Empowering Patients' Lung Cancer Screening Uptake (Empower LCS)
Phase: NA
Conditions: Lung Cancer
Sponsor: University of California, Irvine

 
 
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Empowering patients’ Lung Cancer Screening uptake (Empower LCS) 
 
Principal Investigator  
 Dr. Gelareh Sadigh 
Biostatistician 
Argyrios Ziogas, PhD 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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1. 
PROTOCOL SYNOPSIS 
Study Number 
UCI 23-107 
Study Title 
Empowering patients’ Lung Cancer Screening uptake (Empower 
LCS) 
Development Phase 
II 
Funding Source(s) 
Anti-Cancer Challenge Pilot Award 
Operational 
Changes during the 
COVID-19 
Pandemic 
N/A 
Sources of Study 
Drugs 
N/A 
Number and 
Identity of Study 
Sites 
University of California Irvine Health 
Study Rationale 
Utilization of lung cancer screening (LCS) using Low Dose CT 
(LDCT) among those eligible is low. We are assessing feasibility of a 
multi-level intervention to improve lung cancer screening uptake. 
Study Design 
Single arm longitudinal study 
Study Objectives 
1. Assess feasibility of our multi-level intervention in increasing 
patients’ LCS knowledge, having a LDCT ordered, and patients’ 
receipt of LCS with LDCT. 
2. Assess LCS-eligible patients’ and their providers’ perceptions and 
barriers towards LCS. 
3. Describe patients’ & providers’ experience with the intervention 
using a mixed-methods approach. 
 
Planned and 
Maximum Sample 
Size 
70 patient participants (English, Spanish, and Vietnamese speaking), 
and between 20-40 non-patient participants. 
 
Duration of Study 
Participation 
Patient participants: 6 months. Up to 15 patients will be asked to 
participate in a 30-min interview after 6 months completion of the 
study.  
Non-patient participants: One time. 5 non-patient participants will be 
asked to participate in a 30-min interview within 3 months of last 
patient enrollment.   
Indication(s) Under 
Study 
Patients eligible for lung cancer screening 
Inclusion Criteria 
1. Aged 50- 80 years of age.  

 
 
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2. Be able to Speak English, Spanish, or Vietnamese  
3. Must have a primary care provider 
4. Meeting the LCS eligibility criteria based on self-reported 
smoking history (for UCI and non-UCI Health patients)  as 
well as documented in EMR (for UCI Health patients) and 
confirmed prior to enrollment  
Exclusion Criteria 
1. No prior history of lung cancer  
2. No chest CT for any reason in the last 12 months based on 
self-report (for UCI and non-UCI Health patients)  and UCI 
EMR (for UCI Health patients) 
3. No history of Alzheimer’s disease or dementia 
Study Intervention 
Our proposed intervention, informed by the Health Belief Model19, is 
a multi-level intervention including: (1) PCP notifications of patients’ 
LCS eligibility (addressing provider time constraints and barrier in 
identifying eligible patients); (2) patients’ education (addressing 
knowledge barriers); (3) patients’ referral to financial navigation 
resources (addressing health-related social risks); and (4) patients’ 
reminder to discuss LCS during PCP visit. 
Baseline 
Assessments 
Baseline survey at enrollment 
Efficacy 
Assessments 
Follow-up survey 6 months after enrollment 
Statistical 
Methodology 
Descriptive measures, comparison of pre- and post- intervention 
endpoints 
Efficacy Endpoints 
Primary end point is order of LDCT within 6 months after 
enrollment assessed with self-reported surveys (for UCI and non-
UCI Health patients) and EMR data extraction (for UCI Health 
patients) 

 
 
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Figure 1   
Study Schematic 
 
 
A. Pre-Screening (identify potentially eligible population) 
UCI Health IT Enterprise will be queried for a list of patients 50-80yrs of age and speak English, Spanish, and Vietnamese. 
If they have a history of smoking or an unknow history of smoking and have a Primary Care Provider. Primary care clinics 
list of patients and EMR will also be manually checked for potential eligible patients. We will also distribute study flyers to 
community clinics and Vietnamese and Spanish speaking social media, and news outlets. 
B. Screen/Approach Patients: 
Approaching all potentially eligible patients via Redcap survey, phone, mail or in person in the clinic: 
• Verify study eligibility by a short 2-minute survey.  
• Recruit eligible subjects for participation. 
C. Consent Patients: 
Obtain written informed consent (DocuSign or paper).  
D. Baseline Procedures  
Encourage participants to complete baseline survey.  
F. Follow up Procedures: 
Participants complete a follow-up survey 6 months post-enrollment.  
Non-patient participants (Primary Care Providers) will complete a survey 
G. Qualitative Interview  
15 patients will be randomly selected to undergo a 30-minute interview. 
5 providers with highest number of enrolled patients in the study will undergo a 30-minute interview 
E. Deliver Interventions 
(1) PCP notifications of patients’ LCS eligibility; (2) patients’ education; (3) patients’ referral to financial navigation 
resources; and (4) patients’ reminder to discuss LCS during PCP visit. 

 
 
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Table 1   
Schedule of Events 
 
Pre-
Screen 
Screen 
Baseline 
Primary Care 
Appointment 
6 months 
Follow-up 
Provider 
Survey 
Interview 
UCI Health IT inquiry 
X 
 
 
 
 
 
 
Distribution of flyer to community 
clinics and Spanish and Vietnamese 
speaking social media and news outlet X 
 
 
 
 
 
 
Screening 2-min survey 
 
X 
 
 
 
 
 
Informed Consent 
 
 
Prior to PCP appointment 
 
 
 
 
Baseline Survey 
 
 
After informed consent 
prior to PCP appointment 
 
 
 
 
Intervention delivery 
 
 
 
After baseline 
survey, prior to 
PCP appointment 
 
 
 
Follow-up survey 
 
 
 
 
Within -14 and 
+30 days of 6 
months follow-up 
 
 
Provider Survey 
 
 
 
 
 
Within 3 
months of last 
patient 
enrollment 
 
Interview 
 
 
 
 
 
 
Within 30 days 
of patient or 
provider 
completion of 
their survey. 
 
 
 
 

 
 
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2. 
ABBREVIATIONS AND ACRONYMS 
Abbreviation 
Definition 
AE 
Adverse Event 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DSMB 
Data and Safety Monitoring Board 
EMR 
Electronic Medical Record 
HRPP 
Human Research Protections Program 
LCS 
Lung Cancer Screening 
LDCT 
Low Dose CT 
NCI 
National Cancer Institute 
SAE 
Serious Adverse Event 
USPSTF 
United States Preventive Services Task Force 
 
 

 
 
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3. 
BACKGROUND AND RATIONALE 
Lung cancer is the leading cause of cancer-related mortality, with 1.8 million annual 
deaths worldwide.1 Lung cancer screening (LCS) with low-dose computed tomography 
(LDCT) is shown to decrease mortality rate of lung cancer by 20%, compared with chest 
x-ray alone.2 From 2015, both private and public health insurance began to cover lcs with 
ldct.3 However, lcs uptake remains low,4 with only 12.8% of LCS-eligible patients 
receiving ldct in 2019,5 and 55% of those with a baseline LDCT returning for ldc in the 
subsequent 12-36 months.6  Further, white race is twice more likely to be adherent to lcs 
compared to races other than white.6  The 2021 US Preventive Service Task Force 
(USPSTF) update expanded the eligibility criteria and recommended high-risk 
populations (aged 50–80 years old, have a 20 pack-year smoking history, and currently 
smoke or have quit within the past 15 years) to receive annual LDCT to screen for lung 
cancer.7 
There are several barriers to LCS. Provider barriers includes the failure of the electronic 
medical record (EMR) to notify providers of eligible patients (most common), patient 
refusal, perceived high false-positive rate leading to unnecessary procedures, provider 
time constraints, and patients’ lack of insurance coverage.8 Identifying eligible patients 
through EMR is often challenging as smoking pack-year data is either not complete or 
discordant (92.6% in one study) with patients’ self-reported data obtained during patient-
provider shared decision making conversations regarding LCS.9 This results in lack of 
trust of the primary care providers (PCP) to use EMR data for such purposes.10 Patients’ 
barriers to LCS includes concerns regarding insurance coverage and co-pay for both 
screening and treatment (if diagnosed with cancer), access to convenient care, fear of a 
positive screening result or radiation exposure, and lack of understanding that lung cancer 
correlates with smoking history.11,12 Prior research assessing perceptions and barriers 
towards LCS and interventions to address barriers among diverse non-white and non-
English-speaking population is limited. Interventions addressing LCS knowledge barriers 
have shown an increase in patients’ knowledge or decisional certainty,13,14 but were not 
sufficient to increase receipt of LCS.13-16 On the other hand, interventions involving 
direct patient outreach (e.g., reminders to call and schedule LCS) or patient navigators 
addressing multiple barriers were more successful in increasing LCS uptake.17,18 
Our proposed intervention, informed by the Health Belief Model19, is a multi-level 
intervention including: (1) PCP notifications of patients’ LCS eligibility (addressing 
provider time constraints and barrier in identifying eligible patients); (2) patients’ 
education (addressing knowledge barriers); (3) patients’ referral to financial navigation 
resources (addressing health-related social risks); and (4) patients’ reminder to discuss 
LCS during PCP visit. We propose to assess perceptions and barriers towards LCS and 
test our intervention among 0 English-,  Spanish- and  Vietnamese-speaking LCS-eligible 
patients with a scheduled PCP visit at any of UCI primary care clinics including FQHC 
or at non-UCI Health clinics in the next five months. 
 
 

 
 
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4. 
STUDY OBJECTIVES 
4.1. 
Primary Objective 
4. Assess feasibility of our multi-level intervention in increasing patients’ LCS 
knowledge, having a LDCT ordered, and patients’ receipt of LCS with LDCT. 
4.2. 
Secondary Objectives 
1. Assess LCS-eligible patients’ and their providers’ perceptions and barriers towards 
LCS. 
2. Describe patients’ & providers’ experience with the intervention using a mixed-
methods approach. 
5. 
INVESTIGATIONAL PLAN 
5.1. 
Indications Under Study 
Patients eligible for lung cancer screening 
 
5.2. 
Overall Study Design 
We will conduct a single arm longitudinal clinical trial of 70 LCS-eligible patients with a 
PCP appointment at UCI health within five months after enrollment. All patients will 
complete a baseline survey to assess their perceptions and barriers towards LCS and will 
receive a multi-level intervention. All patients will complete a survey at 6 months post-
enrollment to assess changes in perceptions and knowledge, receipt of an order for LDCT 
or completion of LDCT, and experience with intervention. All primary care providers of 
enrolled patients will be sent a survey 3 months after last patient enrollment to assess 
providers’ barriers to order LCS. We will interview randomly selected up to 15 patients  
and 5 PCP participants with highest enrolled patients in the study, who consent to be 
interviewed to assess experience with the intervention.  
 
5.3. 
 Study Segments and Visits 
The different phases of the study are illustrated in Figure 1, with details of assessments 
schedule in the main study segments given in Table 1.   
5.4. 
Number of Subjects 
70 patient participants, and between 20-40 non-patient participants. 
 

 
 
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5.5. 
Definition of Completers 
Participants who complete all study procedures are considered completers. For patients 
this include consenting, completing baseline survey, receiving study intervention and 
completing the 6 months follow-up survey. 
 
5.6. 
Study Stopping Rules 
Not applicable.  

 
 
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6. 
STUDY POPULATION 
6.1. 
Inclusion Criteria 
Patients with the following characteristics are eligible for enrollment into the study: 
Aged 50- 80 years of age.  
Be able to Speak English, Spanish, or Vietnamese  
Must have a Primary Care Providers. 
.  
Meeting the LCS eligibility criteria based on self-reported smoking history as well as 
documented in EMR and confirmed prior to enrollment (current or former smoker with 
20 pack year smoking history) 
6.2. 
Exclusion Criteria 
The following patients will not be eligible for participation in the study: 
No prior history of lung cancer  
No chest CT for any reason in the last 12 months based on self-report (for UCI-Health 
and non-UCI Health patients) and UCI EMR (for UCI-Health patients) 
No history of Alzheimer’s disease or dementia 
7. 
STUDY PROCEDURES 
7.1. 
Pre-Screening 
UCI Health Patients: 
UCI clinical data warehouse will be inquired every week for a list of patients and their 
contact information, who are 50-80 years old, speaking English, Spanish or Vietnamese, 
and have a primary care provider, who are current or former smokers or have an 
unknown smoking history in EMR, and have no history of lung cancer, Alzheimer’s 
disease or dementia, and have not received a chest CT or LDCT in the last 12 months. 
We will further inquire from primary care providers about their potentially eligible 
patients. EMR will also manually be reviewed to assess eligibility and generate an 
additional list for recruitment. We will take a note of patients with primary care 
appointment in next 5 months so that we have in person outreach. 
 
We will send an email outreach with the study information, an option to opt out if not 
interested, and a short 2-min REDCap survey to verify LCS eligibility if interested in 
participating. For non-English speaking patients, the email outreach and survey will be 
sent in their preferred language. The survey includes questions on smoking history, prior 
history of lung cancer, and prior receipt of chest CT in the last 12 months.  

 
 
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To ensure our sample size is representative of population, we plan to have phone 
outreach, text message outreach, in person clinic visits to directly recruit participants, or 
mailing surveys (by bilingual research team) to patients who do not have an email 
address or do not respond to the email outreach, a common condition among non-English 
speaking patients. 
Non-UCI Health patients 
Additionally, we will conduct outreach to patients outside of the UCI Health system. 
 Outreach materials, such as flyers with QR codes, will be distributed to local clinics 
serving Latino and Vietnamese populations to be placed in their waiting rooms. We will 
also distribute these flyers via social media groups aimed at Spanish- and Vietnamese-
speaking population. Lastly, working with cancer center community outreach program 
we distribute the flyers during community events. We may advertise the flyers with 1-2 
message during local radio or TV outlets.  
 
 Patients who are interested will scan the QR code to easily connect with our team. They 
can also call us or email us if interested. We will also provide drop-off boxes in the 
clinics for interested patients to leave their contact information.  
The 2-minute pre-screening survey for non-UCI Health patients will include inquiring 
about the name and contact information for their primary care doctor. 
 
Non-UCI Health providers will not be engaged with human subject research at any point.  
 
7.2. 
Non-eligible patients 
Patients who do not meet the eligibility criteria based on the survey will be asked to 
complete a HIPAA authorization form sent to them via DocuSign, fax or mail, based on 
patients’ preference. 
Given documenting smoking history in EMR during health encounters is being 
implemented at UCI, we plan to compare EMR smoking history data with patients’ self-
report to assess for accuracy. This only applies to UCI Health patients.  
 
7.3. 
Informed Consent 
Patients who complete the LCS eligibility survey and meet the study eligibility criteria 
will be then contacted via phone by a study coordinator speaking the patients’ language 
for a study overview and consenting. A signed and dated written informed consent form 
(ICF) will be obtained from the patient via DocuSign, fax or mail.  A signed copy of each 
ICF will be given to the patient or they can download it via REDCap. 

 
 
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7.4. 
Screening Confirmation 
Patient information should be entered into OnCore within 5 business day of consent. 
Each site is responsible for assigning subject ID.  
7.5. 
Baseline Survey 
Patients will be asked to complete a 15-min survey either on the phone or online via 
REDCap based on preference. This survey includes validated measures utilizing the 
Health Belief Model20,21 to assess perceived risk of getting lung cancer, benefits and 
barriers to LCS, and self-efficacy for LCS, prior receipt of any screening exam, overall 
willingness to undergo LCS with LDCT, and engage in receiving LCS educational 
information. We will further screen for health-related social risks such as financial 
hardship, difficulties in paying for food, transportation, and housing instability as a 
barrier to receipt of LCS, and query on demographics, insurance, health literacy, zip code 
(to assess neighborhood socioeconomic status), and presence of other comorbidities and 
healthy behaviors. Participants with completed survey will be sent a $15 gift card. Survey 
materials will be available in English, Spanish, and Vietnamese. 
 
7.6. 
Study Intervention 
Consented patients completing baseline survey will receive usual care which includes a 
provider flag in EMR on their eligibility for LCS if their smoking history is complete.  
 
Our intervention includes: 
 (1) Primary Care Provider notification of patients’ LCS eligibility, and their self-reported 
barriers to receipt of LCS based on baseline survey. The notification will be sent using an 
EPIC secure message and via email within 2 weeks prior to scheduled PCP visit. If a 
patient cancels or reschedules the appointment, the message will still be sent within 2 
weeks of the initial appointment. Prior to study activation, all UCI PCPs will be emailed 
and notified of our study.  
 
For non-UCI Health PCPs, reminders to discuss LCS will be sent via secure email or 
direct phone calls to their office. Non-UCI Health PCPs will not directly engage in 
research activities and will instead continue to admisnter standard patient care. Non-UCI 
Health PCPs will not represent the study.  
 
(2) patient education of LCS: patients will be mailed (paper) and emailed (PDF from; if 
have an email address) information (in preferred language) on lung cancer risk, LCS 
benefits, harms, false positive rates, recommendations of follow-up for positive results, 
and exam insurance coverage. Publicly available resource “Should I Screen”22 and 
baseline survey data will be used to create material.  
(3) patients’ referral to financial navigation resources: Patients who self-report needing 
help with health-related social risks at baseline will be mailed (paper) and emailed (PDF 

 
 
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Page 13 of 76 
from; if have an email address) a brochure (in preferred language) from patient advocate 
foundation (PAF), a national non-profit financial navigation organization, where patients 
can self-refer;  
 
(4) patients’ reminder to discuss LCS during PCP visit: within 2 weeks prior to 
appointment, all patients, regardless of their site for care, will receive a text message or a 
phone call (if not having a phone that receives text messaging) encouraging patients to 
discuss the LCS with their provider.   
 
7.7. 
Patient Follow-up 
Patients will be surveyed 6 months after enrollment to assess self-reported LCS 
discussion with PCP, provider order of LDCT, and patients’ receipt of LDCT. We will 
also extract these from EMR only for UC-Health patients. Patients will be queried on 
LCS perceived risks, benefits, barriers, and self-efficacy, experience with intervention 
including educational material, reminders, and self-referral to PAF if PAF brochure was 
received.  
Surveys will be completed online (REDCap), on the phone or paper (mailed with a pre-
stamped pre-addressed envelope) based on patient’s preference. Patients with completed 
survey will receive a $15 gift card.   
7.8. 
Non-patient participant Follow-up 
Any of the UCI Primary Care providers who receive a provider notification of their 
patients’ LCS eligibility as part of the study will be eligible to participate. Three months 
after last patient enrollment, we will send an electronic REDCap information sheet to all 
eligible providers and ask them to complete an online 10-minute survey.  
 
The survey includes questions pertaining to provider demographics, clinical practice, 
perception regarding barriers to LCS, awareness of CMS beneficiary eligibility criteria 
for LDCT using a validated questionnaire,8 providers’ experience with EMR flags they 
receive for patients’ LCS eligibility as part of usual care, as well as their experience with 
the patient-specific LCS eligibility notification they received as part of the study and 
whether that prompted them having a LCS discussion with their patients. Additionally, 
we will inquire about their interest in future development of a provider-directed 
educational material. Survey participants will receive a $15 gift card. We expect 20-40 
providers participate in the survey. 
7.9. 
Qualitative interviews with patient and non-patient participants 
We will conduct in-depth phone interviews with randomly selected 15 patients  and 5 
PCP participants with highest number of enrolled patients in the study. The Reach, 
Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework will be 
used to guide the evaluation questions and examine the effectiveness of the intervention 
and implementation outcomes.101  

 
 
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We will ask patients and providers to describe any barriers to LCS completion (for 
patients) and ordering (for providers) and describe their experience with use of various 
components of the intervention, as well as feedback on what they liked and disliked about 
the intervention, and what they would change to make it more helpful or engaging. 
Participants will be recruited via phone by the study coordinator, and interviews will be 
conducted on the phone, video conference or in person. We expect that patient interviews 
take 30 minutes, and provider interviews take 20 minutes. Interview participants will 
receive a $40 gift card.  
8. 
EFFICACY ASSESSMENTS 
Primary end point is order of LDCT within 6 months after enrollment assessed with self-
reported surveys (for UCI-Health and non-UCI health patients) and EMR data extraction 
(for non-UCI Health patients). Remainder of outcomes is show in Table 2. 
• Any mention of ER is only for UCI Health patients. 
 
9. 
SAFETY AND TREATMENT-EMERGENT ADVERSE EVENT 
REPORTING 
We do not anticipate any adverse events related to participation in this study beyond 
usual care.  
If a participant report feeling distressed as a result of study participation, they may 
choose not to continue or to complete them and/or speak with the research team.  
9.1. 
Reporting Protocol Violations and Protocol Deviations 
Protocol Violation are defined as an accidental or unintentional change to or 
noncompliance with the IRB-approved protocol that increases risk or decreases benefit 
Table 2 . Study Outcomes, Measures and co-variates 
Efficacy Outcomes 
 
 
LDCT order for LCS 
6 mo 
Survey and EMR  
Receipt of LDCT for LCS 
6 mo 
Survey &EMR 
Pt and PCP LCS discussion  
6 mo 
Pt perceived risks, benefit, barriers, and self-efficacy using LCS 
health belief model21 
Baseline & 6 mo 
Survey 
Process Evaluation Outcomes 
 
Rate of concordance of EMR and self-report smoking hx 
Baseline 
Survey& EMR 
 
Showing up to PCP visit 
6 mo 
Self-referral to PAF 
6 mo 
Survey 
Pt and provider experience with intervention components 
6 mo 
Survey& interview 
Provider perceived barriers and knowledge of LCS 
Beginning 9 mo after first 
pt enrollment 
Survey 
Covariates 
 
 
Sociodemographics, insurance, neighborhood deprivation 
index, health literacy, comorbidities 
Baseline 
Survey 
Financial worry23,24  and health-related social risks25 
Baseline & 6mo 
Survey 

 
 
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and/or affects the subject's rights, safety, welfare, and/or the integrity of the data. 
Examples of incidents that may be considered violations include: enrolling a participant 
who does not meet the inclusion criteria; obtaining verbal consent before the initiation of 
study procedures when the IRB requires signed, written informed consent. [Reference: 
Policy #57 UCI HRPP Policy and Procedure Glossary].  
Protocol Deviations are defined as an accidental or unintentional change to the research 
protocol that does not increase risk or decrease benefit or have a significant effect on the 
participant’s rights, safety or welfare, or on the integrity of the data. Deviations may 
result from the action of the participant, researcher, or staff. Examples: a rescheduled 
study visit, or failure to collect an ancillary self-report questionnaire data (e.g., quality of 
life) see Policy #57 UCI HRPP Policy and Procedure Glossary 
(https://www.research.uci.edu/compliance/human-research-protections/hrp-policy-
library/hrppPolicies.htm). 
9.2. 
Standard Reporting Requirements for Adverse Events 
Adverse events, serious adverse events, deviations, violations, and unanticipated 
problems must be entered into the clinical trial management system, OnCore and/or 
Advarra EDC and must also be reported to the following entities according to the 
timelines mentioned in the chart below. Serious adverse events collection will start at the 
time patient signs consent until 30 days after the end of intervention. Adverse events will 
be collected from the time the research patient begins treatment until 30 days after the 
end of intervention. All adverse events/serious adverse events should be followed until 
resolution or stabilization, or the subject dies or withdraws consent from participation in 
the study.  Table 3 lists the various reporting schedules for AEs by event type. 
Table 3   
Standard Reporting Requirements for Adverse Events by Event Type 
Event Type 
Coordinating Center/Principal 
Investigator 
UCI IRB 
CFCCC 
DSMB 
Unanticipated 
Problem  
Within 24 hours from date the site is 
aware of the event, the site should enter 
this information into OnCore and/or 
Advarra EDC.  
Within 5 
business 
days submit 
a report 
within KR 
Protocols. 
Within 5 
days from 
date PI is 
aware of 
the event. 
This 
information 
must be 
reported 
into 
OnCore 
and/or 
Advarra 
EDC.  
AEs and SAEs 
(non-Unanticipated 
Problem)  
Please refer to section 7.5 for reporting 
timeframes on AEs and SAEs.    
N/A  
Please refer 
to section 
7.5  for 
clarification 

 
 
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Event Type 
Coordinating Center/Principal 
Investigator 
UCI IRB 
CFCCC 
DSMB 
on 
reporting 
timeframes 
for AEs 
and SAEs.  
Noncompliance  
N/A 
N/A 
Please refer 
to section 
7.5 for 
reportable 
deviations 
or 
violations. 
Serious or 
continuing 
noncompliance  
Within 24 hours via email  
Within 5 
business 
days submit 
a report in 
Kuali 
Protocols. 
Within 5 
days from 
date PI is 
aware of 
the event.  
Prospective/Planned 
Deviations  
At least 5 business days prior to the 
event via email  
At least 48 
hours prior 
to date the 
request is 
needed by. 
Submit a  
Prospective 
Deviation 
Request 
within Kuali 
Protocols. 
At the time 
of progress 
review as 
aggregate 
reports  
 
Adverse Event/Serious Adverse Events  
Event Type  
Reporting Timeframe 
Serious Adverse Events (all attributions) that meet all of the 
following criteria: 
▪ Unexpected 
▪ Grades 3-5 
▪ Occurring during treatment or within 30 days of the 
end of treatment* 
5 business days from date the PI 
is aware of the event 
Adverse Events that meet all of the following criteria: 
▪ Unexpected 
▪ Study related (possibly, probably, or definitely) 
▪ Grades 3-4 
▪ Occurring during treatment or within 30 days of the 
end of treatment* 
5 business days from date the PI 
is aware of the event 
All other Adverse Events and Serious Adverse Events should 
be reported as noted in the ‘Recording of Events’ section 
Prior to each scheduled progress 
review 

 
 
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* Investigators are not obligated to actively seek information regarding the occurrence of new AEs 
or SAEs beginning after the 30-day post-treatment period. However, if the investigator learns of 
such an event and that event is deemed relevant to the study, he/she should promptly document and 
report the event. 
 
Deviations/Violations 
Event Type  
Reporting Timeframe 
Violations as defined above (e.g. wrong dosage of drug 
administered, safety procedures not being conducted at 
specific time points) 
5 business days from the date the 
PI is aware of the event 
Deviations as defined above, including: 
▪ Planned deviations (e.g. rescheduling a visit that will 
be out of window due to a holiday) 
▪ Unplanned deviations (e.g. rescheduled visit, a 
missed routine safety laboratory test for a participant 
with previously normal values) 
Prior to each scheduled progress 
review 
10. 
STATISTICAL METHODS 
10.1. 
Planned and Maximum Sample Size 
A sample size of 70 patients is feasible given the limits of the study timeline and budget 
and will allow us to characterize key patient variables. 
   
10.2. 
Data Analysis Plan 
This is a minimal risk/Exempt study, as defined in the Chao Family Comprehensive 
Cancer Center (CFCCC)  Data and Safety Monitoring Plan (DSMP), as shown in Table 4. 
Table 4   
Risk Levels as Defined in the Chao Family Comprehensive Cancer 
Center Data and Safety Monitoring Plan 
Risk Level 
Definition 
DSMB 
Monitoring 
Level 1 
High Risk - There is the prospect of direct benefit to the 
subject, trial risks are high, or there is significant uncertainty 
about the nature or likelihood of adverse events. 
 
Example: • Trials where the Principal Investigator holds the 
Investigational New Drug (IND) / Investigational Device 
Exemption (IDE). • Gene therapy, dendritic cell products 
from GMP suite, phase I/II development and phase I studies, 
first in human, etc. 
Every two months 
after 
subject 
enrollment 

 
 
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Level 2  
Medium Risk - Trials where risks are recognized as being 
greater than low risk, but are not considered high. There is a 
medium to high probability of a moderate-severity event 
occurring as a result of trial participation. 
 
Example: • FDA exempt IND/IDE trials of any phase. 
Every six months 
after 
subject 
enrollment 
Level 3  
Low Risk – Trials that are greater than minimal risk (45 CFR 
46.102 (j)). There is a moderate probability (25-50%) of the 
occurrence of a low-severity event (grade 1 and 2) that is 
completely reversible or the likelihood of serious harm 
occurring is low. 
 
Example: • Trials that may include interventions or invasive 
procedures that present low risks, reasonably commensurate 
with those expected in medical or dental practice, but do not 
fit in an IRB-expedited review category • Post-marketing 
studies (e.g. Phase IV drug/device study (as defined by FDA) 
previously determined to be low risk). 
Every 
twelve 
months 
after 
subject enrollment 
 Level 4 
Exempt – Trials that are industry-sponsored, NCTN-
sponsored, and/or trials monitored by an external DSMB. 
Also includes trials that are IRB-exempt and IRB-expedited 
protocols (determined by the IRB as minimal risk). 
 
Minimal risk means that the probability and magnitude of 
harm or discomfort anticipated in the research are not 
greater in and of themselves than those ordinarily 
encountered in daily life or during the performance of routine 
physical or psychological examinations or tests. (45 CFR 
46.102 (j))  
 
Example: • Trials that qualify under IRB expedited categories 
2-7 and category 13. • Trials that are IRB-exempt, and non-
interventional/non-therapeutic trials. 
N/A 
 
 

 
 
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10.3. 
Safety and Tolerability Analyses 
Not applicable 
10.4. 
Statistical Analyses 
We will work with the Biostatistical Shared Resource, and report proportion of LDCT 
order, receipt of LDCT, and LCS discussion using descriptive measures. We will 
compare pre-post measures of perceived risk to lung cancer, LCS benefits, barriers, and 
self-efficacy using paired t-tests or Chi-squared tests, where appropriate. Multivariable 
regression analyses will be performed adjusting for covariates. We will report rate 
concordance of EMR and self-reported smoking history. Qualitative interviews will be 
translated and transcribed verbatim, and they will be reviewed and discussed iteratively 
using a “theoretically-driven thematic analysis” approach.26  The coding sequence will be 
conducted on a line-by-line unit of analysis using the Dedoose online system.27 We will 
use deductive and inductive approaches,103,104 organizing the data according to the 
domains in the interview guide and then open code the transcripts and inductively search 
for specific patterns and themes in each domain. We will develop the codebook based on 
the domains, emergent themes, and discussion.105 Coders will independently (and then 
collectively) examine and assemble coded data to identify themes within categories and 
relationships among them. 
11. 
STUDY MANAGEMENT 
11.1. 
Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, etc.) 
must have the conflict reviewed by their own institution’s Conflict of Interest (COI) 
Committee, with documentation of this process maintained in the study file.  
11.2. 
Institutional Review Board (IRB) Approval and Informed Consent 
It is expected that the IRB will have the proper representation and function in accordance 
with federally mandated regulations.  
The Institutional Review Board (IRB) must review the protocol and the related Informed 
Consent Form (ICF) prior to study initiation and provide signed and dated documentation 
of their approval.  The IRB must also approve any protocol or ICF amendments prior to 
their implementation, again providing signed and dated proof of approval. 
In obtaining and documenting informed consent, the investigator should comply with the 
applicable regulatory requirement(s), and should adhere to Good Clinical Practice (GCP) 
and to ethical principles that have their origin in the Declaration of Helsinki. 
Before recruitment and enrollment onto this study, the patient will be given a full 
explanation of the study and will be given the opportunity to review the consent form. 
Each consent form must include all the relevant elements currently required by the FDA 

 
 
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Page 20 of 76 
Regulations and local or state regulations. Once this essential information has been 
provided to the patient and the investigator is assured that the patient understands the 
implications of participating in the study, the patient will be asked to give consent to 
participate in the study by signing an IRB-approved consent form. 
Prior to a patient’s participation in the trial, the written informed consent form should be 
signed and personally dated by the patient and by the person who conducted the informed 
consent discussion. 
11.3. 
Patient Registration Procedures 
Prior to registration, eligibility criteria must be confirmed by the PI and study team. The 
following items must be reviewed and completed prior to beginning performing any 
Screening Assessments in Cycle 1:  
1. Source documentation required to confirm eligibility which includes patient self-
reported screening survey and data from UCI Health IT Enterprise.  
2. Signed Informed Consent Forms 
11.4. 
Data Completion 
All investigator-initiated treatment trials require that adverse events, serious adverse 
events, deviations, and unanticipated problems be entered into the OnCore clinical trial 
management system and/or Advarra EDC.  All entries must be entered in OnCore and/or 
Advarra EDC within the specified time intervals from the date the Investigator becomes 
aware of the adverse event, serious adverse event, violation, deviation, or unanticipated 
problem.  Adverse events and violations/deviations and adverse events that are 
unanticipated problems that require prompt reporting to the DSMB must be entered into 
OnCore and/or Advarra EDC according to the timelines as specified. 
Data collected in this study will be entered into Advarra EDC. The Investigator is 
responsible for ensuring all entries are accurate and correct. The Investigator must 
maintain accurate source data that support Advarra and OnCore data entry. Details of 
data entry procedures for OnCore can be found in the Study Manual. 
11.5. 
Data Management and Monitoring/Auditing 
11.5.1. 
Quality Assurance 
The CFCCC Stern Center for Cancer Clinical Trials and Research Quality Assurance 
Unit will conduct monitoring and auditing activities as per the UC Irvine CFCCC Quality 
Assurance Monitoring and Auditing Plan and at the discretion of the CFCCC DSMB in 
order to ensure patient safety and data integrity oversight. By conducting internal 
monitoring and auditing, the CFCCC will ensure compliance with high quality standards 
and all applicable regulations, guidelines, and institutional policies. Trial monitoring and 
auditing may be completed remotely or on-site by the Quality Assurance Officer.  

 
 
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11.5.2. 
Data and Safety Monitoring Plan 
This is a minimal risk/Expemt study, as defined in the Chao Family Comprehensive 
Cancer Center (CFCCC) Data and Safety Monitoring Plan (DSMP) because it is a non-
therapeutic trial. 
The Principal Investigator (PI), co-investigator, clinical research coordinator, and 
statistician are responsible for monitoring of data and safety for this study. For studies 
that have stopping rules for safety and efficacy, the PI will be responsible for the 
implementation and make changes as applicable. The CFCCC Data and Safety 
Monitoring Board (DSMB) is an independent body responsible for the safety of study 
subjects as well as the data integrity of the protocol. Data and safety will be reported to 
the DSMB with submission of progress reports that include aggregated reports of adverse 
events, serious adverse events, deviations, and violations. In addition, certain adverse 
events, serious adverse events, deviations, violations, and unanticipated problems will be 
reported promptly to the DSMB for review according to Section 9.2 and Section Error! 
Reference source not found.. 
11.6. 
Adherence to the Protocol 
Except for an emergency situation in which proper care for the protection, safety, and 
well-being of the study patient requires alternative treatment, the study shall be 
conducted exactly as described in the approved protocol. 
Due to restrictions instituted during the COVID-19 pandemic, planned clinic visits may 
be performed via telemedicine at the discretion of the Principal Investigator, following 
the guidelines established in the CFCCC Standard Operating procedure “Interim Standard 
Operating Procedure: Clinical Trial Enrollment and Operations during the COVID-19 
Pandemic” (URL: \\hs.uci.edu\myshare\Cancer Center Research\COVID-
19\Research\SOPs and Guidelines).  Whenever possible, on-site clinic visits will be 
replaced by telemedicine visits between the clinic staff and on-study patients. 
Emergency Modifications may be enacted if needed to ensure the safety, and well-being 
of the study patients.  Investigators may implement a deviation from, or a change of, the 
protocol to eliminate an immediate hazard(s) to trial subjects without prior IRB approval.  
For any such emergency modification implemented, an IRB modification form must be 
completed within five (5) business days of making the change. 
All other planned deviations or violations from the protocol must have prior approval by 
the Principal Investigator and the IRB. Please refer to Section 9.1 for more information 
on how protocol deviations and violations are defined. It will also provide instructions on 
when and who to contact and obtain approval from for prospective deviations. Protocol 
deviations should also be reported to UCI IRB, UCI CFCCC Stern Center policies and 
the participating site’s IRB policies. 
11.7. 
Protocol Amendments 
Should amendments to the protocol be required, the amendments will be originated and 
documented by the Principal Investigator. It should also be noted that when an 

 
 
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amendment to the protocol substantially alters the study design or the potential risk to the 
patient, a revised consent form might be required. Both the amended protocol and the 
amended ICF must be reviewed and approved by the IRB prior to being implemented. 
11.8. 
Record Retention 
Study documentation includes all Case Report Forms, data correction forms or queries, 
source documents, Sponsor-Investigator correspondence, monitoring logs/letters, and 
regulatory documents (e.g., protocol and amendments, IRB correspondence and approval, 
signed patient consent forms). 
Source documents include all recordings of observations or notations of clinical activities 
and all reports and records necessary for the evaluation and reconstruction of the clinical 
research study. 
Government agency regulations and directives require that the study investigator must 
retain all study documentation pertaining to the conduct of a clinical trial. In the case of a 
study with a drug seeking regulatory approval and marketing, these documents shall be 
retained for at least 2 years after the last approval of marketing application in an 
International Conference on Harmonization (ICH) region. In all other cases, study 
documents should be kept on file until 10 years after the completion and final study 
report of this investigational study. 
11.9. 
Obligations of Investigators 
The Principal Investigator is responsible for the conduct of the clinical trial at the site in 
accordance with Title 21 of the Code of Federal Regulations and/or the Declaration of 
Helsinki. The Principal Investigator is responsible for personally overseeing the treatment 
of all study patients. The Principal Investigator must assure that all study site personnel, 
including sub-investigators and other study staff members, adhere to the study protocol 
and all FDA/GCP/NCI regulations and guidelines regarding clinical trials both during 
and after study completion. 
The Principal Investigator at each institution or site will be responsible for assuring that 
all the required data will be collected and entered onto the Case Report Forms. 
Periodically, monitoring visits will be conducted and the Principal Investigator will 
provide access to his/her original records to permit verification of proper entry of data. At 
the completion of the study, all case report forms will be reviewed by the Principal 
Investigator and will require his/her final signature to verify the accuracy of the data. 
12. 
REFERENCES 
1. 
World Cancer Research Fund International. Lung cancer statistcis. Available at:  
https://www.wcrf.org/cancer-trends/lung-cancer-statistics/ Accessed on Oct 20, 2022.  
2. 
Aberle DR, DeMello S, Berg CD, et al. Results of the two incidence screenings in 
the National Lung Screening Trial. N Engl J Med. Sep 5 2013;369(10):920-31. 
doi:10.1056/NEJMoa1208962 

 
 
UCI 23-107 10/02/24 
 
 
Page 23 of 76 
3. 
Bindman A. JAMA Forum: Lung cancer screening and evidence-based policy. 
JAMA. Jan 6 2015;313(1):17-8. doi:10.1001/jama.2014.16429 
4. 
Lewis JA, Petty WJ, Tooze JA, et al. Low-Dose CT Lung Cancer Screening 
Practices and Attitudes among Primary Care Providers at an Academic Medical Center. 
Cancer Epidemiol Biomarkers Prev. Apr 2015;24(4):664-70. doi:10.1158/1055-
9965.EPI-14-1241 
5. 
Liu Y, Pan IE, Tak HJ, Vlahos I, Volk R, Shih YT. Assessment of Uptake 
Appropriateness of Computed Tomography for Lung Cancer Screening According to 
Patients Meeting Eligibility Criteria of the US Preventive Services Task Force. JAMA 
Netw Open. Nov 1 2022;5(11):e2243163. doi:10.1001/jamanetworkopen.2022.43163 
6. 
Lopez-Olivo MA, Maki KG, Choi NJ, et al. Patient Adherence to Screening for 
Lung Cancer in the US: A Systematic Review and Meta-analysis. JAMA Netw Open. Nov 
2 2020;3(11):e2025102. doi:10.1001/jamanetworkopen.2020.25102 
7. 
US Preventive Services Task Force. Available at: 
https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/lung-cancer-
screening Accessed on Oct 20, 2022.  
8. 
Coughlin JM, Zang Y, Terranella S, et al. Understanding barriers to lung cancer 
screening in primary care. J Thorac Dis. May 2020;12(5):2536-2544. 
doi:10.21037/jtd.2020.03.66 
9. 
Modin HE, Fathi JT, Gilbert CR, et al. Pack-Year Cigarette Smoking History for 
Determination of Lung Cancer Screening Eligibility. Comparison of the Electronic 
Medical Record versus a Shared Decision-making Conversation. Ann Am Thorac Soc. 
Aug 2017;14(8):1320-1325. doi:10.1513/AnnalsATS.201612-984OC 
10. 
Reese TJ, Schlechter CR, Kramer H, et al. Implementing lung cancer screening in 
primary care: needs assessment and implementation strategy design. Transl Behav Med. 
Feb 16 2022;12(2):187-197. doi:10.1093/tbm/ibab115 
11. 
Sheppard RS, Beale S, Joseph J, et al. Potential barriers to lung cancer screening 
in a minority population: Assessing attitudes, beliefs, and values towards screening with 
low-dose computed tomography amongst a high-risk minority population. Journal of 
Clinical Oncology. 2021;39(28_suppl):17-17. doi:10.1200/JCO.2020.39.28_suppl.17 
12. 
Sedani AE, Davis OC, Clifton SC, Campbell JE, Chou AF. Facilitators and 
Barriers to Implementation of Lung Cancer Screening: A Framework-Driven Systematic 
Review. J Natl Cancer Inst. Nov 14 2022;114(11):1449-1467. doi:10.1093/jnci/djac154 
13. 
Ruparel M, Quaife SL, Ghimire B, et al. Impact of a Lung Cancer Screening 
Information Film on Informed Decision-making: A Randomized Trial. Ann Am Thorac 
Soc. Jun 2019;16(6):744-751. doi:10.1513/AnnalsATS.201811-841OC 
14. 
Volk RJ, Lowenstein LM, Leal VB, et al. Effect of a Patient Decision Aid on 
Lung Cancer Screening Decision-Making by Persons Who Smoke: A Randomized 
Clinical Trial. JAMA Netw Open. Jan 3 2020;3(1):e1920362. 
doi:10.1001/jamanetworkopen.2019.20362 
15. 
Raz DJ, Ismail MH, Haupt EC, et al. Improving Utilization of Lung Cancer 
Screening Through Incorporating a Video-Based Educational Tool Into Smoking 
Cessation Counseling. Clin Lung Cancer. Mar 2021;22(2):83-91. 
doi:10.1016/j.cllc.2020.12.003 

 
 
UCI 23-107 10/02/24 
 
 
Page 24 of 76 
16. 
Quaife SL, Ruparel M, Dickson JL, et al. Lung Screen Uptake Trial (LSUT): 
Randomized Controlled Clinical Trial Testing Targeted Invitation Materials. Am J Respir 
Crit Care Med. Apr 15 2020;201(8):965-975. doi:10.1164/rccm.201905-0946OC 
17. 
Percac-Lima S, Ashburner JM, Rigotti NA, et al. Patient navigation for lung 
cancer screening among current smokers in community health centers a randomized 
controlled trial. Cancer Med. Mar 2018;7(3):894-902. doi:10.1002/cam4.1297 
18. 
Fabbrini AE, Lillie SE, Partin MR, et al. Initial results of a lung cancer screening 
demonstration project: a local program evaluation. Am J Manag Care. Jun 
2018;24(6):272-277.  
19. 
Hochbaum G., Rosenstock I., Kegels S. (1952). Health belief model. Washington, 
DC: U.S. Public Health Service.  
20. 
Carpenter CJ. A meta-analysis of the effectiveness of health belief model 
variables in predicting behavior. Health Commun. Dec 2010;25(8):661-9. 
doi:10.1080/10410236.2010.521906 
21. 
Carter-Harris L, Slaven JE, 2nd, Monohan P, Rawl SM. Development and 
Psychometric Evaluation of the Lung Cancer Screening Health Belief Scales. Cancer 
Nurs. May/Jun 2017;40(3):237-244. doi:10.1097/NCC.0000000000000386 
22. 
University of Michigan. Should I screen. Available at: 
https://shouldiscreen.com/English/result/male_0.9_no_yes_40_25 Accessed on Feb 27 
2023.  
23. 
de Souza JA, Yap BJ, Hlubocky FJ, et al. The development of a financial toxicity 
patient-reported outcome in cancer: The COST measure. Cancer. Oct 15 
2014;120(20):3245-53. doi:10.1002/cncr.28814 
24. 
de Souza JA, Yap BJ, Wroblewski K, et al. Measuring financial toxicity as a 
clinically relevant patient-reported outcome: The validation of the COmprehensive Score 
for financial Toxicity (COST). Cancer. Feb 1 2017;123(3):476-484. 
doi:10.1002/cncr.30369 
25. 
Center for Medicare and Medicaid Innovation. The Accountable Health 
Communities Health-Related Social Needs Screening Tool. Available at: 
https://innovation.cms.gov/files/worksheets/ahcm-screeningtool.pdf Accessed on Feb 14, 
2022.  
26. 
Braun, V., & Clarke, C. (2006). Using thematic analysis in psychology. 
Qualitative Research in Psychology, 3, 77-101. DOI: 10.1191/1478088706qp063oa.  
27. 
web application for managing, analyzing, and presenting qualitative and mixed 
method research data. SocioCultural Research Consultants, LLC (www.dedoose.com). 
2013.  
 

 
 
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