce TB treatment costs for both patients and the healthcare provider.

Digital adherence technologies (DATs) could improve the person-centeredness of tuberculosis (TB) treatment. DATs are found to be acceptable, though evidence of their effectiveness is varied. Our objective was to understand the fidelity of DAT interventions within five cluster-randomized trials. Two DATs (smart pillbox, medication labels) were assessed, with real-time adherence data available to healthcare providers (HCPs) on a digital platform in Ethiopia, the Philippines, South Africa, Tanzania, and Ukraine. A framework assessed four components of implementation: inputs (training, support, mobile access), processes (SMS, home visits, platform usage), outputs (DAT engagement, manual dosing), and outcomes (people with TB (PwTB)–HCP relationship). Fidelity was evaluated by quantitative indicators, and content analysis of qualitative sub-studies supplemented some indicators. Engagement with DATs was high among PwTB. Pillbox users showed high levels of sustained engagement (box opening), with digitally recorded doses ranging from 82% to 91%. Differences were observed in login frequency by HCPs to the adherence platform. In Ethiopia, Tanzania, and Ukraine, there was at least one login to the platform on 71% of weekdays per facility compared with the Philippines and South Africa at 42% and 52%, respectively. Intervention fidelity varied among countries, suggesting a need for future work on optimizing implementation.

Background: Digital adherence technologies (DATs) are promising tools for supporting tuberculosis (TB) treatment. DATs can serve as reminders for people with TB to take their medication and act as proxies for adherence monitoring. Strong engagement with DATs, from both the person with TB and health care provider (HCP) perspectives, is essential for ensuring intervention fidelity. The Adherence Support Coalition to End TB (ASCENT) project evaluated 2 types of DATs, pillboxes and medication labels (99DOTS), in cluster-randomized trials across 5 countries. Objective: This study aims to investigate participant and HCP engagement with DATs for TB treatment, stratified by DAT type and country. Methods: This study is a subanalysis of data generated through the ASCENT trials, which enrolled adults with drug-susceptible TB. A digital dose was defined as either a pillbox opening (for pillbox users) or a dosing confirmation SMS text message sent by the participant (for label users), both of which were recorded on the adherence platform. Descriptive analysis was used to provide an overview of dose-day outcomes. DAT engagement was assessed from both participant and HCP perspectives. To enhance participant engagement, we summarized the frequency of digital engagement overall and by treatment phase, as well as the frequency of consecutive days without engagement. For HCP engagement, we summarized the frequency of doses added manually, the number of days between the actual dose day and when a manual dose was added, and instances of consecutive manual dosing lasting more than 3 and more than 7 days, where doses were added more than 1 week after the dose day. Results: Of the 9511 participants included, 6719 (70.64%) were using the pillbox, 3544 (37.26%) were female, and the median age was 40 years. Across DAT types, there were 1,384,879 dose days, with 973,876 (70.32%) contributed by pillbox users. Of all dose days, 1,165,195 (84.14%) were recorded as digital, 156,664 (11.31%) as manual, 59,045 (4.26%) had no information, and 3975 (0.29%) were confirmed as missed. Digital dosing decreased slightly from the intensive to the continuation phase. The percentage of digital dose days was higher among pillbox users (851,496/973,876, 87.43%) compared with label users (313,699/411,003, 76.33%). Among label users, manual dosing was most common in the Philippines (37,919/171,786, 22.07%) and least common in Tanzania (11,108/76,231, 14.57%). Among pillbox users, manual dosing was most common in the Philippines (24,015/208,130, 11.54%) and Ukraine (13,209/111,901, 11.80%). Overall, 512 out of 2792 (18.34%) label users and 588 out of 6719 (8.75%) pillbox users experienced a run of more than 7 consecutive nondigital dose days that were resolved more than 1 week after the dose day. The highest occurrence was observed in the Philippines (368/1142, 32.22%, for label users and 224/1351, 16.58%, for pillbox users). Conclusions: There was considerable variation in DAT engagement across countries and DAT types, reflecting differences in how the intervention was implemented. Further refinement of the intervention and improvements in its delivery may be necessary to enhance outcomes.

Background: Tuberculosis remains a leading cause of death globally, particularly in countries with high tuberculosis and HIV burdens. Disruptions caused by the COVID‐19 pandemic may have further impacted tuberculosis outcomes. This study examines on‐treatment mortality and associated risk factors in five countries. Method: We conducted a secondary analysis of data from ASCENT cluster‐randomised trials of digital adherence tools for improved adherence involving 23,799 adults with drug‐sensitive tuberculosis in South Africa, Tanzania, Ethiopia, the Philippines, and Ukraine. Analyses were conducted separately by country. Mortality rates were measured from treatment initiation to the earliest of 6 months, death, or loss to follow‐up. Cox regression models (with random effects or robust standard errors for clustering) assessed the associations between mortality and HIV status, ART use, tuberculosis diagnosis type, and calendar periods (COVID‐19 pandemic and conflict in Ukraine). Results: Mortality rates ranged from 7.6 (Ethiopia) to 23.2 (Tanzania) and 23.3 (Ukraine) per 100 person‐years. Higher mortality was associated with: older age in all countries (age < 30 versus ≥ 60 years, adjusted rate ratio [aRR] ranging from 2.38 to 6.57 by country); HIV status (positive versus negative, aRR ranging from 1.44 to 2.98 by country); tuberculosis diagnosis type (clinical vs. bacteriological, aRR 1.5–1.6 in Ethiopia, Tanzania and South Africa); extrapulmonary tuberculosis (aRR 1.44 to 1.60 in Ukraine and Tanzania). ART versus HIV‐positive not on ART was linked to lower mortality in South Africa and Ukraine but not in Tanzania. Analyses suggested possible mortality variations by calendar period. Conclusion: Our findings suggest variability in tuberculosis mortality across settings, influenced by HIV/ART and diagnosis type. The high mortality rates across countries may reflect underlying causes or potential misdiagnoses. Further investigation into these factors may be needed to improve tuberculosis outcomes globally.

Background: Digital adherence technologies (DATs) could improve the person-centredness of TB treatment. Acceptability of DATs is high, though evidence of their effectiveness is varied. Our objective was to understand the fidelity of DAT interventions within five cluster-randomized trials. Methods: Two DATs (smart pill box, medication labels) were assessed, with real-time adherence data made available to healthcare providers (HCPs) on a digital platform in Ethiopia, the Philippines, South Africa, Tanzania, and Ukraine. The process evaluation framework assessed four components: inputs, processes, outputs, and outcomes. Fidelity of the most important intervention components was evaluated by quantitative indicators, with analysis conducted by country and DAT type. Content analysis of qualitative sub-studies supplemented some indicators. Results: Engagement with DATs was high among persons with TB (PwTB). Pillbox users showed high levels of sustained engagement, with digitally recorded doses ranging from 82% to 91%. Sole ownership of a mobile phone was highest in South Africa (90%) and lowest in the Philippines (63%). Differences were also observed in the frequency of logins by HCPs to the adherence platform and the type of device used. In the Philippines and Ukraine, >50% of logins were from mobile phones. In Ethiopia, Tanzania, and Ukraine there was at least one login to the platform on 71% of weekdays per facility, compared with the Philippines and South Africa at 42% and 52%, respectively. A feeling of connection between PwTB and their HCP was reported by over 95% of participants surveyed in Ethiopia and Tanzania, this was 84% in South Africa and 76% Philippines, a finding underpinned by qualitative data. Conclusion: We observed varying levels of intervention fidelity between countries. Timeliness and intensity of utilization of real-time data, and taking required actions are impacted by staff and health system capacity. Acceptance of DATs is high; therefore, future work should focus on identifying optimal intervention strategies.