Risk factors for poor engagement with a smart pillbox adherence intervention among persons on tuberculosis treatment in Ethiopia.

BACKGROUND: Non-adherence to tuberculosis treatment increases the risk of poor treatment outcomes. Digital adherence technologies (DATs), including the smart pillbox (EvriMED), aim to improve treatment adherence and are being widely evaluated. As part of the Adherence Support Coalition to End TB (ASCENT) project we analysed data from a cluster-randomised trial of DATs and differentiated care in Ethiopia to examine individual-factors for poor engagement with the smart pillbox. METHODS: Data were obtained from a cohort of trial participants with drug-sensitive tuberculosis (DS-TB) whose treatment started between 1 December 2020 and 1 May 2022, and who were using the smart pillbox. Poor engagement with the pillbox was defined as (i) > 20% days with no digital confirmation and (ii) the count of days with no digital confirmation, and calculated over a two evaluation periods (56-days and 168-days). Logistic random effects regression was used to model > 20% days with no digital confirmation and negative binomial random effects regression to model counts of days with no digital confirmation, both accounting for clustering of individuals at the facility-level. RESULTS: Among 1262 participants, 10.8% (133/1262) over 56-days and 15.8% (200/1262) over 168-days had > 20% days with no digital confirmation. The odds of poor engagement was less among participants in the higher stratum of socio-economic position (SEP) over 56-days. Overall, 4,689/67,315 expected doses over 56-days and 18,042/199,133 expected doses over 168-days were not digitally confirmed. Compared to participants in the poorest SEP stratum, participants in the wealthiest stratum had lower rates of days not digitally confirmed over 168-days (adjusted rate ratio [RRa]:0.79; 95% confidence interval [CI]: 0.65, 0.96). In both evaluation periods (56-days and 168-days), HIV-positive status (RRa:1.29; 95%CI: 1.02, 1.63 and RRa:1.28; 95%CI: 1.07, 1.53), single/living independent (RRa:1.31; 95%CI: 1.03, 1.67 and RRa:1.38; 95%CI: 1.16, 1.64) and separated/widowed (RRa:1.40; 95%CI: 1.04, 1.90 and RRa:1.26; 95%CI: 1.00, 1.58) had higher rates of counts of days with no digital confirmation. CONCLUSION: Poorest SEP stratum, HIV-positive status, single/living independent and separated/ widowed were associated with poor engagement with smart pillbox among people with DS-TB in Ethiopia. Differentiated care for these sub-groups may reduce risk of non-adherence to TB treatment.

Evaluating the equity impact and cost-effectiveness of digital adherence technologies with differentiated care to support tuberculosis treatment adherence in Ethiopia: protocol and analysis plan for the health economics component of a cluster randomised trial.

BACKGROUND: Tuberculosis remains a leading infectious cause of death in resource-limited settings. Effective treatment is the cornerstone of tuberculosis control, reducing mortality, recurrence and transmission. Supporting treatment adherence through facility-based observations of medication taking can be costly to providers and patients. Digital adherence technologies (DATs) may facilitate treatment monitoring and differentiated care. The ASCENT-Ethiopia study is a three-arm cluster randomised trial assessing two DATs with differentiated care for supporting tuberculosis treatment adherence in Ethiopia. This study is part of the ASCENT consortium, assessing DATs in South Africa, the Philippines, Ukraine, Tanzania and Ethiopia. The aim of this study is to determine the costs, cost-effectiveness and equity impact of implementing DATs in Ethiopia. METHODS AND DESIGN: A total of 78 health facilities have been randomised (1:1:1) into one of two intervention arms or a standard-of-care arm. Approximately 50 participants from each health facility will be enrolled on the trial. Participants in facilities randomised to the intervention arms are offered a DAT linked to the ASCENT adherence platform for daily adherence monitoring and differentiated response for those who have missed doses. Participants at standard-of-care facilities receive routine care. Treatment outcomes and resource utilisation will be measured for each participant. The primary effectiveness outcome is a composite index of unfavourable end-of-treatment outcomes (lost to follow-up, death or treatment failure) or treatment recurrence within 6 months of end-of-treatment. For the cost-effectiveness analysis, end-of-treatment outcomes will be used to estimate disability-adjusted life years (DALYs) averted. Provider and patient cost data will be collected from a subsample of 5 health facilities per study arm, 10 participants per facility (n = 150). We will conduct a societal cost-effectiveness analysis using Bayesian hierarchical models that account for the individual-level correlation between costs and outcomes as well as intra-cluster correlation. An equity impact analysis will be conducted to summarise equity efficiency trade-offs. DISCUSSION: Trial enrolment is ongoing. This paper follows the published trial protocol and describes the protocol and analysis plan for the health economics work package of the ASCENT-Ethiopia trial. This analysis will generate economic evidence to inform the implementation of DATs in Ethiopia and globally. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR) PACTR202008776694999. Registered on 11 August 2020,  https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12241 .

Evaluation of implementation and effectiveness of digital adherence technology with differentiated care to support tuberculosis treatment adherence and improve treatment outcomes in Ethiopia: a study protocol for a cluster randomised trial.

BACKGROUND: Digital adherence technologies (DATs) are recommended to support patient-centred, differentiated care to improve tuberculosis (TB) treatment outcomes, but evidence that such technologies improve adherence is limited. We aim to implement and evaluate the effectiveness of smart pillboxes and medication labels linked to an adherence data platform, to create a differentiated care response to patient adherence and improve TB care among adult pulmonary TB participants. Our study is part of the Adherence Support Coalition to End TB (ASCENT) project in Ethiopia. METHODS/DESIGN: We will conduct a pragmatic three-arm cluster-randomised trial with 78 health facilities in two regions in Ethiopia. Facilities are randomised (1:1:1) to either of the two intervention arms or standard of care. Adults aged ≥ 18 years with drug-sensitive (DS) pulmonary TB are enrolled over 12 months and followed-up for 12 months after treatment initiation. Participants in facilities randomised to either of the two intervention arms are offered a DAT linked to the web-based ASCENT adherence platform for daily adherence monitoring and differentiated response to patient adherence for those who have missed doses. Participants at standard of care facilities receive routine care. For those that had bacteriologically confirmed TB at treatment initiation and can produce sputum without induction, sputum culture will be performed approximately 6 months after the end of treatment to measure disease recurrence. The primary endpoint is a composite unfavourable outcome measured over 12 months from TB treatment initiation defined as either poor end of treatment outcome (lost to follow-up, death, or treatment failure) or treatment recurrence measured 6 months after the scheduled end of treatment. This study will also evaluate the effectiveness, feasibility, and cost-effectiveness of DAT systems for DS-TB patients. DISCUSSION: This trial will evaluate the impact and contextual factors of medication label and smart pillbox with a differentiated response to patient care, among adult pulmonary DS-TB participants in Ethiopia. If successful, this evaluation will generate valuable evidence via a shared evaluation framework for optimal use and scale-up. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202008776694999, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12241 , registered on August 11, 2020.

Determinants of multidrug-resistant tuberculosis in Addis Ababa, Ethiopia.

Multidrug-resistant tuberculosis (MDR-TB) has been jeopardizing the global effort to prevent and control tuberculosis (TB). However, data on MDR-TB in Ethiopia in general, and in our study area in particular, are very scarce. The aim of this study was to identify determinants of MDR-TB in a cohort of patients managed in two referral hospitals of Addis Ababa, Ethiopia, between April 1, 2013 and June 30, 2013. A health facility-based case-control study was conducted. A total of 710 TB patients (229 confirmed MDR-TB and 481 drug susceptible TB patients) were enrolled in this study. Identified independent determinants for MDR-TB were contact history with a known TB patient (adjusted odds ratio [AOR]: 1.9, 95% CI: 1.1-3.3), previous history of TB treatment (AOR: 11.9, 95% CI: 6.8-21), history of hospitalization (AOR: 4.4 95% CI: 2.2-7.8), sputum-smear positivity (AOR: 1.9, 95% CI: 1.1-3.4), and social stigma (AOR: 5.1, 95% CI: 1.8-14.4). These identified factors should be considered for use in MDR-TB screening tool development if universal drug susceptibility testing is not possible. Moreover, TB infection control practices in health care settings should be further strengthened. As factors may vary from region to region, further broader studies need to be conducted in other parts of Ethiopia.