Heart-Related Multiple Chronic Conditions in Primary Care: Behavioral Technology
Phase: NA
Conditions: Chronic Disease
Sponsor: University of Wisconsin, Madison

 
 
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NCT 03387735 
 
 
Heart-Related Multiple Chronic Conditions in Primary Care: Behavioral Technology 
 
 
Oct 3, 2019 
 
 

 
 
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Heart-Related Multiple Chronic Conditions in Primary Care: Behavioral Technology 
Principal Investigators: David H. Gustafson, Ph.D. 
 
University of Wisconsin - Madison 
 
Industrial Engineering 
 
1513 University Avenue, ME Bldg. Suite 4109 
 
Madison, WI 53706 
 
608-263-4882; Dhgustaf@wisc.edu 
 
Jane Mahoney, Ph.D. 
 
University of Wisconsin - Madison 
 
School of Medicine and Public Health 
610 Walnut St, Room 957d  
Madison, WI 53726 
608-262-5077; jm2@medicine.wisc.edu 
Co-Investigators:    
Randall Brown, PhD 
 
University of WI – Madison 
School of Medicine and Public Health, Wingra Family Medical Ct 
1100 Delaplaine Ct, Room 3832 
Madison, WI 53715 
608-263-6558; 608-263-3111; Randy.Brown@Fammed.Wisc.Edu 
 
Dhavan V. Shah, Ph.D. 
 
University of Wisconsin - Madison 
 
 
Journalism & Mass Communication, Industrial Engineering 
 
5162 Vilas Communication Hall 
 
821 University Avenue 
 
Madison, WI 53706 
 
608-262-0388; dshah@facstaff.wisc.edu 
Marie-Louise Mares, Ph.D. 
University of Wisconsin - Madison 
 
Communication Science 
6140 Vilas Hall 
 
Madison, WI 53706 
608-263-2350; mares@wisc.edu 
MUSC Site PI: 
Philip A. Smeltzer, Ph.D. 
 
Medical University of South Carolina (MUSC) 
 
Department of Public Health Sciences 
 
169 Ashley Avenue, MSC 332 
 
Charleston SC  29425 
 
843-792-6637; SmeltzerP@musc.edu 
UW Study Coordinators: Laura Van Toll, MBA 
Department: Industrial Engineering 
1513 University Avenue, ME Bldg. Suite 4127 
Madison, WI 53706 
608-890-1156; Laura.vantoll@wisc.edu 
Klaren Pe-Romaskho, BS 
Department: Industrial Engineering 
1513 University Avenue, ME Bldg. Suite 4155A 
Madison, WI 53706 
608-263-3322; kspe@wisc.edu  
 
Sponsor:  
National Institutes of Health 

 
 
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Participating Institutions:  
UW Health Clinics, Medical University of South Carolina (MUSC) 
 
 

 
 
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TABLE OF CONTENTS       
Study Summary ............................................................................................................................................. 4 
1.0   Background & Significance   .............................................................................................................. 5 
2.0    Study Objectives .................................................................................................................................. 9 
3.0    Selection of Subjects .......................................................................................................................... 10 
4.0  Registration Procedures ..................................................................................................................... 11 
5.0    Treatment Plan ................................................................................................................................... 12 
6.0    Measurement of Effect ....................................................................................................................... 16 
7.0    Study Parameters ............................................................................................................................... 18 
8.0    Statistical Considerations ................................................................................................................... 18 
9.0    Records to be Kept ............................................................................................................................. 21 
Appendix A: CHESS Data and Safety Monitoring Plan ............................................................................. 22 
10.0  References .......................................................................................................................................... 27 
 
 
 

 
 
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STUDY SUMMARY 
Multiple chronic conditions (MCCs) are not simply aggregates of several individual conditions. They 
represent overlapping conditions that often have common root causes, and when grouped together can 
severely impact treatment options and quality of life for the patient. Primary care providers (PCPs) face 
many challenges in treating patients with MCCs. They need to help patients be motivated and informed 
enough to effectively manage their own conditions, but must balance that with the time demands of their 
practice. 1-5  
MCCs are common and expensive among patients aged ≥65 and are associated with lower quality of life, 
poorer response to treatment, worse medical and psychiatric outcomes, higher mortality, and higher costs 
of care. 7 Treatment of MCCs focuses on medical care, but patient self-management and loneliness matter 
too. Numerous studies indicate that chronic conditions contribute to loneliness and loneliness in turn 
contributes to reduced functionality and chronic illness. 11-13 
The primary purpose of this study is to conduct a randomized clinical trial (RCT) to examine the effects 
of C-CHESS--a web-based intervention--on health outcomes and healthcare use among older adults with 
3 or all of the following 5 common, high-risk chronic conditions: hypertension, hyperlipidemia, diabetes, 
osteoarthritis and BMI of 30+. Patients in the experimental group will receive treatment as usual (TAU) 
plus C-CHESS. Patients in the comparison group will receive TAU+internet and links to helpful websites 
(e.g., NIH SeniorHealth). We assume that about half of participants will have their own computers and 
Internet access; we will give touchscreen laptops and provide Internet access to those who do not. The 
RCT will be conducted in primary care clinics that are part of the University of Wisconsin Department of 
Family Medicine’s primary care network and the Medical University of South Carolina’s Primary Care 
Clinics. The study will involve 330 patients age ≥65 who will be tracked for a total of 18 months--12 with 
access to the interventions and 6 months for follow up, with data collected every 6 months.  
The C-CHESS Intervention 
For the patient, C-CHESS (or ElderTree, as it will be known to participants) provides tools, motivation, 
and social support to help them manage their specific set of chronic conditions and communicate with 
peers and their PCP. 
For the clinic, C-CHESS has a Clinician Report (CR), a visual dashboard of health-tracking data that can 
be customized based on the needs of the clinic. The CR provides alerts to the clinician when a patient 
passes a certain threshold. The dashboard is intended to help clinicians prepare for patient office visits.  
 
BACKGROUND & SIGNIFICANCE 
MCCs are common and expensive among patients aged ≥65. Among Medicare beneficiaries, 65% 
have 3 or more MCCs8 and 23% have 5 or more MCCs. People with MCCs account for 90% of Medicare 
spending.9  Per-capita Medicare expenditures increased with the number of chronic conditions from 
$211/year for beneficiaries with no chronic conditions to $13,973/year for those with 4 or more.8 Among 
Medicare beneficiaries in 2010, hypertension (high blood pressure) and hyperlipidemia (high cholesterol) 
were the 2 most common chronic conditions, affecting 58% and 45% respectively; diabetes affected 28% 
and arthritis 29%.22 
Treatment of MCCs focuses on medical care, not patient self-management. Most PCPs focus on 
managing medication and lab results for MCCs and less on strategies and skills for self-management. 10  
However, treatment adherence, health tracking, and feedback to clinicians are important for patients with 
MCCs, given the challenges of polypharmacy and multiple ongoing treatment needs. Additionally, 
patients need education about how to live with their conditions, given that they are chronic.  
The principles of self-management and support are well documented and relate to an array of health 
behaviors. 14-17 C-CHESS focuses on improving 1) patients’ self-management, 2) patients’ social 

 
 
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engagement and support, and 3) clinicians’ case management (we use clinician to refer to physicians, 
nurse practitioners, and physician assistants). 
Studies show that information and communication technologies can improve self-management and 
healthcare effectiveness. Recent reviews18,19 found positive outcomes in 29 of 32 studies of chronic 
condition interventions delivered via computer and cellphone, with more impact coming from multi-
service programs.20 Our intervention will offer an array of services that can be tailored to each patient’s 
multiple needs and is designed to increase the efficiency and effectiveness of clinic-patient interactions.  
The Center for Health Enhancement Systems Studies (CHESS). CHESS is a research center at the 
University of Wisconsin–Madison. Over the past 30 years, CHESS has acquired an international 
reputation for developing and applying innovative applications of systems engineering principles and 
communication sciences to healthcare, specifically in interactive healthcare technology for patients, 
their family members, and providers. We have extensively studied what it takes to successfully 
implement these technologies within an organization. CHESS research projects are grounded in the 
belief that technology has the potential to transform and improve individual lives as well as the 
healthcare field.  
CHESS researchers and programmers work with patients, family members, and clinicians to create web 
and smartphone applications that help individuals cope with health crises or medical concerns. To date, 
CHESS has created systems for a variety of health conditions, such as breast, colon, and lung cancer; 
asthma; aging; and addiction.  
CHESS has a suite of evolving eHealth web and smartphone based innovations built on the principles of 
continuing care and self-management: long duration26; assertive outreach27; tracking28; prompts29; action 
planning30; problem solving10; self-tailoring10; peer, family, and care coordination.33 In randomized 
clinical trials, previous CHESS innovations significantly improved: 1) asthma control for young children 
(mediated by relatedness)18; 2) quality of life and cost of care in HIV patients35; 3) quality of life and 
self-efficacy in breast cancer patients, including elderly women36; 4) risky drinking39 ; and 5) symptom 
distress and length of survival in lung cancer patients (mediated by competence).67  
Preliminary data 
Most clinical trials of CHESS applications have examined its impact on a single chronic condition. One 
current study, Elder Tree CHESS, targets outcomes and a population similar to those in this study. Elder 
Tree CHESS is a web site that was developed as part of an AHRQ Center of Excellence in Active Aging 
grant to help adults 65 and older remain independent, primarily by reducing loneliness. C-CHESS will 
have as its base the services and design of Elder Tree, but will add new user features and information 
related to the target chronic conditions as well as a Clinician Report for medical staff. 
Elder Tree was tested in an RCT involving 399 older adults from 3 Wisconsin counties (urban, rural, and 
suburban). We followed participants for 18 months and assessed outcomes at 0, 6, 12, and 18 months.41  
Elder Tree subjects were asked to identify their chronic conditions so we could examine data about the 
impact of Elder Tree on those with MCCs. We identified 66 older adults with at least 3 of the 4 target 
MCCs. Subjects’ conditions included (in addition to hypertension, hyperlipidemia, diabetes, and arthritis) 
cancer, pain, depression, anxiety, heart disease, obesity, osteoporosis, and falls. The Elder Tree RCT 
included 4 measures we plan to use in this study: health-related quality of life, use of primary care 
services, relatedness (feeling connected with others), and number of symptoms. For the clusters we 
propose to study in this project, we found moderate (0.4+) to large effect sizes, all favoring Elder Tree, 
with 2 exceptions in which small effects favored Elder Tree. These data helped us conduct power 
analyses and estimate sample sizes for the C-CHESS RCT.  

 
 
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As mentioned above, C-CHESS will add to Elder Tree the Clinician Report (CR), which alerts clinicians 
when thresholds are reached in a patient’s status. We used a similar system in a lung cancer RCT 
comparing CHESS to CHESS+CR. The addition of the CR to CHESS improved (p < .001) symptom 
distress by over 100% (26.2% improvement with CHESS vs. 53% in those with CHESS+CR; n = 71 vs. 
68 respectively). These statistics are averaged across 6 observations over 12 months. We expect the 
proposed CR to increase the effects of C-CHESS compared with Elder Tree. 
Innovation: The intervention is innovative for the following reasons. 
1. Single disease  Multiple diseases. Information and communication technologies have shown promise 
in managing chronic conditions. But most address a single condition without addressing co-occurring 
issues. In contrast, C-CHESS will offer information for specific conditions as well as tools designed to 
improve behaviors that underlie MCCs generally, such as weight management. Patients will select 
behaviors they want to address. C-CHESS will be designed to help any combination of MCCs. 
2. Single intervention  Multiple interventions.23,24 Many healthcare apps rely on one tool (e.g., texting), 
though different people with similar objectives may benefit from different tools. C-CHESS will offer a 
variety of options for online training and support.  
3. Complex  Simple. Many computer-based systems make extensive use of text and are complicated to 
navigate. Additionally, systems on smartphones are often challenging for older adults because vision 
problems and tremors make it difficult to use the small keys. C-CHESS will improve ease of use by 
offering large screens, voice and text options, and simple content.  
4. Clinic-based and periodic  Sustained tracking and just-in-time clinician alerts. Tracking and support 
for patients with MCCs usually consist of periodic, onsite contact with PCPs, who may be unaware of 
and/or cannot respond promptly to changes. Moreover, many patients avoid “bothering the doctor,” 
foreclosing a source of help that might make a difference. C-CHESS will encourage patients to report 
symptoms daily, weekly, and monthly, depending on a patient’s specific conditions and choice. When 
changes warrant just-in-time alerts, they will be automatically sent in a manner that minimizes 
clinician burden.  
5. C-CHESS will address loneliness. Loneliness worsens chronic conditions. C-CHESS will address this 
by giving participants the power to give and receive social support.  
The C-CHESS intervention 
C-CHESS provides tools, motivation, and social support to help patients set, prioritize, track, and 
accomplish goals for managing their specific set of chronic conditions. C-CHESS is consistent with self-
determination theory, which asserts that satisfying 3 fundamental psychological needs contributes to 
adaptive functioning: competence (feeling effective rather than overwhelmed), social relatedness (feeling 
connected to others), and feeling internally motivated (rather than coerced). 43  
The following describes key C-CHESS behavioral services: 
Effect sizes from Elder Tree data 
Chronic Condition Clusters 
n 
Control/ 
Elder Tree 
Quality 
of Life 
Fewer 
Primary Care 
Visits 
Relatedness 
Fewer 
Symptoms 
Hypertension/hyper-lipidemia/arthritis 
17/21 
0.20 
0.61 
0.56 
0.56 
Hypertension/hyper-lipidemia/diabetes 
11/10 
0.40 
0.66 
0.36 
0.45 
Hypertension/arthritis/diabetes 
16/11 
0.96 
0.71 
0.52 
0.53 
Hyperlipidemia/arthritis/diabetes 
14/14 
1.09 
0.56 
0.91 
0.75 

 
 
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• 
Cognitive behavioral therapy (CBT) life skills summaries: Behavior change, problem solving, 
decision-making, managing stress and fatigue,44 and resolving communication problems via skills 
such as cognitive reframing, analyzing your behavior chain, and attentive listening. 
• 
Goal setting and reminders: Helps patients set behavioral goals and reminds them of treatment plan 
activities (e.g., exercise), upcoming appointments, events of interest, skills, online relaxation 
exercises, peer support, and distracting activities. Patients will be asked if they intend to meet certain 
self-determined goals because this has been shown to improve adherence.45  
• 
Treatment plan manager: Helps patients set priorities and reminds them to take medications and 
follow their treatment plan using schedules entered at setup and altered periodically as needed.  
• 
Tracking, triage, and feedback: C-CHESS collects information about how a patient is feeling using 
patient-reported responses to prompts and provides links to relevant resources. Also sends 
inspirational messages and congratulations for patients’ achieving their goals.  
• 
Ask an Expert: Allows patients to anonymously seek advice about managing their MCCs. 
• 
Tips and texts. Ideas on how to manage MCCs and their interactions.42 Patients and clinicians can add 
to or comment on tips, web links (e.g., AARP drug interaction checker46), and other information.  
Social engagement services provide:   
• 
Social interaction options: Patients with MCCs give and receive support via emails, texts, and 
monitored online discussion groups. Past research consistently indicates that participating in social 
interaction via CHESS is associated with better health outcomes (e.g., quality of life, emotional well 
being).47,48    
• 
Private messages: Enables C-CHESS members to communicate privately with other C-CHESS 
members. Along with discussion groups, private messages are one of the most popular services in 
current CHESS systems. 
• 
Healthy Events: Suggests local activities that patients can add to their calendars according to 
guidelines established during setup.  
C-CHESS’s autonomy support tools provide:  
• 
Thought for the Day provides motivational reminders of the importance of maintaining or improving 
health. 
• 
Relaxation services: Games, recordings to guide progressive relaxation, deep breathing, and 
mindfulness. 
• 
Personal stories: Audio/video accounts (based on interviews with MCC patients) focusing on care 
experiences (e.g., what patients would do differently, how they coped, tips they used). 
C-CHESS Clinician Report (CR). MCCs can lead to rapid declines in health.8 The CR can share timely 
information on patient general indicators (e.g., fatigue, mood, nutrition, sleep). C-CHESS will help 
clinicians prepare for patient office visits.  
1.0 
STUDY OBJECTIVES 
This projects will test the use of an eHealth intervention called C-CHESS, to modify health behaviors and 
improve health outcomes in older adults with comorbid chronic diseases and health conditions. 
Aim 1 Refine C-CHESS, using feedback from patients and primary care clinicians.  
Aim 2 Conduct a randomized clinical trial to test 4 hypotheses: 
1. Primary outcomes: Patients assigned to TAU+C-CHESS will have better quality of life and less 
primary care use (fewer visits) than those assigned to TAU+Internet. 
2. Secondary outcomes: Patients assigned to TAU+C-CHESS will have improved composite scores; 
improved individual condition outcomes (mm Hg for hypertension, mg/dL for hyperlipidemia 
(LDL), HbA1c for diabetes, and pain for arthritis); and fewer symptoms from a list than patients 
assigned to TAU+Internet. 
3.  Mediators: Patients assigned to TAU+C-CHESS will have, compared with patients assigned to 
TAU+Internet, greater adherence to medications and appointments as well as improved competence, 

 
 
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relatedness, and autonomy. 
4. Moderators: Improvements in primary outcomes for TAU+C-CHESS vs. TAU+Internet will be 
greater for women than men, those ≥ 75 vs. 65 to 74, and those with 3-5 chronic conditions vs. 6+. 
Aim 3 Analyze data from the RCT and publish results. 
Exploratory questions:  
• 
Does C-CHESS reach a large proportion of targeted patients, get a large proportion of targeted 
clinicians to use CCHESS, get a large proportion of patients to regularly use CCHESS, and 
maintain that performance over time)?  
• 
Does the use of specific C-CHESS services affect outcomes?  
• 
Does the use of C-CHESS affect other health service use? 
Primary Aim 
Patients assigned to TAU+C-CHESS will have better quality of life and fewer primary care visits than 
those assigned to TAU+Internet.  
C-CHESS will contain the Clinician Report to make it easier for PCPs to respond to important patient 
changes, pilot data suggested that primary care visits could be reduced. Reducing the number of primary 
care visits will both lessen provider burden and ultimately reduce healthcare costs.  
Secondary Aim 
Patients assigned to TAU+C-CHESS will have improved composite scores; improved individual 
condition outcomes (mm Hg for hypertension, mg/dL for hyperlipidemia (LDL), HbA1c for diabetes, and 
pain for arthritis); and fewer symptoms from a list than patients assigned to TAU+Internet.  
A composite measure will combine Z scores of outcomes for each of the targeted chronic conditions, but 
because the composite score has not been validated and to help interpret results, we will also report results 
for each condition. Our pilot data showed positive effects for almost all combinations of conditions, and 
previous research (on breast38 and lung40 cancer; asthma34; HIV35; and alcoholism39) has shown that 
CHESS programs improve outcomes for individual chronic conditions. In addition, an extensive review 
of mHealth apps for cardiovascular disease59 found promising results of mHealth in RCTs on 
hypertension and hyperlipidemia. Few of the programs for diabetes have been rigorously tested and 
reported.60 We chose pain as the outcome for arthritis because Internet-based interventions have proven 
effective in reducing pain.64   
Study Coordination 
The UW-Madison Center for Health Enhancement Systems Studies (CHESS) is the coordinating site for 
this study. The UW study coordinator will oversee all recruitment activities which includes:  
• 
developing recruitment and data collection processes that meet study objectives; 
• 
training staff on protocol procedures prior to start of recruitment and continuous monitoring to 
assure compliance with the protocol and human subjects regulation; 
• 
communicating with clinic site staff as needed  via conference calls to monitor progress, inform 
of protocol changes/distribute new version of protocol, and address unanticipated issues or 
challenges; 
• 
and manage all study data. 
2.0 
SELECTION OF SUBJECTS 
Patient Recruitment: We will recruit 330 patients age ≥65. 
Patients are eligible for the study if they: 
1) are ≥65 years old  
2) have been treated in the clinic for at least the previous 18 months with no plans to leave during 
the study period 

 
 
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3) have ≥3 of the following chronic conditions: 
• 
Hypertension 
• 
Hyperlipidemia 
• 
Diabetes 
• 
Arthritis 
• 
BMI ≥30 
• 
Chronic Kidney disease 
• 
Chronic pain 
• 
COPD 
• 
Congestive heart failure 
• 
Arrhythmia/atrial fibrillation 
4) report no current psychotic disorder that would prevent participation 
5) have no acute medical problem requiring immediate hospitalization 
6) do not have a visual or motor impairment that prevents them from using a computer 
7) be able to read and sign the consent form in English 
8) have no known terminal illness;   
9) be willing to share health-related study data and  
• 
Systolic and diastolic BP 
• 
Weight 
• 
BMI 
• 
HDL/LDL 
• 
HbA1C 
• 
pain score 
• 
health care utilization: hospitalizations (admission and discharge), number of ER visits, urgent care 
visits, PC visits, specialty care visits, long-term care visits, and rehab visits 
10) allow researchers to share information with their primary care physician 
We will document and describe eligible people who choose not to participate.  
 
Clinician Recruitment: 15 providers (salaried, credentialed staff) from 5 different clinic sites will be identified 
and recruited to complete 3 qualitative interviews each over the course of the study. Site staff will be identified 
by the clinic and contacted by the UW study coordinator. Details of the study and their participation will 
be explained and if they agree informed consent will be collected. Staff are eligible for the study if they: 
• 
Allow monitoring of their C-CHESS usage 
• 
Are willing to participate in 3 interviews to share information about technology use at their clinic 
and feedback related to C-CHESS. 
• 
Have a patient participating in the intervention arm of this study 
3.0 
REGISTRATION PROCEDURES 
Patient Recruitment  
In January of 2018, research staff will begin recruiting. The trial will involve 330 patients age 65 and 
older, randomized into two groups: 
1. Patients in the experimental group will receive treatment as usual TAU + laptop + Internet access 
+ C-CHESS 
2. Patients in the control group will receive TAU + laptop + Internet access 
 
Patient recruitment will be conducted in primary care clinics within the University of Wisconsin’s 
Department of Family Medicine and General Internal Medicine, as well the Medical University of South 
Carolina. 
School of Medicine and Public Health/MUSC employees will identify from clinic records patients who 
meet inclusion criteria.  

11 
 
 
The UW Clinical Research Data Service (CRDS) will extract the following data to determine patient 
eligibility per the eligibility criteria above. The data will be sent to the UW Office of Clinical Trials via 
REDCap or other secure method. 
• 
First and last name 
• 
Address 
• 
Birth date 
• 
Age 
• 
UW Clinic Location 
• 
Primary Care Doctor 
 
• 
Has ≥3 of the following chronic conditions: 
• 
Hypertension 
• 
Hyperlipidemia 
• 
Diabetes 
• 
Arthritis 
• 
BMI ≥30 
• 
Chronic Kidney disease 
• 
Chronic pain 
• 
COPD 
• 
Congestive heart failure 
• 
Arrhythmia/atrial fibrillation 
• 
# of chronic conditions 
• 
Don’t need an interpreter 
• 
# of primary care visits in the last 18 months 
Potential UW Health participants will either receive an opt-in letter from the UW Office of Clinical Trials 
or be recruited in-person at a scheduled clinic appointment. In the latter case, clinic staff or the Office of 
Clinical Trials will alert research staff when a potential participant has an upcoming clinic appointment. 
Staff will be available at the clinic on the specified date/time to conduct the enrollment visit if the patient 
agrees to speak with them. 
Potential MUSC participants will receive an opt-in letter or MyChart  message sent by the MUSC 
Biomedical Information Specialist. The message will describe the study and have a postage paid return 
letter inviting further contact from the UW study team.  
Only MUSC, the UW Office of Clinical Trials, or SMPH Family Medicine staff will receive the list of 
potential subjects, process the mailings or MyChart messages, or identify upcoming clinic appointments.  
UW study staff will call potential participants who opt-in to provide a detailed study overview including 
the benefits and potential risks of participation. If the patient is interested in participating, they will be 
asked questions to determine final eligibility: 1) do they have any acute medical problem requiring 
immediate inpatient treatment, 2) are they willing to allow their health care provider to supply lab data to 
the study team, or 3) are they willing to allow the study team to share high level information (graph that 
charts weekly scores related to the quality of your sleeping, nutrition, physical activity, memory, falls, 
moods, balance, pain, medication adherence and quality time spent with others, 4) do they have any plans 
to change health care providers in the next 18 months. 
 

12 
 
 
Patients who verbally confirm they want to be in the study and meet the screening criteria will be mailed 
the baseline survey and will receive a home visit where written consent will be obtained, the completed 
baseline collected, randomization determined, equipment set up, and training delivered. The baseline 
survey is expected to take 20-30 minutes to complete and will assess demographics, quality of life, 
symptom management, pain, medication adherence, and health care utilization.  
 
Patients who consent to participate in-person at a clinic appointment will provide signed consent, be given 
the baseline survey, and a home visit will be scheduled to complete the activities described above. 
 
Minority Recruitment Advisors 
In addition to the general recruitment procedures described above, beginning in October 2019 three 
individuals active in the black community in Madison, WI will serve as advisors to the research team. 
They will provide feedback on recruitment materials, recruitment process, and ElderTree content and 
design which will inform future projects. 
 
Patient Consent 
Patients must agree to allow monitoring of their C-CHESS use and agree to allow their clinic to supply 
the study team with health care utilization and EHR related data, specifically lab scores for systolic and 
diastolic BP, weight, BMI, HDL/LDL, HbA1C, and pain. (as applicable to the patient), and diagnoses of 
anxiety, depression, osteoporosis, and cancer. The patient will be given the right not to share specific 
information and will retain the right to revoke their permission at any point. 
The research team will always have a member available during standard operating hours for participants 
to contact with questions or issues. If a patient declines to participate, a research team member will 
determine reasons for non-participation so we can examine how patients who opt out differ from those 
who choose to participate.  
The consent process will inform potential subjects of:  
(1) the nature and purpose of the study 
(2) the types of data that will be collected quarterly from the EHR (by the CRDS) and, for participants in 
the experimental group, from C-CHESS 
• 
Systolic and diastolic BP 
• 
Weight 
• 
BMI 
• 
HDL/LDL 
• 
HbA1C 
• 
pain score 
• 
health care utilization: hospitalizations (admission and discharge), number of ER visits, urgent care visits, PC 
visits, specialty care visits, long-term care visits, and rehab visits 
• 
osteoporosis 
• 
cancer 
 
 (3) for participants in the experimental group, the types of data that will be shared with their primary care 
physician (a graph that charts weekly scores related to the quality of your sleeping, nutrition, physical 
activity, memory, falls, moods, balance, pain, medication adherence and quality time spent with others.) 
(4) study risks and measures taken to mitigate 

13 
 
 
(5) their right to leave the study at any time 
(6) the timeline of the study 
Consent will be documented by obtaining a signed, IRB-approved consent forms from participants. 
Signed forms and other study data will be stored in a locked cabinet at the Center for Health Enhancement 
Systems Studies at the UW. After receipt of the signed consent forms, patients who need them will be 
issued their computer by research staff. Research staff will train patients on Internet safety and security 
and how to use the intervention. Research staff will help participants assigned to the experimental group 
choose a unique login name and password for C-CHESS. Subjects will be asked to use the intervention 
weekly.  
 
Participants who do not already own a computer will be receiving a laptop as part of the study. The laptop 
has an administration interface that allows our technical team to access devices remotely if a participant 
calls tech support or reports a problem.  If a participant loses their laptop or installs something that is 
causing problems, we have the ability to remotely wipe the device, lock it down, restore the operating 
system and/or run a security check. We can also do security updates remotely to make sure patches are up 
to date on each laptop and security software has not been disabled by the user. 
 
Patient Randomization: Once informed consent and baseline measures have been obtained from 
patients, they will be randomized to either the experimental (TAU + C-CHESS) or control (TAU + 
Internet) group, stratified on gender, clinic site, and number of chronic conditions (3-5 vs. 6+). Patients 
who are in the experimental group will be further randomized into two groups, one will be asked to 
identify a health outcome to track and share with their physician using the Clinician Report and the other 
group will not.  
When baseline assessment and consent are complete, the researcher will enter the participant number and 
randomization data into a randomization spreadsheet. The interviewing researcher, once informed of 
group assignment, will provide setup and training.  
The research staff will train participants to use C-CHESS and customize it (e.g. by health condition) 
during a home visit. Participants will be asked to check in regularly, initially at a daily rate with frequency 
of at least weekly over the course of the study.  
 
Patient Qualitative: Data will be gathered via an interview at 3 times from 6 patients at each of the 5 
clinics (N=30).  Each interview is expected to take 30-60 minutes and will take place either in-person at a 
place of the subjects choosing or via phone.  
 
Recruitment: Participants will be identified through a consent form opt-in question and demographics as 
reported on the baseline survey. We will seek a mix of genders and number of chronic conditions. We 
will also look at C-CHESS use data to find a mix of users and non-users. We will contact potential 
participants by messaging them through the C-CHESS application or phoning them. 
 
At setup and training, qualitative data will be gathered by the study team through observing training 
sessions with the participants. Participants will be asked to engage in think-aloud procedures during 
training to provide insights into their initial reactions and difficulties. 
 
The think aloud instructions would be: “I’m going to talk you through the system.  You’re in the driving 
seat, and you’re going to do all the button pressing and clicking.  But it would be really great if you can 
talk out loud about what’s going through your head as you’re doing it.  Anything at all.  You like 
something, you don’t like something, you can’t tell what to do, you don’t know where to click, or you 
can’t read it… whatever you think.   Don’t hesitate to say stuff that you don’t like or that’s confusing. We 

14 
 
 
have broad shoulders, and it’s really important for us to learn from you. 
 
The trainer might tell them to turn on the computer, then click on the ElderTree icon, and then type in a 
user name.  The patient will be asked to give a running commentary as they try to do these things.  They 
may say, for example, that they’re not sure if they’ve pressed the button hard enough and are wondering 
whether to press it again, or that they’re not sure which part of the screen they need to touch to get the 
type-in section for their user name.   They can also comment on things they find interesting or intriguing. 
The point of this is not to categorize patients, but to identify training, instructions or site design issues that 
might need correction or adaptation. 
 
At 6 months, half of the identified qualitative patient participants (n=15) will be interviewed either in-
person or via phone using a standard survey. At12 months, the end of intervention period, the other half 
will be interviewed. Those who agree to meet in person (vs. talk on the phone) will be asked to show how 
they log in and navigate C-CHESS. Patients will be asked about barriers to use and perceived challenges 
and benefits of C-CHESS. At 6 months post-intervention, all will be re-interviewed about 
their experiences post-C-CHESS, including any ongoing effects of the intervention. 
 
Patient Focus groups: Data will be gathered from 2 groups each with 3-7 unique participants who are or 
were enrolled in the experimental group. The focus group will take place in-person in a private meeting 
room at a public facility easily reached by participants (public library meeting room, senior center 
meeting room etc.).  
 
Recruitment: Participants will be identified through consent form opt-in and demographics as reported on 
the baseline survey. We will seek mix of genders and number of chronic conditions. We will contact 
potential participants by messaging them through the C-CHESS application or phoning them. 
 
During the focus groups participants will be asked about community and environmental barriers to 
fulfilling their personal goals, their thoughts on the intervention, and their thoughts on improving the 
system and using it to remove barriers. The focus group will take about 2 hours. Participants will be paid 
$50 for attending. 
Across all UW-Health sites: 
SMPH researchers are responsible for: 
• 
Pulling participant lab data and transmitting to the study team 
• 
Identifying potential subjects and relaying that information to UW Office of Clinical Trials 
UW Office of Clinical Trials staff are responsible for: 
• 
Sending an opt-in letter to potential subjects 
• 
Communicating any patient contacts to SMPH 
UW researchers are responsible for: 
• 
Calling patients who have opted-in to explain the survey and receive verbal consent 
• 
Administering the baseline and written consent 
• 
Setting up the intervention 
Across all MUSC recruitment sites, MUSC research staff are responsible for: 
• 
Pulling participant lab data and transmitting to the study team 
• 
Identifying potential subjects and relaying that information to MUSC Office of Clinical Trials 
• 
Sending an opt-in letter or MyChart message to potential subjects 
• 
Calling patients to explain the survey and receive verbal consent 

15 
 
 
• 
Administering the baseline and written consent 
• 
Setting up the intervention 
Across all recruitment sites, UW researchers are responsible for: 
• 
Follow-up surveys 
• 
Participant technical support 
• 
Qualitative interviews with clinic staff and participants 
• 
Data management 
 
Clinician Recruitment and Consent: 
In February of 2018, research staff will begin recruiting clinicians to conduct qualitative interviews with. 
This will involve a total of 15 total clinicians chosen from at least 5 different clinic sites. There will be no 
randomization, all clinicians will be part of the same study group. 
 
To recruit clinicians, we will ask the participating clinics to identify individuals at the clinic who are 
serving patient participants and provide their name and email addresses. The study coordinator will 
contact them via email to see if they are willing to talk with us. 
 
To be eligible for the study, clinicians must: 
• 
Allow monitoring of their C-CHESS usage 
• 
Be willing to participate in 3 interviews to share information about technology use at their clinic 
and feedback related to C-CHESS. 
• 
Have a patient participating in the study 
 
If the clinician is willing, details of the study and their participation will be explained via a follow-up 
phone call or email. If they agree informed consent will be collected. The consent process will inform 
clinician subjects of:  
(1) the nature and purpose of the study 
(2) study risks and measures taken to mitigate 
(3) their right to leave the study at any time 
(4) the timeline of the study 
 
Qualitative interviews will be conducted with 15 clinic staff 3 times over the course of the study (to 
include one management person, one primary care doc, one nurse or nurse practitioner). Interviews will 
be done via phone or in-person at a location of the clinician’s choosing. Interviews will be done at 
baseline, 12 months and 6 months post-test period. 
 
In the baseline period, clinicians will be asked about anticipated barriers to participation and concerns 
about navigating C-CHESS and incorporating it into their treatment plans. Near the end of a clinic’s 
intervention period, clinicians will be asked about factors that influenced their use of C-CHESS, 
perceptions of short- and long-term effects, and ways in which similar clinics might implement and 
sustain C-CHESS. In the post-test period, clinicians will be asked about enduring effects observed and 
implications of losing C-CHESS for treating their patients. Surveys should take about 15 minutes to 
complete. 
5.0 
TREATMENT PLAN    
Treatment as Usual (TAU). Both the C-CHESS and Internet interventions will be paired with the 
patient’s current care in process at their clinics. The UW and MUSC clinics each have one system for all 

16 
 
 
locations, so certain aspects of care at each site will remain constant, e.g., the use of 1 EHR and billing 
system.  
The C-CHESS intervention. Participants in the C-CHESS group who need computers will receive a 
laptop and Internet access. They will be given log-in privileges to the C-CHESS website (the 
intervention) where they will access to tools, motivation, and social support for managing their specific 
set of chronic conditions.  
When patient subjects use C-CHESS they will be prompted to complete weekly check-ins. They will be 
asked how they are doing specifically about sleep, nutrition, physical activity, memory, falls, moods, 
balance, pain, medication adherence and level of social interactions. These questions will be sent weekly 
on the C-CHESS system and will take about 2-4 minutes to complete. All questions are voluntary. 
Patients are free to refuse to answer any questions they are uncomfortable with. However, by answering 
the weekly questions C-CHESS can direct the patient to information on the site to help them in an area 
they are struggling. In addition, a graph will be created based on their responses and shared with the 
primary care physician via a physician log-in to the C-CHESS program (Clinician Report (CR)). This 
information is being collected and shared via the Clinician Report to allow clinicians to be better 
informed and provide treatment more responsively based on their patients’ needs as they deal with serious 
health issues. All patients will be reminded that they are under no obligation to participate in this study, 
can withdraw from the study at any time, and in no way will their health care be affected by their 
participation in this study. 
The Internet intervention. Participants in the comparison group who need computers will receive a 
similar laptop and Internet access as those in the experimental arm. Comparison-group subjects will 
receive training on how to use the Internet, if desired. Four general health information websites will be 
placed on the desktop of patients in the comparison group so the sites are easily accessible: the CDC 
website, FamilyDoctor.org (American Academy of Family Physicians), HealthFinder (DHS), and NIH 
SeniorHealth. The Medical Library Association recommends these sites. 
Data collection 
Participants will be tracked for a total of 18 months; 12 months with access to the interventions and 6 
months for follow up. Data will be collected from: electronic health records (EHR), participant surveys 
(at months 0, 6, 12, and 18), and C-CHESS data.  
Participant EHR data will be shared by SMPH or MUSC with the study team via RedCap. An employee 
designee of each site will retrieve from files or receive a passworded spreadsheet of participant study id 
via either encrypted email or Box.  
Each participant survey is expected to take 20-30 minutes and will assess: demographic, quality of life, 
resilience, pain, medication adherence, and health care utilization. Surveys will be mailed to participants 
with a stamped return envelope included. 
Participants will be paid $10 for each completed survey. 
Survey data will be entered into REDCap (Research Electronic Data Capture). The UW study 
coordinators conducting surveys will be blind as to group assignment. 
Qualitative participant data will be gathered via interviews with 30 participants conducted 3 times per 
person over the course of the study.  Each interview is expected to take about 30-60 minutes and will take 
place either in-person or via phone.  
Participant focus group data will be gathered 2 times during the study and will be used for system and 
content enhancement and improving the user interface. Focus groups will contain 3-7 unique participants, 
will last 1-2 hours and will be conducted in-person. 

17 
 
 
Use data. C-CHESS use data will be collected in time-stamped log files, including when a patient 
accessed C-CHESS, service(s) used, duration of use, pages viewed, messages posted vs. received, and the 
content of messages.  
Staff subjects. Clinical staff will be consulted in the design and implementation of the Clinician Report 
(CR) feature of the website. They will also be asked as the study progresses about how they are using the 
CR, what they find helpful, and their opinions about the sustainability of C-CHESS in their organization. 
These discussions will be informal and participation is optional.  
Unanticipated Events 
Should any unanticipated problems arise the UW research team will work with the HS IRB to 
immediately address the problem, using the following guide:  
 
Inappropriate use of the application 
It is anticipated that the website may sometimes be used inappropriately. A research staff member will 
review and delete any messages deemed inappropriate (i.e nudity, threats, racism, bigotry). A research 
staff member will then follow up with the author of the inappropriate content. Discussion group 
guidelines have been developed and will be reviewed with participants as part of training.  
Reasons for removing a subject from study 
Cases in which a subject has ongoing borderline behavior will be evaluated individually and the subject 
may be removed from study if we feel it is in the best interest of the individual as well as the others on 
study. 
Privacy and Confidentiality 
What Event is Reported 
When is Event Reported 
By Whom is 
Event Reported 
To Whom is Event 
Reported 
Participant suicide as confirmed by a 
medical professional 
Within 7 calendar days of initial 
receipt of information 
Investigators 
Internal IRB 
Internal DMC 
Fatal or life-threatening unexpected, 
suspected serious adverse reactions 
Within 7 calendar days of initial 
receipt of information 
Investigator 
Internal IRBs 
NHLBI and/or DMC 
Sponsor or 
designee1 
FDA (if IND study) 
Non-fatal, non-life-threatening 
unexpected, suspected serious 
adverse reactions 
Within 15 calendar days of initial 
receipt of information 
Investigator 
Internal IRBs/ 
Institutional Officials 
NHLBI and/or DMC 
Sponsor or 
designee 
FDA  
All participating 
investigators 
Unanticipated adverse device effects Within 10 working days of 
investigator first learning of effect 
Investigator 
Internal IRBs 
NHLBI and/or DMC 
Sponsor or 
designee 
FDA (if IDE study) 
Unanticipated Problem that is not an 
SAE 
Within 14 days of the investigator 
becoming aware of the problem 
Investigator 
Internal 
IRBs/Institutional 
Officials, 
NHLBI and/or DMC 
All Unanticipated Problems2 
Within 30 days of the IRB’s receipt of 
the report of the UP from the 
investigator. 
IRB 
OHRP 
Investigator3 
Internal IRBs and 
DMC 

18 
 
 
To mitigate the risk of patient breaches of confidentiality, all subjects will be assigned a code number. A 
list of subject code numbers will be maintained by the UW project director and stored in a password-
protected spreadsheet. This data will be kept in a secure, limited access server maintained by the College 
of Engineering.  
Patient data will be identified using a unique C-CHESS ID number that will be aligned to the EHR 
Patient ID at each clinic. This approach allows a provider at a clinic to see the combined study and EHR 
data for a given patient, while members of the research team would see research data only. Investigators 
will have no record of client identity for analysis purposes. The Clinician Report is equipped with a log 
that records who accessed what data, at what time, and for how long. 
Study data will be kept in a secure, limited access server maintained by the College of Engineering for 
analysis. The database administrator will grant password-protected accounts to provide access to study 
data at appropriate levels for various members of the research team. Members of the research team will be 
able to view de-identified individual and clinic-level aggregations of variables in the patient RTC. 
When all study activities are complete identifiable information will be destroyed. De-identified study data 
will be stored on the secure servers for potential future unspecified research for which new IRB 
submissions will be initiated. 
Potential Risks 
The principal risks to participants are  
• 
The potential for subjects to receive and act on bad information or misinterpret accurate 
information. To mitigate the risk of providing inaccurate or harmful information to patients, all C-
CHESS content will be screened by Drs. Mahoney and Brown. C-CHESS information will be 
presented in text and audio formats that are easy to understand and accessible by individuals who 
have low literacy skills to reduce the risk of misinterpretation. Additionally, messages exchanged 
within the C-CHESS discussion groups will be monitored to make sure the information is 
accurate and that study participants are using the system for its intended purpose. 
• 
There is a risk that information provided in C-CHESS will be used to the detriment of the 
subjects. Patients will be asked to set up a passcode on the laptop to protect their information in 
the event someone else finds it. All participants will receive information and guidelines on 
Internet safety and security during initial training.  
• 
There could be a breach of confidentiality that could result in disclosure of research data outside 
of the study team. To prevent this, all subjects will be assigned a blind code number. These lists 
will be kept in a locked file in the CHESS office, and will not be shown to staff. Data collected 
from clinic records will have the name removed and a code number attached. Project staff who 
have access to the data will not have access to subject names. No clinic staff who have direct 
contact with the subjects will have access to data until the names are removed and the data is 
labeled with the blind code number. C-CHESS will automatically collect data on how often and 
for how long participants use the specific services within C-CHESS. This information will be 
collected by subjects’ C-CHESS code number only and will not be attached to real names or 
identities. 
• 
Internet service will be stopped after 12 months. Subjects may feel some loss when they no 
longer have this service. Participants will receive notice in advance of internet termination. 
• 
Participants will be asked personal questions related to past or current behaviors and experiences, 
such as struggles with health issues, weight loss etc. that could produce anxiety, distress, 
embarrassment, or feelings of sadness.  

19 
 
 
• 
During study activities we may discover behavior that raises concern about elder abuse, harm to 
self or others. If we see anything that suggests that patient subjects or others face imminent risk of 
harm, we will contact appropriate others to intervene (e.g., State authorities, clinic, and/or police) 
6.0 
MEASUREMENT OF EFFECT  
All scales being used in this study have good psychometric properties with similar populations. Listed 
below are the factors to be measured and measurement instruments with references to validation studies. 
Quantitative analyses. Two types of analyses are planned: 1) a general, whole-sample analysis of 
outcomes not specific to any condition, and 2) analyses of condition-specific outcomes that permit 
integration across condition categories.  
The first, general outcome category includes quality of life and primary care use which will be assessed 
with the same measures and same metrics regardless of conditions. 
The second type of analysis is for condition-specific outcomes: mm Hg for hypertension, md/dL for 
hyperlipidemia, HbA1c for diabetes, and pain for arthritis. These outcomes will be analyzed in 2 ways. In 
one approach, scores on each measure will be transformed to Z scores and combined to create the 
composite score across all 5 outcomes, which will constitute an improper linear model with unit 
weighting; this is a secondary outcome. Thus, patients will be compared based on the pooled composite. 
Because we believe that change in the composite will reflect specific conditions and combinations, these 
factors will be entered as covariates in separate analyses to determine whether particular conditions or 
combinations of conditions are significantly related to the magnitude of treatment effects on the 
composite. Because patients often have more than 3 chronic conditions, we will code for the presence or 
absence of other common chronic conditions (e.g., cancer, pain, depression, anxiety, falls, heart disease, 
diabetes, and osteoporosis). The particular combinations involved will be entered as dummy variables. 
The second approach to the analyses of condition-specific outcomes will involve examining condition-
specific outcomes individually, with only those individuals in the C-CHESS and comparison groups who 
have the pertinent diagnosis contributing data to the analysis (e.g., only those with diabetes will 
contribute data to the analyses involving HbA1c). The analytic approach to symptoms would be similar to 
the approach to the condition-specific tests. We will set a threshold for inclusion in the composite, and 
use as individual dependent variables the symptoms that occur in ≥10% of the sample.  
This analysis plan should allow us to examine treatment-related change with regard to: 1) condition-
specific clinical outcomes; 2) general outcomes reflecting disease coping and burden; and 3) condition-
specific clinical outcomes when modeled as a composite score that reflects status with regard to the 5 
major conditions. 
Effectiveness of TAU+Internet vs. TAU+C-CHESS. We will use separate mixed-effects models to 
evaluate the primary and secondary outcomes. Each model will include fixed effects for TAU+Internet 
vs. TAU+C-CHESS, time (6, 12, and 18 months), and the arm-by-time interaction, including the baseline 
assessment of each outcome as a covariate. We will also determine whether clinic exerts main effects or 
interacts with the treatment condition. The latter will test the consistency of C-CHESS effects over 
different clinics and whether data can be pooled across sites. The initial intercepts will be modeled as 
random variables to estimate variance and covariance of intervention effects at the different fixed 
occasions, and across and between patients. These models account for dependence among successive 
observations made on the same patient and use all available data (not just complete cases). We will 
conduct treatment time contrasts between and within groups to test time-based effects, with our primary 
analysis focused on the C-CHESS effect at 12 months. Generalized linear mixed-effects models will be 
used for the count outcomes addressing primary care use. If a count outcome has sufficient variability, 
Poisson regression will be used; if not, the outcome will be coded as dichotomous (some service use vs. 
none) and logistic regression will be used.  

20 
 
 
Mediation. We will test 4 potential mediators of the intervention’s effect on the primary and secondary 
outcomes. We will also test whether the condition-specific and composite secondary outcomes mediate 
the intervention’s effect on the primary outcomes. Mediation will be tested by individually testing the 2 
paths in the indirect effect and will conclude statistical significance only when the null hypothesis of no 
effect is rejected for both paths in the mediational pathway. To limit the number of analyses, we will use 
Bolt’s approach94 of first using a screening approach that examines only mediational models with 
outcomes and potential mediators significantly affected by the intervention. We will then use separate 
univariate models to determine which mediate the intervention effect on given outcomes. If 2 or 3 
mediators are found, we will simultaneously enter all the significant mediators into the same model. If  
4 mediators are found, we will enter the ‘strongest’ mediator first and then test whether adding remaining 
mediators shows significant mediational effects. 
Moderation. A moderation model holds that the strength of the relation between intervention and 
outcomes is a function of the level of other variables and tries to explain under what conditions the 
treatment model functions. We will test whether gender, age (65-74 vs ≥75), and number of chronic 
conditions (3, 4, or 5) moderate the effect of the intervention on outcomes. Also, when standardized 
composites are used as the dependent variable, type of chronic condition will be used as a moderator to 
determine if the composite varies meaningfully by condition. Participants will list changes in chronic 
conditions at 6 and 12 months. 
Moderated mediation. Although both constructs of mediation and moderation are of interest in our 
research, the process is more complex than just these factors. For example, a variable (e.g., relatedness) 
may act as a stronger mediator for 1 subgroup (e.g., women) than another (e.g., men).  
Qualitative analyses. Through 3 interviews we will gather qualitative data from clinic staff to provide 
additional insights into their use of the CR.  
 
In the baseline interview, clinicians will be asked about anticipated barriers to participation and concerns 
about navigating C-CHESS and incorporating it into their treatment plans. Near the end of a clinic’s 
intervention period, clinicians will be asked about factors that influenced their use of C-CHESS, 
perceptions of short- and long-term effects, and ways in which similar clinics might implement and 
sustain C-CHESS. In the post-test period, clinicians will be asked about enduring effects observed and 
implications of losing C-CHESS for treating their patients.  
Feedback from these interviews will be used anecdotally and will help the research team improve the 
design and delivery of the CR. 
7.0  
STUDY PARAMETERS 
Patients will be randomized on a 1:1 ratio to TAU + internet or TAU+C-CHESS. Subjects will be 
stratified by gender, number of conditions and study site. It is anticipated that up to 330 patient subjects 
will be recruited at the participating clinics. Staff subjects will have access to C-CHESS for the duration 
of the study. Patient will have access to C-CHESS for 12 months.  
8.0 
STATISTICAL CONSIDERATIONS 
Power analyses for primary and secondary outcomes. Our power analysis was based on Elder Tree  pilot 
data and other studies that examined the impact of behavioral interventions on single chronic conditions.95 
A meta-analysis96 of self-management interventions found significant effects on HbA1c for diabetics (d=-
.36), and on systolic blood pressure among hypertensives (d=-.39). Other studies found a moderate effect 
size (d=.61) on pain behavior97 and a small effect on number of primary care visits (d = .28) when 
patients attended self-management and peer-support meetings.98,99  
Because effect sizes vary for interventions of chronic conditions, we want our expected effect sizes to be 
conservative and yet clinically meaningful. We therefore chose an effect size of d=.40 for our primary 

21 
 
 
outcomes (quality of life and primary care use) as well as individual condition measures (secondary 
outcomes) and the composite score based on them. Adequate power (1-β =.80, two-tailed α =.05) would 
require a final sample of N=200 patients (100 per arm).100 Since we will examine 4 clusters, with 3 
conditions per cluster, we will need 132 per arm. Assuming 20% attrition, we will recruit N=330 patients 
(33 per arm per clinic). This should also be sufficient for detecting similar effect sizes (at a power of 1-β 
=.80) for condition-specific changes in diabetes,101 hypertension,102 and arthritis.103 The literature is less 
clear in hyperlipidemia but 50% of patients are non-adherent to statins,104 and statins have a high effect 
size,105 so our goal may be achievable.   
Power for mediation and moderation analyses. Power for detecting parameter changes in the structural 
model was estimated using a procedure of Satorra and Saris106 that approximates the non-central chi-
square distribution. A total N of 220 patients will provide adequate power (> .80) to detect a group 
difference in a parameter by moderate .4 standard deviations. With an N of 264 in our primary analysis, 
we are confident our secondary analysis will have adequate power. 
Impact on power calculations of adding attention control and the Clinician Report. We are using a 
placebo comparison group to remove the Hawthorne effect, not to contribute to managing chronic 
conditions. Conversely, the addition of the Clinician Report to the Elder Tree system upon which C-
CHESS is based should have a positive effect. We compared CHESS to CHESS+CR in a lung cancer 
RCT and found statistically and practically significant improvement in symptom distress by adding the 
CR. Overall, we believe this change will make our power analyses conservative. 
Missingness 
In previous work, we completed 85% of interviews at 4, 8, and 12 months and kept missing data on core 
interview items to about 2%; we expect these rates in this study. In primary care, data are not likely to be 
missing at random (i.e., the probability that data are missing relates to what the data would have been had 
the data been observed). Because this may lead to biased parameter estimates for our models, we will 
identify missing data patterns and use pattern-mixture modeling to test the sensitivity of our longitudinal 
intervention analysis to missing data assumptions,107,108 and conduct other sensitivity analyses after 
imputing missing data with a range of clinically plausible values based on explicit assumptions for the 
missing data (e.g., best-case, worst-case; with and without multiple imputation).109,110  
9.0 
RECORDS TO BE KEPT 
• 
Subject Intake  
• 
Subject Demographics 
• 
Subject Consent Forms 
• 
HIPAA Authorization Form 
• 
Baseline and follow up survey data 
• 
Coded C-CHESS use data   
• 
Coded patient lab scores and health care utilization   
• 
Coded transcripts from focus groups and interviews with patients 
• 
Coded transcripts from interviews with clinic staff 
 
 

22 
 
 
Appendix A 
 
CENTER FOR HEALTH ENHANCEMENT SYSTEMS STUDIES 
Data Monitoring Committee (DMC) 
For this project, the UW ICTR Data Monitoring Committee (DMC) will act as the Monitoring Board to 
oversee the study. The UW ICTR DMC is comprised of experienced members (core plus ad hoc) with 
expertise required to oversee this study. The DMC members will review protocol-specific reports created 
by statisticians using data pulled from the Research Electronic Data Capture (REDCap) data management 
tool. These standard reports will include an overview of study objectives, a review of actual and projected 
accrual rates, an evaluation of patient demographics for balance of randomization, and a summary of the 
number and seriousness of adverse events. An interim analysis of study results may be performed and 
source documents may be reviewed to allow the DMC to independently judge whether the overall 
integrity and conduct of the protocol remain acceptable based on data provided and reported by the 
Principal Investigator. This is a low risk study, but if we do conduct interim analyses our statistician will 
take into consideration the reduction in statistical power that will occur with each iteration. The DMC will 
make recommendations to the Principal Investigator that could include actions of continuation, 
modification, suspension, or termination.  
The composition of the DMC contains experts qualified to review this protocol, including MDs in 
Pharmacy, Cardiology, Critical Care, and Psychiatry.  
In providing oversight for the conduct of this study, the ICTR DMC will meet in-person annually during 
the 5-year study to review all adverse events. Additional meetings may be scheduled as determined by the 
DMC or as requested by the PI.  
The predefined stopping points for this study will include excess rates of hospital re-admissions or quality 
of life determinates, exceeding 30% of pre-test values in both cases. We will submit all events, including 
both serious and non-serious adverse events and unanticipated problems, to the NHLBI, the DMC and the 
UW Health Sciences IRB in accordance with the following timeline: 
What Event is Reported 
When is Event Reported 
By Whom is 
Event Reported 
To Whom is Event 
Reported 
Fatal or life-threatening 
unexpected, suspected serious 
adverse reactions 
Within 7 calendar days of initial 
receipt of information 
Investigator 
Internal IRBs 
NHLBI and/or DMC 
Sponsor or 
designee1 
FDA (if IND study) 
Non-fatal, non-life-threatening 
unexpected, suspected serious 
adverse reactions 
Within 15 calendar days of 
initial receipt of information 
Investigator 
Internal IRBs/ 
Institutional Officials 
NHLBI and/or DMC 
Sponsor or 
designee 
FDA  
All participating 
investigators 
Unanticipated adverse device 
effects 
Within 10 working days of 
investigator first learning of 
effect 
Investigator 
Internal IRBs 
NHLBI and/or DMC 
Sponsor or 
designee 
FDA (if IDE study) 
Unanticipated Problem that is 
not an SAE 
Within 14 days of the 
investigator becoming aware of 
the problem 
Investigator 
Internal 
IRBs/Institutional 
Officials, 
NHLBI and/or DMC 
All Unanticipated Problems2 
Within 30 days of the IRB’s 
IRB 
OHRP 

23 
 
 
REDCap, a secure on-line data entry portal, will be used to standardize data capture between the multiple 
project sites. Project personnel at each study site will have the ability to enter data into REDCap via an 
individual user log-in. The user log-in can be configured to limit access to identifiable data, downloadable 
data sets, and data from other sites. 
This Charter is for the Data Monitoring Committee (DMC) for the Center for Health Enhancement 
Systems Studies.  The Charter will define the primary responsibilities of the DMC, its relationship with 
other trial components, its membership, and the purpose and timing of its meetings. The Charter will also 
provide the procedures for ensuring confidentiality and proper communication, the statistical monitoring 
guidelines to be implemented by the DMC, and an outline of the content of the reports that will be 
provided to the DMC.  
 
 
receipt of the report of the UP 
from the investigator. 
Investigator3 
Internal IRBs and 
DMC 

24 
 
 
UW Institute for Clinical and Translational Research  
Data Monitoring Committee Charter (Update 8/11/2016) 
 
1.1 
INTRODUCTION 
The UW Institute for Clinical and Translational Research (UW ICTR) has developed an organizational 
structure to provide the appropriate oversight and monitoring of clinical research to ensure the safety of 
participants and the validity and integrity of the data.1 
To meet these needs, UW ICTR will convene a group of multidisciplinary experts to: 
1. monitor subject safety and data integrity across the UW-Madison clinical research 
infrastructure, and 
2. serve as the Data Monitoring Committee (DMC) for investigator-initiated clinical research 
protocols that require and request an independent DMC 
 
The UW ICTR Data Monitoring Committee (ICTR DMC) covers responsibilities of entities often 
referred to as a Data and Safety Monitoring Committee (DSMC) or a Data and Safety Monitoring 
Board (DSMB). 
 
The term “clinical research” is used throughout this document as defined by the National Institutes of 
Health (NIH). The NIH definition of clinical research is “(1) Patient Oriented Research: Research 
conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive 
phenomena) for which an investigator (or colleague) directly interacts with human subjects. Patient-
oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical 
trials, and (d) development of new technologies. (2) Epidemiologic and behavioral studies; (3) Outcomes 
research and health services research.2 
 
Changes to this Charter may not be made without approval by the ICTR DMC.  Protocol specific 
information should be included in an addendum or memorandum of understanding approved by the 
DMC. 
2.1 SCOPE 
To monitor participant safety across the infrastructure, the UW ICTR DMC will use the clinical 
research management software, ICTR OnCore or the research electronic data capture application, 
REDCap, to identify trends within and across the spectrum, including the incidence of serious adverse 
events (SAEs), subject accrual, and subject retention. 
As noted, the UW ICTR DMC will provide data monitoring for individual clinical research protocols in 
need of DMC review (as determined by the Principal Investigator (PI), the funding agency, the local 
Scientific Review Committee, or the local Institutional Review Board (IRB), and for which no DMC 
exists). For these studies, the UW ICTR DMC will be the primary data and safety advisory group for the 
PI. The DMC will periodically review study results, evaluate the number and seriousness of adverse 
events, determine whether the basic protocol assumptions remain valid, judge whether the overall 
integrity and conduct of the protocol remain acceptable based on data provided and reported by PI, and 
make recommendations to the PI. Using the UW ICTR DMC will require the use of the clinical research 
management software, OnCore, licensed by UW ICTR to act as the data management tool for the 
protocol under review or the research electronic data capture application, REDCap. 
 
DMC review will be based on the NIH1 and U.S. Food and Drug Administration (FDA) guidelines.3 
Additional attention will be given to UW-Madison investigator-initiated protocols, with a focus on: 
a. Protocols with high-risk subjects 
b. Protocols with high-risk or novel interventions 

25 
 
 
c. Studies in special or vulnerable populations 
d. Protocols with survival as the outcome measurement 
e. Phase III and IV studies 
f. Long duration/long-term studies 
g. Protocols with an investigator held IND or IDE application 
 
Protocols with a formal DMC review process, such as industry sponsored protocols and those being 
conducted under the purview of the UW Carbone Cancer Center Data and Safety Monitoring Committee, 
will be excluded from the ICTR DMC reviews. 
 
In the course of reviewing local Serious Adverse Events (SAEs), the ICTR DMC may review protocols 
that are under the purview of an external DSMC or DSMB in order to monitor the trend of drug- or 
device-related SAEs across disparate protocols and sponsors. 
3.1 
ORGANIZATION 
 
3.1 
Composition of the DMC 
ICTR DMC membership will consist of a core of multi-disciplinary members with experience in 
clinical research including, but not limited to, clinicians, scientists, and statisticians.  In addition, an 
extensive list of ad hoc members will represent expertise to complement that of the core members 
and provide the flexibility to serve the diverse research landscape at UW. 
 
3.2 
Appointment of DMC Members 
The DMC Co-Chairs and members (voting and non-voting) are appointed by the UW ICTR 
Director with input from ICTR Schools and Department Chairs as needed. The DMC core 
members will review all protocols under the purview of the committee. 
 
DMC members will serve three years before rotating off the DMC, with staggered appointments 
to retain institutional experience. If a member is unable to continue participation on the DMC, the 
DMC chairs and members may recommend a replacement to the UW ICTR Director. 
 
4.1 
RESPONSIBILITIES AND FUNCTIONS 
 
4.2 Responsibilities of ICTR DMC: 
The ICTR DMC will function as the official DMC for an individual protocol, as requested by 
the study PI or other group, such as the IRB or Scientific Review Committees. The DMC may 
also identify and review trends within and across the infrastructure in need of independent 
review. Identification of trends will focus on the incidence of SAEs, subject accrual, and 
subject retention with effort to identify the areas where improvement can be made. 
 
When performing its role as official DMC of an individual protocol, the ICTR DMC will 
request initial review of the protocol after Scientific Review Committee approval, and before 
subject enrollment has been initiated for the purposes of; 
 
• 
Reviewing the study protocol and any protocol amendments and making 
recommendations to the PI. 
• 
Reviewing overall data collection methods and safety monitoring procedures and 
recommending additions or adjustments. 
• 
Assisting with the definition of safety and related parameters to be monitored, frequency 
of committee monitoring reviews, methods for review, and establishment of criteria for 
making recommendations to the PI. 

26 
 
 
 
4.3 
Responsibilities of the Principal Investigator 
The PI is responsible to the DMC for the following: 
 
• 
Making resources available to the DMC as required to carry out its designated functions 
including use of ICTR OnCore clinical research management software or the research 
electronic data capture application, REDCap. 
• 
Provide ICTR DMC relevant external information at the time of review (such as data from 
other protocols establishing unequivocal treatment benefit or harm, data from clinical 
practice indicating unsuspected and unacceptable treatment side effects, developments 
superseding current treatment, treatment withdrawal from the market) 
• 
Communication of ICTR DMC actions and all pertinent regulatory information to the 
FDA, the local Scientific Review Committee, the local IRB, and the sponsoring agency 
when applicable. 
• 
Adverse events (AEs) and severe adverse events (SAEs) will be reported to the DMC 
within the same time frame as required for reporting to the IRB. 
• 
Submitting IRB-approved changes of protocol that affect the safety or primary 
outcome(s) to the ICTR DMC. 
 
5.1 
DATA MANAGEMENT RESPONSIBILITIES 
ICTR OnCore or REDCap must be used as the data management tool for protocols utilizing the 
ICTR DMC for their protocols. 
 
ICTR OnCore or REDCap will be used to; 
• 
Electronically capture data needed to address study objective(s) and subject safety. 
• 
Provide data sets containing all data necessary for creating DMC reports to the Data Management 
Center/Core or statistician assigned to the protocol. 
 
The protocol Data Management Center/Core (if applicable), or PI, will be responsible for the following: 
• 
Collection and on-site monitoring of case report forms. 
• 
Ensuring the completeness and accuracy of all data collected to the extent required by the 
DMC. 
 
6.0 
RESPONSIBILITIES OF THE STATISTICAL DATA ANALYSIS CENTER 
OR DESIGNATED STUDY STATISTICIAN 
The designated Statistical Data Analysis Center (SDAC) or designated study statistician is responsible 
for the overall data analysis preparation for review by the DMC, using templates and guidance provided 
by the ICTR DMC. When acting as an ICTR DMC for an individual protocol, review will occur 
annually, at a minimum. The frequency of ICTR DMC review will be determined by the PI and specified 
in the statistical plan of the protocol, including stopping rules. 
 
The designated SDAC or designated study statistician prepares reports for review by the DMC based 
on data generated as part of the study and validated by the Data Management Center.  The SDAC also 
prepares reports based on supporting documentation for events and may receive copies of case report 
forms directly from study participant care physicians for these events. 
 
The SDAC will prepare interim reports that will include recruitment, baseline comparisons of risk 
factors, protocol compliance, primary and secondary outcomes, safety and adverse effects, and a 
limited number of sub-group analyses when relevant. The SDAC will repeat these analyses for the final 
analysis of the protocol. 

27 
 
 
 
7.1 
CONDUCT OF DMC MEETINGS 
7.2 
Scheduled Meetings 
 
7.2.1 Scheduled Meetings when serving as the DMC for the UW-Madison clinical 
research infrastructure. 
 
When acting as an institution-wide DMC to monitor subject safety across the clinical 
research infrastructure, the ICTR DMC will convene in a single location at a minimum 
of once yearly, or more frequently as needed. If necessary, additional meetings may be 
held by conference calls if the DMC so decides. 
 
7.2.2. Scheduled Meetings when serving as the DMC for investigator-initiated clinical 
research protocols that request an independent DMC. 
 
When acting as a DMC for an individual protocol, the ICTR DMC will convene prior 
to initiation of the study to help define safety and related parameters to be monitored, 
frequency of committee monitoring reviews, methods for review, and a priori criteria 
for study discontinuation. A scheduled meeting will convene in a single location at a 
minimum of once yearly. However, the frequency of additional scheduled meetings 
depends on patient enrollment and safety event rates, thus frequency could be greater 
than once yearly.  If necessary, additional meetings may be held by conference calls if 
the DMC so decides. 
 
7.3 
Meeting Format 
 
7.3.1. Open/Closed Meetings 
The ICTR DMC does not meet the definition of a “governmental body” as defined in 
sec. 19.82(1), Wis. Stats., in that it was not created by constitution, statute, ordinance, 
rule or order.  As a result, the ICTR DMC does not operate consistent with the 
Wisconsin Open Meetings law.  The use of the term “open session” herein describes 
that portion of a meeting in which the PI and/or his/her staff are invited to be present at 
the meeting. 
 
The use of the term “closed session” herein describes that portion of the meeting when 
only the ICTR DMC members, staff from the SDAC, and invited guests (such as those 
with a particular needed expertise) are present at the meeting.  Such terms should be 
not be given their meaning under the Wisconsin Open Meetings law. 
 
7.3.2 Format of Meetings when serving as the DMC for the UW-Madison clinical 
research infrastructure. 
 
When acting as an institution-wide DMC to monitor subject safety across the 
clinical research infrastructure, the ICTR DMC meetings will consist of only closed 
sessions. Attendance to these meetings will be restricted to ICTR DMC members 
and administrative staff, staff from the SDAC, and any invited guests.  NHLBI 
staff representatives will be voted in and will be allowed to attend as invited guests. 
 
7.3.3 Format of Meetings when serving as the DMC for investigator-initiated clinical 
research protocols. 

28 
 
 
 
ICTR DMC meetings will follow Robert’s Rules of Order in all cases in which they are 
applicable and not inconsistent with ICTR DMC standard operating procedures. The 
meetings will consist of open and closed portions.  During the initial open portion of a 
meeting, the PI and his/her designated staff may be invited to make brief presentations 
and be available for questions from and discussions with the DMC members without 
revealing interim data.  The open session will only discuss aggregate data to reduce the 
risk of misleading conclusions.  The closed session will be restricted to ICTR DMC 
members and administrative staff, staff from the SDAC, and any invited guests.4  The 
closed session will discuss accumulating data by assigned and unblended treatment 
group. 
 
7.3 
Content of Review 
During the closed session, members will review the DMC report prepared by the SDAC or protocol 
statistician. The report will include the following items; 
a. Study progress (e.g. overall accrual, accrual rates) 
b. Adverse events, especially serious adverse events 
c. External information (such as data from other protocols establishing unequivocal treatment 
benefit or harm, data from clinical practice indicating unsuspected and unacceptable 
treatment side effects, developments superseding current treatment, treatment withdrawal 
from the market) 
d. Interim Data Analysis (if applicable) 
e. Data Quality; to potentially address data quality, the ICTR DMC reserves the right to 
review the data, accompanying source documentation, or other relevant study data 
materials, if requested. 
f. Impact of findings on the risk-benefit ratio 
 
7.4 
Recommended Actions 
In either DMC function – infrastructure reviews or acting as an individual protocol’s DMC – the 
committee will recommend one of the following actions to the study principal investigator: 
a. The protocol can continue without change 
b. The protocol or protocol plan should be modified. Modifications may include, but are not 
limited to, changes in inclusion/exclusion criteria, frequency of visits or safety monitoring, 
alterations in study procedures, adjustments in sample size, changes in duration of observation 
and follow up. 
c. The protocol should be suspended, allowing subject visits to occur as scheduled to monitor 
subject safety, but not allowing new subjects to be enrolled until ICTR DMC concerns have 
been appropriately addressed. 
d. The protocol should be discontinued, or one treatment arm of the protocol should be 
discontinued, (with provision for orderly discontinuation) due to: 
i. 
Serious concerns about subject safety 
ii. 
Serious concerns about the safety of interventions 
iii. 
Benefits do not outweigh the risks to subjects 
iv. 
Protocol outcomes do not justify risk 
v. 
New developments impact subject safety/ethics 
vi. 
Unreasonable degree of difficulty of procedures 
 
Authority for continuing, modifying, suspending, or termination of the protocol is the responsibility of 
the PI, IRB, FDA, or other regulatory authority. The ICTR DMC provides independent 
recommendations. 

29 
 
 
 
Correspondence, to include the date of DMC review, and the committee recommended action, will be 
shared with PI of the study in question. 
 
7.5 
Quorum 
A quorum consists of a simple majority (51%) of ICTR DMC members present at the scheduled or 
unscheduled meeting or participating by phone. 
 
7.6 
Voting 
To vote, a Committee member must be present at convened scheduled meetings, unscheduled meetings, 
or be a participant through conference calls.  For voting purposes, a simple majority of the quorum is 
required to pass a proposal or motion.  The chair of the meeting does not vote. A member may abstain 
from voting, but their presence at the meeting still counts towards quorum. A member may also recuse 
themselves due to a conflict of interest, which will lower the quorum. On a tie vote the proposal, 
motion, or recommendation fails.  Additional discussion and a new proposal, motion, or 
recommendation may be made. 
 
If quorum cannot be achieved, a sub-committee may convene to make recommended actions to the 
study team.  The sub-committee must include at least 3 ICTR DMC members consisting of a chair, 
statistician and member with medical expertise.  In this instance unanimity must be achieved to pass the 
recommendation to the study team. The recommended action will be considered for formal approval at 
the next DMC meeting at which a quorum is reached.  If unanimity is not achieved the review will be 
deferred to the next meeting. 
 
7.7 
Procedures for Sharing Recommended Actions with the Principal Investigator 
Duly voted and passed DMC recommended actions will be transmitted in writing to the PI within 
seven working days of the meeting at which the recommended action was passed.  The PI has the 
responsibility to forward the unedited letter detailing recommended actions and all pertinent regulatory 
information to the FDA, the local Scientific Review Committee, the local IRB, other site IRBs, the 
sponsoring agency, or other oversight bodies when applicable and pertinent. 
 
The PI also has the responsibility of responding to the DMC’s recommended actions within 10 working 
days from the date on the DMC letter.  If the recommended action is termination or suspension due to 
a safety issue, the PI must respond within 2 working days of receiving the DMC letter. 
 
7.8 
Review Notification and Meeting Minutes 
Meeting minutes are prepared by DMC administrative staff with the DMC Chair for each DMC meeting, 
distributed in a timely manner after each meeting, and reviewed and approved at the subsequent meeting. 
 
With the expectation that the PI may be masked to study treatments, and that the meeting minutes may 
contain some data by treatment groups (even if the treatments are designated by code), the meeting 
minutes will not be forwarded to the PI. 
 
Instead, the PI will receive notification that the protocol was reviewed; the date of the review, and the 
committee recommended actions that were passed. This notification will be forwarded to the PI with 
instructions to share the notification with appropriate local and federal oversight bodies. 
 
At the end of the study and after treatment is unblinded, a copy of the meeting minutes will be 
forwarded to the PI with recommendations to forward to appropriate local and federal oversight bodies. 
 

30 
 
 
Correspondence, to include the date of DMC review and the committee recommended action, will be 
shared with the local IRB, in addition to the PI of the study in question. 
 
7.9 
Confidentiality 
All members will treat as confidential the reports, meeting discussions, summary notes and minutes. 
Each member will sign a Confidentiality Non-Disclosure Agreement that will accompany 
documentation that entails their responsibilities as a DMC member.  All ad hoc members, invited 
guests, and SDAC staff will also sign a Confidentiality Non- Disclosure Agreement. 
 
7.10 
Financial Conflict of Interest Guidelines (when acting as a DMC for an individual Protocol) 
When performing its role as official DMC for an individual protocol, a DMC member has a conflict of 
interest if on the protocol under review he or she, or his/her spouse, domestic partner or dependents: 
a. serves as PI, co-investigator, key personnel, or likely author on publications resulting from the 
protocol under review (the DMC may waive this requirement as needed); 
b. is involved in monitoring, analysis, or evaluation of subjects on the protocol under review; 
c. is in a position that gives him or her the ability to influence the conduct of the protocol in any 
role other than that of a DMC member;4 
d. has any intellectual property or financial conflict of interest with the protocol under review. 
 
Additionally, a DMC member has a conflict of interest if he or she, or his/her spouse, domestic partner 
or dependents, buys, sells, or holds stock options with the Sponsor of a protocol under review for the 
following periods:  from the first meeting at which the DMC reviews the protocol until the last meeting 
at which the protocol is reviewed and the study results are made public. 
 
A DMC committee member also has a conflict of interest if he or she, or his/her spouse, domestic 
partner or dependents, serves as a paid consultant to the Sponsor during these same periods.  The 
guidelines also apply to staff at the SDAC.  The ICTR DMC will hold, and update annually, conflict-of-
interest statements from each member. 
 
Certain other activities are not viewed as constituting conflicts of interest but must be reported annually 
to the DMC chair. These include: the participation of a member in educational activities supported by 
the Sponsor, the participation of members in other research projects supported by the Sponsor, and 
occasional scientific consulting to the Sponsor on issues not related to the product in the protocol and 
for which there is no financial payment or other compensation. 
 
Committee members and SDAC staff who have a conflict of interest may answer DMC member 
questions, but must remove themselves during sensitive discussions and recuse themselves from voting 
on the protocol in which they have a conflict, unless the DMC (absent the member or staff person with a 
conflict of interest) determines that these guidelines should be waived. 
 
An ICTR DMC member may be from the same department or research program as the PI whose 
protocol is under review, if none of the above referenced conflict of interest criteria are present. 
 
ICTR DMC will strive to minimize potential perceived conflict of interest, thus may invite ad hoc 
members from nearby institutions outside the UW when their area of expertise is needed. 
 
BIBLIOGRAPHY: 
1. NIH POLICY FOR DATA AND SAFETY MONITORING, Release Date:  June 10, 1998:  
http://grants.nih.gov/grants/guide/notice-files/not98-084.html accessed on 05/08/2008. 
2. Protecting Human Research Participants, NIH Office of Extramural Research;  

31 
 
 
http://grants.nih.gov/grants/funding/women_min/training/tsld007.htm accessed on 10/14/2009 
at 3:03 PM 
3. Guidance for Clinical Trial Sponsors On the Establishment and Operation of Clinical Trial Data 
Monitoring Committees; www.fda.gov/ohrms/dockets/98fr/010489gd.pdf 
4. Ellenberg SS. Independent data monitoring committees: rationale, operations and 
controversies. Stat Med. 2001 Sep 15-30;20(17-18):2573-83. 
5. Task Force of the Working Group on Arrhythmias of the European Society of Cardiology:  The 
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With-special reference to trials in the field of arrhythmias and sudden death.  Circulation 1994; 
89(6):2892-2907. 
 
 

32 
 
 
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