Effectiveness of digital adherence technologies in improving tuberculosis treatment outcomes in four countries: a pragmatic cluster randomised trial protocol

Abstract

IntroductionSuccessful treatment of tuberculosis depends to a large extent on good adherence to treatment regimens, which relies on directly observed treatment (DOT). This in turn requires frequent visits to health facilities. High costs to patients, stigma and burden to the health system challenged the DOT approach. Digital adherence technologies (DATs) have emerged as possibly more feasible alternatives to DOT but there is conflicting evidence on their effectiveness and feasibility. Our primary objective is to evaluate whether the implementation of DATs with daily monitoring and a differentiated response to patient adherence would reduce poor treatment outcomes compared with the standard of care (SOC). Our secondary objectives include: to evaluate the proportion of patients lost to follow-up; to compare effectiveness by DAT type; to evaluate the feasibility and acceptability of DATs; to describe factors affecting the longitudinal engagement of patients with the intervention and to use a simple model to estimate the epidemiological impact and cost-effectiveness of the intervention from a health system perspective.Methods and analysisThis is a pragmatic two-arm cluster-randomised trial in the Philippines, South Africa, Tanzania and Ukraine, with health facilities as the unit of randomisation. Facilities will first be randomised to either the DAT or SOC arm, and then the DAT arm will be further randomised into medication sleeve/labels or smart pill box in a 1:1:2 ratio for the smart pill box, medication sleeve/label or the SOC respectively. We will use data from the digital adherence platform and routine health facility records for analysis. In the main analysis, we will employ an intention-to-treat approach to evaluate treatment outcomes.Ethics and disseminationThe study has been approved by the WHO Research Ethics Review Committee (0003296), and by country-specific committees. The results will be shared at national and international meetings and will be published in peer-reviewed journals.Trial registration numberISRCTN17706019.

Cluster-randomized trial of digital adherence technologies and differentiated care to reduce poor end-of-treatment outcomes and recurrence among adults with drug-sensitive pulmonary TB in Ethiopia

“…Health facilities were randomised (ratio 1:1:1) to either the (i) smart pillbox or (ii) medication labels, both with daily monitoring and differentiated response to patient adherence, or (iii) standard of care arm. This trial was part of the ASCENT consortium which conducted trials in four other countries, under a separate protocol and reported separately due to a different trial design (two-arm studies with no follow-up for recurrence) (15, 28). The pragmatic trial design was chosen as the interest was in how the DAT interventions would work under routine conditions; design choices, therefore, included broad eligibility criteria, delivery of the intervention (primarily implemented by health facility staff), and outcomes relevant to participants.…”

Feasibility and acceptability of the smart pillbox and medication label with differentiated care to support person-centered tuberculosis care among ASCENT trial participants – A multicountry study

“…This was a cross-sectional survey among adults with drug-sensitive tuberculosis (DS-TB) who participated in the ASCENT CRTs in Ethiopia, the Philippines, South Africa, and Tanzania. The design of the trials has been described elsewhere ( 14 , 15 ). The Ethiopian trial was registered at Pan African Clinical Trials Registry (PACTR202008776694999) and the trials in the other countries were registered at International Standard Randomized Controlled Trial Number (ISRCTN 17706019).…”

“…Contextual factors, including socio-demographic, person-related factors, and physical and social environments, may also operate differently on the feasibility or acceptability of DATs to deliver the targeted treatment support that is needed. DATs and associated differentiated care are being assessed in many evaluations including the Adherence Support Coalition to End TB (ASCENT) cluster randomized trials (CRTs), which are being conducted in five countries with varying epidemiology, socioeconomic, geographical, infrastructural and health system factors ( 14 , 15 ). We report findings on feasibility and acceptability of DATs with differentiated response to treatment adherence among adult participants enrolled into CRTs in four countries implementing the ASCENT project.…”

Factors Related to the Utilization of Digital Adherence Technologies in Tuberculosis Care: A Qualitative Study Among Adults in DS-TB Treatment, Health Care Providers and Other Key Stakeholders in Tanzania

“…In order to understand the factors that influence experiences with using and implementing medication labels, smart pillboxes and the EverWell adherence platform, we conducted in depth interviews with people living with drug susceptible TB (DS-TB), HCPs and other key stakeholders in Tanzania. This qualitative study is part of a multi-country, cluster-randomized trials, the Adherence Support Coalition to End TB (ASCENT) consortium [11].…”

“…Training was provided once for two days at the beginning of the project for all HCPs. ASCENT staff also provided monthly technical support on demand throughout the trial implementation period, including quarterly supportive supervision.In Tanzania, DATs were implemented in 36 health facilities [11] as part of the ASCENT…”