Keywords
Sickle cell anemia - asthma - medication adherence - short message service - text
Background and Significance
Background and Significance
Sickle cell disease (SCD) is an inherited red blood cell (RBC) disorder, characterized
by early RBC destruction, vessel occlusion and compromised end-organ perfusion. In
the United States, there are an estimated 100,000 individuals who have with SCD, who
are primarily African American [[1]]. Advancements in the care of individuals with SCD have led to improved life expectancy.
Disease knowledge and effective self-management are critical to the advancement of
SCD care. Health information technology has evolved as a one of the leading catalyst
for increased health care knowledge among consumers.
Health information is one of the leading topics researched by internet users. While
the most likely groups to search for online health information are Caucasians, women
and individuals aged 18–49 years, younger and minority populations are more likely
to use mobile devices to gather information, lending mobile health technology as a
potential strategy for improving access and utilization of electronic health information.
[[2]] The use of mobile health technology to improve health outcomes has been demonstrated
in other chronic disease populations. However, there are large gaps in the literature
regarding the use of technology by the SCD population [[3]], as well as widely-known health care disparities and disparities in health information
technology adoption among African Americans [[4]–[7]].
Vaso-occlusive pain is the most common complication affecting individuals with SCD,
followed by acute chest syndrome (ACS), which is an acute pulmonary condition. Hydroxyurea,
which increases the synthesis of fetal hemoglobin and raises the total hemoglobin,
results in decreased red blood cell sickling, abating the frequency of vaso-occlusive
pain and ACS [[8]–[10]]. In addition to hydroxyurea therapy, early detection and management of asthma is
recommended given the associated risk of increased vaso-occlusive pain rates and ACS
among individuals with SCD and concomitant asthma [[11], [12]]. The National Asthma Education Prevention Program-Expert Panel Report 3 (NAEPP-EPR
3) provides evidence-based guidelines for the detection and management of asthma and
recommends inhaled corticosteroids as the cornerstone treatment for persistent asthma
symptoms [[13]]. Both inhaled corticosteroids and hydroxyurea therapy require daily adherence to
achieve treatment effectiveness.
Daily medication adherence is less than optimal for individuals with SCD, with non-adherence
rates reported as high as 40% in individuals with SCD, compared to an average non-adherence
rate of 24.5% in other chronic disease populations [[14]–[17]]. Adherence in SCD is associated with important clinical outcomes including reduced
risk of SCD-related hospitalization, all-cause and SCD-related emergency department
visits, vaso-occlusive events, and health related quality of life [[14], [18]]. Short message service (SMS) medication reminders are an emerging technology employed
to facilitate behavioral change and decrease medication non-adherence. Johnson et al. observed improved medication adherence and satisfaction with mobile technology but
lower usage in African Americans when compared to Whites. [[19]] A web based application was used and required registration before receiving SMS
text messages. We believe adherence to the use of the technology and medication adherence
should improve because of increased use of patient portals in the general population
[[5], [20]] and the pervasiveness of mobile technologies [[21]–[24]]. A recent pooled meta-analysis demonstrated improvement in medication adherence
with SMS reminders among individuals with chronic illnesses [[25]]. However, the text messaging methodologies from the studies compared in the meta-analysis
included both one-way and two-way messaging, with some studies showing no improvement
in outcomes and no clear delineation of an optimal SMS reminder strategy. A potential
improvement in SMS communication is the use of two-way SMS communication versus one-way
communication. In one-way SMS communication, a text message is sent to a recipient
with no allowance or expectation for a response, while two-way SMS communication permits
a recipient response. While this recent pooled meta-analysis [[26]] did not demonstrate whether one-way or two-way messaging is superior, a more recent
meta-analysis demonstrated that two-way SMS messages are superior in improving medication
adherence as compared to one-way [[27]]. The perceived advantage of two-way SMS communication is the opportunity for patients
and families to demonstrate self-management behaviors prompted by the SMS communication.
Further, two-way SMS communication produces subjective adherence data, which health
care providers can utilize during clinical encounters to provide positive feedback
for high adherence, or explore barriers to medication compliance and suggest alternative
strategies to improve low adherence rates.
Despite the wide access to mobile technologies [[21]–[24]] and that SMS reminders have been shown to produce significant improvement in medication
adherence in individuals with various illnesses [[25]], very few studies have examined SMS medication reminders in children or adults
with SCD. In a retrospective study of one-way SMS reminders, researchers at St. Jude
Children’s Research Hospital demonstrated improved medication adherence in children
with SCD through medication possession ratio and biomarkers [[26]]. While this study showed improved medication adherence with SMS reminders, the
study was limited by a retrospective evaluation of adherence to a single medication
through a one-way text messaging intervention for children with SCD. The purpose of
this prospective, randomized controlled pilot study was to test the feasibility of
two-way SMS medication reminders and to evaluate the impact on adherence to one or
multiple medications and asthma symptom control among children and adults with SCD
or SCD and concomitant asthma. In a prospective feasibility randomized controlled
trial, in children and adults with SCD, we tested the hypothesis that daily two-way
SMS medication reminders over a 60-day period is an acceptable intervention that can
improve adherence to multiple medications and improve asthma symptom control.
Methods
This study was approved by the Vanderbilt University Medical Center Institutional
Review Board. The randomized feasibility trial used a parallel study design with equal
allocation in permuted blocks of 10 participants using GraphPad [[28]]. Study participants were de-identified and blinded from one of the coauthors who
randomly assigned participants to either the intervention or control group based on
GraphPad numbering. Feasibility, the primary outcome, was defined by recruitment rate
(acceptance rate), retention rate (1-attrition rate), adherence with the technology
(or utilization of the technology). The secondary outcomes included medication adherence
and asthma control.
Setting
Study recruitment took place in the Vanderbilt-Meharry Center of Excellence of Sickle
Cell Disease, located in Nashville, TN. Medical care is delivered in one pediatric
and one adult outpatient hematology clinic, located in a tertiary academic medical
center as well as a community-based, integrated pediatric SCD and asthma evening and
weekend clinic located in a community health center in Nashville, TN.
Study participants
Study eligibility criteria included: ages 1–70 years, a confirmed diagnosis of SCD
based on hemoglobin analysis ± a diagnosis of mild, moderate, or severe persistent
asthma with prescribed asthma control therapy and/or hydroxyurea therapy. Given the
time to treatment effect, participants with SCD and asthma, who were prescribed daily
asthma control therapy (such as fluticasone, montelukast or budesonide) and/or hydroxyurea
for a minimum of three months prior to study enrollment, were eligible for participation.
Study participants were randomly allocated to either the treatment arm (daily two-way
SMS medication reminders) or control arm (standard care), stratified by age categories:
adult (≥ 18 years) and pediatric (<18 years). Participants received SMS messages on
their own cell phones. Participants were enrolled for a minimum follow up period of
at least 28 days and up to 60 days based on a common termination date for all participants.
Intervention
SMS medication reminders were sent over a 60-day period using Research Electronic
Data Capture (REDCap) software, a web-based application designed to support survey
development, electronic data capture, and exportation into statistical software for
analysis [[29]]. Daily and twice daily, automated surveys were manually set up in REDCap by two
co-authors (BM and RC) based on prescribed medication regimens. This was accomplished
through the automated invitations feature in REDCap (►[Figure 1]). Automated surveys were manually set up for each of the three arms of the study
(asthma, hydroxyurea, both asthma and hydroxyurea) for all 60 days. Study participants
provided individualized preferences regarding time of day to receive daily SMS medication
reminders based on the times of day they took their hydroxyurea or asthma medications.
The SMS reminders included the following text: “Did you take your [hydroxyurea] [asthma]
medication [this morning] [this evening] [today]?” If the participant was prescribed
both hydroxyurea and asthma medications, a separate text message was sent for each
of the medications. Participants taking hydroxyurea alone received one text message
at the time of day they specified. Participants taking twice-daily asthma medications
received two text messages at two separate times of the day, once in the morning at
a time they specified, and one 10 hours later (to mimic the twice per day medication
schedule). If the participants took both hydroxyurea and asthma medications, they
received two text messages at two separate times of the day, once in the morning at
a time they specified (for the morning asthma medication), and one 10 hours later
asking if they took both their asthma medication and hydroxyurea. Study participants
receiving SMS medication reminders were prompted to reply ‘(1) yes’ or ‘(0) no’ as
to whether they took their medication. Participants that responded ‘(0) no’ received
an additional SMS reminder two hours later reminding them to take their medication.
If the participant did not respond to the initial text message, one additional text
reminder with the same message was sent one hour later. Study participant responses
were captured through REDCap. Monitoring of the study participants’ responses to daily
SMS medication reminders in REDCap was conducted weekly and study updates and reminders
about the study were provided during regularly scheduled clinic encounters to maintain
participant engagement.
Fig. 1 Screenshot of an example of a Research Electronic Capture Database (REDCap) automated
survey invitation.
Sample size calculation
Given the intent of this study to assess feasibility, a sample size large enough for
power to test the null hypothesis was not needed [[30]]. However, a sample size of at least 30, based on the central limit theorem, with
an anticipated attrition rate of 20% was used to set the minimum sample size for this
study. Although not needed for this feasibility study, a sample size of 46 (23 participants
in each treatment group) with 80% power would be needed to detect a clinically significant
change in baseline Asthma Control Test (ACT) scores and the ACT threshold for well-controlled
asthma of 23 and 22 for adults and children, respectively.
Outcome measures
Recruitment rate
Study eligibility was determined through medical record review and confirmation of
inclusion and exclusion criteria. Children and adults with SCD and asthma eligible
for study participation were approached during routine clinic encounters over a six-month
timespan, starting in September of 2015. The recruitment rate was defined as the proportion
of eligible participants approached who enrolled in the study.
Retention rate
Study participants completing both the pre-intervention and post-intervention data
collection phases were designated as completing the study. The retention rate was
defined as the proportion of enrolled participants that completed the study.
Morisky Medication Adherence Scale Scores
The Morisky Medication Adherence Scale-8 (MMAS-8) is a validated, 8-item, self-report
tool designed to capture self-reported adherence to prescribed medication regimens
and circumstances surrounding adherence behavior (►[Figure 2]) [[31]]. This scale has been tested in multiple chronic diseases, including individuals
with SCD [[16], [31]–[33]]. Baseline adherence scores were captured immediately following study enrollment
and after the intervention phase. Parents completed the scale for children participants
younger than 18. Adult participants over 18 completed their own scale. Medication
adherence scores range from 0– 8, with a score <6 indicative of low medication adherence.
Fig. 2 Morisky Medication Adherence Scale. Self-report tool designed to capture medication
adherence behaviors. Each ‘no’ = 1, with the exception of number 5, where ‘yes’ =
1. Item 8 is scored as follows: Never/Rarely = 1, everything else = 0. A score of
≥8 = high adherence; 6 to <8 = moderate adherence; <6 = low adherence.
Asthma Control Test and TRACK Scores
The Asthma Control Test (ACT) is a validated, patient-based tool used to quantify
patients’ and caregivers’ perceptions of asthma symptom control [[34]]. Study participants, 4–11 years of age, with asthma used the Childhood-ACT scoring
tool (►[Figure 3]) and those ≥ 12 years of age with asthma used the Adult-ACT scoring tool (►[Figure 4]). The Test for Respiratory and Asthma Control in Kids (TRACK) is a validated, patient-based
tool designed to assess caregivers’ perceptions of their children’s asthma symptoms,
and was administered to the parents and caregivers of study participants <= 5 years
of age with asthma (►[Figure 5]). Baseline ACT and TRACK scores were captured immediately following study enrollment.
Post-intervention ACT and TRACK scores were assessed at the conclusion of the study
phase. Childhood and Adult-ACT scores ≤19 and TRACK scores < 80 were indicative of
uncontrolled asthma [[35]]. A Childhood-ACT score >22 and Adult-ACT score >23 indicated well-controlled asthma.
Participant ACT and TRACK scores were analyzed as continuous and binary variables
(controlled and uncontrolled). A 2-point change in Childhood-ACT and a 3-point change
in Adult-ACT were considered a clinically meaningful improvement in asthma symptom
control [[35], [36]]. A change in TRACK score of 10 or more was considered a clinically meaningful change
in asthma control [[37]].
Fig. 3 Percent of Participants Responding to Text Messages. Childhood Asthma Control Test.
Patient and caregiver self-report tool of asthma symptoms in children 4–11 years of
age. A score ≤19 indicates uncontrolled asthma.
Fig. 4 Adult Asthma Control Test. Patient self-report tool of asthma symptoms for individuals
≥ 12 years of age. A score ≤19 indicates uncontrolled asthma.
Fig. 5 Test for Respiratory and Asthma Control in Kids. Caregiver self-report tool of asthma
symptoms in children under 5 years of age. A score <80 indicates uncontrolled asthma.
Statistical analysis
Participant demographics were examined using descriptive statistics. Categorical variables
were reported as frequencies and differences between groups assessed with a chi-square
test. Recruitment and retention were calculated as proportions. Pre and post mean
medication adherence and changes in adherence within and between treatment groups
were analyzed using a mixed methods model to account for missing data and correlations
between patient scores. Statistical differences among groups in ACT scores are not
reported because of the limited number of participants in the combined groups defined
by control/treatment and child/adult categories. We performed sub-analyses comparing
the change in medication adherence between the control and intervention groups of
adults, children, asthma medications alone and hydroxyurea alone. Statistical significance
was defined as a p value of < 0.05.
Results
Participant characteristics
Among the 47 study participants enrolled, 51.1% were male, 61.7% were adults, median
age was 20 (range: 3 to 59), and 98% were African Americans. The majority, 89.3% of
study participants had hemoglobin SS SCD phenotype and were on hydroxyurea therapy.
A comorbid diagnosis of asthma was present in 57.4% of the study participants. There
were 26 study participants randomized to the intervention group and 21 in the control
group. No statistically significant differences were noted in participant characteristics
among the intervention and control groups at baseline (►[Table 1]).
Table 1
Baseline characteristics comparing the intervention (medication reminders) and control
groups
|
Total
(%) n=47
|
Intervention group
n=26 (%)
|
Control group
n=21 (%)
|
p value[*]
|
|
Age, Median (IQR)
|
20 (9.5, 25.5)
|
20 (11, 25)
|
20.5 (8.75, 25.5)
|
0.741
|
|
Male
|
24 (51.1%)
|
14 (53.8%)
|
10 (47.6%)
|
0.671
|
|
Race: African American
|
46 (98%)
|
25 (96%)
|
21 (100%)
|
0.392
|
|
Adult
|
29 (61.7%)
|
16 (61.5%)
|
13 (61.9%)
|
0.980
|
|
Asthma diagnosis
|
27 (57.4%)
|
14 (53.8%)
|
13 (61.9%)
|
0.579
|
|
Baseline medication adherence, Mean (SD) (n=45)
|
3.64 (2.20)
|
3.42 (2.15)
|
3.90 (2.28)
|
0.463
|
|
Endpoint medication adherence, Mean (SD) (n=40)
|
5.18 (1.88)
|
5.46 (1.74)
|
4.75 (2.05)
|
0.248
|
|
Retention
|
47 (85.1%)
|
24 (92.3)
|
16 (76.2)
|
0.217
|
* Percentages compared with a chi-square test or a Fisher’s exact test. Age compared
using a Mann-Whitney U test. Morisky Medication Adherence Scale-8 scores compared
using a t test.
IQR=Inter-Quartile Range; SD=Standard deviation
Retention and recruitment rates
The recruitment rate for this feasibility trial was exceptionally high. There were
49 children and adults with SCD and asthma approached for study participation, of
which 95.9% agreed to study participation. Of the 47 participants enrolled, 82.9%
completed the study. Retention rates were not significantly different between the
control and intervention groups (p=0.217).
Variation in proportion of short message reminder participant response
The response to the two-way SMS prompt was mixed; a small group responded to almost
every prompt and an equally small group did not respond to any prompts. Of the 26
participants that were allocated to the intervention arm, one did not receive text
messages due to an error with the technology. Eight of the remaining 25 (32%) never
responded to any text messages. Twenty percent of participants responded on more than
95% of the days that text messages were sent. Usage varied depending on the different
days with an average response rate of 33%, ranging from 21% to 46% (►[Figure 6]). Partial responders, those that responded at least once but less than 95% of the
time, had similar variation as the overall responders (►[Figure 7]). A total of 669 text messages were responded to, with 53 responding ‘no’ indicating
the respondents did not take their medication. There were 35 responses to the second
reminder text. Of these second reminders, 22 responded ‘yes’ meaning that they took
their medications after receiving a second reminder text. All of the second reminder
responses of ‘no,’ indicating that they did not take their medication after two reminders,
came from two participants (►[Table 2]). Participants that received once daily text message reminders had a higher percentage
of days that they responded (median: 21.7%, IQR: 0.0, 83.3%) than those who received
twice daily text message reminders (median:3.3%, IQR: 0.0,85.0%), however this difference
was not significant (p=0.536).
Fig. 6 Percent of Participants Responding to Text Messages. Percent of participants in intervention
group that responded to text messages. The percent of respondents are on the left
y-axis and the total number of participants responding is shown on the right y-axis
for each day of the intervention.
Fig. 7 Percent of Partial Responders Responding to Text Messages. Percent of partial responders
(responded at least once, but less than 95% of the time) that responded to text messages.
The percent of respondents are on the left y-axis and the total number of participants
responding is shown on the right y-axis for each day of the intervention.
Table 2
Responses to text messages: All participants received reminder texts for their medications.
If they responded with a ‘no’ a second reminder was sent an hour later.
|
Number of
texts with
responses
|
‘No’ responses
|
Number of participants that texts
were sent to
|
Number of participants
that responded
|
|
First medication reminder text
|
669
|
53
|
26
|
17
|
|
Second medication reminder text
|
35
|
13
|
12
|
8
|
Short message service reminders improve medication adherence scores
Baseline and endpoint medication adherence rates were not statistically different
between the two groups (►[Table 1]). The intervention group showed a statistically significant improvement in medication
adherence scores (3.42 before, 5.46 after; p=0.001), whereas the control group did not (3.90 before, 4.75 after, p=0.080) The
increase (improvement) on the MMAS-8 was not significantly different between the two
groups (p=0.118, ►[Table 3]). Our sub-analysis demonstrated a greater increase in adherence in the intervention
group compared to the control group in those with asthma medications alone, and of
children alone, but the differences were not statistically significant (asthma medications
alone: p=0.182; children: p=0.156).
Table 3
Changes in medication adherence scores within pediatric and adult patients, patients
on hydroxyurea medication, and on asthma medication, mean (standard deviation).
|
Intervention Group
(n=22)
|
Control Group
(n=16)
|
p value[*]
|
|
All participants
|
1.91 (2.35)
|
0.94 (2.05)
|
0.118
|
|
Children (n=17)
|
1.78 (2.49)
|
0.25 (1.83)
|
0.156
|
|
Adults (n=21)
|
2.00 (2.34)
|
1.62 (2.13)
|
0.289
|
|
Hydroxyurea alone (n=31)
|
2.06 (2.34)
|
1.31 (2.06)
|
0.230
|
|
Asthma medications alone (n=24)
|
1.79 (2.52)
|
0.40 (2.17)
|
0.182
|
* Changes in pre and post mean medication adherence scores between treatment groups
were analyzed using a linear mixed model with time as a repeated factor and an autoregressive
covariance matrix. Mixed models use all available data even when a patient has a missing
score on either the pre or post medication adherence measure.
Medication reminders demonstrate a clinically significant improvement in asthma control
Self-reported asthma symptom control improved clinically with the use of SMS medication
reminders. Among the 27 study participants with SCD and concomitant asthma, 2 were
<4 years of age, requiring the TRACK assessment tool, and were thus excluded from
the analysis. Post-intervention Childhood and Adult-ACT scores for study participants
≥4 years of age improved within both the intervention and control groups. Among study
participants, 4–11 years of age, Childhood-ACT scores improved by a raw score of 5.1
points (19.2 before, 24.3 after) in the intervention group and 2.4 points (18.8 before,
21.2 after) in the control group. Pre and post Adult-ACT scores for the intervention
group were 21.0 and 22.0, respectively. Pre and post Adult-ACT scores for the control
group were 21.67 and 22.67, respectively.
Discussion
Medication adherence is critical to effective chronic disease self-management. Children
and adults with SCD or SCD and concomitant asthma represent high-risk populations
in which daily medication adherence is critical to health outcomes and quality of
life. Perceived medication adherence has been shown to be an accurate surrogate for
measuring adherence to hydroxyurea in SCD. [[16], [18]] In this pilot randomized controlled trial we evaluated the feasibility of two-way
SMS medication reminders for children and adults with SCD and asthma by measuring
recruitment and retention rates, and technology adherence (utilization). We also measured
medication adherence, and overall asthma control. Our results demonstrated improved
medication adherence, as well as high recruitment and retention rates, with the use
of SMS medication reminders, deeming SMS reminders as a feasible and promising intervention
for children and adults with SCD and asthma.
Recruitment and retention rates were used to assess the feasibility of two-way SMS
communication in this SCD cohort. A previous trial examining the efficacy of SMS medication
reminders for children with SCD was done retrospectively; therefore, the feasibility
of conducting a prospective trial among individuals with SCD that involved text messaging
to their mobile phones was not previously known [[26]]. We achieved excellent recruitment (96%) and retention rates (83%) demonstrating
the feasibility of this trial, with higher levels than the previous retrospective
study that had 91% recruitment and 77% retention. Participants received a gift card
incentive for filling out the survey on the first research visit ($15) and the final
research visit ($15). No incentives were given for technology use. Although there
was a small incentive to participate in the study, we postulate that the high recruitment
and retention rates were attributable to the presentation of SMS medication reminders
as a way for patients and families to becomes partners in health and take on more
ownership for improved health outcomes.
Medication adherence improved with the use of daily, two-way SMS medication reminders
in the intervention group but not in the control group. SMS text messaging has been
used successfully to deliver medication adherence reminders; however, two-way text
messaging has not always demonstrated improved medication adherence [[38]–[40]]. Estepp et al. demonstrated improved adherence to hydroxyurea using one-way text messaging in a
retrospective trial in children with SCD [[26]]. Their study demonstrated improved medication possession ratios using one-way text
messaging in children for hydroxyurea, and we found that two-way text messaging improved
self-reported medication adherence using the MMAS-8 in adults and children with SCD.
Our study adds to this preexisting literature indicating that SMS reminders are an
effective strategy for improving self-reported medication adherence in children and
adults with SCD. A sub-analysis of adults, children, asthma medication alone, and
hydroxyurea alone demonstrated improvement in medication adherence but without statistical
significance. The change in adherence was higher in children and in those using asthma
medications alone.
While this feasibility trial was not designed to assess clinical improvement in ACT
scores, we did observe an improvement in ACT scores in the intervention group. Two
SMS messaging studies involving individuals with asthma looked primarily at one-way
text messaging [[41], [42]]. In both of these studies, medication adherence was significantly improved by SMS
messaging, as demonstrated in our study. Lv et al. observed a significant improvement in subjective measures, using the Perceived Control
of Asthma Questionnaire, PCAQ-6) and quality of life with SMS messaging; however,
neither of these studies demonstrated significant improvement in clinical outcomes
such as FEV1% or emergency room visits for asthma in the SMS group as compared to
the control group. Our study did show a trend towards significant change in ACT scores
and a larger sample size may demonstrate similar findings of improved asthma control
as other studies.
Participant response rates varied. Participants fell into one of three groups: non-responders
who never responded, partial responders, and usual responders who responded on more
than 95% of the days. The most common participant type was partial responders. About
one third of all participants responded to the text message reminders on any given
day, whereas other studies have reported 22–100% response rates [[43]]. Johnson et al. demonstrated that most of the African American participants never used their text
messaging intervention [[19]], whereas 98% of our participants were African American with the majority responding
at least once. This could be related to patient engagement as all participants are
from a sickle cell center where providers and healthcare teams actively engage their
patients to know their disease and medications. The providers also promote technology
to help with patient care.
Further research evaluating why participants do not respond could yield better ways
to improve adherence to two-way text messaging responses in the SCD population. Potential
reasons to account for why individuals do not respond to text message reminders include
changing phone numbers without notifying the research team [[44], [45]], failing to respond because they find the messages intrusive,[[41]] finding the messages disruptive to their daily routines [[42], [46]], and changing their behavior from using the system for a short period of time and
no longer feeling the need to reply [[19], [42]]. There may be features to the technology that could be used to address these different
reasons including personalization of messages to decrease intrusiveness, allowing
participants to modify settings so messages are not disrupting their daily routines,
or automatically notifying the research team if there is no response after a few days.
While the researchers received anecdotal information about why users did not use the
system including the fact they did not know the reminders were from the research team
and they changed phones before receiving messages, this study did not explore the
qualitative reasons why some participants responded more often than others, which
is an area for further research. While statistically significant differences were
not observed, we also found that response rates were higher in participants that received
only a single message per day as compared to multiple messages per day. These response
rate differences could demonstrate the poor adherence to the technology due to the
burden of having to respond to message multiple times per day. We observed an improvement
in medication adherence in the intervention group when compared to the control group,
indicating that study participants’ behavior changed irrespective of response rates.
Participant responses decreased with time. The absence of a response to the text message
did not appear to impair medication adherence, indicating that initial SMS messaging
may have prompted habit formation which no longer required rapid-cycle reinforcement.
While our study demonstrated that two-way text messaging improved medication adherence
for individuals with SCD, asthma alone (without SCD), or both over a 30-day period,
further research over longer periods of time is needed to determine the necessity
for persistent responses and the effect of the text messaging system on medication
adherence for prolonged periods. Also, even if participants did not respond, all participants
continued to receive text messages. Quite possibly the ongoing text messaging served
as a prompt sufficient enough for participants to initiate taking their medication,
but the participants were not sufficiently motivated to respond. Further research
is needed to determine if improved medication adherence is due to daily two-way text
message reminders regardless of the participant’s response.
The use of the second reminder varied and may be useful in determining who might need
further interventions to improve medication adherence. Most responses to the initial
reminder indicated that participants remembered to take their medication (92% responded
‘yes’ to the first reminder). Of the ‘no’ responses to the first reminder, about 42%
of the second reminders had a ‘yes’ response, meaning the respondents remembered to
take their medication after forgetting initially and receiving a second reminder.
Only eight of the participants used this feature at least once, likely indicating
that while this feature was not widely used, it was helpful in reminding some participants.
Another advantage of the two-way text messaging system is that health care team members
can monitor how well individuals with SCD take their medications based on self-report.
In this study, there were two participants who missed doses after two reminder messages,
indicating the need for additional interventions by the health care team.
Limitations
This study had several limitations. The intervention phase was of short duration,
ranging from a minimum of 28 days to a maximum of 60 days, leaving room for further
demonstration of treatment effects of SMS medication reminders in regards to asthma
symptom control and SCD-related morbidity. Previous literature on the use of SMS reminders
in SCD demonstrated sustained adherence effects lasting up to 12 months using SMS
reminders for medication adherence [[26]]. This study had a 17.1% attrition rate, potentially diminishing the effect of SMS
medication reminders. This study did not compare the difference in child versus caregiver
receipt of SMS medication reminders. Further research in reporting medication possession
ratios through publicly available databases and clinical outcome data would decrease
this bias. This study used the MMAS-8 to measure medication adherence and did not
evaluate lab markers of adherence, such as mean corpuscular volume (MCV). While a
perceived medication adherence score may have recall bias, the MMAS-8 has been shown
to be an accurate surrogate for measuring adherence to hydroxyurea in SCD [[18]]. This study did not measure important clinical events, such as ER visits or hospitalizations.
Further research in larger cohorts could help determine if text messaging reminders
have effect on clinical outcomes. No behavior change theory was used to design or
inform the study which could limit the findings. Finally, the study was done as a
small feasibility trial at a single institution of a convenience sample of patients,
therefore the results cannot be generalized to a larger study population.
Conclusion
Two-way SMS medication reminders are feasible in children and adults with SCD and
asthma, and could provide more information to health care providers about how to improve
medication adherence. The two-way SMS medication reminders are a low-tech solution
that can improve self-management in a crucial vulnerable population. Larger, multicenter
studies of longer durations are needed to further examine the health-related implications
of SMS medication reminders in children and adults with SCD and asthma, including
objective measures of asthma symptom control, rates of vaso-occlusive pain and ACS,
quality of life, and mortality. The findings from this study lay the foundation for
future studies examining this novel approach designed to improve medication adherence
in individuals with SCD and asthma.
Abbreviations
-
SCD: sickle cell disease
-
RBC: red blood cell
-
ACS: acute chest syndrome
-
NAEPP-EPR 3: National Asthma Education and Prevention Program, Expert Panel Report
3
-
SMS: short message service
-
REDCap: Research Electronic Data Capture
-
ACT: Asthma Control Test
-
TRACK: Test for Respiratory and Asthma Control in Kids
-
PCAQ-6: Perceived Control of Asthma Questionnaire
-
FEV1 : forced expiratory volume in the first second
Clinical Relevance Statement
Clinical Relevance Statement
Medication adherence is critical to effective chronic disease self-management. Individuals
with sickle cell disease are high-risk populations in which daily medication adherence
is critical to health outcomes and quality of life. In this manuscript, we demonstrate
through a pilot randomized clinical trial that mobile applications, such as two-way
SMS messaging, can improve medication adherence in individuals with SCD.
Multiple choice questions
Multiple choice questions
Which of the following is true of using Short Message Service (SMS) text messaging
for medication adherence?
-
Two-way SMS messaging is always superior to one-way text messaging for medication
adherence
-
Two-way SMS messaging improves long-term medication adherence in sickle cell disease
-
Respondents to two-way SMS messaging fall into two categories, those that use it every
day, and those that never use it
-
Large randomized trials are needed to demonstrate that SMS medication reminders can
improve clinical outcomes
-
Most users never respond to two-way SMS medication reminders
Answer: D
