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
Authors: Foster Nicola , Tadesse Amare W , McQuaid Christopher Finn , Gosce Lara , Abdurhman Tofik , Assefa Demelash , Bedru Ahmed , Houben Rein MGJ , Kalmthout Kristian van , Letta Taye , Mohammed Zemedu , Rest Job van , Umeta Demekech G , Weldemichael Gedion T , Yazew Hiwot , Jerene Degu , Quaife Matthew , Fielding Katherine L 
Published: January 2023

Abstract
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, costeffectiveness, 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 into 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 six months of end-of-treatment. For the costeffectiveness 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 costeffectiveness 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.