The impact of digital adherence technologies on health outcomes in tuberculosis: A systematic review and meta-analysis

BackgroundSuboptimal 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. MethodsWe searched MEDLINE, Embase, CENTRAL, CINAHL, Web of Science and preprints from medRxiv, Europe PMC, and clinicaltrials.gov 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. ResultsSeventy 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. ConclusionCertain 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.