Effectiveness of Electronic Reminders to Improve Medication Adherence in Tuberculosis Patients: A Cluster-Randomised Trial

Abstract

BackgroundMobile text messaging and medication monitors (medication monitor boxes) have the potential to improve adherence to tuberculosis (TB) treatment and reduce the need for directly observed treatment (DOT), but to our knowledge they have not been properly evaluated in TB patients. We assessed the effectiveness of text messaging and medication monitors to improve medication adherence in TB patients.Methods and FindingsIn a pragmatic cluster-randomised trial, 36 districts/counties (each with at least 300 active pulmonary TB patients registered in 2009) within the provinces of Heilongjiang, Jiangsu, Hunan, and Chongqing, China, were randomised using stratification and restriction to one of four case-management approaches in which patients received reminders via text messages, a medication monitor, combined, or neither (control). Patients in the intervention arms received reminders to take their drugs and reminders for monthly follow-up visits, and the managing doctor was recommended to switch patients with adherence problems to more intensive management or DOT. In all arms, patients took medications out of a medication monitor box, which recorded when the box was opened, but the box gave reminders only in the medication monitor and combined arms. Patients were followed up for 6 mo. The primary endpoint was the percentage of patient-months on TB treatment where at least 20% of doses were missed as measured by pill count and failure to open the medication monitor box. Secondary endpoints included additional adherence and standard treatment outcome measures. Interventions were not masked to study staff and patients. From 1 June 2011 to 7 March 2012, 4,292 new pulmonary TB patients were enrolled across the 36 clusters. A total of 119 patients (by arm: 33 control, 33 text messaging, 23 medication monitor, 30 combined) withdrew from the study in the first month because they were reassessed as not having TB by their managing doctor (61 patients) or were switched to a different treatment model because of hospitalisation or travel (58 patients), leaving 4,173 TB patients (by arm: 1,104 control, 1,008 text messaging, 997 medication monitor, 1,064 combined). The cluster geometric mean of the percentage of patient-months on TB treatment where at least 20% of doses were missed was 29.9% in the control arm; in comparison, this percentage was 27.3% in the text messaging arm (adjusted mean ratio [aMR] 0.94, 95% CI 0.71, 1.24), 17.0% in the medication monitor arm (aMR 0.58, 95% CI 0.42, 0.79), and 13.9% in the combined arm (aMR 0.49, 95% CI 0.27, 0.88). Patient loss to follow-up was lower in the text messaging arm than the control arm (aMR 0.42, 95% CI 0.18–0.98). Equipment malfunction or operation error was reported in all study arms. Analyses separating patients with and without medication monitor problems did not change the results. Initiation of intensive management was underutilised.ConclusionsThis study is the first to our knowledge to utilise a randomised trial design to demonstrate the effectiveness of a medication mon...

Improving antiretroviral therapy adherence in resource‐limited settings at scale: a discussion of interventions and recommendations

“…None of these EDM studies was powered to assess viral suppression. Additionally, a recent fourarm study using a mix of EDM and SMS for individuals receiving tuberculosis treatment in China found a reduction in incomplete adherence using a combined EDM-SMS approach, but no effect from SMS alone [107].…”

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“…Recently, a limited cluster randomized trial in China found that, while medication monitor reminders led to improved drug compliance for tuberculosis patients, daily two-way SMS reminders did not [18]. Our effectiveness trial gauged the impact of a two-way interactive SMS medication reminder system (Zindagi SMS) on the treatment success of people with drug-sensitive tuberculosis.…”

Harnessing the Potential of Emerging Digital Health and Biological Sampling Technologies for Clinical Drug Development: Promise to Reality

“…In a recent randomized trial of 4,173 tuberculosis patients, text messaging reminders did not significantly improve medication adherence in tuberculosis patients, but smart packaging or smart packaging with reminders did. In the control arm, 29.9% of patients missed at least 20% of doses, while 27.3% and 17.0% and 13.9% missed the same amount of doses in the text reminder, smart packaging, and combined arms, respectively . However, other clinical studies and meta‐analyses have indicated that text message reminders and related digital health apps can increase medication adherence …”

“…In the control arm, 29.9% of patients missed at least 20% of doses, while 27.3% and 17.0% and 13.9% missed the same amount of doses in the text reminder, smart packaging, and combined arms, respectively. 22 However, other clinical studies and meta-analyses have indicated that text message reminders and related digital health apps can increase medication adherence. [23][24][25][26] While a variety of options are emerging for nonpaper-based adherence technologies, additional work is needed cross-industry to understanding their pros/cons for greater implementation.…”