EVarQuit: Extended Pre-quit Varenicline to Assist in Quitting Smoking
Phase: PHASE3
Conditions: Tobacco Smoking
Sponsor: State University of New York at Buffalo

 
1
Trial protocol/Statistical Analysis Plan 
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Complete Research Protocol (HRP-503) 
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HRP-503-Protocol-EVarQuit-Rev-2020-06-30.docx 
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Table of Contents 
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Template Instructions ..................................................................................................................................... 1 
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1.0 
Objectives .......................................................................................................................................... 3 
10 
2.0 
Scientific Endpoints ........................................................................................................................... 4 
11 
3.0 
Background ....................................................................................................................................... 4 
12 
4.0 
Study Design ..................................................................................................................................... 6 
13 
5.0 
Local Number of Subjects ................................................................................................................. 6 
14 
6.0 
Inclusion and Exclusion Criteria ....................................................................................................... 7 
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7.0 
Vulnerable Populations ..................................................................................................................... 9 
16 
8.0 
Eligibility Screening ........................................................................................................................ 10 
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9.0 
Recruitment Methods ...................................................................................................................... 10 
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10.0 
Procedures Involved ........................................................................................................................ 12 
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11.0 
Study Timelines ............................................................................................................................... 22 
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12.0 
Setting .............................................................................................................................................. 22 
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13.0 
Community-Based Participatory Research ...................................................................................... 23 
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14.0 
Resources and Qualifications .......................................................................................................... 24 
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15.0 
Other Approvals .............................................................................................................................. 26 
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16.0 
Provisions to Protect the Privacy Interests of Subjects .................................................................... 26 
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17.0 
Data Management and Analysis ...................................................................................................... 27 
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18.0 
Confidentiality ................................................................................................................................. 29 
27 
A. 
Confidentiality of Study Data ..................................................................................................... 29 
28 
B. 
Confidentiality of Study Specimens ............................................................................................ 31 
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19.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects .................................................... 31 
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20.0 
Withdrawal of Subjects ................................................................................................................... 33 
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21.0 
Risks to Subjects.............................................................................................................................. 34 
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22.0 
Potential Benefits to Subjects .......................................................................................................... 36 
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23.0 
Compensation for Research-Related Injury ..................................................................................... 36 
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24.0 
Economic Burden to Subjects .......................................................................................................... 36 
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25.0 
Compensation for Participation ....................................................................................................... 36 
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26.0 
Consent Process ............................................................................................................................... 38 
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27.0 
Waiver or Alteration of Consent Process ........................................................................................ 41 
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28.0 
Process to Document Consent ......................................................................................................... 41 
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29.0 
Multi-Site Research (Multisite/Multicenter Only) .......................................................................... 42 
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30.0 
Banking Data or Specimens for Future Use .................................................................................... 42 
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31.0 
Drugs or Devices ............................................................................................................................. 43 
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32.0 
Humanitarian Use Devices .............................................................................................................. 44 
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Template Instructions 
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NCT03262662    
 
 
 
 
EVarQuit: Extended Pre-quit Varenicline to Assist in Quitting Smoking 
Trial Protocol/Statistical Analysis Plan 
2020-06-30

 
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Sections that do not apply: 
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• 
In several sections, the addition of checkboxes for Not Applicable have been added to the template as 
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responses.   
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o 
If an N/A checkbox is present, select the appropriate justification from the list.   
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o 
If an N/A checkbox is not present, or if none of the existing checkboxes apply to your 
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study, you must write in your own justification. 
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• 
In addition: 
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o 
For research where the only study procedures are records/chart review:  Sections 19, 20, 
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22, 23, 24, 25, 31, and 32 do not apply. 
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o 
For exempt research:  Sections 31 and 32 do not apply. 
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Studies with multiple participant groups: 
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• 
If this study involves multiple participant groups (e.g. parents and children), provide information in 
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applicable sections for each participant group. Clearly label responses when they differ.  For example: 
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Response:  
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Intervention Group:  
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Control Group: 
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Formatting: 
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• 
Do not remove template instructions or section headings when they do not apply to your study. 
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If you are pasting information from other documents using the “Merge Formatting” Paste option will maintain 
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the formatting of the response boxes. 
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Amendments: 
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• 
When making modifications or revisions to this and other documents, use the Track Changes function in 
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Microsoft Word. 
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• 
Update the version date or number on Page 3. 
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PROTOCOL TITLE: 
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Include the full protocol title. 
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Response:   
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EVarQuit: Extinguishing cigarette smoking via extended pre-quit varenicline 
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PRINCIPAL INVESTIGATOR: 
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Name 
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Department 
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Telephone Number 
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Email Address 
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Response:  
Larry W. Hawk, Jr., PhD 
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Department of Psychology 
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716-645-0192 
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lhawk@buffalo.edu 
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VERSION: 
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3
Include the version date or number. 
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Response:   2020-06-30 
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GRANT APPLICABILITY: 
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Indicate whether this protocol is funded by a grant (e.g. NIH, foundation grant).  For a grant with multiple 
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aims, indicate which aims are covered by this research proposal. 
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NOTE: This question does not apply to studies funded by a sponsor contract. 
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Include a copy of the grant proposal with your submission.     
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Response: All aims of NCI/NIH grant CA206193 are covered by this proposal.   
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 App00-Grant-ExtinctionR01A1-NIHCompleteGrantDownload-2016-03-07.pdf. 
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RESEARCH REPOSITORY: 
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Indicate where the research files will be kept, including when the study has been closed.  The repository 
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should include, at minimum, copies of IRB correspondence (approval, determination letters) as well as 
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signed consent documents.  This documentation should be maintained for 3 years after the study has been 
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closed.   
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Response:  
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Location:   3rd floor, Diefendorf Hall in locked cabinets within locked offices 
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Address:  311 Diefendorf Hall, S Campus, University at Buffalo 
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Department:  Psychology 
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1.0 Objectives 
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1.1 
Describe the purpose, specific aims, or objectives of this research. 
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Response:  
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Aim 1: Evaluate the impact of extended pre-quit varenicline therapy on smoking cessation.  
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Aim 2: Evaluate the impact of extended pre-quit varenicline therapy on smoking behavior and 
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related processes prior to cessation.  
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Aim 3: Evaluate the degree to which changes in pre-quit smoking behavior (Aim 2) truly account 
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for, or mediate, the impact of extended pre-quit varenicline on smoking cessation (Aim 1).  
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UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: As detailed in 
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our administrative supplement request (EvarQuit Admin Supp Application – 2020-04-21.pdf), “…to 
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enhance this R01’s ability to inform and link to precision medicine approaches, we propose to evaluate the 
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role of variants in two families of genes previously associated with varenicline concentrations, nausea, 
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and/or smoking cessation” (select SNPs related to drug transport [OCT2] and nicotinic receptor subunits 
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[CHRNA4/CHRNB2]). 
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1.2 
State the hypotheses to be tested, if applicable. 
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NOTE:  A hypothesis is a specific, testable prediction about what you expect to happen in your study 
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that corresponds with your above listed objectives. 
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Response:  
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We hypothesize that extended run-in varenicline will improve bio-verified continuous abstinence 
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rates at end-of-treatment and at long-term follow-up (6- months), compared to the standard run-
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in. Because extended pre-quit treatment may be particularly helpful for women (Becker et al., 
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2008; Hawk et al., 2012), the study is powered to evaluate moderation of treatment by gender. 
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4
Consistent with extinction theory, we predict that the extended run-in group will exhibit greater 
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pre-quit reductions in smoking (cigarettes per day, CO) than the standard run-in group. Effects 
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on other biological (cotinine, total nicotine exposure), self-report (subjective effects of smoking, 
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craving, withdrawal, nausea, expectancies), and behavioral (laboratory reinforcement task) 
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outcomes will also be evaluated to better characterize potential treatment mechanisms. 
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The extinction model predicts that the cessation benefits of extended run-in varenicline will be 
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explained by greater pre-quit reductions in smoking. We will also test whether this mechanism is 
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particularly strong among women (i.e., moderated mediation). 
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2.0 Scientific Endpoints 
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2.1    Describe the scientific endpoint(s), the main result or occurrence under study.   
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NOTE:  Scientific endpoints are outcomes defined before the study begins to determine whether the 
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objectives of the study have been met and to draw conclusions from the data.  Include primary and 
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secondary endpoints.  Some example endpoints are:  reduction of symptoms, improvement in quality of life, 
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or survival.  Your response should not be a date.   
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Response: 
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Our primary outcome measure (for Aims 1 and 3) is bio-verified self-report of continuous abstinence from 
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smoking during the final four weeks of treatment (Weeks 8-11 post-quit, the typical primary outcome in 
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varenicline trials; e.g., Gonzales et al., 2006; Hawk et al., 2012; Jorenby et al., 2006). Continuous 
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abstinence will also be evaluated for weeks 8-26 and 8-26 post-quit (with bio-verification at 6M  visits, 
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respectively). Secondary clinical outcomes include rates of side effects and pill count measures of 
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adherence. 
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Our primary mediator of interest will be smoking behavior (cigarettes smoked per day, or CPD) during the 
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pre-quit phase of the study (Weeks -5 through -1), as reported during daily morning EMA assessments. 
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Secondary measures for understanding the causal process include expired-air CO and varenicline levels 
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will also be examined, as will laboratory measures of reinforcement, craving, withdrawal, subjective effects 
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of smoking, and nausea. 
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3.0 Background 
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3.1 
Provide the scientific or scholarly background, rationale, and significance of the research based on 
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the existing literature and how it will contribute to existing knowledge.  Describe any gaps in 
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current knowledge.  Include relevant preliminary findings or prior research by the investigator.  
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Response: Cigarette smoking remains the leading preventable cause of death in the US, killing an estimated 
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480,000 people per year and linked to 1 in 3 cancer deaths. The 2014 Surgeon General’s Report (US 
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DHHS, 2014) suggests that the consequences of smoking are even worse than previously thought. Cigarette 
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design changes have increased the risk smoking poses for lung cancer, and smoking is now linked to an 
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even larger number of cancers (including colorectal and liver).  Moreover, emerging evidence suggests that 
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smoking increases the risk for cancer recurrence and treatment toxicity (US DHHS, 2014).  
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Although quitting smoking markedly lowers disease risk and improves health (US DHHS 2014), there are a 
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limited number of effective smoking cessation therapies, and long-term cessation rates remain low. Three 
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evidence-based pharmacotherapies are available for smoking cessation in the US:  nicotine replacement 
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therapy (NRT), bupropion, and varenicline. Both NRT and bupropion approximately double the odds of 
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long-term cessation (6 months or more) when compared to placebo (e.g., Fiore et al., 2008). Varenicline, 
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approved by the FDA in 2006, triples the odds of quitting compared to placebo and outperforms single-
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NRT and bupropion (for a review, see Cahill et al., 2013; c.f. Baker et al., 2016). Nevertheless, long-term 
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abstinence rates remain low, with only 1 in 4 varenicline users smoke free 6+ months after quitting (Cahill 
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et al., 2013). 
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Given the tremendous costs of smoking and the benefits of quitting, the development of cessation 
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approaches with greater efficacy is critical.  The typical drug discovery path is unlikely to generate an 
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answer. Despite enormous investments in evaluating numerous medications in the decade since varenicline 
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reached the US market, “no new smoking cessation aid is nearing…FDA approval” (e.g., Rigotti, 2015). 
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Certainly, there is nothing looking likely to do better than the treatments we already have – but that is 
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exactly what we need. 
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To advance clinical practice, we build on basic research, theory, and compelling preliminary data from 
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small-scale RCTs to evaluate a treatment approach that appears likely to beat our current “best in class” 
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cessation approach, standard varenicline therapy. We take the perspective that improved understanding and 
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targeting of treatment mechanisms is the best path forward (e.g., Kraemer et al. 2006; MacKinnon, 2008; 
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Rigotti, 2015; TRIP, 1988). Varenicline binds to the alpha-4 beta-2 receptor subunit of nicotinic 
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acetylcholine receptors (nAChR), exerting effects as both a partial nicotine agonist, by stimulating 
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dopamine release, and as an antagonist, by blocking the binding of nicotine to this site. In clinical trials, 
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varenicline robustly decreased post-cessation smoking cravings and satisfaction with cigarettes during 
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lapses (e.g., Gonzales et al., 2006; Jorenby et al., 2006). For varenicline, which is typically administered for 
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a week prior to quitting and is hypothesized to work partly by reducing the reinforcing effects of smoking 
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(e.g., Rollema et al., 2007), it is also critical to examine pre-quit treatment mechanisms (e.g., Cummings & 
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Mahoney, 2008; Fiore et al., 2008; Hawk et al., 2015; Rose, 2009, 2011; Rose & Levin, 1991).  
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From a learning perspective, when favorable consequences of a behavior are removed, the behavior 
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decreases in frequency, or is extinguished. Consistent with the hypothesis that varenicline diminishes the 
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reinforcing value of smoking in humans, varenicline dose-dependently reduces self-administration of 
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nicotine in rats (O’Connor et al., 2010; Rollema et al., 2007). For varenicline to promote extinction in 
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human smokers, they must continue smoking while taking the drug in order to learn that the reinforcing 
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effects are attenuated. The typical one-week run-in period for varenicline is likely insufficient, as extinction 
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requires numerous “trials” (see Bouton et al. 2012) and does not generalize well from one situation or 
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context to another (Bouton, 2000, 2004a; Collins & Brandon, 2002; see also Conklin & Tiffany, 2002).  
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How can we effectively promote such extinction in smokers? The pioneering work of Rose et al. (1988) 
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with the nicotine patch suggested a straightforward method: extend the pre-quit run-in medication period to 
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allow greater repeated natural exposure to attenuated reinforcement from smoking prior to the target quit 
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date (TQD). We recently tested this approach in small-RCTs of both bupropion (Hawk et al., 2015 /Prelim 
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Study 1) and varenicline (Hawk et al., 2012 / Prelim Study 2; see also Ashare et al., 2012, Gass et al., 
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2012); treatment-seeking smokers were randomized to either a Standard run-in group (3 weeks of placebo, 
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1 week of pre-TQD medication) or an Extended run-in group (4 weeks of pre-TQD medication); all 
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participants received counseling and typical regimens of post-TQD medication.  Hajek et al. (2011) 
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conducted an independent but very similar small-scale RCT of varenicline. In all three pilot RCTs, the 
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results were consistent with an extinction hypothesis: the extended run-in resulted in greater reductions in 
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smoking rate (and tended to reduce craving and smoking satisfaction) prior to the TQD and improved 
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abstinence rates at short-term follow-up. (In both Hawk et al. studies, there was evidence that the extended 
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run-in had a greater impact among women more than men; Hajek et al. did not examine gender effects). 
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Overall, the results of these three studies are promising, particularly because the control condition was an 
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approved cessation medication; in the case of varenicline, the extended run-in beat the current “best in 
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class” treatment (standard run-in varenicline). However, the studies were limited by their small sample 
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sizes (Ns=60-100) and short-term follow-up (4 weeks – 3 months). 
 
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The proposed study takes the next critical step in evaluating the degree to which extended-run in 
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varenicline will set a new efficacy standard in smoking cessation, a large-scale RCT with long-term follow-
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up. Thus, the primary significance of the proposed RCT is that it will, if successful, provide a marked 
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advance in the treatment of cigarette smoking, the leading preventable cause of death in the US. Moreover, 
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it would do so at far less cost and far more quickly than traditional pharmaceutical development pathways 
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(see Chong & Sullivan, 2007; Collins, 2011). Although every innovation in treatment faces challenges in 
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bridging the science-practice gap, the proposed treatment and RCT are designed to facilitate and inform 
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widespread dissemination and implementation (see the Introduction to the revision), further enhancing the 
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significance of the work. 
229 
 
The proposed RCT will also evaluate the mechanisms by which extended run-in varenicline exerts 
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its clinical effects. This addresses a critical split in our field and gap in our knowledge – whereas most 
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varenicline RCTs have been weak in testing mechanisms with anything other than retrospective self-report 
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at clinic visits (e.g., Gonzales et al., 2006; Jorenby et al., 2006; Ebbert et al., 2015), most laboratory 
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behavioral pharmacology studies of varenicline mechanisms have focused on participants who are not 
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actively trying to quit (Mostchman et al., 2014). As in our pilot RCT with varenicline (Hawk et al., 2012; 
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Prelim Study 2), we will obtain biochemical measures of changes in smoking behavior and real-world, real-
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time measures of smoking reinforcement and related constructs via ecological momentary assessment 
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(EMA). In addition, we have adapted laboratory paradigms from behavioral pharmacology to more 
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thoroughly evaluate changes in reinforcement in the pre-quit period (see Prelim Study 4). Most 
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importantly, we will use these data to directly evaluate the degree to which extinction of reinforcement 
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accounts for, or mediates, the effect of extended run-in varenicline therapy. Our evaluation of putative 
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treatment mechanisms will both advance knowledge and provide clearer targets for subsequent treatment 
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development and personalization (e.g., Kraemer et al., 2006).   Additional details are provided in the 
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attached grant application and administrative supplement application. 
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3.2 
Include complete citations or references.  
245 
Response: All references are included in the attached grant application (App00) and administrative 
246 
supplement application. 
247 
 
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4.0 Study Design 
249 
4.1 
Describe and explain the study design (e.g. case-control, cross-sectional, ethnographic, 
250 
experimental, interventional, longitudinal, observational). 
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Response: This study, which will be conducted 
252 
over a 5-year period, will employ a two-group, 
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balanced, randomized, double-blind, placebo-
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controlled parallel-group design. The research 
255 
design is summarized in the Figure at right. 
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5.0 Local Number of Subjects 
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5.1 
Indicate the total number of subjects that will be enrolled or records that will be reviewed locally. 
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Response: Participants will be 320 treatment-seeking adult smokers (160 female). 
265 
 
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UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: An optional 
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saliva sample for genetic analysis will be obtained from up to 200 of the 320 participants. 
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5.2 
If applicable, indicate how many subjects you expect to screen to reach your target sample (i.e. your 
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screen failure rate).  
270 
Response: To accrue 320 ITT participants across 44 months, we have developed conservative projections 
271 
for accruing 9 ITT participants per month: screening approximately 55 potential participants by phone each 
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month, with 50% (28) of those eligible after phone prescreen, 50% (14) of those attending the intake visit, 
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75% (10) of those at intake consenting and remaining eligible after full screening, and 90% (9) of those 
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eligible ultimately achieve ITT status. 
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2019-11 Update (approved/implemented early 2020-01):  In recent months, we have extensively 
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reviewed our accrual process.  Accrual flow projections that we made in the grant proposal (e.g., 50% 
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eligible on phone screen, 75% eligible at intake visit) have been accurate, with one critical exception.  We 
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7
predicted that we would lose no more than 10% of prospective participants between the intake visit and 
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beginning treatment 1-2 weeks later (and counting as one of our 320 intent-to-treat, or ITT, participants). In 
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reality, we have lost more than twice that many people (21%) at this stage. Importantly, the loss of potential 
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participants between the intake visit and ITT disproportionately affects the representation of racial/ethnic 
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minorities. That is, participant loss at this stage is 36% for people from minorities compared to 15% for 
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non-Hispanic Caucasians.  
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In an effort to improve the proportion of intake-eligible participants who ultimately achieve ITT status, 
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we made the following changes with the 2019-11 IRB modification: 
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1. Increase remuneration for the lab visits (see Section 26.1), which provide no clinical benefit and last 
287 
longer than clinic visits. 
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2. Eliminate the 50% adherence requirement for the device-initiated assessments in the Ecological 
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Momentary Assessment (EMA; see section 11.1). 
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5.3 
Justify the feasibility of recruiting the proposed number of eligible subjects within the anticipated 
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recruitment period. For example, how many potential subjects do you have access to? What 
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percentage of those potential subjects do you need to recruit? 
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Response: Roughly 20% of adults in NY smoke, and most smokers say they would like to quit. Thus, there 
295 
is a large number of eligible participants in WNY. Indeed, our success enrolling 12 ITTs/month in a more 
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demanding and restrictive trial (see Lerman et al., 2015) from 2011-2015 supports the feasibility of meeting 
297 
our accrual target. 
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6.0 Inclusion and Exclusion Criteria 
300 
6.1 
Describe the criteria that define who will be included in your final study sample.  
301 
NOTE:  This may be done in bullet point fashion. 
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Response:  
303 
• 
Baseline smoking rate and CO: 
304 
o 
Prior to 2019-11 modification: Smoking at least 10 cigarettes per day for the past 6 
305 
months and CO >7 at intake. 
306 
o 
Beginning with the 2019-11 modification: Smoking at least 5 cigarettes per day (CPD) 
307 
for the past 6 months. (In November 2019, we noted that smoking 5-9 was the most 
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single common reason for exclusion at phone screen. This was particularly notable for 
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people from racial and ethnic minority groups [e.g., 2% of phone screens for non-
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Hispanic whites vs. 12% of phone screens for Black/African American participants] In 
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light of the growing number of daily smokers who smoke <10 CPD [e.g., Jamal et al., 
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MMWR, 2018) and our desire to increase the diversity and representativeness of the 
313 
sample, we reduced the CPD criterion from 10 to 5. With lighter smokers, the expired air 
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CO criterion would be less accurate/reliable for indexing daily smoking; therefore, it was 
315 
eliminated.) Once the modification is approved, we will contact people who were 
316 
previously deemed ineligible only because they smoked 5-9 CPD and offer to re-screen if 
317 
they are interested.   
318 
• 
At least moderately motivated to quit smoking (3 or 4 on phone screen; modified MTSS) and 
319 
intention to make a quit attempt with varenicline 1 month after treatment begins. 
320 
• 
Planning to remain in western NY during the study period (intake) 
321 
• 
Willing to use varenicline and to refrain from other cessation treatments and tobacco products 
322 
during the study period. (intake) 
323 
• 
Age 18-70 years. (phone screen) 
324 
• 
Fluent English speaker (clinical judgment) 
325 
• 
Capable of providing informed consent, which includes compliance with the requirements and 
326 
restrictions listed in the combined consent and HIPAA form (clinical judgment) 
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8
• 
To be ITT, the participant must complete Lab Visit 1 and meet minimal completion rate for real-
328 
world (EMA) assessments (detailed below; see also Section 6.2). 
329 
• 
Normal or corrected vision required for study. 
330 
6.2 
Describe the criteria that define who will be excluded from your final study sample.   
331 
NOTE:  This may be done in bullet point fashion.  
332 
Response:   
333 
• 
Use of other tobacco products, including e-cigarettes, in past 7 days (phonescreen) 
334 
• 
Use of smoking cessation medication, including nicotine replacement therapy, in the past 14 days? 
335 
(phonescreen) 
336 
• 
Prior allergy/hypersensitivity to varenicline (phone screen) 
337 
• 
Pregnancy (phone screen, plus Urine at Intake) 
338 
• 
Substance use:   
339 
o 
Alcohol:  At phone screen:  “Daily or almost daily” report of drinking 5 (4 for women) or 
340 
more drinks a day in the past year (Nida Quick Screen after explaining drinks per day). 
341 
Intake: AUDIT score > 15 at intake, suggestive of alcohol dependence and warranting 
342 
treatment; for those with scores between 8 and 15, we will advise reducing drinking; 
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Babor et al., 2001; see also Rubinsky et al 2010).  
344 
o 
Medical treatment in past 3 months, including Suboxone (buprenorphine) and methadone 
345 
(at phone screen) 
346 
o 
Using a combination of the NIDA-modified ASSIST (4-26 = moderate risk; 27+ = high 
347 
risk) and urine toxicology screen (both at intake): 
348 
 
Cannabis: ASSIST=27+ (tox screen not used) 
349 
 
Cocaine:  ASSIST=7+ OR positive tox screen 
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 
Methamphetamine: ASSIST=7+ OR positive tox screen  
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 
Inhalants, hallucinogens: ASSIST score = 7+ 
352 
 
Prescription stimulants, sedatives, or sleeping pills: 
353 
• 
With prescription, ASSIST 27+ 
354 
• 
Without prescription, ASSIST 7+ 
355 
 
Opioids: 
356 
• 
With prescription, ASSIST 27+ (note ineligible if prescription is for 
357 
buprenorphine or methadone) 
358 
• 
Without prescription, ASSIST 7+ OR positive tox screen 
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360 
• 
Psychiatric:   
361 
o 
Antipsychotic medications (phone / intake) 
362 
o 
Lifetime history of schizophrenia or bipolar disorder (phone) 
363 
o 
Evidence of current major depression ( per Patient Health Questionnniare (PHQ-9; 
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Kroenke & Spitzer, 2002) score 12+, see Gilbody & McMillan, 2012; Loewe et al, 2004)  
365 
at intake 
366 
o 
Past 10 years suicidal ideation / behavior at intake, using slightly more conservative 
367 
exclusion criteria than in the EAGLES study of neuropsychiatric events when quitting 
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smoking (see Anthenelli et al., 2016), all of the following are exclusionary on the 
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baseline Columbia-Suicide Severity Rating Scale (Posner et al., 2008): 
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 
SI without intent (C-SSRS #1, #2, or #3), if any intensity rating (Frequency, 
371 
Duration, Controllability, Deterrents, or Reasons for Ideation) is > 2.   
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 
SI with intent (C-SSRS #4, or #5), regardless of intensity ratings. 
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 
Suicidal Behavior (any suicide attempt, interrupted attempt, aborted attempt, or 
374 
suicide preparatory acts or behavior on the C-SSRS). 
375 
• 
General Exclusion: 
376 
o 
Any medical condition, illness, disorder or concomitant medication that compromises 
377 
participant safety or treatment, as determined by the Principal Investigator and/or Study 
378 
Physician. 
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9
o 
Inability to provide informed consent or complete any of the study tasks as determined by 
380 
the Principal Investigator and/or Study Physician. 
381 
6.3 
Indicate specifically whether you will include any of the following special populations in your study 
382 
using the checkboxes below.   
383 
 
384 
NOTE:  Members of special populations may not be targeted for enrollment in your study unless 
385 
you indicate this in your inclusion criteria. 
386 
Response:  N/A – We will not include any of the following special populations. 
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☐ 
Adults unable to consent 
388 
☐ 
Individuals who are not yet adults (infants, children, teenagers) 
389 
☐ 
Pregnant women 
390 
☐ 
Prisoners 
391 
6.4 
Indicate whether you will include non-English speaking individuals in your study.  Provide 
392 
justification if you will exclude non-English speaking individuals.  
393 
In order to meet one of the primary ethical principles of equitable selection of subjects, non-English 
394 
speaking individuals may not be routinely excluded from research as a matter of convenience. 
395 
In cases where the research is of therapeutic intent or is designed to investigate areas that would 
396 
necessarily require certain populations who may not speak English, the researcher is required to 
397 
make efforts to recruit and include non-English speaking individuals.  However, there are studies in 
398 
which it would be reasonable to limit subjects to those who speak English.  Some examples include 
399 
pilot studies, small unfunded studies with validated instruments not available in other languages, 
400 
studies with numerous questionnaires, and some non-therapeutic studies which offer no direct 
401 
benefit. 
402 
Response:  We will not include non-English speaking individuals because the study focuses on extensive 
403 
self-report measures, including 35 days of daily assessments with electronic reporting, that have not 
404 
validated in languages other than English. 
405 
 
406 
7.0 Vulnerable Populations 
407 
If the research involves special populations that are considered vulnerable, describe the safeguards 
408 
included to protect their rights and welfare.   
409 
NOTE: You should refer to the appropriate checklists, referenced below, to ensure you have provided 
410 
adequate detail regarding safeguards and protections. You do not, however, need to provide these 
411 
checklists to the IRB. 
412 
7.1 
For research that involves pregnant women, safeguards include: 
413 
NOTE CHECKLIST: Pregnant Women (HRP-412) 
414 
Response:  
415 
☒ 
 N/A:  This research does not involve pregnant women. 
416 
7.2 
For research that involves neonates of uncertain viability or non-viable neonates, safeguards 
417 
include: 
418 
NOTE CHECKLISTS: Non-Viable Neonates (HRP-413), or Neonates of Uncertain Viability (HRP-
419 
414) 
420 
Response:    
421 
☒ 
 N/A:  This research does not involve non-viable neonates or neonates of uncertain viability. 
422 
7.3 
For research that involves prisoners, safeguards include: 
423 
NOTE CHECKLIST: Prisoners (HRP-415) 
424 
Response:   
425 

 
10
☒ 
 N/A:  This research does not involve prisoners. 
426 
7.4 
For research that involves persons who have not attained the legal age for consent to treatments or 
427 
procedures involved in the research (“children”), safeguards include:   
428 
NOTE CHECKLIST: Children (HRP-416) 
429 
Response:  
430 
☒ 
 N/A:  This research does not involve persons who have not attained the legal age for consent to 
431 
treatments or procedures (“children”). 
432 
7.5 
For research that involves cognitively impaired adults, safeguards include: 
433 
NOTE CHECKLIST: Cognitively Impaired Adults (HRP-417) 
434 
Response:  
435 
☒ 
 N/A:  This research does not involve cognitively impaired adults. 
436 
7.6 
Consider if other specifically targeted populations such as students, employees of a specific firm, or 
437 
educationally or economically disadvantaged persons are vulnerable.  Provide information 
438 
regarding their safeguards and protections, including safeguards to eliminate coercion or undue 
439 
influence. 
440 
Response:   
441 
☒ 
 N/A This study does not target vulnerable populations. 
442 
 
443 
8.0 Eligibility Screening  
444 
8.1 
Describe screening procedures for determining subjects’ eligibility.  Screening refers to determining 
445 
if prospective participants meet inclusion and exclusion criteria.  
446 
Include all relevant screening documents with your submission (e.g. screening protocol, script, 
447 
questionnaire).  
448 
Response:  
449 
After obtaining verbal consent, potential subjects will be screened by telephone for eligibility to attend an 
450 
overview and intake visit.  
451 
 EVQ2CRFs - Initial Screen - 2017-08-02.pdf(2017-08-02) 
452 
The intake will begin with informed consent.  Consented participants will complete the following 
453 
assessments: vital signs and CO levels, smoking history, concomitant medication review, baseline side 
454 
effects, urine toxicology screen, urine pregnancy test for women, and brief measures of mood, suicidality, 
455 
depression, and anxiety. A study clinician will carefully review the medical history and complete a focused 
456 
physical examination.    
457 
 Informed consent is App28-InformedConsentWithHIPPA—EvarQuit. 
458 
 Measures are found in: 
459 
o 
EVQ2CRFs - Intake - Self-Report Measures - 2017-08-02.pdf(2017-08-02) 
460 
o 
EVQCRFs - Intake - Staff Instruments - 2017-08-02.pdf(2017-08-02) 
461 
During the baseline lab visit, participants will complete the laboratory reinforcement task 
462 
(discussed below) and will be trained in completing a baseline week of ecological momentary 
463 
assessments (EMA; discussed below). Participants must attend the baseline lab visit and complete 
464 
at least 40% of baseline week (EMAs) in order to continue in the study. (Participants who do not 
465 
meet these requirements can schedule one additional baseline week.) 
466 
 
467 
9.0 Recruitment Methods 
468 

 
11
☐ 
N/A:  This is a records review only, and subjects will not be recruited.  NOTE:  If you 
469 
select this option, please make sure that all records review procedures and 
470 
inclusion/exclusion screening are adequately described in other sections. 
471 
9.1 
Describe when, where, and how potential subjects will be recruited.  
472 
NOTE:  Recruitment refers to how you are identifying potential participants and introducing them to 
473 
the study.  Include specific methods you will use (e.g. searching charts for specific ICD code 
474 
numbers, Research Participant Groups, posted advertisements, etc.). 
475 
Response:  
476 
We plan to enroll participants from January 2017 through January 2021. 
477 
Community participants will be recruited primarily via radio and television ads, internet (e.g., Craigslist, 
478 
Facebook), flyers around the community and via email list serves, and newspaper advertisements, as in our 
479 
recent large-scale trial. We also plan to use researchmatch.org, Urban Family Practice, and the Buffalo 
480 
Research Registry.  
481 
The Urban Family Practice will send a co-signed letter out to their patients, providing them more 
482 
information about the EvarQuit Program. Should a person become interested in the program, they could 
483 
call us for more information. Additionally, names and phone numbers of those to whom letters were sent 
484 
will be provided to our team. We will call those participants that we have not heard from within 2 weeks of 
485 
letter postmark date to see if they received the information (following the attached script). We will only 
486 
make two contact attempts by phone to each person. 
487 
We will also use I2B2 in UB CTSI to recruit participants from the UBMD medical data base. A letter will 
488 
be sent to the Physician (see attached letter) prior to contacting participants (see attached letter). We will 
489 
not contact prospective participants by phone, allowing them greater control over their participation.  
490 
The New York State Department of Health has approved of the New York State Smokers Quit Line 
491 
(NYSSQL) sending out letters to smokers in our region who recently contacted the quit line. We will not 
492 
have access to any names or any contact information. We will not be cosigning the letter. Folks who get the 
493 
letter will have the option of contacting us for more information. 
494 
A project website also allows potential participants to find our information and contact us, if they are 
495 
interested in being screened for our program (see attached screen shots & http://quitforgoodwny.com/). 
496 
9.2 
Describe how you will protect the privacy interests of prospective subjects during the recruitment 
497 
process.   
498 
NOTE:  Privacy refers to an individual’s right to control access to him or herself.   
499 
Response: Most importantly, we will recruit via public advertisements so that interested participants self 
500 
identify, and we will only contact participants and collect study data by methods to which they have 
501 
requested/consented. To enhance privacy and confidentiality during the phone screen, all phone screens 
502 
will be conducted from secure offices on the third floor of Diefendorf Hall, and messages will be quite 
503 
general (see phone script overview, App08-01a).  
504 
9.3 
Identify any materials that will be used to recruit subjects.  
505 
NOTE:  Examples include scripts for telephone calls, in person announcements / presentations, 
506 
email invitations.  
507 
For advertisements, include the final copy of printed advertisements with your submission. When 
508 
advertisements are taped for broadcast, attach the final audio/video tape.  NOTE:  You may 
509 
submit the wording of the advertisement prior to taping to ensure there will be no IRB-required 
510 
revisions, provided the IRB also reviews and approves the final version. 
511 
 Response:  
512 
  EvarQuit Study Facebook Recruitment 
513 
  EVQ Recruitment Letter-Urban Family Practice 
514 

 
12
 EvarQuit Advertising Flyers- provides several flyer versions for the study. 
515 
 Referral Cards 
516 
 Website Screen shots- for www.QuitforGoodWNY.com 
517 
 Recruitment Letter to Participants from NYSSQL 
518 
 App09-01-EvarQuit TV & Radio Advertising 2018-12-13.doc provides the text for radio, craigslist, 
519 
and newspaper advertisements. 
520 
 App09-02a-I2B2 Physician permission Letter Template ver 032417 - EVarQuit2017-06-01.docx 
521 
 App09-02b-I2B2 Recruitment letter to participant template ver 032417 - EvarQuit 2017-06-01.docx 
522 
 App09-03– Phone and Letter Script for Prior CPD Ineligible.docx 
523 
 
524 
10.0 Procedures Involved 
525 
10.1 Provide a description of all research procedures or activities being performed and when they are 
526 
performed once a subject is screened and determined to be eligible. Provide as much detail as 
527 
possible.   
528 
NOTE:  This should serve as a blueprint for your study and include enough detail so that another 
529 
investigator could pick up your protocol and replicate the research.  For studies that have multiple 
530 
or complex visits or procedures, consider the addition of a schedule of events table in in your 
531 
response. 
532 
Response:  Procedures. Study procedures generally follow standard practice and our prior work.   
533 
 
534 
 
Lab visits. In addition to the measures noted in the table above, the two lab visits include two 
535 
additional procedures, described below.  During the baseline lab visit (L1; Week -5), participants will 
536 
complete the laboratory reinforcement task (CBUCC; see below) and will be trained in completing a 
537 
baseline week of EMA assessments (details below). Lab visit 2 (L2; Week -2) is completed in the final 
538 
week of the medication manipulation phase and offers clear experimental data regarding the impact of 
539 
varenicline versus placebo on the laboratory task (CBUCC).  
540 
 For both CBUCC and EMA procedures, see EvarQuit Lab 1 SOP – 2017-09-19.docx.  
541 
 For L2 procedures including the ad-lib period, see EvarQuit Lab 2 SOP – 2019-02-18.docx 
542 
 For questionnaires used at the Lab Visits, see the EVQ2 – CRFs – Lab Visit.pdf. 
543 
 
544 

 
13
 
CBUCC. Participants will be instructed 
545 
to arrive at the lab visits having not smoked 
546 
since midnight; most sessions will be scheduled 
547 
in the morning to provide modest overnight 
548 
abstinence from smoking (expired-air CO must 
549 
be at least 40% lower than the CO obtained at 
550 
intake or the session will be rescheduled). 
551 
During CBUCC (Gass & Tiffany, under review), 
552 
smokers are exposed to a lit cigarette, a cup of 
553 
water, or a portion of highly preferred food (12 
554 
trials each, counterbalanced). These stimuli are 
555 
located behind a movable glass door. On each 
556 
trial, smokers rate their craving in the presence 
557 
of the cue and then indicate the amount of 
558 
money they are willing to spend to gain access 
559 
to the cue. During the task, they will be video 
560 
recorded. This video recording will be used to examine behavior during the lab task via coding paradigm.. 
561 
Participants are given $10 at the beginning of the procedure and told they can keep whatever 
562 
amount they do not spend during CBUCC. Participants may spend $.01 to $.25 on each trial. The 
563 
more the participants spend, the greater the probability that the door will be unlocked and they 
564 
will be able to sample the cue on that trial (probabilities range from 5% to 95%). At each trial, 
565 
participants are shown the CBUCC choice screen. After deciding how much to spend, participants 
566 
are told to try to open the door. If the door is unlocked, they can sample the cue (1 cigarette puff, 
567 
sip of water, or bite of food).  
568 
 
CBUCC generates multiple indices of reinforcement, including self-reported craving, the 
569 
amount of real money paid for the opportunity to puff a cigarette, latency to attempt to open the 
570 
door, and actual consumption (observed puff duration). In contrast to conventional laboratory 
571 
assessments of cigarette choice in which smokers delay smoking a single cigarette in exchange for 
572 
money (e.g., McKee et al., 2012), CBUCC generates multiple indices of smoking motivation and 
573 
reinforcement and does so across numerous trials. Thus, CBUCC produces very reliable estimates 
574 
of these variables within a single laboratory session. Moreover, unlike conventional cigarette 
575 
choice procedures, CBUCC allows us to examine the relative reinforcing value of consumable 
576 
reinforcers. 
577 
 
Ad-Lib Cigarette, Food, and Water Period. Following CBUCC administration at L2 (not 
578 
L1), we will now offer participants a brief ad-lib consumption period. Typically, participants have 
579 
at least 8 cigarettes left after CBUCC, and there is often leftover food/water from the procedure 
580 
that is typically discarded. Participants will have 15 minutes and can choose how much, if any, 
581 
cigarettes, food, and water they wish to consume. During this period, they will be informed that 
582 
research assistants have tasks to complete in the control room , and that they have 15 minutes to 
583 
consume as much or as little as they wish. Participants will continue to be passively recorded 
584 
during this period. We are expecting to use data from this period (i.e., count of cigarettes smoked, 
585 
weight of food eaten, puff number/puff duration/interpuff interval of cigarettes) as an additional 
586 
naturalistic measure of consumption reinforcement against which to measure the behaviors 
587 
obtained during CBUCC. Based on the average times of L2 observed thus far, we do not expect 
588 
that this will significantly lengthen the session on average from what is described in the consent 
589 
(i.e., 2 hours). If they smoke or eat at all, they will also complete the Subjective Effects 
590 
Questionnaire (same questions answered in CBUCC/on EMA).  
591 
UPDATE 2020-06-12 - elimination of lab visits for remaining participants: 
592 
The COVID lockdown obviously took a toll on all clinical research, and now we are modestly behind 
593 
in our accrual. Moreover, there is the concern that, as New York slowly reopens, community members 
594 
will be especially wary of trials such as ours because of the many visits to campus. Finally, there’s 
595 
always the possibility of additional lockdowns if COVID rebounds in the fall.  We have reviewed our 
596 
trial components for opportunities to reduce the number of visits and amount of unnecessary exposure 
597 

 
14
to procedures participants might find most burdensome or concerning – without affecting the overall 
598 
design of the study or our ability to realize the specific aims of the project.  
599 
With the approval of our funding agency (the National Cancer Institute), this modification requests that 
600 
we eliminate the two laboratory assessments of smoking reinforcement for the following reasons:  
601 
- They are the two longest study visits, and they are purely for research purposes, with no therapeutic 
602 
component.  
603 
- The lab task employed in these visits requires participants to repeatedly receive cigarettes, food 
604 
samples, and glasses of water from the researcher. Even thought we take all COVID-19-related 
605 
precautions to reduce the risk of virus transmission, participants may still be concerned/distressed 
606 
about the possibility of contracting the virus during this procedure. 
607 
- Although we value the mechanistic data that comes from the lab visits, these data are secondary to 
608 
our primary outcomes (smoking cessation outcomes, ecological momentary assessments (EMA), and 
609 
biochemical measures of smoking exposure. The core study design (a double-blind, placebo-controlled 
610 
trial with follow-up through 6 months post-quit) is unaffected. 
611 
Training for the EMA will be moved from Lab Visit 1 to the end of the Intake Visit. 
612 
 
613 
 
Ecological Momentary Assessment (EMA). Daily EMA data will be collected for 5 weeks before 
614 
TQD through 4 weeks post TQD (i.e., Weeks -5 to +4) using an application (app) that can be loaded onto 
615 
the participants’ personal smartphone/tablet (significantly reducing participant burden; e.g., Ginexi et al., 
616 
2014) or onto a study cell phone or tablet provided to the participant. The app – mobile EMA (mEMA; 
617 
http://mobileema.com; ilumivu, Inc.) allows de-identified data (linked only to participant ID) to be 
618 
synchronized with a secure server.  EMA training and assessment procedures will follow our recent work 
619 
(Gass et al., 2012; Hawk et al., 2012). During the baseline lab visit, participants will be trained on proper 
620 
use of the app and will demonstrate the ability to complete both self-initiated assessments (questionnaires 
621 
that the participant initiates, e.g., morning assessment) and device-initiated assessments (alerts to 
622 
participant are provided on a pseudo-random basis). Participants will be informed that they will receive $1 
623 
for completing each morning assessment and $1 for completing each device-initiated assessment.  To 
624 
improve adherence and reduce burden/intrusiveness, participants will select a 12-hour period during which 
625 
EMA prompts occur each day. Participants will be contacted by research staff ~3 days into the baseline 
626 
week to review adherence (based on incoming synchronized data) and troubleshoot any problems. 
627 
 
Morning assessment. Participants will be instructed to complete the morning assessment before 
628 
smoking their first cigarette of the day and within one hour of waking. In addition to reporting total number 
629 
of cigarettes smoked during the previous day (CPD), participants will report wake time and medication 
630 
adherence on the previous day. They will also complete a brief measure of craving, withdrawal, or 
631 
nausea/appetite. Altering the domain of assessment reduces both burden and reactivity, and 
632 
counterbalancing will ensure adequate coverage of all domains across the pre-quit period. At the end of this 
633 
assessment, the participants will be thanked for their report and reminded of the remuneration earned. In 
634 
our pilot work, most participants completed far more (mean=94%) than the 43% (3 days per week) 
635 
minimum required (Hawk et al., 2012).  
636 
 
Device-initiated assessments. Device-initiated prompts will be delivered 4 times per day (e.g., 
637 
randomized within 3-hour blocks) to assess time since last cigarette and two of the following four domains: 
638 
subjective effects of smoking, craving, withdrawal, and nausea/appetite (see Measures for details).  Thus, 
639 
each domain will be assessed up to twice per day. Counterbalanced presentation of domains across device-
640 
initiated assessments will maximize coverage of time of day and distribution of domains across each week, 
641 
while reducing participant burden and reactivity compared to assessing every domain in each device-
642 
initiated assessment. Sessions end with a reminder about remuneration earned. In our pilot work, 
643 
participants completed far more than the 50% minimum required (mean = 89%; Gass et al 2012).  
644 
2019-11 update: Note that in the 2019-11 IRB modification, we eliminated the 50% minimum (see 
645 
also Section 6.2) for the device-initiated prompts. Review of data for participants already screened for the 
646 
study demonstrated that participants had little trouble completing the morning assessments. This is 
647 

 
15
important, as the morning assessment contains measures central to the aims of the project. The device-
648 
initiated assessments, which are less critical to the aims of the project, were associated with greater 
649 
challenges for participants, and roughly 10% of participants either had to complete a second week of 
650 
baseline or never met the 50% baseline adherence threshold and were excluded or withdrew. To more 
651 
efficiently complete the trial, we eliminated the 50% requirement for device-initiated assessments. We do, 
652 
of course, continue to encourage and remunerate completion of these assessments. 
653 
UPDATE 2020-06-30 – OPTIONAL TROUBLESHOOTING SOFTWARE: As detailed above, 
654 
participants are required to complete a minimum number of EMA assessments during the baseline week. 
655 
Even after the baseline week, missed assessments reduce both the data available to the project and 
656 
remuneration to participants. Consequently, it is important to quickly resolve any problems participants 
657 
have with the EMA app. To date, troubleshooting has generally required lengthy phone conversations 
658 
and/or ad hoc participant visits to the clinic for assistance. To minimize participant burden and more 
659 
quickly address technical problems with the EMA app, participants will be offered (at Intake) the option 
660 
install a free, HIPPA-compliant app (TeamViewer, https://www.teamviewer.com/en-us/) for 
661 
troubleshooting. Participants have the option to decline having this app installed on their device and, if it is 
662 
installed, participants can remove it at any time. 
663 
It will be explained to participants that, should they choose to install the TeamViewer app: 
664 
• 
TeamViewer allows research staff to, with the participant’s consent, view and remotely control the 
665 
participant’s smartphone for a remote troubleshooting session.  
666 
• 
TeamViewer will only be used for troubleshooting EMA problems. During any troubleshooting 
667 
session, research staff will use TeamViewer only to navigate into the EMA app and related 
668 
settings to address problems and demonstrate how to avoid further issues, all while the participant 
669 
observes the staff member’s actions. 
670 
• 
Staff cannot use the app without real-time consent (the participant must click a pop-up to start a 
671 
session). The participant can continue monitor their phone and view what is being accessed. If the 
672 
participant chooses, they can end the remote session at any time.  
673 
• 
TeamViewer does not collect or store any information. 
674 
 For questionnaire items, see App10.3-04-Questionnaires. 
675 
Study-Within-A-Trial (SWAT) on EMA Remuneration – added to protocol on 2018-12-06. Pending 
676 
funding from the Buffalo CTSI Pilot Studies program, we plan to conduct a SWAT to evaluate methods to 
677 
improve adherence Adherence in the current trial has not been as strong as in the pilot work reported above, 
678 
likely in part because the pilot study was shorter (only 5 weeks of EMA instead of 9). In the current study, 
679 
adherence has been strong at the outset but then dropped, with rates at their lowest during the critical 4-
680 
week post-quit period. We also observe that adherence is lower among African-Americans than among 
681 
Caucasians. The goal of the SWAT is to evaluate two potential methods for improving adherence during 
682 
the post-quit period : increased frequency of payment (from once every two weeks to three times per week) 
683 
and increased amount of payment (from $1/assessment to $2/assessment.  
684 
In order to complete the EMA SWAT, over the course of a one-year period participants (equal 
685 
numbers of male and female, and of Caucasian and African-American) will be randomly assigned to each 
686 
of three conditions in advance of the TQD until we accrue 20 participants in each condition. At the TQD, 
687 
participants in the SWAT will receive a written consent addendum. 
688 
 For the three versions of the addendum, see EvarQuit Addendum – EMA SWAT – 2018-12-06.doc. 
689 
Participants randomly assigned to the standard condition would simply be informed that it is 
690 
important to continue the EMA over the next four weeks. Participants randomly assigned to the increased 
691 
frequency of payment and increased amount of payment will have the opportunity to accept or decline the 
692 
modified payment plan. If they decline, they will simply continue to participate in EVarQuit, but will be 
693 
not be enrolled in the SWAT.  
694 
We chose individualized addenda over a single broad consent form because the SWAT will only 
695 
pertain to a subset of EVarQuit participants. We considered explaining all three conditions to SWAT 
696 

 
16
participants, but ultimately decided against it because doing so could cause unnecessary distress to 
697 
participants randomized to the standard condition (who might feel they were ‘losing out’ even though 
698 
nothing had changed).  
699 
The results of the SWAT will inform our decision of whether to alter remuneration for subsequent 
700 
participants in the EVarQuit project. 
701 
 
Clinic visits (Weeks -4, -3, -1, 0 [TQD], 2, and 4), randomization, and study medication. At Clinic 
702 
Visit 1 (Week -4), participants are randomized (within gender) to the extended or standard run-in group, 
703 
complete study measures (see below), receive brief behavioral counseling (see below) and study 
704 
medication (details below), and are instructed to begin the medication the next day. Subsequent study visits 
705 
are similar in process and content. Randomization. The study statistician (Co-I Dr. Colder) will implement 
706 
and monitor the small-urn randomization (within-gender in urns/blocks of 8 [4 extended run-in, 4 standard 
707 
run-in]), leaving remaining personnel blinded to group membership. Participants are considered part of the 
708 
intent-to-treat (ITT) sample once they are dispensed medication at Clinic Visit 1 (C1). 
709 
 
Study medication. At visit C1 (Week -4), participants will be provided an initial 1-week supply of 
710 
study medication (either varenicline or identical appearing placebo) and instructed on use (one 0.5 mg 
711 
tablet orally daily x 3 days, then one 0.5 mg tablet twice daily x 4 days, then two 0.5 mg tablets twice 
712 
daily). One week prior to TQD (Visit C3 / Week -1), participants assigned to placebo will be switched over 
713 
to varenicline with standard dose increases during the initial week of use.  During the pre-quit period, all 
714 
study medication (active & placebo) will be dispensed as 0.5 mg tablets. This approach was successfully 
715 
used in Hawk et al. (2012) and will facilitate switching over from placebo to active medication while 
716 
maintaining blinding.  From TQD through EOT, all participants will receive open-label varenicline (one 1.0 
717 
mg tablet twice per day).  
718 
Pfizer will provide varenicline and matching placebo for the study at no cost. Should this change, or should 
719 
we run low on study medication between shipments from Pfizer, the research pharmacy will produce 
720 
matching opaque capsules containing varenicline (which they can purchase in bulk) and placebo 
721 
(methylcellulose), as they have done in many prior studies. 
722 
 
Instructions for medication use will be reviewed at each clinic visit. Subjects will return any 
723 
unused medication at the following clinic visit and will be dispensed enough medication to last until the 
724 
next visit.   
725 
 EVQ2CRFs – Intake (self-report and staff) pdfs include our side effect checklist from our previous 
726 
trial, supplemented with additional screening using the Columbia Suicide Severity Rating Scale 
727 
(CSSSRS).  Our emphasis will be on detecting, addressing, and reporting symptoms that are new or 
728 
increase from baseline. Consistent with App10-02, any new or increased suicidal ideation or behavior 
729 
will be evaluated by Drs. Hawk, Tiffany, or Mahoney (all study PIs are either clinical psychologists or 
730 
physicians trained in conducting further evaluation); the study PIs will make external (non-study) 
731 
referrals for additional evaluation or treatment as clinically indicated. 
732 
 
Counseling. As in our prior work (Hawk et al., 2012), participants will receive brief individual 
733 
behavioral counseling at 6 clinic visits (Weeks -4, -3, -1, 0 [TQD], 2, and 4) from counselors blind to 
734 
treatment group. Pre-quit sessions focus on topics common in behavioral counseling, including honing the 
735 
motivation to quit, identification of smoking triggers and trigger management, and social support (e.g., 
736 
Abrams & Niaura, 2003; Fiore et al., 2008), without explicitly discussing extinction. However, to allow 
737 
extinction to occur, we will not include active nicotine fading as part of the counseling. Instead, participants 
738 
will be asked to follow their smoking urges, smoking at least 25% of their baseline rate to allow their 
739 
bodies time to adjust to the medication, as in prior extended pre-quit work (Hawk et al., 2012, 2015; Rose 
740 
et al., 1998). In response to feedback from participants in prior studies, we will also offer brief counseling 
741 
“check-ins” by phone 1 and 7 weeks post-TQD. 
742 
 App10-03a-EVQ2 Counseling SOP 2017-09-21.docx provides the Counselor Manual and App10-03b-
743 
EVQ2 Counseling Handouts 2017-09-21.docx provides the participant workbook. 
744 
 
End-Of-Treatment (EOT) and 6-months post-TQD (6M) visits allow for biochemical verification 
745 
of self-reported abstinence, the primary outcome measure. Retention has been strong in our prior 
746 
varenicline studies (Hawk et al., 2012; Lerman et al., 2015). Clear explanations of the importance of 
747 

 
17
follow-up data for clinical application, ongoing contact with participants (including reminder calls), and 
748 
increased remuneration for attendance at EOT and 6M visits (when medication is no longer being provided) 
749 
bolster retention, which is expected to be 95% at TQD, 82% at EOT, and ~75% at 6M (based on Hawk et 
750 
al., 2012 and the Buffalo varenicline arm data from Lerman et al, 2015). 
751 
Update 2019-11: Retention at EOT and 6M follow-up has been substantially lower than anticipated. We 
752 
believe this is related to several inter-related factors. First, because of the EMA remuneration (up to 
753 
$35/week), remuneration at Clinic Visits is much higher than in our prior studies. Second, remuneration at 
754 
EOT and 6M is actually somewhat lower than in our prior work – we did this in an effort to stay under the 
755 
$600 threshold at which a 1099 would have to be issued, requiring participants to provide us with their 
756 
SSN. We now re-balance the remuneration by shifting some remuneration from Clinic visits (which already 
757 
have greater value because of the treatment received and the EMA remuneration) to the follow-up period 
758 
(see Section 26). 
759 
 
In addition, we have observed that many participants do not answer the reminder calls for follow-
760 
up visits, and when they do not answer the phone call they are very likely (70-90%) to miss the subsequent 
761 
follow-up. After extensive discussion with staff, and consideration of anecdotal information from 
762 
participants, we will replace the reminder calls with brief (1-2 questions) REDCap surveys (see App 11.1 – 
763 
Template for REDCap Follow-Up Survey) delivered via a text message link to the participant’s phone. We 
764 
have designed a plan we believe offers multiple advantages: 
765 
1) Rather than requiring that a participant answer our phone call at a specific time, participants can respond 
766 
to a REDCap survey whenever they are available. Because participants have already completed 9 weeks of 
767 
electronic assessments, this should be convenient and low-burden. 
768 
2) REDCap allows us to automate reminders to participants’ who do not respond to the initial text of a 
769 
survey link. We will send up to 3 reminders for each survey. 
770 
3) In contrast to phone calls, which could be associated with shame or embarrassment for participants who 
771 
report relapsing to smoking, the REDCap surveys allow participants to report electronically without direct 
772 
mention of the behavior to study staff. 
773 
4) Because the surveys are so brief, we can actually have more frequent contact with participants during the 
774 
follow-up period (1, 3, and 5 weeks before EOT and 4 and 8 weeks before 6M follow-up), which should 
775 
enhance retention rates.    
776 
Participant Satisfaction Surveys (C4 and EOT) Participants will be given satisfaction surveys at 
777 
Clinic visit #4 (C4) and the End of treatment (EOT) visits. These surveys will be distributed in an unsealed 
778 
enveloped. The participant will be asked to complete the survey on paper, in private, to answer honestly, 
779 
and to seal the survey into the envelope after completion. Surveys will be delivered to Dr. Hawk; research 
780 
assistants will not read the surveys of their participants. The C4 survey was not completed by those who 
781 
had C4 before the 2019-05 modification. The EOT survey was mailed to participants who completed EOT 
782 
prior to approval of the 2019-05 modification. Please see Satisfaction for EVQ 2019-05-02.docx.  
783 
Update 2020-04 – COVID-19 impact:  Anecdotally, our smoking cessation trial participants have 
784 
reported varied impact of COVID-19 on their quit smoking efforts. To more formally collect qualitative 
785 
and quantitative data regarding the impact of COVID-19, we added a questionnaire (App - COVID-19 
786 
Quitting Questions_v3.5 - EVarQuit 2020-04-20.docx) to be administered once per participant. The 
787 
COVID-19 questionnaire will be assessed at each participant's end-of-treatment (EOT) (remote) visit.  If 
788 
the person has already passed the EOT appointment, but has not yet reached the 6-month visit, we will ask 
789 
them to complete it at the 6-month (remote) visit. The questionnaire is completely optional.  The 
790 
questionnaire would be employed until the stay-at-home order is lifted or all currently enrolled participants 
791 
reach the 6-month milestone or government-mandated social distancing measures are eliminated in New 
792 
York, whichever is later. 
793 
Update 2020-5-21 – Further assessing COVID-19 impact:  The EvarQuit project was forced to 
794 
implement changes to the provision of treatment due to the COVID-19 pandemic.  One of the primary 
795 
changes involved the transition from in-person counseling to remote counseling via Zoom software (when 
796 
possible) or phone calls.  In order to understand the opinions and experiences of participants in the 
797 
EvarQuit project who completed at least one at-home counseling session as a result of the COVID-19 
798 

 
18
pandemic, we will be conducting voluntary individual interviews with about 25 currently enrolled 
799 
participants.  The goal of these one-on-one structured interviews is to improve the quality of the remote 
800 
visits and enhance the subjective experience of our participants.  Trained research assistants will contact 
801 
participants by phone as close as possible following the Clinic 6 visit to introduce the interview.  If the 
802 
participant agrees to the procedures and provides verbal consent, the interview will be audio recorded so it 
803 
can be coded by independent staff members. Audio recordings, labeled only with a participant number, will 
804 
be stored on our secure server, and will be used to generate written transcripts for qualitative analyses. We 
805 
will keep the audio recording for up to 6 months as they will be used to clarify information in the 
806 
transcripts and will help to clarify the context of information obtained during interviews. Participant 
807 
responses will remain anonymous. 
808 
Update 2020-05-29:  COVID-19-related procedural changes:  Per the UB Human Studies guidance 
809 
05212020.docx, the following procedural changes will be implemented in an effort to minimize 
810 
transmission of the virus: 
811 
Engineering Measures:  
812 
• 
The clinic hallway (3rd floor in Diefendorf Hall) is approximately 11 ft wide; taped lines will be 
813 
placed 2.5 ft from either wall all of the way down the hallway.  People moving west to east will walk 
814 
down one side of the hallway and those moving east to west will walk down the other side of the 
815 
hallway.  This will ensure that a distance of > 6ft can be maintained in the hallway at all times.  
816 
• 
Participants typically sit in chairs located in the main hallway of the clinic to wait for their 
817 
appointment to start.  The chairs will be removed from the hallway and participants will be escorted to 
818 
a private interview room upon arrival to the clinic.  
819 
Administrative Measures:  
820 
• 
Staff will be asked to enter the clinic using the elevator OR the stairwell on the east end of the building 
821 
and to leave using the stairwell on the west end. Staff arrival and departure times will be staggered as 
822 
well to minimize stairwell traffic.  
823 
• 
Staff will be asked to wash their hands thoroughly and often, including immediately upon arrival, 
824 
using CDC guidelines and to avoid touching their face.  
825 
• 
Room occupancy will be limited to maintain distances of at least 6 feet between staff and research 
826 
participants except for brief procedures (such as blood pressure), during which staff will wear gloves, 
827 
face mask, and eye protection (consistent with UB Human Studies guidance 05212020.docx).  
828 
• 
Signage outside the elevator and in the hallway will inform participants regarding the above measures 
829 
as well as the need to have only one person on the elevator at a given time.  
830 
Prescreening of Research Participants: 
831 
As per the UB Human Studies guidance 05212020.docx, the following will be done prior to all participant 
832 
visits: 
833 
During the reminder call the day before a visit: 
834 
• 
Participants will be asked to take their temperature; if they don’t have a thermometer, they will be 
835 
asked whether they feel feverish. 
836 
• 
Participants will be asked about the presence of any COVID-19 symptoms including: fever, cough, 
837 
shortness of breath, sore throat, muscle aches, headache, new loss of taste or smell, and repeated or 
838 
shaking chills (as noted on page 2 of the UB Human Studies Guidance 05212020.docx).    
839 
• 
Anyone known to be COVID-19 positive or who exhibits COVID-19 symptoms will be restricted from 
840 
enrollment / attending in-person visits until symptom free and at least 14 days since date of diagnosis. 
841 
For enrolled participants, remote visits (telemedicine) will be scheduled in the interim as the health of 
842 
the participant allows.  
843 
Before leaving home on the day of a visit 
844 

 
19
• 
Participants will be asked to take their temperature at home.  
845 
• 
Participants will be asked to report any new symptoms on the day of the visit to the project coordinator 
846 
prior to coming to the clinic/lab. 
847 
• 
Participants will be asked to wear a face covering prior to entering the building; if they arrive without a 
848 
face covering, a mask will be provided. 
849 
Revised Visit Scheduling Enhances Social Distancing:    
850 
• 
To support physical distancing and prevent congestion, intake appointment times will be arranged so 
851 
that no more than 4 participants are present on site at any one time. There is ample space in Diefendorf 
852 
to assure appropriate physical distancing with up to 8 private office spaces for participant 
853 
interviews/counseling sessions.   
854 
• 
Clinic visits will be scheduled with at least 15 minutes staggering of arrivals and departures of other 
855 
participants and clinic staff, and allocated duration of visits will be increased by 15 minutes to ensure 
856 
time for disinfection of hard surfaces at the conclusion of each visit.  
857 
Consent Addendum:  A consent addendum will be employed that advises participants of all COVID-
858 
related requirements and procedures. See Section 29.0: Process to Document Consent. 
859 
Disinfection of Shared Equipment and Spaces: 
860 
• 
Before and after each in-person appointment or use of a shared room or piece of equipment, all hard 
861 
surfaces such as equipment (including the shared copier), countertops, keyboards, computer mice, 
862 
office chair arms, and doorknobs will be disinfected with EPA-approved disinfectant wipes or spray.  
863 
• 
A disinfecting checklist will be placed on the door of each participant room or shared space; staff will 
864 
provide the date, time, and staff initials after each disinfection.   
865 
• 
Participants will be given a pen to use during their visit that then will then take with them so multiple 
866 
people aren’t using the same pen. 
867 
Remote Study Visits: 
868 
Study visits will be conducted remotely, rather than in person at UB, under the following circumstances. 
869 
• 
If a participant reports COVID-19 symptoms or diagnosis, then remote visits will be scheduled at least 
870 
until the participant is symptom-free and it has been at least 14 days since the date of diagnosis.  
871 
• 
If UB determines that research projects cannot have in-person visits for a period of time (for example, 
872 
if there were a surge of COVID-19 cases in the area), all appointments will be conducted remotely 
873 
during that period of time. 
874 
• 
Other circumstances in which study staff and the participant agree that one or more remote visits are 
875 
appropriate in order to ensure uninterrupted smoking-cessation treatment 
876 
• 
To enhance compliance with follow-up appointments at which primary outcome measures are 
877 
collected, these visits may be conducted remotely as well 
878 
 
879 
Participants will be instructed regarding the details of remote study visits, including the need for privacy, 
880 
the methods for delivery and return of study materials, and the technology (Zoom or telephone; REDCap) 
881 
for completing study visits. Informed consent for remote study visits will be obtained with the aid of the 
882 
attached EVarQuit Consent Addendum – COVID-19.docx. 
883 
 
884 
UPDATE 2020-06-12 - ELIMINATION OF LAB VISITS FOR REMAINING PARTICIPANTS. As 
885 
noted above, due to concerns about enrollment, participant burden, and perceived ppt risks, we are 
886 
eliminating the lab visits for the remaining participants. 
887 
 
888 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS. Consistent with 
889 
the administrative supplement submitted to NCI, ITT participants will be asked to provide an optional 
890 
additional saliva sample for genetic analysis. In brief, 30 minutes after eating, drinking, or smoking, 
891 

 
20
participants who consent to provide a genetics sample will provide a 2 mL saliva sample using an Oragene 
892 
kit (DNA Genotek, Inc.). 
893 
 
For participants enrolled after approval of the genetics sample, an overview and the consent 
894 
addendum (see EVarQuit Genetics Sub-Study - Consent Addendum  - onsite - 2020-06-30.docx) will be 
895 
presented at Clinic 2 (future participants).  Reasons for waiting until Clinic 2 (as opposed to including with 
896 
the initial study consent at intake) include: a) Because the major focus of these analyses is to better 
897 
understand variability in response to varenicline, and varenicline is first measurable at Clinic 2, we do not 
898 
wish to obtain samples from participants who are found ineligible or withdraw prior to Clinic 2, and b) 
899 
Providing the consent addendum in close temporal proximity to obtaining the sample, rather than adding 
900 
the information to the already lengthy consent form at intake, should enhance participant understanding of 
901 
what is required versus optional and improve understanding of the specific issues related to the optional 
902 
genetics sample.  
903 
 
For participants who have already completed Clinic 2, an overview and the consent addendum will 
904 
be presented at their next study visit (see EVarQuit Genetics Sub-Study - Consent Addendum  - onsite - 
905 
2020-06-30.docx). If the participant has already completed all required study visits, study staff will attempt 
906 
to reach the participant by phone and/or email (see EVarQuit Genetics Sub-Study Initial Contact – Phone 
907 
and Email Scripts 2020-06-30.docx). No more than two attempts with each method will be made, to avoid 
908 
“hounding” the participant. If the participant is reached and expresses interest, or if the participant was not 
909 
reached by phone/email, the following will be sent by postal mail: 
910 
 - EVarQuit Genetics Sub-Study – Addendum Cover Letter – 2020-06-30.docx 
911 
 - EVarQuit Genetics Sub-Study - Consent Addendum  - home - 2020-06-30.docx 
912 
Participants who return written consent to providing the sample will be mailed standard DNA Genotek 
913 
Oragene saliva sample kit and pre-paid return mailer. Participants will be remunerated upon receipt of the 
914 
sample (see Remuneration). 
915 
 
916 
Regarding issues relevant to Section 2 of HRP-399 (WORKSHEET: Additional Requirements for Genetic 
917 
Testing (NY State)): 
918 
• 
Consent will be obtained directly from the participant (no samples taken from deceased individuals). 
919 
• 
As described in the consent addendum, samples will be stored independent of other participant 
920 
information, making it impossible that genetic information would ever be incorporated into the records 
921 
of a nonconsenting individual. 
922 
• 
Consent for banking and additional genetic testing are explicitly obtained in the consent addendum. 
923 
• 
As explicitly stated in the consent addendum:  “If you say yes now, but you change your mind later, it 
924 
will not be held against you or affect your participation in EVarQuit. You can always call (716-829-
925 
2323) or email us (EVarQuit@buffalo.edu) to say that you have changed your mind, and the DNA 
926 
sample will be destroyed.”  In such an event, the PI (Dr. Hawk) will contact Dr. Tyndale at the 
927 
University of Toronto to ensure the deidentified sample is destroyed. 
928 
• 
“Family members of an individual who provided a stored tissue sample will NOT be contacted for 
929 
clinical, research, or other purposes without consent from the individual who provided the tissue 
930 
sample with respect to the specific family members who will be contacted and the specific purpose of 
931 
the contact.” (HRP-399) As of this version of the protocol, we do not anticipate ever contacting family 
932 
members of participants and would submit a modification in advance of any such contact. 
933 
• 
“Information about an individual derived from genetic tests performed on stored human tissue or 
934 
information linking an individual with specific results of genetic tests will NOT be released to any 
935 
organization or person without the explicit written consent of the individual who donated the stored 
936 
tissue to release of the information for the purposes set forth in the written consent document” (HRP-
937 
399). 
938 

 
21
• 
“DNA samples will be stored for no more than ten years in the absence of genetic testing, if authorized 
939 
in writing by the subject. If genetic testing will be performed on the stored samples or samples will be 
940 
stored for more than 10 years, informed consent will be obtained” (HRP-399). 
941 
 
942 
10.2 Describe what data will be collected.   
943 
NOTE:  For studies with multiple data collection points or long-term follow up, consider the 
944 
addition of a schedule or table in your response. 
945 
Response: Measures reflect the aims of the project: evaluating the efficacy of a promising approach to 
946 
smoking cessation (Aim 1, with a focus on abstinence at EOT and  6M), and gaining insight into the 
947 
mechanisms and moderators of treatment effects (Aims 2 and 3; with an emphasis on measures obtained 
948 
between Intake and TQD).   Please see the table of assessments and measures in Section 11.1 
949 
 
950 
10.3 
List any instruments or measurement tools used to collect data (e.g. 
951 
questionnaire, interview guide, validated instrument, data collection form).   
952 
 
953 
Include copies of these documents with your submission. 
953 
Response:  
954 
Smoking rate – How many cigarettes did you smoke yesterday? 
955 
 Expired-air CO – Biochemical verification obtained with a hand-held carbon monoxide (CO) meter 
956 
(see CRF – e.g. EVQCRFs - Intake - Staff Instruments). 
957 
 Cotinine/3-hydroxy-cotinine – Biochemical verification and rate of metabolism – patients will provide 
958 
saliva samples at all Clinic visits as well as follow-up visits, (see App10.3-03). 
959 
 Varenicline levels – patients will provide saliva samples at all Clinic visits, EOT and 6 month follow-
960 
up. 
961 
 Validated Questionnaires that assess the following are included in App10.3-04- Questionnaires-2016-
962 
09-23.docx: 
963 
• 
Craving  
964 
• 
Withdrawal 
965 
• 
Subjective effects of smoking 
966 
• 
Nausea 
967 
• 
Treatment expectancies  
968 
 
969 
 The urine collection and drug testing procedure is described in App10.3-05-UrineToxProcedure. 
970 
Our standard side effects assessment (e.g., Hawk et al., 2012; Lerman et al., 2015) has been updated to 
971 
include the CSSRS and is included on the CRFs for intake. 
972 
 2020-04:  App - COVID-19 Quitting Questions_v3.5 - EVarQuit 2020-04-20.docx 
973 
 2020-05-19:  App – COVID-19 Structured Interview-EVarQuit 2020-05-19.docx 
974 
10.4 Describe any source records that will be used to collect data about subjects (e.g. school records, 
975 
electronic medical records). 
976 
Response:   N/A, no external records will be used to collect data about subjects. 
977 
N/A.  We will not obtain external source records. 
978 

 
22
10.5 Indicate whether or not individual subject results, such as results of investigational diagnostic tests, 
979 
genetic tests, or incidental findings will be shared with subjects or others (e.g., the subject’s primary 
980 
care physician) and if so, describe how these will be shared. 
981 
Response: Individual subject results will not be shared with participants or others. 
982 
 
983 
10.6 Indicate whether or not study results will be shared with subjects or others, and if so, describe how 
984 
these will be shared. 
985 
Response: We will maintain a list of participants who would like to be notified of study results and will 
986 
provide those participants with brief summaries of project results in short newsletters in the Fall of 2020, 
987 
2022, and 2024. These summaries will be shared via email or post based on participant preferences. 
988 
11.0 Study Timelines 
989 
11.1 Describe the anticipated duration needed to enroll all study subjects. 
990 
Response: 48 months 
991 
11.2 Describe the duration of an individual subject’s participation in the study. Include length of study 
992 
visits, and overall study follow-up time. 
993 
Response:  
994 
Participants will complete screening, active treatment, and long-term (6-month) follow-up, with an 
995 
estimated total time commitment of ~26.5 23 hours. 
996 
Phone screen  
 
 
 
 
 
~  0.5 hours 
997 
Intake 
 
 
 
 
 
 
~  2.0 hours  
998 
Lab Visit 1 
 
 
 
 
 
~  2.0 hours Eliminated 2020-06-12 
999 
Lab Visit 2 
 
 
 
 
 
~  1.5 hours Eliminated 2020-06-12 
1000 
Clinic visits 1-6 @~1 hour each  
 
 
 
~  6.0 hours 
1001 
Brief counseling check-ins 1-2 
 
 
 
~  0.5 hours 
1002 
EMA @0.33 hours/day X @5 days/wk X 9 wks  
 
~15.0 hours 
1003 
5 1-minute follow-up surveys 
 
 
 
~  0.1 hours 
1004 
EOT/6M/ follow-ups @ .5 hrs each  
 
 
~  1.0 hour 
1005 
11.3 Describe the estimated duration for the investigators to complete this study (i.e. all data is collected 
1006 
and all analyses have been completed). 
1007 
Response: 5.5 years  (begin accrual in month 9; enroll last subject in month 51; complete 6-month follow-
1008 
up in month 57; begin primary analyses) 
1009 
 
1010 
12.0 Setting 
1011 
12.1 Describe all facilities/sites where you will be conducting research procedures.  Include a description 
1012 
of the security and privacy of the facilities (e.g. locked facility, limited access, privacy barriers).  
1013 
Facility, department, and type of room are relevant.  Do not abbreviate facility names.   
1014 
NOTE:  Examples of acceptable response may be:  “A classroom setting in the Department of 
1015 
Psychology equipped with a computer with relevant survey administration software,” “The 
1016 
angiogram suite at Buffalo General Medical Center, a fully accredited tertiary care institution 
1017 
within New York State with badge access,” or, “Community Center meeting hall.” 
1018 
Response:  
1019 
The proposed clinical trial will take place in Dr. Hawk’s lab on the third floor of Diefendorf Hall at the 
1020 
State University of New York at Buffalo. The third floor is secured with swipe card access and video-
1021 
enabled two-way intercoms for enhanced security, privacy, and confidentiality. Within the lab are a range 
1022 
of individual rooms, each of which can be locked independently. Clinical assessments and cessation 
1023 
counseling are easily accommodated in the five interview rooms. Two medical exam rooms allow a range 
1024 

 
23
of health-related assessments.  A room dedicated to phlebotomy and urine toxicology is located adjacent to 
1025 
the lab restrooms; the room is equipped with a -5C freezer for short-term storage prior to transfer of 
1026 
samples to a 17-foot -80C freezer in the adjacent room for long-term storage. The research pharmacy has 
1027 
an on-site, alarmed room for storage of medications, reconciliation and randomization procedures, and 
1028 
relevant documentation. A white noise system enhance confidentiality between assessment rooms. A 
1029 
waiting room and kitchen with refreshments provide a welcome environment for participants, and a large 
1030 
seminar room provides ample space for study overview sessions. 
1031 
Dr. Hawk and project staff will have access to approximately 15 PC computers data-entry, word 
1032 
processing, and clerical activities. All computers are on a network with centrally-maintained backups on a 
1033 
secure server that is accessible through Citrix software; the server is maintained by the Office of Medical 
1034 
Computing.  
1035 
Laboratory assessments of reinforcement will take place in specialized research space dedicated to Dr. 
1036 
Hawk in Farber Hall (Rooms 155 and 157); backup smoking labs dedicated to Co-I Dr. Tiffany on the third 
1037 
floor of Park Hall may be used as a backup.  This separation of laboratory assessments is by design; it 
1038 
separates the clinical smoking cessation and the lab assessments that involve smoking in a controlled 
1039 
environment. Drs. Hawk and Tiffany have offices on both campuses, allowing frequent interaction on the 
1040 
project.  Swipe card (Hawk lab) and punch locks (Tiffany lab) separates the lab from hallway traffic, and 
1041 
each room within the lab is also secured with a standard door lock. Each lab consists of 500+ square feet of 
1042 
testing space, including two subject rooms and a master control room outfitted with equipment for 
1043 
complete CBUCC testing (test apparatus, computers, monitors, modified response boxes, keyboards, mouse 
1044 
for measuring response times with millisecond accuracy), refrigerators, high definition cameras in subject 
1045 
rooms, and secure access to the UB Box server that will maintain all study data. This test space is 
1046 
customized with ventilation and air handling systems that isolate the rooms from the rest of the building 
1047 
and allow for smoking in the test rooms with very high turnover air exchange ventilate directly to the 
1048 
exterior of the building. 
1049 
12.2 For research conducted outside of UB and its affiliates, describe: 
1050 
• 
Site-specific regulations or customs affecting the research 
1051 
• 
Local scientific and ethical review structure 
1052 
NOTE:  This question is referring to UB affiliated research taking place outside UB, i.e. research 
1053 
conducted in the community, school-based research, international research, etc.  It is not referring 
1054 
to multi-site research.  UB affiliated institutions include Kaleida Health, ECMC, and Roswell Park 
1055 
Cancer Institute.   
1056 
Response:  
1057 
☒ 
 N/A:  This study is not conducted outside of UB or its affiliates. 
1058 
13.0 Community-Based Participatory Research 
1059 
13.1 Describe involvement of the community in the design and conduct of the research.  
1060 
NOTE:  Community-Based Participatory Research (CBPR) is a collaborative approach to research 
1061 
that equitably involves all partners in the research process and recognizes the unique strengths that 
1062 
each brings.  CBPR begins with a research topic of importance to the community, has the aim of 
1063 
combining knowledge with action and achieving social change to improve health outcomes and 
1064 
eliminate health disparities. 
1065 
Response:  
1066 
☒ 
 N/A:  This study does not utilize CBPR. 
1067 
13.2 
Describe the composition and involvement of a community advisory board. 
1068 
Response:  
1069 
☒ 
 N/A:  This study does not have a community advisory board. 
1070 

 
24
 
1071 
14.0 Resources and Qualifications 
1072 
14.1 Describe the qualifications (e.g., education, training, experience, expertise, or certifications) of the 
1073 
Principal Investigator and staff to perform the research.  When applicable describe their knowledge 
1074 
of the local study sites, culture, and society.  Provide enough information to convince the IRB that 
1075 
you have qualified staff for the proposed research.  
1076 
NOTE:  If you specify a person by name, a change to that person will require prior approval by the 
1077 
IRB.  If you specify a person by role (e.g., coordinator, research assistant, co-investigator, or 
1078 
pharmacist), a change to that person will not usually require prior approval by the IRB, provided 
1079 
that the person meets the qualifications described to fulfill their roles. 
1080 
Response:  
1081 
Co-PIs Hawk, Mahoney, and Tiffany will share leadership of the study, as described in the attached grant 
1082 
proposal (see Shared Leadership Plan in App00). This team has worked together on previous clinical trials, 
1083 
including the EvarQuit pilot study that led to the current trial (e.g., Hawk et al., 2012). 
1084 
Dr. Hawk is a Professor of Psychology. His doctoral training in clinical health psychology provided him 
1085 
with an excellent background in theory, methods, and interventions for a range of health behaviors, and this 
1086 
expertise was enhanced by his post-doctoral fellowship in the Division of Behavioral Oncology at the 
1087 
University of Pittsburgh Cancer Institute.  Over the past decade, he has developed expertise in smoking 
1088 
behavior and clinical cessation trials; he has conducted numerous smoking studies, including four 
1089 
randomized clinical trials (RCTs; two as Co-I, one as PI, one as site PI), all of which included 
1090 
pharmacotherapy and counseling. The two most recent trials (with Co-PI Mahoney) focused on an 
1091 
extinction-based model, using extended pre-quit pharmacotherapy to enhance smoking cessation; they 
1092 
provide the foundation for the proposed RCT. Dr. Hawk has provided and supervised delivery of cessation 
1093 
counseling and developed the treatment materials for the present study.  Beyond RCTs, Dr. Hawk has 
1094 
published mechanism-oriented experimental work on the effects of nicotine, varenicline (the medication 
1095 
employed in the current proposal), and other drugs on basic reinforcement, cognitive, and subjective 
1096 
processes, as well as the role of these basic processes on the development of substance use. Overall, he is 
1097 
well-suited to serve as PI on the current proposal to evaluate the efficacy and mechanisms of extended pre-
1098 
quit run-in varenicline for smoking cessation.  
1099 
Dr. Mahoney is a Professor of Oncology and Staff Physician at Roswell Park Cancer Insitute (and has an 
1100 
appointment at UB). As PI or co-investigator, Dr. Mahoney has played key roles in the design, successful 
1101 
implementation and analyses of multiple smoking cessation clinical trials which have relied upon a variety 
1102 
of pharmacotherapies/interventions including: nicotine free cigarettes, St. John’s Wort, bupropion, a 
1103 
nicotine conjugate vaccine, a nicotine liquid delivery system and varenicline. Together with Dr. Hawk, he 
1104 
recently participated in a multi-site cessation trial which used nicotine metabolism ratios (NMR) to 
1105 
randomize 1400+ smokers to either varenicline + placebo NRT, NRT + placebo varenicline or placebo.  
1106 
Dr. Tiffany is an Empire Innovation Professor in Psychology. He brings considerable expertise derived 
1107 
from his ongoing research on the assessment of smoking and craving using ecological momentary 
1108 
assessment (EMA) technology (including work with Drs. Hawk and Mahoney; e.g., Gass et al., 2012; 
1109 
Hawk et al., 2012), processes of drug craving, the causes of drug dependence, the diagnosis of dependence, 
1110 
adolescent drug use, and the interaction of biological and psychological factors in the control of addictive 
1111 
behaviors. Dr. Tiffany’s craving work focuses on understanding the role of drug craving in addiction. One 
1112 
of his longstanding interests is on the development and validation of instruments to sensitively and 
1113 
accurately measure drug craving; he has led development of widely used measures of alcohol, cigarette, 
1114 
cocaine, and heroin craving. Dr. Tiffany has also developed and validated multiple methods to study cue-
1115 
specific craving and, of particular relevance to this research, have conducted research on the assessment of 
1116 
cue-reactivity in the natural environments of cigarette smokers. Dr. Tiffany was awarded the American 
1117 
Psychological Association Distinguished Scientific Award for Early Career Contribution to Psychology in 
1118 
1993, and he has served as a member of several NIH scientific review panels. 
1119 
Dr. Colder, who will handle the biostatistics and randomization for the current project, is a Professor of 
1120 
Psychology at UB.  He has actively studied developmental models of psychopathology and adolescent 
1121 

 
25
substance user for over 20 years.  Dr. Colder has been Principal and Co-Investigator on multiple NIH 
1122 
funded longitudinal studies that span infancy to young adulthood.  Dr. Colder’s  background also includes 
1123 
extensive training in quantitative methods, such as hierarchical linear models, structural equation modeling, 
1124 
growth modeling, mixture modeling, and testing moderation and mediation. Dr. Colder and Dr. Hawk have 
1125 
co-authored numerous publications from several collaborative studies at UB over the past 10 years. 
1126 
Jennifer Adams, M.S.W., Research Coordinator, has worked for several years with Drs. Hawk and 
1127 
Mahoney on another large smoking cessation trial. Ms. Adams is familiar with the proposed assessments 
1128 
and procedures and will oversee all day-to-day aspects of the proposed study. She is already assisting with 
1129 
the development of the current IRB proposal and is familiar with UB IRB procedures, monitoring/reporting 
1130 
of side effects and adverse events. Ms. Adams, an M.S.W. with extensive experience in smoking cessation 
1131 
trials, will assist with implementation and training on psychiatric screening and cessation counseling. She 
1132 
will work with the research nurse to oversee sample collection and shipping, as per our standard protocols.  
1133 
Ms. Adams will work closely with Drs. Hawk and Colder to maximize retention at follow-up and interface 
1134 
between research pharmacist and project staff regarding medication disbursement and reconciliation. Ms. 
1135 
Adams will oversee recruitment, data collection and data entry to ensure all study activities are done 
1136 
according to GCP and within the appropriate timeframe.  Ms. Adams will work with Drs. Hawk and other 
1137 
study investigators to refine all study protocols, respond to data management queries, review study charts to 
1138 
ensure the quality of the data captured. 
1139 
Details for additional staff will be provided once the project has begun and we begin hiring. 
1140 
 
1141 
Describe other resources available to conduct the research.  
1142 
14.2 Describe the time and effort that the Principal Investigator and research staff will devote to 
1143 
conducting and completing the research. 
1144 
NOTE:  Examples include the percentage of Full Time Equivalents (FTE), hours per week.  The 
1145 
question will elicit whether there are appropriate resources to conduct the research. 
1146 
Response: Larry Hawk, Ph.D., Principal Investigator, (1.8 academic months and 1.8 summer months in all 
1147 
years). Dr. Hawk will be responsible for the scientific and technical direction of the proposed research. He 
1148 
will supervise most aspects of the project (see leadership plan), including hiring and training staff, 
1149 
supervising data collection, verification, and analysis, and leading manuscript and report preparation. Dr. 
1150 
Hawk will meet at least weekly with Research Coordinator and co-lead biweekly staff meetings and 
1151 
monthly calls with study investigators. Dr. Hawk will supervise the provision of behavioral counseling and 
1152 
lead the development of conference presentations and publications. 
1153 
Stephen Tiffany, Ph.D., Principal Investigator, (1.2 academic months and 0.6 summer months in all years). 
1154 
Dr. Tiffany will take primary responsibility for the laboratory assessments of reinforcement during the pre-
1155 
quit period. He will work closely with Dr. Hawk to coordinate clinical and laboratory assessments and Dr. 
1156 
Tiffany will assist in the management, reduction, and analysis of the laboratory data. Dr. Tiffany will also 
1157 
provide leadership and oversight on the ecological momentary Dr. Tiffany will contribute actively to work 
1158 
with all study investigators to interpret and disseminate results.  
1159 
Craig Colder, Ph.D., Co-Investigator, (1.8 academic months and 0.6 summer months in YR01 and YR05; 
1160 
0.9 academic months and 0.3 summer months in YR02-04). Dr. Colder will oversee the randomization 
1161 
procedures for the trial. Dr. Colder will also assist with tracking and maintaining retention during follow-up 
1162 
period, work with Dr. Hawk to coordinate integrated data management procedures, and lead data analysis 
1163 
as the project statistician. He will work with all study investigators to interpret and disseminate results.  
1164 
Project Manager, TBN (1.2 calendar months in all years). The PM will consult with and assist PIs Hawk 
1165 
and Mahoney and Project Coordinator on high-level implementation and administration, as well as 
1166 
coordination of the proposed study with other projects in the CCF. As needed, she will lead intake visits 
1167 
and assist with staff training. She will also conduct protocol fidelity checks and provide an independent 
1168 
auditor of financial records, as required by institutional policy. 
1169 
Jennifer Adams, MSW, Project Coordinator (12 calendar months in all years). The PC will assist the Co-
1170 
PIs in submitting and maintaining IRB materials and monitoring/reporting side effects and adverse events.  
1171 

 
26
The PC will oversee recruitment, data collection and data entry to ensure all study activities are done 
1172 
according to GCP and within the appropriate timeframe.  
1173 
Nurse/Phlebotomist, TBN (3.6 calendar months in YR01, 4.8 calendar months in YR02-04, 2.4 calendar 
1174 
months in YR05).  As in our recent multi-site cessation trial, the Nurse/Phlebotomist will assist the study 
1175 
MD and staff during the medical screening process. She will also conduct saliva samples and oversee urine 
1176 
toxicology and pregnancy screening at intake visits. She will assist with sample processing, storage, and 
1177 
shipping. 
1178 
TBN, Research Support Specialists, (4@6.0 calendar months in YR01, 5@6 calendar months in YR02-04, 
1179 
4@6.0 calendar months in YR05). The RSSs will aid in recruitment and retention efforts by conducting 
1180 
initial screenings, placing reminder phone calls, sending mail outs, and scheduling visits, under the 
1181 
supervision of the Project Coordinator. RSSs will be trained to conduct most study assessments per 
1182 
rigorous, detailed protocols, including the collection of lab reinforcement data and training participants in 
1183 
use of ecological momentary assessment. RSSs will work with the Coordinator to implement the daily 
1184 
operations of the study, including data entry, maintaining supply levels, and responding to data queries. 
1185 
14.3 Describe the availability of medical or psychological resources that subjects might need as a result 
1186 
of anticipated consequences of the human research, if applicable. 
1187 
NOTE:  One example includes: on-call availability of a counselor or psychologist for a study that 
1188 
screens subjects for depression. 
1189 
Response: Study staff will be available by phone during normal business hours, and they will have prompt 
1190 
access to Co-PIs Hawk (a clinical psychologist) and Mahoney (a physician) for clinical issues that arise in 
1191 
the course of smoking cessation with varenicline, as in our prior trials.  As in our prior work, we will 
1192 
provide participants with contact information and reminder cards and, when appropriate, referrals for 
1193 
resources external to the focus of the project. 
1194 
14.4 Describe your process to ensure that all persons assisting with the research are adequately informed 
1195 
about the protocol, the research procedures, and their duties and functions. 
1196 
Response: All staff will be provided with copies of the grant proposal. Study protocols are provided in 
1197 
binders in the relevant rooms, and training of study staff will include direct observation of mock 
1198 
procedures, followed by supervision in real patient interactions.  Duties will be documented in a 
1199 
continuously updated delegation log that will be signed by the staff member whenever there is a change. 
1200 
15.0 Other Approvals 
1201 
15.1 Describe any approvals that will be obtained prior to commencing the research (e.g., school, 
1202 
external site, funding agency, laboratory, radiation safety, or biosafety). 
1203 
Response:  
1204 
☒ 
 N/A:  This study does not require any other approvals. 
1205 
 
1206 
16.0 Provisions to Protect the Privacy Interests of Subjects 
1207 
16.1 Describe how you will protect subjects’ privacy interests during the course of this research. 
1208 
NOTE:  Privacy refers to an individual’s right to control access to him or herself.  Privacy applies 
1209 
to the person.  Confidentiality refers to how data collected about individuals for the research will be 
1210 
protected by the researcher from release.  Confidentiality applies to the data.   
1211 
Examples of appropriate responses include:  “participant only meets with a study coordinator in a 
1212 
classroom setting where no one can overhear”, or “the participant is reminded that they are free to 
1213 
refuse to answer any questions that they do not feel comfortable answering.”   
1214 
Response: Above (sections 9 and 12) we describe how we will protect subjects’ privacy interests during the 
1215 
recruitment and consent phases. Throughout the research process, we respect participant’s rights to refuse 
1216 
to complete any assessment and to withdraw from the study at any time, thus giving them control of 
1217 

 
27
information access to themselves.  (When appropriate, we will remind participants that refusal to complete 
1218 
assessments may lead the study investigators to withdraw the participant from the trial.) 
1219 
Many of the measures will be self-administered, so participants will directly enter their responses into a 
1220 
computer/tablet/smartphone without the interviewer seeing their responses.  This increases privacy and 
1221 
reduces potential discomfort. 
1222 
Participants will meet individually with study investigators and staff in private offices; privacy is enhanced 
1223 
by the swipe card security system (limiting access) and the white noise system (reducing concerns about a 
1224 
conversation being overheard). 
1225 
UPDATE 2020-05-29: COVID-19: 
1226 
For remote visits during the COVID-19 pandemic, the use of telemedicine technology (Zoom; telephone 
1227 
calls), we will advise participants to attend the visit in a private setting. Zoom meetings will be password-
1228 
protected, and a telephone (audio-only) option will be available. 
1229 
UPDATE 2020-06-30 – OPTIONAL TROUBLESHOOTING SOFTWARE: As noted above, 
1230 
participants will have the option to download the TeamViewer app to assist with EMA app troubleshooting. 
1231 
The purpose of this software is to allow research staff to navigate to the EMA app and its settings to 
1232 
address problems more quickly and remotely so participants are less likely to miss assessments which could 
1233 
negatively impact their study eligibility and payment. The TeamViewer software will not be used for any 
1234 
other purposes beyond addressing problems with the EMA app. Staff will not access private information on 
1235 
the participant phone, such as photos, email, or texts messages, nor will they access functions such as the 
1236 
phone’s camera. Participants have the option to decline having this app installed on their device. 
1237 
Additionally, the TeamViewer app requires the participant to actively consent to a troubleshooting session 
1238 
by clicking a pop-up to allow access each time research staff requests a remote access session. The 
1239 
participant can also end the remote session at any time. 
1240 
16.2 Indicate how the research team is permitted to access any sources of information about the subjects.   
1241 
NOTE:  Examples of appropriate responses include:  school permission for review of records, 
1242 
consent of the subject, HIPAA waiver.  This question does apply to records reviews. 
1243 
Response: Consent of the subject. 
1244 
17.0 Data Management and Analysis 
1245 
17.1 Describe the data analysis plan, including any statistical procedures.  This section applies to both 
1246 
quantitative and qualitative analysis.  
1247 
Response:  
1248 
Our primary outcome of interest (Aims 1 and 3) is smoking cessation, a dichotomous variable indicating 
1249 
bio-verified (cotinine ≤15 ng/ml) self-report (TLFB) of continuous abstinence from smoking assessed at 
1250 
end-of-treatment (weeks 8-11 post-quit) and long-term follow-up (weeks 8-26 post-quit). We also propose 
1251 
to examine potential mechanisms of treatment effects, and our primary mediator of interest will be a 
1252 
continuous variable representing percent reduction in smoking behavior (CPD from daily EMA 
1253 
assessments) during the pre-quit phase of the study ([Week -5 CPD minus Week -1 CPD] / Week -5 CPD). 
1254 
Our proposed analyses and power estimates focus on these primary measures.   
1255 
We focus above on percent reduction in CPD during the pre-quit period (from Week -5 to Week -1) 
1256 
because this measure is both feasible to assess in clinical practice and is emphasized in prior work on pre-
1257 
quit pharmacotherapy (Hajek et al., 2011; Hawk et al., 2012, 2015; Rose et al., 1998). Indeed, some have 
1258 
suggested that achieving a 50% pre-quit reduction in smoking may be a clinically useful target (e.g., Rose 
1259 
& Behm, 2013), a hypothesis that could be evaluated in supplementary analyses. 
1260 
In addition, our assessment strategy will allow us to examine the time course of changes during the pre-quit 
1261 
period in ways that may inform both theory and practice. This is true for reductions in CPD as well as the 
1262 
other proposed mediators.  In prior work with small samples, extended run-in varenicline had, on average, a 
1263 
gradual impact on smoking and craving (Ashare et al., 2012; Hajek et al., 2011; Hawk et al., 2012; Poling 
1264 
et al. 2010). We will explore these trajectories at the group level but also consider individual differences in 
1265 

 
28
change. For example, even among participants with comparable overall reductions in smoking, it is 
1266 
important to determine the degree to which abstinence is associated with a marked early decline in smoking 
1267 
(which may reflect a stronger blockade of reinforcement by pre-quit varenicline) or a more gradual 
1268 
reduction in smoking across the pre-quit period (which would allow more extinction “trials” to occur). 
1269 
Consideration of additional measures of key constructs. Similarly, we plan to explore models of patterns of 
1270 
change across multiple pre-quit variables that are proposed mediators and their relation to smoking 
1271 
outcome. Of particular interest is whether we can identify a group characterized by a decline in smoking 
1272 
during the pre-quit period that is accompanied by declines in smoking satisfaction and/or craving. If the 
1273 
mechanism of the extended run-in operates as we hypothesize, this pattern should be more likely in the 
1274 
extended run-in than the standard run-in treatment group and be predictive of abstinence.  Such analysis 
1275 
would involve growth mixture modeling to identify groups based on trajectories of smoking, smoking 
1276 
satisfaction, and craving during the pre-quit phase. Our team has extensive experience to extend our 
1277 
proposed analysis to growth modeling and growth mixture modeling (Colder et al., 2002, 2006, 2013, 
1278 
2014; Trucco, Wright, & Colder, 2014). 
1279 
In addition, we will have a rich data set to examine a variety of alternative outcomes and potential 
1280 
mediators and moderators; examples are provided below. An advantage of our study is that it includes 
1281 
multiple measures of smoking intake (CPD, CO, COT and 3HC) and additional measures relevant to 
1282 
reinforcement and extinction (subjective effects of smoking; laboratory-based indices of the relative 
1283 
reinforcement from cigarettes, food, and water), and measures of alternative (though not mutually 
1284 
incompatible) mechanisms of treatment effects such as craving, withdrawal, and nausea. This provides 
1285 
broad coverage of the variables that are both theoretically relevant and empirically supported as key 
1286 
processes in abstinence and relapse. Another advantage of our study is that we have assessed many of our 
1287 
variables using multiple methods.  To maximize conceptual clarity and reduce the number of statistical 
1288 
tests, we will use confirmatory factor analysis, including Multitrait-Multimethod Measurement Models  
1289 
(MTMM, Kenny & Kashy, 1992) when appropriate, to inform construction of within-domain composites 
1290 
and/or selection of a subset of secondary measures for analysis. For each of the aims, it will also be 
1291 
important to consider a range of potential moderators and covariates, such as degree of nicotine 
1292 
dependence, NMR, age, education, and treatment outcome expectancies.   
1293 
Primary analyses. Most of our analyses will be done in Mplus and SAS (Proc Mixed and Proc Glmmix), 
1294 
both of which are very flexible and can handle continuous, categorical, and non-normal data, and allow for 
1295 
the inclusion of cases with missing data.  
1296 
Aim 1. We hypothesize that bio-verified continuous abstinence rates at end-of-treatment and at long-term 
1297 
follow-up will be greater in the extended run-in group compared to the standard run-in group.  Logistic 
1298 
regression will be used to test this aim.  Abstinence will be regressed on treatment group (a binary 
1299 
indicator).  Given evidence that extended pre-quit varenicline will be particularly helpful for women (Hawk 
1300 
et al., 2012), we will include gender and the gender x treatment interaction to evaluate the hypothesis that 
1301 
gender moderates the impact of varenicline run-in duration.  
1302 
Aim 2. We hypothesize that the extended run-in group will exhibit greater pre-quit reductions in smoking 
1303 
(percent reduction in CPD, as well as decreases in biochemical measures), as predicted by an extinction-of-
1304 
reinforcement framework. Each hypothesized mediator will be regressed on treatment group (a binary 
1305 
indicator) using regression models appropriate for the nature of the mediator.  As in Aim 1, gender and the 
1306 
gender x treatment group interaction will be included in the model. Comparable models will evaluate pre-
1307 
quit changes in other candidate mediators (withdrawal, craving, subjective effects of smoking, nausea, and 
1308 
behavioral measures of smoking, food, and water reinforcement from the laboratory CBUCC paradigm).  
1309 
Together, these analyses provide critical information about the degree to which run-in group differences in 
1310 
smoking reduction reflect smoking-specific changes in reinforcement and related constructs, such as 
1311 
reinforcer devaluation (i.e., from nausea). In addition to their conceptual and theoretical significance, a 
1312 
clearer understanding of treatment mechanism may be important for predicting success prior to quitting, 
1313 
thereby allowing adjustments to treatment to prevent patients from experiencing a failed quit attempt (e.g., 
1314 
Rose et al., 2013) and providing precise targets to further enhance treatment effectiveness. 
1315 
Aim 3.  We hypothesize that changes in pre-quit smoking behavior (i.e., percent reduction in CPD during 
1316 
the pre-quit period) will mediate the effect of extended pre-quit varenicline on smoking cessation. This aim 
1317 
will be tested with a path model whereby treatment will predict pre-quit reduction in smoking (a continuous 
1318 

 
29
variable), which in turn, will predict smoking abstinence.  Separate models will be estimated for abstinence 
1319 
at EOT and 6M follow-up.  Baseline levels of smoking will be included as a statistical control variable. 
1320 
Bootstrapped indirect effects with asymmetrical confidence bands will be used to test the proposed 
1321 
mediational path (MacKinnon 2008). We will also evaluate whether gender moderates this mediated path 
1322 
(moderated mediation, Preacher et al., 2007). 
1323 
17.2 If applicable, provide a power analysis.   
1324 
NOTE:  This may not apply to certain types of studies, including chart/records reviews, survey 
1325 
studies, or observational studies.  This question is asked to elicit whether the investigator has an 
1326 
adequate sample size to achieve the study objectives and justify a conclusion.  
1327 
Response: Although our analyses will utilize methods to handle missing data (e.g., full-information 
1328 
likelihood estimation; Enders & Bandalos, 2001), we conservatively estimated power based on N=320 ITT 
1329 
participants and attrition estimated to be 5% at TQD, 18% at EOT, and 25% at 6-M (based on our 
1330 
varenicline data from Hawk et al., 2012 and Lerman et al., 2015).  Our power estimates are based on an 
1331 
alpha level of .05 and adequate power considered ≥ .80. For the main effects of treatment run-in group on 
1332 
outcome (Aim 1) and hypothesized mediators (Aim 2), power was computed using Proc Power in SAS 
1333 
based on effect size estimates from Hawk et al. (2012) and Hajek et al. (2011); treatment run-in group 
1334 
effect sizes are expected to be in the range of small to medium for Aim 1 (Odds ratios 1.3 to 2.3) and Aim 2 
1335 
(f2 .05 to .12). Our proposed sample will provide adequate power to detect these effects.  For gender 
1336 
interactions in Aims 1 and 2 and all effects in Aim 3, we estimated power using Monte Carlo simulations 
1337 
estimated in Mplus (Muthén, & Muthén, 2002) with 10,000 replications and parameters taken from our 
1338 
pilot study (Hawk et al., 2012). Our monte carlo simulation suggested adequate power to detect the 
1339 
proposed gender x treatment interactions, with minimal bias in the regression coefficients and 
1340 
corresponding standard errors (bias < 3%). For Aim 3, our Monte Carlo simulation suggested adequate 
1341 
power to detect the proposed mediational pathway (collapsing across gender) with minimal bias in the 
1342 
estimated indirect effect and corresponding standard error (bias < 2%).  Furthermore, our Monte Carlo 
1343 
simulation suggested adequate power to detect the gender x treatment interaction predicting the proposed 
1344 
mediator, and the proposed indirect effect for women with minimal bias for these effects and the 
1345 
corresponding standard errors (bias < 1%).  Hence, we have adequate power to detect moderated mediation. 
1346 
Please note that our power calculations are unusually strong in that all effect size estimates were based on 
1347 
existing data, rather than hypothetical estimates, which we believe provides greater confidence in our 
1348 
calculations. 
1349 
17.3 Describe any procedures that will be used for quality control of collected data. 
1350 
Response:  As part of the data and safety monitoring process, the team will ensure that all  fields are 
1351 
completed appropriately, and all corrections are done according to Good Clinical Practice (GCP). Any 
1352 
inconsistencies/deviations will be documented. The Study Physician will review inclusion/exclusion data 
1353 
for each participant, documenting reviews of each report. The Project Manager will conduct quality control 
1354 
reviews of data on an on-going basis. 
1355 
 
1356 
18.0 Confidentiality 
1357 
 
1358 
A. Confidentiality of Study Data 
1359 
 
1360 
Describe the local procedures for maintenance of confidentiality of study data and any records that will be 
1361 
reviewed for data collection.   
1362 
 
1363 
18.1 
A.  Where and how will all data and records be stored?  Include information about:  password 
1364 
protection, encryption, physical controls, authorization of access, and separation of identifiers and data, as 
1365 
applicable.  Include physical (e.g. paper) and electronic files. 
1366 
Response:  
1367 

 
30
Paper-based records, including source documents and an original consent form, will be maintained in 
1368 
locked filing cabinets in 306/307/308 Diefendorf Hall; keys are maintained in a safe in the office of the 
1369 
project-coordinator.  
1370 
All participants will be assigned a numeric code. Electronic assessments and data management will be set 
1371 
up on secure web-based programs: https://ilumivu.com/solutions/ecological-momentary-assessment-app/ 
1372 
for daily EMA assessments and REDCap for electronic case report forms and overall project data 
1373 
management system. RedCap will temporarily be implemented through the University of Rochester CTSI. 
1374 
Due largely to the newness of our CTSA, UB does not have extensive RedCap support. UB CTSI COO 
1375 
Mary Sienkiewicz connected us with the U of Rochester CTSI (Carrie Irvine) for support. The websites are 
1376 
all HIPPA-compliant, have an SSL certificate (Secure Sockets Layer, a cryptographic protocol that 
1377 
provides communication security over the Internet), and use https (Hypertext Transfer Protocol Secure, a 
1378 
widely used communications protocol for secure communication over a computer network, with especially 
1379 
wide deployment on the Internet). No identifying information will be included in web-based electronic data 
1380 
files. 
1381 
Local computer files (such as the recruitment database and a file linking identifying information with each 
1382 
participant’s unique numeric code) will be maintained on a secure, password-protected UB server subject to 
1383 
regular backup. Files will be accessible only by study investigators and staff. The videos will be stored 
1384 
(labeled only with ID#) in a password protected database, behind an electronic firewall, and will only be 
1385 
accessed by the research team. 
1386 
UPDATE 2020-05-29 – COVID-19: 
1387 
For any remote visits, all assessments will be labeled with the numeric code representing the participant ID; 
1388 
they will not be labeled with the participant’s name or other PII. 
1389 
UPDATE 2020-06-30 – OPTIONAL TROUBLESHOOTING SOFTWARE: During remote 
1390 
troubleshooting sessions, research staff will document, for quality improvement purposes, basic 
1391 
smartphone information (e.g., model, operating system), the nature of the problem reported by the 
1392 
participant, steps taken to resolve the problem, and whether they were successful. No other information or 
1393 
data will be collected. According to the TeamViewer privacy policy, during remote access the software 
1394 
uses “…end-to-end encryption technology. This means that TeamViewer will not be aware of the content 
1395 
and subject matter of such exchanges.” The TeamViewer software will collect and process information 
1396 
during remote access connection including “a Session ID, a meeting ID, and the start and end times of your 
1397 
session.” No personal information is collected by the TeamViewer app during remote access sessions. 
1398 
18.2 
A.  How long will the data be stored? 
1399 
Response:  Records containing identifying information will be stored for 3 years after completion of the 
1400 
project; they will then be destroyed.   
1401 
As described in our grant proposal (App00), we will follow the NIH mandate for data-sharing. Our data-
1402 
sharing plan is consistent with the 2015 Institute of Medicine (IOM) report, Sharing Clinical Trial Data: 
1403 
Maximizing Benefits, Minimizing Risk (National Academies Press); we plan to make the full de-identified 
1404 
analyzable data set with metadata available through the National Addiction and HIV Data Archive Program 
1405 
(NAHDAP) within 18 months of study completion.  NHADAP is a NIDA-funded platform for data sharing.  
1406 
As recommended by NHADAP, we will work with NHADAP staff to begin the data-sharing plan prior to 
1407 
beginning data collection so that maximal study data are available to the public without compromising 
1408 
participant protections. NAHDAP has a standard data deposit form and required list of files 
1409 
(http://www.icpsr.umich.edu/icpsrweb/content/NAHDAP/deposit/index.html). The data deposit includes a 
1410 
standard procedure for ensuring participant protections (including NAHDAP recoding or dropping 
1411 
variables that might compromise confidentiality). 
1412 
18.3 
A.  Who will have access to the data? 
1413 
Response: Access to source documents and identifying information will be limited to project investigators 
1414 
and staff.  
1415 
18.4 
A.  Who is responsible for receipt or transmission of the data? 
1416 
Response: Study investigators and staff. 
1417 

 
31
18.5 
A.  How will the data be transported? 
1418 
Response:  N/A  Data will not be physically transported. 
1419 
B. Confidentiality of Study Specimens 
1420 
 
1421 
Describe the local procedures for maintenance of confidentiality of study specimens.   
1422 
☐ 
N/A:  No specimens will be collected or analyzed in this research.   
1423 
(Skip to Section 19.0) 
1424 
 
1425 
18.6 
B.  Where and how will all specimens be stored?  Include information about:  physical controls, 
1426 
authorization of access, and labeling of specimens, as applicable.   
1427 
Response: Urine samples will be used immediately for on-site drug and pregnancy screening and then 
1428 
discarded. 
1429 
As in our recent trial, and saliva samples will be collected in Diefendorf 329 by the Nurse/Phlebotomist.  
1430 
Samples labeled with unique identifiers will be stored in Diefendorf 330 (which has both a key lock and an 
1431 
alarm), in a -80C freezer until batch shipped to the University of Toronto for analysis, as detailed in App00.  
1432 
UPDATE 2020-06-30 –OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS:  
1433 
As stated in the consent addendum:  “To protect your confidentiality, the DNA sample will be stored 
1434 
without any identifying information, just an identification number. That number will be different from the 
1435 
code used to identify other data you provide in the EVarQuit program. An electronic master list linking 
1436 
your DNA identification number to your EVarQuit participation number will be password-protected and 
1437 
stored securely, separate from your other information.”  
1438 
As with our other saliva samples (for cotinine and varenicline concentrations), the saliva sample for genetic 
1439 
analysis will be assayed in the laboratory of Rachel Tyndale, Ph.D., at the University of Toronto.  To 
1440 
protect participant confidentiality, Dr. Tyndale will not have access to any participant data except the 
1441 
uniquely coded samples. 
1442 
 Samples are obtained, labeled, transferred, stored, and shipped according to detailed protocols. see 
1443 
App10.3-03- Saliva_Collection_PNAT_120111-1_UB.pdf. 
1444 
18.7 
B.  How long will the specimens be stored? 
1445 
Response: All specimens will be destroyed after completion of assays described in the protocol/grant or 
1446 
within one year of completion of the project, whichever comes first. 
1447 
UPDATE 2020-06-30 –OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: Dr. Tyndale’s 
1448 
lab will store the genetic samples for up to 10 years for future analysis for all participants who consent to 
1449 
banking. 
1450 
18.8 
B.  Who will have access to the specimens? 
1451 
Response: PIs, project coordinator, study nurse/phlebotomist, and any other staff member trained in sample 
1452 
acquisition or shipping. 
1453 
18.9 
B.  Who is responsible for receipt or transmission of the specimens? 
1454 
Response: PIs, project coordinator, study nurse/phlebotomist, and any other staff member trained in sample 
1455 
acquisition or shipping. 
1456 
18.10 
B.  How will the specimens be transported? 
1457 
Response: Specimens will be shipped via overnight on dry ice, as in our previous trials. 
1458 
19.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
1459 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review procedures only.  This 
1460 
section does not apply. 
1461 

 
32
 
1462 
NOTE:  Minimal risk studies may be required to monitor subject safety if the research procedures 
1463 
include procedures that present unique risks to subjects that require monitoring.  Some examples 
1464 
include:  exercising to exertion, or instruments that elicit suicidality or substance abuse behavior.  In 
1465 
such cases, N/A is not an acceptable response. 
1466 
 
1467 
19.1 Describe the plan to periodically evaluate the data collected regarding both harms and benefits to 
1468 
determine whether subjects remain safe. 
1469 
Response: In this single-site trial, all participants receive varenicline (Chantix) for its approved use, 
1470 
smoking cessation.  
1471 
Participant safety is a priority. The safety of individual participants will be assessed at each clinic visit, and 
1472 
aggregate data will be reviewed annually by the study team and by the IRB. 
1473 
We will use a two-tiered system to assess potential side effects and adverse events. At each clinic visit, 
1474 
participants will complete an established checklist of symptoms and an open-ended evaluation for potential 
1475 
adverse events. Study staff will be trained to follow the procedures in App10-02 to trigger timely reporting 
1476 
of side effects and potential AEs to the Study Physician. Participants will also be given information 
1477 
(verbally and in a reminder wallet card) regarding how to contact the study personnel and under what 
1478 
circumstances to proceed to the emergency department. At any time, participants will have the option to 
1479 
stop taking the study medication and can drop out of the study if they desire. In addition, if any adverse 
1480 
event requires treatment and follow-up, participants will be provided with appropriate referrals. The Study 
1481 
Physician will determine the course of action for the subject reporting a serious adverse event (e.g., 
1482 
discontinuing medication, dose adjustment). The PI or Study Physician/Clinical Research Nurse will 
1483 
clinically follow all subjects who are discontinued due to a serious adverse event until the event is resolved. 
1484 
In accordance with NIH and IRB guidelines, this study will employ the following mechanisms for adverse 
1485 
event reporting: 1) alert the site IRBs of any and all reports of serious adverse events; 2) inform all 
1486 
members of the study team of any and all reports of serious adverse events; and 3) notify NIH of any 
1487 
actions taken by IRBs with regard to data safety monitoring.  Detailed procedures are formalized in App10-
1488 
02. 
1489 
Although we considered establishing a formal DSMB, this does not appear to be warranted for the current 
1490 
single-site trial that employs varenicline for its approved indication, smoking cessation. However, we do 
1491 
plan to summarize and review rates of side effects, adverse events, and efficacy data – all blind to treatment 
1492 
condition – as part of each renewal application to the IRB.   
1493 
19.2 Describe what data are reviewed, including safety data, untoward events, and efficacy data. 
1494 
Response: Standard assessments of side effects, detailed records of adverse events, and overall rates of 
1495 
smoking cessation. 
1496 
19.3 Describe any safety endpoints. 
1497 
Response: Standard assessments of side effects, detailed records of adverse events. 
1498 
19.4 Describe how the safety information will be collected (e.g., with case report forms, at study visits, by 
1499 
telephone calls with participants). 
1500 
Response: With case report forms at study visits. 
1501 
19.5 Describe the frequency of safety data collection. 
1502 
Response: At all 6 clinic visits, which occur at 1- to 2-week intervals in the first 2 months of treatment. 
1503 
19.6 Describe who will review the safety data. 
1504 
Response: As detailed in App10-02, study staff will review side effect reports at each study visit; standard 
1505 
decision rules are used to trigger reporting to the PI/Study Physician within 24 hours (often within 
1506 
minutes).  
1507 
19.7 Describe the frequency or periodicity of review of cumulative safety data. 
1508 

 
33
Response: Annually. 
1509 
19.8 Describe the statistical tests for analyzing the safety data to determine whether harm is occurring. 
1510 
Response: N/A.  The base rates of serious adverse events are too small to be detected by statistical tests in 
1511 
the proposed sample size. 
1512 
19.9 Describe any conditions that trigger an immediate suspension of the research. 
1513 
Response: Given the nature of the trial, it is hard to foresee conditions that would lead to immediate 
1514 
suspension of the research. However, we would seek IRB input to consider immediate suspension if there 
1515 
were more than 2 SAEs (Codes 3 and 4 in App10-02) determined to be probably/definitely related to study 
1516 
participation during a single calendar month. 
1517 
 
1518 
20.0 Withdrawal of Subjects 
1519 
☐ 
N/A:  This study is not enrolling subjects.  This section does not apply. 
1520 
 
1521 
20.1 Describe anticipated circumstances under which subjects may be withdrawn from the research 
1522 
without their consent. 
1523 
Response: As described in the informed consent document: 
1524 
Can I be removed from the research without my OK? 
1525 
The principal investigator of the study can remove you from the research study without your approval. 
1526 
Possible reasons for removal include: 
1527 
• 
The Principal Investigators feel it is necessary for your health or safety. Such an action would not 
1528 
require your consent, but you would be informed if such a decision was made and the reason for this 
1529 
decision. 
1530 
• 
You have not followed program requirements.  
1531 
• 
The Sponsor, University, or Investigators have decided to stop the program.  
1532 
20.2 Describe any procedures for orderly termination.   
1533 
NOTE:  Examples may include return of study drug, exit interview with clinician.  Include whether 
1534 
additional follow up is recommended for safety reasons for physical or emotional health. 
1535 
Response:  PI or designee will attempt to inform participants (by phone; if unable to contact, then by postal 
1536 
service) of the reason for withdrawal. No additional follow-up is necessary; however, in some situations it 
1537 
may be reasonable to provide alternative referral information, as discussed in other sections of the protocol.  
1538 
20.3 Describe procedures that will be followed when subjects withdraw from the research, including 
1539 
retention of already collected data, and partial withdrawal from procedures with continued data 
1540 
collection, as applicable. 
1541 
Response: As described in App10-02:  “For all side effects that require attention, the site physician, 
1542 
qualified medical staff and PI will determine a course of action (i.e., continuation and monitoring, dose 
1543 
reduction, subject withdrawal). All side effects that are considered a Serious Adverse Event (see below) 
1544 
will be reported to PIs and IRBs …, as well as to the FDA and NIH (see below for protocol for adverse 
1545 
event reporting)… PIs and Study Physicians will determine if any serious adverse event requires additional 
1546 
care. Such events may be referred to the out-patient department … or to the emergency department … 
1547 
(…have access to 24-hour emergency services, including extensive in-patient and out-patient services for 
1548 
psychiatric conditions).” 
1549 
 
1550 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: As also noted 
1551 
in Procedures and explicitly stated in the consent addendum:  “If you say yes now, but you change your 
1552 

 
34
mind later, it will not be held against you or affect your participation in EVarQuit. You can always call 
1553 
(716-829-2323) or email us (EVarQuit@buffalo.edu) to say that you have changed your mind, and the 
1554 
DNA sample will be destroyed.”  In such an event, the PI (Dr. Hawk) will contact Dr. Tyndale at the 
1555 
University of Toronto to ensure the deidentified sample is destroyed. 
1556 
 
1557 
21.0 Risks to Subjects 
1558 
21.1 List the reasonably foreseeable risks, discomforts, hazards, or inconveniences to the subjects related 
1559 
to their participation in the research. Consider physical, psychological, social, legal, and economic 
1560 
risks.  Include a description of the probability, magnitude, duration, and reversibility of the risks.  
1561 
NOTE:  Breach of confidentiality is always a risk for identifiable subject data. 
1562 
Response: The potential risks to participants, and their likelihood and seriousness, are described below. 
1563 
Participants can choose, as an alternative, to not enroll in this study. Overall, there is minimal risk for 
1564 
serious adverse reactions as a consequence of enrolling in this study.  
1565 
Assessments. Subjects may experience emotional distress during assessments from discussing feelings and 
1566 
attitudes about smoking or from learning about the risks from smoking. These events happen very rarely 
1567 
and in almost all cases are short-lived and of low intensity, lasting for 1-2 weeks. Study personnel will be 
1568 
alerted to expect this from a small number of subjects and will be trained to make referrals for mental 
1569 
health services as needed. Personnel will be trained to query for adverse emotional reactions during 
1570 
assessments and will be trained to deal with such reactions and to provide additional referrals if needed. In 
1571 
addition, if assessments indicate psychiatric concerns, referrals to appropriate psychological services will 
1572 
be provided. 
1573 
Withdrawal symptoms following cessation. Most participants will experience some nicotine withdrawal 
1574 
upon quitting. Symptoms include craving, anxiety, irritability, problems concentrating, appetite change and 
1575 
weight gain, and insomnia. Because all subjects will use varenicline, withdrawal severity should be 
1576 
reduced. Moreover, withdrawal symptoms typically decrease markedly within 1-2 weeks. Study counseling 
1577 
will advise participants of these symptoms and discuss methods to cope with them. 
1578 
Varenicline.  In clinical trials, the most common side effects of Chantix include:  nausea, sleep problems 
1579 
(trouble sleeping, changes in dreaming), constipation, gas, and vomiting.  Chantix may also contribute to 
1580 
difficult sleeping, vivid, unusual, or strange dreams. Participants will be informed of the need to use 
1581 
caution driving or operating machinery until they are comfortable with how Chantix might affect them.  
1582 
Chantix should not be used with other quit-smoking products.  
1583 
Some people have had reported changes in behavior, including hostility, agitation, depressed mood, 
1584 
suicidal thoughts or actions while using Chantix to help them quit smoking, with these symptoms 
1585 
developing when they began taking Chantix, and on occasion after several weeks of treatment or even after 
1586 
stopping Chantix. Participants will be counseled on these potential risks and encourage to contact us if they 
1587 
and/or their family/friends notice agitation, hostility, depression, or changes in behavior, thinking, or mood 
1588 
that are not typical, or if they develop suicidal thoughts or actions, anxiety, panic, aggression, anger, mania, 
1589 
abnormal sensations, hallucinations, paranoia, or confusion.  
1590 
Varenicline also carries “warnings and precautions” regarding cardiovascular events, interactions with 
1591 
alcohol, seizures, and accidental injury. Varenicline may be associated with an increased risk of certain 
1592 
cardiac and vascular side effects, including chest pain, heart attack, and stroke.  These risks are rare and are 
1593 
still being studied to determine how real they are.  However, our study staff follows strict procedures to 
1594 
monitor for the presence of these side effects, including monitoring blood pressure at each in person visit 
1595 
and asking specific side effect questions related to cardiovascular events (e.g. chest pain, weakness on one 
1596 
side, etc) during each telephone session.    
1597 
Because varenicline safety for an unborn baby is unknown, participants who are pregnant or nursing a 
1598 
baby, or planning to become pregnant, will be excluded from participation. All women of childbearing 
1599 
potential must agree to use an adequate form of contraception throughout the study and will be asked to 
1600 
take a pregnancy test at study intake. Women who become pregnant during the study will be removed from 
1601 
varenicline therapy but may still participate in counseling and study follow-up. 
1602 

 
35
Threats to privacy/confidentiality. Since self-report and biological data will be collected and stored as part 
1603 
of this study, it is possible that subject privacy or confidentiality can be threatened. 
1604 
 
1605 
UPDATE 2020-05-29 - COVID-19: 
1606 
In the context of the pandemic, any interaction with another person or objects they have touched carries 
1607 
some risk of transmission of SARS-CoV-2, the virus that causes COVID-19. 
1608 
In the case of remote visits, it is possible that subject privacy or confidentiality can be threatened.  
1609 
21.2 Describe procedures performed to lessen the probability or magnitude of risks, including procedures 
1610 
being performed to monitor subjects for safety. 
1611 
Response:  
1612 
To further minimize the likelihood and severity of the aforementioned risks of varenicline: 
1613 
1. We will employ select exclusionary criteria. For example, potential participants will be screened for 
1614 
current suicidal behavior and severe mood disorder and for very high levels of alcohol consumption. 
1615 
2. We will administer the standard varenicline dose run-in and will not exceed the standard dose of 1 mg 
1616 
B.I.D. 
1617 
3. We will discuss the potential risks of varenicline with prospective participants, including their likelihood. 
1618 
We will monitor self-reported side effects and Adverse Events at each of the clinic visits during the 
1619 
treatment period. Study Physician /PI will be alerted to side effects /Adverse Events, following our 
1620 
standardized protocol (see App10-02). The Study MD/PI will review the information provided by the 
1621 
research staff and if applicable, will contact the study participant directly to gather more information and 
1622 
determine the appropriate course of action for the subject. Ultimately, the Study Physician will decide if the 
1623 
AE is related to study medication and whether the subject should discontinue taking study medication.  
1624 
 
1625 
To protect privacy and confidentiality, we have several safeguards against unauthorized access to study 
1626 
data – please see the sections of Privacy and Confidentiality sections of this document for details. We have 
1627 
not experienced the unauthorized use of study data. 
1628 
Procedures for monitoring subjects for safety are presented in detail in Section 19. 
1629 
UPDATE 2020-05-29: COVID-19: 
1630 
Please see Section 11.1, above, for our extensive procedures to mitigate risk of transmission of SARS-
1631 
CoV-2, the virus that causes COVID-19, as well as our monitoring for COVID-19 symptoms.  
1632 
21.3 If applicable, indicate which procedures may have risks to the subjects that are currently 
1633 
unforeseeable. 
1634 
Response: There may be risks that we do not know about at this time. We will notify participants of any 
1635 
new information that may affect their willingness to continue participation in this study. 
1636 
21.4 If applicable, indicate which research procedures may have risks to an embryo or fetus should the 
1637 
subject be or become pregnant. 
1638 
Response: Because varenicline safety for an unborn baby is unknown, participants will be told that they 
1639 
should not become pregnant while on this study. Women on the study should not nurse a baby. If the 
1640 
woman is of childbearing potential, she must use an adequate form of contraception while study medication 
1641 
is being taken and for at least one month after the end of the trial. If the woman is pregnant or breast 
1642 
feeding, she may not participate in this study, and if she becomes pregnant during the study, she will be 
1643 
removed from the study. Women will be asked to take a pregnancy test before starting the study. 
1644 
21.5 If applicable, describe risks to others who are not subjects. 
1645 
Response: We are not aware of any risks of this research to others who are not subjects.  
1646 

 
36
 
1647 
22.0 Potential Benefits to Subjects 
1648 
22.1 Describe the potential benefits that individual subjects may experience by taking part in the 
1649 
research.  Include the probability, magnitude, and duration of the potential benefits.  Indicate if 
1650 
there is no direct benefit.   
1651 
NOTE:  Compensation cannot be stated as a benefit. 
1652 
Response: As described in the consent form – 
1653 
“Will being in this study help me in any way? 
1654 
We cannot promise any benefits to you or others from your taking part in this research. However, possible 
1655 
benefits include learning more about your smoking habit and quitting smoking. All participants receive free 
1656 
smoking cessation counseling and the most effective smoking cessation medication currently available 
1657 
(varenicline). 
1658 
This clinical research study may show us how to make it easier for other smokers to quit smoking with 
1659 
varenicline in the future.” 
1660 
23.0 Compensation for Research-Related Injury 
1661 
☐ 
N/A:  The research procedures for this study do not present risk of research related injury (e.g. 
1662 
survey studies, records review studies).  This section does not apply.   
1663 
23.1 
If the research procedures carry a risk of research related injury, describe the available 
1664 
compensation to subjects in the event that such injury should occur.   
1665 
Response:  As described in the consent form, under What else do I need to know?: 
1666 
It is important that you tell your study doctor if you feel that you have been injured because of taking part 
1667 
in this study.  You can tell the doctor in person or call. You will get medical treatment if you are injured as 
1668 
a result of taking part in this study.  Your study doctor will explain the treatment options to you and tell you 
1669 
where you can get treatment.  Generally, this care will be billed to you, your insurance or other third party. 
1670 
The University at Buffalo has no program to pay for medical care for research-related injury. 
1671 
23.2 
Provide a copy of contract language, if any, relevant to compensation for research related injury. 
1672 
NOTE:  If the contract is not yet approved at the time of this submission, submit the current version here.  
1673 
If the contract is later approved with different language regarding research related injury, you must 
1674 
modify your response here and submit an amendment to the IRB for review and approval. 
1675 
Response: N/A – There is no contract other than the consent form. 
1676 
24.0 Economic Burden to Subjects 
1677 
24.1 Describe any costs that subjects may be responsible for because of participation in the research.   
1678 
NOTE:  Some examples include transportation or parking. 
1679 
Response: Free parking will be made available, so that is not an issue. 
1680 
As described in the consent form:  “Neither you nor your insurance provider will be charged for costs of 
1681 
any of the procedures performed for the purpose of this research study (e.g., screening procedures, 
1682 
experimental procedures, medication, counseling, monitoring/follow-up procedures described above).” 
1683 
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review procedures only.  This 
1684 
section does not apply. 
1685 
25.0 Compensation for Participation 
1686 
25.1 
Describe the amount and timing of any compensation to subjects, including monetary, course 
1687 
credit, or gift card compensation. 
1688 

 
37
Response:   
1689 
As detailed in the consent form, under What else do I need to know: 
1690 
Prior to 2019-11 modification approval in early 2020-01: 
1691 
If you agree to take part in this research study, we will pay you up to $599 for your time and 
1692 
effort. Although you will not receive any compensation for the initial health screening, we will 
1693 
pay you $15 for completing each of the 6 clinic visits in which you receive treatment. For each of 
1694 
the two lab visits, we will pay you up to $47. In return for completing electronic daily assessments 
1695 
on a phone or tablet, you can earn up to $315 over a 9-week period. 
1696 
Because it is particularly important for us to know how you are doing after the treatment ends, we 
1697 
will pay you $15 for completing a brief phone call at 3 months after the planned quit date, and $15 
1698 
for a 6- month call. During each of those 2 calls, we may ask you to come back to UB to provide a 
1699 
saliva sample and complete a few additional measures, for which you would receive an additional 
1700 
$35 each time. 
1701 
Beginning with 2019-11 modification submission (implemented early 2020-01):  
1702 
If you agree to take part in this research study, we will pay you up to $598 for your time and 
1703 
effort. Although you will not receive any compensation for the initial health screening, we will 
1704 
pay you for your time and effort in completing other project requirements. For each of the two 2-
1705 
hour lab visits, we will pay you up to $54. In return for completing electronic daily assessments on 
1706 
a phone or tablet, you can earn up to $315 over a 9-week period ($1 per completion for each of the 
1707 
35 assessments per week). 
1708 
Because it is particularly important for us to know how you are doing over time, we will pay you 
1709 
up to $25 for completing a 1-minute computerized survey sent to your phone at 6, 8, 10, 18, and 
1710 
22 weeks after your Target Quit Date ($5 for each of the 5 surveys). You may also be asked to 
1711 
come back to Diefendorf Hall to provide breath and saliva samples and complete a few surveys at 
1712 
11 and 26 weeks after your Target Quit Date; you would receive $75 for each of those visits.  
1713 
UPDATE 2020-06, to reflect elimination of lab visits: 
1714 
If you agree to take part in this research study, we will pay you up to $490 for your time and 
1715 
effort. Although you will not receive any compensation for the initial health screening, we will 
1716 
pay you for your time and effort in completing other project requirements. In return for completing 
1717 
electronic daily assessments on a phone or tablet, you can earn up to $315 over a 9-week period 
1718 
($1 per completion for each of the 35 assessments per week). 
1719 
Because it is particularly important for us to know how you are doing over time, we will pay you 
1720 
up to $25 for completing a 1-minute computerized survey sent to your phone at 6, 8, 10, 18, and 
1721 
22 weeks after your Target Quit Date ($5 for each of the 5 surveys). You may also be asked to 
1722 
come back to Diefendorf Hall to provide breath and saliva samples and complete a few surveys at 
1723 
11 and 26 weeks after your Target Quit Date; you would receive $75 for each of those visits.  
1724 
 
1725 
Payments will be made with a reimbursable Mastercard (ClinCard), typically at the end of each visit. 
1726 
Although we will not require you to complete tax forms, federal law requires that you report all income to 
1727 
the Internal Revenue Service (IRS).  
1728 
 
1729 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: As stated in the 
1730 
consent addendum, participants who can provide the optional sample on site will receive $25. Participants 
1731 
who complete and mail the sample from home will receive a higher amount of remuneration, $50, because 
1732 
of the additional requirements for collection, preparing the package to mail, and mailing the package. 
1733 
 
1734 

 
38
☐ 
N/A:  This study is not enrolling subjects, or is limited to records review procedures only.  This 
1735 
section does not apply. 
1736 
☐ 
N/A:  There is no compensation for participation.  This section does not apply. 
1737 
 
1738 
26.0 Consent Process 
1739 
26.1 Indicate whether you will be obtaining consent.   
1740 
NOTE:  This does not refer to consent documentation, but rather whether you will be obtaining 
1741 
permission from subjects to participate in a research study.   
1742 
Consent documentation is addressed in Section 27.0. 
1743 
☒ 
Yes 
(If yes, Provide responses to each question in this Section) 
1744 
☐ 
No 
(If no, Skip to Section 27.0) 
1745 
 
1746 
26.2 Describe where the consent process will take place.  Include steps to maximize subjects’ privacy. 
1747 
Response: Consenting will take place in Diefendorf Hall, Rooms 307/308.  An individual overview will be 
1748 
followed by consenting of individual participants.  
1749 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: Participants will 
1750 
be consented individually either in a private interview room on the third floor of Diefendorf Hall or, if all 
1751 
study visits are complete, will have the consent addendum mailed to them for their review at home; 
1752 
questions will be addressed in person, by email, and/or by phone, as needed and preferred by the 
1753 
participant.  
1754 
26.3 Describe how you will ensure that subjects are provided with a sufficient period of time to consider 
1755 
taking part in the research study.   
1756 
NOTE:  It is always a requirement that a prospective subject is given sufficient time to have their 
1757 
questions answered and consider their participation.  See “SOP: Informed Consent Process for 
1758 
Research (HRP-090)” Sections 5.5 and 5.6. 
1759 
Response: After the overview, participants will be invited to take as much time as they like to read the 
1760 
consent form and to ask any questions that they may have. Participants may also take the protocol home 
1761 
with them to review and/or discuss with family, physician, etc.; in this case, the participant would contact 
1762 
us to schedule their intake visit, where we would complete the consent process. Data collection will not 
1763 
begin until the participant has agreed to participate and signed the consent form. 
1764 
26.4 Describe any process to ensure ongoing consent, defined as a subject’s willingness to continue 
1765 
participation for the duration of the research study.   
1766 
Response: Although we will obtain written consent only once in this relatively short term study (each 
1767 
participant is active in the study for ~1 year), participants who raise concerns about continuing participation 
1768 
will always be reminded that they are free to withdraw from the study at any time. 
1769 
26.5 Indicate whether you will be following “SOP: Informed Consent Process for Research (HRP-090).” 
1770 
If not, or if there are any exceptions or additional details to what is covered in the SOP, describe: 
1771 
• 
The role of the individuals listed in the application who are involved in the consent process 
1772 
• 
The time that will be devoted to the consent discussion 
1773 
• 
Steps that will be taken to minimize the possibility of coercion or undue influence 
1774 
• 
Steps that will be taken to ensure the subjects’ understanding 
1775 
Response: Yes, we will follow SOP HRP-090.  In particular, we draw attention to sections 4, 5.1, 5.4, 5.5, 
1776 
5.6, 5.7, 5.8, 5.9, 5.10.3, and 6.1, 6.5. 
1777 
☒ 
We have reviewed and will be following “SOP: Informed Consent Process for Research (HRP-
1778 
090).” 
1779 

 
39
Non-English Speaking Subjects  
1780 
☒  N/A:  This study will not enroll Non-English speaking subjects.   
1781 
(Skip to Section 26.8) 
1782 
26.6 Indicate which language(s) other than English are likely to be spoken/understood by your 
1783 
prospective study population or their legally authorized representatives. 
1784 
 
1785 
NOTE: The response to this Section should correspond with your response to Section 6.4 of this 
1786 
protocol. 
1787 
Response:  
1788 
26.7 If subjects who do not speak English will be enrolled, describe the process to ensure that the oral 
1789 
and written information provided to those subjects will be in that language.  Indicate the language 
1790 
that will be used by those obtaining consent. 
1791 
NOTE:  Guidance is provided on “SOP:  Informed Consent Process for Research (HRP-090).” 
1792 
Response:  
1793 
 
1794 
Cognitively Impaired Adults 
1795 
☒  N/A:  This study will not enroll cognitively impaired adults.   
1796 
(Skip to Section 26.9) 
1797 
26.8   Describe the process to determine whether an individual is capable of consent.  
1798 
Response:  
1799 
 
 
1800 
 
Adults Unable to Consent 
1801 
☒ N/A:  This study will not enroll adults unable to consent.  
1802 
(Skip to Section 26.13) 
1803 
When a person is not capable of consent due to cognitive impairment, a legally authorized representative 
1804 
should be used to provide consent (Sections 26.9 and 26.10) and, where possible, assent of the individual 
1805 
should also be solicited (Sections 26.11 and 26.12). 
1806 
26.9  Describe how you will identify a Legally Authorized Representative (LAR).  Indicate that you have 
1807 
reviewed the “SOP: Legally Authorized Representatives, Children, and Guardians (HRP-013)” for 
1808 
research in New York State.  
1809 
NOTE:  Examples of acceptable response includes: verifying the electronic medical record to 
1810 
determine if an LAR is recorded. 
1811 
Response:  
1812 
☐ 
We have reviewed and will be following “SOP: Legally Authorized Representatives, Children, 
1813 
and Guardians (HRP-013).”  
1814 
26.10  For research conducted outside of New York State, provide information that describes which 
1815 
individuals are authorized under applicable law to consent on behalf of a prospective subject to 
1816 
their participation in the research.  One method of obtaining this information is to have a legal 
1817 
counsel or authority review your protocol along with the definition of “legally authorized 
1818 
representative” in “SOP: Legally Authorized Representatives, Children, and Guardians (HRP-
1819 
013).” 
1820 
Response:  
1821 
26.11  Describe the process for assent of the adults: 
1822 

 
40
• 
Indicate whether assent will be obtained from all, some, or none of the subjects.  If some, 
1823 
indicate which adults will be required to assent and which will not. 
1824 
Response:  
1825 
• 
If assent will not be obtained from some or all subjects, provide an explanation of why not. 
1826 
Response:  
1827 
26.12  Describe whether assent of the adult subjects will be documented and the process to document 
1828 
assent.   
1829 
NOTE:  The IRB allows the person obtaining assent to document assent on the consent document 
1830 
using the “Template Consent Document (HRP-502)” Signature Block for Assent of Adults who are 
1831 
Legally Unable to Consent. 
1832 
Response:  
1833 
Subjects who are not yet Adults (Infants, Children, and Teenagers) 
1834 
☒ 
N/A:  This study will not enroll subjects who are not yet adults.   
1835 
(Skip to Section 27.0) 
1836 
26.13  Describe the criteria that will be used to determine whether a prospective subject has not attained 
1837 
the legal age for consent to treatments or procedures involved in the research under the applicable 
1838 
law of the jurisdiction in which the research will be conducted (e.g., individuals under the age of 18 
1839 
years).  For research conducted in NYS, review “SOP: Legally Authorized Representatives, 
1840 
Children, and Guardians (HRP-013)” to be aware of which individuals in the state meet the 
1841 
definition of “children.”  
1842 
NOTE:  Examples of acceptable responses include: verification via electronic medical record, 
1843 
driver’s license or state-issued ID, screening questionnaire. 
1844 
Response:  
1845 
26.14 For research conducted outside of New York State, provide information that describes which 
1846 
persons have not attained the legal age for consent to treatments or procedures involved the 
1847 
research, under the applicable law of the jurisdiction in which research will be conducted.  One 
1848 
method of obtaining this information is to have a legal counsel or authority review your protocol 
1849 
along the definition of “children” in “SOP: Legally Authorized Representatives, Children, and 
1850 
Guardians (HRP-013).” 
1851 
Response:  
1852 
26.15  Describe whether parental permission will be obtained from: 
1853 
Response:  
1854 
☐  
One parent even if the other parent is alive, known, competent, reasonably available, and shares 
1855 
legal responsibility for the care and custody of the child. 
1856 
☐ 
Both parents unless one parent is deceased, unknown, incompetent, or not reasonably available, or 
1857 
when only one parent has legal responsibility for the care and custody of the child. 
1858 
☐ 
Parent permission will not be obtained.  A waiver of parent permission is being requested. 
1859 
NOTE:  The requirement for parent permission is a protocol-specific determination made by the IRB 
1860 
based on the risk level of the research.  For guidance, review the “CHECKLIST: Children (HRP-
1861 
416).”  
1862 
26.16 Describe whether permission will be obtained from individuals other than parents, and if so, who 
1863 
will be allowed to provide permission.  Describe your procedure for determining an individual’s 
1864 
authority to consent to the child’s general medical care. 
1865 

 
41
Response:  
1866 
26.17  Indicate whether assent will be obtained from all, some, or none of the children.  If assent will be 
1867 
obtained from some children, indicate which children will be required to assent. 
1868 
Response:  
1869 
26.18  When assent of children is obtained, describe how it will be documented. 
1870 
Response:  
1871 
 
1872 
27.0 Waiver or Alteration of Consent Process 
1873 
Consent will not be obtained, required information will not be disclosed, or the research involves 
1874 
deception. 
1875 
☒  N/A:  A waiver or alteration of consent is not being requested. 
1876 
27.1 If the research involves a waiver or alteration of the consent process, please review the 
1877 
“CHECKLIST: Waiver or Alteration of Consent Process (HRP-410)” to ensure that you have 
1878 
provided sufficient information for the IRB to make the determination that a waiver or alteration can 
1879 
be granted.   
1880 
NOTE:  For records review studies, the first set of criteria on the “CHECKLIST: Waiver or 
1881 
Alteration of Consent Process (HRP-410)” applies.  
1882 
Response:  
1883 
27.2 If the research involves a waiver of the consent process for planned emergency research, please 
1884 
review the “CHECKLIST: Waiver of Consent for Emergency Research (HRP-419)” to ensure you 
1885 
have provided sufficient information for the IRB to make these determinations.  Provide any 
1886 
additional information necessary here: 
1887 
Response:  
1888 
 
1889 
28.0 Process to Document Consent 
1890 
☐ 
N/A:  A Waiver of Consent is being requested.   
1891 
(Skip to Section 29.0) 
1892 
28.1 Indicate whether you will be following “SOP: Written Documentation of Consent (HRP-091).” If not 
1893 
or if there are any exceptions, describe whether and how consent of the subject will be obtained 
1894 
including whether or not it will be documented in writing.   
1895 
NOTE:  If your research presents no more than minimal risk of harm to subjects and involves no 
1896 
procedures for which written documentation of consent is normally required outside of the research 
1897 
context, the IRB will generally waive the requirement to obtain written documentation of consent.  
1898 
This is sometimes referred to as ‘verbal consent.’  Review “CHECKLIST: Waiver of Written 
1899 
Documentation of Consent (HRP-411)” to ensure that you have provided sufficient information.  
1900 
If you will document consent in writing, attach a consent document with your submission.  You 
1901 
may use “TEMPLATE CONSENT DOCUMENT (HRP-502)”.  If you will obtain consent, but 
1902 
not document consent in writing, attach the script of the information to be provided orally or in 
1903 
writing (i.e. consent script or Information Sheet).   
1904 
Response:  
1905 
 
Informed consent is App28-InformedConsentWithHIPPA—EvarQuit-2016-09-26 
1906 
☒ 
We will be following “SOP:  Written Documentation of Consent” (HRP-091). 
1907 

 
42
Update 2020-5-21 – Further assessing COVID-19 impact:  Verbal consent will be obtained for newly 
1908 
implemented procedures for this survey only.   
1909 
Update 2020-5-29 - COVID-19-related procedural changes: A consent addendum (EVarQuit Consent 
1910 
Addendum – COVID-19.docx) to be read, discussed, and signed at the Intake Visit, describes all COVID-
1911 
related requirements and procedures. 
1912 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: As described in 
1913 
Procedures, an optional consent addendum (EVarQuit Genetics Sub-Study - Consent Addendum  - onsite - 
1914 
2020-06-30.docx OR EVarQuit Genetics Sub-Study - Consent Addendum  - home - 2020-06-30.docx) will 
1915 
be read, discussed, and signed at Clinic 2 or later (and always prior to obtaining the optional saliva sample 
1916 
for genetic analysis). The consent addendum addresses the requirements of Section 4 of HRP-399 – 
1917 
Additional Requirements for Genetic Testing (NY State) and the procedure for withdrawal of consent and 
1918 
destruction of samples (see Section 2 of HRP-399). 
1919 
 
1920 
29.0 Multi-Site Research (Multisite/Multicenter Only) 
1921 
☒ 
 N/A:  This study is not an investigator-initiated multi-site study.  This section does not apply. 
1922 
 
1923 
29.1 If this is a multi-site study where you are the lead investigator, describe the processes to ensure 
1924 
communication among sites, such as: 
1925 
• 
All sites have the most current version of the IRB documents, including the protocol, consent 
1926 
document, and HIPAA authorization. 
1927 
• 
All required approvals have been obtained at each site (including approval by the site’s IRB 
1928 
of record). 
1929 
• 
All modifications have been communicated to sites, and approved (including approval by the 
1930 
site’s IRB of record) before the modification is implemented. 
1931 
• 
All engaged participating sites will safeguard data as required by local information security 
1932 
policies. 
1933 
• 
All local site investigators conduct the study appropriately. 
1934 
• 
All non-compliance with the study protocol or applicable requirements will be reported in 
1935 
accordance with local policy. 
1936 
Response:  
1937 
29.2 Describe the method for communicating to engaged participating sites: 
1938 
• 
Problems 
1939 
• 
Interim results 
1940 
• 
Study closure 
1941 
Response:  
1942 
29.3 
Indicate the total number of subjects that will be enrolled or records that will be reviewed across 
1943 
all sites. 
1944 
Response:  
1945 
29.4 
If this is a multicenter study for which UB will serve as the IRB of record, and subjects will be 
1946 
recruited by methods not under the control of the local site (e.g., call centers, national advertisements) 
1947 
describe those methods.  
1948 
Response:  
1949 
 
1950 
30.0 Banking Data or Specimens for Future Use 
1951 

 
43
☐  N/A:  This study is not banking data or specimens for future use or research outside the scope of the 
1952 
present protocol.  This section does not apply. 
1953 
30.1 If data or specimens will be banked (stored) for future use, that is, use or research outside of the 
1954 
scope of the present protocol, describe where the data/specimens will be stored, how long they will 
1955 
be stored, how the data/specimens will be accessed, and who will have access to the data/specimens.  
1956 
NOTE:  Your response here must be consistent with your response at the “What happens if I say yes, 
1957 
I want to be in this research?” Section of the Template Consent Document (HRP-502). 
1958 
Response:  
1959 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: With 
1960 
participant consent (see consent addendum), the DNA saliva sample will be banked in the lab of Dr. Rachel 
1961 
Tyndale at the University of Toronto (Room 4326, 1 King’s College Circle, University of Toronto, 
1962 
Toronto, Ontario M5S 1A8, Canada) for up to 10 years for additional genetic analysis. Dr. Tyndale is a 
1963 
Professor of Pharmacology and Toxicology and the Head of Pharmacogenomics at the Centre for Addiction 
1964 
and Mental Health. As noted above, the sample will be stored without any additional information. No one 
1965 
will have access to the genetic data/specimens without permission of Dr. Tyndale, with prior approval from 
1966 
EVarQuit PIs Hawk/Mahoney. 
1967 
30.2 List the data to be stored or associated with each specimen. 
1968 
Response:  
1969 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: None. No data 
1970 
will be stored or associated with each sample. 
1971 
30.3 Describe the procedures to release banked data or specimens for future uses, including: the process 
1972 
to request a release, approvals required for release, who can obtain data or specimens, and the data 
1973 
to be provided with specimens. 
1974 
Response:  
1975 
UPDATE 2020-06-30 – OPTIONAL SALIVA SAMPLE FOR GENETIC ANALYSIS: No banked 
1976 
sample will be released/analyzed without prior IRB approval. As noted in 31.2, no data are stored with each 
1977 
sample. 
1978 
31.0 Drugs or Devices 
1979 
☐ 
N/A:  This study does not involve drugs or devices.  This section does not apply. 
1980 
31.1 If the research involves drugs or devices, list and describe all drugs and devices used in the 
1981 
research, the purpose of their use, and their regulatory approval status.  
1982 
Response: All participants will receive varenicline (Chantix) for its FDA-approved indication, smoking 
1983 
cessation.  
1984 
31.2 Describe your plans to store, handle, and administer those drugs or devices so that they will be used 
1985 
only on subjects and be used only by authorized investigators. 
1986 
Response: Pfizer will provide all study medication for the trial. As in our previous trials, the UB Research 
1987 
Pharmacy (in the school of Pharmacy and Pharmaceutical Sciences) will receive all study medication from 
1988 
Pfizer and will oversee medication packaging, dispensing, accountability logs at study visits, and eventual 
1989 
destruction of unused medication. The Pharmacy has an alarmed room on site (Diefendorf Hall, Room 330) 
1990 
for on-site storage (in a locked cabinet within the alarmed room) and documentation. 
1991 
If the drug is investigational (has an IND) or the device has an IDE or a claim of abbreviated IDE (non-
1992 
significant risk device), include the following information: 
1993 
31.3 Identify the holder of the IND/IDE/Abbreviated IDE. 
1994 
Response: N/A – Study medication is not investigational. 
1995 
31.4 Explain procedures followed to comply with FDA sponsor requirements for the following:   
1996 

 
44
 
Applicable to: 
FDA Regulation 
IND Studies 
IDE studies 
Abbreviated IDE 
studies 
21 CFR 11 
X 
X 
 
21 CFR 54 
X 
X 
 
21 CFR 210 
X 
 
 
21 CFR 211 
X 
 
 
21 CFR 312 
X 
 
 
21 CFR 812 
 
X 
X 
21 CFR 820 
 
X 
 
Response: N/A – Study medication is not investigational. 
1997 
32.0 Humanitarian Use Devices 
1998 
XX  N/A:  This study does not involve humanitarian use devices.  This does not apply. 
1999 
32.1 
For Humanitarian Use Device (HUD) uses provide a description of the device, a summary of how 
2000 
you propose to use the device, including a description of any screening procedures, the HUD procedure, 
2001 
and any patient follow-up visits, tests or procedures. 
2002 
Response:  
2003 
32.2 
 For HUD uses provide a description of how the patient will be informed of the potential risks and 
2004 
benefits of the HUD and any procedures associated with its use. 
2005 
Response:  
2006 
 
2007 

 
 
45
 
008