Implementing a Multilevel Intervention to Accelerate Colorectal Cancer Screening and Follow-up in Federally Qualified Health Centers Using a Stepped Wedge Design
Conditions: Colorectal Cancer
Sponsor: Milton S. Hershey Medical Center

IRB19-1496 
 
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STUDY PROTOCOL 
Title: 
Accelerating Colorectal Cancer Screening and Follow-Up Through 
Implementation Science in Chicago: UH3 Implementation Phase 
 
Short Title: 
ACCSIS UH3 - Chicago  
 
Sponsor: 
National Cancer Institute Moonshot Initiative 
 
IRB Number: 
IRB19-1496 
 
Protocol Date: 
October 27, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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TABLE OF CONTENTS 
 
Table of Contents……………………………………………………………………………………….2 
Abstract………….………..……………………………………………………….……………………..3 
1             BACKGROUND AND SIGNIFICANCE………………………..………...…………………4 
      
1.1 Background…………………………………………………………………………………….4 
1.2 Significance…………………………………………………………………………………….5 
 
2             STUDY OBJECTIVES……………………………………………….………………………..6 
         
        2.1  Objective 1………………………………………………………………………………………6 
        2.2  Objective 2……………………………………………………………………………………...6 
        2.3  Objective 3………………………………………………………………………………………6 
        2.4  Study Duration and Study Sites………………………………………………………………6 
 
3             STUDY DESIGN AND PROCEDURES……………………………………………………..7 
 
        3.1  Study Design……………………………………………………………………………………7 
        3.2  Study Intervention...……………………………………………………………………………7 
        3.3  Recruitment……………………………………………………………………………………10 
        3.4  Inclusion and Exclusion Criteria……………………………………………………………..10 
        3.5  Data Sources………………………………………………………………………………….10 
 
4.             DATA ANALYSES…………………………………………………………………..………11 
 
5.             STUDY MANAGEMENT…………….………………………………………………………12 
         5.1  Data management……………………………………………………………………...……12 
         5.2  Confidentiality……………………………………………………………………………...…12 
         5.3  Regulatory and Ethnical Considerations……………………………………………..……12 
                5.3.1  Risk Assessment……………………………………………..………………………12 
                5.3.2  Potential Benefits………………………………..……………………………………12 
 
6.             REFERENCES……………………………………………………………………………….13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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ABSTRACT 
 
Introduction: 
 
Screening for colorectal cancer (CRC) not only detects the disease early but also 
prevents cancer by finding and removing precancerous polyps.  While the percentage of the 
U.S. adult population that is up-to-date with recommended CRC screening increased to 65% in 
2010, nearly 28% of the eligible adults have never been screened. Underuse of CRC screening 
is frequent among racial/ethnic minorities and low social, economic status populations. These 
populations disproportionately receive health care in safety-net settings, such as federally 
qualified health centers (FQHCs). Thus, FQHCs play a significant role in CRC prevention and 
control.   
 
Objectives: 
 
The overall goal of our project, Accelerating Colorectal Cancer Screening and Follow-Up 
Through Implementation Science in Chicago (ACCSIS-Chicago), is to test a multilevel, 
multicomponent intervention to increase rates of CRC screening, follow-up, and referral-to-care 
among racial/ethnic minority and low-income populations in Chicago, Illinois. The ACCSIS-
Chicago is a two-phase study.  During the UG3 Planning-Exploratory Phase (Year 1), we 
conducted in-depth interviews with one of our FQHC partners in another similar study to 
understand how to best increase the adoption, implementation, and sustainment of a multilevel, 
multicomponent intervention, and use the information to develop implementation support 
strategies (IRB18-1141). In the UH3 Implementation Phase (Year 2 to 5),  we will implement the 
multilevel, multicomponent intervention in four FQHCs using a stepped wedge design and 
evaluate the effectiveness using multilevel modeling.  
 
Study Design/Setting/Participants: 
 
In the UH3 Implementation Phase, we will have 4 clusters of clinics from four different 
FQHCs.  Each cluster will have 5 to 12 clinics and a total of 20 to 35 primary care providers 
(internist, family practice physician, nurse practitioners, and physician assistants). We will 
implement our multilevel, multicomponent intervention in three phases. In phase 1, we will 
implement the provider education and community outreach component to target the provider- 
and community-level influences. In phase 2, we will add the mobile patient reminder, and the 
provider assessment and feedback components to target organization-level influences. In phase 
3, we will add the CRC patient navigation component to address the possible barriers that 
individuals face during the processes of CRC screening and follow-up. 
 
Study Intervention and Measures: 
 
The multilevel intervention components will include 1) provider education, 2) provider 
assessment and feedback, 3) patient reminder using mobile platform, 4) patient navigation, and 
5) community outreach. The first three components will be implemented as part of the quality 
improvement project at the partner FQHCs. During the first six months, we will collect baseline 
data at our partner FQHCs. After we start implementing the multilevel intervention, we will 
collect outcome data every three months until the completion of the 4-year study period. At the 
clinic and provider levels, we will work with the Quality Improvement Department to collect 
outcome data on 1) CRC screening rates, 2) CRC screening order rates, 3) CRC screening 
completion rates, 4) follow-up diagnostic evaluation rates, 5) follow-up diagnostic evaluation 
completion rates, and 5) time to completion of diagnostic evaluation. At the patient level, we will 
collect data on patient navigation service utilization and the satisfaction of the services.  
 
 
 

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1. BACKGROUND AND SIGNIFICANCE 
1.1. Background 
Colorectal Cancer Burden in Illinois 
Colorectal cancer (CRC) is the second leading cause of cancer death in the United 
States. Screening for CRC not only detects the disease early when treatment is more effective 
but also prevents cancer by finding and removing precancerous polyps. Despite strong 
evidence to support CRC screening, nationally, only 65% of adults had up-to-date screening [1].  
Residents in the state of Illinois are no exception, and in fact, Illinois ranks in the last quartile 
(54% to 50%) for 
CRC screening 
rates across the 
nation, as shown 
in Figure 1 [2]. 
This disturbing 
statistic has no 
doubt been a 
contributor to the 
high CRC 
incidence in 
Illinois. In 2013, 
Illinois had the 
13th highest age-
adjusted CRC 
incidence rate in 
the nation at 
42.9/100,000 [2]. 
Among 
communities of 
color, African 
American (AA) males and females in Illinois rank the 8th highest CRC mortality rate in the nation 
[3].  Furthermore, Illinois has the 5th largest number of Hispanic and Asian-American 
populations in the nation. Both Hispanic and Asian Americans have significantly lower CRC 
screening rates compared to Non-Hispanic White and Black [4]. 
  
Colorectal Cancer Burden in Cook County     
Cook County is the most populous county in Illinois and the second-most populous 
county in the United States. According to the 2010 census, Cook County had 5,194,675 
residents, who represented 40% of all residents in the state of Illinois. Furthermore, 24% of 
Cook County residents (or 1,253,354 individuals) were between the ages of 50 and 74 years in 
2010 [5]. Although 
Cook County has a 
similar CRC incident 
rate as Illinois, its 
CRC mortality rate is 
significantly higher 
than the Illinois 
overall rate and 
ranks 3rd across the 
102 counties in 
Illinois [5]. Some of 
Cook County’s 
Figure 1: Percentage of Adults Aged 50–75 Years Who Reported Being Up-to-Date* with 
Colorectal Test Screening, by State. 
Source: CDC (2010) 

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population characteristics may contribute to the colorectal cancer burden. Compared to other 
counties in Illinois, Cook County has the most diverse population with significantly higher 
numbers of African Americans, Hispanics, Asian Americans, as well as people who are living 
below 200% of the poverty level (Table 1) [5]. Studies have consistently shown that racial and 
ethnic minorities, as well as those living in poverty, suffer disproportionately from health 
disparities, and the 2010 National Health Interview Survey (NHIS) found that CRC screening 
rates were significantly lower among racial/ethnic minorities compared to whites (59.8%), Blacks 
(55.0%), Hispanics (46.5%) and Asians (46.9%) [6].  The low socioeconomic indicators and 
poor CRC health outcomes experienced by a disproportionate number of Cook County 
residents underscore the critical need to create a more organized approach to CRC prevention 
and control in the county. Cook County is also home to the City of Chicago, where 
approximately 54% of county residents reside. Chicago is the 3rd most populous city in the U.S., 
and its CRC mortality rate overall is 21.5 deaths per 100,000, higher than the nation’s overall 
colorectal cancer mortality rate of 17.5 deaths per 100,000.  Chicago also has the 2nd largest 
African American population, 4th largest Hispanic population, and 5th largest Asian American 
population in the nation.  Although efforts have been in place to improve CRC outcomes in 
Chicago and Cook County, the lack of coordination across different sectors and attention to 
multilevel influences diminish the impact of such efforts.  
 
Safety-Net Health Care Systems and Colorectal Cancer Control 
  
Although the percentage of the U.S. adult population that is up-to-date with 
recommended CRC screening increased from 54% in 2002 to 65% in 2010 [7], nearly 28% of 
the eligible adults still had never been screened [2]. Individuals who were without health 
insurance and a regular care provider were more likely to have never been screened than those 
with health insurance and with a regular care provider [2]. Racial/ethnic minorities and low 
social, economic status (SES) populations are among those who lack health insurance and a 
usual source of care. Underuse of CRC screening is frequent among these populations [8-10], 
who disproportionately receive health care in safety-net settings, such as federally qualified 
health centers (FQHCs) [7, 11]. FQHCs are designed to provide comprehensive, quality primary 
health care services to medically underserved communities and vulnerable populations. In 
2016, FQHCs served 26 million patients, of whom 23% were uninsured, 62% were racial/ethnic 
minorities, and 92% were living below 200% poverty level [12]. Because many of our nation’s 
most disadvantaged and vulnerable individuals make use of FQHCs to obtain health care, 
FQHCs play a significant role in CRC prevention and control.  
 
  
1.2. Significance 
 
The overall goal of our project, Accelerating Colorectal Cancer Screening and 
Follow-up through Implementation Science in Chicago (ACCSIS-Chicago), is two-fold: 1) to 
understand how to best increase the adoption, implementation, and sustainment of evidence-
based interventions; and 2) to provide the evidence base for multilevel interventions that 
increase rates of CRC screening, follow-up, and referral-to-care among racial/ethnic minority 
and low SES populations. The ACCSIS-Chicago will focus on Cook County geographically, 
especially in Chicago, where 54% of the Cook County population resides. We will partner with 
local FQHCs, community-based organizations, and workplaces to increase rates of CRC 
screening, follow-up, and referral-to-care among racial/ethnic minority and low SES populations. 
The ACCSIS-Chicago project will use two types of implementation strategies to increase rates 
of CRC screening, follow-up, and referral-to-care among racial/ethnic minority and low SES 
populations: 1) a multilevel intervention, which will have multiple components, and 2) 
implementation support strategies to accelerate the adoption, implementation, and sustainment 
of the multilevel intervention. In the UH3 Implementation Phase, we will partner with 4 FQHCs, 
which have 35 clinics in the Chicago area and provide primary care service to racial/ethnic 

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minority and low SES populations. Together, these 4 FQHCs served more than 188,037 
patients in 2016. We will use a stepped wedge cluster randomized trial design to examine the 
effectiveness and impact of our multilevel interventions on increasing rates of CRC screening, 
follow-up, and referral-to-care across these 4 partner FQHCs.  We will also implement a local 
innovation, ILColonCARES Program, and assess its feasibility and effectiveness on the follow-
up of a positive FIT. 
 
  
2. STUDY OBJECTIVES, DURATION, AND STUDY SITES 
2.1.  Study Objectives 
 
Objective 1: Collect baseline data during the first 6 months before implementing any 
intervention component. 
 
Objective 2: Implement the intervention in three phases: 1) provider education plus community 
outreach; 2) add provider assessment and feedback + patient reminder; and 3) add a CRC 
navigator program. 
 
Objective 3: Create a grand model to test the overall effectiveness of the multilevel intervention 
on primary outcomes within and across levels, as well as separate models to access 
effectiveness at each phase. 
 
Objective 4: Identify potential interaction or mediation effects and assess such effects on 
primary outcomes.  
 
Exploratory Objective 5: Implement a local innovation, IL ColonCARES Program, and assess 
its feasibility and effectiveness on the follow-up of abnormality. 
 
2.2.  Study Duration and Study Sites 
 
The ACCSIS – Chicago UH3 Implementation Phase will last for four years (November 
2019 to October 2023).  In the UH3 Implementation Phase, we will have 4 clusters of clinics 
from four different FQHCs.  Each cluster will have 5 to 12 clinics and a total of 20 to 35 primary 
care providers (internist, family practice physician, nurse practitioners, and physician 
assistants).  Table 1 summarizes the characteristics of our FQHC partners. Together, our 

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partner FQHCs served 188,037 patients in 2016, and at least 10% of these patients were ≥ 50 
years old. It is important to point out that three of our partners’ CRC screening rates were in the 
lower third and fourth quartiles compared to other FQHCs in the nation, indicating room for 
improvement. We will continue to monitor their ranking throughout the study.   
 
3. STUDY DESIGN AND PROCEDURES 
3.1 Study Design 
 
We will use a stepped wedge cluster randomized trial design to assess the effectiveness 
of our proposed multilevel intervention. Although it will be preferable to use a traditional cluster-
randomized trial to test our multicomponent, multilevel intervention, we will need a larger 
number of clusters, which will be more expensive and infeasible. Also, it is unacceptable for our 
partner(s) assigned to a control group to not benefit from well-studied evidence-based 
interventions. Since the stepped wedge design retains some elements of randomization and has 
the advantage for multiple data collection points over a long period and allows clusters to act as 
their own control, it is the best alternative to the gold standard. 
 
 
In the UH3 Implementation phase, we will partner with four FQHCs. We will randomize 
the four FQHCs to either group 1 or group 2.  The biostatistician will conduct the randomization 
independently from the research team. The difference between the two groups is that group 2 
will start the implementation later. We will implement our multilevel intervention in three phases. 
In phase 1, we will implement the provider education and community outreach component. In 
phase 2, we will add the mobile patient reminder and the provider assessment and feedback 
components. In phase 3, we will add the CRC patient navigation component. Figure 1 shows 
our stepped wedge study design.   
 
3.2 Study Intervention 
 
CRC screening and follow-up processes are complex and include several steps and 
interfaces. However, very few interventional studies have simultaneously targeted patient-, 
provider-, and organization-level factors. At the patient-level, factors influencing motivation and 
willingness to undergo CRC screening or diagnostic evaluation after a positive result may 
include negative beliefs or attitudes about cancer screening, lack of health insurance coverage, 
suboptimal knowledge about the necessity of screening and/or follow-up diagnostic evaluation, 
and other SES barriers [13-20]. At the provider-level, factors include overburden [21], 

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communication issues [22], lack of a place for referrals [23], and decisions made by the provider 
not to screen or follow-up [24]. At the organization-level, factors include interruption or 
breakdowns in the workflow, nonadherence to organizational policy, and lack of “intra-
organizational” and “inter-organizational” coordination [25]. Interventions that simultaneously 
focus on reducing barriers across several levels will likely be more effective on increasing rates 
of CRC screening, follow-up, and referral-to-care. In this study, we will partner with the Quality 
Improvement Department at each partner FQHC to implement provider education, provider 
assessment and feedback, and mobile patient reminder as part of the organizational CRC 
Screening Quality Improvement Initiative.  
 
3.2.1 Provider-Level Component: 
Provider Education 
CRC screening, follow-up and surveillance guidelines, cultural 
competency and communication training for primary care providers is a must if we are to 
increase CRC screening and follow-up adherence and decrease cancer disparities among 
racial/ethnic and low-income populations, as well as in the general population. Drs. Kim and 
Polite are well-known CRC control experts and will identify critical messages on CRC screening 
guidelines and options, and provide in-person educational training to providers in our partner 
FQHCs. In addition, they will conduct refresher sessions and yearly training. Dr. Kim and Dr. 
Polite will also train a healthcare member of the ACCSIS-Chicago team to serve as a practice 
facilitator, who will have a medical background and understands the clinical practice, to provide 
one-on-one training for new providers and providers whose CRC screening rates fall below the 
benchmark on two consecutive provider assessment and feedback reports. The facilitating 
sessions for providers whose CRC screening rates below the benchmark will be limited to 10-15 
minutes to refresh key messages on CRC screening and to identify possible barriers. In our 
experience, underperformers were often the result of failure to adequately document FIT results 
into the EMR system rather than an unwillingness to screen patients. Tracking these potential 
barriers can significantly improve screening rates. 
 
Provider Assessment and Feedback  
Provider assessment and feedback is designed to 
both evaluate provider performance in recommending and offering screenings to age-eligible 
patients (assessment) and present providers with information about their performance in 
providing CRC screening services (feedback). We will work with the quality improvement team 
at our partner sites to generate clinic- and provider-specific reports on CRC screening 
completion rate, referral rate, as well as follow-up for abnormal results and referral to oncology 
care. Also, we will monitor group performance (e.g., the mean performance for a specific site or 
group). Providers will receive a quarterly report that allows providers to compare their 
performance to that of their peers and to learn from each other’s successes. Our research team 
will deliver the reports in person for the first two quarters to provide support and open discussion 
to address any concerns about the process and the interpretation of the results. Education and 
training will be provided to reinforce compliance when a partner site’s group or individual 
performance is at or below baseline on two consecutive reports.   
 
3.2.2 Organization-level Component 
Patient Text Message Reminder  
Completion of screening and follow-up evaluation involves 
patient compliance with the provider recommendation. It is critical not only to remind providers 
to order the screening test but also remind patients to complete the test. We will work with our 
partner sites to implement a mobile patient reminder as part of the quality improvement 
initiative. The patient reminder app combines technologies in mobile communication and 
artificial intelligence to engage patients and deliver customized messages and timely 
information to empower patients to complete their screening. Text message reminder has been 
reported to have a positive impact on patient compliance. [25-26] 

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CRC Patient Navigation 
Completion of screening and follow-up evaluation involves patient 
compliance with the provider recommendation. Therefore, we will add a CRC navigator to 
facilitate patient compliance at both organization and patient levels. Patient navigation is a 
healthcare delivery support strategy and was first introduced by Harold P/ Freeman in 1990 as a 
way to reduce cancer disparities by eliminating barriers to timely care between the point of 
suspicious finding and the resolution of the finding by diagnosis and treatment [27].  Most 
patient navigation programs have been created to improve rates of CRC screening [28-36], and 
few studies have used patient navigators to improve outcomes related to diagnostic follow-up 
after a positive test result [37-41]. 
 
 
Our partner FQHCs will hire a patient navigator for their CRC Patient Navigation 
Program with support from the research team.  All hired patient navigators will participate in a 2-
day training session. Our patient navigator training includes didactic and clinical training 
sessions, as well as CITI human subject training. Training will take place 3 months before the 
implementation of the component with ongoing training every quarter through the duration of the 
program. Drs. Kim and Polite and the research team will lead the training. The training will focus 
on, but not limited to, the following topics: CRC and CRC screening methods, the follow-up 
process after a positive FOBT/FIT, cancer treatment, navigator roles and responsibilities, 
common patient barriers, communication skills with health care providers and other 
professionals, cultural competency, local community resources, and the oral consent process 
and the participant’s right.  Furthermore, the CRC navigators will have the opportunity to spend 
time in the University of Chicago endoscopy suite with Dr. Kim and the oncology clinic with Dr. 
Polite observing colonoscopies and patient-provider interactions. The goal of these activities is 
to create an interactive environment that allows navigators to gain knowledge through direct 
experience. CRC navigators will undergo pre and post-training evaluation to assess their 
knowledge for CRC screening and follow-up care. All CRC navigators will meet with a research 
team member biweekly to discuss their cases, share information, and address any issues 
associated with their roles and responsibilities. 
 
ILColonCARES Program 
Many safety net settings with low resources offer FOBT/FIT as the 
initial screening option for their patients [42, 43]. However, providers in these settings often face 
an ethical dilemma: whether to offer no screening or to offer the screening knowing that the 
patient with a positive FOBT/FIT result cannot obtain timely follow-up colonoscopy services. In 
Chicago, the lack of specialty services for colonoscopy access within our safety net system is a 
significant problem with the average wait of 18 months to complete a diagnostic colonoscopy.  
This alone can significantly contribute to disparities in colorectal cancer mortality with studies 
showing that a one year delay in follow up for a positive FIT can result in a twofold increase in 
colorectal cancer risk [44]. Thus, it is important to increase the ability of safety net providers to 
access high quality and timely colonoscopies for their underinsured or uninsured patients when 
a follow-up is needed. ILColonCARES Program is a HIPAA compliant web-based portal 
designed and developed using a user experience approach to link non-networked healthcare 
systems. Some hospital health systems in Chicago have committed to providing no-cost 
colonoscopy services to uninsured FIT positive individuals. The ILColonCARES Program 
overcomes many barriers to receipt of colonoscopy services across systems: 1) access to care 
for uninsured patients, 2) point of service scheduling, 3) bidirectional communication. The 
ILColonCARES Portal was created by a CDC funded program and is housed in the University of 
Chicago. Our partner FQHCs will have access to the portal. 
 
 
 

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3.2.3 Community-Level Component 
Community Outreach  
Reliance solely on primary-care settings to promote and provide 
colorectal cancer screenings can only reach those who have regular contact with the health-
care system. In ACCSIS-Chicago, we will partner with the National Outreach Network program 
at the University of Chicago Comprehensive Cancer Center to conduct community outreach 
activities. We will expand the current community outreach networks and will build new 
partnerships with high-risk communities located near our partner FQHCs.  We will continue the 
NCI’s Screen to Save (S2S) Initiative through small media campaigns in the high-risk 
communities and conduct community education events.  For participants without a regular place 
for care, we will work with our partner FQHCs to develop a referral channel for them to obtain 
CRC screening.   
 
3.3 Recruitment For Patient Navigation 
 
We will have recruitment posters and flyers in each exam room and patient waiting area 
at our partner sites. Patients who have a CRC screening order and need help to complete the 
screening, such as making an appointment for the colonoscopy at a local hospital or instruction 
on the preparation for the colonoscopy, can call the patient navigator at each partner site 
directly. Patient navigators help patients with any challenges that may inhibit screening 
completion by discussing the process through a series of up to 4 phone calls. Participation in 
the patient navigation program is voluntary. 
 
3.4 Inclusion And Exclusion Criteria 
 
The inclusion criteria for the patient navigation component include 1) having an order for 
CRC screening, and 2) capable of giving consent. We will not exclude any participants who 
meet the inclusion criteria based on age, gender, language, or racial or ethnic group. 
 
3.5 Data Sources 
 
During the first three months, we will work with the Quality Improvement Department at 
each partner site to collect baseline data on primary outcomes through the existing electronic 
medical record or chart reviews. After we start implementing the multilevel intervention, we will 
collect primary outcome data each quarter until the completion of the 4-year study period.  Table 
2 summarizes the primary outcome measures. 
 
 

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For the CRC navigation component, we will collect data from the navigator activity logs, 
including the number of patients using the service, length of the encounter, types of encounter 
(e.g., transportation arrangement or making an appointment), and types of action taken. We will 
also ask patients who received navigation services to complete a 10-item patient satisfaction 
survey adapted from the patient satisfaction survey developed by the NCI-sponsored Patient 
Navigation Research Program, which has been validated through rigorous structural and 
reliability analysis [45]. For the community outreach, we will collect annual data on the number 
of education events conducted and the number of community members educated. 
 
4. DATA ANALYSES 
 
In order to evaluate the effect of the multilevel, multicomponent intervention, we will take 
a step-by-step approach. First, each intervention effect at each time phase will be estimated 
separately using linear-mixed effects models. The estimate of intervention effect in each model 
will be used to test if additional intervention component significantly affects outcome measures. 
Next, we will develop a grand model including all three intervention effects simultaneously in 
addition to the models described above.  
 
In this study, patients are nested within providers and providers are nested within clinics. 
The problem with nested data structures is that they violate the independence assumption of 
traditional regression models. Thus, we will use multilevel modeling to analyze our data. We will 
start with the unconditional three-level random intercept models: 
       Level – 1: Yijk = β0jk + еijk;  
       Level – 2: Yijk = β0k + ujk + еijk   
       Level – 3: Yijk = β0 + vk + ujk + еijk   
where Yijk is the observed outcome for patient i with provider j in clinic k. β0 is the mean response 
across all clinic. vk is the random effect of clinic k, ujk is the random effect of provider j, and еijk is 
the residual error. The random effects and residual errors are assumed independent of one 
another. 
 
 
Adding predictor variables to the models is straightforward. For example, the level-3 
random intercept and slope model with one predictor measured at each level is Yijk = β0 + β1X1ijk 
+ β2X2jk + β3k + vk + ujk + еijk, where  β0 + β1X1ijk + β2X2jk + β3k is the fixed effect of the model 
and vk + ujk + еijk is the random effect of the model. The fixed effect of the model specifies the 
overall mean relationship between the response and the predictor variables. The random effect 
of the model specifies how the provider and clinic specific relationships differ from the overall 
mean relationship. To assess the potential mediator effect, we will use the causal variable and 
the mediator variable as predictors in the model. To assess the cross-level interaction effects, we 
will add a product term to the model. For example, the model for a level-1 predictor (e.g. age) 
cross-level and interact with a level-2 predictor: Yijk = β0 + β1X1ijk + β2X2jk + β3 (X1ijk ● X2jk) + 
u0jk + u1jk X1ijk + еijk.  Since one of the patient-level (level-1) outcome measures is dichotomous 
(whether the patient adherence to follow-up diagnostic evaluation after a positive result within 9 
months or not), we will add another level-1 model for the binary data:  
 
                        Level – 1:  log [Pijk/ (1 – Pijk)] = β0jk + β1Xijk. 
 
 
In this study, we will use the restricted maximum likelihood (REML) to estimate variances. 
REML treats the regression coefficients as unknown quantities to be estimated based on sample 
data and subtracts the needed degree of freedom when computing variance estimates. Since 
REML only allows for tests of models that differ in their variances, we will calculate the intraclass 
correlation (ICC) to access the variation in response variable across providers and across clinics 
prior to testing the models. At the end of the analysis, we will use the likelihood ratio test to 

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compare the nested models. The deviance values (-2 log Likelihood) for the two models can be 
used to decide which model better fits the data:  
 
                      (-2log LReduced Model) – (-2log LFull Model) = devianceReduced Model – devianceFull Model 
 
Statistical analyses will be conducted using Statistical Package for the Social Science (SPSS) 
version 23.0 and the significant level will set at alpha ≤ 0.05. 
 
 
5. STUDY MANAGEMENT 
 
5.1 Data Management 
 
 
During data extraction from EMR, the medical record numbers will be converted to 
unique study numbers. Data files used for statistical analyses will have only unique study 
numbers and will not contain the 18 HIPAA personal health information identifiers. We will work 
with the University of Chicago Center for Research Informatics' bioinformatics and clinical trial 
management core to manage our data, and all data will be entered into RedCAP (Research 
Electronic Data Capture) at the University of Chicago. REDCap is a clinical data warehouse. 
The data storages at REDCap are secure, encrypted, and compliant with HIPAA. 
 
5.2 Confidentiality 
 
 
All information collected from study participants and medical records during the project 
period will be kept confidential, including information collected and stored in written and 
electronic form. Besides safeguards for confidentiality described under Data Management 
(Section 5.1), we will take additional steps: 
 
1 
Any paper copies of identifying information and other study materials will be maintained in 
locked file cabinets in locked offices. 
2 
Electronic data files will be secured via server maintenance that includes password 
protection, limited access to data by staff, different levels of access depending on the 
person’s specific position on the team, and server securities. 
 
5.3 Regulatory and Ethical Considerations 
 
5.3.1 Risk Assessment 
 
 
Participation in this study (patient navigation component) has minimal risk. Participants 
may feel discomfort answering the survey questions as they include some sensitive questions, 
such as “my navigator makes me feel comfortable.” Participants can choose not to answer the 
question or stop participating in the study at any time without any risks. There are no known 
physical, financial, or legal risks associated with the satisfaction survey. Another potential risk to 
our participants is the possibility of breaches of confidentiality. 
 
5.3.2 Potential Benefits  
 
 
Patients participate in the patient navigation program may find the patient navigation 
service helpful to complete their colorectal cancer screening. In addition, their response to the 
patient satisfaction survey may help us improve patient navigation services. 

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For the societal benefit, there is a pressing need to reduce disparities in CRC outcomes, 
especially among racial/ethnic minority populations and among populations who live in poverty. 
Single level interventions are often insufficient to lead to sustained changes in CRC screening, 
follow-up, and referral-to-care. Multilevel interventions with multiple components will affect not 
only the desired outcomes but also each other that may add additional impacts.   
 
 
 
6. REFERENCES 
 
1.  CDC (2010). Behavioral Risk Factor Surveillance System Survey data. Atlanta, Georgia: 
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