Promoting Smoking Cessation in Lung Cancer Screening Through Proactive Treatment
Phase: NA
Conditions: Smoking Reduction, Tobacco Use, Tobacco Smoking, Tomography, Lung Diseases, Lung Neoplasms
Sponsor: VA Office of Research and Development

 
 
 
 
 
 
 
 
 
Promoting Smoking Cessation in Lung Cancer Screening through Proactive Treatment 
(PROACT) 
Funding Agency: HSR&D 
Principal Investigator: Steven B. Zeliadt 
9/29/21 
 
 

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Abstract 
VA Medical Centers are beginning to offer eligible Veterans lung cancer screening following 
national recommendations including the US Preventive Services Task Force’s “B” 
recommendation for annual screening. 1  Preliminary evidence from the VA Lung Cancer 
Screening Demonstration Project suggests that 900,000 Veterans will be eligible for screening 
and over half will be current smokers with a long history of smoking. 2 3  It is critical that offering 
screening to current smokers reinforces the importance of cessation and does not reduce 
motivation to quit. 4, 5  Providing cessation support as part of lung cancer screening is mandated 
for reimbursement by Centers of Medicare and Medicaid Services, and is recognized by VA as 
a critical component of delivering high quality care. Integrating cessation counseling 
challenging, in part because of limited time and clinic resources, but also because of many 
current smokers’ misperception that screening provides a “protective” effect. 6 In the National 
Lung Screening Trial, primary care providers offering screening adequately addressed smoking 
cessation with only 10% of current smokers. 7  
The PROACT trial will evaluate the value of providing proactive support to current smokers as 
part of participating in lung cancer screening including behavioral and pharmacotherapy 
support. Cessation support guidelines have emphasized the importance of providing both 
behavioral and pharmacotherapy support at every opportunity. Cessation support will be 
integrated with the reporting of screening results. In our pilot study of the proactive telephone 
counseling component of the proposed intervention, we increased participation in behavioral 
cessation treatment to 44% among participants who received proactive counseling from 11% 
among control patients who did not receive proactive counseling, and quit rates more than 
doubled to 19% in the proactive group from 7% in the control group. 8 Screening patients often 
report being motivated to participate in screening to find out how much smoking has harmed 
them. 6 The proactive care activities are designed to convert this level of patient engagement 
into an opportunity to encourage cessation. Integrating the proactive cessation treatment 
approach into the screening process ensures that all screening patients are offered cessation 
support by default, and removes the precondition of providing pharmacotherapy support only to 
patients who agree to set a specific quit date. Over 14 trials 9 have shown that providing 
pharmacotherapy support to all current smokers using an opt-out approach (rather than 
requiring patients to request treatment) significantly increases quit rates, and providers have 
begun adopting opt-out approaches to offering tobacco treatment. 
The PROACT trial is a pragmatic randomized trial targeting the care of current smokers who are 
participating in lung cancer screening at VA Providence (Rhode Island) and VA NY Harbor. 
Primary care providers at VA Providence and VA NY Harbor will be randomized to provide their 
patients either proactive cessation support or unstructured cessation support (as usually 
provided during lung cancer screening). The proactive cessation support will ensure that 
patients receive more elements of care that are currently available in VA but are not always 
systematically provided, specifically including telephone counseling from VA Quitline counselors 
and pharmacotherapy support recommended by VA’s national formulary. The primary endpoint 
is biochemically confirmed 7-day abstinence 12 months after screening. Based on prior trials 
and our pilot data, the trial is powered to detect an improvement in quit rates from 9% with 5A’s 
counseling and unstructured treatment to at least 18% with proactive treatment. 

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Figure 1: Study Overview 
  

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List of Abbreviations 
Provide a list of all abbreviations used in the protocol and their associated meanings. 
5As – Guidelines for recommended approach to providing counseling about tobacco use: Ask 
about tobacco use at every visit, Advise all tobacco users to quit, Assess readiness to quit, 
Assist tobacco users with a quit plan, Arrange follow-up visits 
 
BAA - Business Associate Agreement 
CDW - Corporate Data Warehouse 
CIS - Cancer Information Services 
COIN - Center of Innovation 
CT- Computerized tomography 
FDA - Federal Drug Administration 
FHCRC - Fred Hutchinson Cancer Research Center 
HSR&D - Health Services Research and Development 
ISO - Information Security Officer 
JAMA - Journal of the American Medical Association 
JLV – Joint Legacy Viewer 
LCS – Lung cancer screening 
LSI - Local Site Investigator 
Lung-RADS - Lung Imaging Reporting and Data System  
MI - Motivational Interviewing 
NIH - National Institute of Health 
NRT - Nicotine Replacement Therapy 
PCP – Primary care provider 
SAE - Severe Adverse Events 
VAPSHCS - VA Puget Sound Health Care System 
VHA - Veteran Health Administration 
VINCI - VA Informatics and Computing Infrastructure 
VistAWeb – Portal accessible through CPRS, user interface for VA electronic health record 

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Contents 
Protocol Title: ................................................................................................................................ 6 
1.0 
Study Personnel ................................................................................................................. 6 
2.0 
Introduction ........................................................................................................................ 7 
3.0 
Objectives .......................................................................................................................... 8 
4.0 
Resources and Personnel .................................................................................................. 9 
5.0 
Study Procedures ............................................................................................................. 12 
5.1 Study Design ..................................................................................................................... 12 
5.2 Recruitment Methods ........................................................................................................ 18 
5.3 Informed Consent Procedures .......................................................................................... 20 
5.4 Inclusion/Exclusion Criteria ............................................................................................... 21 
5.5 Study Evaluations .............................................................................................................. 22 
5.6 Data Analysis .................................................................................................................... 23 
5.7 Withdrawal of Subjects ...................................................................................................... 23 
6.0 
Reporting .......................................................................................................................... 24 
7.0 
Privacy and Confidentiality ............................................................................................... 24 
8.0 
Communication Plan ........................................................................................................ 25 
9.0 
References ....................................................................................................................... 26 
 

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Protocol Title:  Promoting Smoking Cessation in Lung Cancer 
Screening through Proactive Treatment (PROACT) 
 
1.0 
Study Personnel 
 
 
Principal Investigator 
Steven Zeliadt, PhD MPH 
Associate Director, Seattle/Denver Center of Innovation for Veteran-Centered and  
   Value-Driven Care 
VA Puget Sound Health Care System 
Research Associate Professor, Department of Health Services, University of Washington 
 
Co-Investigators 
Linda Nici, MD 
Pulmonologist, Chief of Pulmonary and Critical Care Section  
Providence VA Medical Center, Rhode Island 
Professor of Medicine, Brown University 
 
Daniel Becker, MD, MS 
Assistant Professor of Medicine (Clinical), NYU School of Medicine, New York University 
Section Chief, Hematology and Oncology, VA-NYHHS 
VA New York Harbor Health Care System 
 
David Au, MD, MS 
Pulmonologist, Director of Seattle/Denver Center of Innovation for Veteran-Centered and 
  Value-Driven Care 
VA Puget Sound Health Care System 
Professor of Medicine, School of Medicine, University of Washington 
 
Laura Feemster, MD MS 
Pulmonologist, Associate Professor, School of Medicine, University of Washington 
VA Puget Sound Health Care System 
 
Collaborators: 
Jaimee Heffner, PhD 
Clinical Psychologist 
Assistant Member 
Fred Hutchinson Cancer Research Center 
 
2.0 
Introduction 

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Smoking remains the leading preventable cause of death and morbidity among 
Veterans. Cigarette smoking is responsible for over 440,000 deaths annually and adds $193 
billion in direct health care expenditures and productivity losses each year in the U.S. Over 
50% of ever-smokers in the U.S. population have been able to successfully stop smoking. 10 
Quit rates among Veterans are lower than the general population, which has been attributed 
to demographic and socio-economic factors including lower social support, higher levels of 
addiction to nicotine, co-occurring addictions such as alcohol addiction, military trauma and 
post-traumatic stress disorder.11,12 
 
Tobacco treatment is effective but underutilized. Connecting smokers to pharmacotherapy 
and behavioral support has been shown to increase quit rates.13 Although VA has pioneered a 
wide range of cessation services, they are not fully utilized.14,15 While VA has very high rates 
(>80%) of primary care providers following Public Health Service guidelines for addressing 
smoking cessation during clinic visits, including the 5A’s, fewer than 10% of smokers utilize 
pharmacotherapy or other smoking cessation aids.16,17 This is similar to a recent review of 
Medicaid and Medicare data, which found that only 7.6% of current smokers received a 
prescription or order for a nicotine dependence medication.18 Cessation medications have been 
firmly established as a critical component of successfully quitting.19, 20 The value of 
pharmacotherapy support may be especially important for Veterans who currently smoke 
because of their high levels of nicotine dependence. 11,23  
 
No model exists for integrating cessation counseling into lung cancer screening. The 
National Lung Screening Trial (NLST) struggled with providing smoking cessation support to its 
trial enrollees during the screening process. Primary care providers in the NLST were instructed 
to follow the 5As in addressing smoking cessation when offering screening. However, only 10% 
of current smokers received adequate support. 7 Two recent reviews have highlighted the lack of 
knowledge about how best to offer smoking cessation support in the context of lung cancer 
screening, one noting that a proactive approach may be preferred in which all smokers seeking 
lung cancer screening receive access to cessation support regardless of their reported 
motivation to set a quit date. 21 To our knowledge, no studies have investigated proactive 
cessation support or proactive telephone counseling as part of delivery of lung cancer screening 
services. The pragmatic PROACT trial will fill this knowledge gap, and the findings from the trial, 
which utilizes the national VA Quitline, will provide important guidance for how VHA can 
implement proactive smoking cessation support in the context of lung cancer screening across 
all VHAs. 
 
Rationale for including or excluding certain populations. The study targets providers who 
have ordered LCS CT scans for Veterans. No provider subjects will be excluded from the 
pragmatic trial on the basis of gender, race, age, or ethnicity. Vulnerable subject populations will 
not be targeted for inclusion, but pregnant providers will not be excluded from participating.  
 
Patients of these providers who are current smokers participating in lung cancer screening will 
be approached for participating in survey evaluation activities. No patient subjects will be 
excluded on the basis of gender, race or ethnicity. Vulnerable subject populations including 
minorities, prisoners, or institutionalized individuals will not be targeted for inclusion. The age 
criteria for lung cancer screening of 55-80 and the smoking history criteria of 30+ pack-year 
history of smoking will limit eligibility of pregnant women, and if pregnant women meet the 
eligibility criteria for screening they will not be eligible to participate in the study. No children 
(anyone under the age of 18) will be eligible to be included in the subject population. Patient 

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subjects with severe behavioral disorders (identified by ICD-10 codes as specified in IRQ) will 
be excluded. 
3.0 
Objectives 
 
Objectives. We will test the value of systematically providing evidence-based tobacco 
treatment using a pragmatic trial of providers whose patients receive lung cancer screening in 
two VA Medical Centers – New York Harbor and Providence. Currently providers are 
encouraged to ask patients about their readiness to quit and use their judgement to arrange 
treatment (5As framework: Ask, Advise, Asses, Assist, Arrange). Providers have many 
resources to support cessation, including the VA Quitline (1-855-QUIT-VET) for behavioral 
counseling support and VA formulary guidelines for smoking cessation pharmacotherapy. 
Providers will be randomized to two study arms. In one arm, Providers will not receive any 
additional guidance from the study team about how to effectively utilize available VA resource. 
This arm is labeled as the unstructured care arm.  
The study team will develop a proactive, automated structure in which all VA resources are 
combined into a template that is proactively activated by a patient’s screening results letter. This 
template will reflect pharmacy ordering instructions and other pathways activities in place at the 
study site. This will be considered proactive care. Primary care providers offering proactive 
smoking cessation care will be provided guidance to offer cessation pharmacotherapy to all 
current smokers when notifying the patient of the results of their screening test. Patients of 
providers in the proactive care arm will also uniformly receive proactive telephone outreach from 
VA Quitline counselors, which will review the screening results letter and any provided 
pharmacotherapy. Each local screening program will send a standardized letter notifying the 
patient that they will be proactively contacted by a telephone counselor. This letter will be in 
addition to any individualized letters/telephone reporting of results of their screening test by the 
patient’s provider.   
The primary aim of this trial is to: 
 
1. Conduct a pragmatic randomized trial among smokers participating in lung cancer screening 
comparing proactive smoking cessation care with unstructured care.  We will assess the 
differences between the two care approaches on 7-day smoking abstinence 12 months after 
receipt of screening. Assignment of providers to the two care arms will continue until the 
study is on track to have 540 patients responding (270 responders per arm) to the 12-month 
survey. Based on our preliminary findings in a pilot study of proactive care, and related trials 
in other populations of smokers, we hypothesize that smoking abstinence 12 months after 
screening will be twice as high (18%) in the proactive group compared to expected 
abstinence rates in the unstructured group (9%).9 
 
The secondary aims are to: 
2a. Assess whether proactive smoking cessation care impacts three psychological and two 
behavioral change processes derived from health behavior change theory, including: (a) 
motivation, (b) perceived susceptibility to the harmful effects of smoking, (c) self-efficacy for 
quitting, (d) likelihood of making a quit attempt, and (e) likelihood of utilizing 
pharmacotherapy. 

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2b. Assess acceptance of and satisfaction with the proactive care approach among providers 
referring Veterans for lung cancer screening. 
2c. Monitor the costs of implementing the proactive care approach including intervention staff 
effort, provider time, costs of telephone counseling and pharmacotherapy costs. 
 
4.0 
Resources and Personnel 
Coordinating Center. The majority of research activities, which include primarily survey 
evaluation activities and medical record review, will be conducted at the Seattle/Denver HSR&D 
Center of Innovation (COIN) in Seattle, which will serve as the study Coordinating Center. The 
Coordinating Center will identify eligible provider participants by querying the Corporate Data 
Warehouse and identifying patients who have lung cancer screening tests ordered. After 
identifying providers historically performing lung cancer screening at the two study sites, the 
Coordinating Center will send them an information sheet describing the study, including the 
randomization process and procedures for declining participation in the study, via mail, email, 
and Lync instant message.  
In collaboration with providers and lung cancer screening care providers, the Coordinating 
Center will work with local coordinators at the two study sites to structure care for the proactive 
care arm. The local coordinator will be notified by the Coordinating Center of each provider’s 
randomization assignment. Following randomization, providers assigned to the proactive arm 
will be sent an email notifying them of which arm they are assigned to and what intervention 
activities to expect going forward. They will receive a similar notification email after ordering 
their first lung cancer screening test, following the start of the study. No notifications will be sent 
to providers in the unstructured arm. Providers will remain randomized to a single study arm for 
the duration of the trial. If a new provider orders a lung cancer screening test for the first time, 
he or she will be approached similarly recognizing that the care of the patient that alerted the 
Coordinating Center to the provider’s identity may not be influenced by the study if the opt-out 
consent and randomization process cannot occur before the screening test is performed.  
Once providers have been randomized, we will monitor for prospective patients referred for 
screening. The Coordinating Center will review all prospective patients for study eligibility, 
confirming the patient is documented in the EHR as a current smoker.   
 
For providers assigned to the proactive arm, local coordinators will review prior cessation 
medication history in each patient’s chart and enter a note to the provider recommending 
providing cessation medication as patients are receiving their screening results. Local 
coordinators will follow national and local VA treatment guidelines in recommending a cessation 
medication to the provider (https://www.publichealth.va.gov 
/docs/smoking/cessationguidelinepart2_508.pdf#).  Study clinicians (Au, Feemster, Becker) will 
be available to local coordinators to answer any questions with interpreting VA treatment 
guidelines. Local coordinators will be trained by the study team to follow local protocols for 
ordering medications, such as ordering templates created by local pharmacists. The proactive 
note to the provider will provide a summary of clinical logic and confirm that the coordinator 
assessed any potential contraindications, such as unstable angina or serious arrhythmia. Local 
coordinators will also be available to providers to help facilitate all proactive care activities, 
including refill monitoring for prescribed cessation medications.  

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Once a screening result letter has been mailed, the Coordinating Center will send contact 
information for each participant in the proactive care group to the VA Quitline counselors for 
proactive telephone counseling. The study will contract with the VA Quitline, operated out of the 
Fred Hutchinson Cancer Research Center, to perform the proactive telephone counseling 
services and collect information about participation in telephone counseling sessions, including 
the number of sessions completed.  
The Coordinating Center will extract baseline demographic and clinical characteristics of 
participants from the Corporate Data Warehouse at the time of screening, including 
documenting screening results and confirming that the screening test did not identify findings 
suspicious for malignancy requiring immediate biopsy/attention. Approximately 2-4% of patients 
have such findings, and will be withdrawn from the study and will not receive any further study 
activities. 
 
At 3 months and 12 months following screening, the Coordinating Center will conduct an 
evaluation survey to collect outcome data. Telephone follow-up will be conducted by the 
Coordinating Center to increase response rate for the surveys. Additional clinical and outcome 
data will be extracted at 12 months from the Corporate Data Warehouse. 
 
All data analyses will be performed by the Coordinating Center. 
 
Study Staff Table 
Name 
Location 
Role 
PHI 
Recruiting 
Consent 
Survey 
Admin 
Data 
Analysis 
Steven Zeliadt, 
PhD MPH 
Seattle 
PI 
Yes 
No 
No 
No 
Yes 
David Au, MD 
MS 
Seattle 
Co-I 
Clinician 
Yes 
No 
No 
No 
Yes 
Laura Feemster, 
MD MS 
Seattle 
Co-I 
Clinician 
Yes 
No 
No 
No 
Yes 
Spencer Hildie 
Seattle 
Project 
Coordinator 
Yes 
Yes 
Yes 
Yes 
Yes 
Peter Rise, MS 
Seattle 
Data Analyst 
Yes 
No 
No 
No 
Yes 
Lawrence 
Swanson, BA 
Seattle 
Database 
Administrator 
Yes 
Yes 
Yes 
Yes 
Yes 
 
Data Use Agreements (DUAs). DUAs will be executed with the VA National Corporate Data 
Warehouse (CDW) repository and CAPRI/JLV for access and use of data and subject records.  
Data will be obtained electronically from the VA National Corporate Data Warehouse (CDW) 
repository, which the study team will access via the VA Informatics and Computing Infrastructure 
(VINCI) platform. Variables from the CDW will be used to identify referral for lung cancer 
screening and current smoking status at the time of screening.  Patient contact information, 
including phone number, will be accessed for proactive telephone counseling, and mailing 
address information will be used for inviting participants to complete the 3- and 12-month study 
surveys. Social security numbers will be used for research staff to look up patient medical 
records in CAPRI/JLV as well as to enter notes into CPRS. SSNs are also required by the VA 
R&D Purchasing and Fiscal Office to process checks for payments. 
 
The Coordinating Center staff will obtain CAPRI/JLV access following VHA procedures that 
serve as an agreement to adhere to conditions of electronic health records access and use 
stipulated by VA Health Information Access (HIA).  The purpose of accessing patient records is 
to confirm information identified in CDW notes about comorbidities and exclusion criteria to 

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ensure patients are appropriate to contact (i.e., no reported difficulty communicating by 
telephone. If verified, that patient would not be approached).  
 
Contracted Services. We will enter into a contract with the Seattle-based Fred Hutchinson 
Cancer Research Center’s Cancer Information Service (CIS) to provide individualized smoking 
cessation counseling to the patients in the proactive care arm of the study. This will facilitate 
careful tracking of services provided and cost estimates. The CIS is an NCI-funded national 
telephone clearinghouse of cancer information serving individuals who have questions about 
cancer prevention and treatment. They are knowledgeable, caring, and experienced at 
explaining medical information. Their services are confidential. The CIS operates both the 
general information line (1-800-4-CANCER) which helps counsel patients about diagnosis and 
treatment options, and the NCI's Smoking Quitline (1-877-44U-QUIT), which provides free 
cessation information and support to smokers who wish to quit free of charge. 
 
The CIS also contracts nationally with VHA to provide the VA Quitline (1-855-QUIT-VET) which 
is free to all Veterans. We will contract with CIS to develop a database to track utilization and 
conduct counseling calls.  They will use the database to provide information about completed 
telephone sessions, treatment fidelity, and cost of service provision. Veterans’ contact 
information will be sent by secure fax to the CIS team once they are identified as patients of 
providers randomized to the proactive care arm. The telephone counselors will make 3 attempts 
to reach each Veteran, leaving voicemails with a specific telephone number that will reach a VA 
Quitline counselor who is trained in the study counseling activities. (See National telephone 
counselor introductory script). 
 
The VA Quitline counselor will attempt to provide 2 sessions of individualized smoking cessation 
therapy, and will repeat the 3-attempt protocol to conduct the 2nd session.  A Veteran can decline 
participation in the counseling activity. (See National telephone counselor introductory script). 
 
The VA Puget Sound Healthcare System is purchasing services from Cancer Information Service 
at the Fred Hutchinson Cancer Research Center, and will enter into a Data Use Agreement to 
facilitate and allow the exchange of PHI between these two entities. The DUA will follow ORD 
policies regarding data exchange with Non-Federal Entities and will require approval by the 
Privacy Officer and ISO at VA Puget Sound, and authorities at the Fred Hutchinson Cancer 
Research Center (see https://ww.research.va.gov/resources/policies/default.cfm). 
 
The VA Quitline routinely records counseling calls for quality assurance purposes. We have 
applied for a waiver of informed consent to obtain patient data from these quality assurance 
recordings, in order to conduct a fidelity evaluation of a sample of the calls. 
 
5.0 
Study Procedures 
 
5.1 Study Design 
 
Study design. We are proposing a pragmatic cluster-randomized trial comparing usual lung 
cancer screening care to a proactive approach, which will integrate smoking cessation support 
into lung cancer screening. Providers will be randomized to one of two care groups. The 

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randomization protocol will ensure that providers with large panel sizes, and therefore high lung 
cancer screening volume, will be distributed between the two groups. The two provider care 
groups will be called proactive and unstructured. The proactive group will receive guidance 
about providing proactive cessation support that utilizes supplemental counseling from national 
counselors at the VA Quitline. The unstructured care group will not receive any additional 
support. All current primary care providers who may have patients eligible for lung cancer 
screening will be block randomized at the beginning of the study by panel size, as this is a 
surrogate for prior LCS screening volume. New primary care providers will be randomized when 
they are first hired and become eligible to order LCS at one of the study sites. Although national 
lung cancer screening recommendations highlight integrating cessation support for current 
smokers (and reimbursement of lung cancer screening by Medicare is contingent on 
documentation that cessation support was provided), there are currently no established 
methods for how cessation support should be integrated into the delivery of screening care. The 
proactive care activities are designed to reflect guidelines from the broader primary care setting 
based on decades of evidence that both behavioral and pharmacotherapy support should be 
routinely provided to patients. Additionally, the study focuses on testing a proactive care 
approach that has potential for broad dissemination nationally across VA, including centralized 
proactive telephone counseling using VA Quitline counselors and providing cessation 
pharmacotherapy in accordance with VA formulary guidelines. We will standardize study 
activities as much as possible to ensure they are provided uniformly, however, as this is a 
pragmatic trial of care as it is delivered in actual practice, providers may vary how they deliver 
the intended proactive and unstructured care components. 
At the beginning of the study, the Coordinating Center, located in Seattle, will access 
retrospective Corporate Data Warehouse (CDW) patient data to identify providers who have 
ordered lung cancer screening CTs in the past. These data will be from CDW accessed through 
VINCI and will be used to review provider lung cancer screening volume and provider’s 
historical use of cessation medications ordered at the time of lung cancer screening. 
Throughout the study, the Coordinating Center will also prospectively identify patients 
scheduled for lung cancer screening by scanning CDW twice weekly. The Coordinating Center 
will confirm the scheduled patient’s eligibility criteria, including current smoking status through 
CAPRI/JLV. A local clinical coordinator based at either of the intervention sites (NY Harbor or 
Providence, RI) will be notified when patient eligibility is confirmed and the ordering provider is 
identified. The local coordinator will work with the provider subjects at the intervention sites to 
adapt study guidance to the lung cancer screening clinical pathways in use at each of the 
intervention sites.  Once a patient’s screening results are available, the study team will confirm 
continued eligibility (e.g. no indication of a highly suspicious finding requiring biopsy).  
For patients of providers assigned to the proactive study group, the local coordinator will review 
the patient’s cessation medication history in CAPRI/JLV. If the patient is not currently being 
provided cessation support medication, the coordinator will enter a note for the provider about 
the recommended medication indicated by VA formulary guidelines.  
For those patients receiving proactive care, once the screening results are available and 
patients are confirmed to meet eligibility criteria, including not having findings requiring 
immediate follow-up (e.g. LungRADS 4 or 5), each local screening program will send a 
standardized letter notifying the patient that they will be proactively contacted by a telephone 
counselor. This letter will be in addition to any individualized letters/telephone reporting of 
results of their screening test by the patient’s provider.   

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For those patients receiving proactive care, the Coordinating Center will forward information 
about the non-suspicious screening result, s to the VA Quitline via secured fax. A VA Quitline 
counselor will attempt to provide two sessions of proactive telephone support.  
Three months after the date of the screening procedure, the Coordinating Center will invite 
patient participants to participate in an evaluation survey. A second evaluation survey will be 
sent to the patient at 12 months. Participants will be compensated $25 for each returned 
evaluation survey.  
Demographic, clinical and administrative smoking cessation information available in from the 
Corporate Data Warehouse will be extracted for all invited patients, including those who do not 
complete the evaluation surveys.  
Provider participants in the proactive arm will be sent a short evaluation survey via email. The 
survey will assess providers’ evaluation of the value of proactive care. If providers offer lung 
cancer screening to multiple patient, the survey will only be sent once per quarter. 
As a pragmatic trial, provider participants in the proactive arm will be sent periodic study status 
updates via email. These emails will include study level feedback on cessation medication 
prescription rates and reminders to continue proactively prescribing the recommended 
medications. It will also include general study updates as well as feedback by patients provided 
to the local coordinators, coordinating center and Quitline counselors that will be of interest to 
providers and help them understand how patients are responding to participating in the study.  
Cost and resource assessment. Cost and resource data will be collected as part of the study, 
including the cost of provided pharmacotherapy, additional medication fills, and cost of 
telephone counselor contact. A waiver of informed consent to collect this information on all 
study participants is requested. 
Risks associated with provider assignment to intervention. The risks associated with the 
study activities are minimal. All patient participants are current smokers, and VA and US 
Public Health Services guideline recommend clinicians provide cessation support at all clinic 
visits and as part of lung cancer screening.  
 
The difference in risks associated with behavioral counseling between the unstructured and 
proactive arms are minor.  In the unstructured arm, patients receive about cessation 
counseling by their provider and are provided with the VA Quitline’s telephone number (1-
855-QUIT-VET) as a free resource for telephone counseling. In the proactive arm, subjects 
are proactively contacted by telephone counselors to receive this same support. The 
proactive counseling calls may be associated with the following risks: 1) annoyance from 
proactive counseling outreach, or 2) increased anxiety or worry related to discussions around 
lung cancer screening results and smoking cessation with VA Quitline telephone counselors. 
We will mitigate this risk by having the VA Quitline caller remind subjects that participation in 
the proactive calls is voluntary. Notably, in the pilot study 89% of Veterans indicated they 
were completely or somewhat satisfied with the proactive telephone counseling calls, with 1 
individual reporting they were neither satisfied or dissatisfied, and 2 participants declining to 
respond. 
 
The difference in risks associated with pharmacotherapy support between the unstructured 
and proactive arms is also minimal. Although guidelines indicate all smokers should be 
offered pharmacotherapy support at every visit, this happens infrequently. A recent review 
found that only 7.6% of current smokers received a cessation pharmacotherapy order 

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following a primary care visit, 18 and fewer than 10% of smokers participating in screening in 
the NLST received such an order.17  Patients who are current smokers should be 
appropriately provided with smoking cessation support as they participate in lung cancer 
screening, although this doesn’t consistently happen. A potential risk of this study is that 
current smokers receiving care from providers in the unstructured care group who are eligible 
for behavioral counseling or pharmacologic cessation support will not receive it. Another 
potential risk is that providers in the proactive care group will perceive that the study is 
assuming responsibility for providing cessation support and the quality of support offered by 
providers will decrease. The primary difference between the study arms is encouraging 
providers assigned to proactive care to remove the precondition to providing 
pharmacotherapy that the patient set a quit date and offer pharmacotherapy to all screening 
participants who are current smokers. This is intended to result in more patients in the 
proactive care arm receiving pharmacotherapy and may be associated with 1) inappropriate 
use of cessation medications, or 2) risks associated with use of cessation medications. We 
will encourage providers to follow VHA formulary guidelines for recommending 
pharmacotherapy including assessment of contraindications, and all orders are required to be 
signed by a primary care provider associated with the patient. The local coordinator will 
review patients’ medication history as well as any potential medication risk factors and 
provide a note in CPRS with a summary for the provider to assist in assessing potential 
contraindications and facilitating adherence to VHA formulary guidelines.  
 
We also note that following publication of a large double-blind, placebo controlled trial 
specifically designed to assess risks of cessation pharmacotherapies including the nicotine 
patch, varenicline and bupropion, 22 the U.S. Food and Drug Administration (FDA) has 
determined the risk of serious side effects on mood, behavior, or thinking with the stop-smoking 
medicines varenicline and bupropion is lower than previously suspected and removed a black 
box warning previously placed on varenicline. The risk of these mental health side effects was 
equivalent among all forms of medications in the trial. The results of the trial confirm that the 
benefits of stopping smoking outweigh the risks of these medicines, so the main risk in this 
study is that cessation rates will be lower among one of the study arms. 
 
Risks associated with survey and administrative data collection. The main potential 
research risk to patient subjects is loss of confidentiality of personal information, including CDW 
data, information present in their electronic patient medical records, information collected by the 
VA Quitline counselors, or information shared via the study survey.  We will take multiple 
precautions to protect confidentiality while working with primary and secondary data, as well as 
extra precautions with the collection and exchange of subject data with CIS. 
 
Potential risks to patient subjects may also include emotional distress from responding to survey 
questions, which might cause confusion or make them uncomfortable. Patients may also feel 
pressure to participate in the survey unwillingly because they mistakenly fear their access to 
services might be affected if they do not complete the survey. We will reiterate what will also be 
provided in writing in the information sheet: that their decision not to participate in the survey will 
be kept confidential, and will in no way affect their access to services or the quality of care they 
receive at the VA. 
 
Minimization of risk. We will obtain IRB approval prior to initiating any study activities. Prior to 
study commencement, all members of the research team will complete trainings in human 
subject protection and ethical research practices, as required by IRB.  Approvals from the VA 
Information Security Officer (ISO), VA Privacy Officer (PO), and Research and Development 
Committee at all sites will also be obtained prior to commencing research.  

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Protection against emotional distress. All patients will have discussed lung cancer screening 
with their provider and have been determined by their provider to be eligible and appropriate for 
screening. To avoid the possibility of the patient mistakenly thinking they are being contacted by 
the national telephone counselor because they might have lung cancer, the counselor will 
remind the individual of the reason for the call and include a clarifying statement to assure 
patients this is not the reason they are being contacted.  We will emphasize their participation in 
the proactive call from the VA Quitline is being offered by the VA as an option and their 
participation in the call is voluntary. We will reassure them their refusal to participate will in no 
way affect their medical care or access to services at the VA.  All national counselors are 
trained in assessing risks to subjects and will be reminded to be sensitive to expression of 
significant distress around topics of cancer and smoking.  Similarly, when we contact patients 
with 3- and 12-month surveys, we will remind them in the accompanying letter that receipt of 
surveys does not in any way indicate that they have lung cancer, and that their participation in 
the survey is voluntary. 
 
Protection against risks of missing contraindications to cessation medications. All study 
personnel will be trained in VHA formulary guidelines for recommended cessation medications 
including potential contraindications. A primary care provider associated with the patient will 
confirm the appropriateness of all medications suggested by the study. The provider will be 
required to review and sign the order for the suggested medication before it is dispensed. 
Additionally, the study team will work closely with pharmacy providers at each of the study sites 
who are aware of the study activities and will also provide additional review of medications prior 
to dispensing.  A study clinician (Drs. Feemster or Au) will be available to the all study personnel 
for additional guidance if necessary. Although the local coordinator will enter a recommendation 
in the note, the provider may opt for an alternate treatment type within the VA formulary (or 
none at all).  
 
Detailed VA educational materials will accompany all cessation medications and are provided 
by the clinical pharmacy when the medications are sent. These materials will remind patients of 
any potential contraindications. Additionally, VA Quitline counselors will have copies of all 
instructions and will review these medication instructions and potential contraindications with 
each subject based on the type of medication provided. Quitline counselors will help patients 
formulate questions to ask their provider about any medication use, and if necessary contact the 
study team directly and notify a study clinician (Drs. Feemster or Au) with any potential 
concerns about medications. The study clinician will contact the patient’s provider as 
appropriate. 
 
Protection of data. Study staff will execute Data Use Agreements with CDW and CAPRI/JLV 
prior to use of any repository data, and comply with the stipulations outlined in the agreement 
contracts. Strict data protection protocols at the Coordinating Center will be implemented to 
protect the confidentiality of the data, in accordance with the Center of Innovation for Veteran-
Centered and Value-Driven Care (COIN) data security policy. Only IRB-approved project staff 
will have access to study data. All data at the Coordinating Center will be maintained on a COIN 
secure-access drive in permission-restricted folders only accessible to project staff. At no time 
will copies of data will be placed on laptops, computer desktops, hard drives, portable media, or 
any other form of media or hardware. Please see the Data and Safety Monitoring Plan for more 
details about how data will be protected and subject confidentiality will be maintained.  Any data 
included in manuscripts or publications stemming from this study will be presented as aggregate 
data only, and in a way that no individual could be identified.  At the end of the study, after all 
manuscripts are published, all identifiable files and crosswalks will be destroyed in accordance 

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with VA policy - Records Control Schedule 10-1. Electronic media used to store all data will be 
cleaned or destroyed so the data is not retrievable. As a result of these measures, we do not 
expect any invasion of privacy or breach of confidentiality. 
 
Protection against risk: Data and Safety Monitoring Plan.  VA Informatics and Computing 
Infrastructure (VINCI), in conjunction with our COIN Database Administrator, will facilitate the 
secure, electronic data transfer from the VA data repertories, including CDW, and Vital Status 
data to COIN servers. Study staff will execute Data Use Agreements with CDW and CAPRI/JLV 
prior to use of any repository data, and comply with the stipulations outlined in the agreement 
contracts.  
 
We will protect the confidentiality of VA patient data through a number of procedures.  We will 
limit our acquisition of identifiable information to the minimum amount of information necessary 
to link subject data, obtain contact information for recruitment of subjects, and collect pertinent 
data necessary to complete the study aims. To ensure confidentiality and protection of subject 
data, data will only be analyzed and stored electronically on secure servers at the COIN. The 
study team will be trained and reminded to not save copies of data on laptops or portable 
media. Only secure VA remote access will be used to access the data.  Anti-virus protection is 
maintained on all servers and workstations at the COIN office.  All workstations and servers are 
physically secured in locked offices, reside behind the VA firewall, and fully participate in 
Windows NT security. We will store the identifier crosswalk in a separate data file location, 
accessible only by the COIN Database Administrator and study PIs. Access to the study data 
folder will be restricted to those VA study project staff approved by our local VA IRB. The data 
study folder will be further safe-guarded against unauthorized access by network user login 
authentication controls.  In no case will patient identifiers or data be provided to any person or 
entity outside the IRB-approved project team, and we will ensure that all study results are 
presented in a way that no individual can be identified. 
 
In order to ensure Veteran contact data is protected as it is provided to the VA Quitline, we will 
utilize a secure fax line to send instructions to VA Quitline for contacting patients of providers in 
the proactive care group. This will be reviewed by the VA Puget Sound Privacy Officer and 
described in the Data Use Agreement between VA Puget Sound and the VA Quitline.  
 
The VA Quitline will follow current procedures for protecting data with two exceptions. The VA 
Quitline currently conducts quality assurance by having senior staff listen to a sample of calls. 
The study team will develop a fidelity tool for the VA Quitline/Fred Hutchinson Cancer Research 
Center staff to use as part of this quality assurance process and report the summary results of 
the fidelity tool. No audio recordings will be removed from VA Quitline facility. The VA Quitline 
will provide a CD of participation records (number of completed calls/length of calls). 
Instructions for providing this data will be included in the Data Use Agreement between VA 
Puget Sound and the VA Quitline/Fred Hutchinson Cancer Research Center. This CD will 
include only a coded study ID provided by the Coordinating Center and no other identifying 
information. The CD will be sent by certified US mail.    
 
Upon completion of the research project, the PI in conjunction with the VA Information Security 
Officer (ISO), and in accordance with VA policy, will ensure that study data containing sensitive, 
confidential information will be sanitized and removed from all servers, desktops, removable 
storage devices, etc. We will follow Records Control Schedule 10-1 and destroy study materials 
6 years after completion of the study. When any study personnel are no longer a part of the 
research team, the PI will remove that person’s access to all study data and notify the VA 
Information Security Officer of such action. COIN Information Technology personnel will be 

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responsible for maintaining COIN servers where study data will be kept, and will move, backup 
and remove study data from servers and control access to data stored on COIN servers. The PI 
will request termination of data access rights for study personnel who are no longer part of the 
study team.  All study team personnel with access to sensitive patient data will stay current on 
their VA approved information security training and VA approved privacy policy training.  
 
Any data included in manuscripts or publications stemming from this study will be presented as 
aggregate data only, and in a way that no individual could be identified. Current and future use 
of the data will require approval of a written protocol by both the investigator’s controlling IRB as 
well as their local R&D committee.  In no case will patient identifiers or data be provided to any 
person or entity outside the IRB-approved project team, and we will ensure that all study results 
are presented in a way that no individual can be identified.  
 
Analysis of risk vs. potential benefit. The benefits outweigh the risks involved, especially 
given that this is a study assessing the effectiveness of an implementation strategy (using 
proactive notes to providers and a centralized telephone counseling resource) in promoting the 
adoption of what is considered high quality care but often is not routinely provided to patients 
due to limited clinical time. 
 
Subjects receiving proactive care will receive support related to screening and help 
understanding their screening result, counseling about smoking cessation services and support 
for use of cessation medications. The counseling sessions provided by the VA Quitline 
counselors may help patients crystallize their thoughts and feelings about lung cancer screening 
and the health benefits of smoking cessation. The study also encourages providers to provide 
cessation medication, and participants could benefit by receiving and using these medications. 
The intervention could have a positive influence on subjects’ health behaviors, such as 
connecting them to additional smoking cessation services such as group counseling or 
additional telephone counseling. Potential benefits could also come from the overall contribution 
of the study findings to care for future Veterans and help improving the healthcare field in 
general. Possible study findings could lead to implementation of improved care practices and/or 
services, which may include expansion of smoking cessation services through increased 
understanding and funding allocation for smoking cessation resources and heightened public 
awareness of the health benefits of smoking cessation. 
 
5.2 Recruitment Methods 
 
Number of Subjects Needed.  
Patients. We will assess CDW and CAPRI/JLV records for up to 15,000 patients (~10,000 to 
identify retrospective LCS orders, and ~5,000 to identify prospective LCS orders) who were 
offered lung cancer screening at NY Harbor and Providence to identify potential provider 
participants. Of these subjects, only current smokers will be approached. We anticipate 
approaching up to 1,350 eligible potential subjects (mailing them a study invitation packet) to 
invite them to participate in the survey. In order to ensure non-missing data are available on a 
sufficiently powered study sample, recruitment will continue until 270 subjects have completed 
the 12-month assessment survey in each of the care arms (total target n = 540).  
Providers. We expect to recruit approximately 300 providers, 180 from Providence, RI 
and 120 from NY Harbor, in order to reach 540 patients (completed surveys).  

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Identification and Recruitment of Subjects.  
Providers. We will obtain a Waiver of Informed Consent for recruitment to facilitate the 
identification of primary care providers ordering LCS CT scans at the NY Harbor and 
Providence VAs. At the beginning of the study, the study team will examine historical CDW data 
to identify providers who have previously ordered LCS tests. Providers who meet eligibility will 
then be contacted via mail, then email, and finally by Lync/Skype for Business instant message 
and given the recruitment materials. Any new providers who are hired at VA NY Harbor or 
Providence and are eligible to order a LCS CT scan, who were not identified by the historical 
review, will be similarly recruited when they are first identified.  
Patients. We will obtain a HIPAA Waiver and Waiver of Informed Consent for recruitment to 
facilitate the identification of providers’ eligible patients. The study team will query the CDW 
twice weekly over 5 quarters (15 months) to identify study providers’ recently ordered LCS CT 
scans at the NY Harbor and Providence, RI VAs. Upon discovery that a screening CT has been 
ordered, the study team will review the patient’s chart to assess for eligibility/ineligibility criteria 
and, if patient is eligible, enter patient information into a tracking system. At 2.5 months 
following their LCS, we will confirm subject eligibility criteria, including non-urgent LCS result, 
and obtain mailing address information in the electronic medical record. Current smokers 
receiving unstructured or proactive care who meet general eligibility criteria according to the 
National Center for Health Promotion and Disease Prevention Guidelines for lung cancer 
screening (including age, comorbidity, and other health history eligibility criteria, as detailed 
below in Inclusion and Exclusion Criteria) will be contacted by mail at 3 months following their 
LCS. The study packet will include an Information Sheet (included in Appendix) and the printed 
survey (included in Appendix). If the mailed survey has not been received by the study team 
within 10 days, telephone follow-up will be initiated. We will conduct five attempts to complete 
the telephone version of the survey (one call per day; see appendix containing follow-up 
telephone script for unreturned surveys). If no telephone contact can be made, we will mail a 2nd 
attempt of the full survey. We will conduct a 3rd mailing of a shorter survey focusing on the 
primary outcomes to subjects who do not complete the full survey within 14 days of the 2nd 
mailing. This 3rd mailing will be followed by three additional phone attempts, with the goal of 
completing the abbreviated survey over the phone if the subject is willing.  Please refer to the 
telephone script for patient callers requesting additional information or to opt-out of calls 
(included in Appendix) for language to answer potential questions from patients regarding 
privacy and legal concerns. We will offer to mail the patient a copy of the Notice of Privacy 
Practices upon request. We will use an “Address Service Requested” envelope, for automatic 
forwarding to new mailing addresses. The same schedule of mailing and phone calls will be 
followed for the 12-month survey.  Subjects who do not respond to the 3-month survey will be 
mailed a 12-month survey, altered to include some of the questions from the missing 3-month 
survey (included in attachments).   
Payments to Subjects. Subjects will be informed as part of the initial information sheet when 
the surveys are mailed that they will receive a $25 check for completion of each survey (at 3 
and 12 months after lung cancer screening).   
The information sheet also clarifies that the study team and VA Pharmacy are working together 
to ensure that any co-payments for medications received as part of the study will be paid by 
study funds and not by the participant.  
 
5.3 Informed Consent Procedures 

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Providers 
 
Waiver of written documentation of informed consent for provider participation. Providers 
who order lung cancer screening tests are the target for this pragmatic study. Based on recent 
estimates of lung cancer screening participation at VA NY Harbor and VA Providence, 
approximately 300 providers have ordered lung cancer screening procedures for 2000-4000 
Veterans. The purpose of the pragmatic trial is to test a structured approach to supporting 
providers to better integrate smoking cessation as part of reporting screening results to patients.  
A high level of participation of all VA providers who order lung cancer screening tests is critical to 
this pragmatic trial as the goal is to answer if this structured support is both feasible to implement 
and effective at improving patient outcomes. We have designed an opt-out approach to help lead 
to a wide range of provider participation, as requiring providers to opt-in to study participation 
would potentially bias the results or make them generalizable only to a small subset of providers 
and not VA overall. 
 
We will send all primary care providers who are ordering lung cancer screening tests a letter and 
Information Sheet in the postal mail to their office mailing address. We will then send a copy of the 
letter and Information Sheet via email, and finally follow up via Lync/Skype for Business (instant 
message, with link to Information Sheet and invitation letter in PDF format attached). In each 
communication, we will make clear that if we do not hear back from them, they will be enrolled in 
the study.  
 
Patients 
 
A Waiver of Informed Consent is requested for administrative medical record review of 
historical provider screening volumes. In order to ensure balance in randomization by provider 
volume (as some providers order hundreds of screening CTs per year and other providers order 
only one or two), we are requesting access to patient screening data between 1/1/2013 and 
12/31/2017.  We will need to access thousands of records in the Corporate Data Warehouse as 
NY Harbor and Providence have screened an estimated 2000-4000 Veterans. It is impracticable 
to obtain consent for all patients in the database, and the risk for loss of confidentiality is minimal.  
 
A Waiver of Informed Consent is requested to review administrative medical record data in 
the CDW for all prospective patients offered lung cancer screening after provider 
randomization. Patients who participate in lung cancer screening after their provider is 
randomized to one of the two study arms who meet eligible criteria will be considered study 
participants. This record review will be used to identify these patients and invite them to participate 
in survey activities to evaluate outcomes of the care they received.  This waiver also includes 
reviewing medical record data for all participants who do (and do not) respond to the 3- or 12-
month survey in order to document potential differences between patients who complete the 
survey and those who do not (e.g. age/comorbidity), and to conduct an administrative assessment 
of administrative cessation outcomes such as subsequent documentation by the provider in the 
medical record of continued smoking or cessation. 
 
Alteration of Informed Consent Process. We are requesting a waiver of documentation of 
informed consent for survey participation. We will mail participants an evaluation survey at 3 
months and 12 months after the screening CT scan; we are requesting that returning the survey 
serve as a substitute for documentation of informed consent. Requiring participants to complete a 
written informed consent document in addition to the survey would be unnecessarily burdensome. 
 

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Study personnel training. All study staff have been trained and will remain current with the VA 
requirements for Human Subjects Protections and Good Clinical Practices.   
 
 
5.4 Inclusion/Exclusion Criteria 
 
 
Inclusion Criteria 
 
Providers 
• 
All providers who schedule patients for an LCS at NY Harbor and Providence, RI VA 
systems will be eligible 
Patients (assessed via patient information in CAPRI/JLV) 
• 
Offered LCS by a primary care provider at NY Harbor and Providence VA systems 
and scheduled for a LCS visit.  
• 
Meets eligibility criteria according to the National Center for Health Promotion and 
Disease Prevention guidelines (age ≤ 80; history of smoking > 30 pack-years) 
• 
Current smoker and eligible for at least one cessation medication on VA Formulary. 
• 
There are at least 3 business days between the date the lung cancer screening test 
order is identified by the Coordinating Center and when it is scheduled. This is 
necessary to allow the study team time to confirm that there are no exclusionary 
criteria and enter proactive study notes prior to the result of the screening test being 
available to the ordering provider. 
• 
Ability to speak and understand English (no language disability noted in VHA medical 
record) and communicate by telephone (no deafness or difficulty hearing on 
telephone is noted in VHA medical record) 
• 
Phone number and mailing address present in VHA medical record 
 
 
Exclusion Criteria 
 
Providers 
• 
Provider currently systematically provides cessation medication to all current 
smokers. 
 
Patients (assessed via patient information in CAPRI/JLV) 
• 
Patients with urgent findings requiring biopsy/immediate attention on the screening 
CT will be excluded. These patients will not be sent any study surveys, and no 
information will not be provided to the VA Quitline for patients of proactive arm 
providers. (LCS results are anticipated to identify highly suspicious findings requiring 
immediate attention for suspected malignancy among <4% of participants). 
• 
Patients receiving active therapy for cancer, except skin cancer 
• 
Diagnosis of pancreatic, esophageal, or liver cancer – or life expectancy < 6 months 
• 
Prior diagnosis of lung cancer 
• 
Indication in chart review of difficulty communicating or participating in telephone 
counseling sessions, per patient and PCP notes entered in electronic medical record. 
• 
Patients with evidence in CDW of ICD10 codes for severe behavioral disorders will 
be excluded. These include: Manic/bipolar disorder severe – F30.2, F31.1-6; 

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Dissociative/conversion disorders – F44; Paranoid/Unstable personality disorder – 
F60; Mental retardation – F70-F79; Pervasive speech/language development 
disorders – F84. 
• 
Patients with cognitive impairment and/or dementia (including ICD10 codes G31.84; 
F01-F03) 
• 
Pregnant or subjects reporting they may be pregnant  
• 
Temporary beginning 12/12/2019: Patients assigned to primary care providers at 
New York Harbor in the proactive arm who have a “Non-exempt” co-pay status and 
are not already currently being prescribed smoking cessation medications, will be 
excluded until mechanisms with clinical pharmacy have been established to ensure 
these patients do not receive a co-pay.  
 
5.5 Study Evaluations 
 
Patient evaluations. The study team will query CDW twice weekly to identify scheduled LCS 
tests at the NY Harbor and Providence VAs. Eligibility for lung cancer screening requires the 
patient’s provider conduct a thorough assessment of a patient’s smoking history to ensure they 
have smoked at least 30 pack-years over their lifetime. Current smokers who meet general 
eligibility criteria for lung cancer screening including age, comorbidity, and other health history 
eligibility criteria, will be approached. 
Upon identifying LCS screening patients, study staff at the Coordinating Center will enter them 
into a tracking database, recording information such as the date they were screened or are 
scheduled to be screened. We will extract information about their screening results, including 
withdrawing those few individuals (<4%) who are identified with highly suspicious findings who 
are no longer eligible for participation in the study evaluation. For subjects receiving proactive 
care, we will extract information about medications provided by the provider, and date their 
contact information was provided to the VA Quitline.  
The tracking system will prompt Coordinating Center staff at 2.5 months following the date of 
the patient’s LCS test. We will re-confirm their eligibility, reviewing any changes to their 
screening results associated with repeat tests in CDW, and will mail a 3-month assessment 
survey using the mailing address information in the EMR. If the mailed survey has not been 
received by the study team within 10 work days, telephone follow-up will be initiated. We will 
conduct five attempts to complete the telephone version of the survey (one call per day). If no 
telephone contact can be made, we will mail a 2nd attempt of the full survey. We will conduct a 
3rd mailing of a shorter survey focusing on the primary outcomes to subjects who do not 
complete the full survey within 14 days of the 2nd mailing. This 3rd mailing will be followed by 
three additional phone attempts, with the goal of completing the abbreviated survey over the 
phone if the subject is willing.   Please refer to the Telephone Script (included in Appendix) for 
language to answer potential questions from patients regarding privacy and legal concerns. We 
will offer to mail the patient a copy of the Notice of Privacy Practices upon request. We will use 
an “Address Service Requested” envelope, for automatic forwarding to new mailing addresses. 
The sameschedule of mailing and phone calls will be followed for the 12-month survey.  
Subjects who do not respond to the 3-month survey will be mailed a 12-month survey, altered to 
include some of the questions from the missing 3-month survey (included in attachments), 
unless they have contacted the study team requesting to opt out from further contact.  
 

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Provider Evaluations. A brief email survey will be sent to providers participating in the study. 
The main purpose of this brief survey (see Appendices) is to capture any perceptions by 
providers that the study is adding to their workload or saving them time, and to give providers an 
opportunity to share their experiences about the study with the study team. If providers have 
offered LCS to more than one patient, they will only receive this survey once per quarter. 
 
5.6 Data Analysis 
 
Sample size determination. Our target sample size of 270 respondents per arm with complete 
12-month outcome information was selected to have sufficient (80%) power to detect a doubling 
of abstinence rates (Relative Risk = 2) using a multilevel random effects model with patients 
clustered by randomized provider. The assumed intraclass correlation coefficient for the 
provider clustering effect is assumed to be 0.01.  Power is based on a two-sided test with type-1 
alpha error rate of 0.05%. Due to randomization, we do not anticipate needing to adjust for 
patient covariates.  
 
Intent-to-treat (ITT) analysis We will utilize an intent-to-treat approach and include all 
participants who meet study eligibility criteria and are assigned to a study arm, regardless of 
whether they participated in all of the care components of that arm (e.g. declined proactive 
telephone counseling). Our primary analysis will focus on participants for whom we have 
complete 12-month abstinence (target n=270 per arm).  
 
Missing outcome data. For secondary analyses, we will examine outcomes for all eligible 
screening patients who are current smokers offered screening by a participating randomized 
provider during the study period. This analysis will include patients who do not participate in the 
survey assessment of cessation outcomes. We will perform two secondary analyses.  The first 
will assume that patients who do not participate in the survey assessment (e.g. missing 
abstinence outcomes) will be considered continued smokers, which is a typical intent-to-treat 
approach for cessation trials. We do not anticipate differential missing data across study arms.  
Second, we will address potential missing cessation data by requesting a HIPAA waiver and 
waiver of informed consent to review EMR data for all eligible patients to estimate an 
administrative assessment of cessation, based on HealthFactors data and whether patients 
report quitting at a subsequent visit or when they return for annual lung cancer screening. The 
methods developed by McGinnis et al, will be used to construct this administrative cessation 
variable.  
 
(Note, due to COVID pandemic changes in lung cancer screening utilization and study 
enrollment timelines, the missing data protocol using EMR data was adapted for the primary 
outcome. See the Statistical Analysis Plan.) 
 
All data will be maintained and analyzed at the Seattle offices of the Seattle/Denver Center of 
Innovation for Veteran-Centered and Value-Driven Care. Dr. Zeliadt will oversee all project staff 
conducting data analysis activities. See below for description of data and privacy protections at 
our Center of Innovation. 
 
5.7 Withdrawal of Subjects 
 

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Patient participants may be withdrawn without their consent if they no longer meet the study 
eligibility criteria (e.g. their LCS test or a short-term follow-up test identifies lung cancer or a 
highly suspicious finding, or if the subject becomes pregnant which is unlikely given the age 
eligibility for LCS). A participant may also be withdrawn if either of the responsible VA clinicians, 
Drs. Au or Feemster, deems it appropriate to ensure that no harm occurs to the subject.   
Both patient and provider participants may withdraw from the study at any time without incurring 
any consequences. Participants may notify the study team or Principal Investigator at any time 
to withdraw from the study. Contact information will be provided in all communications, including 
on the Information Sheet and survey mailings provided to all participants. Language 
emphasizing the freedom to withdraw at any point during the study will be included on 
communications with study participants. 
 
6.0 
Reporting 
 
Collection of Safety Information. The study activities do not involve any invasive procedure, 
and it is not anticipated that serious adverse events or unanticipated problems will occur, 
including events that would trigger suspension of research. However, in the rare chance such 
an incident does occur, all serious adverse events and unanticipated problems will be reported 
according to regulatory and reporting requirements outlined in the VHA Handbook 1058.01 
within 5 business days of the incident.  The Coordinating Center will complete and submit an 
Unanticipated, Serious Adverse Event (SAE) Report form or Problem Report for each incident to 
the VA Human Subjects Boards as per the regulatory requirements at each site and the study 
protocol. 
 
The project coordinator will be responsible for reporting relevant information to the PI on a 
weekly basis.  Any clinical or data safety concerns will be reported to the PI and responsible VA 
clinician within 24 hours. If the PI is unavailable, the project coordinator will contact an available 
Co-Investigator (Dr. Becker, Dr. Au, Dr. Feemster). The PI will determine whether the event is a) 
serious or non-serious and b) anticipated or unanticipated. The PI will ensure that any 
necessary actions are taken immediately to address the current patient situation, and then will 
decide if the team needs to make any changes in the protocol and/or consent forms to prevent 
future occurrences or better inform future participants. Any deviation to protocol or safety 
concerns resulting from the study will be communicated by the project coordinator via the 
submission of an Unanticipated, Serious Adverse Event (SAE) Report form or Problem Report 
to the VA IRB as per the VHA regulatory requirements and protocol, within 5 business days of 
an incident. 
Method of Collection of Safety Information. If the study is made aware of any Adverse 
Events through notification by a study participant, VA Quitline Counselor, or email/contact from 
a study provider, the project coordinator will be responsible for completing the above safety & 
regulatory report forms (i.e., SAE forms), which the PI will sign prior to submission. Adverse 
Events will be reported to the VA Human Subject Review Board using the appropriate Central 
IRB forms. 
Frequency of Safety Data Collection. Oversight of project activities and data by the PI will 
begin immediately.  Collection of CDW data will begin as soon as IRB approval is obtained.  
Twice-weekly lists of potential subjects will be continued until target recruitment goals are met. 

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Any event that adversely affects participant safety will be recorded as soon as possible after it 
occurs and be reported within 24 hours to the PI. 
Notification of Subjects of Findings Affecting Health and Welfare. This study does not 
involve any invasive procedure, and it is not anticipated that any findings identified by the study 
(e.g. survey results) will require notification. 
 
7.0 
Privacy and Confidentiality 
 
PHI.  Protected Health Information and personal identifying information will be obtained from 
existing sources (Corporate Data Warehouse, CAPRI/JLV) and from patient subjects. Names, 
social security numbers, birthdates, ages, appointment dates, treatment dates, date of CT 
screenings, telephone numbers, and patient addresses will be obtained. Limited screening data 
will be entered into an electronic subject tracking database that will be maintained on secure 
servers at the COIN at VA Puget Sound. The tracking database will be used to log subject 
recruitment and completion of surveys. The tracking database will include subject name, SSN, 
address, phone number, date they were offered lung cancer screening by their VA provider, and 
date of receipt of lung cancer screening. The tracking database will also serve as the crosswalk 
between the subject name and the study ID sequentially assigned by project staff. Data 
collected as part of this study (subject responses to surveys) will include a study ID with no 
other patient identifiers, and will be stored separately from the tracking/ crosswalk data.  
 
Data security.  Data collection, storage and management for this research project will adhere to 
all applicable VA policies, the VA Puget Sound Health Care System’s Automated Information 
Systems Security Policy, and the established Data Security Policy of the Seattle/Denver COIN. 
All electronic study data – including protected health information and de-identified analysis files 
– will be stored in secure, password protected folders and/or SQL databases on the Seattle 
HSR&D network. Access will be restricted to the study team. Protected health information will 
not be disclosed, copied, transmitted by email, or transmitted in total or in part to anyone not 
connected with the approved protocol and not approved by the VA (via a Data Use Agreement, 
if necessary) to access the identifiers.  
 
All electronic study data will be in secured and stored in electronic files on the COIN’s secure 
servers at VA Puget Sound. Files will be secured behind the VA firewall with strong password 
protection restrictions in accordance with VA policy. Access to study files will be restricted to 
study staff only. The data collected in this study will be used solely for the purpose described in 
the study protocol.  
 
At no time will copies of data will be placed on laptops, computer desktops, hard drives, portable 
media, or any other form of media or hardware. Screening data for potential subjects identified 
in Corporate Data Warehouse data repository will be transferred and stored in electronic format 
to the VA Informatics and Computing Infrastructure (VINCI) server using secure server-to-
server, password-protected media/ technology. Data Use Agreements between project staff and 
repositories will be executed prior to all data access. The historical and screening CDW data will 
remain within our designated VINCI workspace environment, which will be restricted to 
approved project staff only. The VINCI workspace will be accessed remotely from workstations 
located within COIN offices at VA Puget Sound.  

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Hardcopies of all study data (such as survey responses) will be kept in locked file cabinets in 
COIN offices. CDs containing participation records obtained from VA Quitline will also be stored 
in locked file cabinets in COIN offices, and will be labeled only with a coded study ID (no patient 
identifiers). 
 
The PIs, co-investigators, and project coordinator will be responsible for monitoring data and 
study activities. Any deviation from the data security or privacy rules will be immediately 
reported to the Database Administrator, Privacy Officer and Information Security Officer. Study 
investigators will access data to identify prospective patients offered lung cancer screening on 
an ongoing (approximately weekly) basis. The project team will hold regular, biweekly meetings 
to provide updates and review analyses. Additional, ad hoc meetings will be scheduled to 
discuss specific findings or challenges.  
 
Upon completion of the research project, the PI in conjunction with the VA Information Security 
Officer (ISO), and in accordance with VA policy, will ensure that, study data containing sensitive, 
confidential information will be sanitized and removed from all servers, desktops, removable 
storage devices, etc. in accordance with Records Control Schedule 10-1.  When any study 
personnel are no longer a part of the research team, the PI will remove that person’s access to 
all study data and notify the VA Information Security Officer of such action. COIN Information 
Technology personnel will be responsible for maintaining COIN servers where study data will be 
kept, and will move, backup and remove study data from servers and control access to data 
stored on COIN servers. All study team personnel with access to sensitive patient data will stay 
current on their VA approved information security training and VA approved privacy policy 
training. 
8.0 
Communication Plan 
 
Each site (NY Harbor and Providence) will submit and obtain R&D approvals. We anticipate NY 
Harbor and Providence R&D committees will provide guidance about requirements for annual 
review and/or submitting presentations/manuscripts prior to publication. 
The project manager at the Coordinating Center in Seattle will be the point of contact for 
ensuring that any changes to the protocol or any Serious Adverse Events or Unanticipated 
Problems will be promptly will be responsible for managing local R&D paperwork and assisting 
with IRB paperwork.  
Dr. Zeliadt assumes primary responsibility for oversight of study logistics; formative evaluation, 
fielding and analyzing survey data; conduct of qualitative interviews; synthesis of formative 
evaluation findings into feedback reports. Dr. Zeliadt will provide oversight of the Project 
Manager. Dr. Zeliadt will assume responsibility for ensuring the study meets overall project 
deadlines and adheres to the proposed timeline; communication with study team members and 
participants about study events and results; and timely reporting of study findings internally to 
operational stakeholders, VA researchers and the scientific community. 

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9.0 
References 
 
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Jackson GL, King HA, McNeil RB, et al. Evaluation of the VA Lung Cancer Screening 
Clinical Demonstration Project – Report Submitted to the Veterans Affairs Office of the Under 
Secretary for Health. Durham, NC: Veterans Affairs Center for Health Services Research in 
Primary Care and National Center for Health Promotion and Disease Prevention 
3.  
Kinsinger L, Anderson C, Kim J, et al. Implementation of Lung Cancer Screening in the 
Veterans Health Administration. JAMA Internal Medicine. 2017;177(3):399–406. 
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Garrett B, Dube S, Trosclair A, Caraballo R, Pechacek T, for and (CDC) C. Cigarette 
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McFall M, Saxon A, Thaneemit-Chen S, et al. Integrating smoking cessation into mental 
health care for post-traumatic stress disorder. Clinical Trials. 2007;4(2):178–189. 
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12.  
Brown D. Smoking Prevalence among US Veterans. Journal of General Internal 
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behavioural interventions for smoking cessation. The Cochrane Library. 2016;3:CD008286. 
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nationally in the Veterans Health Administration.; 2016:183. doi:10.1037/ser0000076. 

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15.  
Sherman S, Takahashi N, Kalra P, et al. Care coordination to increase referrals to 
smoking cessation telephone counseling: a demonstration project. The American journal of 
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Farmer M, Rose D, Riopelle D, Lanto A, Yano E. Gender Differences in Smoking and 
Smoking Cessation Treatment: An Examination of the Organizational Features Related to Care. 
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17.  
Yano E, Rubenstein L, Farmer M, et al. Targeting Primary Care Referrals to Smoking 
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counseling during physician office visits among adults--National Ambulatory Medical Care 
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Interventions to increase adherence to medications for tobacco dependence. The Cochrane 
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doi:10.1002/14651858.CD008286.pub2. 
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provision of smoking cessation aids within the Veterans Health Administration. The American 
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Anthenelli R, Benowitz N, West R, et al. Neuropsychiatric safety and efficacy of 
varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders 
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