The Performance of Digital Technologies for Measuring Tuberculosis Medication Adherence: A Systematic Review
Authors: Zary Miranda , Mohamed Mona Salaheldin , Kafie Cedric , Chilala Chimweta Ian , Bahukudumbi Shruti , Foster Nicola , Gore Genevieve , Fielding Katherine , Subbaraman Ramnath , Schwartzman Kevin 
Published: May 2024

ABSTRACTIntroductionDigital adherence technologies (DATs), such as phone-based technologies, and digital pillboxes, can provide more person-centric approaches to support tuberculosis (TB) medication adherence. We synthesized evidence addressing the performance of DATs for measuring tuberculosis medication adherence.MethodsWe conducted a systematic review (PROSPERO - CRD42022313526) which identified relevant published literature from January 2000 through April 2023 in five databases, and pertinent preprints. Studies reporting quantitative data on the performance of DATs for measuring adherence to medications for TB disease or infection, against a reference standard, with at least 20 participants using the DAT were included. Study characteristics and performance outcomes (e.g., sensitivity, specificity, positive and negative predictive values) were extracted. Article quality was assessed using the QUADAS-2 tool for diagnostic accuracy studies.ResultsOf 5692 studies initially identified by our systematic search, 13 met our inclusion criteria. These studies addressed the performance of medication sleeves with phone calls [branded as “99DDOTS”; N=4], digital pillboxes [N=5], ingestible sensors [N=2], artificial intelligence-based video observed therapy [N=1], and multifunctional mobile applications [N=1]. All but one involved persons with TB disease. For medication sleeves with phone calls, compared to urine analysis, reported sensitivity and specificity was 70-94% and 0-61%, respectively. For digital pillboxes, compared to pill count, reported sensitivity and specificity was 25-99% and 69-100%, respectively. For ingestible sensors, the sensitivity of dose detection was ≥95% in comparison to directly observed ingestion. Participant selection was the most frequent potential source of bias across articles.ConclusionLimited available data suggest suboptimal and variable performance of DATs for dose monitoring, with significant evidence gaps, notably in real-world programmatic settings. Future research should aim to improve understanding of the relationships of specific technologies, settings, user characteristics, and user engagement with DAT performance, and should measure and report performance in a more standardized manner.KEY MESSAGESWhat is already known on this topicSeveral cohort studies have suggested that digital adherence technologies (DATs) can both underestimate and overestimate medication ingestion among persons treated for tuberculosis. No previous review has synthesized available evidence in this regard.What this study addsReports of DAT (medication sleeves with phone calls, digital pillboxes) implementation in real-world treatment settings consistently indicate suboptimal performance for measuring medication adherence. However, available evidence is limited in scope and quality.How this study might affect research, practice, or policySuboptimal dose reporting from DATs potentially compromises their effectiveness, and program efficiency. Future clinical practice will be strengthened by rigorous technology evaluations that reflect more consistent use of reference standards, and clearer benchmarks for medication adherence.