title: Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial.
abstract: Forgetfulness is a major contributor to nonadherence to chronic disease medications and could be addressed with medication reminder devices.
  
  
  
  To compare the effect of 3 low-cost reminder devices on medication adherence.
  
  
  
  This 4-arm, block-randomized clinical trial involved 53 480 enrollees of CVS Caremark, a pharmacy benefit manager, across the United States. Eligible participants were aged 18 to 64 years and taking 1 to 3 oral medications for long-term use. Participants had to be suboptimally adherent to all of their prescribed therapies (with a medication possession ratio of 30% to 80%) in the 12 months before randomization. Participants were stratified on the basis of the medications they were using at randomization: medications for cardiovascular or other nondepression chronic conditions (the chronic disease stratum) and antidepressants (the antidepressant stratum). In each stratum, randomization occurred within blocks defined by whether all of the patient's targeted medications were dosed once daily. Patients were randomized to receive in the mail a pill bottle strip with toggles, digital timer cap, or standard pillbox. The control group received neither notification nor a device. Data were collected from February 12, 2013, through March 21, 2015, and data analyses were on the intention-to-treat population.
  
  
  
  The primary outcome was optimal adherence (medication possession ratio ≥80%) to all eligible medications among patients in the chronic disease stratum during 12 months of follow-up, ascertained using pharmacy claims data. Secondary outcomes included optimal adherence to cardiovascular medications among patients in the chronic disease stratum as well as optimal adherence to antidepressants.
  
  
  
  Of the 53 480 participants, mean (SD) age was 45 (12) years and 56% were female. In the primary analysis, 15.5% of patients in the chronic disease stratum assigned to the standard pillbox, 15.1% assigned to the digital timer cap, 16.3% assigned to the pill bottle strip with toggles, and 15.1% assigned to the control arm were optimally adherent to their prescribed treatments during follow-up. There was no statistically significant difference in the odds of optimal adherence between the control and any of the devices (standard pillbox: odds ratio [OR], 1.03 [95% CI, 0.95-1.13]; digital timer cap: OR, 1.00 [95% CI, 0.92-1.09]; and pill bottle strip with toggles: OR, 0.94 [95% CI, 0.85-1.04]). In direct comparisons, the odds of optimal adherence were higher with a standard pillbox than with the pill bottle strip (OR, 1.10 [95% CI, 1.00-1.21]). Secondary analyses yielded similar results.
  
  
  
  Low-cost reminder devices did not improve adherence among nonadherent patients who were taking up to 3 medications to treat common chronic conditions. The devices may have been more effective if coupled with interventions to ensure consistent use or if targeted to individuals with an even higher risk of nonadherence.
  
  
  
  clinicaltrials.gov Identifier: NCT02015806.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts2Center for Healthcare Delivery Science, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Niteesh K
authors.initials: NK
authors.lastname: Choudhry
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts2Center for Healthcare Delivery Science, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Alexis A
authors.initials: AA
authors.lastname: Krumme
authors.affiliation: CVS Health, Woonsocket, Rhode Island.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Ercole
authors.affiliation: CVS Health, Woonsocket, Rhode Island.
authors.forename: Charmaine
authors.initials: C
authors.lastname: Girdish
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Angela Y
authors.initials: AY
authors.lastname: Tong
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Nazleen F
authors.initials: NF
authors.lastname: Khan
authors.affiliation: CVS Health, Woonsocket, Rhode Island.
authors.forename: Troyen A
authors.initials: TA
authors.lastname: Brennan
authors.affiliation: CVS Health, Woonsocket, Rhode Island.
authors.forename: Olga S
authors.initials: OS
authors.lastname: Matlin
authors.affiliation: CVS Health, Woonsocket, Rhode Island.
authors.forename: William H
authors.initials: WH
authors.lastname: Shrank
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Franklin
mesh_terms: D000293:Adolescent; D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002908:Chronic Disease / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017010:Reminder Systems; D014481:United States; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D000928:Antidepressive Agents