MEDication Focused Outpatient Care for Underutilization of Secondary Prevention
Phase: NA
Conditions: Diabetes, Hyperlipidemia, Hypertension, Cardiovascular Disease
Sponsor: Korey Kennelty

1 
 
 
Study Protocol 
 
 
Date: 11/17/2014 (revised 6/14/2017) 
 
Version: 2.0 
 
Special Note: (This version reflects the changes following the decision of the Data and Safety 
Monitoring Board [DSMB] at their meeting February 2017). The DSMB decision was to 
terminate data collection once all subjects complete their 12-month study visit. That will occur 
on June 30th, 2017. Reference to the data collection termination date below will be that date. 
Some subjects who enrolled in the trial first had a 24-month chart abstraction done prior to that 
date. While we do not plan to use the data from these latter subjects, the following protocol 
reflects the procedures for those subjects who had a 24-month abstraction prior to the data 
collection termination date. 
 
 
Principal Investigators: 
 
Barry L. Carter, Pharm.D., the Patrick E. Keefe Endowed Professor of Pharmacy in the 
College of Pharmacy, and Professor in the Department of Family Medicine, College of Medicine, 
University of Iowa. 
 
Christopher Coffey, PhD., Professor in the Department of Biostatistics and Director of the 
Clinical Trials Statistical and Data Management Center, College of Public Health, University of 
Iowa. 
 
 
Grant Number: NHLBI R18HL116259 
Project/Grant Period: 4/1/2014-3/31/2019 
Clinical Trials Number: NCT02215408 

PROTOCOL APPROVAL PAGE 
Study Title: MEDication Focused Outpatient Care for Underutilization of Secondary 
Prevention 
 
Version: 
Date of 
Issue: 
2.0 
6/14/2017 
 
Study Sponsor: National Heart, Lung and Blood Institute, National Institutes of Health 
The signatures below constitute the approval of this protocol and the attachments and provides 
the necessary assurances that this trial will be conducted according to all stipulations of the 
protocol, including all statements regarding confidentiality, and according to local legal and 
regulatory requirements and applicable U.S. federal regulations 
 
 
 
Co-Principal Investigator 
Date 
(printed) 
 
Christo  her S. Coffey, PhD 
Co-Principal Investigator 
Co-Princip 
(printed) 
 
Date 
/7 

3 
 
 
 
PROTOCOL VERSION AND AMENDMENT TRACKING 
 
Study Title: MEDication Focused Outpatient Care for Underutilization of Secondary 
Prevention 
 
Version Number/Amendment 
Approval Date 
Original Protocol, Version 1.0 
11/17/2014 
Revised Protocol, Version 2.0 
6/14/2017 

4 
 
 
PROTOCOL SYNOPSIS 
 
Protocol Title 
MEDication Focused Outpatient Care for 
Underutilization of Secondary Prevention 
(MEDFOCUS) 
Diagnoses and Main Criteria for 
Inclusion 
Patients who have at least one risk factor for 
cardiovascular disease (CVD) 
Study Objective 
To determine the extent to which a care delivery model 
utilizing a centralized Cardiovascular Risk Service 
(CVRS) will be implemented in medical offices with 
large geographic, racial and ethnic diversity 
Study Design 
A 20 site, two-arm, cluster-randomized trial 
Number of sites 
20 
Study arms 
Each site will be classified as either a high minority 
(estimated ≥40% minority) or low minority (estimated 
<40% minority) site. At the outset of the trial, a 
stratified randomization (stratified by minority status) 
will be used to assign each site in a 1:1 fashion to one 
of two arms: a) the centralized cardiovascular risk 
service (CVRS) group or b) the usual care group, with 
all patients at a given site participating per the site’s 
randomization. 
Each site will consent 20-25 patients to the site’s study 
arm. 
Total Number of Subjects 
400 
Duration of Study Participation 
12 months active, with additional medical record 
abstraction at 24 months for subjects who reach that 
time point prior to the data collection termination date. 
No 24-month abstraction will be performed for the 
remaining subjects. 
Primary Outcome 
The degree to which care adheres with the Guideline 
Advantage standards of care that apply for secondary 
prevention of CVD and other prevention strategies. 
Secondary Outcomes 
1. Adherence to Guideline Advantage standards of 
care in minorities and in African Americans 
2. BP control, mean BP, LDL cholesterol, HgbA1c all 
subjects 
3. Measurement of Stages of Change 
4. Intensity of medication management 
5. Medical Home Index 
6. Provider attitudes to deliver intervention, barriers 
and facilitators to implementation 

5 
 
 
Statistical Analysis Methods 
Guideline Advantage Scoring: We will create a score 
for each subject at baseline and 12 months based on 
the number of applicable Guideline Advantage criteria 
that are met. 
For each subject, the primary outcome will involve a 
determination of the percentage of applicable 
Guideline Advantage criteria met at the end of the 
twelve month active participation period. The analysis 
will use a mixed model, adjusted for adherence at 
baseline and the minority status grouping. 
The same process will be used to calculate a percent 
score for a) the subgroup of all minority subjects and b) 
the subgroup of African-American subjects. 
To evaluate barriers and facilitators to implementing 
the intervention, the relationship between provider- 
level attitudes and beliefs and adherence scores will 
be calculated. 
A cost-effectiveness analysis will assign a cost to 
CVRS pharmacist time (including record review, 
patient assessment, email time, telephone follow-up), 
clinic visits, emergency room visits, hospitalizations, 
and laboratory procedures. Incremental costs as a 
function of differences in guideline adherence, LDL 
cholesterol, blood pressure, or HgbA1c will be 
calculated at baseline and 12 months. These findings 
will be expressed as dollars per incremental 
improvement in guideline adherence or individual 
outcomes such as LDL cholesterol, blood pressure, or 
HgbA1c. 
Futility Analysis 
One futility assessment based on a determination of 
predictive power will be conducted at a time when half 
of the planned active participants have completed their 
twelve month follow-up. Predictive power < 5% will be 
considered an indicator of futility. 
This analysis was conducted for the February 2017 
DSMB meeting. The results met the criteria for futility 
so the DSMB recommended that all subjects 
completethe 12 month visit but that would not be 
collected following the data collection termination date. 

6 
 
 

7 
 
TABLE OF CONTENTS 
Protocol Approval Page 
2 
Protocol Version and Amendment Tracking 
3 
Protocol Synopsis 
4-5 
Table of Contents 
7-9 
List of Abbreviations 
10 
1. Introduction 
1.1 
Background 
11 
1.2 
Clinical Experience with Study Intervention 
11 
1.3 
Rationale 
12 
2. Objective, Aims and Hypotheses 
12-13 
3. Subject Selection 
3.1 
Inclusion Criteria 
13 
3.2 
Exclusion Criteria 
13-14 
4. Study Design 
4.1 
Overview of Study 
14-15 
4.2 
Site Randomization and Treatment Arms 
15 
4.3 
Recruitment Procedures 
4.3.1 
Identification and Contact of Potential Subjects 
16-17 
4.3.2 
Confirmation of Eligibility 
17 
4.4 
Baseline Visit Procedures 
4.4.1 
Informed Consent Procedures 
17-18 
4.4.2 
Surveys 
18 
4.4.3 
Blood Pressure Measurement 
19-20 
4.4.4 
Laboratory Specimens 
21 
4.4.5 
Instruction on IowaPHRM 
21 
4.4.6 
Medical record Abstraction and Verification 
21 
4.5 
4 & 8 Month Medical Record Abstraction (CVRS intervention sites only) 
21 
4.6 
12 Month Visit Procedures 
4.6.1 
Surveys 
22 
4.6.2 
Blood Pressure Measurement 
22 
4.6.3 
Laboratory Specimens 
22 
4.6.4 
Medical Record Abstraction and Verification 
22 

8 
 
4.7  24 Month Medical Record Abstraction (only for subjects who reached 
the 24 month time point prior to the data collection termination date 
22 
4.8 
Study CVRS Intervention 
23 
4.9 
Serious Adverse Event Screening and Reporting 
23-24 
4.10  Study Termination 
4.10.1 
Early Termination 
24 
4.10.2 
End of Study Termination 
24 
5. Outcomes 
5.1   Primary Outcomes 
5.1.1 
Adherence to Guideline Advantage Criteria in all subjects 
25 
5.1.2 
Adherence to Guideline Advantage Criteria in Minority Subjects 
25 
5.2 
Secondary Outcomes 
5.2.1  Adherence to Guideline Advantage Criteria in African-American 
Subjects 
25 
5.2.2 
BP Control, Mean BP, LDL Cholesterol, HgbA1c all subjects 
25 
5.2.3 
Measurement of Stages of Change 
25 
5.2.4 
Intensity of Medication Management 
25 
5.2.5 
Medical Home Index 
26 
6.2.6  Provider attitudes to deliver intervention, barriers and facilitators to 
implementation 
26 
6. Statistical Analysis Plan 
6.1 
Statistical Design 
26 
6.1.1 
Primary Analysis 
27 
6.1.2 
Secondary Analyses 
27 
6.1.3 
Cost Effectiveness Analysis 
28 
6.2 
Covariates 
28 
6.3 
Power and Sample Size 
28-29 
6.4 
Futility Analysis 
29 
6.5 
Strategies to Limit and Handle Missing Data 
29-30 

9 
 
7.   Data and Safety Monitoring 
7.1 
Site Monitoring Roles 
30 
7.2 
Local IRB Monitoring Roles 
30 
7.3 
DCC Monitoring Roles 
30-31 
7.4 
Physician Monitor Roles 
31 
7.5 
DSMB Monitoring Roles 
7.5.1 
DSMB Composition 
31 
7.5.2 
DSMB Tasks 
31-32 
7.6 
CCC Monitoring Roles 
7.6.1 
Dissemination of DSMB Meeting Summary Reports 
32 
7.6.2 
Reports to NHLBI 
32-33 
7.7 
Data Management to Maintain Blinding 
33 
8. Study Responsibilities 
8.1 
University of Iowa Principal Investigator Responsibility 
33 
8.2 
Training 
33 
8.3 
Communication with Sites 
33 
8.4 
Study Documentation 
34 
8.5 
Data Transmittal and Record Retention 
34 
8.6.   Use of IowaPHRM 
34 
8.7 
Study Closeout 
34 
8.8 
Publication Policies 
34-35 
9. Ethical Consideration 
9.1 
Roles of University of Iowa 
35 
9.2 
Informed Consent 
35-36 
9.3 
Confidentiality of Subjects 
35-36 
9.4 
Authorization for Release of Protected Health Information 
36 
9.5 
Human Subjects Protection 
36-37 
9.6.   IRB Review 
37 
10. 
Appendices 
APPENDIX I: 
Participating Sites 
39 
APPENDIX II: 
Study Timetable 
40 
APPENDIX III: 
Inclusion/Exclusion criteria 
41-42 
APPENDIX IV: 
CVRS Intervention Summary 
43 
11. 
References 
44-49 

10 
 
ABBREVIATIONS 
ADA 
American Diabetic Association 
AHA 
American Heart Association 
AHRQ 
Agency for Healthcare Research and Quality 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
BP 
Blood pressure 
CAD 
Coronary artery disease 
CCC 
Clinical Coordinating Center 
CCM 
Chronic Care Model 
CVD 
Cardiovascular disease 
CVRS 
Cardiovascular risk service 
DCC 
Data Coordinating Center 
DSMB 
Data and Safety Monitoring Board 
HgbA1c 
Hemoglobin A1c 
HIPAA 
Health Insurance Portability and Accountability Act 
IowaPHRM 
Iowa Personal Health and Research Management 
IRB 
Institutional Review Board 
LDL 
Low density lipoprotein 
MEDFOCUS 
Medication Focused Outpatient Care for Underutilization of Secondary Prevention 
MI 
Myocardial infarction 
NHLBI 
National Heart, Lung and Blood Institute 
NIH 
National Institutes of Health 
PI 
Principal Investigator 
SAE 
Serious adverse event 

11 
 
1. INTRODUCTION 
 
1.1. Background 
 
Cardiovascular disease (CVD) causes 2,200 deaths in Americans each day, with one death 
occurring every 39 seconds.1 Although evidence suggests that these deaths can be prevented 
with better risk factor management, many risk factors remain uncontrolled. The Patient-Centered 
Medical Home, a system of care in which the patient has an ongoing relationship with a personal 
physician and medical team2-8 and which utilizes self-management and personalized health 
records, has been proposed as a strategy to reduce gaps in care delivery.9   Medical Home 
models often use physician/pharmacist collaboration, a process by which pharmacists work 
directly with patients and physicians to optimize therapy.10,11,12, 13-36The Chronic Care Model 
(CCM),37-48  which includes pharmacists as care managers,37, 38, 42, 44  places particular emphasis 
on self-management support, delivery system redesign and health care organization and 
community resources.8, 40, 43, 49-51 
 
Several Cochrane reviews and meta-analyses have found evidence that adding pharmacists 
to the primary care team improves risk factor control and physician adherence to guidelines.52-54 
And the IOM, Centers for Disease Control and Cochrane center, have called for more research to 
evaluate the use of pharmacists for CVD management.54-57 Over 100 studies on CVD have 
involved pharmacists including studies on heart failure,28, 54,   anticoagulation,23, 29-30 
hypertension,16, 59-61 hyperlipidemia,12, 26, 31, 32, 34 diabetes,33, 58 and multiple risk factors.12, 15 A 
systematic review of 30 trials in patients with CVD found significant improvements in risk factor 
control with pharmacist management.62 However, most studies have involved single disease 
states, single clinics and limited intervention pharmacists. 
 
One managed care organization has found that a centralized cardiovascular risk service 
(CVRS) managed by pharmacists can reduce mortality.12 It is not known, however, if a 
comprehensive CVRS model can be scaled up, implemented and disseminated within numerous, 
diverse primary care settings that are not within an integrated health system. This lack of 
evidence constitutes a major gap in knowledge. 
 
1.2 Clinical Experience with the Study Intervention 
 
The University of Iowa research team has extensive experience using team-based care to 
improve care management of patients with complex medical histories. We have pioneered 
strategies to evaluate team care implementation and guideline adherence using cluster- 
randomized trials.63-64 Iowa investigators have conducted evaluations of physician adherence to 
guidelines60, 65-70 and will use similar strategies for MEDFOCUS. The Iowa research team is a 
national leader in studying models of primary care delivery.17, 19-20, 26, 36, 59, 60, 70-76 Drs. Carter, 
Chrischilles and James have developed and evaluated theoretical models and instruments for 
physician-pharmacist collaboration,35, 77-78 physician knowledge,36, 67, 79 and guideline 
adherence,60, 65-6, 69-70, 79-82 and Dr. Carter has conducted nine health services outcome studies 
funded by National Heart, Lung and Blood Institute (NHLBI) and the Agency for Healthcare 
Research and Quality in the last six years. 
The study will be conducted within our practice-based research network (PBRN), led by Barry 
L. Carter (PI). The CVRS model will provide services by telephone, text messages or 
asynchronous web discussions. The CVRS intervention pharmacist will be integrated into the on- 
site primary care team and frequently have two-way communication with providers. 

12 
 
1.3 Rationale 
 
Adherence to guidelines for CVD is low, and regional and age variations in guideline concordant 
therapy following myocardial infarction (MI) have been found.65, 83-87 The primary barrier is 
suboptimal medication use leading to poor disease control, often because busy providers must 
address acute non-CVD complaints.88-90 Managed care organizations and other settings are 
increasingly hiring clinical pharmacists to improve management of CVD. The present study will 
evaluate an efficient, centralized, web-based CVRS to support primary care providers to improve 
the management of CVD and achieve key performance measures.91 The ultimate goal of the Iowa 
research program is to reduce CVD events when our intervention is implemented more broadly.12 
These findings will be significant because there could be 20-30% fewer coronary deaths and 25- 
40% fewer stroke deaths in the U.S. if this intervention were applied across all medical offices that 
currently utilize clinical pharmacists. This study will meet important targets in the NHLBI strategic 
plan, the Million Hearts Campaign, the American Diabetes Association (ADA) and the American 
Heart Association (AHA) as outlined in the Guideline Advantage program. 
 
2. OBJECTIVE, AIMS, AND HYPOTHESES 
 
2.1 Objective 
 
The objective of this project is to conduct a multi-center, cluster-randomized study utilizing a 
centralized CVRS for medical offices with large geographic, racial and ethnic diversity to 
determine the extent to which the CVRS model will be implemented. We will randomize 20 
primary care offices to either the CVRS arm or a usual care arm and enroll 20-25 patients per 
office for a total of 400 subjects, of which 240 will be from racial minorities. 
 
2.2 Aims and Hypotheses 
 
Our central hypothesis is that a centralized CVRS managed by clinical pharmacists will be 
implemented and significantly improve care adherence to nationally recognized guidelines for 
standards of care when measured utilizing the Guideline Advantage metrics. We will test our 
central hypothesis with three specific aims: 
 
2.2.1 Aim 1: To determine if a web-based CVRS managed by clinical pharmacists will be 
implemented within diverse primary care offices. 
 
2.2.1.1 Primary Hypothesis 1a: Adherence to guidelines for secondary prevention of 
CVD will be significantly greater in patients from clinics randomized to the centralized 
CVRS group compared to the control group. 
 
2.2.1.2 Primary Hypothesis 1b: Adherence to guidelines for prevention of CVD will be 
significantly greater in under-represented minorities from intervention clinics compared to 
the control group. 
 
2.2.1.3 Secondary Hypothesis 1c: Adherence to guidelines for prevention of CVD will be 
significantly greater in African American/Black subjects from intervention clinics compared 
to the control group. 
 
2.2.2 Aim 2: To evaluate barriers and facilitators to implementation and dissemination of 
the intervention. 

13 
 
2.2.2.1 Secondary Hypothesis 2a: Implementation of the CVRS model will be associated 
with positive provider-level variables attitudes and beliefs about the intervention. 
 
2.2.3 Aim 3: To demonstrate a favorable cost for the CVRS using a robust cost- 
effectiveness analysis. 
 
2.2.3.1 Hypothesis 3a: The CVRS will have a favorable cost-effectiveness when 
compared to the control group. 
 
NOTE: due to the results of the futility analysis, a true cost-effectiveness analysis will not 
be done. However, costs to provide the service and costs-effectiveness of secondary 
endpoints will be assessed. 
 
 
3. SUBJECT SELECTION/ELIGIBILITY CRITERIA 
 
3.1 Inclusion Criteria 
 
English speaking males and females 
 
> 55 years of age 
 
Has a history of at least one of the following conditions: 
• Coronary artery disease (CAD) 
• Previous MI (heart attack) 
• Stroke 
• TIA 
• Atrial fibrillation 
• Systolic heart failure 
• Peripheral vascular disease/claudication 
• Carotid artery disease 
• Diabetes with either: 
• Hyperlipidemia with most recent LDL >110mg/dl 
AND/OR 
• Hypertension with the most recent systolic blood pressure ≥ 140 mm Hg OR 
the most recent diastolic blood pressure > 90mmHg 
 
3.2 Exclusion criteria 
 
 
Signs of acute angina, stroke, heart failure or renal failure 
 
Systolic BP > 200 mm Hg or diastolic BP > 114 mm Hg 
 
Significant hepatic disease, including; 
• Cirrhosis 
• Hepatitis B or C infection 
• Serum ALT or AST > 3 times control 

14 
 
• Total bilirubin > 2.0 mg/dl 
 
Pregnancy 
 
Inability to give informed consent or impaired cognitive function 
 
Residence in a nursing home or diagnosis of dementia 
 
No telephone or have a hearing impairment not allowing them to use a phone 
 
Refusal to consider attempting to use the internet at home, community center, library, 
medical office or other source. 
 
A measured arm circumference that exceeds 50 cm 
 
4. STUDY DESIGN 
 
4.1 Overview 
 
The MEDFOCUS study was funded in April 2014 by the National Heart, Lung and Blood 
Institute (NHLBI) of the National Institutes of Health (NIH). The study is being headed by 
University of Iowa co-principal investigators Dr. Barry L. Carter, Professor of Pharmacy and 
Professor in Family Medicine, and Dr. Christopher P. Coffey, Professor of Biostatistics in the 
College of Public Health. 
 
The goal of MEDFOCUS is to conduct a multi-center, cluster-randomized study to 
determine the extent to which medical offices with large geographic, racial and ethnic diversity will 
implement a care delivery model that utilizes a centralized cardiovascular risk service. The study 
will last five years and involve active recruitment of 400 subjects from 20 family practice offices 
across the United States. Participating offices are listed in Appendix I. The project hopes that at 
least 240 subjects will represent minority populations, who face unique challenges related to 
cardiovascular disease. Each participating clinic will be randomized to either the CVRS 
intervention arm or the usual care arm of the study. 
 
All subjects will have an initial visit with the site study coordinator and a 2nd visit 12 months 
later. Each visit will include research blood pressure measurement, phlebotomy for a lipid panel, 
HgbA1c, select chemistries and liver tests (intervention subjects only), and surveys. Site study 
coordinators will also abstract select medical record data, at 4 and 8 months for intervention site 
subjects only, and at 24 months following enrollment for subjects. A timetable for the study is 
provided in Appendix II. 
 
All subjects will have access to the Iowa Personal Health and Research Management 
(IowaPHRM) online personal health record. IowaPHRM will enable subjects to keep track of 
medications, record health-related data (e.g. BP, blood sugar), and enter allergies and health 
conditions. It supports printing reports, including wallet-sized cards to facilitate communication with 
health professionals and provides information for medications patients have entered. IowaPHRM 
will also include key data including medical history, problem list, laboratory values, key 
vaccinations, cancer screening, and medications collected by the study coordinators in intervention 
sites that will be used by the CVRS pharmacists to perform their interventions. IowaPHRM will 
facilitate implementation and measure many of the aspects of the Medical Home. This strategy will 
provide a more efficient approach for managing large populations of patients with multiple chronic 
conditions. 
 
Each subject at intervention arm clinics will receive the CVRS intervention for 12 months. 
Subjects enrolled at control site clinics will receive usual care and will not have any exposure to the 

15 
 
study intervention. The intervention will be evaluated on the degree to which the care provided to 
intervention arm subjects, when compared to control arm subjects, adheres to the Guideline 
Advantage measurement set criteria. 
If successful, the CVRS intervention model could become 
an important strategy to markedly reduce cardiovascular events in the United States. 
 
Key personnel roles on the study are described below: 
 
Key Personnel 
Site Study Coordinator 
Staff member employed within each institution who will recruit 
subjects and collect data 
CVRS Pharmacists 
Clinical pharmacists located centrally within the University of Iowa 
Clinical Coordinating Center who will provide telephonic, web- 
based, and email support for intervention subjects and 
communicate with site clinical pharmacists 
Site Clinical Pharmacist 
Clinical pharmacist working in the clinic who will communicate 
directly with the Iowa CVRS clinical pharmacists and notify primary 
providers about status changes and recommendations for 
treatment regimen changes 
Site Physician Investigator 
The medical provider who will lead the project at the local 
institution 
Site Primary Care 
Providers 
Primary care providers within the clinic 
 
4.2 Site randomization and Treatment Arms 
 
Dr. Coffey (biostatistician) will stratify the 20 participating offices based on lower (<40%) 
versus higher (>40%) numbers of minority population and then randomize the 20 offices in a 
cluster-randomized design to avoid contamination within offices. Each office will be randomized to 
one of two arms: 1) the CVRS intervention arm or 2) the usual care arm. All subjects enrolled at a 
given site will participate in the study arm to which the site was randomized. 
 
All subjects will be able to track their medications, home blood sugar and blood pressure 
measurements, and diagnosed conditions and also receive links to related publications and news 
through an Iowa Patient Health and Research Management (IowaPHRM) online portal. 
 
Only subjects at intervention arm clinics will receive the CVRS intervention. A CVRS 
clinical pharmacist at the University of Iowa will work telephonically with each intervention arm 
subject and communicate with his/her providers to optimize subjects’ pharmacological regimens 
and lifestyle patterns. Each subject at intervention arm clinics will receive the CVRS intervention 
for 12 months. Patients at intervention arm clinics can also communicate with their Iowa clinical 
pharmacist using IowaPHRM. Subjects enrolled at usual care clinics will receive the clinic’s usual 
medical care and will not have any exposure to the CVRS intervention. 
 
The intervention will be evaluated on the degree to which the care provided to intervention 
arm subjects, when compared to control arm subjects, adheres to the Guideline Advantage 
measurement set criteria. 

16 
 
4.3 Recruitment Procedures 
 
4.3.1 Identification and Contact of Potential Subjects 
 
Sites may use the following techniques to identify potential subjects, if approved by the 
local IRB: 
 Run a list of patients who have the ICD9 codes listed in the inclusion/exclusion 
criteria (Appendix III) to compile a pool of potential subjects. 
 Clinic providers may recommend patients to the Study Coordinator. 
 Study Coordinators may look at the daily clinic schedule to identify patients who 
might qualify 
 
For each potential subject that is identified, the Study Coordinator should review the 
medical record over the preceding 24 months to see whether the medical record supports eligibility 
criteria for age, language, and qualifying medical conditions and b) does not include documentation 
of any exclusion criteria. 
 
Documentation of a medical condition in the patient’s problem list is preferred, but explicit 
mention of a diagnosis in a provider note can be used if the problem list has not been regularly 
updated. Qualifying conditions include coronary artery disease, previous myocardial infarction, 
stroke, transient ischemic attack, atrial fibrillation, systolic heart failure, peripheral vascular 
disease/claudication, carotid artery disease; , and diabetes with either uncontrolled hyperlipidemia 
or uncontrolled hypertension (as evidenced from the most recent lab values taken within the 
preceding 12 months). 
 
Exclusion criteria include: signs of acute angina, stroke, heart failure or renal failure; 
systolic BP > 200 mm Hg or diastolic BP > 114 mm Hg; significant hepatic disease, including 
cirrhosis, Hepatitis B or C, serum ALT or AST > 3 times control or total bilirubin > 2.0 mg/dl; 
pregnancy; inability to give informed consent or impaired cognitive function; residence in a nursing 
home; impaired cognitive function; no telephone or have a hearing impairment not allowing them to 
use a phone; refusal to consider attempting to use the internet at home, community center, library, 
medical office or other source; a measured arm circumference that exceeds 50 cm. 
 
Sites may use the following techniques to approach potential subjects, if approved by the 
local IRB: 
 Mail patients who appear to qualify a letter approved by the local IRB inviting 
them to participate. The letter will provide a brief description of the study and 
request they return an enclosed response card and the date by which the card 
should be returned. The letter will include a statement that the clinic study 
coordinator will call the patient if the card is not returned by this date. The letter 
will include an explanation of how the patient can avoid the call by returning the 
card or calling the staff to decline participation. 
Patients who do not respond to the invitation letter may be called up to 3 times to 
assess their interest. 

17 
 
 
 
 The Study Coordinator may approach patients at the time of an unrelated clinic 
visit to ask about their participation in the study. 
 Patients who are referred to the study by a provider may either be mailed an 
invitation letter or approached in the clinic. 
Interested patients will be asked to set up a time for an initial study visit in the clinic with 
the study coordinator. 
 
 
4.3.2 
Confirmation of Eligibility 
 
Once a patient whose medical record review supports their eligibility indicates interest in the 
study, the Study Coordinator should call the patient or speak with the patient in the clinic to answer 
any questions the patient might have. The Study Coordination should also ask the patient two 
additional screening questions: 
1. Is the patient pregnant? Pregnant women cannot be enrolled in the study. No test 
will be required to confirm the absence of pregnancy. 
2. Does the patient have internet access and, if not, would they consider accessing the 
internet either on a home computer or at a public location (e.g., library)? Patients 
who state that they will absolutely not consider having internet access will not be 
allowed to sign consent. Patients will not need to actually access the internet to 
continue in the study. 
If a patient passes both of these screening questions, the Study Coordinator should verify 
with the patient that s/he meets the eligibility criteria. 
 
4.4 Baseline Visit Procedures 
 
4.4.1 Informed Consent Procedures 
 
The study coordinator will describe the study, have the patient read the informed consent 
document and answer any questions. The study coordinator will specifically review the following 
areas of the consent document: 
 
Purpose of the research study, duration of study participation, and the number of 
research visits or study contacts (e.g. telephone calls) required 
 
That subjects will not receive any investigational procedures 
 
The study procedures/requirements 
 
The risks of the study 
 
The voluntary nature of the study: The subject may stop the study at any time 
 
Their decision to participate or not will have no effect on the patient’s relationship 
with their physician or on the clinical care that they receive 
 
When a subject’s participation in the study may be stopped (safety, compliance, 
pregnancy, sponsor stops the study) 

18 
 
 
HIPAA section: The research team must be allowed to have access to the 
participant’s medical information and to create medical information in order for the 
subject to be in the study; the investigators will obtain medical record data for the 
time period that spans the period from two years preceding enrollment until 2 years 
following enrollment in the study 
 
The Research Related Injury section. 
 
Contact information that subjects can use to reach clinic investigators and University 
of Iowa investigators for study-related issues 
 
Patients may take the unsigned consent document with them if they wish to think about 
participation. The Study Coordinator will tell them that s/he will call the patient within a week to 
assess their interest should the patient not contact the Study Coordinator. 
 
Patients may sign informed consent but schedule completion of other baseline visit 
activities for a later date to meet their scheduling needs. 
 
Per policy of the local IRB, a patient who wishes to participate will sign and date the 
consent, and the Study Coordinator will subsequently sign and date the consent. A copy of the 
signed consent will be given to the patient. A scan of the consent will be placed in the medical 
record per the clinic and IRB policy. 
 
4.4.2 Surveys 
 
The study coordinator will ask the questions on the following forms and record subjects’ 
responses: 
1. Eligibility 
2. Contact Information (intervention subjects only) 
3. Demographic Information 
4. Diagnosed Conditions and Care Management (Patient Report) 
5. Medication Reconciliation 
6. Medication Adherence 
7. Cancer Screening 
8. Health Behavior Inventory 
9. Stages of Change 

19 
 
4.4.3 Blood Pressure Measurement 
 
Study Coordinators will measure the subject’s height, weight and research blood pressures. 
Resulting measurements will be documented on the Blood Pressure case report form. 
 
All blood pressures should be obtained (at the baseline visit and again at the 12 month visit) using 
the Omron HEM907XL automated blood pressure device and the following procedures: 
 
Prepare the Subject 
Subjects should refrain from smoking for 20 minutes prior to the blood pressure measurement. 
Have the subject remove all clothing that covers the location of cuff placement. 
The subject should be comfortably seated in a chair, with the back supported, legs uncrossed and 
flat on the floor, the arm supported, ideally at heart level on a desk, and the palm of the hand 
facing upward 
Have the subject sit for at least 5 minutes. Instruct the patient to relax as much as possible. 
Cuff Measurement 
The subject’s arm circumference should be measured at BOTH study visits. A cuff should be 
selected based on the measurement ranges specified for each cuff. Should an arm measurement 
fall on a number that is specified for use on two cuffs, place both cuffs on the arm sequentially and 
choose the cuff for which the INDEX  that is marked on the edge of the cuff better falls within the 
range bar on the cuff. 
Subjects who require use of a thigh cuff at the baseline visit cannot continue in the study. Should a 
subject whose BP was successfully measured at baseline using the Omron monitor gain sufficient 
weight between the baseline and 12 month visits to require a thigh cuff at 12 months, the Study 
Coordinator should take the 12 month BP measurements using a thigh cuff and manual 
sphygmomanometer. 
 
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 patient’s bare upper 
arm. 
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). 
Pull the cuff snugly around the bare upper arm so that you can insert only one finger between the 
cuff and the arm. 
 
Blood Pressure Measurement 
Have the Blood Pressure form and the Omron monitor beside you on the desk. 
Tell the patient that you will be taking at least 4 blood pressure readings and that neither the 
patient nor the study coordinator should talk during the measurements. 

20 
 
1. Take a single sitting BP reading with the MODE selector set to “SINGLE” and record. 
Wait 60 seconds before taking the next blood pressure. 
2. Take a double sitting BP reading with the MODE selector set to “AVG” and record both 
readings. 
3. If either the two systolic readings or the two diastolic readings from the double BP readings 
differ by < 4mm, take one additional sitting BP with the MODE selector set to “SINGLE” 
and record the results. 
4. Have the patient stand for one minute and then take another single BP reading and 
record. 
 
IF YOU GET AN ERROR MESSAGE AT ANY POINT, START THE SEQUENCE OVER. 

21 
 
4.4.4 Laboratory Specimens 
The study coordinator will draw or arrange for usual laboratory draw of blood for the 
following tests: 
 
Lipid panel 
 
HgbA1c 
 
Serum creatinine, sodium and potassium (intervention subjects only) 
 
ALT and AST tests (intervention subjects only). 
Sites may select specific panels that are typically used in their clinic, so long as they include all 
the needed individual tests. Results will be documented on the Laboratory case report form, 
excepting intervention subjects at the baseline visit only, whose results will be reported on the 
Laboratory for Baseline Intervention case report form. 
Laboratory costs should not be billed to the patient or the patient’s insurance. The site should 
request reimbursement of $225.00 for each set of labs through the subaward invoicing 
mechanism. 
 
4.4.5 Instruction on IowaPHRM 
The study coordinator will instruct consented subjects on use of the Iowa Personal Health 
and Research Management (IowaPHRM) system, an online study record that enables subjects to 
keep track of medications, record health-related data (e.g. BP, blood sugar), and enter allergies 
and health conditions. IowaPHRM supports printing reports, including wallet-sized cards to 
facilitate communication with health professionals and provides information for medications 
patients have entered.  IowaPHRM will allow the subject to enter data into his/her record, 
including home blood pressure and blood sugar test results. Each subject will be given a sheet 
with initial login information for the system and told that they should create new login information. 
They will also be given a brochure about the online system. Subjects will not be required to 
access IowaPHRM at any point during the study, but they should be encouraged to try it and 
offered help getting started. Patients who would like help will be telephoned by the PHR support 
team for assistance. 
 
4.4.6 Medical Record Abstraction and Verification 
After the visit, the study coordinator will verify or obtain information documented at the 
patient’s most recent visit with his/her provider to complete the following forms: 
1. 
Diagnosed Conditions-Care Management (Medical Record) 
2. 
Medication Reconciliation 
3. 
Cancer Screening 
 
 
4.5 4 & 8 Month Medical Record Abstraction (CVRS intervention sites only) 
 
At 4 months after enrollment and again at 8 months after enrollment, the Study 
Coordinator will abstract medical record data to complete the 4 & 8 Month Data Collection form, 
which includes data for pertinent laboratory values, new diagnosis, and hospital and emergency 
room visits since enrollment. This form is completed only at CVRS intervention sites to give the 
CVRS pharmacists updated patient status information. 

22 
 
4.6 12 Month Visit Procedures 
4.6.1 Surveys 
The study coordinator will ask the questions on the following forms and record subjects’ 
responses: 
1. Diagnosed Conditions and Care Management (Patient Report) 
2. Medication Reconciliation 
3. Medication Adherence 
4. Health Behavior Inventory 
5. Stages of Change 
6. Serious Adverse Event Screening 
7. Cancer Screening 
 
4.6.2 Blood Pressure Measurement 
The study coordinator will measure height, weight and research blood pressures as 
specified for the baseline visit and document results on the Blood Pressure case report form. 
4.6.3 Laboratory Specimens 
The study coordinator will draw or arrange for usual laboratory draw of blood for the 
following tests, with billing handled as previously designated. Data should be recorded on the 
Laboratory form. 
 
Lipid panel 
 
HgbA1c 
4.6.4 Medical Record Abstraction and Verification 
After the visit, the study coordinator will verify or obtain the following data from the 
subject’s medical record to complete the forms listed below. Data should span the period from 
the baseline visit through the 12 month time point. 
1. Diagnosed Conditions and Care Management (Medical Record) 
2. Medication Reconciliation 
3. Cancer Screening 
4. Serious Adverse Event Screening 
5. Clinic Visit Tracking 
 
4.7 
24 Month Medical Record Abstraction (only conducted on those subjects who 
reach the 24-month time point prior to the data collection termination date) 
The study coordinator will collect the following medical record data for the time period 
extending from the day following the date of the 12 month study visit or medical record data 
abstraction through 13 months following that 12 month time point. No visit will occur at the 24 
month time point. 
1. Diagnosed Conditions and Care Management (Medical Record) 
2. 24 Month Blood Pressure, Laboratory and Medication 
3. Cancer Screening 
4. Serious Adverse Event Screening 
5. Clinic Visit Tracking 

23 
 
4.8 CVRS Intervention 
 
The CVRS clinical pharmacist will undertake the following activities with subjects, 
participating site pharmacists and participating site medical providers in the 10 
intervention offices. A schematic of the intervention is presented in Appendix IV. 
 
Communicate with subjects using email, telephone, text messages or 
IowaPHRM every two weeks x 2 months then at least monthly for 10 
additional months to engage patient and obtain any self-monitoring 
data 
 
Use motivational interviewing to conduct monthly follow-up assessment 
and counseling for medication adherence, side effects, exercise, CHD 
knowledge, weight, diet, tobacco use and alcohol use 
 
Assess stages of change for key issues such as exercise, diet, weight 
management and tobacco use 
 
Provide more frequent contact with the subject if necessary to improve 
or resolve medication problems 
 
Continue to address problems with medication adherence or 
persistence 
 
Develop an action plan that addresses gaps in guideline-concordant 
therapy, update medication list and FAX recommendations for 
medication changes to the primary medical provider and on-site clinical 
pharmacist every 3 months or more frequently if urgent issues are 
identified 
 
Document all patient and provider encounters and time (minutes) for 
each activity in the IowaPHRM database 
 
4.9 Serious Adverse Event Screening and Reporting 
 
Sites will screen for and report all serious adverse events (SAEs) that meet BOTH 
Criterion A AND Criterion B: 
Criterion A. The SAE resulted in an least one of the following outcomes: 
 
 
Death 
 
Life-threatening condition 
 
Hospitalization 
 
Disability 
 
Congenital abnormality 
 
Intervention was required to prevent permanent impairment or damage 
 
The lead provider or pharmacist for the study judged the event to be an 
important medical event 

24 
 
Criterion B. The SAE involved at least one of the following health situations: 
 
 
Loss of consciousness 
 
Hypoglycemia 
 
Hypertensive Urgency/Emergency 
 
Rhabdomyolysis 
 
Stroke 
 
Excessive Bleeding 
 
Myocardial Infarction 
 
Thromboembolism 
 
Diabetic Ketoacidosis 
 
Screening for reportable SAEs will occur at the following two time points: 
12 month study visit: The Study Coordinator will ask the patient about emergency 
room visits and hospitalizations and also review the medical record for SAEs that 
occurred since the baseline visit (submit Serious Adverse Event Screening case 
report form). 
24 month medical record review: The Study Coordinator will review the medical 
record for SAEs that occurred since the 12 month visit (submit Serious Adverse 
Event Screening case report form) for any subjects who completed the 24 month 
review prior to the data collection termination date. No 24 month abstraction will be 
performed for subjects whose 24 month data abstraction is scheduled after the data 
collection termination date. 
 
SAEs that are identified through screening and that meet the criteria for reporting must 
be reported to the DCC using the Serious Adverse Event Reporting case report form and 
uploaded to the study database. In addition Study Coordinators should report all SAEs that 
come to their attention between the key study time points and that meet both Criterion A and 
Criterion B. 
 
 
4.10 Study Termination 
 
4.10.1 Early Termination 
 
Subjects will be terminated early should any of the following situations arise: 
 
The subject withdraws consent 
 
The subject no longer is a patient at the clinic. 
 
The subject dies 
 
Early termination indicates that the site will no longer need to follow the subject, 
complete additional study visits or collect any additional data. 
 
 
 
either: 
4.10.2 End of Study Termination 
Study Coordinators will complete a study termination form for each subject following 
 
a. Completion of the 24 month medical record abstraction 
b. The data collection termination date, for subjects whose 24 month time point 
follows the data collection termination date. 

25 
 
5. STUDY OUTCOMES 
5.1 Primary Outcomes: 
5.1.1 Adherence to Guideline Advantage Criteria in All Subjects 
The primary outcome will be adherence to the Guideline Advantage criteria that 
apply for secondary prevention of CVD. (See link below to the Guideline Advantage Fact 
Sheet.) The criteria reflect drug therapies, meeting guideline goals for specific disease 
conditions, and screening and prevention measures. 
http://www.guidelineadvantage.org/idc/groups/tga- 
public/@wcm/@tga/documents/downloadable/ucm_429605.pdf 
Each eligible criterion will be scored based on whether or not it was met at each of 
the index dates (baseline, 12 months, and 24 months). An algorithm will take the number 
of Guideline Advantage criteria that apply to each patient and then calculate the percent of 
those applicable criteria that are met at each time point.  The resulting single numeric 
value will be used as a surrogate for quality of care. This algorithm will be applied to all 
subjects, with CVRS intervention subjects compared to usual care subjects. 
5.1.2 Adherence to Guideline Advantage Criteria in Minority Subjects 
The same algorithm will also be used to compare adherence between CVRS 
intervention subjects and usual care subjects who represent minority populations. This analysis 
will use a mixed model and an exchangeable correlation structure. 
 
5.2 Secondary Outcomes 
5.2.1 
Adherence to Guideline Advantage Criteria in African-American 
Subjects 
The same algorithm will also be used to compare adherence between CVRS 
intervention subjects and usual care subjects within the African-American population. This 
analysis will use a mixed model and an exchangeable correlation structure. 
 
5.2.2 BP Control, Mean BP, LDL Cholesterol, HgbA1c all subjects 
Direct measurement (at baseline and 12 months) will yield values for BP control, Mean 
BP, LDL cholesterol and HgbA1c. Values will be compared for CVRS intervention subjects and 
usual care subjects. However, since this analysis will include many subjects with controlled 
values at baseline, the effect in those with uncontrolled values will be diluted. 
 
5.2.3 Measurement of Stages of Change 
Scores on the Stages of Change instrument will be compared for CVRS intervention 
subjects and usual care subjects at baseline and 12 months. 
 
5.2.4 Intensity of Medication Management 
The number of recommended medication changes per subject and the percent of 
recommended medication changes that were accepted/implemented. 

26 
 
5.2.5 Medical Home Index 
The lead medical provider at each site will complete the Medical Home Index, a 
validated, self-assessment tool for evaluating primary care practice. Providers will complete this 
tool at the beginning of the project and again following implementation of the study intervention 
to determine how each office has improved on adoption of the Medical Home and if there is 
greater adoption in intervention offices compared to usual care offices. 
 
5.2.6 Provider attitudes to deliver intervention, barriers and facilitators to 
implementation 
 
All clinic providers will be asked to complete two questionnaires at the beginning of the 
project and again following implementation of the study intervention. The first validated 
instrument measures physician-pharmacist collaboration and will be used to evaluate the level 
and type of communication and any increases in the level of communication in the intervention 
group. The second validated questionnaire based on the Theory of Planned Behavior (TPB) will 
be used to evaluate physician adoption of the study intervention, with scores compared between 
CVRS intervention clinic providers and usual care clinic providers. 
 
 
6. Statistical Analysis Plan 
 
6.1 Statistical Design 
 
This study will utilize a two-arm, randomized, cluster design. A total of 400 subjects will 
be enrolled into the trial at 20 primary care offices across the U.S. Offices have been stratified 
into either a high (>40%) minority population site or a low minority population site. After 
stratification, offices were randomized in a 1:1 fashion into either the centralized cardiovascular 
risk service (CVRS) or usual care groups. Each subject will be followed for 12 months, with an 
additional chart abstraction performed at 24 months to assess the extent to which increased 
guideline adherence is sustained after the intervention is discontinued. A total of 400 subjects 
will be enrolled into the trial. 
 
The trial will follow the intent-to-treat principle. The analysis model corresponds to the 
‘compound symmetry’ assumption that implies that all members of a cluster are equally 
correlated with each other – and that members in different clusters are independent of each 
other, a reasonable assumption since physicians and pharmacists only practice in one study 
location. 

27 
 
𝐶 
6.1.1 Primary Analysis 
 
Primary Hypotheses 1 & 2: Adherence to guidelines for CVRS intervention vs. 
control group (in all active observation subjects and restricted to under- 
represented minority groups) 
The primary outcome will be adherence to the AHA Guideline Advantage criteria that 
apply for secondary prevention of CVD at the end of the intervention. For each subject, the 
primary outcome will involve a determination of the percentage of applicable criteria met at the 
end of the twelve week period. Both primary hypotheses will be assessed using a mixed model, 
adjusted for adherence at baseline and the minority status grouping. The only difference for the 
two primary hypotheses is that the first analysis will apply the model to all active observation 
subjects, while the second analysis will be restricted only to minority subjects (whether they 
were enrolled at a high or low minority site). This model will also use an exchangeable 
correlation structure to adjust for the correlation among subjects treated in the same clinic. For 
example, the following model will be fit to these data: 
𝑌𝑖𝑗   = 𝛽0 + 𝛽1𝑋1𝑖 + 𝛽2𝑋2𝑖 + 𝛽3𝑋3𝑖𝑗 + 𝛾𝑖  +  𝜀𝑖𝑗 
where Yij represents the adherence at twelve months for the jth subject in the ith cluster, X1i is an 
indicator variable for the minority status of the ith cluster (=0 if < 40%, =1 if ≥ 40%), X2i is an 
indicator variable for whether the ith cluster was randomized to the CVRS or usual care group, 
X3ij is the baseline adherence score for the jth subject in the ith cluster, γi is the cluster i ‘random 
effect’ with variance 𝜎2, and εij  is the usual random measurement error term with variance σ2. 
Hence, this model corresponds to the ‘compound symmetry’ assumption that implies that all 
members of a cluster are equally correlated with each other – and that members in different 
clusters are independent of each other. Correspondingly, the hypothesis of interest can be 
assessed by performing the following hypothesis test: 
𝐻0: 𝛽2 = 0 
𝑣𝑠. 
𝐻𝐴: 𝛽2  ≠ 0 . 
This test will be implemented using an appropriate contrast statement with the model specified 
above. Because there are two primary hypotheses of interest, we will apply a Bonferonni 
correction and test each hypothesis at the 0.05/2 = 0.025 significance level. 
Because randomization is performed at the site level, it is possible that some other 
important subject-level covariates (age, gender, family history, co-morbidities, number of CV 
medications at baseline, baseline medication adherence, smoking status, education level, 
insurance status, economic status, or marital status) may be imbalanced in this study. Thus, we 
will carefully monitor the ongoing study for any important imbalances among important 
covariates. Should important imbalances occur, we will control for these additional covariates in 
the linear regression model above.  We will also assess the normality assumption involved in 
the model. If this assumption is violated, an appropriate transformation will be employed, or a 
nonparametric model will be fit. 
 
6.1.2 Secondary Analyses 
Secondary Hypothesis 1: Relationship between guideline adherence and provider-level 
variables (attitudes and intent to implement the CVRS model) 
This hypothesis will be assessed in the same manner as the primary hypotheses, except the 
appropriate provider-level variable will be used as a model covariate in place of the 
dichotomous group assignment. 

28 
 
6.1.3 Cost-Effectiveness Analysis 
Costs will be assigned to each activity and CVD and diabetes medication. All CVRS 
pharmacist time including record review, patient assessment, email time, telephone follow-up, 
plus clinic visits, emergency room visits, hospitalizations, and laboratory procedures will have 
costs assigned and analyzed using methodologies previously used. 
 
6.2 Covariates 
Since randomization will be performed at the clinic level, we will control for subject-level 
covariates that might be imbalanced between study arms. These include: age, gender, family 
history, co-morbidities, minority status, number of CV medications at baseline, baseline 
medication adherence, smoking status, education level, insurance status, economic status, and 
marital status. 
 
6.3 Power and Sample Size 
Preliminary estimates for justifying the sample size for the primary outcomes were 
obtained from guideline adherence measures collected in a previous study by the investigators 
(Carter et al, 2009).11 In that study, only 40% of applicable criteria were adhered to for 
hypertension. Additionally, in our evaluation of Medicare patients who suffered an acute MI, only 
34% received all guideline concordant medications.20 Based on this and other information,95, 143 
we expect baseline adherence scores to be 30-35% ± 20% but conservatively assumed baseline 
values of 40% ± 20% for sample size calculations. We expect these scores to increase to 50% ± 
20% in the control group and to 60% ± 20% in the intervention group at 12 months. Further, we 
expect that guideline adherence scores will deteriorate after the intervention is discontinued but 
scores in the intervention group (50% + 20) will remain significantly higher than the control group 
(40% + 20) at 24 months. Finally, further examination of the previous study suggested that the 
observed intra-class correlation coefficient was 0.004.  Based on earlier studies, we believe that 
a 15% lost-to-follow-up rate is a good estimate for the proposed trial. 
Based on the assumptions above, the study would only require 300 subjects to have 93% 
power to assess the primary hypothesis in the overall population. However, it is also important to 
ensure adequate power for the second primary hypothesis, which involves all under-represented 
minority subjects or African Americans/Blacks (AA) (a subset of the population used to assess 
the first primary hypothesis). We expect the intervention to be as effective in racial and ethnic 
minorities compared to Caucasians and the study is powered to detect these differences. We will 
have sufficient Black subjects to evaluate this aim (n=180). The numbers of Hispanics (n=40) will 
have low power but we will use our comparisons as hypothesis generating for future research. 
Table 1 provides power levels for a variety of adjusted sample sizes for the overall 
population, the minority population, and the African-American population. The table shows that 
a sample size of 400 subjects provides reasonable power to detect both primary hypotheses of 
interest, as well as the first secondary hypothesis. This proposed sample size would provide 
greater than 99% power to detect the effect of interest in the overall population, while providing 
83% power to detect these same effects in both the under-represented minority population and 
the African-American population (although one is a subset of the other, the fact that we plan to 
use a significance level of 0.05 for the secondary hypothesis and a significance level of 0.025 
for the second primary hypothesis leads to similar power). 

29 
 
Table 1. Observed Power for Different Adjusted Overall and Minority Sample Size 
Values 
Adjusted 
Overall 
Sample Size 
Adjusted 
Minority 
Sample Size 
Adjusted 
AA 
Sample 
Size 
Power 
(Overall) 
Power 
(Minority) 
Power 
(AA)1 
100 
55 
45 
46% 
25% 
29% 
200 
110 
90 
79% 
50% 
53% 
300 
165 
135 
93% 
60% 
71% 
400 
220 
180 
>99% 
83% 
83% 
500 
275 
225 
>99% 
91% 
90% 
 
1Uses a significance level of 0.05, AA = African Americans/Blacks 
 
Thus, the following assumptions were made: 
 
 
We expect a conservative absolute average of approximately 10% increase in guideline 
adherence at twelve months for subjects enrolled at centralized CVRS sites versus 
subjects at usual care sites. 
 
 
Standard deviation for change from baseline is expected to be 20% for both groups. 
 
 
The intraclass correlation coefficient is conservatively assumed to be less than or equal to 
0.005. 
 
 
Each participating site will be expected to enroll 20-25 subjects. 
 
 
Both primary hypotheses will be tested at the 0.025 significance level. The secondary 
hypothesis will be tested at the 0.05 level. 
 
 
The drop-out rate is expected to be 15%. 
 
 
6.4 Futility Analysis 
One formal futility analysis will be conducted when half of the planned active participants 
have completed their twelve month follow-up. The futility assessment will be based on a 
determination of the predictive power. If this predictive power is below 5% at the time the 
analysis is conducted, then we propose that the trial should stop for futility. 
 
 
6.5 Strategies to Limit and Handle Missing Data 
The primary analysis will follow the intent-to-treat principle. As such, it will be critically 
important to minimize the occurrence of missing data. Our team will use a variety of methods in 
order to minimize the percentage of missing data in this trial, including required data fields for 
critical variables and queries to sites regarding missing data. 

30 
 
For subjects who drop out of the study before their 12 month data can be obtained, we 
propose to use a multiple imputation method to impute their outcome. This multiple imputation 
will be implemented using a model based on guideline adherence at baseline and the 12 month 
guideline adherence values for all subjects with observed data. We will use five separate 
imputations, and will average the parameters across all five imputations for the final analysis. 
 
 
7. Data and Safety Monitoring 
7.1 Site Monitoring Roles 
Each participating site will have the following monitoring responsibilities: 
 
At the 12 month visit, the site Study Coordinator will ask each subject if they have 
had any hospitalizations or emergency room visits. The Study Coordinator will also 
screen each subject’s medical record for documentation regarding these types of 
events. SAEs that meet the qualifying criteria specified in Section 4.8 should be 
reported through the study database. 
 
At the 24 month time point, the Study Coordinator will review each subject’s medical 
record for documented SAEs. Those that meet the qualifying criteria specified in 
Section 4.9 should be reported through the study database. 
 
Should a Study Coordinator or site investigator become aware of an SAE that meets 
the qualifying criteria specified in Section 4.9 at any other time point during a 
subject’s 24 month period in the study, the site Study Coordinator should report that 
event through the study database. 
 
Local site personnel also submit reports of SAEs to their local Institutional Review 
Boards (IRBs) per their IRB’s policy. The Study Coordinator should provide the CCC 
with the notification they receive from a local IRB regarding its decision related to a 
reported event. 
 
Local site personnel forward to their IRB the DSMB summary report from each 
meeting, either when received or at the next continuing review. 
 
7.2 Local IRB Monitoring Roles 
Local IRBs will review all SAEs reported to them by the site per their own procedures. 
The local IRB will make a decision on each case regarding what further action might be needed 
and communicate that decision to the site’s PI. 
7.3 Data Coordinating Center Roles 
The DCC receives submitted reports of SAEs from local investigators, and forwards 
them to the Physician Monitor for review. If an SAE that meets the criteria for expedited 
reporting is identified, the DCC notifies the CCC of the determination. 
The DCC provides a biannual safety report to the DSMB based upon the 12 and 24 
month SAE screenings that are conducted by site Study Coordinators. 
The DCC performs remote and on-site monitoring checks to each participating site per 
the monitoring plan. 

31 
 
7.4 Physician Monitor Roles 
The Physician Monitor for the study, Dr. Paul James, will serve three major roles in the 
evaluation of SAEs for the trial: 
 
 
Perform ongoing, real-time reviews of all individual SAE reports to determine if 
events are unanticipated, related and serious, and suggestive of greater risk; 
 
Perform quarterly reviews of cumulative SAE data to judge whether there are 
concerning trends in the occurrence of events, and the possible relationship of 
those trends to the trial; and 
 
Review any reports of SAEs that meet the NHLBI criteria for reporting (i.e. 
suggests greater risk of harm to study participants than was previously known or 
recognized). 
7.5 Data and Safety Monitoring Board (DSMB) Monitoring Roles 
7.5.1 Board Composition 
The following persons have agreed to serve on the MEDFOCUS Data and Safety 
Monitoring Board (DSMB): 
 
Barry Davis, MD, PhD, University of Texas School of Public Health, an internationally 
recognized researcher who was the PI for the ALLHAT trial, will chair the DSMB. 
 
Keith Ferdinand, MD, Tulane University, a cardiologist and member of the Association of 
Black Cardiologists, led the Community Outreach program for the American Society of 
Hypertension that conducted screening programs in underserved areas of Harlem, New 
Orleans and San Francisco. 
 
Michael Murray, PharmD, MPH, Regenstrief Institute, has conducted numerous 
pharmacist intervention studies in heart failure, asthma and others. 
 
The DSMB members will agree upon a person at one of their institutions to serve as the 
DSMB Executive Secretary. 
7.5.2 DSMB Tasks 
The DSMB is responsible for safeguarding the interests of study participants by 
assessing the safety and efficacy of study procedures and by periodic monitoring of safety data 
and the overall conduct of the study. The DSMB reviews the following types of data provided by 
the DCC: 
 
Bi-annual reports on overall study progress, including enrollment and study completions 
 
One futility assessment conducted when half of the enrolled subjects have completed 
the 12 month study visit 
 
Reviews of the SAE screenings and related SAE reports conducted at 12 months 
 
Individual concerns identified by the Physician Monitor. 
After reviewing pertinent reports, the DSMB determines whether any trend that may be identified 
is related to the trial. 
After each scheduled DSMB meeting, the DSMB chair or his designee sends a summary 
report of the meeting to the CCC that summarizes the DSMB deliberations and 
recommendations.  The CCC forwards the summary report to the study sites for reporting to 
their local IRBs and to the University of Iowa IRB for reporting during the annual continuing 
review. 

32 
 
7.6 Clinical Coordinating Center Monitoring Roles 
7.6.1 Disseminating DSMB meeting summary reports 
The CCC receives the DSMB meeting summary report from the DSMB Chair and 
forwards the summary report to the participating sites, and to the University of Iowa IRB for the 
annual continuing review. 
7.6.2 Reports to NHLBI 
If an SAE is determined to meet the relevant criteria (specified below), it must be 
reported to the NHLBI, the DSMB, and Site Investigators through an expedited reporting 
process.  The procedure for expedited reporting of SAEs is presented below: 
 
The CCC PI submits an expedited report to NHLBI, the DSMB, and the Site 
Investigators for submission to their local IRBs within seven (7) days of learning of an 
SAE that meets both of the following criteria for expedited reporting: 
• The event or problem was unanticipated 
AND 
• The event or problem either could probably have been related to the study 
intervention, or was definitely related to the study intervention. 
 
For unanticipated events or problems suggesting that “the research places subjects or 
others at a greater risk of physical or psychological harm that was previously known or 
recognized”, the CCC PI is responsible for preparing a report for submission to NHLBI 
within 30 days, and to others as directed by institutional procedures and IRB-approved data 
and safety monitoring plans. 
 
Expedited SAE reports to NHLBI should include the following elements: 
• Study title, grant number, PI name 
• Description and date of the event or problem, including why it merits expedited 
reporting 
• When it becomes available, the date on which the SAE was reported to the CCC 
PI, the clinical site PI, NHLBI, and applicable oversight bodies (relevant IRBs, the 
DSMB, Office for Human Research Protections). 
• Any corrective action planned or taken in response to the SAE (e.g., study 
suspension, consent or protocol changes, additional training or security 
measures). Corrective action plans for a UP that occurs at a local site should be 
developed by the site, and then approved by the CCC. 
• Signature of the CCC PI (B. Carter) 
• All communications from the relevant oversight bodies regarding an expedited 
SAE must be reported to NHLBI. 

33 
 
7.7 Data Management to Maintain Blinding 
The physician monitor will usually be blinded, with subjects identified only by a study ID. 
However, during the review of SAE reports, it is possible that content within an SAE report could 
indicate the subject’s treatment arm. 
 
All reports created for the DSMB by the DCC will be blinded to treatment arm by the 
biostatistician. However, the DSMB may request un-blinding to improve the quality of their 
decisions. 
 
8. 
STUDY RESPONSIBILITIES 
8.1 University of Iowa PI 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 GCP, and with all 
applicable federal, state, and local laws, rules, and regulations relating to the conduct of the 
clinical study. 
The CCC PI will provide current copies of the study protocol to all sub-investigators and 
other site personnel responsible for study conduct. 
The CCC PI will provide NIH with copies of all institutional review board (IRB) 
actions regarding the study. 
 
8.2 Training 
The CCC PI will hold a remote webinar/Skype session with site providers and research 
team members at the beginning of the study to review the study and the roles of key personnel. 
The CVRS pharmacists will participate in these sessions for sites randomized to the CVRS 
intervention group. 
 
All study coordinators will attend a 1-2 day session at the University of Iowa for training 
on the protocol and the study database. 
 
 
8.3 Communication with Sites 
The CCC PI and CVRS pharmacists will hold teleconference calls with the site 
pharmacist and lead physician as needed during the first year of the intervention to develop 
strategies to optimize communication, improve implementation of the intervention, if necessary, 
and ensure fidelity to the intervention. 
The CCC PI will hold teleconference calls on an as needed basis with research team 
members at any usual care sites that do not meet expectations for recruitment or data 
collection. 

34 
 
8.4 Study Documentation 
Study documentation includes all electronic and paper forms, data correction forms, 
source documents, monitoring logs and appointment schedules, sponsor-investigator 
correspondence, and regulatory documents (signed protocol and amendments, IRB 
correspondence and approval, clinical supplies receipts and distribution records). 
By signing the protocol, the Site PI acknowledges that, within legal and regulatory 
restrictions and institutional and ethical considerations, study documentation will be promptly 
and fully disclosed to UI appropriate parties upon request. It will also be made available upon 
request for inspection, copying, review, and audit at reasonable times by representatives of UI 
or responsible government agencies as required by law. 
 
 
8.5 Data Transmission and Record Retention 
The study coordinator will enter required data into the DCC study database as soon as 
possible after a data collection activity (study visit or medical record abstraction time point). 
Data will be transmitted via the internet using encryption mechanisms to ensure security and 
confidentiality. Timestamps will be collected to identify the occurrence of data entries and 
changes. Edit checks, electronic queries, and audit trails are built into the data collection 
system to ensure accurate and complete data collection. 
 
Sites will keep hard copy case report forms until both of the following criteria for 
destroying data are met: 1) the CCC informs the site that data may be destroyed and 2) the 
timeframe meets the policy of the local IRB. 
 
8.6 
Use of the Iowa Personal Health and Research Management (IowaPHRM) 
Online Record 
Subjects will be able to enter their own health information into the separate IowaPHRM 
website application. 
IowaPHRM has automated features that subjects may use to reset usernames and 
passwords, assuming that the subject has an active email address. Persons who do not have 
email should call the CCC and request a reset. The CCC will validate subject identity by 
requiring that subject responses match information in the database for (1) first and last name, 
(2) year of birth, (3) full address (current or previous if recently moved) and (4) at least one 
phone number documented for the subject. 
 
8.7 Study Closeout 
Once all study data has been entered and all queries have been resolved, the DCC will 
conduct closeout activities with the site, either at the site or remotely. 
 
8.8 Publication Policies 
The PI will be primarily responsible for creation, review, and submission of publications 
and presentations relating to the major aspects of the study and approved ancillary analyses 
within a timely fashion after completion of the study. 
 
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- 

35 
 
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. 
 
9.1 Role of University of Iowa 
The University of Iowa has overall responsibility for the conduct of the study, including 
assurance that the study meets the sponsor’s regulatory requirements. 
 
9.2 Informed Consent 
The local site investigator has 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. University of Iowa investigators will oversee site 
submission of IRB applications and store local IRB approval letters and consent documents. 
Before and after subject provision of informed consent, research team members will be 
available via email, IowaPHRM, or phone to answer questions or concerns regarding 
procedures and risks. Research team contact information will be included on all study materials 
and the study website. 
 
9.3 Confidentiality of Subjects 
Subject confidentiality will be maintained throughout the clinical study. A unique subject 
ID code will be used to identify all data reported for each subject.  Full name and 
comprehensive contact information will be collected only for subjects in the CVRS intervention 
arm, so that the CVRS pharmacists can contact them upon enrollment. Names and other 
identifying information will not be visible to members of the DCC staff. The only identifiers 
collected for usual care subjects, as well as intervention subjects, will be birthdates and the 
dates of clinic visits. 
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 (eg, case report forms, 
informed consent documents) will be stored in a locked cabinet in a locked office at each 

36 
 
respective site. Identification numbers will be used in place of names on case 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. 
 
9.4 Authorization for Use and Disclosure of Protected Health Information (HIPAA) 
All subjects will consent, through their IRB-approved informed consent document or HIPAA 
release, to release of protected health information to the University of Iowa research teams as 
part of the consent process. 
9.5 Human Subject Protections 
9.5.1 Research Subject Selection 
Before implementation, the investigators at each site will review the study protocol with 
physicians in participating clinics. The physician engagement activities will ensure that the 
involved clinical services approve of the study protocol. 
Subjects will have multiple opportunities, both before and during the first visit, to ask questions 
and read information about the study. After an initial review of the informed consent document, 
patients will be given up to 10 days to decide whether they want to participate. No coercion or 
undue influence on this decision will be used. 
There will be no exclusion from participation in the study on the basis of gender, ethnicity, or 
race. Subjects younger than 55 years of age at the time of screening will be excluded from the 
study. 
 
9.5.2 Compensation to Subjects 
Subjects will be compensated $75 for completion of the baseline visit and $75 for 
completion of the 12 month visit for their time and inconvenience related to the blood draws and 
surveys.  No compensation will be provided for a subject who does not complete a visit. 
Compensation will be provided by the participating site and reimbursed through quarterly 
invoices to the University of Iowa. 
9.5.3 Risks/Discomforts of Study Participation 
Subjects might experience one or more of the risks indicated below from being in this 
study:  
 
Some of the questions that the study coordinator asks might cause a subject to feel 
uneasy or anxious, but subjects may choose not to answer any questions. 
 
Drawing blood for laboratory tests could cause mild and temporary discomfort and 
might also result in bruising, fainting/lightheadedness and/or infection. 
 
There is a risk of loss of data confidentiality. To help protect confidentiality, all 
patient forms completed during study visits will be kept in locked file cabinets in 
locked offices. The study coordinator will send data electronically to study 
researchers at the University of Iowa using a confidential computer system. Only 

37 
 
individuals working on the study will have access to these records. Data will be 
entered electronically using a unique study ID for each subject. All research data 
collected will be stored in password-protected computer files that can be seen only 
by the subject and the research team. The blood samples that are drawn will be 
analyzed in the clinic or hospital laboratory, and the results of those labs will only be 
visible to the research team. If study investigators write a report or article about this 
study or share the study data set with others, individual subjects will not be directly 
identified. 
9.6 Institutional Review Board Review 
The local IRB will approve the protocol and informed consent documents, agree to 
monitor the conduct of the study, and agree to review study progress periodically, at intervals 
not to exceed 1 year. The study investigator will be responsible for submitting any and all 
revisions to the appropriate IRB before implementation of any deviation from the approved 
protocol. The local investigator must provide the CCC with the IRB annual re-approval of the 
protocol and with all approved versions and revisions to the informed consent documents and 
recruitment letters or any amendments to the protocol. 
The CCC will obtain IRB approval from the University of Iowa IRB (UI IRB) and submit 
modifications (when needed) and annual continuing review applications.  The CCC will notify 
the UI IRB when an event occurs that is both unanticipated and deemed by the medical monitor 
to be related to participation in the study. 
The CCC will also track modifications and annual renewals for each participating site. 

38 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
APPENDICES 

39 
 
APPENDIX I: 
PARTICIPATING SITES 
 
Clinic Name 
City/State 
% Minority 
in CAPTION 
LOW MINORITY SITES 
Northeast Iowa Family Practice 
Waterloo, IA 
0% 
Siouxland Family Medicine Center 
Sioux City, IA 
0% 
Pocatello Family Medicine (Idaho State) 
Pocatello, ID 
4% 
Center for Community and Family Medicine (Texas Tech) 
Amarillo, TX 
8% 
Genesis Family Medical Center 
Davenport, IA 
13% 
Sugar House Health Center (University of Utah) 
Salt Lake City, UT 
22% 
Wingra Family Medical Center 
Madison, WI 
22% 
Northeast Family Medical Center (University of Wisconsin) 
Madison, WI 
24% 
Scripps Ranch Family Medicine (UCSD) 
San Diego, CA 
27% 
4th and Lewis Family Medicine (UCSD) 
San Diego, CA 
39% 
HIGH MINORITY SITES 
General Internal Medicine Clinic (UNC) 
Chapel Hill, NC 
56% 
Family Medicine Clinic (USF) 
Tampa, FL 
57% 
Milwaukee Health Services, Inc. (MHSI) 
Milwaukee, WI 
70%* 
Wheaton Franciscan Medical Group Wisconsin Ave 
Racine, WI 
74% 
Physicians at Sugar Creek (Memorial Hermann) 
Sugar Land, TX 
88% 
Family Health Center (UTHSCA) 
San Antonio, TX 
88% 
Family Medicine at Main (University of Florida) 
Gainesville, FL 
89% 
Jefferson Family Medicine Center (SUNY Buffalo) 
Buffalo, NY 
93% 
Advocate Medical Group (Midwestern University) 
Chicago, IL 
100% 
Medicine Group Practice (Temple University) 
Philadelphia, PA 
100% 
*Current minority population per Medical Director’s report; did not participate in CAPTION 

40 
 
 
APPENDIX II: 
STUDY TIMETABLE (months) 
 
 
Activity 
0- 9 
9-18 
19-27 
28-39 
40-50 
51-60 
Stratify and randomize clinics 
Validate web-based data collection 
forms and procedures 
Train CVRS pharmacists 
Train study coordinators in data 
collection, web database 
Train physician leaders/clinical 
pharmacists via webinar 
Recruit active subjects 
200 
enrolled 
200 
enrolled 
CVRS intervention 
Onsite visits and monitoring 
Safety monitoring by DSMB 
Cost effectiveness analysis 
Study close out 
Manuscripts, reports and 
Dissemination of the findings 

Page 1 of 2 
9/23/2015 
 
VERIFICATION OF INCLUSION AND EXCLUSION CRITERIA 
Demographic Criteria 
Has Inclusion 
Criterion* 
English speaking males or females 
Yes 
No 
≥55 years of age 
Yes 
No 
Has been seen in the clinic in the previous 24 months 
Yes 
No 
If the answer to both questions is Yes, then proceed to Section A. If not, then stop. The patient cannot participate in the study. 
Section A: 
Has a history of: 
ICD9 Codes* 
ICD10 Codes* 
Has Inclusion 
Criterion* 
Coronary artery disease (CAD) 
414 
I25 
Yes 
No 
Previous MI (heart attack) 
410, 411, 412 
I21, I25.2 
Yes 
No 
Stroke 
430, 431, 432, 433, and 434 
I60, I61, I62, I63 
Yes 
No 
TIA 
435 
G45 
Yes 
No 
Atrial fibrillation 
427.31,427.3 
I48.0, I48.1, I48.2, I48.91 
Yes 
No 
Systolic heart failure 
428.20. 428.21, 428.22, 
428.23, 428.40, 428.41, 
428.42, 428.43 
I50.2, I50.4 
Yes 
No 
Peripheral vascular disease/claudication 
440.2,  440.3, and 440.4 
I70.2, I70.3, I70,4, I70.5, I70.6, I70.7, I70.92 
Yes 
No 
Carotid artery disease 
433.1 
I65.2, I63.03, I63.13, I63.23 
Yes 
No 
Diabetes and must also have one of both of the 
following conditions: 
250 
E10, E11 
Yes 
No 
Hyperlipidemia 
272 
E78, PLUS most recent chart documented LDL must be > 110 mg/dl 
Yes 
No 
Hypertension 
401, 402, 403, 404, 405 
I10, I11, I12, I13, I15 
PLUS most recent chart documented systolic BP > 140 mm Hg and/or 
most recent diastolic pressure > 90 mm Hg 
Yes 
No 
* If a listed code does not include any digits to the right of a decimal point, then all sub-codes included under the listed code qualify. If a listed code or set of codes includes one or more digits following a decimal 
point, then only those sub-codes that are listed and any codes underneath that sub-code qualify. 
***Must have at least one risk factor from Section A.  If so, proceed to Section B and check for Exclusion Criteria*** 

Page 2 of 2 
9/23/2015 
 
Section B: 
Exclusion Criteria Prior to Consent 
Source or ICD code 
Has Exclusion Criterion* 
Signs of acute angina, stroke, heart failure or renal 
failure 
Direct observation or medical 
record documentation 
Yes 
No 
Systolic BP > 200 mm Hg or diastolic BP > 144 mm 
Hg 
Direct observation or 
most recent value documented in medical record 
Yes 
No 
Significant hepatic disease, including; 
 Cirrhosis 
 Hepatitis B or C infection 
 Serum ALT or AST > 3 times control 
 Total bilirubin > 2.0 mg/dl 
Medical record documentation 
Yes 
No 
Pregnancy 
self-report or 
ICD9: V22, V23, V24 or 
ICD10: 000-008 through 094-09A 
Yes 
No 
Inability to give informed consent or impaired 
cognitive function 
Direct observation or medical 
record documentation 
Yes 
No 
Residence in a nursing home or diagnosis of 
dementia 
Self-report or medical record documentation 
Yes 
No 
No telephone or have a hearing impairment not 
allowing them to use a phone 
Self-report or medical record documentation 
Yes 
No 
Refusal to consider attempting to use the internet 
at home, community center, library, medical 
office or other source. 
Self-report 
Yes 
No 
A measured arm circumference that exceeds 50 cm. 
Direct observation or medical 
record documentation 
Yes 
No 
*** BEFORE THE SUBJECT SIGNS CONSENT, VERIFY THAT S/HE HAS: 
□ AT LEAST ONE “YES” ANSWER FROM SECTION A (RISK FACTORS) 
AND 
□ NONE OF THE EXCLUSION CRITERIA IN SECTION B 

APPENDIX IV:  INTERVENTION SUMMARY 
 
 
 
43 

44 
 
 
 
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