Implementation Of Smoking Cessation Services Within NCI NCORP Community Sites With Organized Lung Cancer Screening Programs
Phase: NA
Conditions: Smoking Cessation
Sponsor: Wake Forest University Health Sciences

 
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COVER PAGE 
 
DCP Protocol #: WF-20817CD 
 
Local Protocol #: WF-20817CD 
 
IMPLEMENTATION OF SMOKING CESSATION SERVICES WITHIN NCI NCORP 
COMMUNITY SITES WITH ORGANIZED LUNG CANCER SCREENING PROGRAMS 
(OaSiS) 
 
 
Consortium Name: 
       
 
Wake Forest NCORP Research Base  
Name of Consortium Multi-           Glenn Lesser, MD 
Principal Investigator:  
 
Wake Forest School of Medicine 
 
 
 
 
 
Department of Internal Medicine  
 
 
Section on Hematology and Oncology 
 
 
 
 
 
Medical Center Boulevard 
 
 
 
 
 
Winston-Salem, NC  27157 
 
 
 
 
 
Telephone: (336) 716-0891 
Fax: (336) 716-6275 
E-mail address: glesser@wakehealth.edu  
 
Consortium Name: 
 
 
Wake Forest NCORP Research Base 
Name of Consortium Multi- 
 
Kathryn Weaver, PhD, MPH  
Principal Investigator: 
 
Associate Professor of Public Health Sciences 
 
 
Department of Social Sciences & Health Policy   
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 713-5062  
 
 
Fax: (336) 716-7554  
 
 
 
 
 
E-mail address: keweaver@wakehealth.edu 
 
Organization Name: 
 
 
Wake Forest School of Medicine  
Protocol Principal Investigator: 
Kristie Foley, PhD 
 
 
Department of Implementation Science  
 
 
Division of Public Health Sciences 
 
 
Medical Center Boulevard 
 
 
Winston-Salem, NC 27157 
 
 
 
 
 
Telephone: (336) 713-5084 
 
 
 
 
 
Fax: (336) 716-7554 
 
 
 
 
 
E-mail address: kfoley@wakehealth.edu  
 
Organization Name: 
 
 
Wake Forest School of Medicine  
Protocol Principal Investigator: 
Caroline Chiles, MD 
 
 
Department of Diagnostic Radiology  
 
 
Medical Center Boulevard 
 
 
Winston-Salem, NC 27157 
 
 
 
 
 
Telephone: (336) 716-9250 
 
 
 
 
 
Fax: (336)-716-4317 
 
 
 
 
 
E-mail address: cchiles@wakehealth.edu  
 
 

 
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Organization:  
 
 
Wake Forest School of Medicine 
Investigator: 
 
Kathryn Weaver, PhD  
 
 
Department of Social Sciences & Health Policy  
 
 
Division of Public Health Sciences  
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 716-0891  
 
 
Fax: (336) 716-7554  
 
 
E-mail address: keweaver@wakehealth.edu  
 
Organization:   
 
 
Wake Forest School of Medicine 
Investigator:  
 
       John Spangler, MD, MPH 
 
 
 
 
 
Department of Family Medicine 
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 716-2238 
 
 
 
 
 
Fax: (336) 716-9126 
 
 
 
 
 
E-mail address: jspangle@wakehealth.edu 
 
Organization:   
 
 
Wake Forest School of Medicine 
Investigator:  
 
 
Erin Sutfin, PhD 
 
 
 
 
 
Department of Social Sciences & Health Policy 
 
 
Division of Public Health Sciences  
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 713-5282 
 
 
 
 
 
Fax: (336) 716-7554 
 
 
 
 
 
E-mail address: esutfin@wakehealth.edu 
 
Organization:   
 
 
Wake Forest School of Medicine 
Investigator:  
 
 
William Jeffrey Petty, MD, MS 
 
 
 
 
 
Department of Internal Medicine  
 
 
Section on Hematology and Oncology 
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 716-3313 
 
 
 
 
 
Fax: (336) 713-5445 
 
 
 
 
 
E-mail address: wpetty@wakehealth.edu 
 
Organization:   
 
 
Wake Forest School of Medicine 
Investigator:  
 
 
Christina R. Bellinger, MD 
 
 
 
 
 
Department of Internal Medicine - Pulmonary 
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 713-5780 
 
 
 
 
 
Fax: (336) 716-7277 
 
 
 
 
 
E-mail address: cbelling@wakehealth.edu 
 
 
 
 

 
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Organization:   
 
 
Wake Forest School of Medicine 
Investigator:  
 
 
David Miller, MD 
 
 
 
 
 
Department of Internal Medicine  
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 713-5218 
 
 
 
 
 
Fax: (336) 716-5168 
 
 
 
 
 
E-mail address: dmiller@wakehealth.edu 
 
Organization:  
 
 
Wake Forest School of Medicine 
RB Statistician  
 
 
Emily Dressler, PhD 
 
 
 
 
 
Department of Biostatistics and Data Science 
 
 
Medical Center Boulevard  
 
 
Winston-Salem, NC 27157  
 
 
Telephone: (336) 713-0917 
 
 
 
 
 
Fax: (336) 713-5308 
 
 
 
 
 
E-mail address:  edressle@wakehealth.edu 
 
Grant #: 
 
 
1R01CA207158-01 
 
Protocol Amendment #: 
5 
Protocol Version Date: 
12/10/2019 
 
Protocol History: 
Initial 
Version 12/15/2017 
This version will be activated but 
patient participant enrollment will 
not be open. Activated 1/31/2018 
Amendment 1 
Version 01/19/2018 
Activated and released on 
3/19/2018 
Amendment 2 
Version 06/29/2018 
Activated and released on 
10/5/2018 
Amendment 3 
Version 12/03/2018 
Activated and released on 
04/29/2019 
Amendment 4 
Version 10/01/2019 
Activated and released on 
12/09/2019 
 
 
 

 
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CONTACT INFORMATION 
For regulatory requirements: 
For patient enrollments: 
For study data submission: 
Regulatory documentation must 
be submitted to the CTSU via 
the Regulatory Submission 
Portal. 
Regulatory Submission Portal: 
(Sign in at www.ctsu.org,            
and select the Regulatory > 
Regulatory Submission.)  
 
Institutions with patients 
waiting that are unable to use 
the Portal should alert the 
CTSU Regulatory Office 
immediately at 1-866-651-2878 
to receive further instruction 
and support. 
 
Contact the CTSU Regulatory 
Help Desk at 1-866-651-2878 
for regulatory assistance. 
Refer to the patient enrollment 
section of the protocol for 
detailed instructions. 
Data collection for this study will 
be done exclusively through 
REDCap. Refer to the data 
submission section of the protocol 
for further instructions.  
 
For assistance, please contact the 
NCORP Research Base Data 
Management Center at:  
(336) 713-3172  
-or- 
(336) 713-6507. 
 
Address: 
Wake Forest Baptist Medical 
Center 
Building 525@Vine, 4th floor  
Medical Center Boulevard 
Winston-Salem, NC 27157 
 
Fax: (336) 713-6476 
Email: NCORP@wakehealth.edu 
Do not submit study data or forms 
to CTSU Data Operations. Do not 
copy the CTSU on data 
submissions. 
 
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific page of the CTSU members’ website (https://www.ctsu.org).  Access to the 
CTSU members’ website is managed through the Cancer Therapy and Evaluation Program - Identity and 
Access Management (CTEP-IAM) registration system and requires log on with CTEP-IAM username 
and password. 
For study related questions (i.e. patient eligibility) please contact the WF NCORP Research Base 
site coordinator at NCORP@wakehealth.edu or (336) 716-0891 or OaSiS Project Manager 
Rebecca Stone at rjstone@wakehealth.edu or (336) 716-6201. 
For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical data 
submission) contact the CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative.  
The CTSU Website is located at https://www.ctsu.org. 
 
 

 
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Participation is limited to the following Wake Forest NCORP Research Base sites: 
 
CTEP ID 
NCORP Site Name 
DE028 
Helen F. Graham Cancer Center 
GA020 
Augusta University Medical Center 
GA106 
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler 
HI010 
Tripler Army Medical Center 
IA003 
McFarland Clinic PC-William R Bliss Cancer Center 
IA008 
Mercy Medical Center - Des Moines 
IL168 
Carle Cancer Center 
LA017 
Louisiana State University Health Sciences Center Shreveport 
MI005 
William Beaumont Hospital-Royal Oak 
MI013 
Saint Joseph Mercy Hospital 
MI132 
Spectrum Health at Butterworth Campus 
MN059 
Ridgeview Medical Center 
MO042 
CoxHealth South Hospital 
MO046 
Missouri Baptist Medical Center 
NC047 
Novant Health Forsyth Medical Center 
ND039 
Sanford South University Medical Center 
NV011 
Saint Mary’s Regional Medical Center 
NV017 
University Medical Center of Southern Nevada 
NY045 
Montefiore Medical Center - Moses Campus 
OH182 
Adena Regional Medical Center 
PA052 
Geisinger Medical Center 
SC060 
Greenville Health System Cancer Institute-Faris 
TN029 
Baptist Memorial Hospital and Cancer Center-Memphis 
VA010 
Virginia Commonwealth University/Massey Cancer Center 
VA205 
Virginia Commonwealth University/Stony Point 
WI011 
Aurora Saint Luke's Medical Center 
WI029 
Gundersen Lutheran Medical Center 
 
 

 
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SCHEMA 
 
IMPLEMENTATION OF SMOKING CESSATION SERVICES WITHIN NCI NCORP 
COMMUNITY SITES WITH ORGANZED LUNG CANCER SCREENING PROGRAMS 
(OaSiS) 
 
 
Study Population: Lung Cancer Screening Patients presenting to 26 Lung Cancer Screening 
Clinics 
 
 
Randomization at the Clinic Level (13 Intervention, 13 Usual Care), matched on organizational 
characteristics (e.g., volume, current cessation services, race/ethnicity composition of patients) 
 
 
 
Intervention: Training of Lung Cancer Screening Personnel on implementation of the US PHS 
Guidelines for Smoking Cessation and Performance Coaching during Implementation Phase of 
the Study 
 
 
Data collection from Patients: demographics, health status, smoking history, quitting behavior, 
perceptions of lung cancer risk and worry, impact of screening on tobacco use behavior, and 
exposure to the intervention. (baseline, ≤14 days, 3 months, and 6 months) 
 
 
Data collection from Key Informants (Lung Cancer Screening Site Personnel):   Feasibility of 
Intervention, Appropriateness, Compatibility, Resources, Acceptability (Implementation Metrics) 
 
 
Primary Endpoint: 7-day smoking abstinence with cotinine validation at 6 months 
 
 
Study Sample: n=minimum 1,114 to a maximum of 1,300 patients who have undergone LDCT 
lung cancer screening  
 
Study Duration: 4.5 years 
 
Brief Eligibility Criteria:  
Clinics: Screened ≥50 patients within the last 6 months; Agrees to have NCORP research 
personnel serve as the study liaison and another person to serve as the cessation program 
champion; Agrees to participate in all aspects of the intervention, randomization, and evaluation  
 
Patients: Age 55-77; Current smoker; Not using medications to quit (use of Bupropion for 
depression only is acceptable); Willing to participate. 
 
 
 

 
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TABLE OF CONTENTS 
 
SCHEMA ...................................................................................................................................................................... 6 
1. 
OBJECTIVES ..................................................................................................................................................... 9 
1.1 
Primary Objectives ...................................................................................................................................... 9 
1.2 
Secondary Objectives .................................................................................................................................. 9 
2. 
BACKGROUND ................................................................................................................................................ 9 
2.1 
Study Disease .............................................................................................................................................. 9 
2.2 
Study Intervention ..................................................................................................................................... 10 
2.3  
Rationale .................................................................................................................................................... 11 
3. 
SUMMARY OF STUDY PLAN ...................................................................................................................... 13 
4. 
STUDY SITE AND PARTICIPANT SELECTION ......................................................................................... 13 
4.1 
NCORP Clinical Site Inclusion Criteria .................................................................................................... 13 
4.2 
Patient  Inclusion Criteria .......................................................................................................................... 15 
4.3 
Patient Exclusion Criteria .......................................................................................................................... 15 
4.4 
Patient Recruitment and Retention Strategy .............................................................................................. 15 
4.5. 
Patients:  Inclusion of Racial/Ethnic Minorities ........................................................................................ 16 
4.6 
Key Informant Inclusion Criteria ............................................................................................................... 17 
4.7 
Key Informant Exclusion Criteria .............................................................................................................. 17 
4.8 
Key Informant Recruitment and Retention Strategy .................................................................................. 17 
4.9 
Key Informants: Inclusion of Women and Minorities ............................................................................... 18 
4.10 Cancer Therapy Evaluation Program Investigator Registration Procedures .............................................. 19 
4.11 Research Base Online Patient Enrollment ................................................................................................. 22 
5. 
AGENT ADMINISTRATION - NA ................................................................................................................ 22 
6. 
PHARMACEUTICAL INFORMATION - NA ................................................................................................ 22 
7. 
CLINICAL EVALUATIONS AND PROCEDURES ...................................................................................... 22 
7.1 
Patient Schedule of Events ........................................................................................................................ 22 
7.2 
Patient Baseline Testing/Pre-study Evaluation .......................................................................................... 23 
7.3 
Patient Evaluation During Study Intervention ........................................................................................... 24 
7.4 
Patient Follow-up Period ........................................................................................................................... 24 
7.5 
Methods for Patient Clinical Procedures- NA ........................................................................................... 26 
7.6 
Clinic Assessment ...................................................................................................................................... 26 
7.7 
Core Elements and Guiding Assumptions of the Intervention ................................................................... 27 
7.8  
Summary of Expectations for Participating in this Study .......................................................................... 30 
7.9 
Develop and Evaluate an Implementation Toolkit..................................................................................... 30 
8.  
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION ............................................................... 33 
8.1 
Summary Table of Endpoints, Measures, Measurement Strategies, and Time Points ............................... 33 
8.2 
Primary Endpoint, Aim 1 (Effectiveness) .................................................................................................. 33 
8.3 
Secondary Endpoints, Aim 1 (Effectiveness) ............................................................................................ 34 
8.4 
Secondary Endpoints, Aim 2 (Implementation) ........................................................................................ 34 
8.5 
Off-Study Criteria ...................................................................................................................................... 35 
8.6 
Study Termination ..................................................................................................................................... 35 
9. 
CORRELATIVE/SPECIAL STUDIES - NA ................................................................................................... 35 
10. 
SPECIMEN MANAGEMENT ......................................................................................................................... 35 
10.1 Laboratories ............................................................................................................................................... 35 
10.2 Collection and Handling Procedures ......................................................................................................... 35 
10.3 Shipping Instructions ................................................................................................................................. 36 
11. 
REPORTING ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS (AEs and SAEs) ....................... 36 
12. 
STUDY MONITORING .................................................................................................................................. 36 
12.1 Data Management ...................................................................................................................................... 36 
12.2 Case Report Forms .................................................................................................................................... 37 
12.3 Source Documents ..................................................................................................................................... 37 
12.4 Data and Safety Monitoring Plan ............................................................................................................... 38 
12.5 Sponsor or FDA Monitoring ...................................................................................................................... 38 
12.6 Record Retention ....................................................................................................................................... 38 
 

 
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13. 
STATISTICAL CONSIDERATIONS .............................................................................................................. 39 
13.1 Study Design/Description .......................................................................................................................... 39 
13.2 Randomization/Stratification ..................................................................................................................... 39 
13.3 Accrual and Feasibility .............................................................................................................................. 39 
13.4 Primary Objectives, Endpoint(s), Analysis Plan ........................................................................................ 40 
13.5 Secondary Objectives, Endpoints, Analysis Plans ..................................................................................... 40 
13.6 Analysis Plan for Key Informant Interviews and Other Qualitative Data Elements .................................. 41 
13.7 Additional Data Elements Required by the SCALE Collaborative ........................................................... 41 
13.8 Reporting and Exclusions .......................................................................................................................... 42 
REFERENCES ............................................................................................................................................................ 43 
 
Informed Consent 
 
Appendices: 
 
Appendix 1: 
Participant Recruitment Flow Chart 
Appendix 2: 
Eligibility Checklist and Patient Enrollment 
Appendix 3: 
Reason for Refusal (Baseline) 
Appendix 4: 
Reason for Refusal (Follow-Up) 
Appendix 5: 
Key Informant Interview for LCS Sites 
Appendix 6: 
Key Informant Interview Guide 
Appendix 7: 
Patient Informational Flyer 
Appendix 8: 
Baseline Organizational Characteristics 
Appendix 9: 
Patient Survey-Baseline (Demographics) 
Appendix 10: 
Patient Survey- Less than 14 Days 
Appendix 11: 
Patient Survey-3 Months 
Appendix 12: 
Patient Survey-6 Months 
Appendix 13: 
Site Invitation to Participate 
Appendix 14: 
Participant Gift Card Log 
Appendix 15: 
Preliminary Site Eligibility Screener 
Appendix 16: 
Timeline and Key Milestones 
Appendix 17: 
Saliva Collection Instructions 
Appendix 18: 
Pre-Randomization Site Checklist 
Appendix 19: 
Lung Cancer Screening Imaging Report 
Appendix 20:  Key Informant Demographics 
Appendix 21:  Key Informant Follow-up Interview for LCS Sites 
Appendix 22:  Key Informant Follow-up Interview Guide 
Appendix 23:  Follow-Up Organizational Characteristics 
 

 
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1. 
OBJECTIVES 
 
1.1 
Primary Objectives  
 
1.1.1. Evaluate a multi-faceted training program to improve immediate (≤14 days after the 
screening visit), short-term (3 months after the screening visit) and sustained abstinence (6 
months after the screening visit) among 1,114-1,300 enrolled smokers who present for 
LDCT lung cancer screening in 26 community-based practices. The primary endpoint is 
sustained abstinence.  We will use a cluster, randomized control trial to achieve this aim. 
Thirteen intervention sites will receive the multi-faceted training program (n=557-650 patients), 
and 13 sites will receive “usual care” (n=557-650 patients).  We expect at least 836 participants to 
complete the 6-month follow-up survey.  Deliverable:  A rigorous test of the effectiveness of the 
multi-faceted intervention to promote quitting among high risk patients who present for LDCT 
lung cancer screening in community-based practices. 
 
1.1.2. Characterize the adoption and adaptation of evidence-based tobacco cessation strategies in 
26 diverse, community-based LDCT lung cancer screening imaging facilities within NCORP 
components/subcomponents.  Community-based practices offering lung cancer screening are 
rapidly evolving; therefore it is unknown how these practices adopt and adapt evidence-based 
cessation strategies.  We will use extensive qualitative data collection methodologies to inform 
this aim, including an analysis of strategic planning SWOT data, analysis of a team blog and 
performance coaching notes, key informant interviews, and observational data in the intervention 
arm. We will also evaluate the implementation of evidence-based cessation strategies in usual 
care clinics. Deliverable: These data will yield critical information on how diverse, community-
based LDCT lung cancer screening practices implement the evidence-based strategies for tobacco 
cessation (with and without the intervention) to inform the development of an implementation 
toolkit for dissemination and scale-up. 
 
1.1.3. Develop and evaluate an implementation toolkit for integrating evidence-based tobacco 
cessation strategies in community-based LDCT lung cancer screening imaging facilities. The 
majority of lung cancer screening will occur in non-academic, community-based settings with 
diverse patient populations. Therefore, it is critical for community-based (non-academic) settings 
to have a resource for implementation that can be used in absence of a research team. We will 
develop an implementation toolkit for LDCT screening sites and invite an external advisory board 
and national stakeholders to evaluate its potential for dissemination and scale-up (e.g., External 
Advisory Board members, Legacy Foundation, Partnership for Prevention, American Cancer 
Society, Lung Cancer Alliance, American Society of Clinical Oncology).  Deliverable: An 
implementation toolkit for community-based LDCT lung cancer screening sites that describes 
how to implement evidence-based tobacco cessation strategies in absence of the research team, 
thereby promoting scale-up and sustainability. 
 
1.2 
Secondary Objectives – N/A  
 
2. 
BACKGROUND 
 
2.1 
Study Disease 
 
Evidence and Opportunity: An estimated 8.7 million US adults may be eligible for low-dose computed 
tomography (LDCT) lung cancer screening, and up to half of patients presenting for lung cancer 
screening are smokers1.  Effective, evidence-based strategies exist to encourage smoking cessation in 
clinical settings.  We will determine how to best implement these strategies in lung cancer screening 

 
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components/subcomponents, leading to increased tobacco cessation rates and decreased tobacco-related 
mortality.    
Tobacco is a leading cause of death: Implementing effective smoking cessation within LDCT chest 
screening is needed, as quitting, even later in life, increases life expectancy,2  decreases risk of competing 
causes of death,3,4 improves survival among lung cancer patients, 5 and maximizes the cost-effectiveness 
of lung cancer screening.6,7 Cessation services can also be used to correct misconceptions about lung 
cancer screening that may inadvertently lower the likelihood of quitting.8  
New Support for Lung Cancer Screening:  In 2011, the National Lung Screening Trial (NLST) 
reported that three, annual LDCT lung cancer screens provided a 20% reduction in lung–cancer specific 
mortality in a high risk cohort relative to screening with single view chest radiograph.1,9 Medical societies 
and the United States Preventive Services Task Force have endorsed annual LDCT screening in 
asymptomatic adults who have a 30 pack-year smoking history and currently smoke or have quit smoking 
within the past 15 years.9  It wasn’t until 2014, however, that The Centers for Medicare and Medicaid 
Services (CMS) added annual LDCT lung cancer screening as a covered service benefit for persons at 
high risk for lung cancer and who meet the eligibility criteria (age 55 – 77 years; asymptomatic for lung 
cancer; tobacco smoking history of at least 30 pack-years; current smoker or a former smoker who quit 
within the last 15 years).10 Today, community-based LDCT screening is rapidly evolving, making this an 
optimal time to understand how to implement evidence-based tobacco cessation services during 
screening. 
Lung Cancer Screening Targets High Risk Smokers: CMS requires that the LDCT imaging center 
“make available smoking cessation interventions for current smokers.”  What is not specified in the 
mandate is what qualifies as “available”.  Services could be as limited as ask, advise, and refer or as 
resource intensive as multi-session individual counseling.  Health care delivery system factors that affect 
the level and intensity of cessation services may include: the referral and follow-up procedures for 
screening; provider willingness and capacity to offer cessation support; reinforcement for cessation by the 
primary care provider before and/or after the screening visit; availability of centralized cessation services 
within a hospital and/or community-based services, etc. 11 Patient factors may also affect uptake of these 
services and quitting, such as receptivity to counseling and pharmacotherapy, willingness to access 
recommended services and therapies (e.g., Quitline, nicotine replacement), self-efficacy to quit, prior quit 
attempts, and familial support for quitting.   
Effective Guidelines for Treating Tobacco Use Exist:  The PHS Guidelines detail clinic, provider, and 
patient strategies for tobacco cessation which are cost-effective and can impact a large number of 
smokers. 12 Strategies include: 1) implement a tobacco user identification system for all patients; 2) 
educate all clinic staff about strategies to promote cessation; 3) dedicate specific personnel responsible for 
organizing each clinic’s efforts to promote cessation; and 4) use effective, evidence-based treatments for 
tobacco cessation including counseling and pharmacologic treatments. Combining systems- and provider-
level services is more effective in promoting cessation than either approach alone .12   
2.2 
Study Intervention  
 
 
Effective strategies for implementing cessation services during LDCT screening are unknown: 
Primary care settings have traditionally been the locale for PHS Guidelines implementation,13 including 
many clinics that meet the needs of health disparate populations.14–16 However, the LDCT screening 
environment is new and distinct from primary care practices.  Accordingly, prior research “cannot be 
applied without consideration of the setting” (RFA-CA-15-011).  While organizational priority of 
integrating smoking cessation within LDCT screening is high, implementation of the strategies that 
“assist” patients with quitting and ensure follow-up care are limited.11  Greater attention is needed to 
understand the barriers to and opportunities for implementing evidence-based smoking cessation into 

 
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LDCT lung cancer screening imaging facilities.   
Implementation of cessation services in the context of a lung cancer screening encounter may present 
unique challenges. Patients come to the clinic for screening and may not be primed for quitting smoking, 
leading to lower motivation to accept cessation support. Patient motivation may be further weakened if a 
negative LDCT screen creates a false sense of security about personal risk of lung cancer.8,17 
Additionally, providers may perceive cessation as secondary to screening and satisfy the CMS mandate 
through an “ask, advise, and refer” mechanism. This “fulfillment” of the mandate may be no more than 
checking a box, and patients might not follow up with referrals.11,18 Finally, lung cancer screening is 
evolving rapidly in varied clinical contexts (e.g., radiology, pulmonology, free standing clinics vs. 
hospital systems). Different clinical contexts may have unique cultures and clinical operations systems 
making a ‘one size fits all’ approach to implementing tobacco cessation services unlikely.  
 
Implementation Science and Practice Change Models Guide our Scientific Approach: 
Implementation science focuses on the translation of scientific discovery into “real world” clinical and 
community-based settings.19 Translating research findings into practice is challenging, taking ~17 years 
for only 14% of research to benefit patient care, discrediting the assumption that efficacious interventions 
are easily implemented in practice-based settings.20 Implementation research is intended to close the gap 
between efficacious interventions (such as the PHS Guidelines) and real-world health care (such as 
community-based LDCT lung cancer screening  imaging facilities).21 Importantly, implementation 
science emphasizes adaptation to the “local context” to embed evidence-based interventions in clinical 
settings.22  Our proposed study uses implementation science principles as an organizing framework to 
embed the PHS Guidelines into lung cancer screening imaging facilities within NCORP 
components/subcomponents. 
 
2.3  
Rationale 
 
Focus on Cancer Care Delivered in the Community: This proposal is innovative because it will 
leverage NCI’s NCORP community sites, an existing resource for conducting large-scale community-
based trials. Concerns have been expressed that rapid expansion of lung cancer screening may affect 
quality of care in community settings.23,24 Our proposal capitalizes on the NCORP research network to 
support cancer care delivery research.25 We will collect data from 26 community-based lung cancer 
screening facilities nationwide, providing excellent geographic and socio-demographic diversity of 
enrolled patients.  The NCORP is a practice-based research network consisting of 34 NCORP community 
sites and 12 Minority-Based NCORP sites, representing approximately 900 practices nationwide. The 
goal of the NCORP program is to expand access to cancer research to patients without easy access to 
tertiary-care centers, including ethnic minority survivors and those in rural communities. 26 Use of 
NCORP also allows our team to take advantage of NCI-funded data collection infrastructure provided 
through the Wake Forest NCORP Research Base and the NCORP community sites. This is not only 
innovative, but critical to ensure our findings our generalizable to diverse patients treated in community 
settings. 
 
Ensuring Participant Diversity Through Inclusion of Community Screening Facilities:  Smoking 
prevalence and lung cancer incidence are higher among economically disadvantaged, rural,  and 
racially/ethnically diverse communities, patient groups who may be less likely to be treated at academic 
medical centers.9 The vast majority of NCORP component/subcomponents are not academic medical 
centers.  Because our project includes 26 NCORP imaging facilities, including those affiliated with 
Minority-Underserved NCORP community sites, we expect to recruit a geographically, 
socioeconomically, and racial/ethnically diverse patient population who present for LDCT lung cancer 
screening.  Since 1999, the Wake Forest NCORP Research Base has recruited 3,345 patients to clinical 
studies: 29% racial/ethnic minorities and 21% rural, as defined by Rural Urban Commuting Area codes. 

 
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Emphasis on Sustainability & Dissemination: Our research team places high value on disseminating 
research findings to non-academic, community-based settings that will ensure rapid translation of 
cessation services in clinical practice.   We will develop an implementation toolkit with community-based 
LDCT lung cancer screening sites as the “end user” to ensure dissemination of evidence-based smoking 
cessation services to clinics and patients outside of research. 
 
Preliminary Data: Our team has extensive, collaborative experience in conducting randomized, clinic-
based trials for smoking cessation interventions,15,28,29, lung cancer screening;30 training on the clinical 
integration of evidence-based tobacco cessation strategies;31–33 and NCORP studies on smoking cessation.  
 
 
In a randomized, clinic-based study to implement the PHS Guidelines in free clinics 
(R21DA024631-01, Foley, PI; Spangler, Sutfin, Co-Is), we demonstrated the need for cessation 
services in free clinics serving low-income, diverse patients and the ability of our research team 
to successfully implement the PHS Guidelines in low-resource settings.15,16,28,34 Our study was 
highlighted as a model program in An Implementation Guide for Community Health Centers, a 
partnership between Legacy Foundation and Partnership for Prevention (Sept 2013).  
 
In an implementation study to integrate evidence-based tobacco cessation strategies on college 
campuses, we conducted regional, accredited training with student health personnel 
(R21CA161664, Sutfin, PI, Foley, Spangler, Co-Is). We demonstrated an increase in patient 
reports of exposure to tobacco cessation signs/brochures and being screened for tobacco use 
among intervention clinics. Interventions among tobacco users, however, did not significantly 
increase after intervention. 
 
In our collaboration “Development of a Web-Based Tobacco Cessation Curriculum” (R25 
CA96562-01A1, Spangler, PI: Foley, Miller Co-Is), we developed interactive, Web-based 
curricula to integrate tobacco cessation into undergraduate medical education to address a major 
gap in medical education training.31–33   
 
Our research team has led two NCORP studies focused on smoking cessation: (a) Feasibility of 
Delivering a Quitline Based Smoking Cessation Intervention in Cancer Patients Receiving 
Outpatient Treatment (CCCWFU 99211, PI: Weaver; 5U10 CA081851); and (b) Randomized 
Placebo-Controlled Phase 2 Pilot Study of Memantine (Namenda) for Smoking Cessation among 
Cancer Survivors (CCCWFU 99311, Spangler, 5U10 CA081851 ).   An enhanced quitline 
smoking cessation intervention appears to be acceptable to participants and to result in a trend 
towards slightly higher cessation at 12 weeks. 
 
Preliminary data from NCORP. Data from the 2017 NCORP CCDR Landscape assessment, indicate 
that 68% of responding practice groups (224 of 301) had low dose CT screening for lung cancer available 
on site. Management/co-management of LDCT lung cancer screening services took place in a variety of 
departments: radiology (69%), pulmonology 52%), surgery (19%), oncology (36%), and general internal 
or family medicine (18%).   
 
To specifically prepare for this study, we conducted an online survey of NCORP 
components/subcomponents who are and are not current members of the Wake Forest NCORP Research 
Base to ascertain their interest and preliminary eligibility for the study. Ninety percent (n=111) of 
responding components/subcomponents (N= 122) reported having LDCT lung cancer screening available 
onsite. Of these 111 sites, 69 reported screening volume consistent with inclusion in this study (at least 50 
screens in the past 6 months). Most (75%) reported having a central coordinator/navigator to facilitate 
patient scheduling, follow-up, and data entry.  A variety of smoking cessation services were being offered 
at components/subcomponent LDCT screening programs: 59% had a designated person to counsel 
patients, 67% routinely advised patients to use nicotine replacement therapy, 21% provided free or low-

 
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cost nicotine replacement therapy, 22% routinely prescribed pharmacotherapy, 24% enrolled patients in 
online resources, 66% referred patients to telephone quitlines, 29% provided telephone follow-up, 84% 
documented cessation support in the medical record, 64% offered cessation support when sharing 
screening results, and 73% provided cessation educational materials to all current smokers. We counted 
the number of services offered to calculate a current services score from 0-10. Among the 69 clinics that 
had sufficient screening volume, six offered 9-10 services. We contacted these clinics by telephone and 
they reported that the services are not routinely offered to all smoking patients, they are not evaluated, 
and many of the services are fulfilled by referral only (i.e., not offered onsite within the imaging facility). 
All believed that their programs would benefit from participation in the study. 
  
Onsite LDCT lung cancer screening is available onsite at a majority of NCORP 
components/subcomponents surveyed through the 2017 NCORP CCDR Landscape Assessment. As we 
hypothesized, community-based lung cancer screening imaging facilities are emerging in varied clinical 
departments, and health care systems are implementing the CMS mandate to offer smoking cessation in 
diverse way. Yet, we do not know: (1) if the cessation services embedded within LDCT are effective at 
promoting quitting (demonstrating the need for an randomized, control trial design); (2) if there are 
certain strategies for cessation that work well in some lung cancer screening programs, but not others 
(demonstrating the need for implementation science); and (3) how to scale-up implementation of 
evidence-based guidelines in the rapidly emerging landscape of diverse LDCT lung cancer programs 
(demonstrating need for dissemination science).   
 
3. 
SUMMARY OF STUDY PLAN 
 
We utilize an effectiveness-implementation hybrid design, employing a cluster, randomized control 
trial of community-based NCORP sites to study the effectiveness of a multi-faceted intervention to 
improve smoking cessation among lung cancer screening patients, as well as dissemination and 
implementation (D&I) science to optimize and accelerate translation of findings into clinical practice.35,36 
We will: (1) Evaluate a multi-faceted training program to improve short-term smoking cessation rates (1-
week post-visit) and sustained abstinence (3 and 6 months) among 1,114-1300 enrolled smokers (557-
650in each trial arm) who present for LDCT lung cancer screening in community-based lung cancer 
screening practices; (2) Characterize the adoption and adaptation of the evidence-based tobacco cessation 
strategies in 26 community-based LDCT lung cancer screening imaging facilities with NCORP 
components/subcomponents; and (3) Develop and evaluate an implementation toolkit for integrating 
evidence-based tobacco cessation strategies in community-based LDCT lung cancer screening imaging 
facilities. The Wake Forest Study Team will collect qualitative data from key informants at participating 
components/subcomponents during and after intervention implementation. Quantitative survey data 
(baseline, ≤14 days after screening, 3 months after screening, and 6 months after screening) and saliva 
specimens (6 months only) will be collected by participating NCORP sites from smoking patients 
receiving screening within these imaging facilities.    
 
4. 
STUDY SITE AND PARTICIPANT SELECTION 
 
4.1 
NCORP Clinical Site Inclusion Criteria 
 
NCORP clinical site eligibility was determined by an online screener in Spring 2017 and a follow-up 
phone call to NCORP personnel when necessary. The unit of randomization is the lung cancer screening 
imaging facility/facilities within NCORP components/subcomponents.  
 
4.1.1 Initial eligibility was collected electronically via a RedCap survey distributed to NCORP 
components/subcomponents. The survey included organizational characteristics: availability of CT 

 
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screening, # of new lung cancer screenings conducted within the past 6 months, presence of a lung 
cancer screening navigator, and types of smoking cessation services currently offered.  
 
Selection will occur at the level of the NCORP community/ minority underserved community site. Once 
an NCORP site is selected to participate, they will be asked to rank order their eligible 
components/subcomponents in preference of participation. The study investigators will select a 
component/subcomponent from each NCORP sites to participate. The Research Base will randomize the 
lung cancer screening imaging facility/facilities within the NCORP. If less than 26 NCORP sites express 
interest in participating, we will select an additional component/subcomponent from interested NCORP 
sites. Selected components/subcomponents may not share personnel across multiple lung cancer screening 
imaging facilities. Up to two components/subcomponents per NCORP community/minority community 
site may be eligible.  
 
Screening programs must meet all of the following eligibility criteria:  
 
4.1.2 
Lung cancer screening imaging facility/facilities within an NCORP components/subcomponents 
screened >= 50 patients for lung cancer within the past six months.  
4.1.3 
Agrees to have NCORP research personnel serve as the study liaison and another person to serve 
as the cessation program champion. The major qualifications of the champion are: availability of 
the champion at the time of the screening visit, a commitment to smoking cessation, 
communication skills, and the capacity to affect change within the imaging facility. Examples of 
appropriate champions include, but are not limited to, the lung cancer screening coordinator or 
navigator, nurse/NP/PA on site who provides cessation services, or physician leader of screening 
program. We will also ask the “program champion” to help identify an assistant who can assume 
this role in the absence of the designated program champion – either for time away, transfer, or 
change in job description.  
 
4.1.4 
Agrees to participate in all aspects of the intervention, randomization, and evaluation.   
 
4.1.5 
The lung cancer screening location at the participating components/subcomponents must be 
rostered with a current CTEP code and have a rostered investigator available to enroll patients. 
 
Randomization of Lung Cancer Screening Imaging Facilities within Components/Subcomponents:  
Three general characteristics will be considered as stratification factors prior to randomizing sites.  These 
include: 1) lung screening volume, 2) current cessation services offered, and  3) race/ethnicity distribution 
of patients screened at the imagining facility.  These three characteristics are included because we believe 
that each should be balanced between the treated and usual care sites to avoid possible confounding that 
could exist if they were imbalanced after randomization. 
 
Prior to randomization, each site will complete the Pre-Randomization Site Checklist (Appendix 18). We 
will assess the distribution of lung cancer screening volume  and % white, non-Hispanic in the population 
of patients seen for lung cancer screening at the imaging facility  and decide on approprite cutpoints for 
strata. For current cessation services offered, we performed a short survey that assessed 10 possible 
cessation support services (e.g., medication, counseling, QuitLine) that could be offered, and determined 
that a threshold of 0-5 versus 6+ should be used to stratify sites.  For the 6 clinics that offered 9-10 
services, we contacted these clinics. These clinics reported that the services are not routinely offered to all 
smoking patients, they are not evaluated, and many of the services are fulfilled by referral only (aka: not 
offered onsite within the imaging facility). Therefore, we will not exclude clinics based on a high ‘self-
reported’ rate of cessation services, but will stratify to ensure balance in cessation services in the 
intervention and usual care arms of the study. The actual values (volume, cessation services score, and % 
white, non-Hispanic) will be available as site level covariates that can be included in final analytical 

 
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models when assessing the intervention effect.  In addition, individual level variables (race/ethnicity) can 
also be adjusted for in the final models if needed. 
 
Rationale for Randomization:  To reduce the likelihood that participants over- or under-state receipt of 
cessation services (e.g., advised to quit, provided with a text-to-quit number) patients will not be informed 
to which type of clinic (intervention vs. usual care) they are randomized.  This is especially important to 
ensure that our implementation outcome, fidelity to the intervention, is not influenced by knowing the 
study arm whereby reducing the likelihood of response bias.  The patient consent form explains, as 
follows: 
 
“You are being invited to participate in a research study. This study has public funding from the National 
Cancer Institute (NCI), part of the National Institutes of Health (NIH) in the United States Department of 
Health and Human Services. The clinic you are visiting is part of a randomized trial designed to test 
whether or not training lung cancer screening staff improves their ability to help patients quit 
smoking.  We are working with 26 clinics across the United States; half of the clinics receive training and 
half of the clinics do not receive training. We are inviting you to participate in this study to help us 
evaluate the effectiveness of our training.” 
 
If patients ask clinic staff if they are in an intervention vs. usual care clinic, staff may inform patients. 
There are two groups of study participants:  patients and key informants. 
 
4.2 
Patient  Inclusion Criteria 
 
4.2.1 
Age 55-77, reflecting the age criteria for the USPSTF guideline-approved referral for lung 
screening.   
 
4.2.2 
Patient participants must also be a current smoker, defined as anyone who responds “every day” 
or “some days” to the question: “Do you smoke cigarettes every day, some days, or not at all?” 
(BRFSS).  
 
4.2.3 
Patients with a history of lung and/or other cancer(s) (who do not have current signs or symptoms 
of lung cancer) will be eligible.   
 
4.3 
Patient Exclusion Criteria 
 
4.3.1 
Current use (previous 30 days) of a tobacco dependence treatment including bupropion, 
varenicline, and nicotine replacement because the person is trying to quit. Use of bupropion for 
depression does not exclude the patient from participating. The occasional use of tobacco 
dependence treatment (e.g., NRT) to avoid using tobacco in public spaces is not considered to be 
an exclusion criteria. 
 
4.3.2 
Individuals who use e-cigarettes and who are not smoking cigarettes.  Dual users (those who use 
both e-cigarettes and cigarettes) will be included in the trial. 
 
4.3.3  The presence of a physical or cognitive impairment that would prevent a person from engaging in 
survey research (such as blindness, deafness, or dementia). 
 
4.3.4  Individual has already completed the intended LDCT lung cancer screening for this study.  
 
4.3.5 
Non-English speaking 
4.4 
Patient Recruitment and Retention Strategy  

 
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The lung cancer screening clinic will provide the site coordinator with information on when patients are 
scheduled to be screened for lung cancer.  The site coordinator will come to the clinic on the day when 
patients are scheduled, invite them to participate, and if interested, screen them for eligibility.  A waiver 
of documentation of written consent is appropriate for eligibility screening because the research presents 
no more than minimal risk of harm to subjects and involves no procedures for which written consent is 
normally required outside of the research context.  Among patients who are eligible, the site coordinator 
will invite patients to participate in the research study, administer a written informed consent, and conduct 
the baseline survey (~10-15 minutes).  By conducting the interview in-person at baseline, we reduce the 
likelihood of having enrolled patients to the study who may otherwise “no show” to their appointment 
and would therefore be enrolled, but never exposed to the intervention. 
 
We will track numbers of individuals approached and screened, and reasons for nonparticipation.  All 
written materials will be at an 8th grade reading level. We will seek participant permission at baseline to 
follow-up with participants via telephone ≤ 14 days of the baseline interview (to assess receipt of the 
intervention and immediate cessation) and at 3-months (short-term cessation) and 6-months (sustained 
abstinence).  Participants will be given the opportunity to drop out of the study at any time. A Participant 
Recruitment Flow Chart and sample recruitment script is provided in Appendix 1. 
 
4.5. 
Patients:  Inclusion of Racial/Ethnic Minorities  
 
 
We will encourage participating components/subcomponents to approach all smoking patients, regardless 
of race/ethnicity and ensure an even distribution of NCORP components/subcomponents with a high 
versus low percentage of racial/ethnic minority patients in our study by including proportion 
minority/white as a stratification factor prior to randomization. All Minority-Underserved NCORPs 
affiliated with the WF NCORP RB have been informed of the study and will be invited to participate. We 
will emphasize the importance of robust minority accrual at our study kickoff meetings and provide 
specific education and discussion about strategies to overcome barriers that underserved patients may 
experience to study participation. Leaders of the Wake Forest Baptist Comprehensive Cancer Center 
Office of Cancer Health Equity will facilitate this aspect of training and have provided feedback on our 
recruitment strategy. We will also ask participating Minority-Underserved NCORPs to provide 
suggestions about strategies for approaching and consenting racial/ethnic minority patients. We will 
monitor minority recruitment rates at our monthly WF NCORP RB executive steering committee 
meetings and provide feedback to the NCORP sites via bi-monthly study teleconference calls. 
Specifically, we will monitor the minority recruitment rate in conjunction with available data about the 
population of patients receiving lung cancer screening at the site to identify sites that are potentially under 
and over performing with regards to minority accrual. Sites with strong minority recruitment will be 
asked to share their experiences with other sites during these calls.   
 
Both men and women (as applicable) and members of all races and ethnic groups are eligible for this trial. 
The table reflects the number of patient participants enrolled at baseline assuming 1114 total enrolled. If 
we recruit up to 1300 to account for attrition and balance across recruitment sites, we anticipate 
maintaining the same cell percentages as described below.  
  
Females 
Males 
Total 
Ethnic 
  
  
  
Hispanic 
5 
13 
18 
Not Hispanic 
463 
633 
1096 
ETHNIC TOTAL 
468 
646 
1114 
  
 
 
 

 
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Females 
Males 
Total 
Racial 
 
 
 
Am Indian 
5 
7 
12 
Asian 
0 
0 
0 
Native Hawaiian 
0 
0 
0 
Black 
47 
64 
111 
White 
416 
575 
991 
RACIAL TOTAL 
468 
646 
1114 
 
4.6 
Key Informant Inclusion Criteria 
 
4.6.1 
Age ≥18 years 
 
4.6.2  Member of the lung cancer screening team who is (or would be) responsible for implementation 
and/or supporting smoking cessation support for patients receiving lung cancer screening. This 
will include the program champion (Intervention Clinic only) and is likely to include:  imaging 
facility program directors, health care providers (e.g., physicians, radiological technicians), and 
other staff (e.g., receptionist). Coordinators of centralized services for tobacco cessation at the 
component/subcomponent would also be eligible. 
 
4.6.3 
Agrees to participate in a confidential 1-on-1 semi-structured interview with the research team. 
 
4.6.4 
Agrees to have the interview taped, transcribed and qualitatively analyzed.  
 
4.7 
Key Informant Exclusion Criteria 
 
 
4.7.1 
<18 years of age 
 
4.7.2 
Unwilling to participate 
 
4.8 
Key Informant Recruitment and Retention Strategy 
 
The NCORP Site Coordinator and the Cessation Program Champion will work with the Wake Forest Study 
Team to identify 3 key informants within each LDCT imaging facility. Key informants should be 
individuals who are (or would be) responsible for implementation and/or supporting cessation support. Key 
informants will include the program champion (Intervention Clinic only) and are likely to include:  imaging 
facility program directors, health care providers (e.g., physicians, radiological technicians), and other staff 
(e.g., receptionist). Coordinators of centralized services for tobacco cessation will also be invited to 
interview, if applicable. Once key informants are identified, the Wake Forest Study Team project manager 
will electronically send the NCI CIRB approved Key Informant informed consent form to each identified 
key informant and conduct consent to the study by phone.  The Key Informant informed consent form will 
be signed by the key informant and returned electronically to the Wake Forest Study Team project manager 
prior to initiating the interview.  A copy of the complete, signed consent form will be provided to the Key 
Informant.  The Wake Forest Study Team will be responsible for consenting Key Informants and 
maintaining records of the signed Key Informant informed consent forms. The structured survey and 
interview guide are found in Appendices 5, 6, 21 and 22.  
 
 
Intervention Sites:  The key informant baseline interviews (which include both structured and open-ended 

 
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questions) will be conducted by telephone prior to the first onsite visit to the imaging facility.  The key 
informant follow-up interviews will be conducted approximately 8 months after baseline (following full 
implementation) and will also be conducted by telephone.    
 
Usual Care Sites:  The baseline interview will be conducted during the same time period as the baseline 
interviews in the intervention sites and will be conducted by telephone. The follow-up key informant 
interviews will occur approximately 8 months later by telephone, and will coincide with the implementation 
training for those clinics that choose to participate in the delayed intervention.   
 
Total number of key informant interviews: 
Intervention Sites:  39 baseline, 39 follow-up (assumes an average of 3 interviews for each of 13 sites) 
Usual Care Sites: 39 baseline, 39 follow-up (assumes an average of 3 interviews for each of 13 sites) 
 
The baseline structured survey (Appendix 5) focuses on the feasibility and appropriateness of the clinic 
offering several different cessation services while the follow-up structured survey (Appendix 21) focuses 
on implementation of smoking cessation strategies and sustainability of those cessation strategies. The 
baseline semi-structured interview (Appendix 6) focuses on: (a) cessation services offered; (b) perceived 
need for integrating cessation strategies within lung screening; (c) compatibility/appropriateness of these 
services within lung screening; (d) relative advantage of offering cessation support as it relates to other 
needs of the patients; (e) resources needed to implement and administer services. The follow-up semi-
structured interview (Appendix 22) focuses on new strategies implemented, sustainability, leadership 
support for cessation services, perceived need for change, and access to necessary resources to ensure the 
cessation services could be implemented and sustained. Key informants in the intervention group will likely 
be in regular contact with members of the study team as part of the intervention, encouraging their retention. 
Usual care sites are encouraged to maintain regular communication with key informants regarding study 
progress. 
   
Our goal is to maintain the same key informants at baseline and follow-up, although we recognize that staff 
may change (e.g., new critical hire, promotions) during the course of the study.  For key staffing positions 
(both new and replacement positions, such as a clinical nurse navigator), we will include these individuals 
in the study at follow-up only and identify these individuals as someone new to the study. 
 
4.9 
Key Informants: Inclusion of Women and Minorities 
 
All nominated key informants, regardless of gender or race/ethnicity will be invited to participate.  
Of 78 total key informants, we expect 70% (n=55) to be women, 5% (n=4) to be Hispanic, and 10% to be 
racial minority (n=8). 
  
Females 
Males 
Total 
Ethnic 
  
  
  
Hispanic 
3 
1 
4 
Not Hispanic 
52 
22 
74 
ETHNIC TOTAL 
55 
23 
78 
  
 
 
 
Racial 
 
 
 
Am Indian 
0 
0 
0 
Asian 
1 
0 
1 
Native Hawaiian 
0 
0 
0 
Black 
6 
1 
7 

 
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Females 
Males 
Total 
White 
48 
22 
70 
RACIAL TOTAL 
55 
23 
78 
4.10 
Cancer Therapy Evaluation Program Investigator Registration Procedures 
 
4.10.1 All sites must register through the CTSU. 
Food and Drug Administration (FDA) regulations and National Cancer Institute (NCI) policy require all 
individuals contributing to NCI-sponsored trials to register and to renew their registration annually.  To 
register, all individuals must obtain a Cancer Therapy Evaluation Program (CTEP) Identity and Access 
Management (IAM) account at https://ctepcore.nci.nih.gov/iam.  In addition, persons with a registration 
type of Investigator (IVR), Non-Physician Investigator (NPIVR), or Associate Plus (AP) (i.e., clinical site 
staff requiring write access to OPEN, RAVE, or TRIAD or acting as a primary site contact) must complete 
their annual registration using CTEP’s web-based Registration and Credential Repository (RCR) at 
https://ctepcore.nci.nih.gov/rcr.   
RCR utilizes five person registration types: 
 
IVR — MD, DO, or international equivalent; 
 
NPIVR — advanced practice providers (e.g., NP or PA) or graduate level researchers (e.g., PhD); 
 
AP — clinical site staff (e.g., RN or CRA) with data entry access to CTSU applications (e.g., 
Roster Update Management System (RUMS), OPEN, Rave,); 
 
Associate (A) — other clinical site staff involved in the conduct of NCI-sponsored trials; and 
 
Associate Basic (AB) — individuals (e.g., pharmaceutical company employees) with limited 
access to NCI-supported systems. 
 
RCR requires the following registration documents: 
Documentation Required 
IVR 
NPIVR 
AP 
A 
AB 
FDA Form 1572 
 
 
Financial Disclosure Form 
 
 
 
NCI Biosketch (education, training, employment, 
license, and certification) 
 
 
 
HSP/GCP training 
 
 
 
Agent Shipment Form (if applicable) 
 
CV (optional) 
 
 
 
 
An active CTEP-IAM user account and appropriate RCR registration is required to access all CTEP and 
Cancer Trials Support Unit(CTSU) websites and applications.  In addition, IVRs and NPIVRs must list all 
clinical practice sites and Institutional Review Boards (IRBs) covering their practice sites on the FDA 
Form 1572 in RCR to allow the following: 

 
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 
Addition to a site roster, 
 
Assigned the treating, credit, consenting, or drug shipment (IVR only) tasks in OPEN, 
 
Act as the site-protocol Principal Investigator (PI) on the IRB approval; and 
 
Assign the Clinical Investigator (CI) role on the Delegation of Tasks Log (DTL). 
In addition, all investigators act as the Site-Protocol PI, consenting/treating/drug shipment, or as the CI on 
the DTL must be rostered at the enrolling site with a participating organization (i.e., Alliance). Additional 
information is located on the CTEP website at  https://ctep.cancer.gov/investigatorResources/default.htm.  
For questions, please contact the RCR Help Desk by email at RCRHelpDesk@nih.gov. 
 
4.10.2 Cancer Trials Support Unit Registration Procedures 
 
This study is supported by the NCI Cancer Trials Support Unit (CTSU).Protocol Documents are found on 
the CTSU website, but supplemental documents may be available on the Wake Forest NCORP Research 
Base website.  
 
IRB Approval:   
 
For CTEP and Division of Cancer Prevention (DCP) studies open to the National Clinical Trials Network 
(NCTN) and NCI Community Oncology Research Program (NCORP) Research Bases after March 1, 
2019, all U.S.-based sites must be members of the NCI Central Institutional Review Board (NCI CIRB). 
In addition, U.S.-based sites must accept the NCI CIRB review to activate new studies at the site after 
March 1, 2019. Local IRB review will continue to be accepted for studies that are not reviewed by the 
CIRB, or if the study was previously open at the site under the local IRB. International sites should 
continue to submit Research Ethics Board (REB) approval to the CTSU Regulatory Office following 
country-specific regulations.  
 
Sites participating with the NCI CIRB must submit the Study Specific Worksheet for Local Context 
(SSW) to the CIRB using IRBManager to indicate their intent to open the study locally. The NCI CIRB’s 
approval of the SSW is automatically communicated to the CTSU Regulatory Office, but sites are 
required to contact the CTSU Regulatory Office at CTSURegPref@ctsu.coccg.org to establish site 
preferences for applying NCI CIRB approvals across their Signatory Network. Site preferences can be set 
at the network or protocol level. Questions about establishing site preferences can be addressed to the 
CTSU Regulatory Office by emailing the email address above or calling 1-888-651-CTSU (2878). 
 
Sites using their local IRB or REB, must submit their approval to the CTSU Regulatory Office using the 
Regulatory Submission Portal located in the Regulatory section of the CTSU website. Acceptable 
documentation of local IRB/REB approval includes:  
 
 
Local IRB documentation; 
 
IRB-signed CTSU IRB Certification Form; and/or 
 
Protocol of Human Subjects Assurance Identification/IRB Certification/Declaration of  
 
Exemption Form.  
 
In addition, the site-protocol Principal Investigator (PI) (i.e. the investigator on the IRB/REB) must meet 
the following criteria to complete processing of the IRB/REB approval record: 
 
Holds an Active CTEP status; 
 
Rostered at the site on the IRB/REB approval and on at least one participating roster; 
 
If using NCI CIRB, rostered on the NCI CIRB Signatory record; 
 
Includes the IRB number of the IRB providing approval in the Form FDA 1572 in the RCR 
 
profile; and 

 
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 
Holds an appropriate CTEP registration type for the protocol. 
 
 
 
Additional Requirements  
 
Additional requirements to obtain an approved site registration status include: 
 
An active Federal Wide Assurance (FWA) number; 
 
An active roster affiliation with the Lead Protocol Organization (LPO) or a Participating Organization 
(PO); and 
 
Compliance with all protocol-specific requirements (PSRs). 
 
Sites participating on the NCI CIRB initiative that are approved by the CIRB for this study are not 
required to submit IRB approval documentation to the CTSU Regulatory Office. For sites using the 
CIRB, IRB approval information is received from the CIRB and applied to the RSS in an automated 
process. Signatory Institutions must submit a Study Specific Worksheet for Local Context (SSW) to the 
CIRB via IRB Manager to indicate their intent to open the study locally.  The CIRB’s approval of the 
SSW is then communicated to the CTSU Regulatory Office.  In order for the SSW approval to be 
processed, the Signatory Institution must inform the CTSU which CIRB-approved institutions aligned 
with the Signatory Institution are participating in the study. 
 
Protocol Specific Requirements for WF-20817CD Site Registration:  
 
• 
IRB approval (For sites not participating via the NCI CIRB; local IRB documentation, an IRB-
signed CTSU IRB Certification Form, Protocol of Human Subjects Assurance Identification/IRB 
Certification/Declaration of Exemption Form, or combination is accepted) 
 
Multi-faceted training program to include: (1) in-person, didactic and case-based training on 
evidence-based strategies to assist patients with quitting and strategies that can be used to arrange 
follow-up services; (2) site-specific SWOT analysis to guide implementation of the PHS 
Guidelines; and (3) performance coaching for eight months during the implementation phase.  
 
Submitting Regulatory Documents:  
 
Submit required forms and documents to the CTSU Regulatory Office via the Regulatory Submission 
Portal on the CTSU website.  
 
To access the Regulatory Submission Portal log on to the CTSU members’ website  Regulatory  
Regulatory Submission.  
 
Institutions with patients waiting that are unable to use the Regulatory Submission Portal should alert the 
CTSU Regulatory Office immediately at 1-866-651-2878 in order to receive further instruction and 
support. 
 
Checking Your Site’s Registration Status: 
You can verify your site registration status on the members’ side of the CTSU website. 
 
 
Log on to the CTSU members’ website; 
 
Click on Regulatory at the top of your screen;  
 
Click on Site Registration; 
 
Enter your 5-character CTEP Institution Code and click on Go. 
 

 
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Note: The status shown only reflects institutional compliance with site registration requirements as 
outlined above. It does not reflect compliance with protocol requirements for individuals participating on 
the protocol or the enrolling investigator’s status with the NCI or their affiliated networks. 
 
4.11 
Research Base Online Patient Enrollment 
 
4.11.1 The Wake Forest NCORP Research Base will randomize at the level of the lung cancer screening 
imaging facility/facilities within NCORP components/subcomponents. The intervention program 
targets the providers and clinic within the intervention arm of the trial.  All patients who present 
for lung cancer screening and are seen in an intervention clinic may be exposed to provider and/or 
clinic level changes that result from intervention. Intervention strategies focus on training and 
performance coaching to support clinics and providers as they implement the PHS Guidelines for 
smoking cessation.  Patients in both arms of the trial who meet eligibility for the study will be 
invited and consented to participate.  
 
4.11.2 Online Patient Enrollment 
 
NCORP site staff will electronically enroll their study participants in the WF CCC REDCap website, 
https://redcap.wakehealth.edu/redcapccc. Step-by-step instructions will be provided by the WF NCORP 
Research Base Data Management Center (DMC). 
 
If you have questions related to the electronic subject enrollment process or require assistance with 
electronic enrollment, please contact the WF NCORP Research Base DMC between 8:00am and 5:00pm 
EST, Monday through Friday at (336) 716-0891; or contact Rebecca Stone at (336) 716-6201. 
REDCap is a secure, web-based and HIPAA compliant forms and research database platform utilized by 
the WF NCORP for many research projects. This study will be using REDCap as the electronic data 
collection platform with electronic Case Report Form (eCRF) for multi-site studies. Site users must have 
current Human Subject Protection (HSP) and Good Clinical Practice (GCP) training certification in order 
to be granted access to the WF CCC REDCap system. Sites may submit user information including user 
name, email, CTEP ID, and training records to NCORP@wakehealth.edu. 
 
5. 
AGENT ADMINISTRATION - NA 
 
6. 
PHARMACEUTICAL INFORMATION - NA 
 
7. 
CLINICAL EVALUATIONS AND PROCEDURES 
 
7.1 
Patient Schedule of Events  
 
Evaluation of the intervention depends on administration of surveys at baseline, within 14 days after the 
lung cancer screening visit, 3-months after baseline, and 6-months after baseline. At 6 months cotinine 
salivary sample will be collected on participants who self-report not smoking within the last 7 days. The 
patient schedule of events is as follows: 
 
Prior to Enrollment:   
 
Eligibility Assessment 
 
Informed Consent 
 
In-Person, Interviewer-Administered Baseline Survey: 
 
Complete the baseline questionnaire at the time the patient presents for screening, prior to their 
scan. 

 
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Survey Between 1-14 Days After the Lung Cancer Screening Appointment: 
 
≤14 Day Telephone Patient Survey  
3-Months after the Lung Cancer Screening Appointment: 
 
Complete the 3-Month Telephone Patient Survey  
 
CRA completes Lung Cancer Screening Imaging Report 
 
6-Months after the Lung Cancer Screening Appointment: 
 
Complete the 6-Month Telephone Patient Survey  
 
Saliva collection only for patients who self-report not smoking within the last 7 days 
 
Evaluation of the intervention depends on surveys (Baseline, ≤14 days of the lung cancer screening visit, 
3-months after baseline, and 6-months after baseline). At 6 months, a cotinine salivary sample will be 
collected on participants who self-report not smoking within the last 7 days.  
 
Study Patient Assessments 
Screen 
In-
person 
Baseline 
In-person  
≤14 days 
Telephone 
3-months 
Telephone 
(7 days 
prior and up 
to 21 days 
after) 
6-months 
Telephone 
(7 days 
prior and up 
to 21 days 
after) 
Eligibility Checklist 
X 
 
 
 
 
Reason for Refusal (Baseline) 
 
X 
 
 
 
Patient Survey Baseline  
 
X 
 
 
 
Reason for Refusal (Follow-up) 
 
 
X 
X 
X 
Patient Survey ≤ 14 Days 
 
 
X 
 
 
Patient Survey 3 Months  
 
 
 
X 
 
Lung Cancer Screening Imaging Report 
 
 
 
Appended 
at time of 3-
month 
survey 
 
Patient Survey 6 Months 
 
 
 
 
X 
Cotinine validation of smoking status, for 
those who self-report not smoking 
 
 
 
 
X 
 
7.2 
Patient Baseline Testing/Pre-study Evaluation 
 
All individuals who visit a participating lung cancer screening program will receive a single page 
document that informs him/her that the site clinic is participating in the study, regardless of his/her 
eligibility or interest. This will be an information-only sheet provided at check-in which describes the 
purpose of the study.  Trained NCORP clinical site personnel will screen individuals for eligibility during 
a regularly scheduled lung cancer screening visit. If the individual meets all eligibility criteria and agrees 
to participate, trained NCORP site staff at each NCORP clinic site will seek interest and written informed 
consent for participating in the study.  
 
Participants taking nicotine replacement therapy or other pharmacotherapy to promote smoking cessation 
(e.g., bupropion) will be excluded if taking these medications at baseline—See exclusion criteria.  The 
NCORP clinical site staff will measure whether the participant begins taking these over-the-counter and 
prescribed medications at the ≤14 day, 3-month and 6-month follow-up surveys in order to measure 

 
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intervention effectiveness.  It is not necessary to obtain concomitant medications for these participants as 
the collection of this information would pose an unnecessary burden to participants and is not needed to 
answer the questions in this research study.  
 
Individuals who decline participation will be asked to complete the brief decline form which includes 
basic demographic information and primary reason for declining study participation. 
 
Patient surveys (baseline, ≤14 days, 3 months, and 6 months) are found in Appendices 9-12. Core 
measures include:  demographics, health status, smoking history, quitting behavior, perceptions of lung 
cancer risk and worry, impact of screening on tobacco use behavior, and exposure to the intervention. The 
baseline assessment will be administered by an interviewer and completed in-person. All responses will 
be hand recorded by NCORP site staff on paper forms and/or entered directly into the online database.  If 
data are collected on paper forms, NCORP site staff will be responsible for entering the data into 
REDCap.  We will also collect contact information from a secondary contact person (Appendix 9) that 
will be stored in a separate de-identified data entry screen. 
 
Participants will receive a $10 gift card at the time the Baseline survey is completed. Gift cards will be 
supplied directly to the NCORP site coordinator at each participating clinic for the baseline data 
collection and given out by the site coordinator/data collector.  They will be distributed at the completion 
of the survey.  
 
7.3 
Patient Evaluation During Study Intervention 
NCORP site coordinator will call each participant to administer a 5-minute telephone survey within 14 
days of the lung cancer screening clinic visit.  Participants will receive a $10 gift card following 
completion of the 14 day telephone survey, distributed by Wake Forest Study Team as described in 
Section 7.4.  This assessment focuses on exposure to the intervention and subsequent quit attempts.   
 
7.4 
Patient Follow-up Period 
Short- and long-term abstinence will be measured by telephone survey at 3 months and by telephone 
survey with cotinine validation for non-smokers 6 months after baseline.  These surveys should take <5 
minutes and will assess quit attempts, smoking cessation, and strategies used to try quitting. Patients will 
be offered a $10 gift card for participation at each wave of the survey and $20 for returning the saliva 
sample. Gift Cards will be mailed to participants by the Wake Forest Study Team. 
To minimize attrition, NCORP study staff will mail pre-printed/pre-postage paid sealed postcards to 
participants 1-2 weeks prior to the 3- and 6-month follow-up surveys.  At least three attempts will be 
made to reach each participant by phone.  As a final step, the team will consider a mailed survey to non-
respondents with an enclosed incentive.   
 
Rationale and Strategies for Minimizing Attrition:  
In a study led by PI Kristie Foley, we trained safety net clinic staff how to integrate the PHS Guidelines 
and support cessation during routine clinical visits.  Ninety-nine percent of patients who were approached 
during their clinical visit agreed to participate in the baseline survey.16 
 
In Strecher et al.,49 of the potential 3256 patients who visited an HMO, 2651 were screened for eligibility 
(81%).  Of those, approximately 60% were eligible to participate (with the main reason for ineligibility 
was too limited smoking or contraindications of NRT usage).  We proposed that we would need to screen 
2500 at baseline to identify 1,114 eligible smokers (45%).  At six month follow-up, 76% were retained in 
the cohort and were contacted by telephone to complete the survey.49  We proposed that 75% of the 

 
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original cohort would be retained at 6-months, consistent with the Strecher et al. study.   
 
 
In Bock et al.,50 low-income smokers were recruited and assessed at baseline, 1 month, 2 months, 6 
months, and 12 months with biochemical verification of smoking status at each of the follow-up time 
points.  In this study 16% of participants dropped out immediately after the baseline assessment. 
 
If we find that we have a higher than expected drop out at our ≤14 day assessment (we expect 7%), we 
will be well-positioned to recruit additional participants to ensure that we sustain at least 75% of the 
original cohort at the 6-month time point (the primary endpoint). We will work closely with our statistical 
team to assess attrition at ≤14 days and 3 months.  
 
The following strategies will be used to minimize attrition: 
 
 
Including secondary contact information as part of the baseline patients survey (maintained in a 
participant de-identified secondary data base) 
 
Sealed reminder post cards, 1-2 weeks prior to the telephone survey 
 
Pre-printed/pre-stamped sealed “thank you” post cards with enclosed gift card, after completing a 
survey 
 
Mailed survey with incentive included in the mailing (as a final resort) 
 
This is a surveillance study and participants are only indirectly targeted by the intervention as a result of 
being screened in intervention clinics, whereby minimizing participant burden and maximizing follow-up.  
Participants will receive a $10 gift card at each wave of the survey and $20 for completing the salivary 
cotinine at 6-months.   
 
We will carefully monitor accrual. Given that we have a ≤14 day follow-up survey, we will be able to 
assess any concerns with early drop out and be able to recruit additional patients to the study. We will 
work closely with our statisticians to ensure adequate accrual and maintenance of the cohort. 
 
Self-reported smoking status will be validated at six months using salivary cotinine among patients who 
report successful quitting during the 6-month telephone survey. When a research participant self-
identifies as a non-smoker at 6-months, this will be an electronically ‘flagged’ response, such that this 
will trigger the distribution of the cotinine assay from the Wake Forest NCORP Research Base Lab 
located in Winston-Salem, NC.  The Wake Forest NCORP Research Base Lab will be responsible for 
shipping kits and receiving the cotinine samples. 
 
Cotinine, a major metabolite of nicotine with a long half-life, is highly sensitive and specific for tobacco 
use, making it an excellent test for confirming tobacco cessation. 37 Patients will receive via mail a 
salivary collection kit (including a salivette—a plastic vial that contains a small cotton roll, like those 
used by dentists) along with written instructions on how to obtain the salivary sample.  The written 
instructions will explain that participants should place the absorbent roll under their tongue for 1-2 
minutes and then replace the roll in the storage tube. They should collect the sample in the morning 
before breakfast and coffee, or drinking, and before brushing their teeth. The completed test kit should be 
returned to Wake Forest NCORP Research Base Lab within one week. This is a validated procedure for 
collecting saliva via mail.48  
 
Saliva samples will be collected from subjects using SalivaBio Oral Swab saliva collection kits available 
from Salimetrics, Inc. (Carlsbad, CA). Saliva specimens will be mailed to the NCORP Research Base 
Core Lab, centrifuged to collect the saliva from the swabs, the volume measured, and transferred to 
smaller freezer tubes for storage of the specimen at -80°C. Cotinine levels will be determined by ELISA 

 
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using the high sensitivity Salivary Cotinine quantitative Enzyme Immuno Assay kit provided by 
Salimetrics, Inc. This is a competitive immune assay kit with a determination range from 0.8 to 200 
ng/mL. Saliva samples will be analyzed in duplicate. When the determined level of a sample is above the 
upper range of the ELISA (200 ng/mL), the assays will be repeated with a higher sample dilution to 
obtain cotinine levels within the standard range of the assay. Analysis will be conducted by the Wake 
Forest NCORP Core Lab located in Winston-Salem, NC.   
 
To maximize validation, NCORP site staff should encourage the return of the saliva kits at the completion 
of the 6 month survey. Participants that do not return the kit within three weeks of mailing will be 
contacted by site staff to determine if the participant did not receive the kit or chose not to complete the 
kit. If the participant indicates that they would still like to participate and complete the kit, an additional 
kit may be mailed to them. Participants will be given a $20 gift card for returning the saliva sample. Once 
the specimen is received, the WF project manager will be notified and the gift card will be mailed by the 
WF project manager. Results of the assay will be recorded by the Core Lab.  
 
7.5 
Methods for Patient Clinical Procedures- NA 
 
7.6 
Clinic Assessment 
 
NCORP sites will be invited to participate in the study via email and participating 
components/subcomponents will be asked to confirm their agreement to participate.  If a 
component/subcomponent chooses not to participate, another component/subcomponent will be selected 
from the remaining eligible components/subcomponents within that NCORP site and/or another NCORP 
site will be invited to participate. 
 
Prior to randomization, each participating component/subcomponent will complete the Pre-
Randomization Site Checklist (Appendix 18). We will assess the distribution of lung cancer screening 
volume  and % white, non-Hispanic in the population of patients seen for lung cancer screening at the 
imaging facility  and decide on approprite cutpoints for strata. For current cessation services offered, we 
performed a short survey that assessed 10 possible cessation support services (e.g., medication, 
counseling, QuitLine) that could be offered, and determined that a threshold of 0-5 versus 6+ should be 
used to stratify sites.  The actual values (volume, cessation services score, and % white, non-Hispanic) 
will be available as site level covariates that can be included in final analytical models when assessing the 
intervention effect.  In addition, individual level variables (race/ethnicity) can also be adjusted for in the 
final models if needed. 
 
Both intervention and usual care clinics will complete the baseline organizational characteristics 
assessment (Appendix 8) and the follow-up organizational characteristics assessment (Appendix 23). Key 
informant interviews will be conducted by phone by a Wake Forest Study Team Member for both 
intervention and usual care clinics. The semi-structured surveys and interviews will be performed at 
baseline and at a follow-up time point, approximately 8 months later.  
 
 
 
 
 
 
 
 
 
 
 

 
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Study Site Assessments 
Eligibility 
Selection 
Randomization  
Baseline 
~8 mo 
Follow-up 
Preliminary Eligibility Checklist 
X 
 
 
 
 
Site Invitation to Participate 
 
X 
 
 
 
Pre-Randomization Site Checklist  
 
X 
 
 
 
Baseline Organizational  
Characteristics 
 
 
X 
 
 
Key Informant Interview & Guide  
(Used by Wake Forest Study Team 
Members when conducting the Key 
Informant Interviews) 
 
 
 
X 
 
Follow-up Organizational 
Characteristics 
 
 
 
 
X 
Key Informant Follow-up Interview 
& Guide (Used by Wake Forest 
Study Team Members when 
conducting the Key Informant 
Interviews) 
 
 
 
 
X 
 
7.7 
Core Elements and Guiding Assumptions of the Intervention 
 
Our multi-faceted training program targets health care delivery system changes (e.g., providers, clinics); 
therefore, all patients seeking LDCT screening at a single site will be in either the intervention or usual 
care arm of the RCT. Usual care clinics will receive instruction in evaluation and invited to attend a 
regional training program during Fall 2019. Intervention clinics will begin the training program via 
webinars. 
 
Our multi-faceted training program includes:  (1) webinars on evidence-based strategies to assist patients 
with quitting and strategies that can be used to arrange follow-up services; (2) in-person site-specific 
SWOT analysis and logic model development to guide implementation of the PHS Guidelines; and (3) 
performance coaching for eight months during the implementation phase.  The rationale for our approach 
is based on the following.  First, we have evidence-based guidelines to promote cessation that have been 
tested in various clinical venues and have demonstrated success via meta-analyses. We cannot assume, 
however, that the Guidelines will be efficacious in the context of LDCT lung cancer screening. Second, 
the strategies that accompany these guidelines are likely to be adopted if they are easy to implement (e.g., 
they are time and cost neutral, they are well-received by the implementers, they fit within the mission of 
the organization) and with implementation support. Third, strategies may be adapted to simplify 
implementation and adaptation can happen without sacrificing the PHS Guidelines integrity. Adaptation 
is an important part of implementation that should be measured and accounted for.   
 
Part 1: Webinar-Based  Training  
The webinar-based training protocol includes: 
 
Tobacco Cessation during Lung Cancer Screening  
 
Overview of the PHS Guidelines 
 
Brief Intervention for Behavior Change, Motivational Interviewing, Pharmacotherapy  
 
Using Logic Models for Implementing the PHS Guidelines 
 
Each webinar will be offered “live” two times (to accommodate different time zones) and will also be 
recorded and stored on the team website so that they may be viewed by personnel who could not 

 
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participate in the training.   
 
Table 2:  Training components of evidence-based smoking cessation strategies include: 
Provider Strategies  
 
Setting, charting, and follow-up on a quit date 
 
Motivational interviewing strategies to promote 
quitting.  (The team will be introduced to common 
misperceptions and rationalizations for not quitting 
identified in the literature to incorporate counseling 
on how to address barriers.) 
 
QuitLine referral 
 
Pharmacotherapy options as outlined in the NCCN 
guidelines (e.g., varenicline, nicotine replacement 
therapy, bupropion)  
 
Identify and refer patients to hospital-based or other 
community resources for quitting, including intensive 
counseling. 
 
Webinars to share with the site clinicians strategies 
for assisting patients with quitting and ensuring 
follow-up. 
Health Care Delivery System Strategies  
 
How to embed electronic prompts 
for assist and arranging follow-up. If 
EHR prompts are not possible, 
identify an easy and low-cost 
“prompt” for providers (e.g., a 
tickler file) to ensure follow-up for 
cessation post-visit. 
 
Enrolling patients in publically-
available and free mobile health 
programs for smoking cessation such 
as iPhone/Android apps, text 
messaging, and web-based resources  
 
Offering intensive counseling for 
patients who resist quitting or who 
fear relapse. 
 
Fax and electronic referrals for the 
QuitLine 
The Wake Forest study team will spend up to $300 per site to purchase environmental cues to 
promote cessation: e.g., “While you wait” videos to promote cessation during the screening 
encounter; low-cost brochures for patients in the waiting rooms; low-cost posters for waiting rooms 
and patient rooms; pre-printed prescription pads designed for pharmacotherapy.  The research team 
has prior experience helping clinics select environmental cues for site-specific tobacco cessation 
materials using low-cost and publicly-available resources.  We will also discuss strategies for 
maintaining a stock of environmental cues. 
 
Part 2:  In-Person, Site-Specific SWOT Analysis and Logic Model Implementation:  This training will 
be conducted onsite at each intervention clinic by at least one clinician and one behavioral scientist. 
 
SWOT is a strategic planning technique to evaluate Strengths, Weaknesses, Opportunities, and Threats to 
assess the likelihood of adopting a new strategy within a health care delivery system. SWOT analysis has 
been used extensively in business contexts, when new programs or policies are introduced. The approach 
is highly applicable to health care delivery systems change, especially when introducing new strategies 
for cessation support within rapidly evolving lung cancer screening programs. This approach recognizes 
that, while the PHS Guidelines offers a common set of strategies for cessation (taught during the morning 
session), that implementation will be influenced by internal and external forces, such as organizational 
structure, screening processes, and culture of each clinic. 
 
Stages of the SWOT Analysis: The trainers will explain the SWOT process, help clinics identify strengths 
within the organization (e.g., dedicated staff for smoking cessation), identification of weaknesses (e.g., 
lack of training of clinicians or other personnel), list opportunities that are external to the organization 
that may affect implementation (e.g., availability of free/low cost resources that promote cessation), 
identify the strategies that are immediately ready for implementation and others that may require support 
after training.  Barriers we may  hear include: provider lack of time to counsel and provide 
pharmacotherapy, fear that smoking cessation counseling during the screening encounter will reduce the 
likelihood of return for their annual LDCT screening, lack of knowledge/skill for counseling and 
pharmacotherapy prescribing; lack of available external resources; lack of support from hospital 

 
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administrators, lack of care coordination between primary care provider and 
screening providers; lack of follow-up with patients after screening is 
complete.    
Logic Model Development & Implementation:  Each clinic will identify 
strategies that can be implemented immediately with limited resources 
(short-term outcomes) and those that will require adaptation or post-training 
support (long-term outcomes). We will prioritize strategies that focus on 
“assisting” patients with cessation and “arranging” follow-up care for patients who want to quit. These 
strategies will be conceptually mapped using a logic model (including inputs, activities, short-term, and 
long-term outcomes) to clearly identify the “points of interventions” for implementing evidence based 
cessation strategies. We will guide each clinic through development of its own logic model, but we expect 
that a few logic model “templates” will emerge that will ultimately allow our team to characterize 
implementation of cessation services within LDCT screening programs (Aim 2).   
 
We will provide a variety of evidence-based cessation strategies, some that require very limited resources 
and are very easily implemented with minimal interruptions to clinic flow. Other cessation strategies 
require more resources and may have a greater impact on work flow.  As a result, we have designed the 
implementation process to be responsive to each clinic’s existing resources and ability to implement 
change. 
 
Our team has experience using SWOT, logic models, and performance coaching to improve the 
translation of science into practice and policy changes in consecutive tobacco control capacity building 
projects (Foley, PI; Spangler, Sutfin-Co-Is). 
 
A Theory-Guided Intervention: The SWOT analysis and strategic planning session uses constructs from 
organizational change theories (e.g., Diffusion of Innovations). These constructs include organizational 
climate and culture (compatibility of the evidence-based tobacco cessation with the clinical mission of 
LDCT screening) .22 We will also measure organizational readiness to implement the evidence-based 
strategies (self-efficacy of the providers and program leaders, as well as relative value of the PHS 
Guidelines services relative to other required services).38 We expect implementation of cessation 
strategies to depend on simplicity of the services (e.g., pharmacotherapy prescribing versus intensive 
onsite counseling), trialability or allowing differing strategies to be used in different clinics (willingness 
to allow clinics to adapt services to the local needs), and observability of clinic, provider, and patient 
benefits (creating systems for feedback on success of cessation services in promoting quitting among 
screening patients).39–42 Following SWOT analysis, the teams will come together for a small group 
meeting to share their logic models and then hear an overview of the performance coaching aspect of the 
training program.   
 
Step 3: Performance Coaching:   Coaching has predominantly been used in performance management as 
a strategy for offering ongoing support and feedback to employees.43,44  Performance coaching is an 
adaptable methodology aligned with the unique needs of lung cancer screening sites. “Coaches” provide 
support and feedback that is timely and clear as a method to help clinics implement smoking cessation 
services.43 There are four main dimensions to coaching in this context: (1) providing direction, which 
includes clear articulation of the goals and values of implementing tobacco cessation services during 
LDCT screening; (2) offering support during implementation (identifying gaps in implementation and 
helping identify improvements); (3) engaging personnel within the LDCT screening process in problem-
solving; and (4) identification and removal of barriers to implementation.  Papadakis et al (2015) have an 
ongoing trial to use performance coaching to enhance quit rates of cessation treatment delivered by 
primary care providers (PCPs).45 This team is offering performance coaching for PCPs for 2-4 weeks 
following a training session on how to ask, advice, and assist patients with quitting.  
 

 
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We will use active and reactive performance coaching.  Each site will have a coaching team: two 
members of our research team including an expert in tobacco cessation and an expert in lung cancer 
screening.  Active coaching includes six, 1-1 ½ hour video exchanges among program sites and coaching 
teams, once every 4-6 weeks over an 8-month implementation phase. One week prior to the call, each site 
will be prompted with an email to inform the coaching team of any challenges associated with 
implementation.  The coaching teams, in consultation with the EAB, will identify potential solutions to 
the identified problems during the call. Reactive coaching:  Unsolicited successes and barriers during 
implementation may also be submitted to a team blog.   
 
The Wake Forest project manager in consultation with the coaching team will identify potential solutions 
during the interim period between active coaching video calls. Using data from the active and reactive 
performance coaching notes, we will develop and continuously update a list of frequently asked questions 
(FAQs) and responses that were generated. The intent using a team blog is to share information with 
NCORP intervention sites is to create a co-learning experience during the implementation phase of the 
project. 46 
 
Who will participate in coaching?    We encourage all Program Champions to participate in each active 
coaching session.  Other personnel who would like to discuss ‘best practices’ for implementing the PHS 
Guidelines, brainstorm strategies to overcome implementation barriers, and discuss new strategies that are 
working well for their clinic are also invited and encouraged to participate, although this is not required.   
 
7.8  
Summary of Expectations for Participating in this Study 
 
 
Webinars:  Cessation Program Champions and staff who are central to implementing the PHS 
Guidelines (expected to vary from site-to-site) are expected to watch the training webinars prior 
to the onsite visit.  We encourage sites to watch the webinars live, but they will be recorded and 
available to maximize the opportunity for staff to watch the training videos.  Total time 
commitment 3.5 hours over a period of 2-3 months, prior to the onsite visit.  Intervention Sites 
only, initially. Available to Usual Care Sites later in the study, post-data collection. 
 
SWOT Analysis and Logic Model Implementation:  Requires onsite visit with Program 
Champion and other key staff central to implementing the intervention.  The intensity of the visit 
will depend on the clinics needs and readiness to engage in the logic model exercise. We 
anticipate the onsite ‘training’ will be ~ 2 hours.  Intervention Sites only, initially. Available to 
Usual Care Sites later in the study, post-patient data collection. 
 
Active Performance Coaching:  A video web conference will be held once every ~6 weeks and 
is expected to last approximately 1 hour. The Program Champion must participate.  Others are 
welcome, but not required.  Intervention Sites Only. 
 
Reactive Performance Coaching:  This is on an as-needed basis, so the time commitment will 
depend on the needs of the clinic.  Intervention Sites Only. 
 
Coordination of Site Visit:  Our team will visit each intervention site twice and each usual care 
site once. We will need local support for managing the site visit and can work with NCORP 
personnel and the Program Champion to identify the best time, venue to minimize disruption to 
the clinic.  Intervention and Usual Care Sites.  
 
Team Blog: The team blog will be developed at Wake Forest with support from the biostatistics team and 
maintained by the Project Manager. We will use WordPress.org as the software platform. WordPress.org 
is an open source software platform allowing our team to build and maintain the blog.  WordPress allows 
for the entire blog to be “private” and password protected. The Program Champion will be given the site 
password and asked to share with the imaging facility staff.  We will explain the use of the blog as part of 
our onsite training.   
 
7.9 
Develop and Evaluate an Implementation Toolkit 

 
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The goal of the Implementation Toolkit is to support the successful implementation of evidence-based 
tobacco cessation strategies into clinical settings with LDCT lung cancer screening programs, in the 
absence of a research study. The Implementation Toolkit will be developed by the research team 
following implementation of the program into the 13 intervention sites in Aim 1 and using extensive, 
qualitative implementation data generated from Aim 2.  NCORP components/subcomponents will not be 
required to participate in this aspect of the research study. 
 
Using the SWOT analyses, the team blog and performance coaching notes, and key informant interviews, 
we will identify challenges faced during implementation and common strategies for overcoming these 
barriers. We will also explore what training tools were most useful and how those could be translated into 
a toolkit. We intend for the Implementation Toolkit to be comprehensive so that it can be used to guide 
the successful implementation of the PHS Guidelines in real-world settings after the research study. The 
research team will meet bi-weekly during a 6-8 month period to develop and refine each section of the 
comprehensive toolkit with monthly calls with EAB members. Sections will be brief and written in clear, 
simple language with step-by-step planning templates (where available). After each section is developed 
and refined, the document will be reviewed by the EAB and program champions from the early 
intervention clinics, as well as national stakeholders from professional medical societies (e.g., ASCO) and 
non-profit agencies committed to cancer prevention and smoking cessation (e.g., ACS, Legacy). This will 
be an iterative process with multiple opportunities for feedback. We have identified potential sections of 
the toolkit in Table 4, however, additional sections will be identified during the development phase. We 
have used a similar process on another study Reducing HIV Disparities among Latinos: Disseminating an 
Effective Intervention (R24MD002774, Rhodes, PI, Sutfin, Co-I). 
Table 4. Toolkit for Implementing Evidence-Based Tobacco Cessation Strategies in LDCT Lung 
Cancer Screening Programs 
Section Title 
Description 
How to use this toolkit 
Explain how to use the Toolkit, its intended audience, and its 
organizational structure.  
Why is smoking cessation 
important for LDCT patients? 
Provide foundational knowledge about the importance of smoking 
cessation for patients being screened for LDCT 
What are the PHS Guidelines 
for Tobacco Use and 
Dependence? 
Provide an overview of the evidence-based strategies used in clinical 
setting to help tobacco-using patients quit. 
Assessing our clinic’s 
readiness to implement the 
evidence-based strategies 
using a SWOT analysis 
Guide a clinic through the stages of SWOT analysis to determine if 
the clinic is ready for program implementation. 
What if our clinic isn’t 
“ready” 
Describe strategies for increasing readiness to adopt. 
What does it take to 
implement the PHS 
Guidelines? 
Describe the personnel and budget resources required, as well as 
support from clinic administrators. 
The role of the program 
champion 
Describe the importance of selection of and role the program 
champion will play. 
Roadblocks, detours, and 
delays 
Help strategize when barriers to implementation arise. 
How to adapt the PHS 
Guidelines to meet our 
clinics’ needs 
Discuss options for adapting systems-level approaches to meet the 
needs of individual clinics. 
Sustainability 
Describe approaches for sustainability. 
Appendices: Assessing patients readiness to quit; Providing quit assistance; An introduction to 

 
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quitlines; What you need to know about smoking-cessation pharmacotherapy 
External Advisory Board: The EAB is charged with providing scientific and pragmatic support to the 
research team on the development of the intervention materials, facilitating and measuring 
implementation of smoking cessation into LDCT lung cancer screening sites, and developing an 
implementation toolkit. The EAB includes national and international experts in smoking cessation, lung 
cancer screening, and implementation science. We anticipate monthly EAB meetings with the research 
team and 8 additional “ad hoc” meeting hours per year. The EAB leader serves as the liaison to the 
research team and provides organizational oversight for the EAB. For his contribution, we anticipate 10 
days per year of service.  
 
Members of the EAB:  
 
Graham Warren, MD, PhD. EAB Leader. Med. Director for Tobacco Control at MUSC. Dr. 
Warren has led the development of cessation programs at Roswell Park Cancer Institute and 
MUSC, using opt-out strategies for cessation support and highly effective dissemination methods. 
He serves as Chair of member for tobacco committees for several leading caner organizations as 
well as the NIH, all devoted to effectively reducing the harms of tobacco through a variety of 
means including implementation of evidence-based support. 
 
Adam Goldstein, MD, Professor of Family Medicine, UNC. Dr. Goldstein has been extensively 
involved at the national, regional, state, and medical school levels in tobacco control research and 
evaluation for over 20 years. He has an exceptionally strong background in clinical tobacco 
cessation, and serves as the director of the UNC Tobacco Intervention Programs. In this position, 
he has implemented evidence-based tobacco cessation practices in the inpatient, outpatient and 
employee health settings. 
 
Judith Ockene, MD, University of Massachusetts, Barbara Helen Smith Chair in Preventive and 
Behavioral Medicine and Professor of Medicine and Chief.  Dr. Ockene has developed tobacco 
cessation training programs for tobacco treatment specialists, medical schools, medical students 
and residents, as well as practicing physicians. These have been local, regional and national in 
scope. She was also part of NCI’s Community Intervention Trial for Smoking Cessation 
(COMMIT) Study group, a very large and well recognized study, which also had a strong 
evaluation component. 
 
Phil Boiselle, MD, Beth Israel Deaconess Hospital. Dr. Boiselle's research focuses upon the 
application of advanced airway imaging methods to a variety of benign and malignant airway 
disorders. Dr. Boiselle served as the site principal investigator for the National Lung Screening 
Trial from 2002 through 2009. In May 2012, he was appointed Associate Dean for Academic and 
Clinical Affairs at Harvard Medical School.  In January 2017, Dr. Boiselle became the Dean of 
the Charles E. Schmidt College of Medicine at Florida Atlantic University in Boca Raton, FL. 
 
Michael Gould, MD, MS is a Senior Scientist and Director for Health Services Research at Kaiser 
Permanente Southern California. He leads NCORP cancer care delivery efforts for Kaiser 
Permanente Southern California through the Kaiser NCORP community site. He will contribute 
expertise on health services research, lung cancer screening, and cancer care delivery research 
within NCORP to the EAB. *As a member of the EAB and with existing cessation services in the 
Kaiser system, Dr. Gould agreed that Kaiser will not participate in the study. 
 
Geoffrey Curran, PhD.  Dr. Curran has expertise in implementation science with a particular 
emphasis on designing and testing implementation strategies to support the adoption and 
sustainability of evidence-based practices.  Additional interests include: 1) formative evaluation 
methods to assist in developing and revising implementation strategies based on data derived 
from local contexts, and 2) “hybrid effectiveness-implementation” designs which combine 
elements of clinical/preventive effectiveness and implementation research to speed the translation 
of EBPs.  He serves on the Editorial Board of Implementation Science. 

 
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 
Alice Ammerman, PhD, University of North Carolina-Chapel Hill. Dr. Ammerman is an expert in 
dissemination and implementation research. With NIH colleagues, she hosted the first annual 
Training Institute on Dissemination and Implementation Research and recently completed a 
tenure on the NIH study section for dissemination and implementation research. 
 
Stakeholders will be asked to evaluate the quality of each section of the toolkit, as well as quality of 
presentation (toolkit design, length, level of interest/engaging material, and perceived usability by LDCT 
screening practices) on a scale of 1 to 5 (1=poor, 3=average, 5=excellent) with an opportunity for 
comments for each rating. In addition, the stakeholders will identify potential dissemination outlets for 
scale-up of the toolkit.  After receiving feedback, we will conduct a conference call with the evaluators to 
aid the research team and EAB to improve the toolkit for dissemination based on the evaluation. Using 
this information, the research team in partnership with the EAB will develop a dissemination plan for the 
Implementation Toolkit. 
 
8.  
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITION 
 
8.1 
Summary Table of Endpoints, Measures, Measurement Strategies, and Time Points 
 
 
Measure 
Measurement 
Strategy 
Time Point(s) 
Primary Endpoint 
(Effectiveness, Aim 1) 
7-day sustained 
smoking abstinence 
with cotinine 
validation 
Patient survey & 
mailed saliva sample 
for non-smokers 
6 months 
Secondary Endpoints 
(Effectiveness, Aim 1) 
Short-term smoking 
abstinence (self-
reported) 
 
Quit Attempts 
 
Patient survey 
3 months after baseline 
 
Secondary Endpoints 
(Implementation, Aim 2 
Fidelity to the 
Intervention 
Patients are asked if 
they received 18 
cessation services 
during the screening 
visit—see Appendix 
10, Questions 4a-4r. 
 
Patient survey 
 
 
 
 
 
 
≤14 days after baseline 
 
 
Secondary Endpoints 
(Implementation Aim 2) 
 
Feasibility & 
Appropriateness of 
offering services that 
promote cessation.  
See Appendix 5 & 21. 
Key informant 
interview- including 
structured survey and 
semi-structured 
interviews  (~3/clinic)  
Baseline 
And Follow-Up (8 
months after baseline)  
 
8.2 
Primary Endpoint, Aim 1 (Effectiveness) 
Six months after the screening visit, the project manager will conduct a 5-minute telephone survey to 
measure long-term abstinence. Items will include current tobacco use, quit attempts in the past 6 months, 
and 7-day nicotine abstinence by asking when they last smoked a cigarette, and any changes in 
demographic characteristics.  The validated question that measures 7-day smoking abstinence is below. 

 
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Have you smoked a cigarette (or other tobacco products), even a puff, in the last 7 days? 
 
Yes 
No  
Refused 
 
Biochemical Validation:  We will validate self-reported smoking status at six months for self-reported 
non-smokers using salivary cotinine among patients who self-report successful quitting at 6-months. 
Cotinine, a major metabolite of nicotine with a long half-life, is highly sensitive and specific for tobacco 
use, making it an excellent test for confirming tobacco cessation.37 Salivary cotinine levels less than 
15ng/ml are consistent with no tobacco use for the prior 7 days. For biochemical verification of smoking 
cessation, we will overnight mail a saliva collection kit with a postage-paid return mailer to participants. 
This will be explained to participants during the 6-month telephone survey so that they will expect the 
saliva collection kit.  We include information regarding salivary cotinine data collection in the patient 
informed consent document.   
 
See Appendix 17 for the information that will be included in the salivary cotinine mailer to participants.   
 
8.3 
Secondary Endpoints, Aim 1 (Effectiveness) 
 
Short-term smoking abstinence (self-reported) and quit attempts will be assessed via patient telephone 
survey 3 months after the lung cancer screening visits. See Appendix 11, Patient Survey 3 Months. 
 
8.4 
Secondary Endpoints, Aim 2 (Implementation) 
 
Fidelity:  Fidelity, in this study, is defined as the adoption of PHS Guidelines for cessation.  We measure 
fidelity in two ways: from the perspective of the patient via telephone survey and from the perspective of 
lung cancer screening staff (aka “key informant” interviews).   
 
For patients, fidelity is measured using the ≤14 days survey (see Appendix 10).  The interviewer asks: 
 
During your (lung cancer screening) visit, did any doctor, nurse or other health care provider offer the 
following support?  Answer “yes” or “no”. 
There is a list of 18 cessation support items on the patient survey.  See the following for examples: 
 
Advise you to quit 
 
Ask how important it is for you to change your tobacco use behavior 
 
Prescribe or recommend any kind of nicotine replacement therapy 
 
Suggest you enroll in a cell phone or tablet-based “Text to Quit” program 
 
Fidelity is also measured from the lung screening staff perspective. We ask the staff (aka “key 
informants”) to indicate how often they provide a list of cessation services. Response options are Never, 
Rarely, Sometimes, Most of the Time, Always (see Appendix 5 and 21). 
 
Appropriateness and Feasibility:  The secondary implementation endpoints, appropriateness and 
feasibility, are measured by asking lung cancer screening staff (aka “key informants”) whether they 
strongly disagree, disagree, agree or strongly agree that cessation services are appropriate and feasible  to 
implement in their clinic.  We ask about 20 different smoking cessation services (see Appendix 5 and 21).  
 
Feasibility:  “Providing (insert cessation service) is feasible for our lung cancer screening clinic.” 

 
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Appropriateness:  “Providing (insert cessation services) is appropriate for our clinic.” 
 
We expect that clinics in the intervention arm will report a greater percentage of cessation services as 
feasible and appropriate at follow-up compared to baseline.  We do not expect to observe a change in the 
control clinic.  
 
8.5 
Off-Study Criteria 
 
Participants may go ‘off-study’ for the following reasons: the protocol intervention and any protocol-
required follow-up period is completed, AE/SAE, lost to follow-up, non-compliance, concomitant 
medication, medical contraindication, withdraw consent, death, determination of ineligibility. For 
participants who go ‘off-study’ or are considered ‘lost to follow-up’ the Reason for Refusal Follow-up 
form (Appendix 4) should be completed.   
 
8.6 
Study Termination 
 
NCI, DCP as the study sponsor has the right to discontinue the study at any time.  
 
9. 
CORRELATIVE/SPECIAL STUDIES - NA 
 
10. 
SPECIMEN MANAGEMENT  
 
10.1 
Laboratories 
 
For biochemical verification of smoking cessation, we will overnight mail a saliva collection kit with a 
postage-paid, pre-labeled return mailer to participants from the Wake Forest NCORP RB Core Lab 
located in Winston-Salem, NC. 
 
10.2 
Collection and Handling Procedures 
 
Patients will receive via mail a salivary collection kit (including a salivette—a plastic vial that contains a 
small cotton roll, like those used by dentists) along with written instructions on how to obtain the salivary 
sample.  The salivary collection kit will be pre-labeled with a study identifier that can later be linked to 
the patient survey data.   
 
The written instructions explain that participants should place the cotton roll under their tongue for 1-2 
minutes and then replace it into the plastic vial.  They should collect the sample at least 30 minutes after 
eating or drinking and before brushing their teeth. The initial informed consent explains the procedure, 
the risks and benefits of participation, the notice that there is no penalty for not participating, information 
on how to contact the IRB and the study team personnel.  Individuals will return the salivary sample using 
a FedEx biospecimen approved mailer. 
 
Saliva samples will be collected from subjects using SalivaBio Oral Swab saliva collection kits available 
from Salimetrics, Inc. (Carlsbad, CA). Saliva specimens will be received in the Research Base NCORP 
Core Laboratory, centrifuged to collect the saliva from the swabs, the volume measured, and transferred 
to smaller freezer tubes for storage at -80°C. Cotinine levels will be determined by ELISA using the high 
sensitivity Salivary Cotinine Quantitative Enzyme Immuno Assay kit provided by Salimetrics, Inc. This is 
a competitive immuneassay kit with a determination range of 0.8 to 200 ng/mL. Saliva samples will be 
analyzed in duplicate. In our experience with other studies, cotinine levels typically fall between two 
extremes with few intermediate values. Nonsmokers have no detectible cotinine whereas smokers often 
have levels above 200 ng/mL. When the determined level of a sample is above the upper range of the 

 
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ELISA (200 ng/mL), we will repeat the assays with a higher sample dilution to obtain cotinine levels 
within the standard range of the assay.  
 
Analysis will be conducted by the WF NCORP RB Core Lab. Salivary cotinine levels less than 15ng/ml 
are consistent with no tobacco use for the prior 7 days. To maximize validation, participants will receive a 
$20 gift card for returning the saliva sample. Responses will be recorded by the Core Lab personnel 
conducting the analysis.  
 
For the Research Team 
Upon receipt of the salivary sample by the research team, the team will follow standard OSHA 
procedures for biospecimens, including wearing gloves while handling the salivettes and extracting the 
dental rolls via forceps.  The Research Assistant will use gloves while handling the salivettes and forceps 
to collect the saliva samples.  All materials used for collecting the saliva samples will be disposed of in 
accordance with OSHA regulations.  
 
Labeling and Tracking 
All salivary collection kits will be labeled with a unique study identifier allowing the data to be linked to 
survey data.  A tracking log will be maintained, which will include the study identifier and the data 
shipped and received.   
 
Temperature & Storage Requirements 
Using the procedures outlined in Etter et al.48, salivettes will be stored, upon reception, in a refrigerator at 
4 degrees Celsius.  Liquid contained in the salivettes will be extracted using centrifugation (500 g/2min) 
and cotton rolls removed.  After centrifugation, saliva samples will be frozen at -20 degrees Celsius until 
ready for analysis by gas-liquid chromatography. Laboratory, centrifuged to collect the saliva from the 
swabs, the volume measured, and transferred to smaller freezer tubes for storage at -80°C.  
 
10.3 
Shipping Instructions 
 
All biospecimens will be mailed in approved biospecimen mailers. Biologic specimens collected during 
the conduct of each clinical trial that are not used during the course of the study will be considered 
deliverables and the property of WF NCORP RB. At study completion, WF NCORP RB will discard any 
unused biological specimen unless otherwise specified in the protocol document.  
 
11. 
REPORTING ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS (AES AND 
SAES) 
 
This is a group randomized controlled trial with minimal risks. NO routine Adverse Events or Serious 
Adverse Events are reported. 
 
12. 
STUDY MONITORING 
 
12.1 
Data Management 
The Eligibility checklist/Registration Form should be completed on-line.  NCORP study site staff will 
enter data directly into the study website within the timeframe given in the table below. 
 
 
 
 
 
 

 
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Patient Forms 
Submission Schedule 
Responsible for 
Data Entry 
Eligibility Form  
within 14 days of registration 
Site Staff 
Patient Informed Consent 
within 14 days of registration 
Site Staff 
Baseline Measures  
within 14 days of completion of baseline 
survey 
Site Staff 
Exposure to the Intervention 
≤14 days) 
within 14 days of completion of baseline 
survey 
Site Staff 
Intermediate Outcomes  (3-
month survey & Lung Cancer 
Screening Report) 
within 14 days of completion of 3-month 
survey and Lung Cancer Screening Report 
Site Staff 
Primary Outcomes (6- month) 
within 14 days of completion of 6-month 
survey 
Site Staff 
 
Site Forms 
Submission Schedule 
Responsible for 
Data Entry 
Pre-Randomization Site 
Checklist  
within 14 days of site selection 
Site Staff 
Site Invitation to Participate 
within 14 days of site selection 
N/A 
Baseline Organizational 
Characteristics 
within 21 days of site randomization 
Site Staff 
Follow-up Organizational 
Characteristics 
within 30 days of completion of the 
follow-up key informant interviews 
Site Staff 
 
12.2 
Case Report Forms 
 
Participant data will be collected using protocol specific case report forms (CRFs). 
 
12.3 
Source Documents 
 
The sources of research material will include information provided through participant surveys, 
intervention sessions, key informant audio-recorded transcripts, and self-report questionnaires specifically 
for this research study. We will also obtain the lung cancer imaging report, de-identify the report, and 
append the report to the survey data.  The imaging report will be obtained to ensure that the Lung RADS 
score (reported by staff on the 3-month survey) is accurate and complete, which is a required element of 
the SCALE collaborative.  
 
A number of steps will be taken to ensure the confidentiality of research data collected during the study. 
All forms will be stored in locked file cabinets. Names will be removed from all forms and records and 
replaced with participant numbers. Audio-recorded sessions will be erased upon completion of 
transcription and transcripts will be recorded without personal identifying information. Information stored 
in the computer will be password protected. Only members of the investigative team will have access to 
any participant information and data. The identities of participants will not be revealed in publications and 
presentations of any results from this project. Procedures specified in the consent form are consistent with 
HIPAA regulations.  
 
An investigator and other designated staff are required to prepare and maintain adequate and accurate 
documentation that records all observations and other data pertinent to the investigation for each 
individual participating in the study. All data recorded in the research record (including data recorded on 
CRFs) must originate in the participant’s medical record, study record, or other official document sources. 
 
 

 
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Source documents substantiate CRF information. All participant case records (e.g., flow sheets, clinical 
records, physicians’ notes, and correspondence) must adhere to the following standards: 
 
 
Clearly labeled in accordance with HIPAA practices so that they can be associated with 
a particular participant or PID; 
 
 
Legibly written in ink; 
 
 
Signed and dated in a real time basis by health care practitioner evaluating or treating the 
participant; and 
 
 
Correction liquid or tape must not be used in source documents or on CRFs. 
 
 
Corrections are made by drawing a single line through the error. Do not obliterate the 
original entry. Insert the correct information, initial, and date the entry. 
 
12.4 
Data and Safety Monitoring Plan 
 
The Data Safety Monitoring Board meets annually to review all phase II and phase III protocols.  The 
Board includes members demonstrating experience and expertise in oncology, biological sciences and 
ethics. The DSMB report is generated by the organization statistician. Areas of review may include the 
following: Date study Opened; Study Objectives; Participant Accrual; Participant Status and Retention; 
Study Status; Last Contact Status; Participant Compliance; Participant Characteristics; Adverse Events; 
Date, Event briefly described, Relationship to Treatment, Arm assigned; Summary of Secondary 
Measures. 
 
Wake Forest University has a university-wide Data Safety and Monitoring committee. Three members of 
this committee as well as the organization statistician will oversee the safety monitoring of the study to 
ensure that the privacy of all participants in the study is protected; ensure that participants' interests are 
primary, that is, above the interests of the scientific investigation; and to ensure that all data collection is 
scrutinized for accuracy, privacy and levels of protection. The committee will perform reviews of the data 
handling and confidentiality, communicate any breaches in data safety to the administration of Wake 
Forest University Health Sciences and comply with recommendations to resolve such problems, and 
maintain written communication of the deliberations and recommendations that arise from their meetings. 
By examining this information, the data and safety monitoring team will keep abreast of critical issues 
regarding recruitment and data integrity. Reports of all DSMB meetings and recommendations will be 
provided to the NCI, CIRB, WF NCORP RB, and participating sites, as requested. 
 
12.5 
Sponsor or FDA Monitoring 
 
The NCI (or their designee) may monitor/audit various aspects of the study. These monitors will be given 
access to facilities, databases, supplies and records to review and verify data pertinent to the study.  
 
12.6 
Record Retention 
 
Clinical records for all participants, including CRFs, all source documentation (containing evidence to 
study eligibility, history and physical findings, laboratory data, results of consultations, etc.), as well as 
IRB records and other regulatory documentation will be retained by the Investigator in a secure storage 
facility in compliance with Health Insurance Portability and Accountability Act (HIPAA), Office of 
Human Research Protections (OHRP), Food and Drug Administration (FDA) regulations and guidances, 

 
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and NCI/DCP requirements, unless the standard at the site is more stringent. Records for this study will 
be retained for at least three years after the completion of the research.  
 
13. 
STATISTICAL CONSIDERATIONS 
 
13.1 
Study Design/Description 
 
We anticipate screening approximately 2,500 participants from 26 clinics in order to enroll a total of 557-
650 participants in the intervention and 557-650 participants in the usual care arms at baseline.  We 
expect ineligible participants to be due to non-smoker status (52%) and lack of interest (5%), and 
anticipate these rates being similar in both arms of the study.  Following enrollment, we expect 90% of 
baseline participants to participate ≤14 day telephone survey, which will ascertain exposure to the 
intervention, and 75% of baseline participants to participate in the 6-month, telephone survey.49,50  
 
13.2 
Randomization/Stratification  
 
The pre-randomization eligibility checklist will include organizational characteristics that may influence 
the adoption and adaptation smoking cessation services.  We will cluster sites according to these 
organizational characteristics (e.g., volume of the screening site, current cessation services, and 
racial/ethnic composition of the screening population) and then randomly select sites from within each 
cluster to receive the intervention (n=13) or usual care (n=13) to maximize balance in the study arms.  
Our multi-faceted training program targets health care delivery system changes (e.g., providers, clinics); 
therefore, all patients seeking LDCT screening at a single site will be in either the intervention or usual 
care arm of the RCT. If clinics opt out post-randomization, another clinic will be selected from the 
remaining eligible clinics within the NCORP site or another NCORP site will be added. 
 
13.3 
Accrual and Feasibility 
 
With over 800 components/subcomponents within the NCORP network, we do not anticipate having any 
challenges with accruing 26 components/subcomponents to participate in this study. On the 2017 CCDR 
Landscape Assessment, 68% of responding practice groups (224 of 301) had low dose CT screening for 
lung cancer available on site. 
 
We anticipate screening approximately 2,500 participants from 26 clinics in order to enroll a total of 557-
650 participants in the intervention and 557-650 participants in the usual care arms at baseline and expect 
to retain 75% of baseline participants to participate in the 6-month telephone survey.49,50 Any participants 
who complete baseline assessments after their LDCT screening or sign consent and do not complete any 
study specific assessments will be replaced.   
 
Challenges with recruitment and attrition of participants could limit our ability to adequately test the 
effectiveness of the intervention. We will attempt to minimize attrition by sending postcard reminders of 
the upcoming surveys.  We anticipate a capacity to enroll at least 50 smokers per clinic, but at present 
only require an average of 43 per clinic at baseline in order to retain 32 at 6-months (75% of the original 
cohort). We will allow clinics to enroll up to 50 smokers total for a maximum of 1300 (although we do 
not anticipate all clinics will enroll the maximum allowed). Because we anticipate some high volume 
clinics, we expect that we could oversample some participants in some clinics if needed.  We could also 
increase the desired sample size per clinics should a clinic (post randomization and training) elect to drop 
out of the study.  Alternatively, we can extend data collection longer than the 16-month accrual window.  
Our team has experience in conducting randomized clinical trials and can adjust both methodologically 
and/or analytically to address challenges that could affect statistical power.   
 

 
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13.4 
Primary Objectives, Endpoint(s), Analysis Plan 
 
13.4.1 Analysis Plan 
 
In order to compare groups, a multi-level logistic regression model approach will be used.51 This 
model allows for both fixed and random effects to be included. 51 This model allows for both 
fixed and random effects to be included.  In these models, clinics will be random effects and both 
clinic and participant level characteristics can be included as fixed effects.  The initial model for 
the primary analysis will include two fixed effects: cluster (used in the randomization) and 
intervention and one random effect, clinic. The model can be written as Yijk = µ+ γk+αj+ βk(j)  + 
εi(jk), where Yijk is the outcome (i.e. 6-month smoking abstinence) measured on the ith participant, 
under the jth intervention in the kth clinic; µ is the grand mean; γk is the cluster (stratum) for clinic 
k; αj is the fixed treatment effect for group j; βk(j) is the random effect of the kth clinic nested 
within the exposure group; and εi(jk) is the error term for the ith participant nested within the 
treatment group and clinic. Other fixed effects can be added at the patient level (e.g. age, gender, 
race). The random clinic effect allows the possibility of correlated observations (participants) 
within clinics. Of primary interest is the treatment effect (αj), which indicates difference in the 
dependent variable (7-day smoking abstinence) between groups.  Additional longitudinal 
modeling can be explored using a Generalized Estimating Equations (GEE) approach that 
accounts for the participants being nested within clinic and also allows the early (1 week) 
endpoint to be included with the 6-month endpoint in the analyses.  We can also explore if there 
are particular patterns of abstinence behavior (i.e., examine the 4 possible patterns between 7 
days and 6 months: abstain/abstain, not abstain/abstain, etc.) to see whether there are any specific 
participant level risk factor profiles that may differentiate the response patterns. 
 
13.4.2 Statistical Power 
 
Sample size estimates are based on the following data.  Approximately 48% of patients who 
present for lung cancer screening are current smokers, the percentage of persons who successfully 
quit smoking in the previous year ranges from 4.9% (among 45-65 year olds) to 7.4% (among 
persons 65 and older). 52 Receipt of counseling to promote cessation (vs. no counseling) increases 
abstinence 1.3 to 2.3 fold (low versus high intensity counseling), while pharmacotherapy (vs. 
placebo) increases the odds of abstinence 2.3-3.1 fold (patch vs. varenicline).27.  Weanticipate 
that final sample sizes of 418 in the intervention and 418 in the usual care group will be obtained 
by enrolling 13 clinics with an average of 32 participants who will complete the 6-month survey.  
With this sample size, we have 80% power to detect a difference in the primary outcome (7-day 
abstinence) between groups. This calculation assumes that the control group abstinence rate will 
be 10% and the intervention group rate will be 20% using a 2-sided Z-test for comparing 
proportions with alpha=0.05 (2-sided).  For this calculation, in order to account for the cluster 
randomized design we used an intra-class correlation value of 0.03.53.  This calculation should be 
conservative since the control group abstinence rate may be lower than 10% which would mean 
that the intervention effect could also be less and still lead to statistical (and clinical) significance. 
To allow for flexibility in clinic accruals and loss to follow-up rates and maintain an analyzable 
minimum size of 418 in each group, we plan to enroll at least 1114 up to a maximum of 1300 
patients (or approximately 42-50 per site) to conservatively allow for 25% to 35.5% loss to 
follow-up at 6 months respectively. 
 
13.5 
Secondary Objectives, Endpoints, Analysis Plans – N/A 
 
 
 

 
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13.6 
Analysis Plan for Key Informant Interviews and Other Qualitative Data Elements  
 
The qualitative data from key informants will be digitally audio-recorded and transcribed.  Data will be 
cleaned by comparing transcripts to original audio-recordings and notes.  
 
The qualitative data from the Team Blog and Performance Coaching Notes will be abstracted in text 
format using Microsoft Word. 
 
All qualitative data will be imported into Atlas.ti software for data management and coding purposes. 
Codebook will be developed collaboratively, and data will be coded in Atlas.ti. Transcripts and coded text 
will be iteratively reviewed. Themes regarding care coordination will be reported using supporting 
quotations. Analysis will include an integrative synthesis of data (identification of key points, potential 
themes, areas of further exploration).  
 
Evidence Integration:  Using an evidence integration triangle (EIT), which combines multiple sources of 
qualitative data (team blog, performance coaching notes, and key informant interviews), we will 
determine the  concrete attributes and cessation approaches used by LDCT lung cancer screening 
programs.46 EIT is a methodology intended to synthesize data crossing multiple levels and requires 
information about the intervention, implementation process, and measures of progress using data 
generated from key stakeholders. This will be a process that will engage the entire research team and 
EAB members as we assign relative importance and feasibility to each cessation strategy (and under 
which conditions).  EIT analysis will be supported by the EAB members, Drs. Curran and Ammerman 
who have extensive experience with qualitative data analysis and synthesis of multiple sources of 
qualitative data.  Please refer to Section 7.9 for more information on the EAB members, their expertise 
and their level of commitment to support this process.  
 
Data generated from Aim 2 will allow our team to characterize implementation of tobacco cessation 
strategies within LDCT screening sites, according to: (1) extent of training and coaching needed for 
adoption and adaptation and in response to the specific RFA requirements of fidelity, feasibility, and 
appropriateness; (2) organizational characteristics that promote or hinder implementation of the PHS 
strategies; and (3) characteristics of the evidence-based tobacco cessation strategies that make them more 
or less adoptable and adaptable in different types of community-based screening programs.  These data 
will lead to an implementation toolkit that will be evaluated for disseminated and scale-up by national 
stakeholders (Aim 3). The toolkit will be developed with support from the EAB and will not require 
NCORP personnel participation. 
 
13.7 
Additional Data Elements Required by the SCALE Collaborative 
 
 
 
Fidelity:  The degree to which an intervention was implemented as it was prescribed in the 
original protocol or as it was intended. 
o 
We will use self-reported data from patients (≤14 days of their screening visit) and ask if 
they experienced various cessation strategies. 
o 
Each clinic will have agreed to offer certain cessation strategies (based on the training 
and implementation planning). 
o 
We can create a measure of fidelity based on what clinics agreed to offer with what 
patients say was offered.   
 
Patient Acceptance of the Intervention.  We agreed to use the following question, which we 
include on the ≤14 day patient survey. 
o 
“Did you receive smoking cessation support during your visit?” (CORE Item) 
o 
“If yes, how satisfied were you with the smoking cessation support you received?” 
(Optional Item from the SCALE collaborative) 

 
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 
Patient Reach 
o 
As expected by the SCALE Collaborative, we will: 
 
Calculate the percentage of current smokers enrolled  
 
Representativeness of participating patients (compared to non-enrolled 
participants), by age, sex, race, ethnicity. 
 
These data are included in the patient baseline survey (for those who are 
enrolled) and are also included in the “Reason for Refusal” information at 
baseline and follow-up assessments (see Appendix 3 and 4) 
 
Feasibility/Appropriateness/Workflow Fit  
o 
We will measure feasibility and appropriateness using the Key Informant Interviews for 
intervention and usual care clinics.  These will be measured at baseline and at follow-up 
(8 months after baseline) for all clinics regardless of treatment arm. 
o 
The measure is a structured survey, consistent with the expectation of the SCALE 
collaborative and can be found in Appendix 5 and 21. 
 
Cost  
o 
Cost was not an original measure in our protocol. Therefore, we have agreed to partner 
with the Georgetown University team leading a CISNET modeling approach 
(Investigators:  Rafael Meza, PhD, Jeanne Mandelblatt, MD, MPH, David Levy, PhD, 
Jinani Jayasekera, PhD, and Kathryn Taylor, PhD-PI).   Data provided to the CISNET 
team include fixed costs (e.g., overhead, phone, interventionists, etc.) and variable costs 
(e.g., time spent in intervention, interventionists).  Participation in the CISNET group 
will require addition time from the research team, but will require no additional data 
collection, support, or time from the NCORP personnel, the cessation program champion, 
or the lung cancer imaging personnel.    
 
Lung RADS 
o Lung RADS will be obtained from the lung cancer imaging report.   We request the 
complete, de-identified imaging report for data quality purposes (the consent form 
includes this language). For example, a patient with a Lung RADS category 2S means 
that there is a significant finding. The type of significant finding (e.g., coronary arterial 
calcification) will be unknown without obtaining the full imaging report (a score alone 
may have limited utility for a more in-depth analysis of the influence of Lung RADS on 
smoking cessation). 
 
13.8 
Reporting and Exclusions 
 
Missing Data Considerations: Our primary models use a mixed, multi-level models approach, which 
provides a valid approach for handling missing data if they are considered to be missing at random 
(MAR).  If the missing data mechanism is not MAR, we may consider using a propensity score-weighted 
approach to compare groups.  Each patient will have an estimated conditional probability of dropping out 
(propensity score) based on his/her characteristics pre-randomization; the propensity scores can be used 
as weights when making group comparisons.  This analysis will be used to determine what impact 
missing data may have on the inferences made. Dr. D’Agostino’s expertise in propensity score and 
missing data methods will be useful if needed. 54–56 
 
All of the participants who met the eligibility criteria will be included in the main analysis. All 
conclusions regarding effectiveness will be based on all eligible participants. 
 
 
 

 
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