Screening More Patients for CRC Through Adapting and Refining Targeted Evidence-Based Interventions in Rural Settings (SMARTER CRC)
Phase: NA
Conditions: Colorectal Carcinoma
Sponsor: OHSU Knight Cancer Institute

 
1 
 
OHSU Knight Cancer Institute 
Cancer Prevention, Control and Epidemiology Protocol 
 
Screening More patients for CRC through Adapting and Refining Targeted Evidence-based 
Interventions in Rural settings (SMARTER CRC) 
 
Funding Agency: 
 
National Cancer Institute / Cancer Moonshot Initiative 
 
 
 
 
 
 
Type of Award: 
UH3CA244298   
 
ClinicalTrials.gov ID:  
NCT04890054 
Principal Investigators:  
Melinda M. Davis, PhD 
 
 
 
 
3181 SW Sam Jackson Park Rd.  
 
 
 
 
Portland, OR 97239 
 
 
 
 
503-494-4365  
 
 
 
 
 
Gloria Coronado, PhD 
 
Kaiser Permanente Northwest 
 
Portland, OR   
 
503-335-2400  
 
 
 
 
 
 
 
 
Initial Protocol Date:  
11/1/2019 
 
 
Protocol Revision Dates:  
 1/13/2020 
 
 
 
7/22/2020 
 
11/2/2020 
 
3/17/2021 
 
6/3/2021 
 
8/16/2022 
 
5/15/2023 
 
06/07/2023 

 
2 
 
 
Contents 
1.0  
ABSTRACT (required) ..................................................................................................................... 3 
2.0  
BACKGROUND / RATIONALE (required).................................................................................... 3 
3.0  
OBJECTIVES (required) .................................................................................................................. 4 
4.0  
STUDY POPULATION (required) .................................................................................................. 4 
5.0  
INCLUSION/EXCLUSION CRITERIA (required) ......................................................................... 5 
6.0  
METHODOLOGY (required) ........................................................................................................... 6 
7.0  
STUDY PROCEDURES AND SCHEDULE OF EVENTS (required)............................................ 6 
8.0  
TIME LINE AND MILESTONES (required) .................................................................................. 9 
9.0  
BIOSTATISTICAL CONSIDERATIONS (required) .................................................................... 11 
10.0 
ETHICAL AND REGULATORY REQUIREMENTS .................................................................. 12 
10.1 
Protocol Review (required) ......................................................................................................... 12 
10.2 
Informed Consent (only if applicable) ........................................................................................ 12 
10.3 
Changes to Protocol (required) ................................................................................................... 12 
10.4 
Privacy, Confidentiality, and Data Security (required) ............................................................... 13 
10.5 
Maintenance of Records (required) ............................................................................................. 13 
10.6 
OHSU IRB Reporting of Unanticipated Problems and Adverse Events (only if applicable) ..... 13 
10.7 
MedWatch Reporting (only if applicable) .................................................................................. 14 
10.8 
OHSU Knight Cancer Institute Data and Safety Monitoring Plan (only if applicable) .............. 14 
10.9 
Inclusion of Women, Minorities and Children (only if applicable) ............................................ 14 
10.10 
Inclusion of Children (only if applicable) ............................................................................... 15 
11.0  
REFERENCES (required)........................................................................................................... 15 
12.0 
APPENDIX I - TOXICITY CRITERIA (only if applicable) ......................................................... 16 
 

 
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1.0  
ABSTRACT  
This two-phase project is designed to achieve the Cancer Moonshot objectives by reducing the burden of 
CRC on the US population. Specifically, we aim to improve CRC screening rates, follow-up colonoscopy, 
and referral to care in rural Medicaid patients by implementing a direct mail fecal testing program with 
targeted outreach and patient navigation for follow-up colonoscopy. We leverage partnerships with the 
Oregon Rural Practice-based Research Network (ORPRN), Kaiser Northwest Center for Health Research, 
and Medicaid Health Plans and deliver training and implementation support to participating rural primary 
care clinics using practice facilitation. For the pragmatic trial, we anticipate working with 3 CCOs and 30 
clinics reaching approximately 4,500 Medicaid patients. For the scale up trial, we anticipate partnering 
with 20 organizations to facilitate program implementation with 130 primary care clinics (reaching 
17,000+ rural Medicaid patients). The mailed FIT and patient navigation interventions will be 
implemented as part of standard care by health system or clinic staff. 
 
In Phase I (Year 01), we will conduct a milestone driven pilot to build the necessary infrastructure for a 
large-scale trial, including adapting the clinic-health plan-vendor supported direct mail program for rural 
Medicaid patients that have not established care and/or never been screened; conducting a pilot study 
testing the feasibility and acceptability of patient navigation to support follow-up colonoscopy following 
an abnormal fecal test; engaging Medicaid Health Plans and recruiting 30 primary care clinics located in 
rural and frontier counties in Oregon; and developing the training and support materials needed to 
implement a large-scale trial in these settings.  
 
In Phase II (Years 02-05), we will test our intervention using a two-arm cluster randomized control trial 
in 30 rural primary care clinics using program training and practice facilitation to support implementation. 
Participating clinics will be randomized into two groups: Intervention and Usual Care. Randomization 
will be stratified on health system. As in the pilot, the intervention combines: (1) a clinic-health plan-
vendor supported direct-mail fecal testing program with targeted outreach for patients who have never 
been screened or who have yet to establish care and (2) patient navigation for those who are referred for 
colonoscopy as either the primary screening or for follow-up from an abnormal fecal test. We will 
evaluate effectiveness, implementation, and maintenance of the intervention through quantitative and 
qualitative measures. Results from the trial will inform scale-up of the program through partnerships with 
20 regional and national organizations that serve rural/frontier primary care clinics using webinars, train-
the-trainer workshops and collaborative learning activities. 
2.0  
BACKGROUND / RATIONALE  
Colorectal cancer (CRC) is the third-leading cause of cancer deaths in the United States2 and the second 
leading cause among Oregonians.3 CRC is 90% curable with timely detection and appropriate treatment 
of precancerous growths.1 If not found until a patient is symptomatic, however, survival rates drop to 
50%.4 However, 1 in 3 age-eligible adults is not up-to-date for CRC screening.5 Projections indicate that 
increasing CRC screening to 80% from current levels could prevent 277,000 cases and 203,000 deaths 
from the disease over the next 12 years.6 Achieving this goal will require concerted efforts as 
approximately 25 million US adults aged 50–75 (33%) are not currently up-to-date.7   
 

 
4 
 
CRC screening rates are particularly low among adults in rural communities and sub-populations within 
these settings (e.g., Medicaid enrollees, Hispanic patients, Native Americans).1,8-10 Rural areas cover 97% 
of the US land area and are home to approximately 60 million people. Within rural areas, frontier counties 
are the most remote and sparsely populated (having fewer than 7 people per square mile).11 CRC 
incidence and mortality are disproportionately high among residents of rural regions;9,12 disparities driven 
in part by differences in adherence to screening guidelines.9,13 Medicaid enrollees are a key underserved 
group in rural areas. In 2016, Medicaid provided health insurance and access to preventive health services 
to 82 million people, including 1 million in Oregon.14 Medicaid covers nearly 1 in 4 rural resident under 
age 65 (24%).15 This is important as Medicaid members aged 50-64 years have relatively low rates of 
CRC screening, as demonstrated in national data (47% for Medicaid vs. 60% for private/Medicare aged 
50-64)16 and Oregon data for CRC screening in newly age eligible patients (34.9% for Medicaid vs. 
42.8% for private).17 Medicaid members also display less favorable CRC outcomes compared to 
commercially insured adults.18,19  
Interventions are needed to address disparities is CRC screening, follow-up, and treatment in rural 
Medicaid patients. While mailed FIT and patient navigation are effective methods of improving screening 
and follow-up, no existing program incorporates these strategies into a resource-efficient, sustainable 
program that can be broadly implemented in rural geographic regions. Our study, Screening More patients 
for CRC through Adapting and Refining Targeted Evidence-based Interventions in Rural settings 
(SMARTER CRC), supports implementation of a targeted, multilevel program that incorporates tailored 
outreach, direct mail and patient navigation to address CRC disparities in rural Medicaid patients. A 
primary component of these interventions will be supporting collaborations between clinics, Medicaid 
health plans operating as ACOs, and commercial vendors to optimize and sustain program components. 
Through the course of a pilot test, large-scale pragmatic trial, and scale-up study, we anticipate working 
with 30 regional and national organizations to facilitate the program’s implementation with an estimated 
130 rural primary care clinics (17,000+ rural Medicaid patients). We will assess drivers of program 
success at the patient-, clinic-, and community-levels. SMARTER CRC will produce an implementation 
guide and resources to support program spread across rural settings serving Medicaid enrollees and other 
underserved populations.  
SMARTER CRC is a partnership between faculty and staff at the Oregon Rural Practice-based Research 
Network (ORPRN) at Oregon Health & Science University (OHSU) and at the Kaiser Permanente 
Northwest Center for Health Research. This study fills key evidence and implementation gaps and 
supports Biden’s Cancer Moonshot objectives by providing a model for how to rapidly adapt and scale-up 
multilevel interventions through clinic-health plan partnerships to reduce the burden of CRC on the US 
population.  
 
3.0  
OBJECTIVES   
Primary Objective:  
Adapt, pilot, then test the implementation and scale-up of targeted direct mail and patient navigation 
programs. 
 
4.0  
STUDY POPULATION   
The study team will recruit eligible CCOs and rural clinics, and we will work in turn with clinics to 
engage providers, staff, and patients. Our eligibility criteria for CCOs, clinics, clinics staff, patients and 
organizational partners are below.  
 

 
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CCOs/CCO staff: 1) serving a majority of counties that are predominantly rural based on 2010 
RUCA Codes (Codes 4-10); 2) willing to participate in data collection activities (e.g., producing 
claims data, interviews). 
 
Clinics: 1) Clinics will be eligible for the cluster randomization if there are 30 or more patients 
eligible for screening, 2) are classified as rural according to RUCA (Codes 4-10) or Oregon 
Office of Rural Health designations, 3) are served by CCOs agreeing to participate in the project; 
and 4) willing to implement the intervention into their clinic for the study. 
 
Clinic Staff/Providers: 1) employed as a clinician or ancillary staff member in a participating 
clinic; 2) willing to participate in data collection activities (e.g., interviews, observation, surveys). 
 
Patients: 1) attributed to participating clinic; and 2) are enrolled in Medicaid or Dual eligible; 3) 
eligible for CRC screening;  
a. For the subset of patients that will be invited to participate in key informant 
interviews, a 5th eligibility criteria is consent to participate.  
 
Exclusion criteria: Clinics are excluded if they have current or ongoing participating in other 
mailed fecal testing research projects in the Medicaid population. Patients are excluded if they are 
current for screening, have comorbid conditions that make patients poor candidates for screening 
based on clinical judgment (e.g., end-stage renal disease, enrollment in hospice), are not an 
established patient or for other reasons documented by the clinics.  
 
Community or regional/organizational partners (includes endoscopy providers, community-based 
outreach workers, or leaders from regional or national organizations who participate in the pilot, 
pragmatic trial, or scale-up study) 1) involved in study activities (training, care delivery); 2) 
willing to participate in data collection activities (e.g., trainings, interviews, surveys). 
 
For this project, we expect to recruit at least three CCOs and 33 Oregon clinics, which allows up to a 10% 
attrition rate to achieve our target of 30 rural primary care clinics. Based on Census Bureau data 
(https://www.census.gov/quickfacts/or), as of 2017, Oregon residents are 50.4% female and 13.1% 
Hispanic or Latino. Also based on Census data, Oregon resident diversity consists of 2.2% African 
American, 1.8% American Indian or Alaskan Native, 0.4% Native Hawaiian and other Pacific Islander, 
4.7% Asian, 87.1% white, and 3.8% two or more races. Based on the Census Bureau’s data, we expect the 
participating individuals to make up a representative sample of Medicaid individuals across the state. 
  
5.0  
INCLUSION/EXCLUSION CRITERIA   
Inclusion criteria:  
 
Included 
Excluded 
Children 
 
All patients we recruit will be at 
least 45 years of age or older, and 
clinic/CCO staff will be at least 18 
years of age or older. 

 
6 
 
Elderly 
Yes – we anticipate that a limited number of 
clinic and CCO staff, or community 
organization representatives may be elderly; we 
limit our patient recruitment to those aged 45-
75. 
 
Rural 
Yes  
 
Inner City 
No 
 
Low Income 
Yes 
 
Disabled 
Yes  
 
Chronic Care 
Yes  
 
End of Life 
Yes - This is possible, but we predict limited 
numbers because of the types of individuals we 
are recruiting: clinic and CCO staff, and 
patients who are not currently in hospice care. 
 
Minorities 
Yes 
 
Both Genders 
Yes 
 
 
This study will not include any vulnerable populations. We will not collect any information about 
subjects’ status as prisoners, pregnant women, children, neonates, and/or adults lacking capacity. 
 
6.0  
METHODOLOGY 
Throughout this trial we will collect data from multiple sources to assess process and outcomes data and 
drivers of program success at the patient-, clinic-, and community-levels aligned with a social ecological 
model for the quality of cancer care. These sources of data include: 
• 
CCO interview, readiness assessment, and survey 
• 
Clinic survey, readiness assessment, observation and interviews 
• 
Patient interviews 
• 
Interviews and surveys with regional and organizational partners 
• 
Patient outcomes data (e.g., claims, vendor reports and electronic health record) and patient 
navigation registry data 
 
7.0  
STUDY PROCEDURES AND SCHEDULE OF EVENTS  
CCO interview, readiness assessment, and survey: CCOs that express interest in participating in the trial 
will be invited to participate in a semi-structured interview (in-person or via phone) and complete a 
baseline survey to confirm CCO characteristics (e.g., size, number of primary care clinics in rural/frontier 
counties) as well as information about CCO data infrastructure, relationships with clinics, and quality 
improvement capacity. Readiness questions will be drawn from the literature and explore the CCO’s prior 
experience with payment and quality improvement initiatives related to CRC screening and follow-up 
care. 
 
Clinic survey, readiness assessment, observation and interviews: For clinics expressing interest in the 
trial, we will conduct semi-structured interviews (in-person or via phone) with clinic leadership to assess 
clinic characteristics, capacity and readiness to adopt the program and participate in the trial. Clinic 
characteristics will include descriptive data (e.g., ownership, primary care clinician number and FTE, 
EHR vendor and version), baseline CRC screening rates and if the clinic currently utilizes audit and 

 
7 
 
feedback, and details on current workflows related to CRC screening and follow-up (including provider 
CRC screening modality preferences). Capacity questions will explore general capacity as well as specific 
capacity related to CRC screening. Readiness questions will draw on prior work by Weiner, Hannon, and 
others,20 and utilize a clinic-level readiness survey piloted by our team during Dr. Davis’ K07. 
We will conduct clinic surveys, interviews, and observations with clinic staff in various roles related to 
the program (e.g., outreach workers, patient navigators, quality improvement leads) to assess clinic/health 
system level factors that may influence outcomes. These assessments will happen at baseline and after 
implementation of the pilot as well as for each arm of the trial (post-implementation at 6-9 months as well 
as implementation context, maintenance, and sustainability approximately 12 months later [i.e., clinic exit 
interviews]).  
 
Patient interviews: We will conduct one-on-one interviews with patients who receive the direct mail and 
patient navigation programs. Interviews will explore patient experiences with the program, including 
reaction, acceptability, satisfaction, and perceptions of usefulness; facilitators of, and barriers to, 
participating in the program and obtaining a follow-up colonoscopy; unintended consequences; and 
suggestions for improvement 
 
Interviews and surveys with regional and organizational partners: To assess perceptions of the 
intervention and its impact on the broader community, we will interview CCO leaders, endoscopy 
providers (e.g., GI specialists, general surgeons, primary care clinicians) who treated study participants, 
and community organizations, including transportation service providers. Up to three interviews will 
occur throughout the duration of the study, including at baseline (pre-implementation), at the mid-point 
(approximately 12 months after the first-year implementation start), and post-implementation 
(approximately 12 months after the second-year implementation start). To evaluate the impact of scale-up 
activities we will conduct interviews and brief evaluation surveys with organizational leaders who 
participate in the trainings. 
 
Patient outcomes data and patient navigation registry (Evaluation): Direct mail outreach and patient 
navigation activities will be tracked using reports from direct mail vendors, claims data from participating 
Medicaid health plans, clinic data from the electronic health record, chart abstraction data conducted by 
ORPRN or clinic staff, and data on navigation from a REDCap database. The mailed FIT and patient 
navigation interventions will be delivered by clinic and health plan staff as part of standard care. Clinics 
will be randomized to implement the interventions in different years to provide comparison groups. 
Claims data will be sent to the research team at OHSU from the participating payers based on their data 
pull of patients eligible for CRC screening in the clinics randomized to implement the intervention. 
Vendor reports will be sent to the CCO and research team based at OHSU. A clinic-level chart audit will 
be used to evaluate CRC screening and follow-up colonoscopy for patients with an abnormal FIT in 
intervention and control clinics. 
Data for this project (i.e., process and survey data elements and patient navigation outcomes (such as 
number of patients who received patient navigation, number of patients with missed / canceled 
appointments or inadequate bowel preparation), will be stored in OCTRI's installation of REDCap, a 
highly secure and robust web-based research data collection and management system. 
 
Features of REDCap that protect participants' privacy and data security include: 
• 
Physical Security: OCTRI's REDCap software is housed on servers located in ITG's Advanced 
Computing Center providing locked physical security 

 
8 
 
• 
Electronic Security: The REDCap servers are housed behind both the OHSU firewall and a 
second ACC firewall.  All transmissions of data from the application are encrypted over HTTPS 
with the industry standard TLS 1.1 protocol (AES 256-bit encryption).  
• 
Controlled User Access: REDCap employs a robust multi-level security system that enables 
researchers to easily implement "minimum necessary" data access for their research staff, 
including specification of data fields that are identifiers. This feature includes “single click” 
ability to provide completely deidentified (removing all identified data fields and shifting dates) 
for analysis or other purposes.  User activities are logged to enable auditing of all data 
access.   Access is integrated with OHSU's network such that users who are also OHSU 
employees are authenticated against their OHSU network credentials.   
• 
Data Integrity: REDCap is jointly managed in accordance with OHSU Information Security 
Directives by ACC staff and members of OCTRI's Biomedical Informatics Program, ensuring 
fidelity of database configuration and back-ups.  User activities are logged to enable auditing of 
all data changes. 
 
Data from the vendor and REDCap database will be merged with claims data to generate evaluation 
reports. To avoid bias in colonoscopy capture across baseline and follow-up time-points, ORPRN practice 
facilitators will perform a chart audit on all patients who were eligible for the direct mail program. The 
chart audit will confirm FIT completion and monitor for colonoscopy referral and receipt, pathology 
results, and referral to care (i.e. surveillance or cancer treatment), as indicated.  
Researchers are requesting a waiver of authorization to access medical record data. ORPRN study staff 
plan to conduct the chart audit at each clinic over the course of 1-3 days. Data will be stored on the OHSU 
instance of REDCap or stored securely on OneDrive and ORPRN staff and select Kaiser Permanente 
research team members will have access to the data by utilizing a password-protected file on OneDrive or 
a REDCap user login. OneDrive and REDCap user permissions will be matched to roles as described in 
the established Data Use Agreement between Kaiser Permanente and OHSU and to the IRB. PHI will 
never be disclosed outside of the study team and all PHI will be destroyed upon completion of the study. 
Through data use agreements, a limited dataset will be shared with the sponsor, the National Cancer 
Institute. The following data elements will be included in the limited data set: patient identifier, age 
group, sex, Hispanic or Latino origin, race, state of residence, county of residence and primary health 
insurance. When possible, the data set will also include primary language, ZIP code of residence, 
individual history of CRC, most recently performed screening test date and result, and diagnostic 
colonoscopy date and result. 
SCHEDULE OF EVENTS 
   
 
 

 
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8.0  
TIMELINE AND MILESTONES   
Phase I practice and CCO participants will be recruited Fall 2019, with the pilot intervention complete by 
the end of year 1. Phase II practice and CCO participants will be recruited in Fall/Winter 2020-2021 and 
first year of implementation will occur in 2021, with second-year implementation occurring in Spring 
2022.  
Phase I Milestones and Timeline 
Aim  
Milestones 
Information 
sources 
Measurement / Validation  
Timeline 
1. Adapt direct mail 
materials and outreach to 
hard-to engage rural 
patients 
a. Identify and recruit rural Medicaid 
patients to participate in Boot Camp 
Translation. 
ORPRN, 
CHARA, 
CCOs, primary 
care clinics 
Number approached and 
engaged. Demographic and 
geographic characteristics 
Oct 2019 – 
Dec 2019 
b. Host Boot Camp Translation 
sessions; adapt program and identify 
outreach for patients at risk 
(unestablished, never screened). 
Boot Camp 
Translation, 
relevant 
literature 
Session attendance, evaluations, 
modifications of program 
messaging, timing, materials 
Jan – May 
2020 
2.  Conduct pilot to test 
the feasibility, 
effectiveness and 
acceptance of patient 
navigation program. 
a. Update registry tools (tools will 
track total FIT kit mailings, test 
results, receipt of follow-up care, and 
display patient’s previous CRC 
screening history). Implement patient 
navigation pilot. 
Claims, 
vendor/lab data, 
EHR data 
 
Navigation 
registry 
Registry; vendor to identify 
patients needing follow-up; tools 
for tracking navigated patients 
and CRC-related outcomes in 
EHR or registry. 
Oct 2019 – 
Apr 2020 
b. Obtain data on patients participating 
in direct mail program and FIT results; 
Assess the pilot intervention’s 
preliminary reach and effectiveness 
based on receipt of direct mail, FIT or 
colonoscopy completion, and 
proportion of patients receiving 
navigation.  
Claims, 
vendor/lab data, 
EHR data 
N FITs completed / FITs mailed; 
across stratification variables. 
 
N patients with abnormal FITs; 
documented receipt of navigation 
and outcome.   
Apr – Jul 
2020 
c. Assess the interventions feasibility 
and acceptance, based on one-on-one 
interviews with patients and debrief 
interviews with clinic/CCO staff. 
Relevant 
literature  
 
Feedback from patients and 
providers. 
Apr – Jul 
2020 

 
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Aims 
Assessment/ 
Measurement 
Data Sources 
Description 
Timeline 
Aim 1. Conduct a large-scale 
pragmatic study, cluster 
randomized control trial, to 
assess the implementation, 
effectiveness, and maintenance 
of the program piloted in Phase I 
in 30 rural primary care clinics (n 
~ 3,960 patients aged 45 – 75) 
using practice facilitation to 
support implementation. Using a 
mixed methods approach, 
identify patient-, clinic/health 
system-, and 
payer/policy/community-level 
factors that are associated with 
reach, effectiveness, 
implementation and maintenance 
and to assess program 
adaptations.   
 
Assessment of 
effectiveness (patient 
and clinic level). 
 
Administrative 
data, claims data, 
EHR data from 
clinics, vendor 
data, laboratory 
data, survey data. 
Patient Level Outcome (Primary): Completion of 
any CRC screening 
Clinic Level Outcome: Proportion of Medicaid 
patients screened for CRC  
We will compare the intervention vs. control clinics 
after adjusting for baseline at 6 and 12 months. The 
primary endpoint is 6 months. Secondary outcomes: 
completion of testing types (fecal testing, FIT-
DNA, CT Colonography, Colonoscopy, Flex 
Sigmoidoscopy; patient level) and % completion 
(clinic level); time to screening from study-eligible 
patient list pull (patient level); FIT results (patient 
level); follow-up colonoscopy completion (patient 
level); time to colonoscopy from abnormal FIT 
result (patient level); and adenomas or cancers 
detected (patient level). 
2021-Sep 
2024 
Assessment of 
implementation 
(compliance rate with 
program components 
at clinic level). 
Administrative 
data, claims data, 
vendor data, 
laboratory data, 
survey data 
including debriefs. 
Proportion of core activities performed (e.g., mailed 
FITs, patient navigation calls) by clinics/CCOs 
 
2021-2024 
Assessment of 
maintenance 
(compliance rate with 
program over time at 
clinic level). 
Administrative 
data, claims data, 
vendor data, 
laboratory data, 
survey data. 
Proportion of intervention clinics sustaining 
program in second year (N core activities sustained 
in second year/ N core activities, in intervention 
clinics/CCOs). Effectiveness of the program in 
intervention clinics in Year 2. 
 
2021-2024 
Assessment of 
maintenance 
(compliance rate with 
program at patient 
level) 
 
Proportion of patients who completed FIT in Year 1 
who complete in Year 2, in intervention clinics. 
 
Phase I Milestones and Timeline 
Aim  
Milestones 
Information 
sources 
Measurement / Validation  
Timeline 
3. Engage CCOs and 
recruit clinics; conduct 
baseline assessment; use 
results from pilot to 
prepare to conduct a 
large-scale, pragmatic 
implementation-
effectiveness trial and 
scale-up (see Phase II). 
a. Creation of a list of inclusion and 
exclusion criteria for CCOs and clinic 
participation in Phase II. 
Relevant 
literature, 
statistical power 
requirements 
Feedback from local advisory 
board on inclusion and exclusion 
criteria 
Jan – Mar 
2020 
b. Develop CCO and clinic 
recruitment materials 
Relevant 
literature 
Feedback from local advisory 
board  
Jan – Mar 
2020 
b. Successfully engage 3 CCOs and 30 
rural/frontier clinics for the main trial 
Feasibility data 
from pilot study 
List of participating CCOs and 
selected clinic characteristics 
Mar – Sep 
2020  
d. Develop manual outlining trial 
protocols (including quality assurance 
protocols), scopes of work, and 
associated budgets. 
Feasibility data 
from pilot study 
Feedback from advisory board on 
recruitment materials; study 
protocol; scope of work 
Apr – Sep 
2020 

 
11 
 
 
Assessment of 
program second year 
implementation and  
adaptations. 
Clinic/CCO 
surveys and 
interviews. 
Types of and reasons for program adaptations, 
based on Wiltsey-Stirman FRAME framework.  
May 2023- 
Sep 2024 
Aim 2. Partner with regional and 
national organizations (n~20) to 
scale-up the program to 
additional clinics serving rural 
and underserved patients in high 
priority geographic regions of the 
US (n ~ 130 clinics; 17,000+ 
patients) using webinars, train-
the-trainer workshops and 
collaborative learning 
approaches. Assess trainings 
delivered, program adoption and 
adaptations and determinants of 
dissemination success. 
 
 
 
 
a. Assessment of 
adoption by clinics and 
community 
organizations. 
 
Participation in 
workshops, 
training, and 
collaborative 
learning activities; 
survey data; use of 
program tools and 
implementation 
materials. 
N clinics, community organizations, and staff that 
participate in training workshops, train-the-trainer 
sessions, and collaborative learning activities. 
Adoption as reported on 6-month survey data of 
workshop participants. 
Use of program tools; downloads of training and 
implementation materials. 
2021-2024 
 
b. Assessment of 
program adaptations. 
Clinic and 
community 
organization 
surveys and 
interviews. 
Types of and reasons for program adaptations.  
Oct 2023- 
Sep 2024 
 
 
 
9.0  
BIOSTATISTICAL CONSIDERATIONS   
 
Phase I: Because this is the pilot phase, in which the primary purpose is to examine the feasibility and 
acceptability of the intervention and not to test a hypothesis, we have not performed a power analysis to 
determine the required sample size for this phase. Instead our primary goal was to evaluate the feasibility 
and acceptability of the program.21-23  
 
Phase II, Aim 1 (Implementation-Effectiveness Trial): We will test our hypotheses using a two-arm 
cluster randomized control trial. Participating clinics will be randomized into two groups: Intervention 
and Usual Care. Randomization will be stratified on health system. Our study design aligns with the core 
principles of the PRECIS-2 framework.24-26 Our eligibility criteria are broad and consistent with the 
realities of rural primary care (e.g., small sample sizes, limited quality improvement capacity). Our 
patient recruitment approach for the direct mail and navigation programs is aligned with routine care and 
standard quality improvement approaches and requires no individual consent. Participating clinics will 
serve populations that display CRC screening disparities, and be diverse in terms of EHR, rural 
geographic locations, and populations served. Our intervention is flexible and is designed to be adapted 
according to payer and clinics’ resources and preferences. Our primary outcome, completion of any CRC 
screening, is pragmatic and relevant to patients, clinics, and payers (CCOs), and our primary analysis 
follows the intention-to-treat concept.27 We will collect data 6 times from the CCOs. Data will be 
transferred every 6 months from the Spring of 2021 to the Fall of 2023 to be able to capture up to 18 
months of follow-up following each mailing.  
 

 
12 
 
The primary effectiveness outcome of this study at the patient level is the completion of any colorectal 
cancer (CRC) screening (for study-eligible patients). Consistent with the pragmatic nature of the trial, we 
will use claims, vendor data, and EHR data for calculating CRC screening outcomes. Comparing the 
likelihood of receiving CRC screening between intervention and usual care groups at 6-month post 
participant list-pull date, we hypothesize that CRC screening will be more likely in patients allocated to 
the intervention group versus the usual care group. To examine the effectiveness of the program CRC 
screening completion at 6 months, we will use the generalized form of the hierarchical linear model 
(HLM; using a logit link and binomial distribution, aka multilevel logistic regression) to account for the 
clustering of patients within clinics and the assignment to arm at the clinic level. The variables that will 
be included in the model are the clinic baseline screening rate (if available) and a binary indicator of arm 
(1=tailored, 0=standard) as fixed effects and clinic is a random effect. A positive and significant 
coefficient for arm would provide support for the effectiveness of the intervention. We will do a 
moderator analysis at all levels to explore the impact of patient and clinics characteristics (see outcomes 
table above), and implementation components affecting outreach on completion likelihood in groups of 
patients determined at analysis (e.g. never screened, Hispanic, etc.).  
 
10.0 
ETHICAL AND REGULATORY REQUIREMENTS 
 
10.1 
Protocol Review  
The protocol and informed consent form for this study must be reviewed and approved in writing  by the 
OHSU Knight Cancer Institute (Knight) Clinical Research Review Committee (CRRC) and appropriate 
Institutional Review Board (IRB) prior to any patient being registered on this study.   
10.2 
Informed Consent 
We are requesting a waiver of documentation of written consent for participation in the main trial. The 
waiver of informed consent is requested because CRC screening is standard care and all activities 
proposed to be undertaken with the research project are minimal risk. There are no interventions or other 
procedures for participants for which written documentation of consent is normally required for research 
activities.  
We intend to collect verbal consent from participants who participate in qualitative interviews. 
Researchers will disseminate an information sheet for the surveys and interviews and will obtain verbal 
consent from participants before continuing with the study interview. Completion of the survey will serve 
as consent to participate. We will obtain verbal consent prior to the interview.  
The research team will conduct chart review for all participants who are eligible for CRC screening. The 
high number of charts to be reviewed renders contact of each individual to obtain written authorization 
impractical as contact information may not be available and the time and resources it will require to 
obtain written consent is not commensurate with a low-risk chart audit review. A Waiver of Authorization 
for the chart review components of this study is included with the application. All data collected via chart 
audit will be handled per section 10.4. 
10.3 
Changes to Protocol  
Any modification of this protocol must be documented in the form of a protocol revision or amendment 
signed by the principal investigator and approved by the CRRC and IRB, before the revision or 
amendment may be implemented. The only circumstance in which the amendment may be initiated 
without regulatory approval is for a change necessary to eliminate an apparent and immediate hazard to 
the patient. In that event, the investigator must notify the CRRC and IRB in writing within 5 working 
days after the implementation. Investigators holding the IND must notify FDA of substantive changes to 
the protocol. 

 
13 
 
10.4 
Privacy, Confidentiality, and Data Security 
This research study involves minimal risk to human subjects. The magnitude of harm or discomfort 
anticipated in the proposed research is not greater in and of itself than that ordinarily encountered in 
everyday life. The information sheet will describe the project purpose, study activities, participant’s 
rights, benefits, and who to contact with questions and will be used to obtain consent.  
Data entered or sent to the study offices will be handled in a highly confidential manner consistent with 
the high standards established at OHSU and ORPRN.  Data presented in all presentations and 
publications will not be associated with the name of any participating person or practice. All computer 
systems at OHSU and ORPRN are protected from possible external access using network security 
systems.  Only study researchers and staff at ORPRN and Kaiser Permanente will have access to the data. 
We will use industry standard Secure Sockets Layer (SSL) technology with server and client certificates 
to insure the confidentiality of data use and any data transfer. 
Surveys and interview transcripts will be de-identified; unique numerical identifiers will be assigned for 
clinic and practice participants. The audio recordings from interviews will be destroyed after analysis. 
Text files will be stored in a password protected, encrypted computer file on a secure workstation at 
OHSU.  
10.4a. Risks and Benefits 
• 
Risks to Subjects 
There is minimal foreseeable risk, discomfort, hazard, or inconvenience to the subjects relating to this 
chart review. There is a minimal risk of breach of confidentiality. The unlikely event of a loss of 
confidentiality could occur through a data transfer oversite.  
• 
Potential Benefits to Subjects 
There are no direct benefits to subjects.  
 
10.5 
Maintenance of Records  
Study data will be stored on OHSU’s secure Box.com.  
If the investigator relocates or for any reason withdraws from the study, the study records will be 
transferred to OHSU Knight Cancer Institute Clinical Research Management. Records will be maintained 
according to sponsor requirements.  
OHSU is one of multiple study sites funded by the National Cancer Institute (NCI) through this funding 
opportunity called the Accelerating Colorectal Cancer Screening and Follow-up through Implementation 
Science (ACCSIS). NCI is establishing a data use agreement with each ACCSIS grantee for submission 
of a limited consolidated data set in order for NCI to establish a repository for further evaluation of 
funded activities. 
10.6 
OHSU IRB Reporting of Unanticipated Problems and Adverse Events  
Unanticipated Problems (UP) and Adverse Events (AE) will be reported to IRB according to the policies, 
procedures and guidelines posted on the OHSU IRB web site:  
• 
Fatal and life-threatening UP will be reported to OHSU IRB within 5 days of notification of the 
event.  All other UP reports will also be submitted to OHSU IRB no later than 5 days of 
occurrence or notification of the event. Copies of the report documents will be kept in the study 
regulatory binder.  
• 
UP and AE reports are submitted through OHSU eIRB and will be reviewed by OHSU Knight 
Cancer Institute and IRB.  Monthly accumulative reports will be reviewed by a DSMC 
Oncologist and forwarded to the CRRC.   

 
14 
 
10.7 
MedWatch Reporting  
Not applicable. 
10.8 
OHSU Knight Cancer Institute Data and Safety Monitoring Plan 
Not applicable. Patients will not be treated under this protocol.  
10.9 
Inclusion of Women, Minorities and Children 
The projected gender, racial, and ethnic composition of the study will represent that of the state of 
Oregon.  
Table 1: Population Demographics - Oregon (%)              
 
Source:   U.S. Census Bureau, 2010    *Totals may not equal 100 due to rounding. 
 
Table 2: Projected Accrual for the Present Study  
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Hispanic or Latino 
1,159 
1,141 
- 
2,299 
Not Hispanic or Latino 
7,756 
7,633 
- 
15,389 
Unknown 
- 
- 
- 
- 
Ethnic Category: Total of all subjects* 
8,915 
8,774 
- 
17,688 
Racial Category 
 
American Indian or Alaskan Native 
178 
176 
- 
354 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
5.85 
5.85 
11.7 
Not Hispanic or Latino 
44.15 
44.15 
88.3 
Ethnic Category: Total of all subjects* 
50 
50 
100* 
Racial Category 
 
American Indian or Alaskan Native 
0-1 
0-1 
1.4 
Asian 
1.85 
1.85 
3.7 
Black or African American 
0-1 
0-1 
1.8 
Native Hawaiian or other Pacific Islander 
0-1 
0-1 
0.3 
White 
41.8 
41.8 
83.6 
More than one race 
1.9 
1.9 
3.8 
Unknown/Other 
2.65 
2.65 
5.3 
Racial Category: Total of all subjects* 
50 
50 
100* 
TOTALS 
50.4 
49.6 
100* 

 
15 
 
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Asian 
356 
351 
- 
708 
Black or African American 
178 
176 
- 
354 
Native Hawaiian or other Pacific Islander 
90 
87 
- 
177 
White 
7,756 
7,632 
- 
15,389 
More than one race 
356 
351 
- 
708 
Unknown 
- 
- 
- 
- 
Racial Category: Total of all subjects* 
8,915 
8,774 
- 
17,688* 
 
Source:   Adapted from U.S. Census Bureau, 2010    *Totals may not equal 100 due to rounding. 
 
10.10 Inclusion of Children 
This protocol does not include children for the following reason: We are surveying and interviewing adult 
staff working in primary care practices and CCOs. Patients who are interviewed are in the CRC 
screening-eligible population (50-75 years old).  
 
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12.0 
APPENDIX I - TOXICITY CRITERIA 
Not applicable.