Tuberculosis Treatment Supervision Research Articles

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: Astepped-wedge cluster-randomized trialin Uganda.

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. 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. 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. Pan-African Clinical Trials Registry (PACTR201808609844917).

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. 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. Trial Registration: This trial is registered with the Pan-African Clinical Trials Registry (PACTR201808609844917). Funding: Stop TB Partnership’s TB REACH initiative Declaration of Interests: The authors report no conflicts of interest. Ethics Approval Statement: The trial was approved by institutional review boards at Makerere University School of Public Health and the University of California San Francisco, and by the Uganda National Council for Science and Technology. A waiver of informed consent was granted to access patient demographic and clinical information recorded in TB treatment registers.

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

IntroductionLow-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...

Variation in tuberculosis treatment outcomes and treatment supervision practices in Uganda

BackgroundVariation in healthcare delivery is increasingly recognized as an important metric of healthcare quality. Directly observed therapy (DOT) has been the standard of care for tuberculosis (TB) treatment supervision for decades based on World Health Organization (WHO) guidelines. However, variation in implementation of DOT and associated TB treatment supervision practices remains poorly defined. MethodsWe collected individual patient data from TB treatment registers at 18 TB treatment units in Uganda including District Health Centers, District Hospitals, and Regional Referral Hospitals. We also administered a survey and did observations of TB treatment supervision practices by health workers at each site. We describe variation in TB treatment outcomes and TB treatment supervision practices. ResultsOf 2767 patients treated for TB across the 18 clinical sites between January 1 and December 31, 2017, 1740 (62.9%) were men, most were of working age (median 35 years, interquartile range [IQR] 27 – 46), 2546 (92.0%) had a new TB diagnosis, and nearly half (45.9%, n = 1283) were HIV positive. The pooled treatment success proportion was 69.4% (95% confidence interval [CI] 67.8 – 71.1) but there was substantial variation across sites (range 42.6 – 87.6%, I-squared 92.7%, p < 0.001). The survey and observation of TB treatment practices revealed that the majority of sites practice community-based DOT (66.7%, n = 12) and request a family member, who receives no additional training or supervision, to serve as a treatment supporter (77.8%, n = 14). At TB medication refill visits, all sites screen for side effects and most assess adherence via self-report (83.3%, n = 15). Only 7 (38.9%) sites followed-up patients who missed appointments using either phone calls (22.2%, n = 4/7) or community health workers (16.7%, n = 3/7). All 18 sites counseled patients at treatment initiation, but none provided additional counseling at refill visits other than addressing poor adherence or missed appointments. ConclusionThere was substantial variation in implementation of DOT, including observation and documentation of daily dosing, training and supervision of treatment supporters, and follow-up for missed clinic visits. Identifying best practices and reducing uncontrolled variation in the delivery of TB treatment is critical to improving treatment outcomes.