<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "journalpublishing.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="2.0" xml:lang="en" article-type="review-article"><front><journal-meta><journal-id journal-id-type="nlm-ta">JMIR mHealth and uHealth</journal-id><journal-id journal-id-type="publisher-id">mhealth</journal-id><journal-id journal-id-type="index">13</journal-id><journal-title>JMIR mHealth and uHealth</journal-title><abbrev-journal-title>JMIR mHealth and uHealth</abbrev-journal-title><issn pub-type="epub">2291-5222</issn></journal-meta><article-meta><article-id pub-id-type="publisher-id">49741</article-id><article-id pub-id-type="doi">10.2196/49741</article-id><title-group><article-title>Digital Health Interventions to Enhance Tuberculosis Treatment Adherence: Scoping Review</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><name name-style="western"><surname>Lee</surname><given-names>Sol</given-names></name><degrees>MPH</degrees><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="fn" rid="equal-contrib1">*</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name name-style="western"><surname>Rajaguru</surname><given-names>Vasuki</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff2">2</xref><xref ref-type="fn" rid="equal-contrib1">*</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Baek</surname><given-names>Joon Sang</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Shin</surname><given-names>Jaeyong</given-names></name><degrees>MD, MPH, PhD</degrees><xref ref-type="aff" rid="aff4">4</xref><xref ref-type="aff" rid="aff5">5</xref></contrib><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Park</surname><given-names>Youngmok</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="aff5">5</xref><xref ref-type="aff" rid="aff6">6</xref></contrib></contrib-group><aff id="aff1"><institution>Yonsei University Health System, Yonsei University</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff><aff id="aff2"><institution>Department of Healthcare Management, Graduate School of Public Health, Yonsei University</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff><aff id="aff3"><institution>Department of Human Environment &#x0026; Design, Yonsei University</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff><aff id="aff4"><institution>Department of Preventive Medicine, College of Medicine, Yonsei University</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff><aff id="aff5"><institution>Institute for Innovation in Digital Healthcare, Yonsei University</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff><aff id="aff6"><institution>Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine</institution>, <addr-line>Seoul</addr-line>, <country>Republic of Korea</country></aff><contrib-group><contrib contrib-type="editor"><name name-style="western"><surname>Buis</surname><given-names>Lorraine</given-names></name></contrib></contrib-group><contrib-group><contrib contrib-type="reviewer"><name name-style="western"><surname>Sim</surname><given-names>Boram</given-names></name></contrib><contrib contrib-type="reviewer"><name name-style="western"><surname>Perimal-Lewis</surname><given-names>Lua</given-names></name></contrib></contrib-group><author-notes><corresp>Correspondence to Youngmok Park, MD<email>0mokfv@yuhs.ac</email></corresp><fn fn-type="equal" id="equal-contrib1"><label>*</label><p>these authors contributed equally</p></fn></author-notes><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>4</day><month>12</month><year>2023</year></pub-date><volume>11</volume><elocation-id>e49741</elocation-id><history><date date-type="received"><day>21</day><month>06</month><year>2023</year></date><date date-type="rev-recd"><day>05</day><month>10</month><year>2023</year></date><date date-type="accepted"><day>27</day><month>10</month><year>2023</year></date></history><copyright-statement>&#x00A9; Sol Lee, Vasuki Rajaguru, Joon Sang Baek, Jaeyong Shin, Youngmok Park. Originally published in JMIR mHealth and uHealth (<ext-link ext-link-type="uri" xlink:href="https://mhealth.jmir.org">https://mhealth.jmir.org</ext-link>), 4.12.2023. </copyright-statement><copyright-year>2023</copyright-year><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">https://creativecommons.org/licenses/by/4.0/</ext-link>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR mHealth and uHealth, is properly cited. The complete bibliographic information, a link to the original publication on <ext-link ext-link-type="uri" xlink:href="https://mhealth.jmir.org/">https://mhealth.jmir.org/</ext-link>, as well as this copyright and license information must be included.</p></license><self-uri xlink:type="simple" xlink:href="https://mhealth.jmir.org/2023/1/e49741"/><abstract><sec><title>Background</title><p>Digital health technologies are widely used for disease management, with their computing platforms, software, and sensors being used for health care. These technologies are developed to manage chronic diseases and infectious bacterial diseases, including tuberculosis (TB).</p></sec><sec><title>Objective</title><p>This study aims to comprehensively review the literature on the use of digital health interventions (DHIs) for enhancing TB treatment adherence and identify major strategies for their adoption.</p></sec><sec sec-type="methods"><title>Methods</title><p>We conducted a literature search in the PubMed, Cochrane Library, Ovid Embase, and Scopus databases for relevant studies published between January 2012 and March 2022. Studies that focused on web-based or mobile phone&#x2013;based interventions, medication adherence, digital health, randomized controlled trials, digital interventions, or mobile health and ubiquitous health technology for TB treatment and related health outcomes were included.</p></sec><sec sec-type="results"><title>Results</title><p>We identified 27 relevant studies and classified them according to the intervention method, a significant difference in treatment success, and health outcomes. The following interventions were emphasized: SMS text messaging interventions (8/27, 30%), medicine reminders (6/27, 22%), and web-based direct observation therapy (9/27, 33%). Digital health technology significantly promoted disease management among individuals and health care professionals. However, only a few studies addressed 2-way communication therapies, such as interactive SMS text messaging and feedback systems.</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>This scoping review classified studies on DHIs for patients with TB and demonstrated their potential for the self-management of TB. DHIs are still being developed, and evidence on the impact of digital technologies on enhancing TB treatment adherence remains limited. However, it is necessary to encourage patients&#x2019; participation in TB treatment and self-management through bidirectional communication. We emphasize the importance of developing a communication system.</p></sec></abstract><kwd-group><kwd>tuberculosis</kwd><kwd>patient compliance</kwd><kwd>digital health</kwd><kwd>medication adherence</kwd><kwd>text messaging</kwd><kwd>mobile apps</kwd><kwd>application</kwd><kwd>medication</kwd><kwd>text</kwd><kwd>scoping review</kwd><kwd>disease management</kwd><kwd>chronic disease</kwd><kwd>communication</kwd><kwd>feedback</kwd><kwd>self-management</kwd><kwd>PRISMA</kwd></kwd-group></article-meta></front><body><sec id="s1" sec-type="intro"><title>Introduction</title><p>Until the COVID-19 pandemic, tuberculosis (TB) was the leading cause of death from a single infectious disease, affecting approximately 10.6 million people in 2021 [<xref ref-type="bibr" rid="ref1">1</xref>]. TB can be cured with appropriate medications; however, treatment adherence is affected by the complexity, tolerability, and long duration of the available regimens. Since low adherence increases the risk of poor treatment outcomes, several interventions have been attempted to enhance TB medication adherence [<xref ref-type="bibr" rid="ref2">2</xref>].</p><p>Digital health interventions (DHIs) are promising for patient-centered care, as they allow for the remote monitoring of patients and can be used to conveniently remind patients to take their medications. Numerous studies have addressed how to enhance medication adherence during treatment by using mobile technologies, such as SMS text messaging [<xref ref-type="bibr" rid="ref3">3</xref>], directly observed therapy (DOT) [<xref ref-type="bibr" rid="ref3">3</xref>-<xref ref-type="bibr" rid="ref5">5</xref>], video calls, phone call reminders [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref6">6</xref>], and web-based reports [<xref ref-type="bibr" rid="ref3">3</xref>-<xref ref-type="bibr" rid="ref7">7</xref>]. Studies have reported satisfaction [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref8">8</xref>], accuracy [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref8">8</xref>], acceptable uptake [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref8">8</xref>], improved drug adherence [<xref ref-type="bibr" rid="ref3">3</xref>-<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref9">9</xref>], higher rates of treatment success [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref7">7</xref>,<xref ref-type="bibr" rid="ref8">8</xref>], and user acceptance [<xref ref-type="bibr" rid="ref7">7</xref>-<xref ref-type="bibr" rid="ref10">10</xref>] with regard to DHIs in TB management.</p><p>This review aims to summarize the existing literature on DHIs for TB treatment adherence, classify DHI techniques, identify the different types of interventions and their effects on treatment effectiveness, and evaluate adherence and health outcomes in TB treatment. This study reports on treatment outcomes, self-care management, follow-up, and the value of mobile-based communication activities that aim to improve TB treatment adherence.</p></sec><sec id="s2" sec-type="methods"><title>Methods</title><p>We followed Arksey and O&#x2019;Malley&#x2019;s [<xref ref-type="bibr" rid="ref11">11</xref>] 5-stage scoping review framework, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [<xref ref-type="bibr" rid="ref12">12</xref>], and the Joanna Briggs Institute protocol [<xref ref-type="bibr" rid="ref13">13</xref>].</p><sec id="s2-1"><title>Identifying the Relevant Studies</title><p>We conducted a literature search in the PubMed, Cochrane Library, Ovid Embase, and Scopus databases for relevant studies published between January 2012 and March 2022. A comprehensive search strategy was developed to identify relevant studies, which included but was not confined to the following search string: <italic>(&#x201C;Tuberculosis&#x201D; OR &#x201C;TB&#x201D; OR &#x201C;Tuberculosis infection&#x201D;) AND (&#x201C;RCT&#x201D; OR &#x201C;Randomized controlled trial&#x201D; OR &#x201C;Experimental study&#x201D;) AND (&#x201C;Behavior therapy&#x201D; OR &#x201C;Cognitive behavioral treatment&#x201D; OR &#x201C;Digital intervention&#x201D; OR &#x201C;Digital therapeutics&#x201D; OR &#x201C;App-based&#x201D; OR &#x201C;Web-based&#x201D; OR &#x201C;mHealth&#x201D; OR &#x201C;uHealth&#x201D;) AND (&#x201C;treatment adherence&#x201D; OR &#x201C;medication adherence&#x201D; OR &#x201C;selfcare&#x201D; OR &#x201C;Management&#x201D; OR &#x201C;Persistence&#x201D; OR &#x201C;Compliance&#x201D;)</italic>. The search terms and strategies are presented in <xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>.</p></sec><sec id="s2-2"><title>Eligibility and Exclusion Criteria</title><p>We included articles that met the following criteria: (1) published in peer-reviewed journals, (2) included TB treatment adherence and health outcomes as part of the study design, (3) written in English, (4) had full text available, and (5) published between January 2012 and March 2022. Studies were excluded if they were published before 2011 or did not focus on DHIs for TB. Reviews, case studies, reports, letters, conference proceedings, and abstract-only articles were also excluded.</p></sec><sec id="s2-3"><title>Study Selection and Data Synthesis</title><p>Duplicates were eliminated from each database and recorded in the first stage. The second stage involved reviewing study titles and abstracts to ensure that articles were research studies that focused on digital health technology as a main intervention tool to improve the treatment adherence of patients with TB. The full texts of the articles were scrutinized in the last stage to verify whether they satisfied the key requirements.</p><p>Data were extracted by 1 reviewer (SL), and 2 independent reviewers (VR and YP) charted the data on different characteristics, including authors, publication year, country, study design, target population, number of participants, type of DHI, duration, follow-up, outcome measures, and major findings.</p><p>The retrieved data suggested that the core attributes of digital intervention strategies fell under the following three domains, which were based on the DHIs found in the selected articles: sending reminders via SMS text messages, monitoring progress, and tracking follow-ups for the self-management of TB treatment outcomes.</p></sec><sec id="s2-4"><title>Quality Assessment and Risk of Bias</title><p>Two independent reviewers (SL and YP) evaluated the risk of bias as part of the quality assessment, using the Cochrane Collaboration&#x2019;s tool for assessing the risk of bias (RoB 2 [Risk of Bias 2]; version: August 9, 2019) [<xref ref-type="bibr" rid="ref14">14</xref>]. The risk of bias was assessed based on 5 domains, and bias scores were assigned (&#x201C;low risk,&#x201D; &#x201C;some concern,&#x201D; or &#x201C;high risk&#x201D;).</p></sec></sec><sec id="s3" sec-type="results"><title>Results</title><sec id="s3-1"><title>Search Results</title><p>The literature search retrieved 305 articles; 72 duplicates were excluded, and 172 did not meet the inclusion criteria, based on the title and abstract review. As a result, 61 articles were screened for the full-text review, and 34 were excluded owing to implications regarding the exclusion criteria and unavailability of full texts. Ultimately, 27 studies were finalized for the data synthesis (<xref ref-type="fig" rid="figure1">Figure 1</xref>).</p><fig position="float" id="figure1"><label>Figure 1.</label><caption><p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram for selection of articles. RCT: randomized controlled trial.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="mhealth_v11i1e49741_fig01.png"/></fig></sec><sec id="s3-2"><title>Characteristics of the Selected Articles</title><p>Given the novelty of digital health technology in TB treatment, the number of publications was observed to have increased since 2018. A total of 27 articles [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref41">41</xref>] were selected; their characteristics are described in <xref ref-type="supplementary-material" rid="app2">Multimedia Appendix 2</xref>. Most of the studies (19/27, 70%) were published in or after 2019 [<xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref24">24</xref>-<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref33">33</xref>-<xref ref-type="bibr" rid="ref41">41</xref>].</p><p>With regard to the study designs, 17 studies were randomized controlled trials (RCTs) [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref19">19</xref>-<xref ref-type="bibr" rid="ref21">21</xref>,<xref ref-type="bibr" rid="ref24">24</xref>-<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref38">38</xref>], 8 were RCT protocols [<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref23">23</xref>,<xref ref-type="bibr" rid="ref33">32</xref>,<xref ref-type="bibr" rid="ref35">33</xref>,<xref ref-type="bibr" rid="ref36">35</xref>,<xref ref-type="bibr" rid="ref39">36</xref>,<xref ref-type="bibr" rid="ref40">39</xref>,<xref ref-type="bibr" rid="ref32">40</xref>], and 2 were quasi-experimental studies [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref41">41</xref>]. Further, 13 studies were published in low- and middle-income countries (LMICs), including countries in Africa [<xref ref-type="bibr" rid="ref18">18</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref23">23</xref>,<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref40">40</xref>] and Asia [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref19">19</xref>,<xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref41">41</xref>]. Digital health technology for TB is actively used in LMICs due to the high prevalence of TB (<xref ref-type="supplementary-material" rid="app3">Multimedia Appendix 3</xref>). The combined study population was aged &#x003E;18 years and included participants who were diagnosed with TB or were taking TB medication. The average number of participants was 400.</p></sec><sec id="s3-3"><title>Types of DHIs</title><p><xref ref-type="table" rid="table1">Table 1</xref> and <xref ref-type="fig" rid="figure2">Figure 2</xref> present the most common technologies used in DHIs, including the duration, frequency, and outcomes of interventions. The commonest DHIs were SMS text messages and reminder messages (8/27, 30%) [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref22">22</xref>], DOT (9/27, 33%) [<xref ref-type="bibr" rid="ref23">23</xref>-<xref ref-type="bibr" rid="ref31">31</xref>], medication event reminder monitors (MERMs; 6/27, 22%) [<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref37">37</xref>], and mobile apps (4/27, 15%) [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref41">41</xref>]. DOT-based DHIs included video observation therapy (VOT) [<xref ref-type="bibr" rid="ref25">25</xref>], electronic DOT (e-DOT) [<xref ref-type="bibr" rid="ref31">31</xref>], and wearable bracelet self-DOT [<xref ref-type="bibr" rid="ref23">23</xref>]. Some studies evaluated a mix of interventions, including mobile app&#x2013;based video observations [<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>,<xref ref-type="bibr" rid="ref39">39</xref>], a web intervention [<xref ref-type="bibr" rid="ref24">24</xref>], WhatsApp (Meta Platforms Inc) [<xref ref-type="bibr" rid="ref38">38</xref>], and WeChat (Tencent Holdings Ltd) [<xref ref-type="bibr" rid="ref39">39</xref>]. MERMs [<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref37">37</xref>] were also used to determine the feasibility of a web-based follow-up [<xref ref-type="bibr" rid="ref36">36</xref>] and a mobile-based (ie, evriMED1000 [Wisepill Technologies]) follow-up with phone call [<xref ref-type="bibr" rid="ref34">34</xref>] reminders to enhance treatment adherence.</p><table-wrap id="t1" position="float"><label>Table 1.</label><caption><p>Description of digital health technology tuberculosis (TB) interventions and related outcomes.</p></caption><table id="table1" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom">Study</td><td align="left" valign="bottom">Intervention</td><td align="left" valign="bottom">Main outcome</td><td align="left" valign="bottom">Secondary outcomes</td><td align="left" valign="bottom">Duration</td><td align="left" valign="bottom">Frequency</td></tr></thead><tbody><tr><td align="char" char="." valign="top">Bediang et al [<xref ref-type="bibr" rid="ref15">15</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment adherence, multidrug resistance, and satisfaction</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">van der Kop et al [<xref ref-type="bibr" rid="ref16">16</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment adherence and treatment completion</td><td align="left" valign="top">9 mo</td><td align="left" valign="top">Weekly</td></tr><tr><td align="char" char="." valign="top">Mohammed et al [<xref ref-type="bibr" rid="ref17">17</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment adherence and physical health measures</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Hermans et al [<xref ref-type="bibr" rid="ref18">18</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Risk of LFU<sup><xref ref-type="table-fn" rid="table1fn1">a</xref></sup> in the first 2 mo of treatment</td><td align="left" valign="top">Treatment success, completion, adherence, satisfaction, and knowledge</td><td align="left" valign="top">2 mo</td><td align="left" valign="top">Other<sup><xref ref-type="table-fn" rid="table1fn2">b</xref></sup></td></tr><tr><td align="char" char="." valign="top">Farooqi et al [<xref ref-type="bibr" rid="ref19">19</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Treatment default</td><td align="left" valign="top">TB treatment results according to the WHO<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup><sup>,</sup><sup><xref ref-type="table-fn" rid="table1fn4">d</xref></sup></td><td align="left" valign="top">2 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Bediang et al [<xref ref-type="bibr" rid="ref20">20</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Self-reported adherence regarding attending appointments and satisfaction</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Moriarty et al [<xref ref-type="bibr" rid="ref21">21</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">TB treatment results according to the WHO<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup></td><td align="left" valign="top">Smoking cessation, reduction in alcohol use, and treatment adherence</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Twice weekly</td></tr><tr><td align="char" char="." valign="top">Sahile et al [<xref ref-type="bibr" rid="ref22">22</xref>]</td><td align="left" valign="top">SMS text messaging</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">ACTG<sup><xref ref-type="table-fn" rid="table1fn5">e</xref></sup>, VAS<sup><xref ref-type="table-fn" rid="table1fn6">f</xref></sup>, and clinic appointment attendance</td><td align="left" valign="top">2 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Huang et al [<xref ref-type="bibr" rid="ref23">23</xref>]</td><td align="left" valign="top">e-DOT<sup><xref ref-type="table-fn" rid="table1fn7">g</xref></sup></td><td align="left" valign="top">TB treatment results according to the WHO<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup></td><td align="left" valign="top">Treatment adherence, MGLS<sup><xref ref-type="table-fn" rid="table1fn8">h</xref></sup>, knowledge, and quality of life</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Browne et al [<xref ref-type="bibr" rid="ref24">24</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Positive detection accuracy</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Other<sup><xref ref-type="table-fn" rid="table1fn9">i</xref></sup></td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Holzman et al [<xref ref-type="bibr" rid="ref25">25</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Proportion of all prescribed treatment</td><td align="left" valign="top">Other<sup><xref ref-type="table-fn" rid="table1fn9">i</xref></sup></td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Story et al [<xref ref-type="bibr" rid="ref26">26</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Treatment outcomes and health-related quality of life</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Khachadourian et al [<xref ref-type="bibr" rid="ref27">27</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment adherence, depressive symptoms, quality of life, and social support as nonclinical outcomes</td><td align="left" valign="top">4-5 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Crowder et al [<xref ref-type="bibr" rid="ref28">28</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Reduced risk of LFU and cost-effectiveness</td><td align="left" valign="top">14 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Ravenscroft et al [<xref ref-type="bibr" rid="ref29">29</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Treatment success at 12 mo</td><td align="left" valign="top">4 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Doltu et al [<xref ref-type="bibr" rid="ref30">30</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Living conditions, health insurance before TB, previous treatment history, and mode of intensive phase</td><td align="left" valign="top">3 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Burzynski et al [<xref ref-type="bibr" rid="ref31">31</xref>]</td><td align="left" valign="top">e-DOT</td><td align="left" valign="top">Completed doses and percentage differences between electronic vs in-person DOT<sup><xref ref-type="table-fn" rid="table1fn10">j</xref></sup></td><td align="left" valign="top">Proportion of medication doses, patient adherence, and quality of care</td><td align="left" valign="top">Other<sup><xref ref-type="table-fn" rid="table1fn11">k</xref></sup></td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Lewis et al [<xref ref-type="bibr" rid="ref32">32</xref>]</td><td align="left" valign="top">MERM<sup><xref ref-type="table-fn" rid="table1fn12">l</xref></sup></td><td align="left" valign="top">TB treatment results according to the WHO<sup><xref ref-type="table-fn" rid="table1fn3">c</xref></sup></td><td align="left" valign="top">Adherence outcomes and cost-effectiveness outcomes</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Manyazewal et al [<xref ref-type="bibr" rid="ref33">33</xref>]</td><td align="left" valign="top">MERM</td><td align="left" valign="top">Treatment adherence and sputum conversion</td><td align="left" valign="top">Adverse treatment outcomes, cost-effectiveness, and usability</td><td align="left" valign="top">15 d</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Ratchakit-Nedsuwan et al [<xref ref-type="bibr" rid="ref34">34</xref>]</td><td align="left" valign="top">MERM</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment adherence and patients&#x2019; experiences</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Maraba et al [<xref ref-type="bibr" rid="ref35">35</xref>]</td><td align="left" valign="top">MERM</td><td align="left" valign="top">Treatment adherence</td><td align="left" valign="top">Treatment success, acceptability of the intervention, and cost-effectiveness</td><td align="left" valign="top">18 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Tadesse et al [<xref ref-type="bibr" rid="ref36">36</xref>]</td><td align="left" valign="top">MERM</td><td align="left" valign="top">Composite unfavorable outcome: treatment failure or death</td><td align="left" valign="top">Longitudinal technology engagement and fidelity to the intervention</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Acosta et al [<xref ref-type="bibr" rid="ref37">37</xref>]</td><td align="left" valign="top">MERM</td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment adherence, clinical failure, and LFU</td><td align="left" valign="top">4 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">NoorHaslinda and Juni [<xref ref-type="bibr" rid="ref38">38</xref>]</td><td align="left" valign="top">mHealth<sup><xref ref-type="table-fn" rid="table1fn13">m</xref></sup><sup>,</sup><sup><xref ref-type="table-fn" rid="table1fn14">n</xref></sup></td><td align="left" valign="top">Treatment success and treatment adherence</td><td align="left" valign="top">N/A<sup><xref ref-type="table-fn" rid="table1fn15">o</xref></sup></td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Wei et al [<xref ref-type="bibr" rid="ref39">39</xref>]</td><td align="left" valign="top">mHealth<sup><xref ref-type="table-fn" rid="table1fn14">n</xref></sup></td><td align="left" valign="top">Rate of poor adherence</td><td align="left" valign="top">TB treatment results according to the WHO</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Byonanebye et al [<xref ref-type="bibr" rid="ref40">40</xref>]</td><td align="left" valign="top">mHealth<sup><xref ref-type="table-fn" rid="table1fn14">n</xref></sup></td><td align="left" valign="top">Treatment success</td><td align="left" valign="top">Treatment success, acceptability of the intervention, and cost-effectiveness</td><td align="left" valign="top">6 mo</td><td align="left" valign="top">Daily</td></tr><tr><td align="char" char="." valign="top">Santra et al [<xref ref-type="bibr" rid="ref41">41</xref>]</td><td align="left" valign="top">mHealth<sup><xref ref-type="table-fn" rid="table1fn14">n</xref></sup></td><td align="left" valign="top">Treatment adherence and MGLS</td><td align="left" valign="top">N/A</td><td align="left" valign="top">Other<sup><xref ref-type="table-fn" rid="table1fn16">p</xref></sup></td><td align="left" valign="top">Daily</td></tr></tbody></table><table-wrap-foot><fn id="table1fn1"><p><sup>a</sup>LFU: loss to follow-up.</p></fn><fn id="table1fn2"><p><sup>b</sup>Compliance notifications (2, 7, and 11 d after the most recent appointment), appointment notifications (every 2 wk), and educational quizzes (3, 6, 9, and 12 d after the most recent appointment).</p></fn><fn id="table1fn3"><p><sup>c</sup>Cured, treatment completed, treatment failed, died, lost to follow-up, not evaluated, or treatment success.</p></fn><fn id="table1fn4"><p><sup>d</sup>WHO: World Health Organization.</p></fn><fn id="table1fn5"><p><sup>e</sup>ACTG: AIDS Clinical Trial Group adherence questionnaire.</p></fn><fn id="table1fn6"><p><sup>f</sup>VAS: visual analog scale.</p></fn><fn id="table1fn7"><p><sup>g</sup>e-DOT: electronic directly observed therapy.</p></fn><fn id="table1fn8"><p><sup>h</sup>MGLS: Morisky, Green, and Levine Adherence Scale.</p></fn><fn id="table1fn9"><p><sup>i</sup>Until TB treatment completion.</p></fn><fn id="table1fn10"><p><sup>j</sup>DOT: directly observed therapy.</p></fn><fn id="table1fn11"><p><sup>k</sup>Completed 20 medication doses using 1 DOT method, then switched methods for another 20 doses.</p></fn><fn id="table1fn12"><p><sup>l</sup>MERM: medication event reminder monitor.</p></fn><fn id="table1fn13"><p><sup>m</sup>mHealth: mobile health.</p></fn><fn id="table1fn14"><p><sup>n</sup>Smartphone mobile app.</p></fn><fn id="table1fn15"><p><sup>o</sup>N/A: not applicable.</p></fn><fn id="table1fn16"><p><sup>p</sup>DOT for a minimum period of 30 d and a maximum of 90 d.</p></fn></table-wrap-foot></table-wrap><fig position="float" id="figure2"><label>Figure 2.</label><caption><p>Types of digital health interventions and the number of articles published by year. e-DOT: electronic directly observed therapy; MERM: medication event reminder monitor; mHealth: mobile health.</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="mhealth_v11i1e49741_fig02.png"/></fig></sec><sec id="s3-4"><title>Components of the DHIs and Outcomes</title><p><xref ref-type="table" rid="table2">Table 2</xref> presents the components of DHIs that were derived from the primary and secondary outcomes of the selected articles, including (1) sending reminders for treatment adherence via reinforcement SMS text messages [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref22">22</xref>], (2) monitoring treatment adherence by using digital technology [<xref ref-type="bibr" rid="ref23">23</xref>-<xref ref-type="bibr" rid="ref31">31</xref>], and (3) tracking treatment adherence through the use of mobile apps and mobile health (mHealth) technology [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref41">41</xref>] via treatment adherence [<xref ref-type="bibr" rid="ref42">42</xref>] and modified behavior adherence [<xref ref-type="bibr" rid="ref43">43</xref>] models. <xref ref-type="fig" rid="figure3">Figure 3</xref> presents a modified adherence model.</p><table-wrap id="t2" position="float"><label>Table 2.</label><caption><p>Distribution of digital health interventions (DHIs) and related interventions (N=27).</p></caption><table id="table2" frame="hsides" rules="groups"><thead><tr><td align="left" valign="bottom" colspan="2">Components and DHIs</td><td align="left" valign="bottom">Articles, n (%)</td><td align="left" valign="bottom">References</td></tr></thead><tbody><tr><td align="left" valign="top" colspan="4"><bold>Reminding</bold></td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">SMS text messaging</td><td align="char" char="." valign="top">8 (30)</td><td align="char" char="." valign="top">[<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref22">22</xref>]</td></tr><tr><td align="left" valign="top" colspan="4"><bold>Monitoring</bold></td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">DOT<sup><xref ref-type="table-fn" rid="table2fn1">a</xref></sup> (e-DOT<sup><xref ref-type="table-fn" rid="table2fn2">b</xref></sup>, VOT<sup><xref ref-type="table-fn" rid="table2fn3">c</xref></sup>, and WOT<sup><xref ref-type="table-fn" rid="table2fn4">d</xref></sup>)</td><td align="char" char="." valign="top">9 (33)</td><td align="char" char="." valign="top">[<xref ref-type="bibr" rid="ref23">23</xref>-<xref ref-type="bibr" rid="ref31">31</xref>]</td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">MERM<sup><xref ref-type="table-fn" rid="table2fn5">e</xref></sup></td><td align="char" char="." valign="top">6 (22)</td><td align="char" char="." valign="top">[<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref37">37</xref>]</td></tr><tr><td align="left" valign="top" colspan="4"><bold>Tracking</bold></td></tr><tr><td align="left" valign="top"/><td align="left" valign="top">Mobile app and mHealth<sup><xref ref-type="table-fn" rid="table2fn6">f</xref></sup></td><td align="char" char="." valign="top">4 (15)</td><td align="char" char="." valign="top">[<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref41">41</xref>]</td></tr></tbody></table><table-wrap-foot><fn id="table2fn1"><p><sup>a</sup>DOT: directly observed therapy.</p></fn><fn id="table2fn2"><p><sup>b</sup>e-DOT: electronic directly observed therapy.</p></fn><fn id="table2fn3"><p><sup>c</sup>VOT: video observation therapy.</p></fn><fn id="table2fn4"><p><sup>d</sup>WOT: wireless observation therapy.</p></fn><fn id="table2fn5"><p><sup>e</sup>MERM: medication event reminder monitor.</p></fn><fn id="table2fn6"><p><sup>f</sup>mHealth: mobile health.</p></fn></table-wrap-foot></table-wrap><fig position="float" id="figure3"><label>Figure 3.</label><caption><p>Adherence to tuberculosis treatment is a repeated and ongoing self-management behavior. In this figure, <italic>reminding</italic> refers to reminding patients to take medications as prescribed (ie, correct dose, frequency, and time), <italic>monitoring</italic> refers to using digital health technology (eg, an app) to check whether patients are taking their medication at the prescribed frequency over the initial period, and <italic>tracking</italic> refers to following patients over time to determine whether they taking medications as prescribed [<xref ref-type="bibr" rid="ref43">43</xref>].</p></caption><graphic alt-version="no" mimetype="image" position="float" xlink:type="simple" xlink:href="mhealth_v11i1e49741_fig03.png"/></fig></sec><sec id="s3-5"><title>Quality Assessment of the Selected Articles</title><p>A risk of bias assessment was performed to assess the quality of the selected articles. Only 8 of the 27 articles used an RCT design [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref24">24</xref>,<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref37">37</xref>]. The risk of bias results are shown in <xref ref-type="supplementary-material" rid="app4">Multimedia Appendix 4</xref> [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref24">24</xref>,<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref31">31</xref>,<xref ref-type="bibr" rid="ref37">37</xref>] and <xref ref-type="supplementary-material" rid="app5">Multimedia Appendix 5</xref>.</p></sec></sec><sec id="s4" sec-type="discussion"><title>Discussion</title><sec id="s4-1"><title>Principal Results</title><p>This review aimed to identify DHIs related to TB treatment and management. We retrieved the relevant articles from electronic databases by using standard search terms and identified 27 articles published between 2012 and 2022. DHIs for improving treatment adherence were categorized as DHIs for sending reminders [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref22">22</xref>], DHIs for monitoring [<xref ref-type="bibr" rid="ref23">23</xref>-<xref ref-type="bibr" rid="ref31">31</xref>], and DHIs for tracking [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref41">41</xref>]. We identified various types of DHIs, including SMS text messaging [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref22">22</xref>], DOT [<xref ref-type="bibr" rid="ref23">23</xref>-<xref ref-type="bibr" rid="ref31">31</xref>], MERMs [<xref ref-type="bibr" rid="ref32">32</xref>-<xref ref-type="bibr" rid="ref37">37</xref>], and mobile apps [<xref ref-type="bibr" rid="ref38">38</xref>-<xref ref-type="bibr" rid="ref41">41</xref>], which improved the effectiveness of self-management, treatment adherence, and the prevention of TB in clinical and community settings.</p><p>A total of 19 studies focused on different types of interventions for reminding patients about treatment adherence and included outcomes such as medication adherence [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref21">21</xref>-<xref ref-type="bibr" rid="ref23">23</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref37">37</xref>,<xref ref-type="bibr" rid="ref41">41</xref>], self-reported survey satisfaction [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref22">22</xref>], and appointment attendance [<xref ref-type="bibr" rid="ref20">20</xref>]. Treatment adherence was primarily accomplished through daily reminder SMS text messages [<xref ref-type="bibr" rid="ref15">15</xref>-<xref ref-type="bibr" rid="ref22">22</xref>] and phone calls [<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref28">28</xref>,<xref ref-type="bibr" rid="ref41">41</xref>] that requested confirmation of adherence. Furthermore, additional reminders were sent to patients for encouragement or motivation [<xref ref-type="bibr" rid="ref15">15</xref>,<xref ref-type="bibr" rid="ref20">20</xref>] if they did not respond within a given time period [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref23">23</xref>,<xref ref-type="bibr" rid="ref28">28</xref>]. Studies also reported sending compliance reminders through daily quizzes [<xref ref-type="bibr" rid="ref18">18</xref>]; sending reinforcement SMS text messages twice weekly for 12 weeks [<xref ref-type="bibr" rid="ref21">21</xref>]; and sending system reminders or additional messages to remind patients about the time of medication use [<xref ref-type="bibr" rid="ref17">17</xref>], confirm daily doses [<xref ref-type="bibr" rid="ref28">28</xref>], notify patients about a consultation service for their upcoming monthly visits [<xref ref-type="bibr" rid="ref32">32</xref>], encourage the use of an app [<xref ref-type="bibr" rid="ref21">21</xref>], and promote self-satisfaction [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref22">22</xref>,<xref ref-type="bibr" rid="ref27">27</xref>]. Rather than demonstrate treatment efficacy, SMS text messaging&#x2013;based reminder interventions increased patient satisfaction [<xref ref-type="bibr" rid="ref17">17</xref>,<xref ref-type="bibr" rid="ref19">19</xref>]. SMS text messaging&#x2013;based digital technology supports and helps patients and health care professionals to enhance health practices and clinical outcomes. An interactive reminder, such as an SMS text message or video conversation, should be developed according to the required medical monitoring process and incorporated into clinical practice.</p><p>Numerous studies have examined the use of DOT to monitor treatment adherence, including 99DOTS [<xref ref-type="bibr" rid="ref28">28</xref>], VOT [<xref ref-type="bibr" rid="ref4">4</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref39">39</xref>], asynchronous VOT [<xref ref-type="bibr" rid="ref30">30</xref>], wireless observation therapy [<xref ref-type="bibr" rid="ref24">24</xref>], and e-DOT [<xref ref-type="bibr" rid="ref40">40</xref>]. DOT also includes treatment regimen monitoring interventions that are based on technology, such as wearable devices [<xref ref-type="bibr" rid="ref23">23</xref>], mHealth apps [<xref ref-type="bibr" rid="ref29">29</xref>], and wireless devices [<xref ref-type="bibr" rid="ref24">24</xref>]. We identified 8 articles that reported e-DOT interventions for TB treatment adherence. Prior studies reported that participants preferred e-DOT over traditional therapy for supporting daily TB medication use during the long-term phase of TB treatment [<xref ref-type="bibr" rid="ref24">24</xref>,<xref ref-type="bibr" rid="ref27">27</xref>,<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>]. e-DOT should be tested in areas with a high risk of TB contraction, as e-DOT could greatly enhance the development of programs for treating the disease in LMICs. In addition, VOT interventions for new TB cases were used in combination with a mobile app [<xref ref-type="bibr" rid="ref26">26</xref>], WeChat (for education and knowledge) [<xref ref-type="bibr" rid="ref39">39</xref>], and treatment follow-up (with a maximum follow-up interval of 6 months). Story et al [<xref ref-type="bibr" rid="ref26">26</xref>] reported that VOT resulted in an 80% medication adherence rate in 2 months when compared to DOT, and Ravenscroft et al [<xref ref-type="bibr" rid="ref29">29</xref>] reported that VOT resulted in about a 45% decrease in nonadherence, which was statistically significant. Further, smartphone-enabled video surveillance of TB therapy has been proven successful and has many advantages over conventional DOT. Wade et al [<xref ref-type="bibr" rid="ref44">44</xref>] found that VOT increased the proportion of observed treatment doses when compared to DOT; however, the effect on the treatment adherence rate was not statistically significant. Thus, audio- and video-based DHIs may be useful in reducing attrition and improving treatment adherence and health outcomes in acute care settings.</p><p>In this review, 4 RCT protocols for MERM-related monitoring interventions were also included [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref33">33</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref36">36</xref>] to obtain data on the methodological pattern of treatment adherence. Most MERMs are designed to ensure drug compliance, such as evriMED500 [<xref ref-type="bibr" rid="ref32">32</xref>,<xref ref-type="bibr" rid="ref33">33</xref>] or evriMED1000 [<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref36">36</xref>]. Maraba et al [<xref ref-type="bibr" rid="ref35">35</xref>] developed an MERM for the daily monitoring of patients and children with drug-susceptible TB during a 6- to 12-month follow-up. Additionally, Ratchakit-Nedsuwan et al [<xref ref-type="bibr" rid="ref34">34</xref>] conducted a clinical trial of an MERM for patients with pulmonary TB for approximately 6 months; a total of 54 doses were delivered over 70 days, and the adherence rate was approximately 90%. Further, Acosta et al [<xref ref-type="bibr" rid="ref37">37</xref>] reported that an MERM was significantly more effective than DOT. Hence, we suggest that further RCTs using MERM-based digital intervention strategies should be conducted to enhance TB treatment adherence and clinical outcomes. Since most outcomes were self-reported, additional trials are recommended to determine the accuracy of MERM system&#x2013;based adherence rates.</p><p>Tracking and guiding patients remain important for the follow-up of treatment adherence in a therapeutic context. We found that 4 smartphone-, mHealth-, and mobile app&#x2013;based digital devices were used to evaluate TB treatment adherence [<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref40">40</xref>,<xref ref-type="bibr" rid="ref41">41</xref>] and acceptability [<xref ref-type="bibr" rid="ref38">38</xref>]. Patients with pulmonary TB who received intervention through the WhatsApp TB@Clicks module (an mHealth-based DHI) were approximately 4.1 times more likely to have favorable treatment results than a control group [<xref ref-type="bibr" rid="ref38">38</xref>]. Another DHI for daily drug tracking resulted in drug adherence rates increasing from 85.5% to 96.4% over time [<xref ref-type="bibr" rid="ref41">41</xref>], and a health-related VOT resulted in decreased nonadherence rates within 4 days [<xref ref-type="bibr" rid="ref29">29</xref>]. Some apps were combined with a mobile-based pillbox system for a second consultation, resulting in satisfaction and confidence among patients [<xref ref-type="bibr" rid="ref34">34</xref>]. These outcomes must be incorporated into future clinical trial designs that adopt trustworthy quantitative methods to determine the relative contribution of each digital health technology component.</p><p>This review&#x2019;s findings revealed that DHIs encouraged self-management among patients with TB and empowered them to participate in collaborative discussions during consultations. However, we found that studies on real-time, conversation-based digital technology are lacking; such technology could improve treatment adherence and foster positive health outcomes in various clinical settings. Due to the rapid development of artificial intelligence technologies, including digital tool kits and generative artificial intelligence, 2-way communication&#x2013;based chatbots in TB treatment may lead to improved self-management in patients with TB.</p></sec><sec id="s4-2"><title>Limitations</title><p>This review had some limitations. First, our review included studies that focused on treatment outcome&#x2013;based interventions rather than health care delivery. Therefore, we did not focus on other details, such as TB prevalence, costs, or health insurance. Second, this study focused on the effects of commonly used DHIs on TB treatment outcomes in clinical and community settings. Further studies should determine how DHIs vary between the two contexts and how they interact with multidomain therapies. Third, this study did not specifically describe treatment adherence and self-management. There are no clear differences between the accurate meaning and measurement of treatment adherence in a clinical trial setting and those of self-management in a clinical or community context, and few studies have attempted to provide answers [<xref ref-type="bibr" rid="ref45">45</xref>-<xref ref-type="bibr" rid="ref47">47</xref>]. Fourth, many of the included studies (13/27, 48%) were conducted in LMICs because of the high prevalence of TB cases, even though high-income nations have a considerable number of studies. This could be attributed to our study&#x2019;s selection criteria, such as our criterion for language. Therefore, additional studies are required to identify DHIs across the entire TB care continuum.</p></sec><sec id="s4-3"><title>Conclusions</title><p>This study examined 27 studies published between 2012 and 2022 and selected the most recent articles. The following three domains were identified from the selected studies: reminding, monitoring, and tracking. The preponderance of treatment adherence was reinforced by mHealth strategies, such as the use of SMS text messaging, mobile apps, mHealth technology, and MERMs. Our findings have implications for TB-related digital health research, which frequently fails to adequately address patients with TB. To preserve treatment adherence and self-care management, patients should have access to real-time, conversation-based interventions (dialogue or communication between patients and health care professionals), such as mobile- or app-based chats, regardless of the restrictions imposed by the COVID-19 pandemic. This scoping review study was conducted before our ongoing chatbot project, which focuses on a mixed methods study on chatbot communication for the treatment adherence of patients with TB. Thus, we emphasize the importance of developing a communication system. DHIs provide several advantages, including improved patient engagement, availability, and accessibility, in addition to lower workloads for practitioners. These results should be considered in the context of national TB control programs and policies to establish a strategy for sustaining TB control and health outcomes. We propose that these developments can significantly improve TB treatment adherence through global collaboration and investment.</p></sec></sec></body><back><ack><p>This study was supported by the Severance Hospital Research Fund for Clinical Excellence Grant (grant number: C-2022-0017).</p></ack><fn-group><fn fn-type="con"><p>YP, JSB, and JS conceived and designed this study and were responsible for the methodology. SL and VR conducted the data extraction. SL, VR, and YP conducted the formal analysis. SL and VR wrote the manuscript. All authors contributed to manuscript revision.</p></fn><fn fn-type="conflict"><p>None declared.</p></fn></fn-group><glossary><title>Abbreviations</title><def-list><def-item><term id="abb1">DHI</term><def><p>digital health intervention</p></def></def-item><def-item><term id="abb2">DOT</term><def><p>directly observed therapy</p></def></def-item><def-item><term id="abb3">e-DOT</term><def><p>electronic directly observed therapy</p></def></def-item><def-item><term id="abb4">LMIC</term><def><p>low- and middle-income country</p></def></def-item><def-item><term id="abb5">MERM</term><def><p>medication event reminder monitor</p></def></def-item><def-item><term id="abb6">mHealth</term><def><p>mobile health</p></def></def-item><def-item><term id="abb7">PRISMA</term><def><p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p></def></def-item><def-item><term id="abb8">RCT</term><def><p>randomized controlled trial</p></def></def-item><def-item><term id="abb9">RoB 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United Kingdom and Moldova).</p><media xlink:href="mhealth_v11i1e49741_app3.png" xlink:title="PNG File, 27 KB"/></supplementary-material><supplementary-material id="app4"><label>Multimedia Appendix 4</label><p>Quality assessment and risk of bias based on the five RoB 2 (Risk of Bias 2) domains. Domain 1: randomization process; domain 2: deviations from intended interventions; domain 3: missing outcome data; domain 4: measurement of the outcome; domain 5: selection of the reported result; domain 6: overall.</p><media xlink:href="mhealth_v11i1e49741_app4.png" xlink:title="PNG File, 80 KB"/></supplementary-material><supplementary-material id="app5"><label>Multimedia Appendix 5</label><p>Quality assessment and risk of bias, by intention-to-treat percentage, based on the five RoB 2 (Risk of Bias 2) domains. Domain 1: randomization process; domain 2: deviations from intended interventions; domain 3: missing outcome data; domain 4: measurement of the outcome; domain 5: selection of the reported result; domain 6: Overall.</p><media xlink:href="mhealth_v11i1e49741_app5.png" xlink:title="PNG File, 19 KB"/></supplementary-material><supplementary-material id="app6"><label>Checklist 1</label><p>PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist.</p><media xlink:href="mhealth_v11i1e49741_app6.docx" xlink:title="DOCX File, 49 KB"/></supplementary-material></app-group></back></article>