Digital Adherence Technology for Tuberculosis Treatment Supervision: A Stepped-Wedge Cluster Randomized Trial

Background: Tuberculosis (TB) treatment completion rates are below global targets. 99DOTS is a low-cost digital adherence technology (DAT) that could increase TB treatment completion. Methods: 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 eight months (December 1, 2018-July 31, 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 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). Findings: 2224 eligible patients initiated treatment at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively). During the intervention period, 463 (52.0%) patients were enrolled on 99DOTS. Odds of treatment success with the 99DOTS-based intervention did not differ from the control period in the ITT analysis (adjusted odds ratio [aOR] 1.04, 95% CI 0.68-1.58, p=0.87) but were higher in the PP analysis (aOR 2.89, 95% CI 1.57-5.33, p=0.001). Similarly, the odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were improved in PP but not ITT analyses.Interpretation: 99DOTS-based treatment supervision improved treatment outcomes among patients who received the intervention but not in the population as a whole. These findings support scale-up of 99DOTS as an alternative to directly observed therapy while also highlighting the need to address barriers to access and implementation of DATs. Table Effectiveness of the 99DOTS-based intervention. class="MsoNormal" style="margin: 0in; font-size: medium; font-family: Calibri, sans-serif;"> ITT: intention to treat, PP: per protocol* Primary outcome ** Secondary outcome Adjusted for time (trial month, discrete variable), sex, HIV status, disease class (bacteriologically confirmed vs.clinically diagnosed), TB type (new vs. retreatment) as fixed effects and site as a random effect ^ Proportion difference calculated as intervention minus control P value for adjusted intervention effect