Epilepsy & Behavior 116 (2021) 107794

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Epilepsy & Behavior

journal homepage: www.elsevier.com/locate/yebeh

The development and efficacy of a mobile phone application to improve

medication adherence for persons with epilepsy in limited resource
settings: A preliminary study
Pranav Mirpuri a,1, P. Prarthana Chandra c, Raghu Samala a, Mohit Agarwal a, Ramesh Doddamani a,
Kirandeep Kaur b,e, Bhargavi Ramanujan b, P. Sarat Chandra a, Manjari Tripathi d,⇑
a
Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi, India
b
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
c
Hamdard Institute of Medical Sciences and Research, New Delhi, India
d
Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
e
MEG Facility, National Brain Research Centre, Manesar, Haryana, India

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Persons with epilepsy (PWE), especially those with limited education backgrounds from devel-
Received 14 October 2020 oping countries, are challenged by complicated medication regimens, debilitating seizures, and stigmati-
Revised 4 January 2021 zation in their daily life. Consequently, it is difficult for physicians to ensure medication adherence. This
Accepted 4 January 2021
study validates a novel mobile application which was hypothesized to increase medication adherence
Available online 10 February 2021
and self-management skills in PWE. Created by medical professionals, the application included behav-
ioral and educational components and was built to be easy-to-understand for those of socio-
Keywords:
economically disadvantaged backgrounds.
Mobile application
eHealth
Methods: This was a parallel, two-armed randomized controlled trial in which a total of 96 participants
Epilepsy were enrolled from a Neurology Outpatient Department into a control standard care group and a mobile
Medication adherence application group that used the smartphone application (app) in addition to the standard medical treat-
Self-management ment. The app was intuitive and easy to understand for those coming from a socio-economically disad-
Self-efficacy vantaged background. Medication adherence and self-efficacy were assessed with the Morisky Green and
Levine Scale (MGLS) and the Epilepsy Self Efficacy Scale (ESES). Patients were reassessed 12 weeks later.
Change in seizure frequency following administration of the application was a secondary outcome.
Results: In an intent-to-treat analysis, the mobile application interventional group showed over a 60%
increase in the proportion of medication adherence (P < 0.0001). The mean self-efficacy score for the
mobile application group was increased from 269.5 to 289.75 (P < 0.0001). The control group showed
no statistically significant increases in either the proportion adherent or mean self-efficacy scores.
Significance: This study demonstrated the statistically significant performance of a mobile application in
improving medication adherence and self-management skills in Indian persons with epilepsy.
Ó 2021 Elsevier Inc. All rights reserved.

1. Introduction achieve seizure remission with antiepileptic medications (AEDs)

Epilepsy is a neurological disorder which imposes serious dis-
ability, morbidity, and stigmatization against persons with epi-
lepsy (PWE) [1]. As a developing country, India is estimated to
have a mean prevalence of epilepsy at 5.7 per 1000 people (range
of 2.5–11.9) [2]. Of this population, up to 70% can effectively
⇑ Corresponding author. Fax: +91 11 26594494.
E-mail address: mantriaiims@gmail.com (M. Tripathi).
1
Present Address: Chicago Medical School, Rosalind Franklin University of
Medicine and Science, North Chicago, IL, USA.
[3]. In contrast, the diagnosis of drug-resistant epilepsy (DRE) has
significant implications on the treatment strategies as surgery is
the only option for these patients [4–6]. Thus, in cases of seizure
recurrence due to ‘‘treatment failure”, it is crucial to determine
whether the failure is the result of true drug resistance or resulting
from other factors such as inappropriate pharmacological manage-
ment, the presence of ‘‘pseudo-seizures”, or poor adherence to the
therapeutic regimen.
According to the World Health Organization, ‘‘poor adherence
to prescribed medications is considered to be the main cause of
unsuccessful drug treatment for epilepsy” and is directly associ-

https://doi.org/10.1016/j.yebeh.2021.107794
1525-5050/Ó 2021 Elsevier Inc. All rights reserved.
P. Mirpuri, P. Prarthana Chandra, R. Samala et al.
ated with disease progression and a decreased quality of life. The
WHO also noted that rates of medication nonadherence vary from
20% to 80% in PWE around the globe, being significantly greater in
developing countries [7]. Furthermore, studies conducted in India
have demonstrated that lower rates of medication adherence are
associated with greater severity of seizures and duration of epi-
lepsy [8].
Pharmacological management is but one aspect of epilepsy
therapy as PWE must also adapt various psychosocial and behav-
ioral lifestyle adjustments to manage their disease. A range of pos-
sible adjustments exist including sleep hygiene maintenance,
alcohol/tobacco abstinence, minimization of emotional stress,
and frequent exercise. Disease self-management is deliberate and
self-initiated goal setting aimed at promoting medication adher-
ence, symptom monitoring, and the adoption of healthful behav-
iors improve quality of life and overall health. Epilepsy Self-
Management (ESM) is in line with the modern trend of shared-
decision making between the patient and doctor; it transfers equal
responsibility for the disease management to the patient as well as
the doctor [9]. The importance of ESM is well-recognized by the
epilepsy community in the treatment of epilepsy and promotion
of a good quality of life in PWE [10–12].
ESM interventions described in the literature with behavioral
and educational components have been efficacious in improving
therapeutic adherence in PWE. Thus, we hypothesized that a
mobile application would improve medication adherence and
self-management skills in Indian PWE, especially in those with
basic or low levels of literacy.
Mobile applications are well-recognized and popular modes of
enhancing self-management in PWE. Fittingly, there has been a
rapid increase in the number of apps available to patients over
the years; from the end of 2008 to 2013, the number of epilepsy-
related apps on the market increased from 0 to 34. Pandher and
Bhullar in their 2016 assessment of 28 apps aimed at PWE
described these apps as having varied quality. They found that epi-
lepsy education, as well as treatment, triggers, and lifestyle factors
were poorly covered in most apps. An ongoing relationship
between the patient and caregiver team was facilitated by only
two apps. Medication tracking systems were poorly utilized,
though seizure diaries were well-implemented across several apps.
Few were associated with medical expertise, and 16/28 apps
reported no medical input whatsoever in the app development
[13].
In a 2018 systematic review, Escoffery et al. analyzed 20 epi-
lepsy self-management applications qualitatively and quantita-
tively with the Mobile App Rating Scale (MARS). The MARS has
domains in engagement, functionality, esthetics, information pro-
vision, satisfaction, and quality. Of the apps reviewed, the authors
found that the highest average MARS rating scores were function-
ality and esthetics, while scores for user engagement and informa-
tion provision were lower. Furthermore, they described that many
available apps were limited in their functionality or were two-
dimensional in their approach. For example, an app may have
had good esthetics, but it lacked adequate channels for communi-
cation with healthcare providers, limiting its use to the patient.
Other apps may have had many functionalities, such as a seizure
diary or medication reminder system, but they utilized a limited
range of behavioral strategies to optimize patient engagement
resulting in poor utilization of the app. In addition, no application
provided adequate comprehensive patient education. Perhaps
most notably, there was a complete lack of evidence provided by
any app regarding their success in improving the epilepsy self-
management skills or clinical outcomes of their users [14].
Our application is evidence-based and created by medical pro-
fessionals. It incorporates an array of enduring features including
educational material and doctor/patient collaboration paired with
2
Epilepsy & Behavior 116 (2021) 107794
an interactive medication reminder system, seizure diary, and a
daily lifestyle checklist. The medication reminder system is aimed
at addressing the two primary causes of medication nonadherence:
complexity in addressing multiple medications and forgetfulness
[15–17]. Furthermore, our application is built to be intuitive and
easy to use for patients of varying educational backgrounds. First,
the application language can be set to Hindi or English at the dis-
cretion of the user. Next, to minimize misinterpretation, the appli-
cation uses pictograms in place of text wherever possible. This
technique has been shown to be helpful for patients to remember
medication timings, dosages, and indications [18,19]. Furthermore,
once a patient creates a profile and uploads a picture of their pre-
scription, their medication regimen is set up by their care team,
thereby decreasing the error of entering the incorrect regimen. This
study describes the development, validation, and performance of
our novel mobile application.
2. Methods
2.1. Study design and randomization
This parallel, two-armed randomized clinical trial (RCT)
assessed the efficacy of a novel mobile application in increasing
medication adherence and self-management skills in PWE. It was
undertaken in the neurology outpatient department of a tertiary
care hospital in North India. The study was randomized by the
sealed envelope method and included allocation concealment. 96
opaque envelopes were created prior to the recruitment phase of
the trial. Each contained a sheet of paper with the letter ‘‘I” or
‘‘C” (intervention or control groups). The researcher interviewing
the patient opened each envelope sequentially only upon patient
consent to enter the trial. To satisfy study inclusion requirements,
patients had to be 18 years of age and above, without physical
dependencies, independent in taking medications, in possession
of a smartphone, at least one year into treatment for epilepsy,
and able to return for a follow-up interview at the hospital.
Informed consent was obtained from all participants.
2.2. Procedures
Patients in the interventional mobile application group down-
loaded the mobile application, created an account, and were coun-
seled as to the use of the application in a 10-min session during the
initial encounter. Patient counseling was performed by a Senior
Researcher with a background in module development. Medication
regimens were processed and entered into the application by the
same researcher who counseled patients. The control group
received no mobile application and were advised treatment as
per the usual outpatient prescription. The study duration was
12 weeks, following which patients underwent reassessment on
the outcome measures.
The trial was registered with the Indian Clinical Trial Registry
with registration number CTRI/2019/05/019318.
2.3. Outcome assessment
The primary outcomes of medication adherence and self-
management skills were measured by the 4-Point Morisky, Green
and Levine Adherence Scale (MGLS) and the Epilepsy Self-Efficacy
Scale (ESES), respectively. At the initial encounter, patients were
administered the MGLS and ESES. Participants filled out the ques-
tionnaires themselves, and the researcher present explained any
items they found confusing. Either English or Hindi versions were
used depending on the patient’s preference. At the final encounter,
the researcher once again administered the MGLS and ESES. Sei-
P. Mirpuri, P. Prarthana Chandra, R. Samala et al.
zure frequency was measured simply as ‘‘decreased”, ‘‘increased”,
or ‘‘unchanged” based on the patient report at the initial and final
encounters. This was further confirmed by noting the duration and
frequency of seizure in the seizure diary. Baseline population char-
acteristics including demographics, individual seizure frequencies,
epilepsy syndrome, antiepileptic medications, and treatment dura-
tion were taken pro forma. Socioeconomic status was calculated
using the updated Kuppuswamy scale [20].
At the final encounter, feedback on the mobile application was
solicited from the interventional group. Participants were verbally
asked what features of the mobile application they utilized most,
which features they preferred, and if they had any opinion on
how to improve the app. The data was recorded by the authors
in an excel sheet. Participant engagement of the mobile application
was divided into two categories: passive and active. Active users
were those who used the interactive features of the application
(medication reminder system, seizure diary, and lifestyle check-
list), whereas passive users utilized the application mostly for
reminders or the educational information, inputting data intermit-
tently if at all. The data was available for review through the physi-
cian portal at any time by the authors.
2.4. Measures
The MGLS has been used in a variety of chronic disease settings
and languages [21]. Furthermore, psychometric analyses have
shown high internal consistency (Cronbach alpha = 0.61). The
MGLS measures adherence through four Yes/No response ques-
tions which are designed to account for the various reasons for
nonadherence; forgetfulness, carelessness, and the stoppage of
medications by the patient when they feel either better or worse.
A response of ‘‘Yes” is graded as 0 and ‘‘No” is graded as 1. Thus,
MGLS scores range from 0 to 4, with scores of 4 indicating high
adherence, a score of 2–3 indicating moderate adherence, and
scores of 0–1 indicating low adherence [22]. Though the risk of
response bias is significant, it is widely acknowledged that ques-
tionnaires such as the MGLS are a reliable and cost-effective
method for screening adherence [23]. Furthermore, the MGLS has
been used previously to measure medication adherence in Indian
populations with epilepsy. Nonadherence, as measured by the
scale (scores of 0–3), has been considerably associated with
increased severity of seizures, increased duration of seizures, and
increased seizure recurrence in Indian populations [8,24]. Thus,
patients who scored from 0–3 were considered nonadherent and
patients who scored a four were considered adherent in this study.
The scale was cross-culturally adapted to Hindi with permission
from the originators of the scale. The process included 3 steps: for-
ward translation, expert panel back-translation, pre-testing and
the final version per Brislin’s back-translation model [25]. Medica-
tion adherence was measured independently of self-management
as it is the prevalent dimension of disease self- management [8,12].
The ESES is a 33-item scale that measures the different aspects
of self-efficacy in the self-management of epilepsy. Each item is
graded on an 11-point Likert Scale, with responses ranging from
0 (I cannot do it at all) to 10 (I can do it always). Thus, ESES scores
range from 0 to 330, with a larger number indicating higher self-
efficacy [26]. Cronbach’s alpha for samples from two studies ran-
ged from 0.91 to 0.93 and the test–retest reliability was 0.81. The
scale was developed based on the construct of self-efficacy as
defined by Albert Bandura in 1997 as one’s belief in their ability
to succeed in stressful situations [27]. Studies have shown that
high rates of patient self-efficacy in chronic disease self-care lead
to effective disease self-management. We decided that the ESES
would be a more effective measure of self-management skills than
DiIorio’s Epilepsy Self-Management Scale (ESMS) because the
3
Epilepsy & Behavior 116 (2021) 107794
ESMS measures the access to self-management tools as well as
the availability of self-management support. Since we provided
the patients with a self-management tool, we measured self-
efficacy as the main domain of self-management skills likely to
change [12,28]. Furthermore, extensive research has demonstrated
self-efficacy as a valid construct that predicts self-management
behaviors of PWE [29]. A validated, Hindi-language version of this
scale was provided by Dash et al. [24].
2.5. Statistical analyses and sample size calculation
Statistical Analysis and Sample Size Calculation: Based on the lit-
erature review, we expected a 45% effect size in the intervention
group and a 10% effect size in the control group [18,24]. With a
power of 90%, an alpha value of 0.05 and an attrition rate of 20%,
the sample size was calculated at n = 48 for each group (total
n = 96). Baseline population characteristics were reported with a
mean and a standard deviation and were compared between
groups using Chi-square, Mann–Whitney, and T-tests. Categorical
variables were reported in percent frequency. Continuous and cat-
egorical variables were compared inter-group and intra-group
using a paired T-test. Levene’s test was carried out to ensure equal-
ity of variance for between group T-tests of ESES scores. Intention-
to-treat statistical analysis was carried out using SPSS version 16
for Windows.
2.6. Development of the mobile application
The mobile application was designed by a group which included
three epileptologists and two researchers. This group informed the
content of the application including its functionality, educational
information, esthetics, and engagement (including simple gamifi-
cation techniques). The application was developed by the private
company Healthcius Private LimitedÒ (AIMEO) under the direction
of this core group. Through each step of the development process
and the execution of this study, the epileptologists and researchers
were engaged with AIMEO. AIMEO provided the application for
this study free of cost and tested the app’s usability and reliability
to minimize any technical issues. No financial reimbursements
were given for their work.
2.7. Mobile application components and design
Users can navigate to the different features of the mobile appli-
cation from its home screen (Fig. 1). The reminder system not only
notifies the user when it is time to take a medication but also
requires the user to check a box when the medication has been
taken, thus increasing traceability of the action. Rudimentary gam-
ification techniques are also employed such that when participants
successfully take a dose and check the box in the application, the
section turns from red to green. There also appears a ‘‘smiley-
face emoticon” or a ‘‘frowny-face emoticon” on the home screen
of the application depending on whether the medications were
appropriately taken that day. The seizure diary, lifestyle checklist,
and educational material features are aimed at improving self-
management techniques through the provision of relevant tools.
Finally, patient treatment progress and past performance can be
viewed by a patient’s healthcare team as well as the patient.
The mobile application had the following components:
1. Medication Reminder System: The application reminds patients
with notifications at preset times (entered by the patient) to
take their medications. Once the notification appears, partici-
pants ‘‘check the box” in the application to demonstrate that
they had taken the medication (Fig. 1A–C).
P. Mirpuri, P. Prarthana Chandra, R. Samala et al. Epilepsy & Behavior 116 (2021) 107794

Fig. 1. (A) Patient view of the home screen. Application language can be set to Hindi or English. The ‘‘frowny-face emoticon” in the upper-right hand corner indicates that the
medications have not been appropriately taken. The red color of the medications box is similarly indicative incomplete adherence (B) shows the same items in English. The
‘‘Habits” section is the lifestyle checklist and the ‘‘Vitals” section is the seizure diary. The patient can click on the calendar below the smiley to review their previous
performance by date. (C) Patient View of the Reminder System. Note that there are three pictograms representing morning, evening, and night. The patient checks the circle
on the right-side when they have taken their appropriate medication. The boxes with the names of the medications are colored green because they have been taken and
checked off. Users can also navigate to other sections of the application from this screen by clicking on the tabs in the top row. (D) Patient view of the Daily Lifestyle Checklist
System (left). (E) Patient view of the Daily Seizure Diary (F & G) (Inset): These pictures show the physician’s view of the patient’s medicine adherence. (F) Shows the
adherence of various patients and (G) shows adherence of the individual patient. (For interpretation of the references to colour in this figure legend, the reader is referred to
the web version of this article.)

2. Seizure Diary (Titled ‘‘Vitals” in application): Patients can
record the number of seizures they have in the application daily
(Fig. 1A, B, E).
3. Lifestyle Checklist (Titled ‘‘Habits” in application): The daily
checklist of exercise, sleep, and stress relief goals were built
per literature review and with input from attending epileptolo-
gists. Patients were asked to sleep adequately for 8 hours
nightly, exercise regularly, and manage emotional stress
through activities like listening to music for 30 min (Fig. 1A,
B, D).
4. Health Education: The educational material includes topics
such as the nature of epilepsy, first aid for seizures that can
be administered by family members, and instructions to the
patient regarding what they should bring to each outpatient

4
P. Mirpuri, P. Prarthana Chandra, R. Samala et al. Epilepsy & Behavior 116 (2021) 107794

appointment. This material was requested from a study per-

formed on the effects of health education on medication adher-
ence and self-care in the North Indian population [24]. Their
health education program was developed by a group of three
epilepsy nurses, two epileptologists, and two social workers.
5. Physician’s portal and real-time progress tracker: The portal
allows physicians (or caregiving team) to monitor individual
patient and group progress (Fig. 1F & G).

3. Results

A total of 96 participants were enrolled in the study, with 48

patients allocated to each group. 43/48 of the participants in the
mobile application group and 41/48 of the control group com-
pleted the study for an overall attrition rate of 12.5% (Fig. 2).

3.1. Outcome evaluation

Table 1 shows the baseline demographic and clinical variables

of interventional and control groups. They were comparable across
both groups except for marital status and education. 51.0% of our
participants were in the Upper Middle Class (according to Kup-
puswamy SES scale) and 66.7% had at least a 12th grade-level edu-
cation. As measured by the MGLS, the pretest proportion of
medication adherent patients was 16.7%, whereas the posttest pro-
portion adherent was 68.8%, which was a statistically significant
difference (P < 0.0000) in the mobile application group. The pretest
and posttest proportions of the control group were 29.2% and
39.6%, respectively, which were not statistically different
(P = 0.0588). Furthermore, there was a statistically significant
greater proportion adherent in the mobile application group versus
the control group (Table 2). Table 3 shows that the mean posttest
ESES score of the mobile application group of 289.75 was signifi-
cantly greater than the pretest score of 269.5 (P < 0.0000). The
mean posttest ESES score of the control group of 274.4 showed a
statistically significant decrease from the mean pretest ESES score
of the control group of 279.5 (P = 0.0292). The mean posttest ESES
score of the mobile application group was significantly greater
than that of the control group (P = 0.0126). Table 4 shows the tab-
ulated data of the secondary outcome of seizure frequency. There
were no significant changes between or within groups with rela-
tion to seizure frequency (P = 0.425) for those who completed the
follow-up interviews.
3.2. Mobile application usage, usability, and satisfaction
Of the mobile application group participants who completed
the trial, 79.0% (34/43) considered the application to be useful.
72.1% (31/43) used the application throughout the study duration;
71.0% (22/31) of those were active users (those using the interac-
tive features of the application), and 29.0% (9/31) were passive
users (those who used primarily used the noninteractive features
of the app). Of the 12 participants (27.9%) who used the application
for two weeks or less, two stopped using it because of the eye
strain, one was admitted for complications and was not able to
use the app, two found it too complicated to use, and seven felt
that the application was not useful for them.
With regard to the mobile application group participants who
used the application throughout the study duration (n = 31, as
described above), the interactive portion of the ‘‘Reminder System”
was the most popular with 77.4% of participants (24/31) using it,
followed by the noninteractive ‘‘Reminder System” with 67.7%
(21/31) of participants using it. Passive users of the reminder sys-
tem relied on the notifications to assist them in taking their med-
ications appropriately, but they did not ‘‘check the box” (i.e.,
interact with the application).
5
Fig. 2. Randomization of Participants and Group Attrition.
4. Discussion
Interventions for improving medication adherence and patient
self-management skills have historically been behavioral, educa-
tional, or of a combined nature [30]. Behavioral interventions aim
to modify patient behavior toward medications. They can include
cognitive-behavioral techniques and therapies, motivational inter-
viewing, homecare visits, or simple reminder systems in the form
of text messages, pagers, interactive voice response systems, med-
ication dosette boxes, or personalized reminder packaging. These
approaches may serve to assist people in remembering to take
medications and in scheduling follow-up visits to their physicians
[31]. Behavioral interventions to decrease nonadherence have
shown variable levels of success. The most effective behavioral
interventions are those which integrate multiple techniques,
though these are often not easily implemented into daily practice.
For example, significant professional investment is required to
implement CBT sessions, and there can be a large equipment cost
to procure items like medication dosette boxes [32,33].
Educational interventions which consider patient beliefs, val-
ues, and attitudes have been shown to improve medication adher-
ence and self-management skills in PWE [34]. For example, Dash
et al. in a randomized controlled trial demonstrated the effective-
ness of health education in improving medication adherence and
self-management skills in Indian PWE with a low educational
background (P = 0.001) [24]. Other noteworthy educational inter-
ventions include the SEE program (Sepulveda Epilepsy Education)
and the MOSES (Modular Service Package Epilepsy) program. The
MOSES program participants (RCT, n = 242) demonstrated higher
levels of knowledge relating to epilepsy, greater ability to cope
with their disease, and improvements in seizure outcome [35].
The SEE program participants (RCT, n = 38) similarly demonstrated
higher levels of knowledge relating to epilepsy, a decrease in the
fear of seizure, and a decrease in hazardous medical self-
P. Mirpuri, P. Prarthana Chandra, R. Samala et al. Epilepsy & Behavior 116 (2021) 107794

Table 1 Table 3
Demographic Profile of Participants. Mean and standard deviation of Epilepsy Self-Efficacy Scale (ESES) scores in Control
and Mobile Application Group (Intent-to-Treat Analysis).
Mobile Control Group P-
Application (n = 48) Value Epilepsy Self-Efficacy Scale Pre- Post- Within-group
Group (n = 48) intervention intervention Paired T Test P-
value
Age (Means ± Standard 27.35 ± 6.71 30.73 ± 10.22 0.059
Deviation) Mobile Application Group Mean with Mean with <0.0001
Sex (Percent Male:Female) 33.3%: 66.7 % 47.9%: 52.1% 0.146 (n = 48) SD: SD:
Marital Status (Percent 35.4%: 64.6% 62.5%: 37.5% 0.008 269.5 ± 29.4 289.75 ± 28.4
Married:Unmarried) Control Group (n = 48) Mean with Mean with 0.0292
Employed (Percent 70.8%: 29.2% 64.6%: 35.4% 0.513 SD: SD:
Employed:Unemployed) 279.5 ± 26.7 274.4 ± 30.5
Education Education Above Education Above 0.045 Between group Levene’s 0.2988 0.7383 –
12th Grade: 12th Grade: Test for Equality of
79.2% 60.4% Variances P-value
Education Below Education Below Between group Two- 0.0858 0.0126 –
12th Grade: 12th Grade: Sample Test with equal
20.8% 39.6% variances P-value
Socioeconomic Status Upper: 16.7% Upper: 12.5% 0.090
Upper Middle: Upper Middle:
57.1% 43.8%
Lower Middle: Lower Middle: Table 4
18.8% 33.3% Changes in Seizure Frequency Post-Intervention (3 months).
Upper Lower: 2% Upper Lower:
Change in Seizure Mobile Application Control P-
Lower: 0% 10.4%
Frequency After 3 Months Group (n = 43) Group value
Lower: 0%
(n = 41)
Urban:Rural (Percent) 81.25%: 18.75% 81.25%: 18.75% 1.000
Presence of comorbid Illness 10.4%: 89.6% 10.4%: 89.6% 1.000 Decreased Frequency 3 (7.0%) 4 (9.8%) 0.425
(Percent Present:Absent) Unchanged Frequency 33 (76.7%) 34 (82.9%)
Diagnosis Generalized Generalized 0.288 Increased Frequency 7 (16.3%) 3 (7.3%)
Epilepsy: 37.5% Epilepsy: 27.1%
Focal Epilepsy: Focal Epilepsy:
39.6% 54.2%
Focal- Focal- interactive modules [38,39]. DiIorio et al. enrolled 148 PWE in an
Generalized Generalized RCT to assess the performance of the program and found that users
Epilepsy: 8.3% Epilepsy: 2.1% of WEBEASE demonstrated improvements in medication adher-
Unknown: 14.6% Unknown:16.7% ence, sleep quality, self-efficacy, and social support, though mea-
Treatment Duration in Years 12.81 ± 7.4 13.64 ± 10.4 0.977
sured outcomes were self-reported. The WEBEASE trial suffered
(Mean ± Standard
Deviation) from significant attrition, suggesting that the highly interactive
AED Regimen 3.0 ± 2.0 2.94 ± 1.5 0.691 structure of the intervention was not optimal for many patients,
(Mean ± Standard even though it was self-paced. In contrast, our application has
Deviation)
interactive (e.g. the seizure diary) and noninteractive domains
(medication reminders) which may appeal to a broader audience.
Another multifaceted interventional program described as the
Table 2 PACES in Epilepsy trial aimed to improve self-management tech-
Proportion Adherent in Control and Mobile Application Group Pre- and Post-
Intervention as measured by Morisky, Green Levine Adherence Scale (MGLS).
niques including patient’s medical, life role, and emotional man-
agement skills through an 8-week group therapy session led by a
Morisky, Green Pre- Post- Within-Group psychologist and a peer with epilepsy [40]. The PACES program is
Levine Adherence intervention intervention Chi Square P-
Scale value
somewhat different from our application in that they addressed
emotional management skills and epilepsy self-management.
Mobile Application Proportion Proportion <0.0001
Group (n = 48) Adherent: 16.7% Adherent: 68.8%
However, they were able to improve self-management, self-
(8) (33) efficacy, and quality of life, in addition to depression through their
Control Group Proportion Proportion 0.0588 program. In accomplishing the goal of improving self-management
(n = 48) Adherent: 29.2% Adherent: 39.6% skills, therapy sessions represent a larger resource burden in con-
(14) (19)
trast to our streamlined application.
Between Group Chi 0.145 0.002 –
Square P-value There are few evidence-based, theory-driven mobile applica-
1-sided Fisher’s 0.112 0.004 – tions intended for PWE self-management described in the litera-
exact ture. A randomized controlled trial was conducted in 2020 by Si
et al. examining the effects of their novel mobile application on
self-management and seizure control in adults with epilepsy
management practices [36]. The limitation of these interventions is (n = 380). Their app consisted of a medication calendar, online edu-
that the educational sessions require significant professional time cational material, a facility for prompt online reporting of seizures
investment, and they must be implemented regularly. and online consultations, and online questionnaires. The results
The most effective approaches have included a combination of revealed that participants who received the application had
behavioral and educational components that involve collaborative improvements in the domains of epilepsy knowledge, medication
care such as pharmacist-led interventions, multidisciplinary coun- management, and safety management. There was a larger propor-
seling sessions, or reminder devices in conjunction with individu- tion of patients which were seizure free at the 6-month follow-up
ally tailored educational sessions [37]. One such approach, in the app group [41]. We also found corroborative evidence that a
WEBEASE (Epilepsy Awareness, Support, and Education), is an mobile application has the potential to positively impact self-
online self-management program developed to improve medica- management in PWE. Although the authors did not describe what
tion adherence, perceived stress, and sleep quality in PWE through aspects of the app contributed to the measured differences in the

6
P. Mirpuri, P. Prarthana Chandra, R. Samala et al.
outcome, the overlap between their application and ours is sugges-
tive of the importance of a medication reminder system, seizure
diary, and educational material. A notable limitation of their study
is that they developed and validated the scale used as the primary
outcome measure (C-ESMS), and as such there are no data avail-
able regarding the psychometric properties of the scale.
Le Marne et al. developed and evaluated a mobile application
(EpApp) designed to improve knowledge acquisition as a primary
outcome and medication adherence and self-efficacy as secondary
outcomes in adolescents with epilepsy. Their app included features
of a seizure diary, educational content, and noninteractive medica-
tion reminder system. In their prospective cohort study of 51 par-
ticipants, the authors found significant increases in epilepsy
knowledge, but no improvements in psychosocial parameters or
seizure burden. This lack of improvement may be attributed to
the small sample size, short follow-up period of one month, and
self-reported outcome measures. Participants stated that the most
helpful app features were the educational content and the nonin-
teractive medication reminder system, which is similar to our find-
ings [42].
Our mobile application represents a patient-centered mode for
targeting poor adherence and self-management skills in persons
with epilepsy. Created by medical professionals, it incorporates
multiple behavioral strategies and provides educational support
to PWE. In contrast to the aforementioned alternatives (such as
educational sessions or motivational interviewing appointments),
significant time investments from healthcare team are not regu-
larly required. The app can also provide a wealth of data with rela-
tion to patient demographic information, disease parameters
including severity, frequency, and more which can be used to
inform clinical decision making and to better understand risk fac-
tors in the population. In addition, the app is accessible for people
of varying educational backgrounds through its extensive use of
pictograms, changeable language settings and the fact that the
medication regimen is entered by the caregiver team rather than
the patient to minimize errors. Finally, our app also uniquely
allows providers to follow up and work closely with patients to
improve their adherence and self-management skills on a personal,
continuous level through the physician portal.
Seventy-nine percent of the mobile application users who com-
pleted the trial considered the application to be useful. Participants
particularly liked the ability to modify their medication timings
and lifestyle goals, which many participants broadened into gen-
eral health goals rather than keeping them specific to epilepsy. Fur-
thermore, some participants requested more educational
information on epilepsy after reading through the material in the
app, stating that it helped them understand their symptoms better
and served as a personal reference when they had to explain the
disease to interested parties. Twenty-nine percent of the mobile
application group did not use the intervention for a variety of rea-
sons; notably, seven participants felt that it was irrelevant, as they
did not find it difficult to manage their medications or their disease
in general.
There were statistically significant differences between the con-
trol and intervention group with respect to the demographic vari-
ables of education and marital status. However, there is a plethora
of literature that has reported no statistically significant associa-
tions between educational attainment and medication adherence.
O’Rourke and O’Brien in 2017 reviewed three studies (n = 385,
n = 184, n = 408) which showed no associations between medica-
tion adherence and either educational attainment or marital status
in PWE [43]. Similarly, two studies of African origin (n = 450,
n = 272) found no association between medication adherence and
either educational attainment or marital status in their analyses
of the predictors for medication nonadherence in PWE [44,45]. In
particular, Gurumurthy reported the same result in a study with
7
Epilepsy & Behavior 116 (2021) 107794
a large sample size (n = 451) in Indian PWE [34]. Overall, these
studies reviewed had robust sample sizes (n > 134) and measured
adherence with both subjective (self-report scales) and objective
(Medication Event Monitoring System measurement or data amal-
gamation from patient notes).
Nonwithstanding these findings, there is literature that sug-
gests that marital status may play a role in social support, which
is implicated in improved medication adherence [28,46,47]. In
our case, the proportion of married patients was significantly
greater in the control group than in the intervention group. Thus,
if there was a positive effect on medication adherence or self-
efficacy, it is the control group which would have been artificially
elevated. Despite this, the baseline adherence between control and
intervention groups is not statistically different as described in the
results. Furthermore, there was no statistically significant differ-
ence in pre-intervention medication adherence between married
and unmarried participants with X2 (1, N = 96) = 0.124, P = 0.911.
Similarly, there was no statistically significant difference between
married and unmarried participants post-intervention with X2 (1,
N = 96) = 0.353, P = 0.851.
There also exists contrary evidence suggesting educational level
has a role in medication adherence [48]. However, there was no
statistically significant difference in pre-intervention medication
adherence between participants with less than a 12th grade educa-
tion and those with an education greater than 12th grade with X2
(1, N = 96) = 0.117, P = 0.733. Similarly, there was no statistically
significant difference between participants with less than a 12th
grade education and those with an education greater than 12th
grade post-intervention with X2 (1, N = 96) = 1.045, P = 0.306.
We do not believe that these differences in baseline demo-
graphics between the control and interventional groups affected
the results and conclusions of this study. Thus, no adjustments
were made in the statistical analysis.
Overall, statistically significant increases in medication adher-
ence and self-efficacy scores were noted in the mobile application
group. Taken together, these results demonstrate that the usage of
a mobile application tailored for a patient population can be hugely
efficacious in increasing medication adherence and improving
patient self-management skills given that mobile applications offer
a cost-effective, customizable, scalable and easy- to-administer
method of ensuring improvement.
4.1. Study limitation
A longer follow-up period and a larger sample size would have
helped delineate the long-term efficacy of the application and
potentially captured differences in seizure frequencies between
groups. Preferences of certain demographics to specific features
of the application may have also been elucidated with a longer
follow-up and larger sample size. Next, our study is based on
self-reported data, which could have biased our results. In addition,
narrowing the inclusion criteria to include only patients who were
initially medication nonadherent or struggling to manage their dis-
ease may have yielded more striking results (such as seizure fre-
quency improvements), as seven participants in the mobile
application group found the application to be superfluous. Finally,
delineating which app features contributed more to the measured
outcomes will require further analysis.
5. Conclusion
The aim of this study was to validate a mobile application
designed to curb medication nonadherence and improve self-
management skills in persons with epilepsy. In an intent-to-treat
analysis, the mobile application intervention group showed over
P. Mirpuri, P. Prarthana Chandra, R. Samala et al.
a 60% increase in the proportion of medication adherent versus
only a 10% increase in the control group. Furthermore, there was
a statistically greater increase in participant self-efficacy skills in
the intervention group versus the control group. The study findings
showed that the mobile application was efficacious in increasing
participant’s medication adherence and self-management skills.
Conflict of interest
None of the authors has any conflict of interest to disclose
Ethical publication statement
We confirm that we have read the Journal’s position on issues
involved in ethical publication and affirm that this report is consis-
tent with those guidelines.
Acknowledgement
This research was partly funded by a research grant from the
Office of Principal Scientific Advisor to the Government of India.
The commercial application of this app is being developed by Tim-
ble Technologies pvt ltd.
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