Implementation, feasibility, and acceptability of 99DOTS-based supervision of treatment for drug-susceptible TB in Uganda.

99DOTS is a low-cost digital adherence technology that allows people with tuberculosis (TB) to self-report treatment adherence. There are limited data on its implementation, feasibility, and acceptability from sub-Saharan Africa. We conducted a longitudinal analysis and cross-sectional surveys nested within a stepped-wedge randomized trial at 18 health facilities in Uganda between December 2018 and January 2020. The longitudinal analysis assessed implementation of key components of a 99DOTS-based intervention, including self-reporting of TB medication adherence via toll-free phone calls, automated text message reminders and support actions by health workers monitoring adherence data. Cross-sectional surveys administered to a subset of people with TB and health workers assessed 99DOTS feasibility and acceptability. Composite scores for capability, opportunity, and motivation to use 99DOTS were estimated as mean Likert scale responses. Among 462 people with pulmonary TB enrolled on 99DOTS, median adherence was 58.4% (inter-quartile range [IQR] 38.7-75.6) as confirmed by self-reporting dosing via phone calls and 99.4% (IQR 96.4-100) when also including doses confirmed by health workers. Phone call-confirmed adherence declined over the treatment period and was lower among people with HIV (median 50.6% vs. 63.7%, p<0.001). People with TB received SMS dosing reminders on 90.5% of treatment days. Health worker support actions were documented for 261/409 (63.8%) people with TB who missed >3 consecutive doses. Surveys were completed by 83 people with TB and 22 health workers. Composite scores for capability, opportunity, and motivation were high; among people with TB, composite scores did not differ by gender or HIV status. Barriers to using 99DOTS included technical issues (phone access, charging, and network connection) and concerns regarding disclosure. 99DOTS was feasible to implement and highly acceptable to people with TB and their health workers. National TB Programs should offer 99DOTS as an option for TB treatment supervision.

Digital adherence technology for tuberculosis treatment supervision: A stepped-wedge cluster-randomized trial in Uganda.

BACKGROUND: Adherence to and completion of tuberculosis (TB) treatment remain problematic in many high-burden countries. 99DOTS is a low-cost digital adherence technology that could increase TB treatment completion. METHODS AND FINDINGS: We conducted a pragmatic stepped-wedge cluster-randomized trial including all adults treated for drug-susceptible pulmonary TB at 18 health facilities across Uganda over 8 months (1 December 2018-31 July 2019). Facilities were randomized to switch from routine (control period) to 99DOTS-based (intervention period) TB treatment supervision in consecutive months. Patients were allocated to the control or intervention period based on which facility they attended and their treatment start date. Health facility staff and patients were not blinded to the intervention. The primary outcome was TB treatment completion. Due to the pragmatic nature of the trial, the primary analysis was done according to intention-to-treat (ITT) and per protocol (PP) principles. This trial is registered with the Pan African Clinical Trials Registry (PACTR201808609844917). Of 1,913 eligible patients at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively), 38.0% were women, mean (SD) age was 39.4 (14.4) years, 46.8% were HIV-infected, and most (91.4%) had newly diagnosed TB. In total, 463 (52.0%) patients were enrolled on 99DOTS during the intervention period. In the ITT analysis, the odds of treatment success were similar in the intervention and control periods (adjusted odds ratio [aOR] 1.04, 95% CI 0.68-1.58, p = 0.87). The odds of treatment success did not increase in the intervention period for either men (aOR 1.24, 95% CI 0.73-2.10) or women (aOR 0.67, 95% CI 0.35-1.29), or for either patients with HIV infection (aOR 1.51, 95% CI 0.81-2.85) or without HIV infection (aOR 0.78, 95% CI 0.46-1.32). In the PP analysis, the 99DOTS-based intervention increased the odds of treatment success (aOR 2.89, 95% CI 1.57-5.33, p = 0.001). The odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were similarly improved in PP but not ITT analyses. Study limitations include the likelihood of selection bias in the PP analysis, inability to verify medication dosing in either arm, and incomplete implementation of some components of the intervention. CONCLUSIONS: 99DOTS-based treatment supervision did not improve treatment outcomes in the overall study population. However, similar treatment outcomes were achieved during the control and intervention periods, and those patients enrolled on 99DOTS achieved high treatment completion. 99DOTS-based treatment supervision could be a viable alternative to directly observed therapy for a substantial proportion of patients with TB. TRIAL REGISTRATION: Pan-African Clinical Trials Registry (PACTR201808609844917).

Study protocol and implementation details for a pragmatic, stepped-wedge cluster randomised trial of a digital adherence technology to facilitate tuberculosis treatment completion.

INTRODUCTION: Low-cost digital adherence technologies (DATs) such as 99DOTS have emerged as an alternative to directly observed therapy (DOT), the current standard for tuberculosis (TB) treatment supervision. However, there are limited data to support DAT scale-up. The 'DOT to DAT' trial aims to evaluate the effectiveness and implementation of a 99DOTS-based TB treatment supervision strategy. METHODS AND ANALYSIS: This is a pragmatic, stepped-wedge cluster randomised trial, with hybrid type 2 effectiveness-implementation design. The trial will include all adults (estimated N=1890) treated for drug-susceptible pulmonary TB over an 8-month period at 18 TB treatment units in Uganda. Three sites per month will switch from routine care (DOT) to the intervention (99DOTS-based treatment supervision) beginning in month 2, with the order determined randomly. 99DOTS enables patients to be monitored while self-administering TB medicines. Patients receive daily automated short message service (SMS) dosing reminders and confirm dosing by calling toll-free numbers. The primary effectiveness outcome is the proportion of patients completing TB treatment. With 18 clusters randomised into six steps and an average cluster size of 15 patients per month, the study will have 89% power to detect a 10% or greater increase in treatment completion between the routine care and intervention periods. Secondary outcomes include more proximal effectiveness measures as well as quantitative and qualitative assessments of the reach, adoption and implementation of the intervention. ETHICS AND DISSEMINATION: Ethics approval was granted by institutional review boards at Makerere University School of Public Health and the University of California San Francisco. Findings will be disseminated through peer-reviewed publications, presentations at scientific conferences and presentations to key stakeholders. TRIAL REGISTRATION NUMBER: PACTR201808609844917.