Medication Adherence
Conditions
Keywords
adherence, reminders, text messages, SMS, mHealth
Brief summary
The main aim of this phase II proposal is to continue and complete development of a cellular phone-based system that assists patients with their medication adherence. Adherence reports will be developed with feedback from patients and providers. Software for patients to report their four day recall adherence through text messaging or short message service (SMS) or interactive voice response (IVR) will be built. An initial qualitative study will evaluate the adherence reports, 4-day adherence recalls, and inform the development of content for reminder text messages that could be resistant to user fatigue. A redesigned system will be tested through a 3-week longitudinal study of 15 patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS). An intervention module will have an analytics engine to track adherence levels and personalize delivery of reminder messages. A clinic appointment module will perform patient appointment reminders. The final system with these modules will be tested through a 24-week efficacy study. A total of 115 patients and providers will be involved in the three user studies.
Detailed description
The specific study aims are described below: 1. Organize the Design, Evaluation, and Implementation Teams: The development of ARemind will be guided by design, evaluation and implementation teams. The design team will build the software architecture and execute the software development with inputs from the user studies. The evaluation team will prepare the institutional review board (IRB) submissions, develop the qualitative instruments, and analyze the qualitative and quantitative data. The implementation team will guide clinical and commercial design aspects including input on the remote adherence assessments, the intervention and clinic appointment modules, and the commercialization plan. 2. Run first user study as a qualitative assessment of patient and provider preferences of ARemind: A web-based adherence report for providers will be developed. Software modules to assess adherence over the phone through 4-day SMS or IVR recalls will be created along with a protocol for performing phone-based unannounced pill counts. The interfaces will be tested as a part of in-depth qualitative semi-structured interviews with 15 providers and 15 patients to guide the system design. 3. Study the content preferences through a second user study: A new version of ARemind (version 2.0) will be built based on the feedback from the first user study. It will include the three remote adherence assessment modules. It will be tested longitudinally for 3 weeks on 15 patients with HIV/AIDS. The patients will use Medication Event Monitoring System (MEMS) software, in the form of MEMS caps, and have weekly clinic visits with adherence counselors who will generate a composite adherence score at each visit. MEMS caps are electronic devices attached to a pill bottle which detect and record the time at which the bottles are opened and closed, using this as an estimate for the number of pills taken. These will be compared to the adherence scores from the remote adherence assessment modules. The patients will give qualitative feedback at each visit on the reminder messages to guide the design of content resistant to user fatigue. 4. Explore the feasibility of ARemind through a third user study: An intervention module with an analytics engine will be built. It will personalize reminder messages based on adherence levels and facilitate patient phone calls with social workers/adherence counselors when appropriate. A clinic appointment reminder module will be created and interfaced with the health information exchange of Boston Medical Center (BMC). A new version of ARemind (version 3.0) will contain these new modules and content improved based upon the second study. ARemind 3.0 will be tested through a 24-week longitudinal study of 70 patients. Thirty five patients will be randomized to use cell phones with ARemind 3.0 (intervention) while 35 patients will use beepers (control). Patients will use MEMS caps for composite adherence scores that will be done at each of their 9 adherence visits during the study. Analysis of feasibility, efficacy, user-fatigue and cost-savings from improved adherence to medications and clinic appointments will be performed in this aim. NOTE: OF THESE THREE USER STUDIES, THE FIRST TWO ARE CONSIDERED FEASIBILITY STUDIES WHILE THE LAST IS A MORE LONGITUDINAL CLINICAL STUDY. THIS REGISTRATION IN CLINICALTRIALS.GOV DEALS WITH THE THIRD USER STUDY, WHICH IS THE LONGEST, INVOLVES THE MOST PARTICIPANTS, AND DEMONSTRATES THE HIGHEST NUMBER OF INTERVENTIONS.
Interventions
DEVICEBeeper
Beepers are handheld portable devices which can be attached to a belt. At regular intervals corresponding to the participant's preferred reminder time, they buzz for a few minutes or until the participant presses a button to stop the buzzing.
DEVICEARemind
ARemind will personalize reminder messages based on adherence levels and facilitate patient phone calls with social workers/adherence counselors when appropriate. It will also consist of a text-messaging or interactive voice response (IVR) or phone-based pill count remote adherence assessment module.
Sponsors
Boston University
Boston Medical Center
Harvard Medical School (HMS and HSDM)
National Institute of Mental Health (NIMH)
Dimagi Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stable ART (no change of ART for 3 months) * Greater than 18 years of age * Self-report adherence \< 85%
Exclusion criteria
* HIV-infected patients not on ART * Non-English speaking * Dementia (via mini mental status exam) * Incarceration * Legally blind and./or deaf * User of pillboxes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adherence to Anti-retroviral Therapy | Assessed at Baseline and 8 timepoints (every 3 weeks) over 24 weeks. T1 (Baseline), T2 (12 weeks), and T3 (24 weeks) reported here. | MEMS pill caps or boxes will be used to monitor adherence. Each participant will place the drug containing the protease inhibitor, or, if no such drug is being taken, the drug with the highest dosing frequency, inside of a MEMS device, which automatically records each time the pillbox was opened. Participants will bring this to the clinic during their regularly scheduled visits, and those daily measurements will be downloaded to a clinic machine. |
| Self-Report | Assessed at Baseline and 8 timepoints (every 3 weeks) over 24 weeks. T1 (Baseline), T2 (12 weeks), and T3 (24 weeks) reported here. | Participants were asked to recall what pills they took and what they missed. Adherence was measured by self report as well as Wise Pill and pill count. |
| Pill Count | Assessed at Baseline and 8 timepoints (every 3 weeks) over 24 weeks. T1 (Baseline), T2 (12 weeks), and T3 (24 weeks) reported here. | During the clinic visits ever 3 weeks over the course of the study, participants will be asked to bring all their pill bottles and count the contents of each bottle with assistance from the study coordinator. This count will be compared with the refill history for that patient from the pharmacy in order to get a sense of how many pills they have taken. |
Countries
United States
Participant flow
Recruitment details
Patients receiving HIV care at Boston Medical Center were eligible to participate if they were 18+ years of age and prescribed an ART regimen for at least 90 days. Participants were recruited between 2011-2012 during their doctor visit and/or via study flyers in the clinic. Eligibility was confirmed in person or via telephone pre-screening.
Participants by arm
| Arm | Count |
|---|---|
| Beeper (Control) Patients randomized to the control arm (Beeper) will receive the standard of care at each clinic visit. Although the frequency of the study visit is higher than what is observed in standard of care, the subjects will simply asked to bring their HIV medications every 3 weeks (MEMS measure, pill count) and questioned on their adherence to antiretroviral therapy (ART) in the past 7 days. They will not receive any text messages addressing their adherence to ART between each study visit. Their providers will not be receiving any adherence reports but will be asked to assess their adherence at at the start of the trial (Time 1 or T1) and at subsequent clinic visit scheduled according to a frequency defined by standard of care. The decision to restrict the provision of adherence reports to providers and adherence reinforcement messages to intervention group subjects is appropriate, as it is not yet known whether or not the interventions are more effective than the standard of care. | 36 |
| Cell Phone (Intervention) Participants will receive a text message reminder at scheduled intervals, with varying frequency. They will also be subject to a remote adherence assessment, over text messages, interactive voice response (IVR), or a remote pill count with assistance over the phone from a counselor. Those who demonstrate lower adherence rates may receive a call from a counselor.
ARemind: ARemind will personalize reminder messages based on adherence levels and facilitate patient phone calls with social workers/adherence counselors when appropriate. It will also consist of a text-messaging or interactive voice response (IVR) or phone-based pill count remote adherence assessment module. | 30 |
| Total | 66 |
Baseline characteristics
| Characteristic | Beeper (Control) | Cell Phone (Intervention) | Total |
|---|---|---|---|
| Age, Continuous | 48.11 years STANDARD_DEVIATION 10.49 | 46.73 years STANDARD_DEVIATION 9.04 | 47.48 years STANDARD_DEVIATION 9.81 |
| Baseline CD4 (per mm3) | 523.5 cells/mm^3 | 600 cells/mm^3 | 554.5 cells/mm^3 |
| Baseline Viral Load | 20.0 copies/mL | 23.5 copies/mL | 20.0 copies/mL |
| Country of Birth Another Country | 1 Participants | 5 Participants | 6 Participants |
| Country of Birth United States | 28 Participants | 22 Participants | 50 Participants |
| Country of Birth US Territory | 7 Participants | 3 Participants | 10 Participants |
| Education High School or Less | 21 Participants | 20 Participants | 41 Participants |
| Education More than High School | 15 Participants | 10 Participants | 25 Participants |
| Employment Employed | 6 Participants | 9 Participants | 15 Participants |
| Employment Unemployed | 30 Participants | 21 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 3 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 27 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Living Homeless | 0 Participants | 3 Participants | 3 Participants |
| Living Not homeless | 36 Participants | 27 Participants | 63 Participants |
| Primary Language English | 35 Participants | 28 Participants | 63 Participants |
| Primary Language Non-English | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black | 18 Participants | 21 Participants | 39 Participants |
| Race/Ethnicity, Customized Other | 11 Participants | 4 Participants | 15 Participants |
| Race/Ethnicity, Customized White | 7 Participants | 5 Participants | 12 Participants |
| Relationship Married | 2 Participants | 3 Participants | 5 Participants |
| Relationship Not married | 34 Participants | 27 Participants | 61 Participants |
| Sex: Female, Male Female | 9 Participants | 13 Participants | 22 Participants |
| Sex: Female, Male Male | 27 Participants | 17 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 36 | 0 / 30 |
| serious Total, serious adverse events | 0 / 36 | 0 / 30 |
Outcome results
Primary
Adherence to Anti-retroviral Therapy
MEMS pill caps or boxes will be used to monitor adherence. Each participant will place the drug containing the protease inhibitor, or, if no such drug is being taken, the drug with the highest dosing frequency, inside of a MEMS device, which automatically records each time the pillbox was opened. Participants will bring this to the clinic during their regularly scheduled visits, and those daily measurements will be downloaded to a clinic machine.
Time frame: Assessed at Baseline and 8 timepoints (every 3 weeks) over 24 weeks. T1 (Baseline), T2 (12 weeks), and T3 (24 weeks) reported here.
Population: A total of 66 Boston Medical Center HIV-positive patients participated in this study. All patients in the study had stable ART prior to enrollment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Beeper (Control) | Adherence to Anti-retroviral Therapy | T1 | 0.69 proportion adherence | Standard Deviation 0.28 |
| Beeper (Control) | Adherence to Anti-retroviral Therapy | T2 | 0.62 proportion adherence | Standard Deviation 0.27 |
| Beeper (Control) | Adherence to Anti-retroviral Therapy | T3 | 0.5 proportion adherence | Standard Deviation 0.3 |
| Cell Phone (Intervention) | Adherence to Anti-retroviral Therapy | T1 | 0.73 proportion adherence | Standard Deviation 0.25 |
| Cell Phone (Intervention) | Adherence to Anti-retroviral Therapy | T2 | .67 proportion adherence | Standard Deviation 0.24 |
| Cell Phone (Intervention) | Adherence to Anti-retroviral Therapy | T3 | .64 proportion adherence | Standard Deviation 0.26 |
Primary
Pill Count
During the clinic visits ever 3 weeks over the course of the study, participants will be asked to bring all their pill bottles and count the contents of each bottle with assistance from the study coordinator. This count will be compared with the refill history for that patient from the pharmacy in order to get a sense of how many pills they have taken.
Time frame: Assessed at Baseline and 8 timepoints (every 3 weeks) over 24 weeks. T1 (Baseline), T2 (12 weeks), and T3 (24 weeks) reported here.
Population: A total of 66 Boston Medical Center HIV-positive patients participated in this study. All patients in the study had stable ART prior to enrollment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Beeper (Control) | Pill Count | T1 | .59 proportion of pills taken as scheduled | Standard Deviation 0.34 |
| Beeper (Control) | Pill Count | T2 | .62 proportion of pills taken as scheduled | Standard Deviation 0.22 |
| Beeper (Control) | Pill Count | T3 | .58 proportion of pills taken as scheduled | Standard Deviation 0.24 |
| Cell Phone (Intervention) | Pill Count | T1 | .66 proportion of pills taken as scheduled | Standard Deviation 0.41 |
| Cell Phone (Intervention) | Pill Count | T2 | .6 proportion of pills taken as scheduled | Standard Deviation 0.24 |
| Cell Phone (Intervention) | Pill Count | T3 | .62 proportion of pills taken as scheduled | Standard Deviation 0.25 |
Primary
Self-Report
Participants were asked to recall what pills they took and what they missed. Adherence was measured by self report as well as Wise Pill and pill count.
Time frame: Assessed at Baseline and 8 timepoints (every 3 weeks) over 24 weeks. T1 (Baseline), T2 (12 weeks), and T3 (24 weeks) reported here.
Population: A total of 66 Boston Medical Center HIV-positive patients participated in this study. All patients in the study had stable ART prior to enrollment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Beeper (Control) | Self-Report | T1 | .93 proportion of 7-day adherence | Standard Deviation 0.1 |
| Beeper (Control) | Self-Report | T2 | .95 proportion of 7-day adherence | Standard Deviation 0.07 |
| Beeper (Control) | Self-Report | T3 | .93 proportion of 7-day adherence | Standard Deviation 0.1 |
| Cell Phone (Intervention) | Self-Report | T1 | .95 proportion of 7-day adherence | Standard Deviation 0.07 |
| Cell Phone (Intervention) | Self-Report | T2 | .95 proportion of 7-day adherence | Standard Deviation 0.07 |
| Cell Phone (Intervention) | Self-Report | T3 | .95 proportion of 7-day adherence | Standard Deviation 0.06 |