The Influence of a Medication Adherence Smartphone Application on Medication Adherence in Chronic Illness
Phase: NA
Conditions: Medication Adherence, Self Efficacy
Sponsor: Vanderbilt University

Title: The Influence of a Medication Adherence Smartphone Application on 
Medication Adherence in Chronic Illness 
NCT #: 05098743 
Date of Protocol and Statistical Analysis Plan: 12/03/2021

Protocol for Dissertation Study 
Christa E. Hartch 
Version: 12-3-2021 
1 
Study Protocol: 
A) RECRUITMENT : The principal investigator (PI) will use the following recruitment strategies:
in-person recruitment and clinician referral through use of the study flyer/referral form.
In-person recruitment: The PI will be present at the health center(s) on multiple days/week when health 
care providers (HCPs) and clinic staff see patients. The PI will work closely with HCPs and clinic staff to 
identify eligible patients and to how/when best approach eligible patients to introduce them to the 
study, anticipating it might be at the end of the visit in the exam room. The HCPs and clinic staff will 
introduce the PI to potentially eligible patients to introduce the study prior to the PI approaching the 
patient. Once the patient expresses interest in learning more about the study or indicates they would 
like to participate, the PI will follow the procedures as outlined in the study procedure section below. 
Eligibility: 1) adults aged 18 years and older 2) speak and understand English 3) personally own and use 
an Android or iOS smartphone which is capable of downloading the Medisafe app and 
4) take at least 1 medication for a chronic illness based on their computerized medical record at the
health center.
Clinician referral: Study flyer/referral forms will be available in the patient exam rooms and/or 
in the medicine department’s clinician office as determined/approved by clinic staff.  Once a 
clinician identifies a potentially eligible patient, they or the patient may complete the study 
flyer/referral form. If the PI is present at the clinic, the form can be given directly to the PI.  If 
the PI is not available, they will place it in a locked and secured collection box labeled 
“Smartphone App Study” only accessible by the PI. The box will be located in the general 
medicine department’s clinician office or the appropriate exam rooms or as otherwise deemed 
necessary by clinic staff. The box will be checked, and forms collected at least once a week by 
the PI. Any patients who fill out a form will be contacted via their preferred method i.e., phone 
call, email or text message (see scripts for a phone call, email or text message) within one week 
by the PI.   
Study flyer/referral form: Study flyers/referral forms will provide study information and a place 
for patients interested in participation to provide their contact information as well as a space 
for the referring HCP signature to confirm that the patient’s medications listed in the Electronic 
Medical Record are correct and up-to-date. The flyers will be kept in exam rooms deemed 
appropriate by clinic staff and will be returned to the HCP. The HCP will then either give them 
to the PI or place them in a secured collection box labeled “Smartphone App Study” which will 
only be accessible to the PI. The box will be checked at least once a week, and forms will be 
collected at that time by the PI.  
B) STUDY PROCEDURES:
Once patients are contacted, the completed flyer/referral forms will be placed in a locked file 
cabinet at the clinic accessible to only the PI. The patient’s name, contact information and 
preferred mode of contact will be housed in REDCap, a HIPAA compliant, password protected 
database application.  

Protocol for Dissertation Study 
Christa E. Hartch 
Version: 12-3-2021 
 
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For patients who are available in-person: If a patient expresses interest in participating, the PI 
will meet with the patient in a private room at the clinic to confirm eligibility, describe the 
study, answer questions and, based on patient preference, obtain e-consent using an iPad or a 
hard copy of the consent form. Once the patient is consented, the PI will obtain a printed-out 
copy of the patient’s updated, current medication list from the EMR. The medication list will be 
reviewed by the PI to confirm that the patient regularly takes at least 1 prescribed medication 
for a chronic illness. Based on patient preference, the PI will then either give them a hard copy 
of the survey, or direct them to the REDCap survey on the PI’s iPad. While patients complete 
the survey, the PI will remain in the room to be available should questions arise, but will be 
distanced away from the patient.  
 
For patients whose completed flyer/referral form is collected from the lock box:   
Once the PI contacts patients and they indicated an interest to participate, the PI will obtain 
their permission to email them the link to the IRB approved econsent form, which will be 
followed by the REDCap survey, if they prefer this method. If they prefer scheduling a time to 
complete this at the clinic, a time will be arranged.  
 
Informed consent: For eligible patients interested in participation, the PI will obtain either in-
person written consent or in-person IRB-approved e-consent via REDCap on an iPad. If the 
patient is not present in the clinic and would like to receive the IRB approved e-consent form 
via email, the patient will be sent an email link to the REDCap e-consent survey to access study 
information. Hard copies of consent forms will be kept in the locked file cabinet. 
 
C) DATA COLLECTION METHODS:  
 
1.) Survey  
 
a)Baseline Data Collection (Time 1): Survey (both intervention and waitlist control groups): Once 
consent is obtained, the PI will administer the baseline questionnaire as either a hard copy 
survey or the REDCap electronic survey on a password protected iPad if the patient prefers. The 
patient will complete the baseline questionnaire independently, unless they ask for the PI to 
assist, in which case the PI will read each question to the patient with the patient indicating 
their answer on either the iPad or the hard copy survey. Only if the patient requests that the PI 
indicate their responses on the survey will the PI fill out the questionnaire for the patient. The 
PI will be present to answer any questions patients may have during data collection.  
 
Hard copy surveys: The completed hard copy surveys will be kept in a locked file cabinet 
at the health center. All hard copy surveys will be assigned the unique study identifier (REDCap 
ID) and any patient identifiers will be removed / blacked out prior to storage. The PI will enter 
data collected using hard copy surveys once into the main REDCap database and into a second 
REDCap database to enhance data integrity by allowing for a comparison of the data entered, 
to identify inconsistencies between the two databases and to verify the correct data points by 
reviewing the hard copy surveys. This will be done prior to data analysis commencing.   

Protocol for Dissertation Study 
Christa E. Hartch 
Version: 12-3-2021 
 
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REDCap surveys: As described earlier, patients might access the survey and complete 
consent and the study measures by using the REDCap survey link. If patients have not 
responded to the initial patient contact and completed the consent and survey within 2 weeks, 
two reminders will be sent by phone, email, or text messaging. 
 
b). Follow-up Questionnaire (Time 2):  
After one month, the patient will receive a follow-up survey via REDCap consisting of the study 
measures. Patients might also choose to  set up an appointment with the PI to meet them at 
the health center to complete the questionnaire via iPad or hard-copy questionnaire. 
Additionally, they may choose to complete this survey as a paper copy and return it to the PI in 
a return stamped envelope the PI will provide to the patient. The PI can also call the patient by 
telephone, read the questions aloud and record their answers within REDCap on the PI’s iPad. 
Lastly, the PI will also consider meeting the patient at a public location if the patient prefers. 
These additional follow-up surveys will be kept in a locked file cabinet at the health center 
along with the other study documents which will only be accessible to the PI.  If patients have 
not completed the follow-up survey within 10 days of the one-month follow-up date, two 
reminders will be sent by phone, email, or text messaging. 
 
Once patient recruitment ceases, the survey will be closed. The de-identified data will be 
downloaded from REDCap and stored on a password protected computer. Dr. Mary Dietrich, 
the PI, and Dr. Stolldorf (faculty advisor) will be the only persons with access to the data. The 
data will be cleaned and prepared for data analysis.  
 
Patient incentives: At the completion of the baseline survey and app set up for intervention 
group patients and baseline survey and review of medication list for wait-list control patients, 
both groups will be given a $25.00 gift card to compensate them for their time and effort in 
reviewing the medication list, using the app, entering key information and completing the 
surveys. Upon completion of the follow-up survey, both intervention group and wait-list control 
patients will receive an additional $35.00 gift card for their time. 
 
Survey Study Measures: 
Patients will complete two surveys, representing medication and refill adherence and self-
efficacy for appropriate medication use, medication knowledge and medication social support 
and the first will also gather demographic information. At the end of the study, the follow-up 
survey will gather information regarding the patient’s feedback regarding the smartphone app 
or use of the printed out medication list. These surveys will take approximately five to ten 
minutes to complete.  
1. Medication and Refill Adherence: Patients will complete the Adherence to Refills and 
Medications Scale (ARMS) to measure both medication and refill adherence. The ARMS is a 
global (continuous) 12-item scale, with a possible score of 12-48, patients with low ARMS 
scores indicate better adherence, it is valid and reliable in a low-literacy chronic disease 
population. Subscales include taking medications as prescribed (8 items) and refilling 

Protocol for Dissertation Study 
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Version: 12-3-2021 
 
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medications on schedule (4 items). Responses range from 1 (none) to 4 (all of the time). Overall 
internal consistency has been established at Cronbach’s alpha = 0.814.  
2. Self-efficacy for Appropriate Medication Use: Patients will complete the Self-efficacy for 
Appropriate Medication Use Scale (SEAMS) to measure self-efficacy for medication adherence. 
It is a global (continuous) 13-item scale, with a possible score of 13-39. Patients with higher 
scores indicate higher levels of self-efficacy for medication adherence. It is valid and reliable in 
low-literacy chronic disease populations. Patients are asked their level of confidence about 
taking medications correctly. Responses range from 1 (not confident) to 3 (very confident). 
Overall internal consistency has been established at Cronbach’s alpha = 0.89.  
3. Medication Knowledge: Patients will complete the Okere-Renier Survey Medication 
Knowledge Subscale to measure medication knowledge. It is a global (continuous) 5-item scale 
with responses ranging from (1) strongly disagree to (5) strongly agree. A mean score is then 
calculated. Scores range from 5-25 with higher scores indicating greater medication knowledge. 
Overall internal consistency has been established at Cronbach's alpha = 0.83. 
4. Medication Social Support: The measurement named Social Support: Medication-specific, 
consists of 8 items ranging from (0) never to (4) very often. It is a continuous measure, and a 
mean score is calculated. Higher scores reflect more medication support. Overall internal 
consistency has been established at Cronbach's alpha = 0.92.  
5. Intervention process (intervention group only): Feedback about the smartphone app and 
additional features as well as an open-ended question will be a part of the second survey to 
ascertain opportunities and challenges of using the smartphone app and describe aspects of the 
app, they found most useful and least useful. Survey questions were developed and tested 
specifically for this purpose during the pilot study for use in this RCT. Patients will be asked if 
they plan to continue using the app after study completion. 
6. Hard copy medication list (wait list control group only): Feedback about the usefulness of 
the hard copy medication list will be obtained at the end of the study.  
 
 2.) Chart Extraction:   
The medication list from the patient’s EMR will be provided by the patient. This printed-out 
medication list will be used to a) obtain name, medical record number (MRN) and date of birth 
(DOB) to establish identity and be validated by the patient and b) to confirm with the patient 
medications to be entered into the app. If there are any discrepancies between what the 
patient says they are taking and what is listed on their medication list, the PI will consult with 
the patient directly. All identifying information on the printed-out copy of the medication list 
will be blacked out and replaced by the patient’s REDCap Record ID. The medication list and the 
flyer/referral form will be kept in a locked file cabinet in the health center.  
 
3.) Behavioral Observation: 
While the patients are entering their medication information, the PI will be observing and 
recording on a checklist developed by the PI for this purpose the following: a) if the patient had 
difficulty visualizing the app; b) if they had difficulty with dexterity while using the app, and c) 
how many times the patient's input of medications needed to be corrected when entering their 
medications. The length of time from starting to download the app to completing set-up and 

Protocol for Dissertation Study 
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Version: 12-3-2021 
 
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reviewing the app will also be recorded. The observation will occur once and will be recorded 
on a checklist by the PI while the patient is setting up the app with the help of the PI. 
 
D) RANDOMIZATION  
Once patients complete the baseline survey, patients will be randomized within each site to 
help reduce the likelihood of site bias. Patients will be randomized to either a wait list control 
group or the app intervention group. Randomization will be done by the PI automatically 
through REDCap. Intervention group patients will use the medication adherence app for 1-
month and wait-list control group patients will receive a printed out copy of their medication 
list and have the name, dose, frequency and indication for their medications reviewed verbally 
with them by the PI. Both the intervention and wait-list control group will be contacted within 
the first week of enrolling in the study to see if they have any questions regarding the app or 
their medications in the case of the wait-list control. The follow-up measures will be completed 
by study patients in both the intervention and the wait-list control groups. At study completion, 
those randomized to the wait-list control group will be offered assistance by the PI to set up 
and use the app.   
 
 
E) INTERVENTION  
1.Intervention Group: The PI will assist the patient to download and set up the free Medisafe 
app on their smartphone at the clinic. The PI will use a unique URL, which can be texted or 
emailed to the patient, to facilitate the patient download of the HIPAA compliant app on their 
mobile smartphone. The PI will educate patients on how to use the app using educational 
materials developed for the study by the PI. The PI will also show patients the App “Help & 
Support” page, which answers commonly asked questions. This will be referred to as a “tutorial 
session.” Fidelity will be enhanced through the use of a “Checklist for App Set-Up” developed 
by the PI for the study to guide the App set-up process. The checklist with the patient record ID 
will be stored with the other study documents. 
 
The following steps will be taken by the PI in this tutorial session:  
1) Guide the patient with downloading the app to their phone.  
2) Once the download is completed, the medication list, extracted from the chart, can 
be entered.  
o Show patients how to enter the medication name, dosage, medication 
appearance (color and format of pill), frequency (every day, every other day, 
specific days of the week, etc.), the time the medication is regularly taken, and 
the number of pills left for the refill reminder (if the patient wants that option).  
o If patients are having difficulty entering their medications, demonstrate the 
process by entering one of their prescribed medications. This will ensure the 
patient understands how to enter medications in the app.  
o After the scheduled medications are added, show the patients how to access 
their list of medications in the app and how to edit a medication that was 
already in their list, e.g., change the medication dosage.  

Protocol for Dissertation Study 
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Version: 12-3-2021 
 
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o In addition, for some of the medications already in the app’s database, show the 
patient how to access information about the specific medication, including 
written information and a video about what the medication is for, what it may 
interact with, side effects etc.  
3) Patients can choose what language they would like to use when using the App by 
toggling to the desired language.  
4) Show the patient how to indicate that the medication was taken, skipped or 
rescheduled when they receive a reminder alarm to take their medication.  
5) Introduce patients to additional app features including:  
a) Reports: how to check their weekly adherence report in which their adherence 
was calculated based on the number of times they clicked that the medications were 
taken.  
b) Medfriend: how to invite a family member or friend to be a Medfriend in the 
app. This process entails the patient adding the family members/friend’s contact 
information in the form of a cell phone number and email and inviting them to 
download the app and obtain access to the patient’s medication list and then they will 
receive an alert if the patient misses a scheduled medication dose.  
c) Under settings, how to set Medtones, snooze time, receive a morning 
reminder to take their medications with them and change the home screen style.  
d) How to access the help and support section.  
 
The patient will be given the PI’s contact information in case of any questions or concerns. The 
PI will follow up with the patient through text, email or phone call (whichever the patient 
prefers). This preference will be noted on the flyer/referral form as well as in an instrument 
entitled Subject Information in REDCap. 
 
2. Wait-list Control Group: The wait-list control group patients will receive a printed out copy 
of their medication list and have the name, dose, frequency and indication for their 
medications and reviewed by the PI. They will be contacted within the first week of enrolling in 
the study to see if they have any questions regarding their medications. The follow-up 
measures will be completed by study patients in both the intervention and the wait-list control 
groups and feedback on the usefulness of the printed-out medication list and ways they used it 
to facilitate medication management. At study completion, The PI would make available the use 
of the app and will assist patients in setting up the app, as described above.  
 
Screenshots of Android Screens:  

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    Adding med            Daily overview timeline      Med reminder          Take dialog 
 
 
 
 
Drug interactions            Updates feed               Medfriend                   Status report 
 
 
 
 
 
 
 
Screenshots of iOS Screens: 

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Version: 12-3-2021 
 
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Daily overview              Med reminder          Drug interactions     Updates feed 
 
 
Med cabinet                 Status report 
 
F. DATA ANALYSIS 
 
IBM SPSS Statistics will be used for the quantitative summarization of the effects of the use of 
the app on the change in self-efficacy (SEAMS) and medication adherence (ARMS) from 
baseline to 1-month. Descriptive statistics will summarize sample characteristics and study 
measures. Raw change values from T1 to T2 in the adherence (ARMS), self-efficacy (SEAMS), 
medication social support, and medication knowledge scores will be calculated. Tests on the 
effects of the Medisafe app on those outcome measures will be conducted using multiple linear 
regression models. Given measurement error inherent in self-report measures, a reliable 
change index (RCI) criterium will be generated for each self-report measure. Each patient’s raw 
change value will be evaluated against that criterium to determine whether the change was 
reliable or not and the direction of that change.