Digital Health Interventions to Enhance Tuberculosis Treatment Adherence: Scoping Review

Background: 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). Objective: 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. Methods: We conducted a literature search in the PubMed, Cochrane Library, Ovid Embase


Introduction
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 [1].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 [2].
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 [3], directly observed therapy (DOT) [3][4][5], video calls, phone call reminders [5,6], and web-based reports [3][4][5][6][7].Studies have reported satisfaction [6][7][8], accuracy [6][7][8], acceptable uptake [5,7,8], improved drug adherence [3][4][5]7,9], higher rates of treatment success [5,7,8], and user acceptance [7][8][9][10] with regard to DHIs in TB management.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.

Methods
We followed Arksey and O'Malley's [11] 5-stage scoping review framework, the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement [12], and the Joanna Briggs Institute protocol [13].

Identifying the Relevant Studies
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: ("Tuberculosis" OR "TB" OR "Tuberculosis infection") AND ("RCT" OR "Randomized controlled trial" OR "Experimental study") AND ("Behavior therapy" OR "Cognitive behavioral treatment" OR "Digital intervention" OR "Digital therapeutics" OR "Appbased" OR "Web-based" OR "mHealth" OR "uHealth") AND ("treatment adherence" OR "medication adherence" OR "selfcare" OR "Management" OR "Persistence" OR "Compliance").The search terms and strategies are presented in Multimedia Appendix 1.

Eligibility and Exclusion Criteria
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.

Study Selection and Data Synthesis
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.
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.
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.

Quality Assessment and Risk of Bias
Two independent reviewers (SL and YP) evaluated the risk of bias as part of the quality assessment, using the Cochrane Collaboration's tool for assessing the risk of bias (RoB 2 [Risk of Bias 2]; version: August 9, 2019) [14].The risk of bias was assessed based on 5 domains, and bias scores were assigned ("low risk," "some concern," or "high risk").

Search Results
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 (Figure 1).

Components of the DHIs and Outcomes
Table 2 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 [15][16][17][18][19][20][21][22], (2) monitoring treatment adherence by using digital technology [23][24][25][26][27][28][29][30][31], and (3) tracking treatment adherence through the use of mobile apps and mobile health (mHealth) technology [38][39][40][41] via treatment adherence [42] and modified behavior adherence [43] models.Figure 3 presents a modified adherence model.Adherence to tuberculosis treatment is a repeated and ongoing self-management behavior.In this figure, reminding refers to reminding patients to take medications as prescribed (ie, correct dose, frequency, and time), monitoring 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 tracking refers to following patients over time to determine whether they taking medications as prescribed [43].

Quality Assessment of the Selected Articles
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 [17,20,24,26,27,29,31,37]. The risk of bias results are shown in Multimedia Appendix 4 [17,20,24,26,27,29,31,37] and Multimedia Appendix 5.
A total of 19 studies focused on different types of interventions for reminding patients about treatment adherence and included outcomes such as medication adherence [16,[21][22][23]29,33,35,37,41], self-reported survey satisfaction [17,20,22], and appointment attendance [20].Treatment adherence was primarily accomplished through daily reminder SMS text messages [15][16][17][18][19][20][21][22] and phone calls [22,27,28,41] that requested confirmation of adherence.Furthermore, additional reminders were sent to patients for encouragement or motivation [15,20] if they did not respond within a given time period [16,17,23,28].Studies also reported sending compliance reminders through daily quizzes [18]; sending reinforcement SMS text messages twice weekly for 12 weeks [21]; and sending system reminders or additional messages to remind patients about the time of medication use [17], confirm daily doses [28], notify patients about a consultation service for their upcoming monthly visits [32], encourage the use of an app [21], and promote self-satisfaction [17,20,22,27].Rather than demonstrate treatment efficacy, SMS text messaging-based reminder interventions increased patient satisfaction [17,19].SMS text messaging-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.
Numerous studies have examined the use of DOT to monitor treatment adherence, including 99DOTS [28], VOT [4,29,39], asynchronous VOT [30], wireless observation therapy [24], and e-DOT [40].DOT also includes treatment regimen monitoring interventions that are based on technology, such as wearable devices [23], mHealth apps [29], and wireless devices [24].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 [24,27,29,30].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 [26], WeChat (for education and knowledge) [39], and treatment follow-up (with a maximum follow-up interval of 6 months).Story et al [26] reported that VOT resulted in an 80% medication adherence rate in 2 months when compared to DOT, and Ravenscroft et al [29] 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 [44] 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, audioand video-based DHIs may be useful in reducing attrition and improving treatment adherence and health outcomes in acute care settings.
In this review, 4 RCT protocols for MERM-related monitoring interventions were also included [32,33,35,36] to obtain data on the methodological pattern of treatment adherence.Most MERMs are designed to ensure drug compliance, such as evriMED500 [32,33] or evriMED1000 [35,36].Maraba et al [35] developed an MERM for the daily monitoring of patients and children with drug-susceptible TB during a 6-to 12-month follow-up.Additionally, et al [34] 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 [37] 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-based adherence rates.
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-based digital devices were used to evaluate TB treatment adherence [34,40,41] and acceptability [38].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 [38].Another DHI for daily drug tracking resulted in drug adherence rates increasing from 85.5% to 96.4% over time [41], and a health-related VOT resulted in decreased nonadherence rates within 4 days [29].Some apps were combined with a mobile-based pillbox system for a second consultation, resulting in satisfaction and confidence among patients [34].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.This review'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-based chatbots in TB treatment may lead to improved self-management in patients with TB.

Limitations
This review had some limitations.First, our review included studies that focused on treatment outcome-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 [45][46][47].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's selection criteria, such as our criterion for language.Therefore, additional studies are required to identify DHIs across the entire TB care continuum.

Conclusions
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.

Figure 1 .
Figure 1.PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram for selection of articles.RCT: randomized controlled trial.

Figure 2 .
Figure 2. 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.

Figure 3 .
Figure 3.Adherence to tuberculosis treatment is a repeated and ongoing self-management behavior.In this figure, reminding refers to reminding patients to take medications as prescribed (ie, correct dose, frequency, and time), monitoring 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 tracking refers to following patients over time to determine whether they taking medications as prescribed[43].

Table 1 .
Description of digital health technology tuberculosis (TB) interventions and related outcomes.
a LFU: loss to follow-up.bCompliancenotifications (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).c Cured, treatment completed, treatment failed, died, lost to follow-up, not evaluated, or treatment success.d WHO: World Health Organization.e ACTG: AIDS Clinical Trial Group adherence questionnaire.f VAS: visual analog scale.g e-DOT: electronic directly observed therapy.h MGLS: Morisky, Green, and Levine Adherence Scale.i Until TB treatment completion.j DOT: directly observed therapy.k Completed 20 medication doses using 1 DOT method, then switched methods for another 20 doses.l MERM: medication event reminder monitor.m mHealth: mobile health.n Smartphone mobile app.o N/A: not applicable.p DOT for a minimum period of 30 d and a maximum of 90 d.
a DOT: directly observed therapy.b e-DOT: electronic directly observed therapy.c VOT: video observation therapy.d WOT: wireless observation therapy.e MERM: medication event reminder monitor.f mHealth: mobile health.