Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial

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Choudhry NK,et al. "Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial". JAMA Internal Medicine. 2017. 177(5):624-631.
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Clinical Question

In poorly adherent patients, would implementing low cost reminder devices, compared to not implementing reminder devices, improve adherence to therapy?

Bottom Line

There is no improvement in adherence by using low-cost reminder devices among poorly adherent patients who were talking up to 3 medications.

Major Points

The goal of this study was to determine if implementing low cost reminder devices improved therapy adherence in patients that were previously determined to be poorly adherent (less than 80% adherent to therapy). Poor adherence can lead to instances of morbidity and mortality that were otherwise avoidable coupled with an increase in health care spending. The most common cause on poor adherence is forgetfulness. In attempts to improve adherence, the study implemented and distributed 3 different tools: pill boxes, pill boxes with toggles, and digital timer caps that provided an auditory alert when it was time for a patient to take their medication. The 53,480 patients across the US included in the trail were taking 1-3 maintenance medications, were 18-64 years of age, and considered to be poorly adherent. They received one of the above devices by mail with a set of instructions. The study was a “pragmatic, block-randomized, controlled, 4-arm comparative effectiveness study” that was analyzed with intention-to-treat parameters. The primary outcome was the medication possession ratio (MPR) as a measure of adherence, analyzed at the 12 month follow-up session. Based on the results, it was concluded that there was no meaningful difference in the adherence of those who received any of the low cost reminder devices compared to those who did not receive any. Overall, this was a well-designed study that was carried out appropriately. However, some of the statistically significant results could have been caused by chance due to the fact that many comparisons were brought to light and many hypothesis tests were conducted. Additionally, several patients lost their insurance coverage throughout the course of the study, which could have contributed to the null results. Their method of determining adherence had proven to be an invalid and inaccurate measure of adherence since patients could potentially stop taking a particular medication in the middle of a fill. This was a poor interpretation based on the fact that there was no differentiation between someone who took a medication as needed or someone who discontinued taking a particular medication. Additionally, individuals could be enrolled in ready fill programs that automatically filled their prescriptions each month. Overall, though, the study was well conducted and analyzed


Guidelines

{no guidelines}

Design

  • a pragmatic, block-randomized, controlled, 4-arm comparative effectiveness study
  • Number of patients randomized: 53,480
  • Experimental arm: 44,600
  • Chronic Disease Stratum: 37,532
  • Antidepressant Stratum: 15,948
  • Standard arm: 8,880
  • Setting: Many households across the US
  • Enrollment: February 12, 2013- March 21, 2015
  • Mean follow-up: 12 months
  • Analysis: Intent-to-treat
  • Primary outcome: adherence using the medication possession ratio (MPR)

Population

Inclusion Criteria

Individuals aged between 18 to 64 years old who:

  • Must have prescription drug benefits administered by CVS Caremark
  • Must have received permission from their plan sponsor to be contacted for this study
  • Must have pharmacy benefit eligibility for 12 months before the start of study
  • Must have filled between 1 and 3 maintenance medications for the treatment of cardiovascular disease, non-depression chronic condition, or depression in the 12 months before the start of the study.
  • Must be identified as suboptimally adherent with a medication possession ratio between 30% and 80%.

Exclusion Criteria

Individuals aged 65 years or older whose primary payer is Medicare Individuals taking more than 3 maintenance medications


Baseline Characteristics

For the Block A participants (with medications dosed once daily), who were assigned a digital timer cap:

  • Number of participants in group: 6,198
  • Mean Age: 48.7
  • % Female: 46.5
  • Income in region: 59,729
  • % Black race in region: 10.4
  • % Participants in a given region of the country:
  • Mid-West: 16.6
  • North-East: 15.3
  • South: 27.5
  • West: 5.6
  • Mean number of targeted medications: 1.4
  • Baseline adherence: 43.9
  • Mean follow-up: 336.5

Potentially clinically relevant differences between the treatment arms included % female within the groups and the participants’ baseline adherence.

Interventions

Study participants were given one of three possible low-cost adherence device interventions. The devices utilized were a pill bottle with an attached strip with toggles that slide out after each dose is taken (Take-n-Slide), a pill bottle cap with a digital timer that displayed the time since the last dose was taken (Rx Timer Cap), and a standard plastic, week-long pillbox.

Outcomes

Primary Outcomes

Primary Outcomes

All CVD and Anti-Depression Maintenance Medications (vs Control)
Stand pillbox vs control: OR, 1.03; 95% CI 0.95 - 1.13
Digital Timer Cap vs control: OR, 1.00; 95% CI 0.92 - 1.09
Pill Bottle Strip with Toggles vs control: OR, 0.94; 95% CI 0.85 - 1.04
All CVD and Anti-Depression Maintenance Medications (Head-to-Head Comparison)
Standard pillbox vs Digital Timer Cap: OR, 1.03, 95% CI 0.96 - 1.11
Standard pillbox vs Pill Bottle Strip with Toggles: OR, 1.10; 95% CI 1.00 - 1.21
Digital Timer Cap vs Bottle Strip with Toggles: OR, 1.05; 95% CI 0.95 - 1.15

Summary of data: None of the data are statistically significant (for either 1. vs control or 2. Head-to-Head Comparison)

Secondary Outcomes

All CVD Medications (vs Control)
Standard pillbox vs Control: OR, 1.03; 95% CI 0.94 - 1.13
Digital Timer Cap vs Control: OR, 1.01; 95% CI 0.92 - 1.11
Pill Bottle Strip with Toggles vs Control: OR, 0.95; 95% CI 0.86 - 1.06
Antidepressants (vs Control)
Standard pillbox vs Digital Timer Cap: OR 1.02, 95% CI 0.89 - 1.18
Standard pillbox vs Pill Bottle Strip with Toggles: OR 0.97; CI 0.84 - 1.11
Digital Timer Cap vs Bottle Strip with Toggles: OR 0.93; CI 0.79 - 1.11
All CVD Medications (Head-to-Head Comparison)
Standard Pillbox vs Digital Timer Cap: OR, 1.02; 95% CI 0.94 - 1.10
Standard Pillbox vs Pill Bottle Strip with Toggles: OR, 1.08; 95% CI 0.98 - 1.19
Digital Timer Cap vs Pill Bottle Strip with Toggles: OR, 1.04; 95% CI 0.94 - 1.43
Antidepressants (Head-to-Head Comparison)
Standard Pillbox vs Digital Timer Cap: OR, 1.14; 95% CI 1.02 - 1.29
Standard Pillbox vs Pill Bottle Strip with Toggles: OR, 1.14; 95% CI 0.97 - 1.33
Digital Timer Cap vs Pill Bottle Strip with Toggles: OR, 1.03; 95% CI 0.88 - 1.21

Summary of the data: None of data but Standard Pillbox vs Digital Timer Cap are statistically significant. According to data, Digital Timer Cap improves adherence of patient’s medication taking in comparison to Standard Pillbox.

Subgroup Analysis

Patient subgroup analysis was performed in terms of patient age, sex, pre-randomization adherence, and number of medications. The clinically significant features included sex with the use of the pill bottle strip with toggles and pre-randomization adherence with the Digital Timer Cap. For the pill bottle with toggles, females (OR 0.86; CI 95% (0.79-0.93)) vs males (OR 0.95; CI 95% (0.90-1.01)) had improved adherence (P value-<.0001). For patients with lower adherence (MPR < 0.55) (OR 0.96; CI 95% (0.90-1.03)) vs higher adherence (MPR > 0.55) (OR 1.07; CI 95% (1.01-1.15)) had significantly increased adherence (P-value .02).


Adverse Events

There were no adverse events associated with any other the interventions.

Criticisms

  • Some of the statistically significant results could have been caused by chance due to the fact that many comparisons were brought to light and many hypothesis tests were conducted.
  • Multiple patients lost their insurance coverage before the adherence devices were mailed out and another group of patients lost their insurance coverage prior to follow-up completion.
  • Medication dispensing data was analyzed to determine adherence. This method had proven to be an invalid and inaccurate measure of adherence since patients could potentially stop taking a particular medication in the middle of a fill. This also was not a good interpretation based on the fact that there was no differentiation between someone who took a medication as needed and someone who discontinued taking a particular medication.
  • Some medications patients were taking are not intended for life-long use.
  • Some patients may have been enrolled in an automatic refill program which fills their prescription automatically every month when their medication runs out.
  • The findings may not be entirely generalizable due to the fact that the elderly population (65+), Medicare-insured, and patients with more complex medication regimens were excluded from this study.

Funding

“This study was supported by an unrestricted grant to Brigham and Women's Hospital from CVS Health.” CVS Health helped point out the participants that met the inclusion criteria and randomization and was responsible for the mailing of study adherence devices.

Further Reading

Choudhry, Niteesh K., et al. “Effect of Reminder Devices on Medication Adherence: The REMIND Randomized Clinical Trial.” JAMA Internal Medicine. 27 Feb. 2017, pp. 624–631. doi:10.1001/jamainternmed.2016.9627.