In-Person vs Electronic Directly Observed Therapy for Tuberculosis Treatment Adherence
Authors: Joseph Burzynski, Joan M. Mangan, Chee Kin Lam, Michelle Macaraig, Marco M. Salerno, B. Rey deCastro, Neela D. Goswami, Carol Y. Lin, Neil W. Schluger, Andrew Vernon, Sapna Bamrah-Morris, Sheridan Bowers, Shannon Carberry, Christine Chuck, Matthew Dias, Grace Gao, Richard Garfein, Vernard Green, Lon Gross, Gary Henry, Andrew Hill, Sarah Kiskadden-Bechtel, Meena Lakshman, Nikolaos Mitropoulos, Diana M Nilsen, Margaret Oxtoby, Patrick Philips, Michael Reaves, Errol Robinson, Charlene Sathi, Brock Stewart, Anila Thomas, Zhanna Tolochko, Lisa Trieu, Carla Winston
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Electronic directly observed therapy (DOT) is used increasingly as an alternative to in-person DOT for monitoring tuberculosis treatment. Evidence supporting its efficacy is limited. <h3>Objective</h3> To determine whether electronic DOT can attain a level of treatment observation as favorable as in-person DOT. <h3>Design, Setting, and Participants</h3> This was a 2-period crossover, noninferiority trial with initial randomization to electronic or in-person DOT at the time outpatient tuberculosis treatment began. The trial enrolled 216 participants with physician-suspected or bacteriologically confirmed tuberculosis from July 2017 to October 2019 in 4 clinics operated by the New York City Health Department. Data analysis was conducted between March 2020 and April 2021. <h3>Interventions</h3> Participants were asked to complete 20 medication doses using 1 DOT method, then switched methods for another 20 doses. With in-person therapy, participants chose clinic or community-based DOT; with electronic DOT, participants chose live video-conferencing or recorded videos. <h3>Main Outcomes and Measures</h3> Difference between the percentage of medication doses participants were observed to completely ingest with in-person DOT and with electronic DOT. Noninferiority was demonstrated if the upper 95% confidence limit of the difference was 10% or less. We estimated the percentage of completed doses using a logistic mixed effects model, run in 4 modes: modified intention-to-treat, per-protocol, per-protocol with 85% or more of doses conforming to the randomization assignment, and empirical. Confidence intervals were estimated by bootstrapping (with 1000 replicates). <h3>Results</h3> There were 173 participants in each crossover period (median age, 40 years [range, 16-86 years]; 140 [66%] men; 80 [37%] Asian and Pacific Islander, 43 [20%] Black, and 71 [33%] Hispanic individuals) evaluated with the model in the modified intention-to-treat analytic mode. The percentage of completed doses with in-person DOT was 87.2% (95% CI, 84.6%-89.9%) vs 89.8% (95% CI, 87.5%-92.1%) with electronic DOT. The percentage difference was −2.6% (95% CI, −4.8% to −0.3%), consistent with a conclusion of noninferiority. The 3 other analytic modes yielded equivalent conclusions, with percentage differences ranging from −4.9% to −1.9%. <h3>Conclusions and Relevance</h3> In this trial, the percentage of completed doses under electronic DOT was noninferior to that under in-person DOT. This trial provides evidence supporting the efficacy of this digital adherence technology, and for the inclusion of electronic DOT in the standard of care. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03266003