title: Effectiveness of Electronic Reminders to Improve Medication Adherence in Tuberculosis Patients: A Cluster-Randomised Trial.
abstract: BACKGROUND
  Mobile 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  This study is the first to our knowledge to utilise a randomised trial design to demonstrate the effectiveness of a medication monitor to improve medication adherence in TB patients. Reminders from medication monitors improved medication adherence in TB patients, but text messaging reminders did not. In a setting such as China where universal use of DOT is not feasible, innovative approaches to support patients in adhering to TB treatment, such as this, are needed.
  
  
  BACKGROUND
  Current Controlled Trials, ISRCTN46846388.
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Liu
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lewis
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Jiangsu Province Center for Disease Control and Prevention, Nanjing, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Chongqing Provincial Tuberculosis Dispensary, Chongqing, Chongqing, China.
authors.forename: Shun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Heilongjiang Provincial Tuberculosis Dispensary, Harbin, Heilongjiang, China.
authors.forename: Guilan
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Hunan Provincial Tuberculosis Dispensary, Changsha, Hunan, China.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Bai
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Hongguang
authors.initials: H
authors.lastname: Chen
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Liu
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Chen
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Chi
authors.affiliation: Dafeng County Center for Disease Control and Prevention, Dafeng, Jiangsu, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.affiliation: China Office, Bill & Melinda Gates Foundation, Beijing, China.
authors.forename: Shitong
authors.initials: S
authors.lastname: Huan
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Cheng
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Wang
authors.affiliation: National Center for Tuberculosis Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Jiang
authors.affiliation: China Office, Bill & Melinda Gates Foundation, Beijing, China.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Chin
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Fielding
mesh_terms: D000995:Antitubercular Agents / Q000008:administration & dosage*; D002681:China; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D017010:Reminder Systems; D060145:Text Messaging; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents