Impact of a Pharmacist-Led Education Program on Medication Adherence and Treatment Effectiveness of Direct Oral Anticoagulants in Patients With Atrial Fibrillation: A Randomized Controlled Trial
Phase: NA
Conditions: Atrial Fibrillation (AF)
Sponsor: National Taiwan University

Study Protocol with Statistical Analysis Plan (SAP) 
 
Oﬃcial Title: Impact of a Pharmacist-Led Education Program on Medication 
Adherence and Treatment Eﬀectiveness of Direct Oral Anticoagulants in Patients with 
Atrial Fibrillation: A Randomized Controlled Trial (PharmAD-AF) 
NCT Number: NCT pending 
Date: December 19, 2024 
Version: Protocol v4.0 

V4 2024/12/19 
                                                                                                       
 
 
 1 
Impact of A Pharmacist-Led Education Program on Medication Adherence and 
Treatment Effectiveness of Direct Oral Anticoagulants in Patients with Atrial 
Fibrillation: A Randomized Control Trial 
 
 
SPECIFIC AIMS 
The goal of this study is to evaluate the impact of a pharmacist-led education program on patients’ 
medication adherence and treatment outcomes in patient with atrial fibrillation (AF) newly prescribed 
direct oral anticoagulants (DOACs) for stroke prevention. In addition, we aim to understand patients’ 
medication use behavior by comparing self-reported data and administrative claims data, and to explore 
the potential utility of DOAC blood concentration as a biomarker for medication adherence and treatment 
outcomes.  
We propose a five-year project to evaluate the effectiveness of a pharmacist-led education 
program on patients’ medication adherence and treatment outcomes by a pragmatic, randomized control 
trial. We will collect data on medication use behavior, including medication adherence and refill 
adherence, as well as DOAC blood concentration during follow-up. In addition to primary data collection, 
we will also utilize currently available data sources, including electronic medical records and 
administrative claims data, to understand patients’ baseline characteristics and to assess treatment 
outcomes. We will achieve our study goal by completing the following aims:     
 
Aim 1: To evaluate the impact of a pharmacist-led patient education program on patients’ 
medication adherence and treatment outcomes.  
The primary endpoint of this pragmatic trial is medication adherence. Patients diagnosed with AF 
who are newly prescribed DOACs for stroke prevention will be recruited into the trial. Eligible patients 
will be randomized into the intervention group and the control group. In the intervention group, patients 
will receive one-time patient education from a clinical pharmacist or a well-trained senior Pharm.D. 
students at the time of the initial prescription of DOACs. Two follow-up visits with the clinical 
pharmacist will be scheduled for patients in the intervention group to further reconcile issues related to 
DOAC use and monitor laboratory tests. Patients in the control group will receive usual care. DOAC 
adherence will be measured at patients’ three-month and six-month follow-up visits to the physician, 
using the Adherence to Refills and Medications Scale (ARMS). The mean ARMS score will be compared 
between the intervention and the control groups.  
The secondary endpoint of this trial is treatment outcomes, including effectiveness and safety 
events. We will capture the one-year and two-year thromboembolic and bleeding events following the 
DOAC therapy initiation using the National Health Insurance (NHI) claims data. Effectiveness will be 
measured by systemic thromboembolic events, and safety will be measured by major bleeding events. 
The event rates will be compared between the intervention group and the control group.  
 
Hypothesis: We hypothesize that the pharmacist-led education program will improve patients’ medication 
adherence and treatment outcomes.  
 
Aim 2: To understand patients’ DOAC usage behavior by comparing self-reported data and 
administrative claims data.  
 
The second part of this study aims to provide a comprehensive understanding about patients’ 
medication use behavior, including medication adherence and refill adherence. Self-reported medication 
and refill adherence will first be report descriptively. We will next explore the reasons for non-adherence 
by assessing patients’ response to each of the eight questions that measure medication adherence in the 
ARMS. Understanding the reasons for non-adherence will help us to refine our education program by 
providing additional explanations or education materials on factors contributing to poor adherence.  
In addition, we will compare self-reported medication and refill adherence from the ARMS to the 
pharmacy records from the NHI claims data. In the claims data, medication adherence will be measured 

 
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by proportion of day covered (PDC) during three and six months of follow-up, and refill adherence will 
be measured as number of refills during three and six months of follow-up. Given the easy access and low 
copayment of pharmaceutical care, we anticipate observing a discrepancy between medication adherence 
and refill adherence. Specifically, we expect a high prescription refill rate for both the intervention and 
the control groups but suboptimal medication adherence in the control groups. 
 
Aim 3: To explore the potential utility of DOAC blood concentration as a biomarker for medication 
adherence and treatment outcomes. 
Because of the predictable pharmacokinetic and pharmacodynamic profiles, DOACs do not 
require routine blood monitoring. While the lack of requirement for monitoring blood concentrations is 
one of the advantages of DOACs, the absence of data on blood concentration also contributes to the 
uncertainty in therapeutic monitoring of DOACs. DOAC testing and monitoring may be necessary for 
certain patients, such as those who with low adherence or at critical conditions.1 We therefore aim to 
provide further evidence on the correlation between DOAC concertation and medication adherence and 
treatment outcomes.  
At the three-month and six-month follow-up physician appointments, in addition to assessing 
medication adherence, we will also measure patients’ DOAC trough concentration. The proportion of 
patients with blood concentration in the expected range will be compared between the intervention and 
the control groups. We will also evaluate the correlation between patients’ self-reported medication 
adherence and their DOAC blood concentration.  
 
Finally, we will evaluate the association of DOAC blood concentration with the treatment 
outcomes as proposed in Aim 1. Both effectiveness and safety events will be assessed. We expect to see 
that a higher proportion of patients in the control group displays low DOAC concentration compared to 
the intervention group. In addition, the occurrence of thromboembolic events is more frequent in the 
control group compared to the intervention group. 
 
Together, these three aims will provide a comprehensive evaluation on the effectiveness of the 
pharmacist-managed education program on patient care, further enhance our understanding on patients’ 
medication use behavior, and advance our knowledge on pharmacokinetic and clinical management of 
DOACs. To the best of our knowledge, this will be the first study that evaluates the impact of a 
pharmaceutical care program by a pragmatic trial in Taiwan. 
 
BACKGROUND AND SIGNIFICANCE 
AF is the most common type of arrhythmia, characterized by irregular contractions of the atria due 
to abnormal electrical impulses. Individuals with AF face a 4 to 5-fold increased risk of ischemic stroke 
compared to those without AF.2,3 DOACs are the first line therapy for stroke prevention for patients with 
AF.4,5 DOACs have been shown to be effective in stroke prevention and with a lower risk of bleeding 
compared to the warfarin.6-9 In addition, unlike warfarin, DOACs do not require regular laboratory 
monitoring and have fewer complicated drug interactions,10 which makes them the preferred therapeutic 
choice. Despite of the therapeutic advantages of DOACs, ensuring patient adherence remains crucial for 
optimizing the effectiveness and safety of DOAC therapy. DOACs adherence has been reported to be 
suboptimal; one-third of the patients had adherence <80%.11 A Taiwanese study also found that 
adherence to DOACs was not better than that to warfarin.12 Non-adherence to DOACs is associated with 
an increased risk of thromboembolism and bleeding.13,14  
 
One way to improve patient adherence is through patient education. It has been reported that 
pharmacist-led anticoagulation clinic (ACC) services can improve the quality of warfarin therapy and 
reduce thromboembolic and bleeding events.15 However, there is limited evidence regarding the impact of 
pharmacist-led ACC services on DOAC therapy. An U.S. study demonstrated that pharmacist-led 
interventions, such as providing ACC services and tailoring monitoring frequency, were associated with 
improved DOAC adherence.16 Another study from China demonstrated that pharmacist-led remote 
monitoring of DOAC therapy via telephone during the COVID-19 pandemic resulted in reduced bleeding 
incidents and hospital readmissions.17 While these two studies provide some data on the effectiveness of 

 
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pharmacist-led interventions on patients adherence and outcomes, the evidence is still preliminary. Based 
on our understanding, there is currently no studies investigating the reasons behind DOAC non-adherence 
in Taiwan. Understanding the reasons for poor medication adherence is essential for establishing and 
refining an effective medication education program. Further assessment of the effectiveness of 
pharmacist-led interventions with a robust study design and comprehensive evaluation is needed. 
 
Our study is prominent and innovative because of the following reasons. To our knowledge, this 
will be the first pragmatic, randomized control trial that evaluates the impact of a pharmacist-led patient 
education program on patients’ adherence on DOACs and treatment outcomes in Taiwan. Through the 
experimental design, our study results will be more robust than the previous findings, providing more 
solid evidence on pharmacist-led health services. The one-time health education intervention used in this 
study can be easily applied to other situations, making it adaptable in various pharmacotherapy scenarios. 
In addition, the pragmatic design of this study ensures that our findings are applicable to real-world 
settings, holding direct clinical and policy application value. As mentioned earlier, this study will be the 
first to investigate the reasons for DOAC non-adherence in Taiwan. This information will not only help 
tailor the design of our intervention program but also improve the design of future medication education 
programs. Finally, our study is innovative because it will be the first study that correlates DOAC blood 
concentration and medication use behavior. Unlike warfarin, which can be monitored by international 
normalized ration (INR), common therapeutic monitoring tests for DOACs are unreliable. It is therefore 
especially important to understand the potential role of DOAC blood concentration as a potential 
biomarker for DOAC therapeutic monitoring. Our study will fill the current gap in evidence by providing 
further insight into the association between DOAC blood concentration and treatment outcomes. 
 
RESEARCH DESIGN AND METHODS 
Study Design and Setting 
This two-arm, pragmatic, randomized control trial will be conducted at National Taiwan 
University Hospital (NTUH), a tertiary medical center located in Taipei, Taiwan. Two data sources will 
be utilized in this study: the electronic medical records (EMRs) from the NTUH and the NHI claims data 
from the Health and Welfare Database. The NTUH EMRs will be used for patients’ baseline assessment 
and screening for eligibility. The NHI claims data will be used for event follow-up and medication use 
behavior assessment.  
Patients who are newly prescribed DOACs for stroke prevention will be recruited from outpatient 
clinics of the NTUH. Eligible patients who are randomized to the intervention group will be referred to a 
pharmacist-led ACC for patient education. The NTUH ACC was established in 2012, and is operated by 
two clinical pharmacists. The ACC provides comprehensive education and follow-up services for patients 
under oral anticoagulant therapy (both warfarin and DOAC). The ACC has been providing high-quality 
services to over 1,000 patients; more than 80% of the warfarin users achieved their therapeutic goals after 
the pharmacists’ intervention. Figure 1 below provides an overview of the study design and process. 
 
 

 
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Figure 1. Graphical illustration of study design and process 
 
DOAC: direct oral anticoagulant. 
 
Study Population and Randomization 
 
In this trial, we will include patients with AF who are newly initiate DOAC therapy for stroke 
prevention. Patients who are 18 years or older, with an AF diagnosis, and are expected to receive DOAC 
therapy for at least three months for stroke prevention will be recruited. Patients will be excluded if they 
are illiterate, have cognitive impairment, receive off-label DOAC regimens, or are pregnant or 
breastfeeding.  
 
Patients will be recruit from the NTUH outpatient clinics. We will collaborate with two attending 
physicians at the NTUH who will help to screen the potential study subjects. Those patients will be 
referred to the research team for further evaluation of the eligibilities. Patients eligible to the trial will be 
randomized in a 1:1 ratio into the intervention and the control groups. Patients in the intervention group 
will receive a baseline DOAC education intervention by a clinical pharmacist or a well-trained senior 
Pharm.D. student at the ACC. Participants in the study and pharmacists providing care will be aware of 
the intervention assignment. The principal investigator will be blinded until the end of the trial when all 
follow-up data are collected, and remain blinded for data analysis.   
We plan to recruit a total of 400 patients for this study, with 200 for primary prevention and 200 for 
secondary prevention. We will first stratify patients by their level of prevention (i.e., primary and 
secondary) and then randomize them into the intervention and the control groups. The sample size was 
estimated using G*Power software.18,19 The required sample size was 128 to detect a moderate effect in 
adherence, with a power of 0.80 and a significance level of 0.05. Given that the effect of the pharmacist-
led intervention will be evaluated separately for DOAC primary and secondary prevention, we propose 
recruiting 200 patients for each group, resulting in a total of 400 patients. 
 
Intervention 
 
Patients in the intervention group will be referred to the pharmacist-led ACC. At the first ACC 
visit, a comprehensive DOAC education will be provided, including information on (1) the indication and 
the reason of DOAC prescription, (2) the name and the appearance of the DOAC agent, (3) the dose, 
frequency, time of administration, (4) the mechanism of action, (5) management of missed doses, (6) 
potential side effects and self-monitoring, and (7) perioperative management. Patients will receive an 
education leaflet about DOACs to improve their understanding. An example of the DOAC education 
leaflet is provided in Figure 2. 
 

 
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Figure 2. Example of DOAC education leaflet   
 
In addition to the education leaflet, patients will receive a pillbox and a medication diary to help 
improve adherence to DOACs. They will also be encouraged to join the official ACC LINE app account 
for prompt consultation regarding drug-related issues, such as missed doses, side effects, and planned 
procedures. The pharmacist will also arrange two follow-up ACC visits, one at three months and the 
second at six months after the first visit. At the baseline ACC visit, the pharmacist will review patients’ 
EMRs to ensure an on-labeled DOAC dose regimen is prescribed. If the regimen is incorrectly prescribed, 
the pharmacist will contact the physician for prescription adjustment. During the follow-up visits, the 
pharmacist will identify any changes in laboratory tests and concurrent medications between the two 
visits. If there are drug related problems, the pharmacist will contact the prescribers for adjustments. The 
key components of the pharmacist-led ACC services are provided in Figure 3.  
 
 
 

 
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Figure 3. Key components of the pharmacist-led anticoagulant clinic services 
 
DOAC: direct oral anticoagulant. 
 
Study Endpoints 
The primary endpoint of this study is medication adherence, measured by the ARMS. The ARMS 
is a 12-item scale, with eight items measuring medication-taking adherence and four items measuring 
refill adherence.20 The items are structured using a 4-point Likert scale to assess the frequency of missed 
doses or refills, ranging from 1 “none of the time”, 2 “some of the time”, 3 “most of the time”, to 4 “all of 
the time”. A higher ARMS score indicates a lower adherence. The ARMS has good internal consistency 
and test–retest reliability, and it has been shown to be strongly correlated with the medication-taking and 
refill adherence.20 The ARMS will be administered to all study participants at their three-month and six-
month physician follow-up appointments as shown in Figure 1.  
The secondary endpoint is the treatment outcomes, including effectiveness and safety. 
Effectiveness will be measured by systemic thromboembolism, which are ischemic stroke (IS), transient 
ischemic attack (TIA), myocardial infarction (MI), coronary artery disease (CAD), peripheral artery 
disease (PAD), and venous thromboembolism (VT). Safety will be measured by major bleeding, which 
are intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and other major bleeding events. 
Clinical events will be measured at one-year and two-year follow-up by the NHI claims data, defined as 
inpatient admissions with a primary discharge diagnosis code corresponding to the conditions listed 
above.  
 
DOAC blood concentration 
In addition to the study endpoints, we will perform an auxiliary analysis that assess the correlation 
between DOAC concentration and medication adherence as well as treatment outcomes. For all patients 
enrolled in the trial, DOAC concentration will be measured at the three-month and six-month physician 
follow-up visits. The blood sample will be collected through venous puncturing in a K2EDTA (BD 
Vacutainer®) tube containing citrate. The time of sampling is trough, defined as at least 10 hours from 
last dose of dabigatran or apixaban, or at least 22 hours from the last dose of rivaroxaban or edoxaban.  
The blood sample will be centrifuged with a standard procedure and stored at -80 degrees Celsius. The 
DOAC concentration will be measured by using the ultra-high-performance liquid chromatography with 
tandem mass spectrometry (UHPLC-MS/MS). The method has been validated and published before.21 
The instrument that will be used is an Agilent 1290 UHPLC system coupled with an Agilent 6460 
triple quadrupole mass spectrometer (Agilent Technologies, Santa Clara, CA). A Kinetex reversed-phase 

 
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core-shell C18 column (2.1 × 50 mm, 2.6 µm, 100 Å, Phenomenex, Torrance, CA, USA) will be used for 
the separation. The mobile phase will consist of 0.1% formic acid in water (solvent A) and 0.1% formic 
acid in ACN (solvent B). The flow rate will be 0.35 mL min-1. The gradient profile will start with 1% B 
for 0.5 min, then change to 15% B in 0.1 min and remain at 15% B for 0.9 min, and then increase to 
100% B in 0.6 min and is maintained for 1.4 min. Finally, the column will be re-equilibrated to 1% B for 
1.5 min until the next injection. The temperature of the sample reservoir will be maintained at 4°C, and 
the column oven will be set at 40°C. The injection volume will be 3 µL. The JetStream electrospray 
ionizer will be employed as the ion source. The MS parameters will be set as follows: a 350°C drying gas 
temperature, a 10 L/min drying gas flow rate, a 45 psi nebulizer pressure, a 350°C sheath gas 
temperature, an 11 L/min sheath gas flow rate, a 3500 V capillary voltage, and a 500 V nozzle voltage. 
MS acquisition will be executed in multiple reaction monitoring mode and the mass transitions were 
472.2→289 and 472.2→144 for dabigatran, and 478.2→295.1 for the isotopic internal standard [13C6]-
Dabigatran; 460.2→443.1 and 460.2→199 for apixaban, and 464.2→203.1 for the isotopic internal 
standard [13C, d3]-apixaban; 436.1→144.9 and 436.1→72.9 for rivaroxaban, and 442.1→144.9 for the 
isotopic internal standard [13C6]-rivaroxaban; 460.2→443.1 and 460.2→199 for Edoxaban, and 
554.1→372.1 and 554.1→153 for the isotopic internal standard [d6]-Edoxaban. We will collaborate with 
the NTU Medical School Drug Research Center for blood sample analysis.22  
 
Statistical Analysis 
 
In Aim 1, we will first report and compare patients’ baseline characteristics by arms with 
descriptive statistics. Continuous variables will be compared by t-tests, and dichotomous or categorical 
variables will be compared by chi-square tests. The significance level will be set at 0.05 with a two-sided 
approach. We will use the intention-to-treat approach to analyze data from all randomized patients. For 
the primary endpoint, we will use both t-tests and linear regressions to evaluate the between-group 
differences and the magnitude of change in ARMS scores between the two arms, respectively. For the 
secondary endpoint, we will use the time-to-event approach to compare the hazard of event development 
between the two arms.  
 
In Aim 2, to understand the reasons of non-adherence to medication, we will begin with a report 
on the frequency and percentage of patients’ responses to the items related to medication taking in the 
ARMS. The summary score of the eight items measuring medication adherence in the ARMS will be 
correlated with the PDC measured in the NHI claims using Spearman correlation. Likewise, we will 
correlate the summary score of the four items measuring refill adherence in the ARMS to the refill 
records in the NIH claims data using Spearman correlation.  
 
In Aim 3, to understand the correlation between the DOAC blood concentration and medication 
adherence, we will dichotomize patients into high and low adherence groups based on the median ARMS 
score. Subsequently, we will compare the proportion of patients with blood concentrations within the 
therapeutic range between the two adherence levels by chi-square tests. Similarly, to understand the 
correlation between the DOAC concentration and treatment outcomes, we will first categorized patients 
into three groups based on their DOAC concentration: above the therapeutic range, within the therapeutic 
range, and below the therapeutic range. We will then compare the proportion of patients experiencing an 
event among those three groups by chi-square tests. 
 
To better understand the potential heterogeneity in the effect of patient education across different groups, 
we will first analyze the entire study population based on the randomization results to assess the overall 
effectiveness of pharmacist-led education. Next, we will conduct stratified analyses by the level of 
prevention (primary or secondary) to evaluate whether the effectiveness differs between these two 
subgroups. 
 
Study Timeline 
 
The overall timeline proposed for this study is five years. We plan to recruit eligible patients in the 
first two years. All patients will be followed for six months, and patient follow-up will occur from year 
one to year three. Once we complete the follow-up and data collection, we will analyze data on DAOC 

 
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use behavior, including medication adherence and refill adherence in year two and three. Analysis on 
DOAC blood concentration is expected to occur between year two and year four, depending on the 
capacity of the NTU Medical School Drug Research Center. Finally, in year four and five, we will 
acquire the NHI claims data for clinical event follow-up. As the Health and Welfare Data Science Center 
typically releases the NHI claims data from the previous year in the second quarter of the current year, we 
will need to wait until year four to get the complete patient follow-up data. We therefore plan to analyze 
patients’ one-year follow-up outcomes in year four and the two-year follow-up outcomes in year five. 
Figure 4 below presents the study timeline by aims.  
 
Figure 4. Graphical illustration of the study timeline by study aims 
 
NTUH: National Taiwan University Hospital; NHI: National Health Insurance; DOAC: direct oral anticoagulant. 
 
ANTICIPATED RESULTS 
 
Findings from this trial will enhance our understanding about the impact of pharmacist-led 
intervention on patients’ adherence and treatment outcome. We expect that the intervention will improve 
patients’ medication adherence and treatment outcomes. While our study focuses on DOAC users, the 
results should be applicable to other medication treatments for chronic conditions, as the primary goal of 
most treatments for chronic conditions is to prevent future events. Moreover, the frequency of medication 
administration for DOACs is comparable to that of medications used to treat other common chronic 
conditions. For instance, DOACs are typically administered once or twice daily, a regimen similar to that 
of common treatments for hypertension, diabetes, and hyperlipidemia. The simplicity of our intervention 
increases its relevance to routine practice. Our intervention, which consists of one-time patient education 
and two follow-up visits spaced three months apart, features a straightforward design that can be readily 
adapted to other therapeutic areas.  
 
In Aim 2, we expect to find good refill adherence but suboptimal medication adherence among 
patients taking DOACs. While we anticipate that most patients in Taiwan will refill their prescriptions 
due to the low out-of-pocket costs and easy access to healthcare services, there may still be instances 
where patients do not adhere to their prescribed medication regimen after obtaining their refills. 
Importantly, this pattern of medication non-adherence cannot be detected by secondary data sources such 

 
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as EMRs or claims data. Our results will provide further insight on the reasons behind non-adherence. 
Understanding the reasons for non-adherence will enable pharmacists and other healthcare providers to 
customize patient education, improving patient communication. For example, through this project, we 
will be able to understand whether patients miss doses due to forgetfulness or a perceived control of their 
condition, leading to a reduction in medication frequency. The findings from Aim 2 can also serve as 
valuable input for shaping the structure and content of future patient education initiatives. 
 
In Aim 3, we expect to observe a significant correlation between DOAC blood concentration and 
medication adherence. A higher proportion of patients with good adherence are anticipated to have a 
DOAC blood concentration falling within the expected range. We expect to find a low-to moderate 
correlation between DOAC blood concentration and treatment outcomes because of two reasons. First, 
the incidence rate of thromboembolism and major bleeding during DOAC therapy reported in clinical 
trials are low (approximately 1.7% and 3.0%, respectively). The rate will be even lower in patients using 
DOAC for stroke prevention. Second, DOAC concentration may not completely reflects the medication 
adherence as DOACs are medications that have rapid onset. Therefore, we design repeated DOAC 
concentration measurement in this study. Despite of these concerns, the association between DOAC 
concentration and clinical outcomes has been well-established.23-25 Understanding this correlation will 
help us to understand the role of DOAC level on measurement of drug adherence, and further enhance the 
DOAC management. 
Finally, students involving in this project will receive comprehensive training on study designs, 
patient education, data collection, and gain hands-on experience on data analysis. This project will also 
create chances for cooperation between the academic and the clinical settings, which will allow students 
to have multi-disciplinary training. Students and all the personnel in our research team will have the 
chance to attend international conference to present our study findings. We also expect to have peer-
reviewed journal publications from this project.   
 
HUMAN SUBJECTS 
 
In this study, we will recruit patients aged ≥18 years old, diagnosed with AF, and are expect to 
receive DOAC for at least three months for stroke prevention. We will exclude patients who are illiterate, 
have cognitive impairment, receive off-label DOAC regimens, or have a history of thromboembolic 
events. Eligible patients for this study will receive clear explanations about the intervention, including 
patient education, surveys regarding medication use behavior, and blood draws for DOAC concentration. 
Patients will also be informed about the two additional ACC follow-up visits, as well as the utilization of 
their EMRs and the NHI claims data for baseline assessment and follow-up, respectively. Since the EMRs 
contain all the required information about the patients, no additional information will be collected from 
the patients, except the medication taking behavior. Only patients who signed the informed consent form 
will be included in the study, and patients will be informed that they can withdraw from the study at any 
time after the recruitment without any reasons.  
 
All participants will receive standard care regardless of their intervention assignment. This study 
will not infringe patients’ right of seeking medical care or treatment, and only minimal risk will be 
involved. After each ACC visit, the participants will receive a gift card valued at $200.  
 
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