Using Connected Health to Increase Lung Cancer Screening: Single Center Randomized Pilot Trial
Phase: NA
Conditions: Lung Cancer
Sponsor: University of Pennsylvania

 
 
 
Using Connected Health to Increase Lung Cancer Screening: 
 Single Center Randomized Pilot Trial 
 
 
Principal Investigators:  
 
 
 
 
 
 
 
 
 
 
Funding Agency: 
 
 
IRB Protocol Number:  
 
Clinical Trials Number: 
 
UPCC Protocol Number: 
 
Version Date: 
 
 
Katharine Rendle, PhD, MSW, MPH 
Assistant Professor of Family Medicine & 
Community Health 
katharine.rendle@pennmedicine.upenn.edu 
215-662-9147 
 
Anil Vachani, MD, MS 
Associate Professor of Medicine 
Anil.vachani@pennmedicine.upenn.edu 
215.573.7931 
 
Abramson Cancer Center Support Grant, 
Population Sciences Center of Excellence 
 
844390 
 
NCT04612946 
 
17520 
 
February 1, 2021 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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Protocol Summary 
 
Title 
Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
Short Title 
Increasing Lung Cancer Screening 
Co-Principal 
Investigators 
Katharine Rendle, PhD, MSW, MPH 
Anil Vachani, MD, MS 
Co-Investigators 
 
Design 
Prospective, randomized controlled trial 
Objectives 
Aim 1. To pilot test the effect and feasibility of using direct outreach and 
telemedicine referral to increase lung cancer screening (LCS) 
counseling and uptake among screening-eligible patients. 
Aim 2. To explore the moderating effects of individual and cognitive 
moderators (patient characteristics, risk factors, and psychological 
beliefs) on LCS screening intention and uptake. 
Trial Duration 
1.5 years 
Study Sites 
The University of Pennsylvania Health System 
Sample Size 
Approximately 600 patients  
Patient Eligibility 
Aged 55-77 
Had a primary care visit at UPHS within the last 24 months 
Never had a low-dose CT for lung cancer screening 
Heavy smokers (30+ pack year and current smoker or quit within 15 
years)  
Access to phone and internet 
English-speaking 
Have an assigned primary care provider at UPHS (excluding Lancaster 
General and Princeton)  
No history of lung cancer 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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Interventions 
1) 
Following enrollment, all patients will be asked to complete a brief 
baseline survey assessing demographics, smokingand LCS cancer 
beliefs, and screening intention using measures previously applied in 
other studies, and will receive $20 upon completion. 
2) 
Following completion of the baseline survey, patients will be 
randomized into one of the two treatment arms. All patients will 
receive brief information on lung cancer screening risks and benefits 
adapted from validated decision support tool. Following survey 
completion: a) Patients in the usual care arm will be provided with 
contact information for the Penn LCS Program and encouraged to 
discuss LCS with their providers and b) Patients in the intervention 
arm will be offered to be directly referred to the LCS telemedicine 
program and asked for their permission to provide their phone 
number to the Penn LCS navigator. 
3) 
All patients will be re-contacted approximately 6-8 weeks after 
enrollment to conduct a brief survey assessing decision-making, 
quality of shared decision-making and telehealth visit (if completed). 
Patients will receive an additional $10 upon final survey completion. 
Outcomes 
Primary Outcome: 
Completion of LCS counseling, defined by completion of a telemedicine 
visit, in-person counseling visit (CPT G0296), or documentation of 
counseling in EHR provider notes. 
Secondary Outcome: 
Completion of LDCT scan for LCS 
Exploratory Outcomes: 
Decisional conflict and screening preferences 
Quality of shared decision making and telehealth visit 
Referral to smoking cessation program 
Primary Analysis 
• 
Intention-to-treat (ITT) analyses using logistic regression to assess 
the overall effect of the intervention on completion of LCS 
counseling. 
Secondary Analyses • 
Baseline survey and clinical data will be used to explore potential 
predictors (demographics, belief and cognitive biases, and other 
factors) on screening intention and LCS uptake. We will fit 
multivariable regression models with intervention, moderator, and 
interaction terms to assess effect modification based on significance 
of the interaction term.  
Study Oversight 
• 
Trial oversight will be conducted by the University of Pennsylvania 
Institutional Review Board. 
• 
Safety will be monitored on an ongoing basis by the co-PIs and study 
team. 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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Table of Contents 
Principal Investigators: ............................................................................................................................ 1 
Funding Agency: ....................................................................................................................................... 1 
Protocol Summary .................................................................................................................................... 2 
1. 
Background and Rationale ....................................................................................................... 6 
2. 
Objectives ................................................................................................................................... 6 
2.1. 
Specific Aims .............................................................................................................................. 6 
2.2. 
Primary Outcome ....................................................................................................................... 6 
2.3. 
Secondary Outcome .................................................................................................................. 7 
2.4. 
Exploratory Outcomes .............................................................................................................. 7 
3. 
Study Design .............................................................................................................................. 7 
3.1. 
Overview ..................................................................................................................................... 7 
3.2. 
Study Setting .............................................................................................................................. 7 
3.3. 
Schema ........................................................................................................................................ 7 
3.4. 
Accrual and Duration ................................................................................................................ 8 
3.5. 
Study Timeline ........................................................................................................................... 8 
3.6. 
Inclusion Criteria ........................................................................................................................ 8 
3.7. 
Participant Remuneration ......................................................................................................... 8 
4. 
Randomization ........................................................................................................................... 8 
4.1. 
Groups ......................................................................................................................................... 9 
4.2. 
Assignment ................................................................................................................................. 9 
5. 
Study Procedures ...................................................................................................................... 9 
5.1. 
Eligibility Screening: Penn Chart Review .............................................................................. 9 
5.2. 
Recruitment ................................................................................................................................ 9 
5.3. 
Waivers of Informed Consent and HIPAA Authorization ................................................... 10 
5.4. 
Blinding ..................................................................................................................................... 10 
5.5. 
Allocation .................................................................................................................................. 10 
5.6. 
Baseline Survey ....................................................................................................................... 11 
5.7. 
Intervention Assignment ........................................................................................................ 11 
5.8. 
Telemedicine LCS Counseling Visits ................................................................................... 11 
5.9. 
Post-Intervention Surveys ...................................................................................................... 11 
6. 
Data Management .................................................................................................................... 11 
6.1. 
Data Collection ......................................................................................................................... 11 
6.2. 
Data Management .................................................................................................................... 11 
6.3. 
Study and Data Monitoring .................................................................................................... 12 
6.4. 
Risks .......................................................................................................................................... 12 
6.5. 
Benefits ..................................................................................................................................... 12 
6.6. 
Risk-Benefit Ratio .................................................................................................................... 12 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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7. 
Analysis ..................................................................................................................................... 12 
7.1. 
Primary Endpoint ..................................................................................................................... 12 
7.2. 
Sample Size and Statistical Power Calculations ................................................................ 12 
7.3. 
Statistical Methods .................................................................................................................. 12 
8. 
Study Monitoring and Safety ................................................................................................. 13 
8.1. 
Investigative Team ................................................................................................................... 13 
8.2. 
Regulatory Approvals ............................................................................................................. 13 
8.3. 
Safety and Adverse Event Monitoring .................................................................................. 13 
9. 
References ................................................................................................................................ 16 
10. 
Appendices ............................................................................................................................... 17 
Appendix A: Patient recruitment letter/email ..................................................................................... 17 
Appendix B: Eligibility screener .................................................................. Error! Bookmark not defined. 
Appendix C: Consent statement .................................................................. Error! Bookmark not defined. 
Appendix D: Surveys ..................................................................................... Error! Bookmark not defined. 
Appendix E: Lung Cancer Screening Decision Aid .................................. Error! Bookmark not defined. 
 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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1. 
Background and Rationale  
 
Recommendations for annual lung cancer screening (LCS) are largely based on the results of the 
National Lung Screening Trial (NLST) that found a 20% reduction in lung-cancer specific mortality with 
annual low-dose computed tomography (LDCT) in comparison to chest radiography (1-2). In addition to 
potential benefits, substantial harms are linked to LCS including high rates of false positives, radiation 
exposure, and surgical complications (3). Based on this evidence, in 2013, the United States 
Preventive Services Task Force (USPSTF) provided a Grade “B” recommendation for annual LCS for 
asymptomatic adults aged 55-80 who are or have been heavy smokers (≥30 pack-years of smoking 
and quit-date < 15 years ago), and are able to undergo surgery (4). In 2015, The Centers for Medicare 
and Medicaid Services (CMS) issued national coverage for LCS requiring that LCS counseling, which 
must include shared decision-making and tobacco cessation counseling, occur prior to LCS (5). CMS 
also provides reimbursement for LCS counseling to further support providers to engage in meaningful, 
collaborative conversations about LCS with patients (6, 7). Despite widespread support, uptake and 
implementation of LCS across the United States has been low (estimated 3-5% screening-eligible 
population screened) (8). Locally, since the onset of the Penn Medicine LCS Program in 2014, over 
3,500 individual patients have received LCS; however, documentation and reimbursement of LCS 
counseling (under CPT G0297) is very low.  
 
Challenges of implementing LCS include substantial barriers to identifying screening-eligible patients, 
supporting high-quality decision-making, and remaining uncertainties regarding risks and benefits 
(9,10). For other types of cancer screening, insights from behavioral economics have been applied to 
understand how cognitive biases impact screening uptake (11-13). Yet for LCS, there is limited to no 
evidence on how these biases effect screening behaviors (14). Given the complexities of LCS, in which 
the benefits do not clearly outweigh the harms, understanding how these biases impact screening can 
help inform development of intervention strategies that both support informed decision-making and 
increase uptake among eligible patients. Leveraging the Penn LCS Program, and existing LCS 
database developed within our Penn Population Center of Excellence in Precision Lung Cancer 
Screening Project, we will combine insights from behavioral economics and connected health strategies 
to pilot test connected health approaches including telemedicine visits to improve frequency and quality 
of LCS counseling, and to explore cognitive moderators of LCS screening intention and uptake. 
 
Results from this study will be used to develop tailored outreach and identify effective strategies for 
expanding our pilot study. We will seek R01-level funding to assess how proposed strategies and 
outreach impacts screening uptake across diverse populations. The long-term goal is to decrease lung 
cancer burden by increasing utilization of LCS and providing clinicians and patients with effective 
strategies to deliver high-quality, patient-centered care. This study will also advance scientific 
understanding of the mechanisms that drive or hinder health behavior in the context of cancer 
prevention. 
 
2. 
Objectives 
 
2.1. 
Specific Aims 
The specific aims of this single-center pilot randomized trial are: 
1. 
Pilot test the effect and feasibility of using direct outreach and telemedicine referral to 
increase LCS counseling and LCS uptake among screening-eligible patients. 
2. 
Explore the moderating effects of individual and cognitive moderators (patient 
characteristics, risk factors, and psychological beliefs) on screening intention and uptake. 
 
2.2. 
Primary Outcome 
The primary outcome measure is completion of LCS counseling, defined by completion of a 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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telemedicine visit, in-person counseling visit (CPT G0296), or documentation of counseling in EHR 
provider notes. 
 
2.3. 
Secondary Outcome 
The secondary outcome is completion of LDCT scan for LCS.  
 
2.4. 
Exploratory Outcomes 
Exploratory outcomes include quality of decision making and telehealth visits (evaluated by patient 
survey) and referral to smoking cessation program (evaluated by EMR data). 
 
3. 
Study Design 
 
3.1. 
Overview 
This study will consist of two primary aims designed to help advance quality and utilization of LCS 
across our patient population. For Aim 1, we will first use routinely-collected medical record data to 
identify screening-eligible adults for LCS. All patients who meet the study population criteria will be 
invited to participate, but only those who confirm screening eligibility will be eligible to enroll. Patients 
who confirm eligibility and agree to participate will be randomized into two study arms: 1) usual care or 
2) telemedicine LCS counseling referral. For Aim 2, each arm will first complete a baseline survey to 
explore how cognitive biases impact screening intention and uptake. Patients in both arms will also 
receive brief information on lung cancer screening using the validated AHRQ LCS decision tool, and 
asked to report screening knowledge and preferences before and after exposure to the information. All 
interventions will be administered using a secure, web-based platform (REDCap). 
 
3.2. 
Study Setting 
We will test the interventions among patients who meet LCS and study criteria in the outpatient setting 
within the University of Pennsylvania Health System (UPHS). We will not include patients who are 
receiving primary care at Princeton Health or Lancaster General. 
 
3.3. 
Schema 
This is a single center 2-arm prospective randomized controlled trial. Patients who meet eligibility and 
complete baseline survey will be randomized (1:1) to either usual care or treatment arm. 
 
Figure 1. Study Schema 
 
 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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3.4. 
Accrual and Duration 
To ensure our study is aligned with workflows of the Penn LCS Program, we will invite 
potentially eligible adults in randomly sampled, sequential batches (approximately four batches 
of 1,500 each for a total of 6,000 invited patients). Based on previous pragmatic trials (15), we 
anticipate that approximately 20% of these patients will respond to the invitation. Of these 
estimated 1,200 adults, we anticipate that 50% will meet screening criteria and will enroll into 
the study, resulting in an estimated sample size of 600. After each batch, we will assess and 
adapt as needed to reach the sample size and to align with clinical capacity. 
 
3.5. 
Study Timeline 
 
Project Timeline 
2020 
2021 
2022 
  
 
N D 
J 
F 
M A 
M 
J 
J 
A S O N 
D 
J 
F 
Study Preparation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Finalize study materials 
• 
• 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Refine telehealth workflow 
• 
• 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRB & staff training 
• 
• 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Trial Activities 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Invite & Enroll  
 
 
 
B1 B1 
 
B2 B2 
 B3 B3 
 
B4 B4 
 
 
 
LCS Counseling Visits 
 
 
 
 B1 B1 B1 B2 B2 B2 B2 B3 B3 B4 B4 B4 
 
Rapid Assessment 
 
 
 
 
 
B2 
 
 
B3  
 
B4 
 
 
 
 
 
Post-Survey Administration 
 
 
 
 
 
B1 B1 
 
B2 B2 
 
B3 B3 
 
B4 B4 
 
Data Ascertainment & Analysis  
 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
 
3.6. 
Inclusion Criteria 
All of the following patient inclusion criteria must be met: 
1) 
Aged 55-77 
2) 
Had a primary care visit at UPHS within the last 24 months 
3) 
No history of lung cancer 
4) 
Heavy smokers (30+ pack year and current smoker or quit within 15 years)  
5) 
Access to phone and internet 
6) 
English-speaking 
7) 
Have an assigned primary care provider at UPHS (excluding Lancaster General and 
Princeton)  
8) 
Never received LCS at Penn Medicine 
 
3.7. 
Participant Remuneration 
All enrolled patients will be asked to complete a brief baseline survey and will receive $20 upon 
completion of the baseline survey. Additionally, all patients will be re-contacted approximately 4-
8 weeks after enrollment to conduct a brief post-intervention survey. Patients with a scheduled 
telehealth visit (treatment arm) will be contacted within 1 week of completed appointment if the 
scheduled visit is longer than 8 weeks from enrollment. Patients who complete this post-
intervention survey will receive an additional $10 upon post-trial survey completion. 
 
Patients will receive payments through issuance of GreenPhire ClinCards that will be mailed to 
participants within 10 days of enrollment and completion of baseline survey. These ClinCards 
can be used in the same manner as a credit card. ClinCards can be re-loaded remotely with 
additional funds by study team members after completion of study activities. 
 
4. 
Randomization 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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4.1. 
Groups 
We plan to compare the effectiveness of two care arms, as follows: 
 
Arm 1: Usual care 
Patients in the usual care arm will be provided with contact information for the Penn LCS 
Program and encouraged to discuss LCS with their providers. 
 
Arm 2: Intervention 
Patients in the intervention arm will be invited to complete a telemedicine LCS counseling visit 
and asked for permission to be referred (name and phone number) to the LCS navigator at 
Penn Medicine to schedule the visit. 
 
4.2. 
Assignment 
Participants will be randomized individually to 1 of the 2 arms using REDCap randomization 
module (1:1 stratified by study batch). Patients will be randomized at the point of survey 
invitation due to the structure of REDCap randomization module and the study design. 
 
5. 
Study Procedures 
 
5.1. 
Eligibility Screening: Penn Chart Review 
In order to assess potential eligibility, we will abstract the following variables from Penn Chart 
and/or Clarity: 
• 
Name  
• 
Address  
• 
Email 
• 
Birth date  
• 
Prior lung cancer screening 
• 
Smoking history (social history) 
• 
Medical and family history (including cancer diagnoses and comorbidities) 
• 
Phone number  
• 
Medical record number  
 
Patients who meet the following criteria will be invited to participate: a) aged 55-77; b) had a 
primary care or pulmonary visit at UPHS within the last 24 months (2019-2021); c) have never 
had a LDCT scan for lung cancer; d) are listed as current smoker within the medical record; e) 
English-speaking; f) have never been diagnosed with lung cancer; and g) have an assigned 
UPHS primary care provider listed in the medical record. All patients who meet eligibility 
screening criteria will be invited via email or mailed letter for study involvement. However, only 
patients who confirm additional eligibility for lung cancer screening based on US Preventive 
Services Task Force recommendations will be eligible for study enrollment assessed 
electronically prior to administration of baseline survey (Appendix B). 
 
5.2. 
Recruitment 
We will send electronic invitations and/or mail paper letters to all UPHS patients who meet the 
initial eligibility screening (Appendix A). Patients with an email listed in the medical record or 
with an active patient portal will be send the study invitation via email. Up to two reminder 
emails will be sent to patients who do not respond. Patients without an active email or active 
patient portal account will be mailed the invitation via letter. The invitation letter will indicate that 
study eligibility will be confirmed at the time of enrollment and provide brief details about the 
study.  

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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To ensure our study is aligned with workflows of the Penn LCS Program, we will invite 
potentially eligible adults in randomly sampled, sequential batches (approximately four batches 
of 1,500 each for a total of 6,000 invited patients). Based on previous pragmatic trials (15), we 
anticipate that approximately 20% of these patients will respond to the invitation. Of these 
estimated 1,200 adults, we anticipate that 50% will meet lung cancer screening criteria and will 
enroll into the study, resulting in an estimated sample size of 600. After each batch, we will 
assess and adapt as needed to reach the sample size and to align with clinical capacity. 
 
5.3. 
Waivers of Informed Consent and HIPAA Authorization 
Consent Process: 
Following confirmation of study eligibility within REDCap (Appendix B), participants will be given 
consent information prior to study commencement. Consent information will lay out the potential 
benefits and risk of participating in the study. Consent information will also clearly state that 
participation is completely voluntary. 
 
Waiver of Written Consent: 
This study involves no more than minimal risk to subjects. Lung cancer screening is 
recommended for eligible adults by the USPSTF, and LCS counseling is required for CMS 
reimbursement. Under the Affordable Care Act, LCS is provided without co-pay and is covered 
by insurance. Additionally, study questionnaires and materials present no more than minimal 
risk of harm and involve no procedure for which written consent is normally required. Consent 
information will be available to all participants for review prior to enrollment and their completion 
of study tasks indicates their ongoing consent (Appendix C). Patients will be instructed to 
document agreement to participate via REDCap before moving to the baseline survey but not 
required to sign their name. 
 
Waiver of HIPAA authorization: 
For purposes of recruitment and linkage of survey data to EMR data (primary outcomes), we are 
requesting a waiver of HIPAA authorization. This clinical trial meets the three criteria for a 
waiver of HIPAA authorization in accordance with the provisions for using protected health 
information (PHI) set forth in 45 CFR 46, § 164.512 (i) as follows: (1) the researchers require 
access to protected health information (PHI) in order to conduct the research, (2) The research 
cannot be practicably conducted without the waiver, and (3) the use or disclosure of PHI poses 
no more than minimal risk to participants. A request for Waiver of HIPAA form has been 
included in this protocol application. 
 
5.4. 
Blinding 
 
The primary analyst will be blinded to the randomization assignment. Drs. Rendle and Vachani 
(PIs) and the research coordinator will be unblended to facilitate referral to the LCS program. 
The research coordinator will record the randomization assignments on a master list and enter 
into REDCap using the randomization module. Assignments will be maintained by the research 
coordinator on a password protected computer in a locked office. The blind may be broken in 
the case of an emergency.  
 
5.5. 
Allocation 
Participants will be randomized in the REDCap platform to one of the two study arms, as 
described in §4.1. Patients are considered assigned to the Intention-to-Treat analyses upon 
confirmation of eligibility and enrollment in the study. 
 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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5.6. 
Baseline Survey 
Following enrollment, all patients will be asked to complete a brief baseline survey (See 
Appendix D) accessible through REDCap, assessing demographics, lung cancer screening 
attitudes and beliefs, decisional conflict and satisfaction, smoking beliefs, and screening 
intention using measures previously applied in other studies (16-19).  
 
5.7. 
Intervention Assignment 
Following consent, patients will be randomized into one of the two treatment arms. Participants 
will subsequently receive follow-up information specific to their randomization arm. Participants 
in both arms will receive brief information within REDCap describing the benefits and harms of 
LCS using information from a validated decision tool developed by AHRQ 
(https://effectivehealthcare.ahrq.gov/decision-aids/lung-cancer-screening/patient.html). Patients 
in the usual care arm will then be provided with contact information for the Penn LCS Program, 
and encouraged to discuss LCS with their providers. Patients in the intervention arm will be 
invited to complete a telemedicine LCS counseling visit, and asked for permission to be referred 
directly to the LCS navigator in order to help schedule an appointment. They will also be given 
the option to directly contact the LCS navigator to schedule a telehealth appointment. For those 
patients in the treatment arm who agree to be referred, the research team will provide their 
name and phone number to the LCS navigator and s/he will contact the patients directly. 
 
5.8. 
Telemedicine LCS Counseling Visits 
Telemedicine counseling visits will be conducted using established clinical procedures for virtual 
or telephone visits at Penn Medicine and as recommended by the American College of 
Radiology for LCS. In accordance with reimbursement policies for lung cancer screening, these 
visits will be conducted by a physician or nurse practitioner within the Lung Cancer Screening 
Program at Penn Medicine. Counseling visits are covered without co-pay as standalone visits 
according to USPSTF guidelines and costs will not be covered by the study. LCS is an 
evidence-based practice and considered standard of care for those who are eligible and desire 
to be screened. Clinicians and patients retain full control regarding decisions to complete (or 
not) LCS counseling or LDCT. 
 
5.9. 
Post-Intervention Surveys 
All patients will be re-contacted approximately 6-8 weeks after enrollment to conduct a brief 
survey assessing quality of shared decision-making (if completed LCS counseling) (21), and 
LCS decision-making (16-19). Those who complete a telehealth visit will also be asked to 
evaluate their telehealth experience (20). 
 
 
6. 
Data Management 
 
6.1. 
Data Collection 
All research data will be captured electronically via the EHR and REDCap. UPHS uses EPIC as 
its EHR platform. We will use REDCap for conducting the baseline and post-intervention 
surveys. We will extract clinical data directly from Epic including data on lung cancer screening 
counseling and uptake following enrollment, progress notes discussing LCS, and other data 
pertinent (e.g. patient and provider characteristics) to measuring primary outcomes. 
 
6.2. 
Data Management 
This study is staffed by a research support team that includes a data manager and statistical 
analyst who will have direct access to data submitted by patients. Additional study staff (project 
manager, research coordinator, investigators) will have access to patients’ contact information 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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in order to coordinate study activities. Access to all study data will be limited to specifically 
designated researchers.  
 
To link the survey data with the EHR data (to evaluate receipt of LDCT or LCS by primary care 
provider), we will send individualized links or access codes to each participants. REDCap is a 
secure survey and authorized to collect protected health information. For distribution of research 
incentives, patients will be asked to provide mailing address information.  
 
6.3. 
Study and Data Monitoring 
The co-Principal Investigators will monitor this study with the research team on a bi-weekly 
basis. They will review the study progress through regular electronic and in person 
communications. 
 
6.4. 
Risks 
The risks associated with this study are no more than minimal. There is the potential risk of 
breach of confidentiality. We will minimize this risk by using de-identified information whenever 
possible and by maintaining all identifiable information on a secure drive and/or in a HIPAA-
compliant system (e.g. REDCap).  Other risks include possible discomfort in disclosing 
information on screening knowledge, beliefs or practices. To minimize any discomfort with 
discussing this information, participants are free to skip any survey question. 
 
6.5. 
Benefits  
Participants may indirectly benefit from the study through improved awareness regarding lung 
cancer screening and by learning of their potential eligibility for lung cancer screening. For the 
health of society, the benefits of the study are substantial and include potential increase in the 
uptake of routine lung cancer screening, and increased knowledge of the cancer screening 
options and recommended screening intervals.  
 
6.6. 
Risk-Benefit Ratio 
Given the limited risk associated with participation in surveys, we anticipate that the benefits of 
this study will far outweigh the risks involved. 
 
7. 
Analysis 
 
7.1. 
Primary Endpoint 
The primary endpoint is completion of LCS counseling, defined by completion of a telemedicine 
visit, in person counseling visit (CPT G0296), or documentation of LCS counseling in EHR 
provider notes. Secondary endpoints include completion of LDCT for LCS, reach (defined as 
proportion of patients who engage with the direct outcome divided by those who are invited to 
engage with the outreach), and referral or completion of tobacco cessation treatment. 
 
7.2. 
Sample Size and Statistical Power Calculations 
With a sample size of 600 patients across the two arms, the study be powered (1-β=80%, Two-
sided α=0.05) to detect a minimum difference of 5.9- 11.4% in the primary outcome (LCS 
counseling) between the study arms, depending on completion rate (10-90%) of in controls. 
 
7.3. 
Statistical Methods 
Primary Analysis: 
Intention-to-treat (ITT) analyses using logistic regression to assess the overall effect of the 
intervention on completion of LCS counseling among those who enroll. 
 

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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Secondary Analysis: 
Baseline survey and clinical data will be used to explore potential predictors (demographics, 
cognitive biases, and other factors) on screening intention and LDCT uptake. We will also 
explore potential differences by patient groups based on age, race, and sex. We will fit 
multivariable regression models with intervention, moderator, and interaction terms to assess 
effect modification based on significance of the interaction term. These analyses are 
exploratory.  
 
8. 
Study Monitoring and Safety 
   
 
8.1. 
Investigative Team 
The study team is led by co-Principal Investigators, Drs. Katharine Rendle and Anil Vachani.  
 
Dr. Rendle is an interdisciplinary behavioral scientist with expertise in healthcare delivery 
research, mixed-methods, observational data analysis and cancer prevention. Her work has 
focused primarily on cancer care delivery, cancer screening across organ types, shared 
decision-making, and patient-reported outcomes. As the co-PI, Dr. Rendle will be directly 
responsible for the design, execution, analysis, and reporting of all research activities and 
management. 
 
Dr. Vachani is a pulmonary physician scientist with clinical and research interests in thoracic 
oncology and lung cancer screening. He is the Director of the Lung Nodule Program and is Co-
Director of the Penn Lung Cancer Screening Program. As a Co-I and clinical partner, Dr. 
Vachani will oversee all aspects of the study and help to align study with clinical workflows and 
capacity. 
 
All study investigators and staff at Penn have completed the online training program, 
Collaborative Institutional Training Initiative (CITI), and will maintain active certifications 
throughout the study. Penn team members are further required to maintain HIPAA certification 
and Good Clinical Practice certification. In aggregate, these materials provide systematic 
training in the fundamental issues underlying the responsible conduct of research. 
 
8.2. 
Regulatory Approvals 
The University of Pennsylvania IRB will serve as the IRB of record for this trial. The study has a 
dedicated project manager who will ensure that the most current version of the study protocol 
and supplementary materials are added into Penn’s Human Subjects Electronic Research 
Application (HS-ERA) system. The project manager will additionally be responsible for 
submitting protocol-wide modifications and for reporting any deviations, exceptions, and 
reportable events within required timeframes to the co-PIs and IRB. A formal closure request 
will be submitted once study activity has been completed and there is no further access to 
identifiable subject data for research purposes.  
 
8.3. 
Safety and Adverse Event Monitoring 
 
Definitions 
Adverse Event: An adverse event (AE) is any symptom, sign, illness or experience that 
develops or worsens in severity during the course of the study. Intercurrent illnesses or injuries 
should be regarded as adverse events.  Abnormal results of diagnostic procedures are 
considered to be adverse events if the abnormality:  
• 
results in study withdrawal  

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
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• 
is associated with a serious adverse event  
• 
is associated with clinical signs or symptoms  
• 
leads to additional treatment or to further diagnostic tests  
• 
is considered by the investigator to be of clinical significance  
  
Serious Adverse Event  
Adverse events are classified as serious or non-serious.  A serious adverse event is 
any AE that is:   
• 
fatal  
• 
life-threatening  
• 
requires or prolongs hospital stay  
• 
results in persistent or significant disability or incapacity  
• 
a congenital anomaly or birth defect  
• 
an important medical event  
  
Important medical events are those that may not be immediately life threatening, but are clearly 
of major clinical significance. They may jeopardize the subject, and may require intervention to 
prevent one of the other serious outcomes noted above. For example, drug overdose or abuse, 
a seizure that did not result in in-patient hospitalization, or intensive treatment of bronchospasm 
in an emergency department would typically be considered serious.  All adverse events that do 
not meet any of the criteria for serious should be regarded as non-serious adverse events.   
  
Recording of Adverse Events  
At each contact with the subject, the investigator will seek information on adverse events by 
specific questioning.  Information on all adverse events will be recorded immediately in the 
source document, and also in the appropriate adverse event module of the case report form 
(CRF).  All clearly related signs, symptoms, and abnormal diagnostic procedures results 
should recorded in the source document, though should be grouped under one diagnosis.  
  
All adverse events occurring during the study period will be recorded.  The clinical course of 
each event will be followed until resolution, stabilization, or until it has been determined that the 
study intervention or participation is not the cause.  Serious adverse events that are still ongoing 
at the end of the study period will be followed up to determine the final outcome.  Any serious 
adverse event that occurs after the study period and is considered to be possibly related to the 
study intervention or study participation will be recorded and reported immediately.  
  
Relationship of AE to Study   
The relationship of each adverse event to the study procedures will be characterized by the PIs 
and will be classified as either definitely related, probably related, unlikely to be related, or 
unrelated.  
  
Reporting of Adverse Events, Adverse Device Effects and Unanticipated Problems  
The PI and study team will conform to the adverse event reporting timelines, formats and 
requirements of the IRB and DSMC.  If a narrative report is submitted, the following 
information will be provided to all reviewing entities:  
• 
Study identifier  
• 
Study Center  
• 
Subject number  
• 
A description of the event  
• 
Date of onset  
• 
Current status  
• 
Whether study intervention was discontinued  
• 
The reason why the event is classified as 
serious  
• 
Investigator assessment of the association 
between the event and study intervention  

Using Connected Health to Increase Lung Cancer Screening (CH-LCS) 
15 
 
 
  
Any other events will be recorded and reported in accordance with institutional and federal 
policies.  
  
Follow-up report  
If an SAE has not resolved at the time of the initial report and new information arises that 
changes the investigator’s assessment of the event, a follow-up report including all relevant new 
or reassessed information will be submitted to the IRB and DSMC. The PI will be responsible for 
ensuring that all SAE are followed until either resolved or stable.   
  
Investigator Reporting: Notifying the Penn IRB   
The investigator will submit reports to the IRB within ten working days (with one exception) of 
events that meet the definition of an unanticipated problem involving risks to subjects or 
others.  Exception: If the adverse event involved a death and indicates that participants or 
others are at increased risk of harm, the investigator will submit a report to the IRB within three 
days.  
  
The investigator will submit reports to the IRB and DSMC in accordance to their current 
reporting requirements:  
• 
All Grade 3 or higher events (AE or SAE) within 10 business days of knowledge.  
• 
All unexpected deaths within 48 hours of knowledge.  
• 
All others deaths within 30 days of knowledge. Deaths of subjects greater than 90 days 
from the 
last study treatment/intervention are not reportable unless a longer time frame is specified in the 
protocol. 
 
Stopping Rules: n/a  
   
Data and Safety Monitoring Plan  
Safety will be monitored on an ongoing basis by the PIs and the study team. The PI or designee 
will review the study charts to evaluate events at each subject interaction to ensure the grade, 
relationship to the study procedure, expectedness and the course of action for each subject is 
documented. The PI or Sub-investigator is ultimately responsible for assigning grade and 
attribution.   
 
 

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16 
 
 
 
 
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10. 
Appendices