The Impact of Digital Adherence Technologies on Health Outcomes in Tuberculosis: A Systematic Review and Meta-Analysis

Background Suboptimal tuberculosis (TB) treatment adherence may lead to unsuccessful treatment and relapse. Digital adherence technologies (DATs) may allow more person-centric approaches for supporting treatment. We conducted a systematic review (PROSPERO-CRD42022313166) to evaluate the impact of DATs on health outcomes in TB. Methods We searched MEDLINE, Embase, CENTRAL, CINAHL, Web of Science and preprints from medRxiv, Europe PMC, and [clinicaltrials.gov][1] for relevant literature from January 2000 to April 2023. We considered experimental or cohort studies reporting quantitative comparisons of clinical outcomes between a DAT and the standard of care in each setting. Results Seventy studies (total 58,950 participants) met inclusion criteria. They reported SMS-based interventions (k=18 studies), feature phone-based interventions (k=7), medication sleeves with phone calls (branded as “99DOTS,” k=5), video-observed therapy (VOT; k=17), smartphone-based interventions (k=5), digital pillboxes (k=18), ingestible sensors (k=1), and interventions combining 2 DATs (k=1). Overall, the use of DATs was associated with more frequent treatment success in TB disease (OR = 1.18 [1.06, 1.33]; I2 = 66%, k = 46), a decrease in loss to follow up (OR = 0.71 [0.53, 0.94]; I2 = 80%, k = 36) and an increase in adverse event reporting (OR = 1.53 [1.26, 1.86]; I2 = 0%, k = 9). VOT was associated with an increased likelihood of treatment success in TB disease (OR 1.54 [1.09; 2.19]; I2 = 0%, k = 8) and treatment completion in TB infection (OR 4.69 [2.08; 10.55]; I2 = 0%, k = 2) as well as an increased frequency of adverse event reporting (OR = 1.79 [1.27; 2.52]; I2 = 34%, k = 4). Other interventions involving smartphone technologies were associated with increased treatment success in TB disease (OR 1.98 [1.07; 3.65]; I2 =56%, k = 5) and a decreased frequency of loss to follow up (OR = 0.31 [0.13; 0.77]; I2 = 36%, k = 5). Digital pillboxes were also associated with an improvement in treatment success (OR = 1.32 [1.00; 1.73]; I2 = 71%, k = 11). However, improved treatment success was only seen in high- and upper middle-income countries. SMS-based interventions, feature-phone interventions and 99DOTS were not associated with improvements in short-term clinical outcomes. Conclusion Certain DATs--notably VOT and smartphone-based interventions, in higher income settings and sometimes combined with other supportive measures—may be associated with improvements in treatment success and losses to follow-up, compared to standard care. However, evidence remains highly variable, and generalizability limited. Higher quality data are needed. ### Competing Interest Statement This review was supported by a grant from the Bill and Melinda Gates Foundation (grant INV-038215). Competing Interests: Dr. Kevin Schwartzman reports research funding from the Canadian Institutes of Health Research. He has also served as chair of the Data Safety and Monitoring Board for a COVID-19 therapeutic investigated by Laurent Pharmaceuticals. ### Clinical Protocols ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This is a systematic review and aggregate meta-analysis of publicly available data no IRB review required. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][2]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Most relevant information is within the Supporting Information files. However, all raw data and instruments will be posted publicly on the McGill International TB Centre website following acceptance for publication. [1]: http://clinicaltrials.gov [2]: http://ClinicalTrials.gov