The EPICS (Engaging Primary Care in Cancer Survivorship) Study: A Trial of Novel Models of Care for Cancer Survivors
Phase: NA
Conditions: Breast Cancer, Colorectal Cancer
Sponsor: Kaiser Permanente

EPICS Study 
 
Version 4.0 
Protocol R01CA249419 
 
02 October 2023 
 
 
 
 
The Engaging Primary Care in Cancer Survivorship 
(EPICS) study* 
 Protocol Number*: R01CA249419 
National Clinical Trial (NCT) Identified Number:  NCT04745754 
Principal Investigator*: Erin E. Hahn, PhD, MPH 
Sponsor: Kaiser Permanente Southern California, Department of Research and 
Evaluation 
Grant Title: The EPICS (Engaging Primary Care in Cancer Survivorship) study: A 
trial of novel models of care for cancer survivors 
Grant Number*: 1R01CA249419-01 
Funded by: National Cancer Institute (NCI) 
Version Number:  v.4.0 
October 2, 2023

EPICS Study 
 
Version 4.0 
Protocol R01CA249419 
 
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Summary of Changes from Previous Version: 
 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
Face Page 
Updated protocol number; 
version number and date from 
3.0 to 4.0 
Protocol number updated to reflect 
amendments below 
Section 1.3 
Updated survey recruitment 
schedule 
Survey recruitment schedule is based on 
initial consultation for intervention 
participants and matched dates for 
controls 
Section 5.5 
Updated incentive plan for survey 
participant recruitment 
Updated due to feasibility 
Section 9.3 
Details on matching plan for 
intervention and control patients  
Matching approach expanded to 
address potential imbalances between 
arms 
Section 10.111; 10.112 
Details on consent/assent and 
other informational documents 
provided to participants 
We received a waiver of written 
informed consent Patient-Reported 
Outcomes surveys 
 
CONFIDENTIALITY STATEMENT 
This document is confidential communication. Acceptance of this document constitutes agreement by the 
recipient that no unpublished information contained herein will be published or disclosed without prior 
approval of the Principal Investigator or other participating study leadership and as consistent with the 
NIH terms of award.  
 

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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
INVESTIGATOR’S SIGNATURE .............................................................................................................................. 2 
1 
PROTOCOL SUMMARY ............................................................................................................................... 3 
1.1 
Synopsis ................................................................................................................................................ 3 
1.2 
Schema ................................................................................................................................................. 5 
1.3 
Schedule of Activities .......................................................................................................................... 6 
2 
INTRODUCTION ............................................................................................................................................ 7 
2.1 
Study Rationale .................................................................................................................................... 7 
2.2 
Risk/Benefit Assessment .................................................................................................................... 9 
2.2.1 
Known Potential Risks ..................................................................................................... 9 
2.2.2 
Known Potential Benefits .............................................................................................. 10 
2.2.3 
Assessment of Potential Risks and Benefits .............................................................. 10 
3 
OBJECTIVES AND ENDPOINTS .............................................................................................................. 11 
4 
STUDY DESIGN ........................................................................................................................................... 12 
4.1 
Overall Design .................................................................................................................................... 12 
4.2 
Scientific Rationale for Study Design.............................................................................................. 15 
4.3 
Justification for Intervention ............................................................................................................. 15 
4.4 
End-of-Study Definition ..................................................................................................................... 16 
5 
STUDY POPULATION ................................................................................................................................ 16 
5.1 
Inclusion Criteria ................................................................................................................................ 16 
5.2 
Exclusion Criteria ............................................................................................................................... 17 
5.3 
Lifestyle Considerations .................................................................................................................... 17 
5.4 
Screen Failures .................................................................................................................................. 17 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 18 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ............................................ 20 
6.1 
Study Intervention(s) or Experimental Manipulation(s) Administration ...................................... 20 
6.1.1 
Study Intervention or Experimental Manipulation Description ................................. 20 
6.1.2 
Administration and/or Dosing ....................................................................................... 21 
6.2 
Fidelity ................................................................................................................................................. 23 
6.2.1 
Interventionist Training and Tracking .......................................................................... 23 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 23 
6.4 
Study Intervention/Experimental Manipulation Adherence.......................................................... 23 
6.5 
Concomitant Therapy ........................................................................................................................ 23 
6.5.1 
Rescue Therapy ............................................................................................................. 23 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ......................................................................................... 23 
7.1 
Discontinuation of Study Intervention/Experimental Manipulation ............................................. 23 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 24 
7.3 
Lost to Follow-Up ............................................................................................................................... 24 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 25 
8.1 
Endpoint and Other Non-Safety Assessments .............................................................................. 25 
8.2 
Safety Assessments .......................................................................................................................... 27 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 27 
8.3.1 
Definition of Adverse Events ........................................................................................ 27 
8.3.2 
Definition of Serious Adverse Events .......................................................................... 28 

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8.3.3 
Classification of an Adverse Event .............................................................................. 28 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 29 
8.3.5 
Adverse Event Reporting .............................................................................................. 30 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 30 
8.3.7 
Reporting Events to Participants ................................................................................. 30 
8.3.8 
Events of Special Interest ............................................................................................. 30 
8.3.9 
Reporting of Pregnancy ................................................................................................ 30 
8.4 
Unanticipated Problems .................................................................................................................... 31 
8.4.1 
Definition of Unanticipated Problems .......................................................................... 31 
8.4.2 
Unanticipated Problems Reporting .............................................................................. 31 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 32 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 32 
9.1 
Statistical Hypotheses ....................................................................................................................... 32 
9.2 
Sample Size Determination .............................................................................................................. 32 
9.3 
Populations for Analyses .................................................................................................................. 36 
9.4 
Statistical Analyses............................................................................................................................ 36 
9.4.1 
General Approach .......................................................................................................... 36 
9.4.2 
Analysis of the Primary Endpoint(s) ............................................................................ 37 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 38 
9.4.4 
Safety Analyses .............................................................................................................. 38 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 38 
9.4.6 
Planned Interim Analyses ............................................................................................. 39 
9.4.7 
Sub-Group Analyses ..................................................................................................... 39 
9.4.8 
Tabulation of Individual Participant Data .................................................................... 39 
9.4.9 
Exploratory Analyses ..................................................................................................... 39 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 39 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 39 
10.1.1 
Informed Consent Process ........................................................................................... 39 
10.1.2 
Study Discontinuation and Closure ............................................................................. 40 
10.1.3 
Confidentiality and Privacy ........................................................................................... 40 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 41 
10.1.5 
Key Roles and Study Governance .............................................................................. 42 
10.1.6 
Safety Oversight ............................................................................................................. 42 
10.1.7 
Clinical Monitoring .......................................................................................................... 43 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 43 
10.1.9 
Data Handling and Record Keeping ............................................................................ 44 
10.1.10 
Protocol Deviations ........................................................................................................ 44 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 45 
10.1.12 
Conflict of Interest Policy .............................................................................................. 47 
10.2 
Additional Considerations ................................................................................................................. 47 
10.3 
Abbreviations and Special Terms ................................................................................................... 47 
10.4 
Protocol Amendment History ........................................................................................................... 48 
11 
REFERENCES ............................................................................................................................................. 50 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be carried out in accordance with International Council on Harmonisation Good Clinical 
Practice (ICH GCP) and the following:  
 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 21 
CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and/or 21 CFR Part 812).  
 
National Institutes of Health (NIH)-funded investigators and clinical trial site staff who are responsible 
for the conduct, management, or oversight of NIH-funded clinical trials have completed Human 
Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval. Approval of both the protocol and the consent form(s) 
must be obtained before any participant is consented. Any amendment to the protocol will require 
review and approval by the IRB before the changes are implemented to the study. All changes to the 
consent form(s) will be IRB approved; a determination will be made regarding whether a new consent 
needs to be obtained from participants who provided consent, using a previously approved consent 
form. 
 
 

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INVESTIGATOR’S SIGNATURE 
The signature below constitutes the approval of this protocol and provides the necessary assurances 
that this study will be conducted according to all stipulations of the protocol, including all statements 
regarding confidentiality, and according to local legal and regulatory requirements and applicable US 
federal regulations and ICH guidelines. 
 
Principal Investigator or Clinical Site Investigator: 
Signed: 
 
Date: 
 
 
Name*:  Erin E. Hahn, PhD, MPH 
 
Title*: Research Scientist / Associate Professor 
 
Investigator Contact Information 
Affiliation*: Kaiser Permanente Southern California, Department of Research and Evaluation 
Kaiser Permanente Bernard J. Tyson School of Medicine, Department of Health Systems Science 
Address: 100 S. Los Robles, 2nd Floor, Pasadena, CA 91101 
Telephone: 626-564-3505 
Email: Erin.E.Hahn@kp.org 
 
 
 
 

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1 
PROTOCOL SUMMARY 
 
1.1 
SYNOPSIS  
 
Title: 
The Engaging Primary Care in Cancer Survivorship (EPICS) study 
Grant Number: 
1R01CA249419-01 
Study Description: 
This is a quasi-experimental pre/post with control group trial of two 
models of cancer survivorship care in early-stage colorectal and breast 
cancer survivors cared for in a community-based, integrated health care 
setting. The trial will test the efficacy of an embedded primary care 
provider (PCP) model (experimental condition) in which survivorship-
trained PCPs are embedded within an oncology practice to care for low-
risk survivors who will be transitioned at 6-36 months post-treatment 
for comprehensive survivorship care. We hypothesize that a) patients in 
the PCP model will have superior receipt of recommended care 
compared to usual care; b) patients in the PCP model will perceive 
significantly better care coordination, self-efficacy, and confidence in 
their PCP compared to usual care; and c) use of unplanned and non-
recommended care will be less in the PCP model compared to usual care.  
Objectives*: 
 
Primary Objective: To determine the efficacy of an embedded PCP model 
(experimental condition) compared to usual care on use of 
recommended cancer surveillance and preventive care services. 
Secondary Objectives: 1) To determine the efficacy of an embedded PCP 
model (experimental condition) compared to usual care on patient-
reported outcomes; 2) to compare use of unplanned and non-
recommended care in the PCP model compared to usual care. 
Endpoints*: 
Primary 
Endpoint: 
Receipt 
of 
guideline-recommended 
cancer 
surveillance and preventive care services assessed over a 36-month 
period.  
Secondary Endpoints: 1) Patient reported outcomes: Validated 
measures of patient and provider communication, and coordination of 
survivorship care; important covariates will include quality of life,  
physical and mental health, assessment of survivorship care delivery, 
and satisfaction with health decisions; 2) Receipt of non-recommended 
surveillance care based on current clinical guidelines, and use of non-
planned hospitalization, emergency department, and urgent care 
services. 

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Study Population: 
Patients: Adult (21+) Kaiser Permanente Southern California members 
diagnosed and treated for first primary early-stage breast (stage 0, I, II) 
or colorectal (stage I, II) cancer within Kaiser Permanente Southern 
California. Patients will be at low-risk for recurrence and treatment-
related toxicities, as determined by our risk algorithm. Physicians: For 
centers in the embedded PCP model, PCPs selected to participate must 
be Board Certified in a relevant primary care specialty; hold a valid and 
current MD or advanced practitioner license; and be employed by the 
Southern California Permanente Medical Group. 
Phase* or Stage: 
This is a single site phase III National Institutes of Health Clinical Trial 
Description of 
Sites/Facilities Enrolling 
Participants: 
This trial will be conducted in a community-based integrated system, 
Kaiser Permanente Southern California (KPSC). KPSC medical oncology 
departments in the intervention group will enroll eligible patients into 
the intervention. KPSC oncology departments in the control group will 
passively enroll patients for tracking of utilization.  
 
Description of Study 
Intervention/Experimental 
Manipulation: 
Embedded PCPs will provide comprehensive care for eligible survivors at 
intervention sites, including cancer surveillance services, preventive 
care, and management of long-term therapy and associated side effects 
(e.g., endocrine therapy in breast survivors). A comprehensive multilevel 
approach will prepare survivors and PCPs.  
Intervention: Embedded PCP.  Embedded PCPs will be enrolled in a 4-
month course of initial training and education, followed by ongoing 
education via tailored survivorship information for low-risk survivors 
transitioning to their care. Initial training features 3 core components to 
build capacity, skill, and knowledge: 1) Individual didactic learning; 2) 
Small in-person group sessions; and 3) Observation.   
Intervention: Patient-level. Eligible patients in the embedded PCP model 
will be provided with tailored education regarding the planned transition 
prior to the transition. After cessation of active treatment, the care team 
will provide printed information including the planned course of 
survivorship care, what to expect from embedded PCP care, when the 
transition will occur, and reassurance that the oncology team will be 
available via telephone and email, and that PCPs will refer back to the 
oncologist for any concerning signs or symptoms.  
Intervention: System-level. Tailored alerts in the electronic medical 
record for recommended cancer surveillance and preventive care 
services that include rationale, links to guidelines, and references for 
questions (scheduled to fire when survivors have an outpatient office 
visit with their embedded PCP, following the same rationale for the 
alerts to fire during oncology visits). 
Study Duration*: 
60-months 
Participant Duration: 
36-months 
 

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1.2 
SCHEMA  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 Embedded PCP centers 
(Intervention) 
Patient Identification and Risk Stratification at all sites (N=2450 
over 18 months) 
Low-risk survivors 
(N=450, Intervention)  
 Low-risk survivors 
(N=2000, Control) 
10 Usual care centers            
(Control) 
PCP survivorship training 
Usual care 
 
Transition to embedded PCP 6-36 
months post-treatment 
Up to 36-month follow-up period for intervention and control                    
Retrospective data collection for utilization 
measures, 01/01/2015-12/31/2019 
Utilization Data Collection and Analysis 
Time Period: 
Year 1 Q1 - Year 
Time Period: 
Year 1 Q3 – Year 
2 Q
Time Period: 
Year 1 Q3 – Year 
3 Q4 
Time Period: 
Year 2 Q3 – Year 
5 Q2 
Time Period: 
Year 4 Q3 – Year 
5 Q4 

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1.3 
SCHEDULE OF ACTIVITIES  
 
 
Year 1 
Year 2 
Year 3 
Year 4 
Year 5 
 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Q1 
Q2 
Q3 
Q4 
Administrative and 
regulatory tasks 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Center assignment 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pre-period data 
collection and 
analysis 
 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Initiate primary 
care training at 
intervention sites 
 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Annual PCP survey 
of knowledge, 
confidence in 
survivorship care 
 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
Patient 
identification, risk 
stratification at all 
sites 
 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment period 
into intervention 
or usual care, 
N=2450  
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Follow-up period 
for intervention or 
usual care (up to 
36 months) 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Patient survey at 
12 months post-
transition (rolling 
recruitment) 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Survey analyses 
(Aim 2) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 
 
Refine EMR-based 
measures of 
utilization  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
Obtain EMR data 
on utilization, 
initiate analyses 
(Aims 1, 3) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
 

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2 
 
INTRODUCTION 
2.1 
STUDY RATIONALE  
Advances in treatment and detection of cancer have led to a rapidly growing population of cancer 
survivors. Significant growth of cancer patients, particularly those ≥65 years, is predicted within the U.S 
over the next 20 years.[1] The majority of these patients will enter into a prolonged post-treatment phase 
of care and considered cancer survivors.[2] Cancer survivor is commonly defined as from the time of 
diagnosis through the balance of his or her life, as originally articulated by the National Coalition for 
Cancer Survivorship.[3] For this proposal, we are focusing on the transition from the end of active cancer 
treatment (e.g., surgery, chemotherapy, radiation) to the post-treatment survivorship phase, which may 
include extended hormonal or other chronic therapy. Survivors require coordinated, comprehensive care 
addressing the major domains of survivorship as described by National Academy of Medicine, the 
American Society for Clinical Oncology (ASCO) and others, including surveillance for recurrence, screening 
for new cancers, screening and management for long-term and late effects, symptom management, and 
preventive care (e.g., vaccinations, screening for other diseases).[4-13]  Older survivors (>65 years), who 
make up the majority of cancer survivors, also have a higher prevalence of comorbid conditions requiring 
management and coordination of care.[1]  
We are facing unprecedented challenges in survivorship care delivery. Currently, survivorship care 
delivery is unsystematic, occurs in a variety of settings, and is often poorly coordinated.[14-16] Serious 
gaps in survivorship care have been identified, including underuse of guideline-recommended cancer 
surveillance services, such as annual mammography for breast cancer survivors and colonoscopy for 
colorectal cancer (CRC) survivors,[17-22] and underuse of recommended preventive care services such as 
vaccinations, lipid testing and cardiovascular risk management, and cancer screenings.[23-27] In addition, 
the frequent overuse of non-recommended services that provide limited benefit exposes patients to 
significant harms, as exemplified by use of non-recommended serum tumor marker tests and high-
intensity imaging for surveillance of early stage CRC and breast cancer.[17, 28-36] Breast and CRC 
survivors have characterized their survivorship care as lacking in information for follow-up and providing 
inadequate support to address their needs.[37] Compounding these issues, our current oncology 
workforce is insufficient to care for the rapidly growing population of survivors.[1, 38, 39] Estimates from 
ASCO show a projected growth in demand of approximately 50% and only 14% growth in clinician supply, 
with demand exceeding supply as soon as 2020.[40, 41] This demand is increasing wait times for oncology 
services across the U.S.[42]  The current approach to delivering survivorship care, which is typically with 
oncology specialists with limited or no coordination with primary care, is inadequate and fails to meet the 
needs of many survivors.[6] In this study, we will evaluate a new approach to survivorship care that 
embeds survivorship-trained primary care providers (PCPs) into the oncology setting to provide 
survivorship care for low-risk survivors, potentially alleviating demand for oncology services while 
maintaining quality care.  
PCP-led survivorship care is feasible, but critical barriers must be addressed. In observational studies, 
survivors who receive care that involves PCPs (whether physicians or advance practice providers) received 

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higher quality of care. [23, 25, 43-46] Most survivors expect PCPs to manage their general preventive 
care.[47] PCPs are well-positioned to counsel survivors regarding lifestyle choices such as physical 
activity,[48] disease prevention,[49] screening for psychosocial health needs,[50] and tobacco 
cessation.[51] Receipt of CVD preventive care in cancer survivors was strongly associated with PCP 
involvement.[52] PCPs receive high ratings on care coordination and comprehensive care during 
survivorship.[53] However, lack of knowledge and other barriers must be addressed for PCPs to assume 
primary responsibility for survivorship care; for example, a recent survey of PCPs found that less than half 
of guideline-recommended services for breast cancer survivors were routinely used.[54] Additionally, 
survivors may not be comfortable transitioning to a PCP for survivorship.[55, 56] Some survivors may 
prefer oncology-led cancer surveillance based on emotional reasons and feeling connected to their 
oncology team.[57, 58] Other barriers perceived by clinicians and survivors include poor communication 
with oncology,[59] lack of knowledge regarding existing guidelines,[60] limitations of health information 
technology and support,[61] and inadequate survivorship training and education.[58, 60, 62-66] 
Survivorship care plans (SCPs), summative documents intended to help improve communication and 
coordination of survivorship care,[7] may be a necessary but insufficient tool to address these issues. SCPs 
have been shown to help PCPs feel more prepared and knowledgeable about survivorship care 
delivery,[67] improve PCP-reported care coordination and communication,[68] and may improve quality 
of survivorship care[69-71] and patient self-efficacy.[72] However, results from most randomized 
controlled trials (RCTs) have found little to no effect of SCPs on distress, quality of life, or satisfaction with 
care.[73, 74] Thus, SCPs alone may be a necessary but insufficient component to engage PCPs and improve 
quality of survivorship care.[73, 75-77] We will address these barriers identified in the empirical literature 
in our study with multi-level interventions (patient, provider, system) incorporating robust education, 
training, and support for survivorship care. 
The need for risk-stratified survivorship care. Risk-stratified survivorship care has been suggested as a 
potential model for U.S. survivors.[10, 41, 78-80] Risk-stratification involves evaluation of cancer and 
treatment characteristics, risk of complications, comorbid conditions, and other patient characteristics.  
In this approach, survivors with less complicated cancer treatments and at low-risk for recurrence or 
treatment toxicities are triaged to a less intense pathway (e.g., PCP-led or self-management) and patients 
with more complex cancer treatments/stage of disease are triaged to specialist oncology care for ongoing 
follow-up.[41, 80] This type of stratification has been implemented within the National Health Service in 
the U.K.,[81-83] and a similar approach has been implemented in Northern Ireland.[84] Recent data show 
successful triage of half of CRC survivors and approximately 80% of breast survivors to a low-intensity 
survivorship pathway.[82] In the U.K. the stratified pathways have been found to improve access to 
oncology specialists and are projected to save approximately £90 million over 5 years.[80] We will 
integrate a risk-stratified approach in our study to identify and triage low-risk CRC and breast cancer 
survivors, incorporating these evidence-based recommendations.  
To address these issues, we will conduct a pre/post with control trial of two models of cancer survivorship 
care in early-stage colorectal and breast cancer survivors cared for in a community-based, integrated 
health care setting. Building on our pilot work[57] and drawing on the empirical literature, we will test the 
efficacy of an embedded PCP model (experimental condition) in which PCPs are embedded within an 

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oncology practice, and will care for low-risk survivors who will be transitioned approximately 6-36 months 
post-treatment for comprehensive survivorship care. These PCPs will be given training in cancer 
survivorship care focused on cancer surveillance and chronic disease prevention. This model will be 
compared to the extant oncology physician model (usual care) that is the default condition in the health 
care system. The primary outcome will be receipt of guideline-recommended care (e.g., cancer 
surveillance, preventive care), assessed over a 36-month period. Secondary outcomes will include 
validated patient-reported outcomes (PROs), as well as utilization of unplanned care (hospitalizations, 
urgent care) and receipt of non-recommended care. We will also explore PCP perceptions of confidence 
in delivery of survivorship care. We will conduct this trial in large medical centers of an integrated health 
care system, Kaiser Permanente Southern California (KPSC), with approximately 2450 survivors. Data from 
multiple studies conducted by our team demonstrate the need to improve survivorship care in this 
setting[31, 32] and our recent pilot study demonstrates the feasibility of the embedded PCP model in this 
setting.[57] KPSC is an exceptional setting to conduct the proposed research with unparalleled access to 
longitudinal data, a large and diverse patient population, and engaged clinicians. 
2.2 
RISK/BENEFIT ASSESSMENT  
2.2.1 KNOWN POTENTIAL RISKS  
 
There are minimal physical, psychological, social, legal, privacy or other risks from participating in this 
study. Individual patients and clinicians will not be recruited for Aims 1 or 3, thus there is minimal risk to 
loss of privacy or confidentiality; demographic, clinical and utilization data for these Aims will be collected 
from EMR and/or claims data with no participant interaction.  Data on potential adverse events and 
serious adverse events will be collected and reported to our Data Safety and Monitoring Board as 
described in Section 8.2 below.  
 
For this study, a waiver for informed consent will be required to ensure a scientifically valid comparison 
of the embedded PCP (ePCP) model to current usual care.  
 
We do not foresee any risks to potential participants by not directly consenting them to participate in the 
trial. This study poses minimal risk to the patient because survivorship cancer care will be performed as 
part of routine medical care, and both the ePCP and the oncology-based model for survivorship cancer 
care are consistent with guidelines from professional societies and organizations with regard to the 
delivery of safe, appropriate, and usual care practices. We also believe that such a waiver of consent is 
not only widely recognized as necessary and appropriate, but also scientifically necessary and ethically 
justifiable under the “Common Rule” for protection of research participants (45 CFR 46.116d) – (e.g., 1) 
the research involves no more than minimal risk to the subjects; 2) the waiver of alteration will not 
adversely affect the rights or welfare of the subjects; 3) the research could not practicably be carried out 
without the waiver or alteration; and 4) whenever appropriate, the subjects will be provided with 
additional pertinent information after participation in the form of a summary sheet of survey findings 
after completion of the study). 
 

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Throughout the study phases, we will work closely with our Institutional Review Board, clinical chiefs, and 
operational leaders to ensure patient safety, with regular review and reporting of adverse events and 
protocol deviations. 
 
Patients will be individually recruited for patient-reported outcome surveys under Aim 2, initially through 
email and subsequently through mail and telephone. If email addresses are unavailable, we will use mailed 
letters as the initial contact. Recruitment scripts will describe the purpose of the research, the selection 
process for participation, the study structure and time commitment (one-time survey), and risks of 
participating. We will obtain written or oral consent from all participants for participation in the surveys. 
Survey consents and opt out options will be built into an electronic template as part of the initial survey 
screens.  
 
For utilization data captured under Aim 3 from the EMR, individual patients will not be recruited and the 
ethical justification of the waiver of individual consent, the “Common Rule” for protection of research 
participants (45 CFR 46.116d), is outlined above. 
 
A rare but serious harm that could occur is loss of confidentiality of personal health information (PHI), but 
every effort will be made to protect PHI. Specifically, each survey participant will be given a unique alpha-
numeric identification number. No data collection form will be linked to an actual participant name. Any 
document linking the participant name to an identification number will be kept in a locked file separate 
from data collection files. All records from the study will be kept in locked files. Identifying information 
will be removed from the final data sets and stored in a linked file to which only the Principal Investigator 
or designee has access. Individual participants will not be identified in any reports. Additionally, study 
reports will be aggregated so that individual participants are not identified. All investigators and research 
staff at participating sites will be required to maintain up-to-date training in human subject protection 
and 
good 
clinical 
practice 
through 
Collaborative 
Institutional 
Training 
Initiative 
(CITI; 
https://www.citiprogram.org/default.asp) and HIPAA training. Additional security precautions include 
encryption, digital certification, audit logs, and firewall protection. 
2.2.2 KNOWN POTENTIAL BENEFITS  
 
There are no direct benefits to the participants in this proposed study. There are potential societal benefits 
from our findings. Our study is innovative, among the first trials in the U.S. comparing two survivorship 
models of care and one of the first to use a novel risk-stratified approach that will triage low-risk breast 
cancer and CRC survivors to one of these models of care. In addition, the study uses a multi-level approach 
that includes patient-, provider- and system-level components. Furthermore, the ePCP training materials 
and resources that will comprise a study “toolkit” are mostly free, widely accessible materials and our 
risk-stratification methods are easily replicable, making our findings from this study well-poised for scale-
up and dissemination. 
2.2.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 

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There are minimal physical, psychological, social, legal, privacy or other risks from participating in this 
study. Individual patients and clinicians will not be recruited for Aims 1 or 3, thus there is minimal risk to 
loss of privacy or confidentiality; demographic, clinical and utilization data for these Aims will be collected 
from the EMR and/or claims data with no participant interaction. A rare but serious harm that could occur 
is loss of confidentiality of PHI. However, participant confidentiality will be maintained at all times using 
the specific steps and procedures outlines in section 2.31 above. 
 
This research is essential to advance the field of survivorship cancer care. Definitive evidence on effective 
models of care that engage primary care physicians and patients in survivorship with equivalent or 
superior outcomes to oncology-led models would allow clinicians, health system leaders, and policy 
makers to widely and confidently implement a new approach to survivorship that optimizes patient 
outcomes and efficiently employs resources.  
3 
OBJECTIVES AND ENDPOINTS  
 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
Primary 
 
 
 
To determine the efficacy of 
an ePCP model (experimental 
condition) compared to usual 
care on use of recommended 
cancer surveillance and 
preventive care services.  
 
 
 
Receipt of 
guideline-
recommended 
cancer surveillance 
and preventive 
care services 
assessed over a 
36-month period  
 
ePCPs trained to provide care to cancer survivors will 
provide superior care for preventive services and 
equivalent cancer surveillance care compared to the 
usual care model. 
Secondary 
 
 
 
To determine the efficacy of 
an ePCP model (experimental 
condition) compared to usual 
care on patient-reported 
outcomes.  
 
 
Validated, reliable 
measures of  
patient-provider 
communication, 
and coordination 
of survivorship 
care. 
 
We will include 
quality of life,  
physical and 
mental health, 
assessment of 
survivorship care 
delivery, and 
satisfaction with 
 
ePCPs trained to provide care to cancer survivors will 
have superior communication and care coordination 
compared to usual care.  

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR ENDPOINTS 
health decisions as 
important 
covariates.   
 
 
 
To determine the efficacy of 
an ePCP model (experimental 
condition) compared to usual 
care on utilization of 
emergency, urgent, hospital, 
and non-recommended care.  
 
 
Utilization: 
Unplanned care 
(hospitalizations, 
emergency 
department, and 
urgent care); and 
receipt of non-
recommended 
cancer surveillance 
care as described 
by clinical practice 
guidelines (e.g., 
ASCO Choosing 
Wisely) 
 
ePCPs trained to provide care to cancer survivors may 
have different rates of patients with unplanned care or 
non-recommended care. 
Tertiary/Exploratory  
 
 
 
To explore knowledge and 
confidence in survivorship 
care between ePCPs and 
PCPs at usual care centers.  
 
 
Confidence in 
delivery of 
survivorship care 
and knowledge of 
survivorship care 
guidelines, 
assesses using 
validated survey 
questions.  
 
 
Causal mechanism: ePCPs exposed to our multi-level 
intervention of education, training, and support will 
demonstrate superior knowledge and confidence in 
delivery of survivorship care compared to PCPs at the 
usual care centers, who are not exposed.  
 
4 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
 
Our study was originally designed as a cluster randomized trial of two models of cancer survivorship 
care. However, as a result of the SARS-CoV-2 pandemic (COVID) and the overwhelming clinical demands 
experienced by out study sites from multiple COVID surges, we re-designed our study from a cluster 
randomized trial to a quasi-experimental pre/post with control group design. This design allows us to 
meet our originally proposed aims and scope.  

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As a result of the pandemic and the overwhelming COVID surges in the Southern California region, 
Kaiser Permanente Southern California (KPSC) clinical and administrative staff and facilities entered into 
‘surge’ mode. Surge plans, which are prepared to cope with emergencies such as this pandemic, re-
deploy clinical and administrative staff as needed to new positions and assess and redistribute/close 
medical facilities. During the initial 6 months of the pandemic, many KPSC medical office buildings were 
closed or had limited services and primary care physicians were re-deployed as hospitalists, ICU relief 
staff, and as virtual care consultants. Nursing teams from both primary care and oncology were re-
deployed into hospital care, urgent care, virtual care, and into new roles such as COVID education and 
COVID testing. This had a serious impact on our study as medical centers that had committed to 
participate in our originally proposed design were no longer confident that they had the primary care 
resources and staff to participate, as our study requires significant clinical time from primary care for 
training and patient care. Several of our centers informed us they could only participate if they could be 
assigned to the control condition.  
To address these extraordinary circumstances, and to preserve our ability to meet our study aims and 
scope, we re-designed our study from a cluster randomized trial to a quasi-experimental pre/post with 
control group design. As we no longer have the element of randomization, we have increased the 
number of participating medical centers from 8 to 14 (4 intervention, 10 control). This increases our 
projected number of prospective patient participants from 2,000 to an estimated minimum of 2,450. We 
have also added a ‘pre’ data collection period to collect retrospective patient utilization data from all 
participating centers to allow for comparison of pre-intervention and post-intervention outcomes (Aims 
1 and 3).  Additionally, to address the potential differences between our intervention and control sites, 
we have fielded a brief survey to all center Medical Directors about the impact of COVID and other 
factors that may have contributed to their decision/ability to participate in the study. We are also 
collecting data on clinician, patient, and geographic factors. This adaptation to the study design was 
approved via telephone discussion by our program officer at the National Cancer Institute in accordance 
with NIH Grants Policy Statement, 8.1.2 on October 5, 2020. 
Updated Design. This is a single site (KPSC), multi-center (multiple KPSC medical centers) trial using a non-
randomized pre/post control group design to compare the effectiveness of 2 risk-stratified models of 
survivorship care, an ePCP model with a survivorship-trained PCP providing cancer surveillance, symptom 
management, and preventive care, compared to an oncology-led model, where the survivor stays with 
their oncology team (usual care within the KPSC system). We will address the barriers to PCP involvement 
from the empirical literature and propose to measure recommended quality outcomes including receipt 
of recommended care, PROs, and utilization of hospital, urgent, and non-recommended care. 
 
This trial will evaluate the efficacy of 2 models of cancer survivorship care on receipt of recommended 
care for early-stage, low-risk colorectal and breast cancer survivors (primary outcome), PROs (secondary 
outcome), and use of unplanned and non-recommended care (secondary outcomes). This trial will be 
conducted in a community-based integrated system, KPSC, with medical centers non-randomly assigned 
to the ePCP or usual care model, with the models running for up to 36 months. We will retrospectively 
(pre-period) and prospectively (post-period) identify early-stage breast and colorectal cancer patients at 

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all sites during their initial cancer treatment using a combination of pathology data and text information 
extraction algorithms. Potentially eligible survivors will be assigned a binary risk score (low risk/non-low 
risk) based on data readily available in the EMR including cancer stage, risk of recurrence, and other 
factors derived from current consensus-based recommendations. Embedded PCP participants will be 
transitioned to a trained PCP at 6-36 months after the cessation of active treatment. Multi-level 
components for this model include empirically-derived survivorship care interventions, such as provider 
education and training, using established training curriculum for PCPs engaging in survivorship care, 
health IT support (e.g., proactive office encounter alerts, links to guidelines), and patient education on the 
transition in care, signs and symptoms to be aware of, and what to expect from their PCP for surveillance 
and prevention.  Usual care participants will be followed by their treating oncologist or surgeon, which is 
current “usual care” within KPSC.  
 
Our specific aims and hypotheses (H) are:  
Aim 1. To determine the efficacy of the PCP model relative to the usual care control group on receipt of 
recommended care (primary outcome). We will construct a composite measure of guideline-
recommended cancer surveillance and age-appropriate preventive care services for the 18-month pre-
period and 18-month post-period, identifying utilization from EMR data.  
H1. Patients in the PCP model will have superior receipt of recommended care 
compared to usual care.  
Aim 2. To compare patient-centered outcomes on coordination of survivorship care, self-efficacy in 
managing care, and confidence in their PCP to provide survivorship care between the 2 models 
(secondary outcomes).  
H2. Patients in the PCP model will perceive significantly better care coordination, self- 
efficacy, and confidence in their PCP compared to usual care 
Aim 3. To assess utilization of unplanned hospitalizations, use of urgent care, and receipt of non-
recommended cancer surveillance services between the 2 models (secondary outcomes).  
H3. Use of unplanned and non-recommended care will be significantly less in the PCP 
model compared to usual care.  
Exploratory Aim. We will explore PCP knowledge of and confidence in providing survivorship care, 
comparing PCPs who participate in the embedded PCP model to PCPs practicing at centers assigned to 
the usual care model. 
 
Assignment and consent. Selection of participating centers will occur prior to PCP educational 
interventions and enrollment of patients. A scientifically valid comparison of the embedded PCP model to 
current usual care would only be possible with population-based enrollment and outcome assessment of 
low-risk survivors. Consequently, a waiver of the usual requirement for informed consent will be required. 
We believe that such a waiver of consent is not only widely recognized as necessary and appropriate but 
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on the Common Rule, 45 CFR 46.116d (e.g., use of routine care practices, no investigational drugs or 
devices, little risk of physical or psychological harm). We will work closely with our Institutional Review 
Board (IRB), clinical chiefs, and operational leaders to ensure patient safety, with regular review and 
reporting of adverse events and protocol deviations. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
Despite widespread recognition and interest in survivorship in the U.S., there has been little research on 
models of survivorship care, or uptake of PCP survivorship models. Extant research has focused mainly on 
observational studies, such as the recent Patient-Centered Outcomes Research Institute (PCORI)-funded 
study “Evaluating different types of survivorship care” (study HSRP20143084, Mead et al.) that focused 
primarily on identifying model types among 236 Commission on Cancer-accredited organizations; a 
patient survey evaluated PROs. Findings indicate 3 major models of care (specialist consultative, mid-level 
provider longitudinal, and oncology-based) and few differences in PROs.[85, 86]  While valuable, the study 
was not prospective, did not randomize, and did not evaluate important outcomes such as utilization. 
Eight ‘Survivorship Centers of Excellence’ were developed across the U.S. from 2006-11 with investment 
from the Lance Armstrong Foundation (one led by Dr. Patricia Ganz in collaboration with Dr. Hahn, Co-I 
and PI respectively for this proposal).  These Centers implemented a variety of different models of care 
within their cancer centers, but did not conduct head-to-head comparisons of the models as a part of 
their implementation and research agenda.[87, 88] Multiple review papers and an AHRQ technical brief 
have categorized observed survivorship models of care and developed recommendations on potential 
model types, content, and structure.[2, 6, 10, 14, 15, 78, 79, 89-91] A review by Howell et al. determined 
that further research is needed to evaluate the efficacy of models of care;[15] McCabe et al. had a similar 
conclusion.[90] This paucity of high-quality research, particularly in community-based settings, seriously 
limits our ability to implement policy or practice decisions regarding survivorship care delivery, or to 
address the impact of clinician shortages and rising health care costs impacting systems, patients, and 
families.   
4.3 
JUSTIFICATION FOR INTERVENTION 
Our proposed research builds on the foundational evidence from observational studies summarized 
above. Survivorship care provided by oncology specialists alone focuses on cancer surveillance and 
screening, but often lacks attention to preventive care or management of comorbid conditions.  In 
contrast, care provided by PCPs is more likely to include age appropriate preventive care, as well as 
management of comorbid conditions and psychosocial concerns, without sacrificing timely detection of 
cancer recurrence or other adverse events, and may provide increased capacity and access to oncology 
services for newly-diagnosed patients.[25, 43-46] In our pilot study we found an embedded PCP model to 
be highly feasible and acceptable for low-risk patients.[57]  Reviews of survivorship models have identified 
examples of primary care physician-led or “embedded PCP” models in the U.S., albeit a limited 
number.[79] These examples describe setting, domains of care, and care processes (e.g., strategy for 
managing long-term and late effects).[92, 93] However, as noted above, there are few, if any, evaluations 
of these models.  

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Collectively, this evidence demonstrates the feasibility and capability of PCPs assuming the primary role 
in providing survivorship care for early-stage, low-risk survivors, as well as the need for evaluation of 
survivorship care models. Thus, we will conduct a non-randomized pre/post with control trial to compare 
the effectiveness of an embedded PCP model, with a survivorship-trained PCP embedded into the 
oncology clinic to provide comprehensive survivorship care (e.g., cancer surveillance, symptom 
management, preventive care) as compared to an oncology-led model (usual care), where the survivor 
stays with their treating oncology team and sees their regular PCP in parallel, but in an uncoordinated 
fashion. We will address the barriers to PCP involvement identified in the empirical literature in the 
development of the intervention. Guided by the Framework for Quality Survivorship Care,[11] we propose 
to measure highly relevant outcomes including receipt of recommended care, PROs, including patient-
provider communication and quality of life, and utilization of hospital, urgent, and non-recommended 
care.  
4.4 
END-OF-STUDY DEFINITION 
 
A participant is considered to have completed the study if he or she has: 
 
• 
Been identified and enrolled into either the ePCP or the oncology model of care 
• 
Completed the 36-month follow-up period after enrollment into the intervention 
• 
Completed the survey at 12-months post-transition (rolling recruitment) 
• 
Truncated person-time will be accounted for in case of membership end or death 
 
5 
STUDY POPULATION 
5.1 
INCLUSION CRITERIA 
 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
Provider population: 
PCPs selected to participate must be Board Certified in a relevant specialty; hold a valid and current MD 
or advanced practitioner license; and be employed by the Southern California Permanente Medical Group 
(SCPMG).  
 
Patient population: 
• 
Adult (21+) KPSC members diagnosed and treated for pathologically confirmed first primary early-
stage breast (stage 0, I, II) or colorectal (stage I, II) cancer within KPSC 
• 
Completed active cancer treatment within the past 6-36 months; active treatment includes cancer-
directed surgery, chemotherapy (includes Herceptin (trastuzumab)), radiation therapy, and ovarian 
suppression therapy (e.g., Goserelin (Zoladex)) 
• 
Completed at least one office visit within KPSC medical oncology 

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• 
At low-risk for cancer recurrence and treatment-related toxicities based on stage of disease and 
treatment modalities 
 
For our Aim 2 survey: 
• 
Primary language of English or Spanish (although we will assess our Aim 1 participants for recorded 
preferred spoken language and adjust translations as needed) 
• 
Ability to complete surveys of patient-reported outcomes  
Individuals of all races, ethnicities, and genders are eligible for this study. Children will not be included in 
the study, because they are rarely, if ever, affected by breast or colorectal cancer. 
5.2 
EXCLUSION CRITERIA 
 
An individual who meets any of the following criteria will be excluded from participation in this study: 
 
• 
Pre-existing cancer diagnosis (other than non-melanoma skin cancer) 
• 
Less than 120 days of KPSC membership after index diagnosis of primary breast cancer or colorectal 
cancer 
• 
Patient undergoing workup for suspected primary cancer recurrence or new primary cancer 
• 
Enrollment on other cancer clinical trial 
• 
Received treatment indicative of metastatic or high-risk disease including breast cancer patients 
treated with neoadjuvent chemotherapy 
• 
Serious medical or psychiatric condition that would detract from study participation and 
measurement of PROs 
 
For the provider survey, there are no exclusions; all sex/gender, racial, and ethnic group members are 
eligible to participate. 
5.3 
LIFESTYLE CONSIDERATIONS 
 
N/A 
 
5.4 
SCREEN FAILURES 
 
We will retrospectively (pre-period) and prospectively (post-period) identify early-stage (stage 0-II) breast 
and early-stage (stage I, II) colorectal patients at our assigned intervention condition medical centers early 
in their treatment course using our comprehensive pathology database, Co-Path, combined with a text-
information extraction system. We will identify the end of active treatment (surgery, chemotherapy, 
radiation, ovarian suppression injection treatment) using our treatment databases (e.g., Beacon 
chemotherapy, Mosaiq radiation) and EMR data. At the end of treatment, we will assess salient risk factors 
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risk/non-low-risk) based on: stage of disease, risk of recurrence, treatment-related toxicity, and 
potentially pre-existing comorbidity burden, with assessment of potential interaction of treatment and 
comorbidity (e.g., breast patients with CVD who receive anthracyclines might be at high-risk for 
treatment-related CVD events). For patients enrolled in the intervention (post-period), we will send 
treating oncologists monthly lists of survivors to confirm as low-risk and eligible for the study; treating 
oncologists may have information beyond what is available in our structured EMR data that may affect 
risk status. Eligible survivors receiving care in embedded PCP model will receive an automated referral 
and patient education. This same identification algorithm will be applied to control centers to passively 
identify eligible patients and track utilization over time.  
 
Screen failures are defined as participants with early-stage breast or colorectal cancer who are categorized 
as low-risk for recurrence and treatment toxicities but are subsequently determined to be not at low risk 
by either the treating oncologist or ePCP. Patients determined to be not at low risk will be excluded from 
the study and will receive their survivorship care under usual care conditions, with their treating 
oncologist.  
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
 
For Aim 1, there is no individual participant recruitment or contact and patients will not be individually 
enrolled in this study; rather entire medical centers will be intervention or control with patients passively 
enrolled. We will prospectively identify early-stage (stage 0-II) breast and colorectal patients at our 
medical centers assigned to the intervention condition early in their treatment course to introduce the 
program and initiate tracking. Therefore, anyone who meets the eligibility criteria will be included in either 
the ePCP or usual care model. Our target enrollment size is 2450 subjects.  
 
There are no specific strategies that will be used to recruit and retain historically under-represented 
populations in order to target sample size and conform with the NIH Policy on Inclusion of Women and 
Minorities and Inclusion of Individuals Across the Lifespan as Participants in Research Involving Human 
Subjects. Individuals of all races, ethnicities, and genders are eligible for this study. KPSC has an extremely 
diverse member population, and no survivor would be excluded from participation in the care models 
based on spoken language (comprehensive interpreter services are available at all centers). KPSC patients 
are socioeconomically diverse with insurance coverage that includes commercial plans, Medicare 
Advantage, Medicaid, and individual insurance with options for high-, medium-, and low-deductible plans, 
and reside in urban, suburban, and rural communities. KPSC medical center characteristics are similar on 
distribution of age and gender, with distribution of race/ethnicity echoing the race/ethnicity distribution 
of Southern California.  
 
Children will not be included in the study, because they are rarely, if ever, affected by breast or colorectal 
cancer.  
 
 
 

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Estimated distribution of age for early-stage breast and colorectal cancer survivors:  
 
  
Breast 
Colorectal 
Mean Age 
61.2 
65.3 
<=40 
5% 
2% 
41-50 
16% 
11% 
51-60 
26% 
23% 
61-70 
31% 
28% 
71-80 
17% 
23% 
81+ 
6% 
13% 
 
Identification of participants will begin in the 2nd quarter of Year 2.  
 
Under Aim 2, we will use Dillman’s Tailored Design Method to guide all survey activities including 
recruitment. This approach has three fundamental goals: 1) minimize all possible sources of survey error, 
including coverage, sampling, nonresponse, and measurement error.  Our mixed mode approach will keep 
our sources of error low by reducing survey burden and increasing coverage; 2) tailor to the survey 
population by developing survey and recruitment methods that consider participant characteristics and 
that interact and work together to encourage response; 3) use procedures that create positive social 
exchange and encourage response.  We designed our recruitment procedures to encourage response and 
minimize nonresponse by using multiple modes of contact, multiple modes of response (e.g., direct link 
to web survey, paper survey, text reminders), and incentives. Mixed-mode strategies such as the one we 
propose have been shown to be effective and efficient and help minimize total survey error. Key Tailored 
Design features of our approach include: promising completion incentives, using unified design elements 
across modes, using multiple modes of communication and multiple contacts, and using recruitment 
materials tailored for the study population (e.g., stressing the knowledge gained to improve cancer 
survivorship care).  
 
Participants will receive a $20 gift card for completing the survey.  These are nominal incentive levels 
widely used in current studies within our department for survey completion; therefore, we anticipate no 
undue influence or coercion by providing this level of incentive to potential participants. 
 
The invitation letter will include a short URL for the web survey leading directly to the survey and will 
include a toll-free number and email for opting out of further contact or asking questions. We will use 
KPSC branding to provide legitimacy for KPSC members. The letter will stress the potential impact of 
knowledge gained from the survey in helping future cancer survivors and the importance of the 
participant’s expertise in this topic, following social exchange theory principles. We will also indicate our 
intention to share the results with participants to further establish trust and improve response. We will 
include a self-addressed stamped return envelope for paper surveys. Non-responders will be sequentially 
contacted first by email and/or text message (when available), mail (with a paper survey included), and 
finally by telephone (for an interviewer-administered survey).  

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A secure internal study database will permit us to track the recruitment status of each member of the 
original survey sample at every phase. We will conduct rolling recruitment over a 1-year period by making 
ordered contacts in waves. Using real-time reporting, we will continually assess response rates and adjust 
the timing and order of contacts, as needed, to most effectively achieve the desired sample size and 
diversity (i.e. sex, race/ethnicity). The content of recruitment materials may also be modified based on 
participants’ feedback and response. By employing multiple avenues for recruitment (mail, phone, and 
email), we can ensure a strong response. 
 
For Aim 3, there is no participant contact; we will obtain utilization data from the KPSC electronic medical 
record and associated research databases for eligible participants at the embedded PCP (experimental) 
and usual care arm. This aim is to determine utilization of unplanned hospitalizations, urgent care, and 
non-recommended cancer surveillance services, using CPT and ICD codes to identify hospitalizations 
related to cancer, use of urgent care, and use of non-recommended care. Non-recommended care 
measures will be identified from relevant guidelines (e.g., ASCO Choosing Wisely, American Cancer Society 
(ACS) Survivorship guidelines). 
 
Exploratory Aim. We will invite our ePCPs and a random sample of PCPs from our both arms arm to 
participate in a brief, online survey of knowledge and confidence in cancer survivorship care. Recruitment 
methods for KPSC clinicians will include email, letter, and/or telephone outreach. The overall PCP 
population at KPSC (N=2,932) consists of 34% white, 49% Asian, 11% Hispanic, and 5% black; 48% are 
female. We anticipate our PCP sample at participating centers to reflect these characteristics. 
 
Retention. 
Aims 1 and 3 will rely on a passive retention approach, as there is not participant contact and patients will 
not be individually enrolled in this study. Patients who maintain active KPSC membership status will be 
retained. 
 
Under Aim 2, retention is not applicable, because the PRO survey is a one-time cross-sectional study; we 
will invite all eligible survivors to participate in the PRO survey at 12 months after their transition to the 
ePCP or the oncology model. Therefore, we do not propose active follow-up of participants who 
participate in this one-time survey. 
6 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) 
6.1 
STUDY INTERVENTION(S) OR EXPERIMENTAL MANIPULATION(S) ADMINISTRATION 
6.1.1 STUDY INTERVENTION OR EXPERIMENTAL MANIPULATION DESCRIPTION 
 
Embedded PCPs will provide comprehensive care for survivors, including cancer surveillance services, 
preventive care, and management of long-term therapy and associated side effects (e.g., ongoing 

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endocrine therapy in breast survivors). We have designed a comprehensive multilevel approach to 
prepare survivors and PCPs (physicians and/or advance practice providers).   
 
Intervention: Embedded PCP. We will enroll ePCPs in a 4-month course of initial training and education, 
followed by ongoing education via tailored survivorship information for low-risk survivors transitioning to 
their care. We will use widely and freely available resources to help ensure generalizability and scalability 
of the training approach. Initial training features 3 core components to build capacity, skill, and 
knowledge, guided by the ASCO Core Curriculum for Survivorship Training: 1) Individual didactic learning; 
2) Small in-person group sessions; and 3) Observation. For individual learning, we will use the “Cancer 
Survivorship E-Learning Series for Primary Care Providers” training modules, a freely available online 
educational series developed by expert clinicians, researchers, and survivors at the National Cancer 
Survivorship Resource Center in collaboration with the ACS. Next, small group sessions with the research 
team, including clinical co-investigators from primary care and oncology, to review survivorship resources 
and address questions for 60 minutes each session for 4 weeks, with pre-session work of 1-2 hours per 
week for sessions 1-3. Lastly, observational learning will take place via shadowing oncologists for 5-10 
hours per week for 2 weeks, again leveraging PCP education time, and attending tumor boards (ongoing). 
We will conduct a brief annual online survey to assess PCP knowledge and confidence in survivorship care 
and will compare ePCPs to PCPs in the usual care arm (Exploratory Aim). When survivors transition to the 
ePCP, we will include a tailored packet of educational information and reminders for the ePCP: the ACS 
survivorship guidelines for breast or CRC cancer, which are designed to assist PCPs in care of survivors. 
We will include a standardized letter reminding the ePCP about goals of care and how to work with the 
oncology team. Importantly, this letter will include when to refer the survivor back to oncology/surgery. 
Typically, this will include unremitting symptoms such as shortness of breath or pain.  
 
Intervention: Patient-level. Eligible patients in the ePCP model will be provided with tailored education 
regarding the planned transition prior to the transition, a critical factor according to our formative 
evaluation. After cessation of active treatment, the care team will provide printed information including 
the planned course of survivorship care, what to expect from ePCP care, when the transition will occur, 
and reassurance that the oncology team will be available via telephone and email, and that PCPs will refer 
back to the oncologist for any concerning signs or symptoms. This will be mailed to participants and/or 
provided by their treating oncologist, included as part of the standard KPSC survivorship binder provided 
at the end of treatment, as well as uploaded to the kp.org patient portal. 
 
Intervention: System-level. Working with our health IT team, we will create tailored alerts in the EMR for 
recommended cancer surveillance and preventive care services that include rationale, links to guidelines, 
and references for questions. These will fire when survivors have an outpatient office visit with their ePCP. 
6.1.2 ADMINISTRATION AND/OR DOSING 
 
Intervention: Embedded PCP. We will engage ePCPs in a 4-month course of initial training and education, 
followed by ongoing education via tailored survivorship information for low-risk survivors transitioning to 

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their care. Initial training features 3 core components to build capacity, skill, and knowledge: 1) Individual 
didactic learning; 2) Small in-person group sessions; and 3) Observation. 
 
When survivors transition to ePCP care, our ePCPs will have a tailored resource packet to guide care, 
including links to relevant guidelines for breast or CRC cancer, which are designed to assist physicians in 
care of survivors (e.g., the National Comprehensive Cancer Network surveillance guidelines), oncology 
team information (e.g., department chief, oncology social workers), and local available resources.  
 
Intervention: Patients. After cessation of active treatment, the care team will provide information about 
the ePCP survivorship clinic along with a letter from the treating oncologist describing what to expect 
from ePCP care, when the transition will occur, and reassurance that the oncology team will be available 
via telephone and email, and that PCPs will refer back to the oncologist for any concerning signs or 
symptoms. This will be mailed to participants and/or provided by their treating oncologist, included as 
Embedded PCP survivorship training activities 
Weeks 1-8 
Didactic learning from online survivorship care for PCPs modules[94] 
Module 1, 2 
Overview; role of PCPs 
Late effects, symptom management 
Module 3, 4 
Psychosocial needs 
Preventive care 
Module 5, 6 
Care coordination 
Cancer recovery 
Module 7, 8 
Colorectal survivors 
Breast survivors 
Weeks 9-12 
Small group sessions with research team and clinical leaders 
Session 1 
Health and wellness for cancer survivors: Live webinar lead by KPSC physicians with Q&A 
 
Session 2 
Signs and symptoms of local disease recurrence, managing pain:   Live webinar lead by KPSC 
physicians with Q&A  
 
Session 3 
Working up potential breast cancer recurrence; unusual presentations of metastatic disease:  Live 
webinar lead by KPSC physicians with Q&A 
  
Session 4 
Managing long-term endocrine therapy:  Live webinar lead by KPSC physicians with Q&A 
 
 
Session 5 
Risk reduction and cancer prevention for survivors:  Live webinar lead by KPSC physicians with 
Q&A 
 
Session 6 
Review available resources and discuss current educational/resource needs, health IT support, other 
ad hoc questions  
Includes:  ACS Survivorship Guidelines, Long-Term Survivorship Care After Cancer Treatment[95]; 
From Cancer Patient to Cancer Survivor: Lost in Transition[96]; Cancer Survivorship in Primary Care 
[97];ASCO Treatment Plan and Summary Resources[12, 98]  
 
Session 7 
Colorectal cancer survivorship and recurrence: Live webinar led by KPSC physicians with Q&A 
 
Weeks 13-16 
Observation 
Weeks 13-14 
Shadow breast and colorectal oncologists to observe cancer care processes 
Weeks 13-16+ 
Attend tumor boards and oncology staff meetings  
Care transition 
Provided with survivorship resource guide 
Evaluation 
Brief online survey on perceived confidence and knowledge of survivorship care;[60]  
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part of the standard KPSC survivorship binder provided at the end of treatment where possible/applicable, 
as well as uploaded to the patient’s kp.org portal. 
 
Intervention: System-level. Health IT alerts will fire when survivors have an outpatient office visit with 
their embedded PCP using the same programming methodology as for oncology visits.  
6.2 
FIDELITY 
6.2.1 INTERVENTIONIST TRAINING AND TRACKING 
We will assess center compliance with the study protocol monthly, with review of relevant data. We will 
collect utilization data for services with the ePCP, the treating oncology team, and with the patient’s 
assigned KPSC PCP. We will check for patterns of utilization indicative non-compliance with the ePCP 
protocol (e.g., no or limited visits with the ePCP, continued use of oncology for patients in the ePCP arm). 
We will have regular interactions with the study sites to discuss and review these data.  
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
 
N/A. This is quasi-experimental pre/post with control group design.  
6.4 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION ADHERENCE 
 
Participant adherence at the patient level does not apply to this study. Participants may or may not have 
visits with their ePCP and/or oncology team.  
6.5 
CONCOMITANT THERAPY 
 
N/A 
6.5.1 RESCUE THERAPY 
 
N/A 
 
7 
STUDY INTERVENTION/EXPERIMENTAL MANIPULATION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
DISCONTINUATION OF STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 
When a subject discontinues from the ePCP model but not from the study, remaining study procedures 
will be completed as indicated by the study protocol.  If a clinically significant finding is identified after 
enrollment, the investigator or qualified designee will determine if any change in participant management 
is needed. Any new clinically relevant finding will be reported as an adverse event (AE). 
 

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The data to be collected at the time of study intervention discontinuation will include the following: 
• 
The reason(s) for discontinuing the participant from the intervention, and methods for determining 
the need to discontinue 
• 
Where the participant will be receiving survivorship care. 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
 
Participants are free to withdraw from participation in the study at any time.  An investigator may 
discontinue a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance, unless varying compliance is an aspect of the study 
objectives; 
• 
Lost-to-follow up; unable to contact subject (see Section 7.3, Lost to Follow-Up) 
• 
Any event or medical condition or situation occurs such that continued collection of follow-up study 
data would not be in the best interest of the participant or might require an additional treatment that 
would confound the interpretation of the study; 
• 
The participant meets an exclusion criterion (either newly developed or not previously recognized) 
that precludes further study participation. 
 
The reason for participant discontinuation or withdrawal from the study will be recorded on the EPICS 
Case Report Form (CRF). Subjects who receive the study intervention, and subsequently withdraw, or are 
discontinued from the study, will not be replaced. 
7.3 
LOST TO FOLLOW-UP 
 
For our utilization aims (Aim 1, 3) we will track all utilization within KPSC until disenrollment or death. 
 
For the participant survey, a participant will be considered lost to follow-up if he or she does not respond 
to multiple contacts to complete the survey after agreeing to do so.  
 
The following actions must be taken if a participant fails to return the survey: 
 
• 
The site will attempt to contact the participant, resend the survey, and ascertain if the participant 
wishes to and/or should continue in the study 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls and, if necessary, 
a certified letter to the participant’s last known mailing address or local equivalent methods). 
These contact attempts will be documented in the participant’s study file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study aim with a primary reason of lost to follow-up. 
 

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8 
STUDY ASSESSMENTS AND PROCEDURES 
8.1 
ENDPOINT AND OTHER NON-SAFETY ASSESSMENTS 
Background Characteristics and Potential Confounders. Demographic information (e.g., age, race, 
ethnicity, census-level education and income) and clinical information (e.g., date of cancer diagnosis, age 
at diagnosis, disease stage, cancer treatment, endocrine therapy) will be collected from the EMR for all 
participants. Self-reported demographics will be collected from those who participate in the PRO survey.  
We will collect for clinician variables such as clinician gender, race, and years in practice from the EMR. 
Sex as a potentially important biologic factor will be included in all analyses. 
Receipt of Recommended Care (Aim 1). We will construct composite measures of recommended care for 
cancer surveillance and for preventive care, based on recommendations from the NCCN survivorship 
guideline. Cancer surveillance for early-stage breast cancer includes annual mammography and 2-4 
physician visits with history and physical (H&P) for the first 3 years; CRC surveillance includes colonoscopy 
within first year, annual chest/abdominal/pelvic CT, and 2-4 H&P visits and CEA lab tests annually for the 
first 3 years. Preventive care measures will be based on United States Preventive Task Force 
recommendations including appropriate cancer screening (other than for surveillance of primary cancer) 
for CRC, cervical, breast, and lung cancers, vaccinations (flu, pneumococcal), counseling for smoking 
cessation, and management of hyperlipidemia and hypercholesterolemia. These recommendations will 
be tailored to individual age, cancer type, health behaviors, and prior care (e.g., for breast cancer survivors 
≥50, colonoscopy every 10 years or annual FIT Kit for CRC cancer screening). We will use validated 
algorithms from our prior work based on CPT and ICD codes to identify use of services.[17, 31, 32, 99-102] 
We will identify receipt of recommended care for up to 36 months, starting 12 months after cessation of 
active treatment. Recommended care will be assessed in 12-month periods, with a binary outcome of 
received/did not receive for recommended cancer surveillance and for preventive care. We will also 
compare rates of individual services (e.g., rates of vaccination). Survivors with a pattern indicative of 
recurrence, based on validated recurrence algorithms,[103, 104] will be excluded from analysis of 
recommended cancer care.  We will identify use of services from oncology, ePCP, and the member’s 
assigned KPSC PCP to evaluate the impact of the model on utilization of services. 
Patient Reported Outcomes (Aim 2). We will use validated, reliable measures from existing national 
surveys that have been used in our target population. Most measures come from well-established surveys 
such as the Medical Expenditure Panel Survey (MEPS), the European Organisation for the Research and 
Treatment of Cancer (EORTC) Quality of Life, the Consumer Assessment of Healthcare Providers and 
Systems (CAHPS), and the Patient-Reported Outcomes Measurement Information System (PROMIS). We 
will assess patient-reported coordination of care, patient-provider communication, physical and mental 
health, assessment of survivorship care delivery, satisfaction with health decisions, and other measures 
relevant to survivorship care. We will also collect socioeconomic, demographic, and health behavior data 
(e.g. smoking). To evaluate our secondary outcome of patient-provider communication and coordination, 
we will use validated measures from the MEPS Experiences with Cancer Supplement CAHPS surveys (i.e., 
Patient-Centered Medical Home CAHPS coordination items). The MEPS patient-provider communication 

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scale evaluates discussions about: 1) cancer follow-up care; 2) late or long-term treatment effects; 3) 
lifestyle recommendations; and 4) emotional or social needs, with response options discussed in detail, 
briefly discussed, did not discuss, and I don’t remember. We will also examine CAHPS care coordination 
that includes six items on how often providers had appropriate information about: care provided by 
specialists; medical records and information about care; patient prescriptions and medications; follow-up 
regarding patient labs, X-rays, or other tests; and managing care between different providers.  The 
response set for these items is a 4-point Likert scale ranging from “Never” to “Sometimes” to “Usually” to 
“Always.” We will use design principles of Dillman et al. to order questions to minimize testing order 
effects, ensure the survey is appropriately and consistently designed for multiple modes, and minimize  
participant burden.[105]  
Utilization of unplanned hospitalizations, urgent care, and non-recommended cancer surveillance 
services (Aim 3). Using a similar approach to Aim 1, we will use CPT and ICD codes to identify 
hospitalizations related to cancer, using primary ICD code to identify reason for admission, as well as use 
of urgent care and use of non-recommended care. Non-recommended care measures are identified from 
relevant guidelines (e.g., ASCO Choosing Wisely, ACS Survivorship).[115-117] For early-stage breast 
cancer, this includes serum tumor markers and high-intensity imaging (e.g., CT and PET scans); for CRC, 
PET scans.  
Exploratory Aim. We will explore PCP knowledge of and confidence in providing survivorship care, 
comparing the embedded PCPs to PCPs practicing at centers assigned to the usual care model.  
 
Measures for Key Constructs for Patient Survey 
All measures have been previously validated and used in cancer research 
Construct 
Measure 
Patient-provider 
communication about 
survivorship care 
Medical Expenditure Panel Survey (MEPS) 2016, Experiences 
with Cancer Supplement, Section 7, Medical Care for 
Cancer[106]  
Quality of life 
European Organisation for the Research and Treatment of 
Cancer Quality of Life Questionnaire Core 30 (EORTC)[107] 
Coordination and continuity of 
cancer care  
Cancer Consumer Assessment of Healthcare Providers and 
Systems (CAHPS)[108] 
Self-efficacy  
PROMIS self-efficacy for managing symptoms[109] 
Overall health 
PROMIS Global Health Scale[109]  
Receipt of treatment summary 
and/or care plan  
Receipt of treatment summary from Health Information and 
National Trends Survey (HINTS 4, Cycle 2)[110, 111] 
Delivery of survivorship care  
Delivery of Survivorship Care Scale[63]   
Symptom burden 
Patient-Reported Bother From Side Effects of Cancer 
Therapy[112] 
Satisfaction with health care 
decisions 
Patient satisfaction with health care decisions: the 
satisfaction with decision scale[113]  
Confidence in care 
Questions adapted from ‘Confidence in managing 
survivorship care’ Casillas et al[114] 

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8.2 
SAFETY ASSESSMENTS 
 
Collection of observational data from administrative and clinical databases, self-reported demographics 
from the PRO surveys, and intervention activities at the KPSC medical centers will be collected and 
discussed at weekly project meetings. During monthly investigator meetings, data and recruitment 
summary reports of demographic and clinical information will be presented. Recruitment strategies will 
be brainstormed for optimization as needed. Recruitment success by racial/ethnic categories will be 
monitored closely and reported in National Institutes of Health (NIH) progress reports and to the Project 
Officer (PO)/Data Safety Monitoring Board (DSMB) no less than annually. 
 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
8.3.1 DEFINITION OF ADVERSE EVENTS 
 
We believe this study poses no more than minimal risk to subjects and the protocol uses the definition of 
adverse event (AE) from the KPSC IRB: (a) any unfavorable medical or psychological events experienced 
by a study participant during clinical research, including: a) a new symptom; b) worsening of an existing 
condition; or a clinically significant abnormal lab finding. AEs are considered a reportable unanticipated 
problem (UP) -- e.g., reportable to the KPSC IRB -- if they meet all three criteria for an unanticipated 
problem: 
 
• 
Unexpected in nature, severity, or frequency 
• 
Related or possibly related to participation in the research 
• 
Suggests greater risk to participants or others than previously known 
 
In the event that an AE is determined, it must be reported to the IRB within 10 business days and at the 
continuing review period. 
 
Because patients with early stage cancer will be enrolled in the study, we expect that approximately 2-
5% of breast cancer survivors will have a breast cancer recurrence [118], and 5-15% of colon and rectal 
cancer survivors will have a recurrence. [119] We expect this rate to be comparable across study arms. 
In terms of cancer-related mortality, the 5-year relative survival for localized breast cancer is 99% and 
regional is 86%; for colon and rectal cancers the localized 5-year relative survival is 91% and regional is 
72%. [120] Our study will follow patients for up to 36 months, thus we anticipate cancer-related 
mortality in each arm; again, we expect these to be comparable in both arms. Cancer-related 
hospitalization outside of hospitalization related to cancer recurrence will be very rare, as these patients 
will be 12 months out from their active treatment (surgery, chemotherapy, radiation, ovarian 
suppression injection). We will capture metrics on cancer recurrence, mortality, and hospitalizations as 
part of our safety monitoring plan.  
 

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AE/SAE Attribution Scale. We will calculate overall rates of occurrence of SAEs (number of SAEs per 
person-month) by extracting EMR/administrative data monthly to identify signals that might indicate 
potential harm.   
 
Expected Risks. Based on data from randomized controlled trials and observational studies, [81, 82, 84, 
121-123] we expect the SAEs rate to be comparable across study arms. These clinical events are risks 
inherent in the population and would occur regardless of study enrollment. We do not expect that the 
risk of adverse outcomes is heightened as a function of being enrolled in the study. Risks associated with 
collection of PRO data and potential loss of confidentiality and study procedures to minimize such risks 
were reviewed above.  
 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS 
 
As defined by the KPSC IRB, a serious adverse event (SAE) includes: 
 
• 
Death 
• 
Life threatening condition/situation 
• 
An enduring or significant incapacity or substantial disruption of the ability to conduct normal life 
functions 
• 
The delivery of a child with congenital anomaly or birth defect 
• 
Other medical events that the PI determines require intervention to prevent the above outcomes 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
 
The Principal Investigator must take action to protect the study participant(s) or others from the 
unexpected risk of harm. For AEs not included in the protocol defined grading system, the following 
guidelines will be used to describe severity: 
 
• 
Mild - Events require minimal or no treatment and do not interfere with the participant’s daily 
activities. 
• 
Moderate – Events result in a low level of inconvenience or concern with the intervention measures. 
Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating.  Of note, the 
term “severe” does not necessarily equate to “serious 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION/EXPERIMENTAL MANIPULATION 
 

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All AEs will have their relationship to study procedures, including the intervention, assessed by an 
appropriately trained clinician based on temporal relationship and his/her clinical judgment. The degree 
of certainty about causality will be graded using the categories below.  
 
• 
Related – The AE is known to occur with the study procedures, there is a reasonable possibility 
that the study procedures caused the AE, or there is a temporal relationship between the study 
procedures and the event. Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study procedures and the AE. 
• 
Not Related – There is not a reasonable possibility that the study procedures caused the event, 
there is no temporal relationship between the study procedures and event onset, or an alternate 
etiology has been established. 
 
8.3.3.3 EXPECTEDNESS  
 
The Principal Investigator will determine if the event or incident is unexpected in nature, severity, or 
frequency, taking into consideration: 
 
• 
The protocol-related documents, including: 1) IRB-approved research protocol or research 
application; or 2) other sources of information 
• 
The Principal Investigator’s knowledge of the characteristics of the study population 
• 
The expected progression of any underlying diseases or conditions of the participants 
• 
The participant’s pre-existing conditions and risk profile for the event 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
 
The occurrence of an AE or SAE may come to the attention of study personnel from review of electronic 
medical record data or from a study participant presenting for medical care within the embedded PCP or 
the oncology model. 
 
All AEs, not otherwise precluded per the protocol, will be captured on the appropriate CRF. Information 
to be collected includes event description, time of onset, clinician’s assessment of severity, relationship 
to study procedures (assessed only by those with the training and authority to make a diagnosis), and 
time of resolution/stabilization of the event. All AEs occurring while on study will be documented 
appropriately regardless of relationship. All AEs will be followed to adequate resolution. 
 
Any medical or psychiatric condition that is present at the time that the participant is screened will be 
considered as baseline and not reported as an AE. However, if the study participant’s condition 
deteriorates at any time during the study, it will be recorded as an AE.  
 

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Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. Documentation of onset and duration of each episode will be 
maintained for AEs characterized as intermittent. 
 
The Principal Investigator and/or project manager will record events with start dates occurring any time 
after informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.   
 
8.3.5 ADVERSE EVENT REPORTING  
 
The Principal Investigator will report AEs that are determined to be unanticipated problems to the KPSC 
IRB within 10 business days of discovery and at the continuing review period. 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
 
The Principal Investigator will be responsible for conducting an evaluation of a SAE based on the 
unanticipated problem analysis and shall report the results of such evaluation to the NIH and the KPSC 
IRB as soon as possible, but no event later than 10 working days after the investigator first learns of the 
event. In the event of the death of a study participant, reporting will fall under one of the following 
pathways: 
 
1. Death of an intervention study participant + unanticipated problem determination – the Principal 
Investigator will report to the Institutional Review Board within 1 business day of discovery and at 
continuing review 
2. Death of an intervention study participant + NOT an unanticipated problem – the Principal 
Investigator will report at continuing review 
3. Death of a non-interventional study participant – the event is not reportable 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
 
N/A 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
 
N/A 
 
8.3.9 REPORTING OF PREGNANCY  
 
N/A 

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8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS 
 
As per the definition provided by the KPSC IRB we will consider any AE under this protocol a reportable 
UP if the event meets all three criteria: 
 
• 
Unexpected in nature, severity, or frequency 
• 
Related or possibly related to participation in the research 
• 
Suggests greater risk to participants or others than previously known 
 
Corrective actions or changes that may be considered in response to a UP are: 
• 
Modification of inclusion or exclusion criteria to mitigate the newly identified risks 
• 
Implementation of additional safety monitoring procedures 
• 
Suspension of consenting/enrollment of new participants or halting of study procedures for 
consented/enrolled participants  
• 
Modification of informed consent documents to include a description of newly recognized risks 
• 
Provision 
of 
additional 
information 
about 
newly 
recognized 
risks 
to 
previously 
consented/enrolled participants 
8.4.2  UNANTICIPATED PROBLEMS REPORTING  
 
The Principal Investigator will report UPs to the reviewing KPSC IRB.  The UP report will include the 
following information: 
 
• 
Protocol identifying information: protocol title and number, Principal Investigator’s name, and 
the IRB project number 
• 
A detailed description of the event, incident, experience, or outcome  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP 
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are SAEs will be reported to the IRB and the study funding agency within 10 business 
days of the investigator becoming aware of the event; within one day in the event of the death of 
a participant if determined a UP. 
• 
Any other UP will be reported to the IRB and to the funding agency within 10 business days of the 
investigator becoming aware of the problem  

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8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
 
N/A 
 
9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
 
Primary Endpoint(s):  
To determine the efficacy of the ePCP model relative to the usual care group on receipt of recommended 
care. We will construct a composite measure of guideline-recommended cancer surveillance and age-
appropriate preventive care services, identifying utilization from EMR data. We hypothesize that patients 
in the ePCP model will have superior receipt of recommended care compared to usual care. 
 
Secondary Endpoint(s): 
1) To compare patient-reported outcomes (PROs) including patient-provider communication, 
coordination of survivorship care, and quality of life between the two models. We hypothesize 
that patients in the ePCP model will perceive significantly better care communication, self-
efficacy, and confidence in delivery of survivorship care compared to usual care, as collected by 
PRO surveys. 
 
2) To compare utilization of unplanned hospitalizations, use of urgent care, and receipt of non-
recommended cancer surveillance services between the two models. We hypothesize that use of 
unplanned and non-recommended care will be significantly less in the ePCP model compared to 
usual care.  
 
9.2 
SAMPLE SIZE DETERMINATION 
 
Based on recent literature, expected prevalence of surveillance items in the first year of breast cancer 
survivorship range from 15% for assessment of bone health to 80% for mammography.[124]  For CRC 
surveillance, a meta-analysis has shown that adherence ranged from 18-61% for colonoscopy and 17-71% 
for CEA tests. For preventive measures, Snyder et al. found that 30% of breast cancer survivors received 
recommended CRC screening, 32% received lipid testing, and 53% received an influenza vaccine. In our 
original cluster randomized design, we had 8 total medical centers, 4 intervention and 4 control, and 
anticipated 2,000 patients (approximately 250 per site). Under the original design, we modeled a range of 
expected values from 15% to 80% and found that a study this size would provide 90% power to reject the 
null hypothesis when the mean difference between groups is between 5.5% and 7.2%, with computed 
minimum detectable effect sizes for fixed power (0.8) and level of significance (0.025), using superiority 
hypotheses for the primary (receipt of recommended care) and secondary (patient-reported) outcomes. 

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As we expect the embedded PCP model to provide more comprehensive care, superiority hypotheses for 
these outcomes are warranted.    
Receipt of recommended care (Aim 1):.  Our new study design, necessitated by pressures from the 
COVID pandemic, is a quasi-experimental pre/post with control group design. While we have lost the 
element of randomization, we have increased our number of participating medical centers from 8 to 14 
and increased our anticipated number of participants to 2450. We have also added a pre-period analysis 
of health care utilization (Aims 1 and 3) for early-stage breast and colorectal cancer patients in 
survivorship between 2015-2019. We will use difference-in-difference (DID) analyses to compare the 
average changes pre- vs post-implementation and between the study arms.  Assuming, rather 
conservatively, that there will be no pre-period differences in receipt of recommended care across the 
14 study sites (4 treatment, 10 control), we calculated the minimum detectable differences that could 
achieve 80% power to detect superiority (varying the superiority margin from 0% to 10%), assuming no 
clustering and a level of 0.025.  Given the accrual challenges noted above, we used our new sample size 
expectations to re-calculate the minimum detectable differences, which previously ranged from about 
5.5% to 15.6% across the range of superiority margins.  Based on our current projected accrual, these 
differences now fall in the range of being as small as 6% to 16% for our most optimistic projection (640 
intervention patients), and as large as 7.6% to 16.5% for our least optimistic projection (450 intervention 
patients).  Should we observe significant pre-period differences between arms, the minimum detectable 
differences reported here will be over- or under-estimated depending on the direction and magnitude 
of the former.  

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PROs (Aim 2):  
Based on our prior experience with this population, we anticipate a 30% survey response rate with an 
estimated 840 responders. For our secondary outcome of patient-provider communication, from prior 
studies using the MEPS measure we expect that 32% of patients will report high-quality communication, 
with responses to individual questions ranging from 29% to 62%. As for Aim 1 above, we re-estimated the 
minimum detectable differences to reflect our current projected accrual, and under the same response 
rate assumptions, our sample size expectation for the intervention group is now 192.  In order to achieve 
80% power to detect superiority (varying the superiority margin from 0% to 10%), the smallest detectable 
difference for patient-provider communication ranges from 10.9% to 21.5%, under the alternative 
hypothesis that the primary care group is superior to usual care. The minimum detectable differences for 
the individual questions fall within a similar range.  These further assume no clustering and a significance 
level of 0.025. 
 
 
For Aim 3, we will use CPT and ICD codes to identify hospitalizations related to cancer, using primary ICD 
code to identify reason for admission, as well as use of urgent care and use of non-recommended care. 
Non-recommended care measures are identified from relevant guidelines (e.g., ASCO Choosing Wisely, 
ACS Survivorship).[115-117] For early-stage breast cancer, this includes serum tumor markers and high-
intensity imaging (e.g., CT and PET scans); for CRC, PET scans.  
 

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9.3 
POPULATIONS FOR ANALYSES 
 
The analyses will follow an intent-to-treat (ITT) strategy, i.e. analyses will include all survivors in the groups 
to which their medical centers were assigned, regardless of their individual adherence with the model. 
 
Each intervention patient will be matched to four eligible patients from control medical centers using a 
greedy match algorithm that requires the intervention patients and matched unexposed patients have 
the same cancer diagnosis (breast or colorectal cancer), cancer stage at diagnosis, year of last 
treatment, and race/ethnicity group. Exact matches are required for diagnosis, stage, and last treatment 
year; race/ethnicity can be flexible. For intervention patients, the start of follow-up is their first study 
survivorship primary care (PCP) physician visit. After matching, the time between the last treatment 
date and the first survivorship PCP visit date is calculated among enrolled patients, then added to the 
last treatment dates of their matched controls to create a comparable start of follow-up date for the 
patients in the control arm. 
 
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
 
Descriptive statistics will be calculated prior to conducting the primary analyses, and these will be 
compared between the pre- and post-implementation periods to assess for potential imbalances in 
patient and caregiver characteristics. For all analyses, data consistency and assumptions required, e.g., 
normality of responses, will be checked. Any data transformation or alternative methods necessary to 
analyze the data will be determined by examining the data structure. Individual patients and caregivers 
will be the unit of analysis. To address the fact that our study design will now be pre-post with a control 
group, the primary analytic approach will be difference-in-differences (DID), as it will be of specific interest 
to compare the average changes pre- vs post-implementation between the study arms. The analytical 
plans corresponding to the major study aims are detailed below. We expect minimal missing data for 
baseline patient and provider characteristics and will respectively use mean/median or reference group 
imputation for continuous and categorical covariates.  While this approach has potential for introducing 
bias, some of those biases may be “differenced out” in the DID models, especially those for which we have 
measurements on the same patients or providers in both time periods.  As a sensitivity analysis, we will 
compare the results from that approach to complete case analysis for primary outcomes. We also expect 
that baseline differences in potential confounders will also be “differenced out”, at least at the medical 
center level and likely at the provider level too, save for some providers who either may not be in our 
system during both study periods, or who may cross study arms over time.  Given that confounding and 
selection bias (mainly for PROs) due to patient characteristics may be unavoidable, we will explore the 
use of propensity-score based approaches (IPTW, matching weights, etc.) for addressing these concerns. 
 

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9.4.2 ANALYSIS OF THE PRIMARY ENDPOINT(S) 
 
For utilization data in both the pre- and post-periods, we will construct a composite measure of 
recommended care for cancer surveillance and for preventive care, based on recommendations from the 
ACS survivorship guideline. Cancer surveillance for early-stage breast cancer includes annual 
mammography and 2-4 physician visits with history and physical (H&P) for the first 3 years; CRC 
surveillance includes colonoscopy within first year, annual chest/abdominal/pelvic CT, and 2-4 H&P visits 
and CEA lab tests annually for the first 3 years. Preventive care measures will include appropriate cancer 
screening (other than for surveillance of primary cancer) for CRC, cervical, breast, and lung cancers, 
vaccinations (flu, pneumococcal), counseling for smoking cessation, and management of hyperlipidemia 
and hypercholesterolemia. These recommendations will be tailored to individual age, cancer type, health 
behaviors, and prior care (e.g., for breast cancer survivors ≥50, colonoscopy every 10 years or annual FIT 
Kit for CRC cancer screening). We will use validated algorithms from our prior work based on CPT and ICD 
codes to identify use of services.[17, 31, 32, 99-102] We will identify receipt of recommended care for up 
to 36 months, starting approximately 12 months after cessation of active treatment (see Study Timeline, 
section 2.7 of the Study Record). Recommended care will be assessed in 12-month periods, with a binary 
outcome of received/did not receive for recommended cancer surveillance and for preventive care. We 
will also compare rates of individual services (e.g., rates of vaccination). Survivors with a pattern indicative 
of recurrence, based on validated recurrence algorithms,[103, 104] will be excluded from analysis of 
recommended cancer care.  We will identify use of services from oncology, embedded PCP, and the 
member’s assigned KPSC PCP to evaluate the impact of the model on utilization of services. 
For the primary outcomes, we will use the DID framework (see equation 1) with different link functions 
to address the different types of outcomes (continuous, categorical, or counts).  Outcome 
measurements are denoted yijkt, where i indexes the individual patients, j indexes the providers with 
whom patients had follow-up visit at site k, and during study time period t. The first two parameters on 
the right-hand side of equation 1 denote a random clinician intercept (δ0j) to represent the baseline 
variation between physicians in receiving recommended care, and δ1 denotes the level difference for 
the Oncology-led model of care at the beginning of the post-implementation follow-up period.  The 
other two DID parameters δ2 and δ3 specify the average difference between Embedded-PCP and 
Oncology-led models at baseline and the difference-in-differences, the latter of which is the main 
quantity of interest.  The remaining parameters correspond to a flexible function of time, and fixed 
effects for respective patient, provider, and site characteristics.  
Equation 1: f(E(yijkt))= δ 0j + δ1I(post=1) + δ2I(Embedded PCP=1) + δ3I(post=1)I(Embedded PCP =1) + f(t) 
+ Xiα+Xjβ+Xkγ  

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9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
 
The main outcomes for Aim 2 will be analyzed using the same general modeling approach outlined in 
Equation 1 but dropping the parameters for the time difference and difference-in-difference(δ1 and δ3) 
since we will only be measuring those items once during follow-up.  In this case, for example, yijk could 
denote the probability that patient i reports ‘high quality’ patient-provider communication during study 
period k.  Other parameters in the model may be interpreted in the same manner as described above.   
 
 
Outcomes for Aim 3 will follow the same approach as Aim 1, but for categorical outcomes such as any 
inpatient visits, while using linear or log link functions where needed for continuous or count outcomes.   
 
9.4.4 SAFETY ANALYSES 
 
N/A 
 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Demographic information (e.g., age, race, ethnicity, census-level education, and income) and clinical 
information (e.g., date of cancer diagnosis, age at diagnosis, disease stage, cancer treatment, endocrine 
therapy) will be collected from the EMR for all participants and compared between intervention and 
control groups.  

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9.4.6 PLANNED INTERIM ANALYSES  
 
N/A 
 
9.4.7 SUB-GROUP ANALYSES 
We will test for differences by gender and race/ethnicity between the intervention and control groups on 
utilization and patient-reported outcomes. Prior studies of utilization in cancer survivors do not suggest 
or negate significant differences in intervention effect among subgroups; thus, it is important for our study 
to examine potential differences.   
 
9.4.8 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
 
We will not tabulate individual participant data.  
 
9.4.9 EXPLORATORY ANALYSES 
We will explore PCP knowledge of and confidence in providing survivorship care, comparing the 
embedded PCPs to PCPs practicing at centers non-randomly assigned to the usual care model. We will 
compare embedded PCPs to usual care PCPs using 2-sided chi-square tests. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 INFORMED CONSENT PROCESS 
10.1.1.1 CONSENT/ASSENT 
AND 
OTHER 
INFORMATIONAL 
DOCUMENTS 
PROVIDED 
TO 
PARTICIPANTS 
 
For this study, a waiver for informed consent is required to ensure a scientifically valid comparison of the 
ePCP model to current usual care. We do not foresee any risks to potential participants by not directly 
consenting them to participate in the trial. This study poses minimal risk to the patient because 
survivorship cancer care will be performed as part of routine medical care, and both the ePCP and the 
oncology-based model for survivorship cancer care are consistent with guidelines from professional 
societies and organizations with regard to the delivery of safe, appropriate, and usual care practices. We 
also believe that such a waiver of consent is not only widely recognized as necessary and appropriate, but 
also scientifically necessary and ethically justifiable under the “Common Rule” for protection of research 
participants (45 CFR 46.116d). 
 

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Patients will be recruited for PRO surveys under Aim 2. We obtained a waiver of written informed consent 
from all participants for participation in the surveys. Opt out options are built into an electronic template 
as part of the initial survey screens. Study information sheets in lieu of written informed consent 
describing in detail the survey procedures and risks are given to the participants as part of the recruitment 
contact. These sheets also include study contact information for further opt out options. All procedures 
were approved by our IRB prior to conducting any patient contact for the surveys under this Aim. 
  
For utilization data captured under Aim 3 from the EMR, individual patients will not be recruited or 
consented (falling under the waiver of informed consent for Aim 1). 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
 
For Aims 1 and 3, consenting procedures are not applicable.  
 
For Aim 2, study information sheets in lieu of written informed consent describing in detail the survey 
procedures and risks will be given to the participant.   
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be provided 
by the suspending or terminating party to study participants, investigator, funding agency, and regulatory 
authorities. If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the KPSC IRB, and sponsor/funding agency and will provide the 
reason(s) for the termination or suspension. Study participants will be contacted, as applicable, and be 
informed of changes to study visit schedule. 
 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
The study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the funding agency, KPSC IRB, or other relevant regulatory or oversight bodies (OHRP, DSMB).] 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
 

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Participant confidentiality will be maintained at all times. Each survey participant will be given a unique 
alpha-numeric identification number. No data collection form will be linked to an actual participant name. 
Any document linking the participant name to an identification number will be kept in a locked file 
separate from data collection files. All records from the study will be kept in locked files within the KPSC 
Department of Research and Evaluation. Identifying information will be removed from the final data sets 
and stored in a linked file to which only the Principal Investigator or designee has access. Individual 
participants will not be identified in any reports. Additionally, study reports will be aggregated so that 
individual participants are not identified. All investigators and research staff at participating sites will be 
required to maintain up-to-date training in human subject protection and good clinical practice through 
Collaborative Institutional Training Initiative (CITI; https://www.citiprogram.org/default.asp) and HIPAA 
training. Additional security precautions include encryption, digital certification, audit logs, and firewall 
protection.  
 
The study monitor, other authorized representatives of the sponsor or funding agency, or representatives 
of the KPSC IRB may inspect all documents and records required to be maintained by the investigator, 
including but not limited to, medical records (office, clinic, or hospital) for the participants in this study. 
The clinical study site will permit access to such records. At the end of the study, all records will continue 
to be kept in a secure location for as long a period as dictated by the KPSC IRB. 
 
Measures Taken to Ensure Confidentiality of Data Shared per the NIH Data Sharing Policies. The Principal 
Investigator will ensure all mechanisms used to share data will include proper plans and safeguards for 
the protection of privacy, confidentiality, and security for data dissemination and reuse (e.g., all data will 
be thoroughly de-identified and will not be traceable to a specific study participant; see Section 10.1.4 for 
details). Plans for archiving and long-term preservation of the data will be implemented, as appropriate.  
A Certificate of Confidentiality is not required for this study. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
We are committed to the open and timely dissemination of study data and research outcomes to the 
broader community of health care providers, investigators, patients, health care systems, and public 
health personnel. The investigators agree to abide by the principles for sharing research resources as 
described by the National Cancer Institute’s Cancer Moonshot public access and data sharing policy. 
Publications based on the study will adhere to the NIH Public Access Policy. Study data will be de-identified 
and made available for use in subsequent studies by other investigators to the extent feasible, pursuant 
to details as outlined below. We will invite other investigators to submit ancillary study proposals using 
the data from the study. 
The study will also produce deliverables that will be freely available to the cancer care community 
including protocols for the interventions as well as EMR algorithms (e.g., risk-stratification), and clinician 
and patient educational tools. We will engage in presentation and publication of findings, and have 

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structured each Aim to have publishable results, with an expectation of multiple opportunities for 
scientific presentations and manuscripts.  
Our plan to support efforts by other researchers to replicate this study in other oncology settings and 
practices, as well as for other healthcare systems that wish to test and/or implement the resulting 
products, includes: 1) sharing of a complete, detailed study protocol; 2) sharing of intervention tools 
developed during the study; and 3) sharing of datasets. Each of these activities will ensure transparency 
as well as replication so that other researchers will be able to apply the same study procedures, measures 
and analytic approaches to similar or novel populations. Our sharing of de-identified data will allow 
researchers to consider additional or associated questions or as a basis for collecting new data using this 
study design.  
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principal Investigator 
Erin E. Hahn, PhD, MPH, Res. Scientist  
Kaiser Permanente Southern California 
Department of Research & Evaluation 
100 S. Los Robles, 2nd Floor 
626-564-3505 
Erin.E.Hahn@kp.org 
 
We have assembled an Advisory Board with expertise in complementary areas to the study team. We will 
also include patient members who have experienced cancer, recruited through the KPSC Regional 
Member Advisory Committee. The role of the Board will be to provide input and guidance on the overall 
study design and progress, including refinement of model components (e.g., PCP training, health IT alerts), 
measurement of outcomes, and discussion of results. We will convene quarterly advisory board meetings 
each year. We will rely on stakeholder engagement strategies to ensure that our work is relevant and 
responsive, following the general approach of the Six Stage model for engagement. 
 
10.1.6 SAFETY OVERSIGHT 
The Data and Safety Monitoring Plan (DSMP) for this study includes monitoring recruitment procedures 
and potential adverse events resulting from data collection (observational data from clinical and 
administrative databases, and survey data) and from the intervention. There are minimal physical, 
psychological, or other risks associated with the proposed research based on the Common Rule, 45 CFR 
46.116d, because this study involves the use of routine care practices, no investigational drugs or devices, 
and poses little risk of physical or psychological harm to patients in either the embedded PCP or oncology 
model (standard of care) arm under Aim 1.   

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We have appointed a Data and Safety Monitoring Board (DSMB) consisting of a biostatistician, a cancer 
epidemiologist, and an oncologist. The DSMB will meet with the investigators during the start-up phase 
to approve the final study protocol. Yearly meetings will occur via conference calls to monitor recruitment 
and adverse events. 
10.1.7 CLINICAL MONITORING 
N/A 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
 
Quality control (QC) procedures will be implemented as follows: 
 
Informed consent ---  
• 
Aim 1, not applicable. The medical center sites will not consent participants under Aim 1.  
• 
Aim 2, not applicable. A waiver of written informed consent was approved by our IRB. A study 
information sheet is provided to participants at each survey recruitment contact, describing in detail 
the survey procedures and risks.  
• 
Aim 3, not applicable.  
 
Source documents and the electronic data --- Data for this study are obtained from clinical and 
administrative databases (Aim 1) and participant self-report for the surveys (Aim 2). For utilization data 
under Aim 3, we will use a similar approach to Aim 1 – e.g., CPT and ICD codes will be used to identify 
hospitalizations related to cancer, use of urgent care, and use of non-recommended care. Non-
recommended care measures will be identified from relevant guidelines (e.g., ASCO Choosing Wisely, ACS 
Survivorship). We will collect data in order to initiate participation identification at all sites in Years 1 and 
2 (Aim 1); we will collect PRO survey data in Years 2-4 (Aim 2); we will collect utilization data in Year 5 
(Aim 3).  
Intervention Fidelity — We will assess compliance with the study protocol monthly, with review of 
relevant data. We will collect utilization data for services with the ePCP, the treating oncology team, and 
with the patient’s assigned KPSC PCP. We will check for patterns of utilization indicative non-compliance 
with the ePCP protocol (e.g., no or limited visits with the ePCP, continued use of oncology for patients in 
the ePCP arm). We will have regular interactions with the study sites to discuss and review these data.  
Clinical EMR data on utilization has a high degree of accuracy but will be reviewed at regular intervals to 
ensure quality and accuracy (e.g., chart review of outliers).  Interim data checks will be done in aggregate, 
with means, median, and range checks performed quarterly.  
 
Protocol Deviations – Throughout the study phases, we will work closely with our Institutional Review 
Board, clinical chiefs, and operational leaders to ensure patient safety, with regular review and reporting 
of adverse events and protocol deviations. 

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Should independent monitoring become necessary, the Principal Investigator will provide direct access to 
all trial related sites, source data/documents, and reports for the purpose of monitoring and auditing by 
the sponsor/funding agency, and inspection by local and regulatory authorities. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
Demographic information (e.g., age, race, ethnicity, census-level education and income) and clinical 
information (e.g., date of cancer diagnosis, age at diagnosis, disease stage, cancer treatment, endocrine 
therapy) will be collected from the EMR for all participants (Aim 1) by study programmers under the 
oversight of Dr. Hahn. Self-reported demographics will be collected from those who participate in the PRO 
survey (Aim 2). We will collect clinician variables such as clinician gender, race, and years in practice from 
the EMR. 
 
Clinical EMR data on utilization (Aim 3) will be reviewed at regular intervals to ensure quality and accuracy 
(e.g., chart review of outliers).  Interim data checks will be done in aggregate, with means, median, and 
range checks performed quarterly. 
 
All investigators and research staff at participating sites will be required to maintain up-to-date training 
in human subject protection and good clinical practice through Collaborative Institutional Training 
Initiative (CITI; https://www.citiprogram.org/default.asp) and Health Insurance Portability and 
Accountability Act (HIPAA) training. Additional security precautions include encryption, digital 
certification, audit logs, and firewall protection. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 
Study documents will be retained for a minimum of 2 years after cessation of study analyses. These 
documents should be retained for a longer period, however, if required by local regulations or additional 
studies using these data and resources.  
 
10.1.10 
PROTOCOL DEVIATIONS   
 
This protocol uses the KPSC definition of protocol deviation: a protocol deviation is a departure from the 
IRB approved research plan that – a) does not place the safety, rights, or welfare of one or more study 
participants at risk AND b) does not impact the integrity of the study. As a result of deviations, corrective 
actions will be developed by the site and implemented promptly.  
 

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It will be the responsibility of the Principal Investigator to use continuous vigilance to identify and report 
deviations at the next continuing review period of identification of the protocol deviation. All deviations 
will be addressed in study source documents, reported to the KPSC IRB for review per their policies. The 
site investigator will be responsible for knowing and adhering to the KPSC IRB requirements. 
10.1.11 
PUBLICATION AND DATA SHARING POLICY  
 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
NIH Public Access Policy, which ensures that the public has access to the published results of NIH funded 
research. It requires scientists to submit final peer-reviewed journal manuscripts that arise from NIH funds 
to the digital archive PubMed Central upon acceptance for publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-reviewed 
journals.  Data from this study may be requested from other researchers up to 5 years after the 
completion of the primary endpoint by contacting Dr. Erin E. Hahn. Considerations for ensuring 
confidentiality of these shared data are described in Section 10.1.3. 
 
Details of data sharing include but are not limited to: 
1. Sharing of a complete, detailed study protocol and publications 
We will ensure our study protocol is registered on ClinialTrials.gov prior to initiation of enrollment 
procedures. At the end of the study, we will provide an updated, detailed study protocol describing all 
aspects of the study including the following: a) description of the study population, risk-stratification, 
sampling methods and resulting study sample; b) study design; recruitment and enrollment procedures; 
and primary care intervention components and implementation; c) data collection including programming 
algorithms to extract CPT-based utilization data; and d) copies of survey measures and data collection 
schedules and procedures. Our grant application becomes the initial draft of this protocol. This protocol 
will be updated at the end of the study planning phase to ensure that it provides a concrete, detailed, and 
specific step-by-step manual to allow replication. For reproducibility and for full transparency, any code 
or tools developed will be published along with the manuscript either through the journal website and/or 
GitHub or Open Science Framework website, which is hosted by the Center for Open Science (funded in 
part by the NIH and the National Science foundation) and is open to the public. We will also seek to publish 
this protocol in a relevant scientific journal. This and other publications generated from this study will: 
1. Be deposited in PubMed Central with proper tagging of metadata after acceptance by a journal; 

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2. Will be published under the Creative Commons Attribution 4.0 Generic License or an equivalent 
license, or otherwise dedicated to the public domain; 
3. To the extent feasible, underlying primary data will be shared simultaneously with the publication. 
2. Sharing of de-identified data for replication and additional studies  
For this study, the Investigators will provide these research data in a controlled manner to outside 
researchers who are willing to enter into formal research relationships to ensure that the data will be used 
for scientific purposes in the public interest, that patient privacy will be protected, and that all other risks 
to participants will be minimized. All such requests will be reviewed by the Investigators for scientific 
merit, human subjects considerations, and KPSC legal obligations. Primary data will reside locally within 
the Kaiser Permanente Department of Research and Evaluation. After approval of the request, a data 
sharing agreement will be created, approved, and signed. Conditions may be placed on the use of the 
data, including but not limited to, no distribution to third parties, a KPSC researcher included on the study 
teamproper acknowledgement and citation of the data providers (as indicated in the data sharing 
agreement) and the NIH grant funding, exclusive use by the data recipient in connection with a specific 
research project, for which the recipient has sole responsibility and which is explicitly described, and 
agreement not to use the data in any effort to establish the identity of the study subjects. The data 
recipient will be subject to applicable federal, state, and local laws or regulations and institutional policies 
providing additional protections for human subjects.  
De-identification of data: In order to protect the privacy rights of participants and confidentiality of their 
data, we will de-identify all data according to the standards set forth in the Health and Human Services 
Regulations for the Protection of Human Subjects; primary data will also be stripped of identifiers 
according to the HIPAA Privacy Rule. With input from the KPSC IRB, we will assess consent materials to 
determine whether data may be shared as contemplated in this policy. 
If de-identified data can be shared, the following process and procedures is to be followed: 
1. Requests will be evaluated individually by the Principal Investigator of this study in conjunction 
with the Senior Director of Research and/or the Executive Committee of the Department of 
Research and Evaluation. 
a. Requests must be from a qualified, doctorate-level researcher;  
b. Requests must have a stated, achievable purpose and detailed plan that is of value to the 
clinical and/or research community. 
2. A data use agreement and/or data transfer agreement must be executed for all requests. This 
must include: 
a. What data elements are to be included;  
b. How the data will be used; 
c. Details of any subsequent disclosure and prohibition of additional disclosure without an 
amendment; 
d. How long the data can be used; 
e. What will happen to the data when the project is complete; 

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f. Opportunity for review and comment. 
3. De-identified datasets to be made available under this Plan must: 
a. Follow the definitions of de-identification as outlined by Health and Human Services 
Regulations for the Protection of Human Subjects and the HIPAA Privacy Rule;   
b. Use relative dates and round birth dates/ages; 
c. De-identify entity/site of care to be to the extent possible; 
d. Only include data to support publication. 
4. An approval process will be in place, with required approvals from: 
a. SCPMG practice leader (typically Regional Chief of relevant specialty) 
b. SCPMG Area Medical Director 
c. Senior Director of Research, Department of Research and Evaluation 
5. There will be no associated fees. 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 
Any actual conflict of interest of persons who have a role in the design, conduct, analysis, publication, or 
any aspect of this trial will be disclosed and managed. Furthermore, persons who have a perceived conflict 
of interest will be required to have such conflicts managed in a way that is appropriate to their 
participation in the design and conduct of this trial. The study leadership in conjunction with the National 
Cancer Institute (NCI) has established policies and procedures for all study group members to disclose all 
conflicts of interest and will establish a mechanism for the management of all reported dualities of 
interest. 
10.2 ADDITIONAL CONSIDERATIONS 
 
N/A 
 
10.3 ABBREVIATIONS AND SPECIAL TERMS 
 
AE 
Adverse Event 
ACS 
American Cancer Institute 
AHRQ 
Agency for Healthcare Research and Quality 
ASCO 
American Society for Clinical Oncology 
CAHPS 
Consumer Assessment of Healthcare Provider and Systems 
CEA 
Carcinoembryonic Antigen 
CFR 
Code of Federal Regulations 
CITI 
Collaborative Institutional Training Initiative 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CRC  
Colorectal Cancer 
CRF 
Case Report Form 
CVD 
Cardiovascular Disease 

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DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
EORTC 
European Organisation for the Research and Treatment of Cancer 
EMR 
Electronic Medical Record(s) 
ePCP 
Embedded Primary Care Physician 
FITKit 
Fecal Immunochemical Test Kit 
GCP 
Good Clinical Practice 
H&P 
History and Physical 
HIPAA 
Health Insurance Portability and Accountability Act  
ICC 
Intracluster Correlation 
ICD 
International Classification of Diseases 
ICH 
International Conference on Harmonisation 
IRB 
Institutional Review Board 
IT 
Information Technology 
ITT 
Intent to Treat 
KPSC 
Kaiser Permanente Southern California 
MEPS 
Medical Expenditure Panel Survey 
MOP 
Manual of Procedures 
NCI 
National Cancer Institute 
NIH  
National Institutes of Health 
OHRP 
Office for Human Research Protections 
PCORI 
Patient-Centered Outcomes Research Institute 
PET 
Positron Emission Tomography 
PHI 
Protected Health Information 
PO 
Project Officer 
PROs 
Patient-Reported Outcomes 
PROMIS 
Patient-Reported Outcomes Measurement Information Systems 
QA 
Quality Assurance 
QC 
Quality Control 
RCT 
Randomized-Controlled Trial 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SCPs 
Survivorship Care Plans 
SCPMG 
Southern California Permanente Medical Group 
SMC 
Safety Monitoring Committee 
SO 
Safety Officer 
UK 
United Kingdom 
UP 
Unanticipated Problem 
URL 
Uniform Resource Locator 
US 
United States 
 
 
 
 
10.4 PROTOCOL AMENDMENT HISTORY 

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Version 
Date 
Description of Change  
Brief Rationale 
1.0 
01-14-2021 
N/A; First version 
 
2.0 
07-28-2021 
Updates to: 1) study design and 
statistical analysis plan; 2) 
Intervention components; 3) risk 
stratification 
In response to the Covid 
pandemic, we had to change 
the study design from a 
randomized trial to a non-
randomized quasi-experimental 
design; 2) We adapted the 
intervention materials in 
response to clinician request, 
including live webinars (rather 
than just pre-recorded); 3) 
Updated risk 
stratification/exclusions based 
on clinician feedback 
3.0 
 
Updates to: 1) Patient eligibility 
window; 2) Recruitment timeline; 3) 
Power and statistical analysis  
Impacts from COVID have 
resulted in fewer early stage 
breast cancer and CRC patients 
diagnosed at early stage during 
2020-2021, necessitating 
changes to our eligibility and 
power/analysis plan; COVID has 
also impacted clinical staff 
availability, necessitating a 
longer recruitment timeline 
4.0 
10-02-2023 
Updates to: 1) survey recruitment 
schedule; 2) incentive plan for 
survey; 3) matching plan for 
intervention and control condition 
patients; details on consent/assent 
Changes to the survey schedule 
and incentive plan were based 
on feasibility issues and 
matching intervention and 
control patients is necessary for 
the statistical plan. 
 
 
 
 
 
 
 
 
 
 

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EPICS Study 
 
Version 4.0  
Protocol R01CA249419 
 
02 October 2023 
NIH Behavioral and Social Intervention Clinical Trial Protocol Template v3.0 - 20180827 
 
 
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