A Pharmacist Intervention for Monitoring and Treating Hypertension Using Bidirectional Texting
Phase: NA
Conditions: Hypertension
Sponsor: Linnea Polgreen

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PharmText BP 
A Pharmacist Intervention for Monitoring and Treating Hypertension 
Using Bidirectional Texting 
 
Study Protocol 
 
 
Date: 9/21/2020 
Version: 5.0 
 
Principal Investigators: 
Barry L. Carter, Pharm.D., Professor Emeritus, Department of Pharmacy Practice and 
Science, College of Pharmacy and Department of Family Medicine, College of Medicine, 
University of Iowa 
Linnea A. Polgreen, Ph.D., Associate Professor, Department of Pharmacy Practice and 
Science, College of Pharmacy, University of Iowa 
 
Grant Number: HL144880 
 
Project/Grant Period: September 15, 2019 – August 30, 2024 
 
Clinical Trials Number:  NCT03986931 
 
 

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Protocol Approval Page 
 
 
 

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Protocol Version and Amendment Tracking 
 
Study Title: A Pharmacist Intervention for Monitoring and Treating Hypertension Using  
 
         Bidirectional Texting 
 
 
Version Number/Amendment 
 
 
Approval Date 
 
Original Protocol, Version 1.0 
 
 
8/3/2019 
 
Revised Protocol, Version 2.0 
 
 
11/27/2019 
 
Revised Protocol, Version 3.0 
 
 
12/30/2019 
 
Revised Protocol, Version 4.0 
 
 
7/17/2020 
 
Revised Protocol, Version 5.0  
 
 
9/21/2020 
 
 
 
 
 
 

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Protocol Synopsis 
 
 
Protocol Title 
 
 
A Pharmacist Intervention for Monitoring and Treating 
Hypertension Using Bidirectional Texting 
 
 
Main Criteria for Inclusion 
 
 
Clinic measured blood pressure of ≥ 145 mmHg or ≥ 95 
mmHg at two previous clinic visits or one previous clinic visit 
and on the day of enrollment.  Previous clinic visit BPs must 
be within the past 18 months and measured at least 2 weeks 
apart from each other. 
 
 
Study Objective 
 
To evaluate whether our scalable SMS approach combined 
with a pharmacist-based intervention improves BP 
management and that is cost effective. 
 
 
Study Design 
 
 
A single-site, two-arm, single-blind randomized trial  
 
Number of Sites  
 
1 site, 3-4 clinic locations 
 
 
Study Arms 
 
2 Study Arms 
a) Intervention Group- Text 7 morning and 7 evening BP 
values at baseline. Monitored by a study pharmacist for 12 
months. Research visits at 6 and 12 months 
b) Control Group- Text 7 morning and 7 evening BP values 
at baseline. Research visits at 6 and 12 months 
 
 
Total Number of Subjects 
 
420 
 
 
Duration of Study Participation 
 
12 months  
 
 
Primary Outcomes 
 
Mean difference in systolic blood pressure between the 
control and intervention groups at 12 months. 
 
 
Secondary Outcomes 
 
Mean difference in diastolic blood pressure between the 
control and intervention groups at 12 months. 
 
Total number of medication changes (i.e., dose, 
discontinuation, initiation, etc.) from baseline to 12 months.  
 

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Total cost of medications, time spent by research staff, and 
clinic visits per patient from baseline to 12 months. 
 
 
Statistical Design and Power 
 
The analysis will be done on an intent-to-treat basis 
regardless of the number of reported BP readings or the 
number of pharmacist interactions with the participant.  
 
Our primary outcome will be a comparison of mean SBP 
values at 12 months. We will use a linear mixed effects 
model with mean BP at 12 months as the outcome. We will 
use random effects for clinic and physician nested within 
clinic to account for practice heterogeneity between clinics 
and providers.  
 
Based on prior work with the CAPTION trial, we expect a 
mean decrease in SBP of 17.3 (SD = 17.7) mmHg in the 
intervention arm and a decrease of 11.6 (SD = 18.2) mmHg 
in the control arm. We expect a difference of 5.65 mmHg 
between the groups with an expected pooled standard 
deviation of 17.9 with equal sized groups. In order to have 
85% power to detect a difference of 5.7 mmHg or larger 
decrease in SBP with a Type I error rate of 5% and a 
standard deviation of 17.9 mmHg, we would need 180 
subjects per arm or 360 subjects total.   
 
In preliminary work in the CAPTION trial, 13.4% of control 
subjects dropped out or were lost to follow-up. 14.0% of 
subjects dropped out of the intervention arm during the first 9 
months. In order to retain power after reasonable attrition 
rates over 12 months, we will recruit an additional 14% in 
each group to ensure we have at least 85% power. In 
addition, the sample size should slightly increase to 
accommodate the interim analyses.  This increases our total 
sample size to 420.  
 
One interim analysis is planned after outcome data is 
received and the results are reported to the Data Safety and 
Monitoring Board from the first half of the study. The interim 
monitoring method of Lan and DeMets will be used with 
O’Brien-Fleming alpha spending function for the interim 
analyses. Accordingly, type I error rate of 0.00305 for the 
interim analysis and 0.4695 will be used for the final 
analyses. The current sample size of 420 patients total 
accommodates the interim analyses. 
 
 
Futility Analysis 
 
To be determined by the Data and Safety Monitoring Board 
 
 

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Table of Contents 
 
Study Protocol............................................................................................................................ 1 
Protocol Approval Page ............................................................................................................. 2 
Protocol Version and Amendment Tracking ............................................................................... 3 
Protocol Synopsis ...................................................................................................................... 4 
Table of Contents ....................................................................................................................... 6 
Table of Appendices .................................................................................................................. 7 
Abbreviations ............................................................................................................................. 8 
1. Introduction ......................................................................................................................... 9 
1.1 Background ................................................................................................................... 9 
1.2 Clinical Experience with the Study Intervention ............................................................. 9 
2. Objectives, Aims, and Hypotheses ....................................................................................10 
2.1 Objective ......................................................................................................................10 
2.2 Aims and Hypotheses ..................................................................................................10 
3. Subject Inclusion/Exclusion Criteria ...................................................................................10 
3.1 Inclusion Criteria ..........................................................................................................10 
3.2 Exclusion Criteria .........................................................................................................11 
4. Study Design .....................................................................................................................11 
4.1 Overview ......................................................................................................................11 
4.2 Recruitment/Screening Procedures ..............................................................................12 
4.3 Baseline Visit Procedures ............................................................................................14 
4.4 Randomization and Treatment Arms ............................................................................17 
4.5 6-Month Visit Procedures .............................................................................................18 
4.6 12-Month Visit Procedures ...........................................................................................19 
4.7 Adverse Event Reporting and Determination................................................................19 
4.8 Unanticipated Problem Reporting .................................................................................19 
5. Study Outcomes ................................................................................................................20 
6. Statistical Design and Power .............................................................................................21 
7. Data Safety and Monitoring ...............................................................................................24 
8. Study Responsibilities .......................................................................................................24 
9. Ethical Considerations .......................................................................................................24 
 

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Table of Appendices 
 
Appendix 1: Participating Sites ..................................................................................................26 
Appendix 2: Study Procedures Timeline....................................................................................27 
Appendix 3: REDCap Screening Form ......................................................................................28 
Appendix 4: Consent Forms ......................................................................................................31 
Appendix 5: Baseline REDCap Form ........................................................................................44 
Appendix 6: BP Medications .....................................................................................................49 
Appendix 7: Drug Codes for Antihypertensive Agents ...............................................................50 
Appendix 8: Compensation Form ..............................................................................................57 
Appendix 9: Group Assignment REDCap Form .........................................................................58 
Appendix 10: Pharmacist REDCap Forms ................................................................................59 
Appendix 11: 12 Month Exit Survey ..........................................................................................65 
Appendix 12: Patient-Reported ER Visits or Hospitalizations ....................................................66 
Appendix 13: Clinic/Quick Care Visits, Emergency Room Visits, and Hospitalizations ..............67 
 
 
 
 

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Abbreviations 
 
AICc 
Akaike Information Criterion with Correction 
AWP 
Average Wholesale Price 
BP 
Blood pressure 
ICER 
Incremental Cost Effectiveness Ratio 
GCP 
Good Clinical Practice 
GLM 
Generalized Linear Mixed Effects Model 
LMM 
Linear Mixed Effects Models 
RUCA 
Rural-Urban Commuting Area  
SMS 
Short message service 
WyBP 
What’s your BP? 
 
 
 
 

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1. Introduction 
1.1 Background 
 
 
Hypertension causes an estimated 395,000 deaths in the US each year: one out of 
every six deaths. Hypertension is second only to smoking as a modifiable cause of death in the 
US. Poor blood pressure (BP) control increases the risk of myocardial infarction, stroke and 
death and is often due to delays in treatment intensification. In our prior work, we demonstrated 
that a physician-pharmacist collaborative intervention with pharmacists embedded within the 
medical offices reduced BP and it was cost effective. However, pharmacists spent a 
considerable proportion of their time obtaining and aggregating patients’ home BP 
measurements. Thus, we have developed a telehealth service called Centralized Healthcare 
Solutions that has successfully delivered clinical pharmacy services remotely to private 
physician offices, especially in small medical offices and rural locations. We have also 
developed an additional mhealth solution called What's your BP? (WyBP), a custom-built bi-
directional SMS based (short message service, or texting) platform. WyBP is inexpensive (i.e., 
does not require investment in smartphone technology, or WiFi), acceptable to a broad range of 
patients (including the elderly and rural populations), scalable to subject volume observed in 
busy clinical settings, and easily integrated into typical clinic workflows. In two pilot studies, we 
demonstrated a high rate of adherence, indicating that patients were willing and able to take 
home BP measurements and send them to our research team.  
 
 
This proposal combines our two prior efforts to use remotely located pharmacists and bi-
directional texting to improve efficiencies, reduce cost and improve access to a dedicated 
pharmacist. A major gap in our knowledge is whether the potency of a “virtual” team member 
can be improved by home BP monitoring with technological support, especially in small medical 
offices that are unable to employ clinical pharmacists. The goal of this proposal is to evaluate 
whether our scalable SMS approach combined with a pharmacist-based intervention improves 
BP management cost effectively. To achieve this objective, we will determine if our intervention 
leads to decreases in BP; determine if our intervention leads to intensification of therapy; and 
determine the cost effectiveness of the intervention. At the end of this project, we expect to 
provide a novel, scalable and cost-effective approach for treating hypertension in rural 
populations by expanding the feasibility, scalability and dissemination of the Centralized 
Healthcare Solutions intervention. The intervention has important public health relevance: if this 
intervention could be implemented broadly in primary care practices and lead to a decrease of 5 
mmHg BP, heart-disease deaths could be reduced by 15-20% and stroke deaths by 20-30%. 
 
1.2 Clinical Experience with the Study Intervention 
 
 
Dr. Polgreen has conducted clinical trials to capture blood pressure (BP) measurement, 
and she has been involved in observational research in the field of hypertension. She performed 
the cost effectiveness analysis for Dr. Carter’s CAPTION trial. She is also performing the cost 
analyses for his current NHLBI-funded studies: ICARE and MedFOCUS. In addition, she 
published a paper on trends in inpatient admissions for HTN. Her previous K-award “Treatment 
Effectiveness Using Observational Data: Which Method is Best?” was based on HTN treatment 
using angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and she is 
using multiple statistical and data analytic techniques to determine treatment effectiveness. 
 
 
Dr. Carter is a certified hypertension clinician (2016-2026). He practiced as a clinical 
pharmacist faculty member in Family Medicine residency training programs at the University of 
Iowa (1980- 1988) and Baylor College of Medicine (1988-1991) where he provided physician 

10 
 
education and direct patient management. He also practiced in the pharmacist-managed 
hypertension clinic at the West Side VA in Chicago (1991-1995). He was a member of the 
NHLBI Coordinating Committee of the National High Blood Pressure Education Program (1991-
2010), and he was a member of the last four national guideline committees (JNC-5, 6, 7 & 8 
[renamed the 2014 guidelines]). He also was asked to take the lead on a writing group on 
thiazides and dysglycemia by NHLBI. He was a member of the NHLBI workshop to develop 
research strategies to improve BP control in African Americans and another recent workshop to 
identify research strategies in Federally Qualified Health Centers. 
 
2. Objectives, Aims, and Hypotheses 
 
2.1 Objective 
 
 
The objective of this study is to evaluate whether our scalable SMS approach combined 
with a pharmacist-based intervention improves BP management and that it is cost effective. 
 
2.2 Aims and Hypotheses 
 
2.2.1 Aim 1: Determine if our intervention leads to decreases in BP.  
2.2.1.1 Hypothesis: Mean systolic BP in the pharmacist-intervention 
group will be significantly lower than mean systolic BP in the control 
group at 6 and 12 months.  
2.2.1.2 Hypothesis: Mean diastolic BP in the pharmacist-intervention 
group will be significantly lower than mean diastolic BP in the control 
group at 6 and 12 months.  
 
2.2.2 Aim 2: Determine if our intervention leads to intensification of therapy.  
2.2.2.1 Hypothesis: Participants in the pharmacist-intervention group will 
have more treatment changes, on average, than those in the control 
group.  
 
2.2.3 Aim 3: Determine the cost effectiveness of the intervention.  
2.2.3.1 Hypothesis: The intervention will be cost effective when compared 
to the control group.  
 
3. Subject Inclusion/Exclusion Criteria 
 
3.1 Inclusion Criteria 
 
 
English or Spanish speaking males and females. 
 
21 – 100 years of age. 

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 
Clinic measured blood pressure of ≥ 145 mmHg or ≥ 95 mmHg at two 
previous clinic visits or one previous clinic visit and on the day of 
enrollment.  Previous clinic visit BPs must be within the past 18 months 
and measured at least 2 weeks apart from each other. 
 
Lives in a zip code that is scored as a 4-10 on the Rural-Urban 
Commuting Area (RUCA) Codes. 
3.2 Exclusion Criteria 
 
 
Currently pregnant or planning to become pregnant in the next year. 
 
Upper arm circumference over 50 cm (20 in) 
 
Prisoner status. 
 
Unable to provide own informed consent. 
 
4. Study Design 
 
4.1 Overview 
 
 
The PharmText BP study was funded in September 2019 by the National Heart, Lung, 
and Blood Institute (NHLBI) of the National Institutes of Health (NIH). The study is being led by 
University of Iowa co-principal investigators Dr. Linnea A. Polgreen, Associate Professor of 
Pharmacy Practice and Science and Dr. Barry L. Carter, Professor Emeritus of Pharmacy 
Practice and Science and in the Department of Family Medicine.  
 
 
The goal of PharmText BP is to conduct a study to evaluate whether our scalable SMS 
approach combined with a pharmacist-based intervention will improve BP management and that 
it will be cost effective. The entire study will last 5 years and involve recruitment of 420 
participants from 3-4 clinics within 35 miles of University of Iowa Hospitals and Clinics.  
Participating clinics are listed in Appendix 1. All participants will live in areas that are 
considered rural by Rural-Urban Commuting Area Codes. The study aims to enroll at least 125 
participants (30%) who represent minority populations.  
 
 
All participants will have an initial screening/enrollment/baseline visit, a 2nd visit at 6 
months, and a final visit at 12 months with a research intern. Each in-person visit will include 
research blood pressure measurements (Omron HEM 907-XL), interviews, and medical record 
review. In addition to the in-person visits, all participants will be provided with a home BP cuff 
(Omron 5 Series), enrolled in our bi-directional text-messaging platform, WyBP, and asked to 
submit 7 morning and 7 evening BP measurements via text message following the baseline 
visit. Text message prompts asking for these BP measurements will stop after the 14 
measurements have been submitted, or after 15 days, whichever occurs first. Following the 
home BP measurements, participants will be randomized to either the pharmacist intervention 
arm or the texting-only control arm using a randomized block design with random block sizes 
with stratification according to clinic.  
 

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A timeline for the study procedures is provided in Appendix 2. 
 
 
Key personnel roles for the study are described below: 
 
Key Personnel 
 
Research Interns 
 
3-5 full time staff members employed by Internal Medicine at 
UIHC who will recruit participants and collect data.  
   
 
Research Pharmacists 
 
2-3 clinical pharmacists will provide the intervention and at least 2 
are certified hypertension clinicians as designated by the 
American Society of Hypertension. Pharmacists will provide 
telephone, text message, and email support for intervention 
participants and communicate with participant’s doctors via the 
electronic medical record. 
  
 
 
4.2 Recruitment/Screening Procedures 
 
 
Research interns will review the electronic medical record for patients who are 
scheduled to visit each of the participating clinics. They will screen the record for the past 18 
months to ensure that the eligibility criteria are met and that no exclusionary criteria exist (the 
REDCap screening instrument is provided in Appendix 3). If they are unsure about any of the 
inclusion/exclusion criteria for a specific patient, they will defer to the medical staff in the clinic.  
 
 
Inclusion Criteria:  
 
English or Spanish speaking males and females. 
 
21 – 100 years of age. 
 
Clinic measured blood pressure of ≥ 145 mmHg or ≥ 95 mmHg at two 
previous clinic visits or one previous clinic visit and on the day of 
enrollment.  Previous clinic visit BPs must be within the past 18 months 
and measured at least 2 weeks apart from each other. 
 
Lives in a zip code that is scored as a 4-10 on the Rural-Urban 
Commuting Area (RUCA) Codes. 
 
Exclusion Criteria: 
 
Currently pregnant or planning to become pregnant in the next year. 
 
Upper arm circumference greater than 50 cm (20 in) 
 
Prisoner status. 
 
Unable to provide own informed consent. 
 
 
Once a potential participant has been identified, the research intern will notify the 
appropriate medical staff that the patient is eligible for the study. If the medical staff confirms 
that the BP study is appropriate for the patient, they will inform the patient about the study 

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during the appointment and ask for permission for the research intern to explain the study 
further. If the patient is interested in learning more, the research intern will either meet with the 
patient in the exam room, or move the patient to a research-dedicated room, whichever has a 
lesser impact on clinic flow for that day. The screening questions will be reviewed again with the 
patient to ensure accuracy (particularly whether or not a female patient is planning to become 
pregnant in the next year, as that will not be reflected in the medical record).  
 
 
If a patient indicates that they are not interested in participating in the study at any time, 
they will be thanked for their time and allowed to leave the clinic.  
 
 
If all eligibility criteria are confirmed and they wish to participate, the research intern will 
describe the study, give the patient time to read the consent form, and answer any questions 
that the patient may have.  Specifically, the research intern will explain the following areas of the 
consent document:  
o Purpose of the research study, duration of study participation, and the number of 
research visits and study contacts (i.e., texting, phone calls, emails) required. 
o The study procedures and requirements. 
o The risks of the study.  
o The voluntary nature of the study. The participant may drop out of the study at 
any time.  
o That their decision to participate or not will have no effect on their relationship 
with or care from their physician or on the clinical care that they receive. 
o HIPAA information: The research team must have access to the participant’s 
medical information and to create medical information in order for the participant 
to be in the study; the investigators will obtain medical record data for the time 
period that spans 18 months preceding enrollment until 12 months following 
enrollment.  
o The research-related injury section.  
o Contact information that participants can use to reach investigators for study-
related issues. 
 
 
If the patient agrees to participate, they will be asked to sign two copies of the consent 
form. The research intern will sign the consent forms as the witness. One copy will be given to 
the participant and one copy will be kept and filed securely in the research team office. The 
patient will be enrolled in the research study in the electronic medical record via IRB and 
hospital policy.  
  
 
Patients may take an unsigned consent form with them to think about participation. They 
will be given contact information to schedule a follow-up appointment with an intern at a later 
date if they choose to participate.  
 
 
Patients may also sign the consent form but schedule completion of other baseline 
activities for a later date to meet their scheduling needs. 
 

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The English and Spanish consent forms are provided in Appendix 4.  
 
4.3 Baseline Visit Procedures 
 
 
4.3.1 Baseline Data Collection 
 
 
After the consent form has been signed, the research intern will continue with the other 
baseline activities. Together, the intern and participant will complete the demographic 
information that is collected on the Baseline Data REDCap form (Appendix 5). 
 
 
4.3.2 Blood Pressure Measurement 
 
 
Trained research interns will measure the participant’s blood pressure and document it 
on the Baseline Data REDCap form (Appendix 5). All measurements will be taken using the 
Omron HEM-907-XL using the following procedures: 
Prepare the Participant: 
• 
Participants should refrain from smoking for 20 minutes prior to the blood pressure 
measurement. 
• 
The participant should remove all clothing that covers the location of the cuff placement. 
• 
The participant should be comfortably seated in a chair, with the back supported, legs 
uncrossed and flat on the floor, the arm supported at heart level on a desk, with the palm 
facing upward. 
• 
The participant should sit for at least 5 minutes before the first measurement and should 
relax as much as possible. 
Cuff Measurement: 
• 
The participant’s arm circumference should be measured during screening to ensure the 
appropriate size cuff is used and to exclude morbidly obese participants where the cuff 
size is too small for their arm. The appropriate cuff should be chosen based on the 
measurement ranges specified for each cuff. If an arm measurement falls on a number 
that is specified for two cuffs, both cuffs should be placed on the arm sequentially and 
the cuff for which the INDEX arrow that is marked on the cuff falls within the range bar 
should be chosen.     
• 
If upper arm circumference is >50 cm (20 in) the participant will be thanked and 
excluded from the study.  
Cuff Placement:  
• 
Do not allow a sleeve to form a tourniquet on the arm.  
• 
Palpate the brachial artery in the antecubital fossa and place the ART ↓that is marked 
on the midline of the bladder of the cuff so that it is over the arterial pulsation of the 
participant’s bare upper arm.  

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• 
The lower end of the cuff should be ½ to 1 inch above the inner side of the elbow joint.  
• 
The middle of the cuff should be at the level of the right atrium (the mid-point of the 
sternum).  
• 
Place the cuff snugly around the bare upper arm so that you can only insert one finger 
between the cuff and the arm. 
Blood Pressure Measurement: 
• 
Use the Omron HEB-907-XL and record values in the Baseline Data REDCap form 
(Appendix 5).  
• 
Tell the participant that you will be taking 3-4 blood pressure measurements and that 
neither of you should talk during the measurements. 
o Take a single sitting BP reading with the MODE set to “SINGLE” and record. 
Wait at least 60 seconds before taking the next blood pressure. 
o Repeat this two more times. 
o The average of the 2nd and 3rd readings will be used as the research BP for this 
visit.  
o If the 2nd and 3rd BP values are more than 4 mmHg apart, a 4th value will be 
obtained and the two nearest values will be averaged. This will serve as the 
research BP for that visit. 
 
IF YOU GET AN ERROR MESSAGE AT ANY POINT, START THE SEQUENCE OVER.   
 
4.3.3 Blood Pressure Medications 
 
 
Research interns will record all BP medications (and dosage) that the participants are 
currently taking at the baseline appointment in the REDCap BP Medication Form (Appendix 6). 
This REDCap form is linked to the Master Drug Data Base Clinical Drugs BioPortal Ontology 
Service so that when a research intern begins typing a medication name, an appropriate 
spelling of the drug and all of the available dosages will automatically populate. This will 
substantially reduce data entry mistakes. If a participant is taking more than one BP medication, 
the REDcap form will allow them to create multiple entries. The research interns will use the 
updated Drug Codes for Antihypertensive Agents form used in the CAPTION trial to help them 
determine which of the patient’s medications are appropriate to record (Appendix 7). 
 
4.3.4 Enrollment in WyBP 
 
 
Before leaving the baseline appointment, the participants will need to be enrolled in 
WyBP so that they can send home-BP measurements via text message.  
o Go to https://vinci.cs.uiowa.edu/meditext2/home/ 
o Log in with your username and password. 
o Select the PharmText BP study from the dropdown menu. 
o Click the green Enroll Patient button in the top right corner. 
o Enter the participant’s phone number starting with the area code, click Next. 

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o Enter the participant’s Record ID from REDCap in the Subject identifier field. 
o Leave the email field blank. 
o Choose the participant’s preferred language (English or Spanish), click Submit. 
o You will be taken to an Edit Patient screen that shows the phone number you just 
registered along with a note at the top saying that the patient was successfully 
created in the study. Click the green Update button to be taken to the next step. 
o Back at the Home Screen, you will see that the Study Summary now shows an 
additional enrollment and progress made toward the overall enrollment goal. 
Click the Patients button to assign text message subscriptions to the participant 
you just enrolled. 
o Click on the Patient for whom you need to assign a text message subscription. 
o Click the green Add Subscription button in the top right corner. 
o Choose the PharmText Baseline Protocol. Set the Start Date to be tomorrow’s 
date. Set the End Date to be 15 days from tomorrow. Set the frequency to 1. 
Choose the appropriate morning and evening Send Times for the participant to 
receive the text messages (NOTE: the morning Send Time should be a time after 
the patient will wake up, but before they take any morning medications.  The 
evening Send Time should be a time that is convenient for the participant 
between dinner and going to bed.). Make sure both the Send End Message and 
Send End Email to Managers are checked. Click the green Submit button.  
 
A second set of subscriptions will need to be created for all intervention participants so 
that they can send their 3 days of BPs each month.  These subscriptions will be created by our 
software developer (unblinded). He will check REDCap once per week to see which new 
participants have been randomized to the intervention group. Then, he will create subscriptions 
for them to send 3 days of BPs each month beginning on the date that the participant was 
enrolled (i.e., if a participant was enrolled on August 15, they will submit their first day of BPs on 
the 15th, 16th, and 17th of each month throughout follow up). This strategy will allow the 
pharmacists to see a variety of BPs from different days of the week. The software developer will 
create the subscriptions using these steps: 
o Create subscriptions 2-12 for the participant for the 3 days of text messages 
each month throughout the 12 months of follow up.  
o Click the Patients button to assign a subscription to the appropriate participant.  
o Click on the Patient for whom you need to assign a text message subscription.  
o Click the green Add Subscription button in the top right corner.  
o Choose the PharmText Ongoing Protocol. Set the Start Date to be today’s date 
next month (i.e., if the participant enrolled on April 15th, you would set this Start 
Date to be May 15th). Set the End Date to be 2 days later. Set the frequency to 1. 
Choose the same morning and evening Send Times as the previous 
subscription. Do not check the Send End Message and Send End Email to 
Managers options until you are creating the final subscription.  
 

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4.3.5 Compensation 
 
 
Once a participant has completed the baseline appointment, a research intern will 
submit a form for a $50 compensation check to be mailed to the participant’s home using the 
university’s online eVoucher system. They will log this submission using the REDCap 
Compensation Form (Appendix 8).  
  
4.4 Randomization and Treatment Arms 
 
 
Dr. Emine Bayman created the stratified randomization lists for each clinic site. These 
lists are being uploaded to a website created by our software developer (unblinded). As 
participants have completed their home BP measurements, the research pharmacists will log 
into this website using a unique username and password. They will input the Record ID for the 
participant they need to randomize as well as the clinic location from which the participant 
enrolled. The website will inform the pharmacist of group assignment and they will record that in 
the Group Assignment REDCap form (Appendix 9). The website will store a log with a date and 
time stamp of which pharmacist randomized each participant to ensure that pharmacists do not 
intentionally or unintentionally alter the randomization in any way. This strategy should ensure 
that a relatively equal number of intervention and control participants are enrolled at each clinic.  
 
4.4.1 Control Group: 
 
 
Once the research pharmacist is informed of the participant’s group assignment, they 
will contact the participants. The pharmacist will discuss their home BP measurements and only 
provide general education on hypertension. If the BP values remain elevated on home 
monitoring, the pharmacist will advise the participant to make an appointment with their 
physician to address BP elevations.  This will be the only pharmacist contact for the control 
group. 
 
4.4.2 Intervention Group:   
 
 
The pharmacists will have access to the participants’ electronic medical records, all 
information collected by the research interns, and the home BP values that are submitted via 
text message. Pharmacists will employ a patient-centered approach to improve participant’s BP 
by providing support, education, and recommendations for treatment intensification, as 
necessary. They will communicate with participants via phone, text message, or email, based 
on participant preferences. They will not follow a specific protocol, but will base treatment 
decisions on current BP guidelines. They may schedule more home BP measurements than the 
3 days per month. Recommendations to physicians will primarily be made through the electronic 
medical record to quickly improve BP control. They will also recommend laboratory testing if 
indicated (e.g., serum potassium or creatinine).   
 
 
The pharmacists will review the home BP values with the intervention subjects.  If the 
home BP values are controlled, the pharmacist will continue to monitor home BP values.  

18 
 
However, if the pharmacist identifies issues such as poor medication adherence, inability to 
afford medications or other issues, they will work with the patient and physician to optimize 
therapy and/or reduce cost. If the pharmacist suspects white coat hypertension, they will make a 
recommendation to the physician to refer the patient to the University of Iowa ambulatory blood 
pressure service.  
 
 
If BP values are elevated, the pharmacist will assess medication adherence, ability to 
pay for medications and whether the regimen is optimal to control BP based on patient 
demographics and co-existing conditions.  The pharmacist will communicate recommendations 
for lifestyle and other changes directly to the subject.  If medication changes are needed, the 
pharmacist will communicate to the physician through the electronic medical record.  The 
pharmacist may recommend: 
1. Increased dose of a medication. 
2. Addition of a medication. 
3. Discontinuation of a medication. 
4. Modification of the regimen to optimize therapy, improve convenience (e.g. fixed-
dose combinations) or reduce cost. 
 
 
All participants in the pharmacist intervention group will continue to have access to a 
research pharmacist for the entire 12 months of follow up. Additionally, they will be asked to 
continue measuring and texting BP values (1 morning, 1 evening) for 3 days each month 
throughout the 12-month follow up.  
 
 
The pharmacists will typically contact with the participants every 2 weeks while BP is not 
controlled. Once BP is controlled, they will continue monitoring the participant’s records and 
home BPs and make contact at least every 2 months to support adherence and reassess BP 
control.  
 
 
The REDCap forms that the pharmacists will use to record data are shown in Appendix 
10 
 
4.5 6-Month Visit Procedures 
 
 
All participants will be asked to return to the clinic where they enrolled at for a 6-Month 
appointment with a research intern. To allow for flexibility with scheduling, 6-Month 
appointments will be allowed to occur anytime between 5 Months and 7 Months after the 
enrollment date. This BP value will be the outcome BP value. If a participant is not able to make 
it to the clinic during this window, but does want to come in after the 7 Month date, this will be 
allowed and all data will be collected, however, it will not be counted in the 6-month outcome 
and the 6-month outcome will be considered missing. In this case, a note will be placed in the 
participant’s record and these data may not be used in analyses.  
 
 
At the 6-Month appointment, the research intern will collect the research BP values, any 
BP medications that the participants are currently taking, the last 3 BP values that were 

19 
 
recorded by the participant’s home BP cuff, and test the home BP cuff for accuracy. If the home 
BP cuff appears to be measuring inaccurately, it will be replaced. The participant will be sent 
another $50 compensation check. All of the procedures outlined at baseline will be followed 
again, but the data will be collected on separate 6 Month REDCap forms (not shown). 
 
4.6 12-Month Visit Procedures 
 
 
All participants will be asked to return to the clinic for a 12-Month appointment with a 
research intern. To allow for flexibility with scheduling, 12 Month appointments will be allowed to 
occur anytime between 11 Months and 13 Months after the enrollment date. If a participant is 
not able to make it to the clinic during this window, these data will be missing. 
 
 
At the 12-Month appointment, the research intern will collect the research BP values, 
any BP medications that the participants are currently taking, a 12-Month Exit Survey 
(Appendix 11) asking for the participant’s feedback about the study, and send another $50 
compensation check. All of the procedures outlined at baseline will be followed again, but the 
data will be collected on separate 12-Month REDCap forms (not shown). Participants will also 
be asked about any hospitalizations or emergency room visits that occurred over the 12-month 
follow up period, especially those that occurred outside of the University of Iowa system 
(Appendix 12).  
 
 
Additionally, the research team will conduct a 12-Month Medical Record Review for each 
participant. This chart review will occur separately from the 12-Month visit and will not require 
any effort on the part of the participant. A member of the research team will screen the 
participant’s medical record for all clinic/quick care visits (documenting reason), any emergency 
room visits (documenting reason), and any hospitalizations (documenting reason and length of 
stay). These data will be recorded on the REDCap forms in Appendix 13. Again, multiple 
entries will be allowed by REDCap.    
 
4.7 Adverse Event Reporting and Determination 
 
 
As this is a low-risk study, we do not anticipate many adverse events. However, if any 
member of the research team becomes aware of a potential adverse event, they will report it to 
Dr. Peter Snyder (peter-snyder@uiowa.edu). He will review the event and make a ruling as to 
whether the adverse event is related to the study or not. If he determines that an adverse event 
has occurred, the DSMB and IRB will be notified as quickly as possible. Until an official ruling 
has been made by Dr. Peter Snyder, other members of the research team should not be 
notified, because they are blinded to group assignment.  
 
4.8 Unanticipated Problem Reporting  
 
 
There are other types of incidents, experiences, and outcomes that occur during the 
conduct of human subjects research that represent unanticipated problems but are not 
considered adverse events. For example, some unanticipated problems involve social or 

20 
 
economic harm instead of physical or psychological harm associated with adverse events. In 
other cases, unanticipated problems place subjects or others at increased risk of harm, but no 
harm occurs. If an unanticipated problem occurs that does not involve an adverse event, it will 
still be reported to the DSMB and the IRB under HHS regulation 45 CFR Part 46 (Unanticipated 
Events HHS Policy). 
 
5. Study Outcomes 
 
 
The study will have one primary outcome and three secondary outcome measures for 
the three specific aims. The primary outcome is change in SBP 12 months after the start of the 
intervention. The secondary outcomes are change in DBP 12 months after the start of the 
intervention, the number of medication changes as a measure of treatment intensification, and 
the additional cost of the intervention. 
 
Aim 1: Determine if our intervention leads to decreases in SBP. 
 
Our working hypothesis is that there will be greater decreases in both SBP and DBP 
among the pharmacist-intervention group than among controls. We will compute the change in 
SBP for each subject at 12 months compared to their initial SBP. The SBP readings will be 
collected at enrollment and at 12-months by research assistants. The primary outcome measure 
for Aim 1 will be the difference in mean SBP between the control and intervention groups at 12 
months.  
 
Aim 2: Determine if our intervention leads to intensification of therapy. 
 
Our working hypothesis is that there will be a greater number of medication changes in 
the intervention group compared to the control group. We will count the number of medication 
changes (dose increased, dose decreased, drug stopped, drug started) during the 12 months 
following the start of the intervention. The total number of medication changes will be the 
primary outcome measure for Aim 2. In addition, we will determine the number of pharmacist 
recommendations that were accepted by physicians. These are process measures: we found in 
our previous studies that BP improvement was primarily related to medication changes. We are 
assuming that changes are a sign of close monitoring. Indeed, we have used this measure 
previously. However, we realize that not all medication changes are equal, and thus we will 
record both medication trends and final treatment for each patient. 
 
Aim 3: Determine the cost effectiveness of the intervention. 
 
Our working hypothesis is that our intervention will be cost effective when compared to 
the control group. In addition, we will compare these results to previous pharmacist 
interventions. Because much pharmacist time is spent on non-direct patient care activities, we 
are convinced that our bi-directional texting approach will be both labor and cost saving. We will 
compute the incremental cost effectiveness ratio (ICER) using the total costs of doctor visits, 
pharmacist time, medications and medication changes during the 12 months of the trial. The 
ICER will be the difference between the control and intervention groups in average total cost 

21 
 
divided by the difference in average decrease of SBP and DBP. The ICER will be expressed in 
the dollars per mmHg reduction in BP and will be the primary outcome in this Aim.  
6. Statistical Design and Power 
 
 
Aim 1 Analysis: The analysis will be done on an intent-to-treat basis regardless of the 
number of reported BP readings or the number of pharmacist interactions with the participant. 
Our primary outcome will be a comparison of mean SBP values at 12 months. We will use linear 
mixed effects models (LMMs) with BP as the outcome. We will explore the timing of the change 
by also evaluating BP at 6 months. To test the intervention, we will include time (baseline, 6 
month, 12 month) as a fixed effect factor and its interaction with treatment arm. We will use 
random effects for clinic and physician nested within clinic to account for practice heterogeneity 
between clinics and providers. Temporal correlation will be accounted for by using an 
autoregressive error structure. Specifically, the model will be given as 
𝐵𝐵𝑃𝑃𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐= 𝜏𝜏𝑡𝑡+ 𝛼𝛼𝑐𝑐+ 𝛾𝛾𝑐𝑐𝑐𝑐+ ൫𝜔𝜔𝑡𝑡+ 𝜈𝜈𝑡𝑡𝑡𝑡+ 𝜉𝜉𝑡𝑡𝑡𝑡𝑡𝑡൯𝑋𝑋𝑐𝑐𝑐𝑐𝑐𝑐+ 𝜖𝜖𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐, 
 𝑐𝑐= 1, … , 𝐶𝐶,
𝑝𝑝= 1, … , 𝑃𝑃𝑐𝑐,
𝑖𝑖= 1, … , 𝑛𝑛𝑐𝑐𝑐𝑐,
𝑡𝑡∈{0,6,12}, 
൫𝛼𝛼𝑐𝑐, 𝛾𝛾𝑐𝑐𝑐𝑐൯
′ ∼
iid 𝑁𝑁(0, 𝐺𝐺1), 
(𝜈𝜈0𝑐𝑐, 𝜈𝜈6𝑐𝑐, 𝜈𝜈12𝑐𝑐)′ ∼
iid 𝑁𝑁(0, 𝐺𝐺2), 
൫𝜉𝜉0𝑐𝑐𝑐𝑐, 𝜉𝜉6𝑐𝑐𝑐𝑐, 𝜉𝜉12𝑐𝑐𝑐𝑐൯
′ ∼
iid 𝑁𝑁(0, 𝐺𝐺3), 
൫𝜖𝜖𝑐𝑐𝑐𝑐𝑐𝑐0, 𝜖𝜖𝑐𝑐𝑐𝑐𝑐𝑐6, 𝜖𝜖𝑐𝑐𝑐𝑐𝑐𝑐12൯
′ ∼
iid 𝑁𝑁(0, 𝑅𝑅), 
where 𝐶𝐶 is the number of clinics, 𝑃𝑃𝑐𝑐 is the number of providers within the 𝑐𝑐𝑡𝑡ℎclinic, 𝑛𝑛𝑐𝑐𝑐𝑐 is the 
number of subjects recruited under the 𝑝𝑝𝑡𝑡ℎ provider in the 𝑐𝑐𝑡𝑡ℎ clinic, 𝐵𝐵𝑃𝑃(𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐) is the blood 
pressure at time 𝑡𝑡 for the 𝑖𝑖𝑡𝑡ℎ subject under the 𝑝𝑝𝑡𝑡ℎ provider within clinic 𝑐𝑐, 𝜏𝜏𝑡𝑡 is the control mean 
at time 𝑡𝑡, 𝛼𝛼𝑐𝑐 and 𝛾𝛾𝑐𝑐𝑐𝑐 are the random control effects for the clinic and provider-nested-within-
clinic respectively, 𝜔𝜔𝑡𝑡 is the treatment effect at time 𝑡𝑡, 𝜈𝜈𝑡𝑡𝑡𝑡 and 𝜉𝜉𝑡𝑡𝑡𝑡𝑡𝑡 are the random treatment 
effects for the clinic and provider-nested-within-clinic respectively, 𝑋𝑋𝑐𝑐𝑐𝑐𝑐𝑐 equals 1 if the 𝑖𝑖𝑡𝑡ℎ subject 
under the 𝑝𝑝𝑡𝑡ℎ provider within clinic 𝑐𝑐 is assigned to the treatment group and zero otherwise, 𝜖𝜖𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 
is the (auto-correlated) noise term, and 𝐺𝐺1, 𝐺𝐺2, 𝐺𝐺3, and 𝑅𝑅 are covariance matrices for the 
random effects. This model will also be estimated for DBP. 
Second, transition to control for patients who were uncontrolled at their baseline visit will be 
modeled using a generalized linear mixed effects model (GLMM) based on the Bernoulli 
distribution with a logistic link. We will test the intervention by including a fixed-effects term for 
the treatment assignment (intervention versus control).  As before, we will include random 
effects for provider nested within clinic. Specifically, the model will be 
logit ቀℙ൫𝑍𝑍𝑐𝑐𝑐𝑐𝑐𝑐6 = 1ห𝑍𝑍𝑐𝑐𝑐𝑐𝑐𝑐0 = 0൯ቁ= 𝜏𝜏+ 𝛼𝛼𝑐𝑐+ 𝛾𝛾𝑐𝑐𝑐𝑐+ ൫𝜔𝜔+ 𝜈𝜈𝑐𝑐+ 𝜉𝜉𝑐𝑐𝑐𝑐൯𝑋𝑋𝑐𝑐𝑐𝑐𝑐𝑐, 
൫𝛼𝛼𝑐𝑐, 𝛾𝛾𝑐𝑐𝑐𝑐൯
′ ∼
iid 𝑁𝑁(0, 𝐺𝐺1), 
൫𝜈𝜈𝑐𝑐, 𝜉𝜉𝑐𝑐𝑐𝑐൯
′ ∼
iid 𝑁𝑁(0, 𝐺𝐺2), 
where 𝑍𝑍𝑖𝑖𝑖𝑖 equals 1 if the  𝑖𝑖𝑡𝑡ℎ subject under the 𝑝𝑝𝑡𝑡ℎ provider within clinic 𝑐𝑐 is controlled at time 𝑡𝑡, 
𝑡𝑡∈{0,6}, and zero otherwise. 

22 
 
Third, we will assess the duration of the change by modeling the odds of having controlled BP at 
12 months among those uncontrolled at baseline but controlled at 6 months using a GLMM 
similar to that described above. All three models will contain any covariates (e.g., age, sex) that 
were not sufficiently addressed through randomization. In all analyses, the random effects 
incorporated into the final model will be chosen via Akaike Information Criterion with correction 
for small sample sizes (AICc). 
 
 
Power: Based on prior work with the CAPTION trial, we expect a mean decrease in SBP 
of 17.3 (SD = 17.7) mmHg in the intervention arm and a decrease of 11.6 (SD = 18.2) mmHg in 
the control arm. We expect a difference of 5.65 mmHg between the groups with an expected 
pooled standard deviation of 17.9 with equal sized groups. In order to have 90% power to detect 
a difference of 5.7 mmHg or larger decrease in SBP with a Type I error rate of 5% and a 
standard deviation of 17.9 mmHg, we would need 180 subjects per arm or 360 subjects total.  
 
In preliminary work in the CAPTION trial, 13.4% of control subjects dropped out or were 
lost to follow-up. 14.0% of subjects dropped out of the intervention arm during the first 9 months. 
In order to retain power after reasonable attrition rates over 12 months, we will recruit an 
additional 14% in each group to ensure we have at least 85% power. In addition, the sample 
size should be slightly increased to accommodate the interim analyses.  This increases our total 
sample size to 420.  
One interim analysis is planned after outcome data are received and the results are 
reported to the Data Safety and Monitoring Board from the first half of the study. The interim 
monitoring method of Lan and DeMets will be used with O’Brien-Fleming alpha spending 
function for the interim analyses. Accordingly, type I error rate of 0.00305 for the interim analysis 
and 0.4695 will be used for the final analyses. The current sample size of 420 patients total 
accommodates the interim analyses.  
 
Aim 2 Analysis: The analysis will be done on an intent-to-treat basis regardless of the 
number of reported BPs or the number of pharmacist interactions with the subject. Our primary 
outcome will be the number of medication changes over 12 months in the control and 
intervention groups. We will use a GLMM based on the Poisson distribution with a log link 
function, and as in Aim 1 we will incorporate random effects for clinic and physician nested 
within clinic to account for practice heterogeneity between clinics and providers. As the 
observed treatment effects in those clusters are likely to be non-independent, we will include 
both random intercepts and random treatment effect for the intervention factor. Specifically, the 
model will be given as 
log ቀ𝔼𝔼൫𝑌𝑌𝑐𝑐𝑐𝑐𝑐𝑐൯ቁ= 𝜏𝜏+ 𝛼𝛼𝑐𝑐+ 𝛾𝛾𝑐𝑐𝑐𝑐+ ൫𝜔𝜔+ 𝜈𝜈𝑐𝑐+ 𝜉𝜉𝑐𝑐𝑐𝑐൯𝑋𝑋𝑐𝑐𝑐𝑐𝑐𝑐, 
൫𝛼𝛼𝑐𝑐, 𝛾𝛾𝑐𝑐𝑐𝑐൯
′ ∼
iid 𝑁𝑁(0, 𝐺𝐺1), 
൫𝜈𝜈𝑐𝑐, 𝜉𝜉𝑐𝑐𝑐𝑐൯
′ ∼
iid 𝑁𝑁(0, 𝐺𝐺2), 

23 
 
where 𝑌𝑌𝑐𝑐𝑐𝑐𝑐𝑐 is the number of medication changes for the  𝑖𝑖𝑡𝑡ℎ subject under the 𝑝𝑝𝑡𝑡ℎ provider within 
clinic 𝑐𝑐. The random effects incorporated into the final model will be chosen via AICc. 
 
Power: Based on existing work, we expect an average of 4.9 medication changes in the 
intervention group (SD = 5.1) and an average of 1.1 medication changes in the control group 
(SD = 1.6). We would expect a difference of 3.8 changes per year with a pooled standard 
deviation of 3.8. In order to have 85% power to detect a difference of 3.8 or more changes with 
a Type I error rate of 5% and a standard deviation of 3.8, we would need 19 subjects per arm 
or 38 total. Considering both 14% loss to follow-up and adjusting the type I error rate for interim 
analysis, power of the study with our sample size of 420 will be more than adequate. 
 
Aim 3 Analysis: The analysis will be performed on an intent-to-treat basis regardless of 
the number of reported BP measurements or the number of pharmacist interactions with the 
subject. The perspective of this cost analysis is society in general. For each patient encounter, 
pharmacists will record the number of minutes spent in the following activities: medical record 
review, consultation, patient assessment, ordering medications, medical education, lifestyle 
education, BP measurement education, making recommendations, and documentation in the 
medical record. Pharmacist costs will be estimated by multiplying the time spent by their 
compensation rate. Costs for clinic visits will be obtained from the university. Utilization 
measures will be converted to costs per subject using the Medicare fee schedule for visits. 
Pharmacist and physician salaries will be obtained from the Bureau of Labor Statistics. The 
average wholesale drug cost for prescription medications will be obtained from Lexicomp Online 
(https://online.lexi.com). Generic prices will be used when available. The drug cost per 
prescription for each subject will be calculated by multiplying the average wholesale price 
(AWP) by frequency and dose.  
We assume that subjects in the intervention and control groups will have similar characteristics. 
However, if there are significant differences between the subjects in these groups, costs will be 
predicted using a multivariate generalized linear model with a gamma family and a log link to 
control for these differences. 
We will determine the cost of the intervention by subtracting the average total cost (pharmacist, 
clinic, and drugs) for the intervention group from the average total costs for the control group. 
The ICER is calculated as the cost differential from the intervention divided by the outcome 
differential from the intervention. Our primary outcome will be average decrease in SBP, and the 
outcome differential will be the average decrease in SBP for the control group minus the 
average decrease in SBP for the intervention group. The result of this analysis will be an ICER, 
which gives the additional cost of the intervention per mm Hg of SBP decrease.  
We will conduct at least two sensitivity analyses. Because the drug costs (average wholesale 
prices) from Lexicomp often overstate the actual prices paid by insurance companies and 
patients, we will adjust our drug costs and re-estimate our cost-effectiveness analysis. 
Specifically, the Kaiser Family Foundation estimates that average wholesale prices are, on 
average 17% higher than weighted acquisition costs for brand-name drugs, and 80% higher for 
generic drugs. In addition, pharmacist time can be represented by either wages per hour, or the 

24 
 
amount that pharmacists can bill Medicare for each activity. We will consider both ways to 
measure the value of pharmacists’ time. 
7. Data Safety and Monitoring 
 
 
All procedures and protocols will be developed by the PIs and the study coordinator with 
protection of the participants and data as the highest priority. All procedures will be reviewed by 
the University of Iowa IRB as well as the Data and Safety Monitoring Board prior to being 
implemented (additional information about DSMB members and responsibilities can be found in 
the DSMB Charter). The study coordinator will thoroughly train and monitor all research interns 
during the course of the study and will be available to answer questions via phone when not in 
the clinic.  
 
8. Study Responsibilities 
 
 
By signing this protocol, the study’s two PIs agree to be responsible for implementing 
and maintaining quality control and quality assurance systems to ensure that all work incidental 
to this protocol is conducted and data are generated, documented, and reported in compliance 
with the protocol, with accepted standards of Good Clinical Practice (GCP), and with all 
applicable federal, state, and local laws, rules, and regulations relating to the conduct of the 
clinical study.  
 
 
Once the study activities are completed, the PIs will be primarily responsible for creation, 
review, and submission of publications and presentations relating to major aspects of the study 
and approved analyses within a timely fashion.  
 
The manuscript containing the overall study results will be distributed to all study 
investigators at the University of Iowa for review and comment before submission to a peer- 
reviewed journal with a reasonable period for review, but the final content will be at the 
discretion of the PIs. Any other manuscripts containing these data, including abstracts, will 
be distributed to all relevant study investigators who are participating on such publications 
before submission, with a reasonable period for review. Submitted publications will conform 
to international standards for biomedical manuscripts, including those regarding authorship. 
 
9. Ethical Considerations 
 
By signing this protocol, the PI agrees to conduct the study in compliance with the 
protocol; the Declaration of Helsinki; and all applicable federal, state, and local laws, rules, 
and regulations relating to the conduct of the clinical study. 
 
The University of Iowa has overall responsibility for the conduct of the study, 
including assurance that the study meets the sponsor’s regulatory requirements. 
The PIs have both ethical and legal responsibility to ensure that each subject being 
considered for inclusion in this study is given a full explanation of the study. Informed 
consent will be obtained from all subjects before any data are collected and before any 
study-related procedures are performed. Before and after subject provision of informed 

25 
 
consent, research team members will be available via email or phone to answer questions or 
concerns regarding procedures and risks. 
Subject confidentiality will be maintained throughout the clinical study. Subject 
information collected in this study will comply with the standards for protection of privacy of 
individually identifiable health information as promulgated by HIPAA and as mandated in Title 
45 CFR Parts 160 and 164. All records will be kept confidential, and the subject’s name will 
not be released to non-authorized persons or entities at any time.  Subject records will not be 
released to anyone other than members of the research team at each site who have a need 
for such information, and responsible regulatory authorities when requested. In all cases, 
caution will be exercised to assure the data are treated confidentially and that the subject’s            
privacy is guaranteed. 
Hard copy records containing subject data collected at sites (informed consent 
documents) will be stored in a locked cabinet in a locked office. Identification numbers will be 
used in place of names on report forms.  All electronic study data will be stored on encrypted, 
password-protected servers located within security firewalls, such that only members of the 
research team who need access will be allowed access to study files. Subject data will not be 
reused or disclosed to any other person or entity, except as required by law, for authorized 
oversight of the study, or for other research for which disclosure of the requested data would 
be permitted by the HIPAA Privacy Rule. If needed, any transport of electronic data will occur 
via a password-protected disk or secure transfer protocol. 
 
All subjects will consent, through their IRB-approved informed consent document to 
release of protected health information to the University of Iowa research teams as part of 
the consent process. 
 
 
 
 
 

26 
 
Appendix 1: Participating Sites 
 
 
Clinic Name  
and Location 
 
 
Lead Physician Name 
 
Population in 2010 
Census 
 
Minority/ 
Rural 
Population 
 
UI River Crossing 
Riverside, Iowa 
 
 
David Bedell, MD 
 
2,800 in 
surrounding 
communities 
 
70% Hispanic 
0.8% Black 
43.8% Rural 
 
 
Scott Blvd 
Iowa City, Iowa 
 
 
Katherine Imborek, MD 
 
3,736 in West 
Liberty, Iowa 
 
52.2% Hispanic 
0.4% Black 
12.5% Rural 
 
 
UIHC 
Iowa City, Iowa 
 
 
Daniel Fick, MD 
 
67,862 
 
5.3% Hispanic 
5.8% Black 
18.7% Rural 
 
 
IRL  
Coralville, Iowa 
 
 
 
Daniel Fick, MD 
 
 
 
North Liberty 
North Liberty, Iowa 
 
 
 
Daniel Fick, MD 
 
 
 
Muscatine 
Muscatine, Iowa 
 
 
Michael Maharry, MD 
 
22,886 
 
16.6% Hispanic 
2.3% Black 
23.7% Rural 
 
 
 
 
 
 
 
 

27 
 
Appendix 2: Study Procedures Timeline 
 
Time 
 
 
Activity 
 
 
Control Group 
 
Intervention Group 
 
Day 0 
 
Screening 
 
Consent 
 
Baseline 
Appointment 
 
X 
X 
 
Day 1 –  Days 7-15 
 
 
Home BP measured 
and returned via text 
message 
 
X 
X 
 
Days 7-15 – Day 18 
  
 
Participants 
randomized; 
Pharmacists review 
home BP values, 
contact participants 
 
X 
X 
 
Day 18 – 6 Months 
 
Participants text 
home BP values 3 
days per month 
 
Pharmacists monitor 
BP, adjust treatment 
as needed 
 
 
X 
 
6 Months 
 
Participants return to 
clinic for appointment 
 
X 
X 
 
6 Months – 12 
Months 
 
Participants text 
home BP values 3 
days per month 
 
Pharmacists monitor 
BP, adjust treatment 
as needed 
 
 
X 
 
12 Months 
 
Participants return to 
clinic for appointment 
 
X 
X 

28 
 
 
Appendix 3: REDCap Screening Form 
 
 
 

29 
 
 

30 
 
 

31 
 
Appendix 4: Consent Forms 
 
 
INFORMED CONSENT DOCUMENT 
 
Project Title: 
A Pharmacist Intervention for Monitoring and Treating Hypertension Using 
Bidirectional Texting. 
Principal Investigator: 
Linnea Polgreen, PhD 
Research Team Contact: 
Shelby Francis 319-678-8037 
This consent form describes the research study to help you decide if you want to participate.  This form 
provides important information about what you will be asked to do during the study, about the risks and 
benefits of the study, and about your rights as a research subject.   
• If you have any questions about or do not understand something in this form, you should ask 
the research team for more information.   
• You should discuss your participation with anyone you choose such as family or friends.   
• Do not agree to participate in this study unless the research team has answered your 
questions and you decide that you want to be part of this study.  
WHAT IS THE PURPOSE OF THIS STUDY? 
This is a research study.  We are inviting you to participate in this research study because you are an 
adult between the ages of 21 and 100 years, have had at least 2 blood pressure measurements of ≥145 
mmHg systolic or ≥95 mmHg diastolic in the past 18 months, live in a rural area, and do not have an 
upper arm circumference greater than 50 cm (20 in).  
The purpose of this research study is to determine whether our text messaging approach combined with 
a pharmacist-based intervention improves blood pressure management in a cost-effective manner.  
HOW MANY PEOPLE WILL PARTICIPATE? 
Approximately 800 people will take part in this study conducted by investigators at the University of 
Iowa.   
HOW LONG WILL I BE IN THIS STUDY? 
If you agree to take part in this study, your involvement will last for 12 months.  The initial appointment 
will last approximately 30 minutes.  You will return to the clinic for appointments at 6 and 12 months.  
These appointments are expected to last for approximately 30 minutes.  
WHAT WILL HAPPEN DURING THIS STUDY? 
A member of the research team will take your blood pressure up to 4 times during the baseline 
appointment and will also collect additional data (age, sex, race, rural residence, ethnicity and language, 
marital status, insurance, body mass index, other conditions, blood pressure medications, smoking and 
vaping status, current alcohol intake, and distance from your home to the clinic) from you and your 
medical record. They will also ask you to provide the name and phone number for a friend or family 
member who will know how to reach you during the 12 months of follow up should the research team 

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FORMULARIO DE CONSENTIMIENTO INFORMADO  
 
Título del Proyecto: Una intervención de farmacéutico para la supervisión y tratamiento de la 
hipertensión usando mensajes de texto bidireccional. 
Investigator Principal: 
 
 
Linnea Polgreen 
Contacto del equipo de investigación: 
Shelby Francis 319-678-8037 
Este formulario de consentimiento describe el estudio de investigación para ayudarle decidir si quiere 
participar. Este formulario proporciona información importante sobre lo que se le pedirá durante el 
estudio, sobre los riesgos y beneficios del estudio, y sobre sus derechos como sujeto de investigación.  
• Si tiene preguntas, o si no entiende algo de este formulario, debe de preguntarle al equipo 
de investigación por más información.  
• Usted debería discutir su participación con cualquier persona que elija, como la familia o 
los amigos.  
• No este de acuerdo en participar en este estudio a menos de que el equipo de 
investigación haya contestado sus preguntas y decida qué quiere ser parte de este estudio. 
¿QUE ES EL OBJETIVO DE ESTE ESTUDIO? 
Este es un estudio de investigación. Le invitamos a participar en este estudio de investigación porque 
eres un adulto de una edad elegible y has tenido por lo menos 2 medidas de presión arterial mas de 145 
mmHg sistólica y/o mas de 95 mmHg diastólica y vives en una zona rural.  
El objetivo de este estudio es para determinar si nuestros mensajes de texto combinado con una 
intervención de farmacéutico mejora la administración de la presión arterial en una manera costo-
efectiva.  
¿CUANTAS PERSONAS PARTICIPARAN? 
Aproximadamente 800 personas tomaran parte en este estudio realizado por investigadores en la 
Universidad de Iowa.  
¿CUANTO TIEMPO ESTARE EN ESTE ESTUDIO? 
Si usted acepta tomar parte en este estudio, su participación tendrá una duración de 12 meses. La cita 
inicial durará 20 minutos. Regresará a la clínica para citas en mes 6 y en mes 12. Se espera que estas 
citas duren aproximadamente 30 minutos.  
¿QUE PASARA DURANTE ESTE ESTUDIO? 
Un miembro del grupo de investigación tomará su tensión arterial 3 veces durante la cita de referencia y 
también coleccionará datos adicionales (edad, sexo, raza, residencia rural, pertenencia étnica y lengua, 
estado civil, seguro, índice de masa de corporal, enfermedades crónicas, medicamentos, cualquier efecto 
secundario de medicamentos, y distancia de su casa a la clínica) de su registro médico. después de la cita 
de referencia, se le asignará al azar al grupo de control (solo mensajes de texto) o al grupo de 
intervención (mensajes de texto más farmacéutico). Esto significa que cualquier asignación de estudio 
que recibas se determinará puramente por casualidad, cómo lanzar una moneda. Tendrá la misma 
posibilidad de recibir una de las dos asignaciones de estudio. 

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Appendix 5: Baseline REDCap Form 
 
 
 
 

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Appendix 6: BP Medications 
 
 
 
 
 

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Appendix 7: Drug Codes for Antihypertensive Agents 
 
 

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Appendix 8: Compensation Form 
 
 
 
 
 
 

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Appendix 9: Group Assignment REDCap Form 
 
 
 
 
 
 

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Appendix 10: Pharmacist REDCap Forms 
 
 
 

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Appendix 11: 12 Month Exit Survey 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Appendix 12: Patient-Reported ER Visits or Hospitalizations 
 
 
 
 

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Appendix 13: Clinic/Quick Care Visits, Emergency Room Visits, and 
Hospitalizations 
 
 
 
 
 
 

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