Treating Tobacco Dependence in Smokers With Severe Mental Illness
Phase: PHASE2
Conditions: Smoking Cessation, Cigarette Smoking, Schizophrenia, Psychotic Disorders, Major Depressive Disorder, Bipolar Disorder I, Bipolar II Disorder, Mental Illness
Sponsor: University of Minnesota

PROTOCOL TITLE: Treating tobacco dependence in smokers with severe mental illness 
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PROTOCOL TITLE: 
 
Treating Tobacco Dependence in Smokers with Severe Mental Illness 
 
PRINCIPAL INVESTIGATOR: 
 
Harry Lando, PhD 
Department of Epidemiology and Community Health 
School of Public Health, University of Minnesota 
Lando001@umn.edu 
612-624-1877 
 
Co-PRINCIPAL INVESTIGATOR: 
 
Andrew Busch, PhD 
Hennepin Healthcare Research Institute 
Hennepin County Medical Center 
Andrew.busch@hcmed.org 
612-873-6681 
 
Co-INVESTIGATOR: 
Linda Skalski, PhD 
Department of Psychiatry 
University of Minnesota 
lskalski@umn.edu 
612-273-9823 
 
 
NCT03822416 
 
VERSION NUMBER/DATE: V1.5 July 16, 2019 
 
 

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Protocol Title 
Treating tobacco dependence in smokers with severe 
mental illness 
Principal 
Investigator/Faculty 
Advisor 
Name: Harry Lando  
Department: Division of Epidemiology and Community 
Health  
Telephone Number: 612-624-1877 
Email Address: lando001@umn.edu 
Student 
Investigator 
Name: 
Current Academic Status (Student, Fellow, Resident): 
  
Department: 
Telephone Number: 
Institutional Email Address: 
Scientific 
Assessment 
Not required, Minimial Risk Study 
IND/IDE # (if 
applicable) 
NA 
IND/IDE Holder 
NA 
Investigational 
Drug Services # (if 
applicable) 
NA 
Version 
Number/Date: 
V1.5 July 16, 2019 
 

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REVISION HISTORY 
 
Revision 
# 
Version 
Date 
Summary of Changes 
Consent 
Change? 
1 
October 11, 
2018 
Response to IRB letter 
Yes 
2 
January 2, 
2019 
Adding exclusionary criteria and 
changes to NRT distribution 
No 
3 
February 18, 
2019 
Fixing a discrepancy – replacing 
“gum” in a few places with 
“lozenge”. Also deleting 
“additional community resources” 
from the control group 
information.  
Yes 
4 
May 1, 2019 
Adding contact letters to mail to 
participants between 
assessments 
no 
5 
July 16, 
2019 
Adding 1) that we will pay non-
eligible candidates $10 for 
coming in, 2) end of study 
satisfaction questions, 3) asking 
participants for an additional 
contact person.  
yes 
 
 
 
 
 
 
 
 
 
 
 

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Table of Contents 
 
1.0 
Objectives ................................................................................................... 6 
2.0 
Background ................................................................................................ 6 
3.0 
Study Endpoints/Events/Outcomes ............................................................ 7 
4.0 
Study Intervention(s)/Investigational Agent(s) ............................................ 7 
5.0 
Procedures Involved ................................................................................... 8 
6.0 
Data and Specimen Banking .................................................................... 11 
7.0 
Sharing of Results with Participants ......................................................... 11 
8.0 
Study Population ...................................................................................... 11 
9.0 
Vulnerable Populations............................................................................. 13 
10.0 Local Number of Participants ................................................................... 14 
11.0 Local Recruitment Methods ...................................................................... 14 
12.0 Withdrawal of Participants ........................................................................ 16 
13.0 Risks to Participants ................................................................................. 16 
14.0 Potential Benefits to Participants .............................................................. 16 
15.0 Statistical Considerations ......................................................................... 17 
16.0 Confidentiality ........................................................................................... 17 
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants ........ 18 
18.0 Provisions to Protect the Privacy Interests of Participants........................ 18 
19.0 Compensation for Research-Related Injury .............................................. 19 
20.0 Consent Process ...................................................................................... 19 
21.0 Setting ...................................................................................................... 20 
22.0 Multi-Site Research .................................................................................. 20 
23.0 Resources Available ................................................................................. 20 
24.0 References ............................................................................................... 21 
 

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ABBREVIATIONS/DEFINITIONS 
 
SMI - Severe mental illness 
 
NRT – Nicotine Replacement Therapy 
 
ECRC – Epidemiology Clinical Research Center 
 
SOP – Standard operating procedures 
 
 

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1.0 
Objectives 
1.1 Purpose: 
This is a pilot study to assess the following research aims:   
1) 
Is our approach is feasible? Can we recruit smokers with SMI, deliver 
counseling and NRT, and keep participants engaged over the six 
months of intervention? Can we minimize attrition and loss to follow 
up? 
2) 
Are our proposed treatments acceptable? How much counseling 
will we be able to deliver? How many participants will adhere to 
recommended NRT? Will participants utilize options for re-treatment 
after relapse or failing to initiate a quit/reduction attempt? 
 
3) 
How do 7-day abstinence outcomes (and continuous abstinence, 
quit attempts, and reduced smoking) compare between 
intervention and control conditions at 1- and 6-month follow-ups?  
2.0 
Background 
2.1 Significance of Research Question/Purpose:  
There have been dramatic drops in overall smoking prevalence both 
in Minnesota and in the US as a whole (Cook et al. 2014; Steinberg 
et al. 2015). However, there are a number of subpopulations with a 
high continuing prevalence of tobacco use including those with 
serious mental illness (Gfroerer et al 2013). For those with severe 
mental illness (SMI) tobacco use is perhaps the leading factor 
implicated in their dramatically increased risk for morbidity and early 
mortality (Cook et al 2014; Kelly et al 2011; Lawn & Lucas, 2016; 
NIMH, Prochaska 2011). People with SMI die sooner than adults 
without SMI from illnesses such as heart disease, cancer, diabetes, 
and stroke (Kelly et al 2011; McGinty et al. 2012.) Clinical 
practitioners often fail to prioritize tobacco cessation because they 
are more focused on psychiatric issues (Lawn & Lucas, 2016; 
Prochaska 2011). 
There is evidence that smokers with SMI want to quit, are 
receptive to offers of cessation treatment, and can quit 
successfully. We are seeking to deliver an intensive but low cost 
and widely disseminable intervention to smokers with SMI that 
addresses tobacco dependence as a chronic disease. 
2.2 Preliminary Data: 
This is a pilot study with the intent of gathering preliminary data on this 
subject.  
2.3 Existing Literature:  
The 2008 US Clinical Practice Guideline Treating Tobacco Use and 
Dependence (on which Dr. Lando was a panel member) states that all 

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smokers with psychiatric disorders should be offered tobacco dependence 
treatment (AHRQ 2018; Fiore et al 2008). The American Psychiatric 
Association recommends that psychiatrists assess the smoking status of all 
patients, including readiness to quit, level of nicotine dependence and 
previous quitting history. Clinicians are encouraged to use this information 
to provide explicit advice to motivate patients to stop smoking (Prochaska, 
Gill, & Hall 2004). 
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome:  
The primary outcome of our study is to determine the proportion of patients 
in the intervention and control conditions who achieve 7-day point 
prevalence abstinence at 8 weeks and 6 months after enrollment  
3.2 Secondary Endpoint(s)/Event(s)/Outcome(s):  
The secondary outcome of our study is to determine the proportion of 
patients in the intervention and control condition who achieve continuous 
abstinence, reduced number of cigarettes per day, and self-reported 
minimum 24 hour quit attempts. 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description:  
This randomized trial will include in-person meetings and phone counseling 
sessions with participants. We will seek to deliver treatment that optimally 
follows current guidelines, provides for substantial counseling support, 
includes an option for NRT, and keeps patients engaged in quitting. 
Drug/Device Handling:  
We will be using different types of NRT in this study including lozenge and 
patches. Only study staff who have been trained to follow standard 
operating procedures for handling and distributing the NRT drugs used in 
this study will have access to them. These NRT drugs are currently FDA 
approved, on the market, over-the-counter medicines that do not require a 
doctor or pharmacist for distribution. All NRT drugs will be kept in the locked 
Drug Supply Room at the ECRC. The study coordinator will maintain a Drug 
Accountability Record of the purchase and distribution of all NRT drugs. 
Patients will be offered the nicotine patch (dose based on number of 
cigarettes per day) and/or the nicotine lozenge (2 or 4 mg if less or 
greater than 30 minutes to first cigarette in the morning respectively) 
depending on participant preference and how much they are smoking 
based on FDA guidelines for use. We will follow FDA guidelines for the 
length of time a participant should use their NRT, anywhere between 8 
and 12 weeks, depending on cigarette use, addiction level, and type of 
NRT. Participants will receive a four-week supply of NRT during the 
baseline visit. If participants are using and want to continue using NRT, 

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the remainder of their supply will be distributed to them at 4 weeks. We 
will either mail subsequent NRT in puncture resistant packaging to the 
participants or participants come to the ECRC to pick up their remaining 
supply.  
 
4.2 Biosafety: N/A 
4.3 Stem Cells: N/A 
5.0 
Procedures Involved 
5.1 Study Design:  
This is a randomized clinical trial that will enroll patients with documented 
SMI (ICD-10 codes) including schizophrenia, any other psychotic 
disorder, bipolar I and II disorder, and/or recurrent/chronic major 
depressive disorder into either a counseling intensive smoking cessation 
program or the control group. 
5.2 Study Procedures:  
This intervention is tailored to the needs of SMI smokers including 
addressing barriers to quitting and the need for continued supportive 
contact. Following is an outline of the study procedures: 
Baseline assessment 
Trained study staff will: 
 Conduct informed consent 
 Collect demographic and smoking history information along with current 
interest in quitting, readiness to quit, confidence in ability to quit, and 
nicotine dependence. We also will include mood, general psychiatric 
health, and quality of life questionnaires. (SMI Smokers BL Interview 
V1.1, SMI Smokers BL Self Report V1.1)  
 Collect the name and phone number of an additional contact. Study 
staff will call the contact in the case of an emergency with the 
participant or if staff are unable to reach the participant for study visits. 
Staff will explain the two reasons for needing the additional contact 
person to the participant during the baseline visit.  
 Randomize participants: prior to the baseline visit, we will complete a 
1 to 1 non-stratified randomization. The randomization results will be 
put in envelopes to be opened during the baseline visit, determining if 
a participant will be allocated to the intervention or the control group.   
 Conduct or schedule session one with those in the intervention group 
 Distribute materials/resources to all participants.  
 
Follow up assessments: 
 Conducted at 8 weeks and 6 months post baseline assessment. (SMI 
Smokers 8 Week Interview V1.0,  SMI Smokers 6 Month Interview V1.0, 

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and SMI Smokers 8W 6M Self Report V1.0, Study Satisfaction Survey 
V1.0 will be administered only at the 6 month assessment and only to 
participants in the Intervention group).  
 Conducted in person when possible, but a phone option will be available. 
 Measures will include current smoking status, quit attempts, self-reported 
number of cigarettes per day for those who currently are smoking, and 
interest and confidence in quitting/continued abstinence. 
 Reported 7-day abstinence at 8 weeks and 6 months will be validated 
by an expired carbon monoxide sample. 
 
The intervention group activities include the following:  
Session 1: 
 1 hour in person visit 
 Will include population specific information about smoking and mental 
illness  
 Counselor will provide a strong and personalized recommendation to 
quit 
 The remainder of Session 1 will be guided by current clinical practice 
guidelines and the National Cancer lnstitute's Clearing the Air patient 
workbook 
o The counselor will cover: past attempts to quit (reframing these as 
learning opportunities), and education on the risks of smoking and 
benefits of quitting both in general and for SMI patients. 
o Emphasis will be placed upon personal reasons for quitting or 
reducing number of cigarettes, especially those that are 
intrinsic 
o The counselor will discuss coping strategies and will focus on 
identifying strategies that are appropriate for the individual patient. 
o The counselor will provide tips for how to elicit support and for 
managing cravings 
o The counselor will address planning for behavior change including 
preparation for a quit date when applicable and anticipating 
challenging situations 
 For those patients who initially choose to reduce rather than quit, the 
focus will be on reduction strategies including substituting NRT 
lozenge for individual cigarettes 
 Patients who want to quit will be offered a nicotine patch and/or the 
nicotine lozenge.  
 The counselor will review correct placement and/or use. 
 Counselor also will address the efficacy and safety of nicotine 
replacement 
Follow up counseling calls: 
 Counselors will make 6 calls over 8 weeks after initial in person session. 
 There will be assessments of current smoking status, NRT use and side 

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effects, and motivation to continue/restart quitting/reduction plan. NRT use 
will be encouraged. 
 For those who have discontinued use or who have encountered problems 
with NRT, the counselor will review the patient's experience and consider 
alternatives including advice to try a different form of NRT 
 If the patient is abstinent, the counselor will reinforce their success, 
discuss any times since the previous session when the participant 
struggled with cravings, will review strategies for managing triggers and 
cravings, and problem solve upcoming challenges to continued 
abstinence. 
 If the patient is smoking, the counselor will reinforce any efforts that 
the patient made including cutting down or attempting to quit and will 
apply brief motivational strategies to prompt further reduction or a 
subsequent quit attempt. 
 The counselor will seek to keep all patients engaged in active behavior 
change. 
Additional counseling phone calls: 
 3 calls (minimum) from 8 weeks to 6 months  
 Telephone calls will be supplemented by supportive text messages 
when agreed to by participants during this phase.  
 Those who choose to initiate a new quit/reduction attempt will be 
eligible for multiple telephone calls (up to six in one or more new 
rounds of intervention before the end of 6 months). 
   
The control group activities include the following:  
Participants in the control group will complete the baseline assessment 
interview and self-report and follow-up assessments at 8 weeks and 6 
months. They will also receive information about smoking and mental illness 
and referrals to the QUITPLAN helpline. 
 
Contact Letters 
 
Participants in both the intervention and control groups will receive three 
letters by mail from the study. The first letter will be mailed approximately four 
weeks post baseline, the second approximately six weeks post 8-week 
assessment, and the last letter will be mailed approximately 12 weeks post 8-
week assessment (Contact Letters V1.0) 
 
5.3 
Study Duration:  
This study will enroll participants beginning fall of 2018 and continue 
enrollment until we recruit 60 participants or until time will no longer allow us 
to recruit based on the funding deadlines. As this is a two-year grant with no 
opportunity for a no-cost extension, all study related activities should be 
completed within two years.  

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5.4 
Individually Identifiable Health Information:  
 
As part of the recruitment process, study staff at UMN will call potential 
participants whose names are on a list they receive from the Clinical 
Research Advocate within the UMN Department of Psychiatry. The people 
on this list have given written consent and have agreed to be contacted for 
study recruitment purposes. UMN staff may also receive calls from patients 
who self-identify in response to flyers hung in the UMN Department of 
Psychiatry. If an individual self-identifies and diagnosis needs to be verified, 
Dr. Linda Skalski, an Assistant professor in the Department of Psychiatry, 
clinical psychologist, and Co I on this study, is authorized to review patient 
charts and can verify diagnosis for study purposes. Patients who are taking 
the medications Clozapine/Clozaril or Chantix/Varenicline will not be 
allowed in the study. Dr. Skalski will also be reviewing charts to ensure 
otherwise eligible patients are not currently taking these medications. 
HCMC screeners will be accessing individual medical charts of HCMC 
patients to verify a diagnosis of SMI, collect contact information, and 
perform screening. 
 
5.5   Use of radiation: N/A  
5.6 Use of Center for Magnetic Resonance Research: N/A 
   
6.0 
Data and Specimen Banking 
N/A 
7.0 
Sharing of Results with Participants 
7.1 No individual results will be shared. If a participant requests the results of 
the study, a summary of the study results will be provided at study 
conclusion.  
8.0 
Study Population 
8.1 Inclusion Criteria:  
Study participants will be between the ages of 18 and 65, have diagnosed 
SMI, and be current daily smokers willing to attempt to quit or reduce their 
daily smoking. They must exhibit current stable psychiatric illness. Patients 
must be willing to either plan for a quit attempt or for cigarette reduction with 
a long-term goal of quitting. 
8.2 Exclusion Criteria:  
8.3 
Our exclusion criteria include anyone who has had an active 
psychotic episode or been hospitalized within the past six months 
due to suicidal ideation or suicidal behavior. Anyone judged unable 
to give valid informed consent and unable to tolerate NRT will also 

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be excluded. Anyone who has had a heart attack in the past two 
weeks will be excluded. Additional exclusion criteria include 
regular use of tobacco products other than cigarettes, terminal 
illness (life expectancy of less than 12 months), or lack of a local 
address and telephone. If patients are currently taking the 
medications Clozapine/Clozaril or Chantix/Varenicline, they will be 
excluded from the study. Screening:  
Hennepin County Medical Center Screening: 
Patients at HCMC will be recruited into the study through two 
routes. The first is to receive a letter from HCMC that includes a 
brief description of the study and an HCMC phone number to 
call with questions. This letter will also give patients information 
on opting out of the chart review and subsequent screening 
phone call. The second is to get a referral to the study from the 
patient’s medical/psychiatric provider. For those who do not opt 
out and for those who have a provider referral, an HCMC 
employee will reach out to patients over the phone to discuss 
the study and complete an eligibility screening. (SMI Smokers 
Screening Form V1.1) If a patient is eligible to proceed and 
interested in participating, the HCMC screener will forward the 
patient’s information on to the UMN study staff who will reach 
out to schedule the in person baseline visit.   
 
University of Minnesota Clinics Screening:  
The outpatient Psychiatry Clinic in the Department of Psychiatry at the 
University of Minnesota provides new patients the opportunity to indicate 
whether they are interested in being contacted to hear about research 
studies or whether they prefer to not be contacted. Patients have the 
opportunity to sign the Psychiatry Research Registry Authorization form to 
participate in the Psychiatry Recruitment Registry when they come to the 
outpatient clinic for a visit. This authorization form gives the Clinical 
Research Advocate (CRA) access to their contact and health information to 
be added to the Psychiatry Research Recruitment Registry so that 
researchers recruiting for a study may contact them and inform them about 
possible opportunities they might be eligible for. Access to this contact 
information is managed by the Department of Psychiatry CRA. The CRA will 
provide us with a list of patients who have given their written consent to be 
contacted for research study opportunities and who meet our study’s 
minimum requirements to be screened. The CRA will also hang posters and 
hand out study cards containing contact information to patients in the 
Department of Psychiatry. (Recruitment Card SMI Smoking and UMN SMI 
Smoking Recruitment Poster) UMN study staff will contact people on the list 
received from the CRA and complete an eligibility screening (SMI Smokers 
Screening Form V1.1). This same screening form will be used by UMN 
study staff if they are contacted directly by an interested patient.   

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9.0 
Vulnerable Populations  
9.1 Vulnerable Populations:  
☐ Children 
☐ Pregnant women/Fetuses/Neonates 
☐ Prisoners 
☒ Adults lacking capacity to consent and/or adults with diminished capacity 
to consent, including, but not limited to, those with acute medical 
conditions, psychiatric disorders, neurologic disorders, developmental 
disorders, and behavioral disorders 
☐ Approached for participation in research during a stressful situation such 
as emergency room setting, childbirth (labor), etc. 
☐ Disadvantaged in the distribution of social goods and services such as 
income, housing, or healthcare 
☐ Serious health condition for which there are no satisfactory standard 
treatments 
☐ Fear of negative consequences for not participating in the research (e.g. 
institutionalization, deportation, disclosure of stigmatizing behavior) 
☐ Any other circumstance/dynamic that could increase vulnerability to 
coercion or exploitation that might influence consent to research or 
decision to continue in research 
☐ Undervalued or disenfranchised social group 
☐ Members of the military 
☐ Non-English speakers 
☐ Those unable to read (illiterate) 
☐ Employees of the researcher 
☐ Students of the researcher 
☐ None of the above 
 
9.2 Additional Safeguards:  
The target population for this study is adults who have a diagnosis of a 
severe mental illness and who smoke. We will take all precautions 
necessary to ensure participants fully understand the purpose of the study, 
the requirements of participation, and what participation would entail. We 
will address any confusion about the study through a clear informed consent 
process that will include using the UCSD Brief Assessment of Capacity to 
Consent for Minimal Risk research. As mentioned in our background 
section, this is a population that is often overlooked for smoking cessation 
programs and that has voiced an interest in quitting smoking. Patients with 

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SMI tend to die at earlier ages than those without and it is important to 
reduce health risks, especially smoking.  
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented:  
We plan to recruit 60 participants for the study.  However, we are requesting 
permission to enroll up to 80 participants to allow for early dropouts and 
inability to reach participants following initial enrollment in the study.  
 
11.0 Local Recruitment Methods 
11.1 Recruitment Process:  
Patients will be recruited from those attending smoking cessation and/or 
psychiatric clinics at Hennepin County Medical Center (HCMC) and the 
University of Minnesota (UMN). We may also be displaying flyers at both 
HCMC and UMN clinics with a brief study description and contact 
information so that interested patients have the option to contact us as well. 
(Recruitment Card SMI Smoking, UMN SMI Smoking Recruitment Poster, 
HCMC SMI Smoking Recruitment Poster) 
Hennepin County Medical Center Recruitment: 
Patients at HCMC will be recruited into the study through two 
routes. The first is to receive a letter from HCMC that includes a 
brief description of the study and an HCMC phone number to 
call with questions. This letter will also give patients information 
on opting out of the chart review and subsequent screening 
phone call. The second is to get a referral to the study from the 
patient’s medical/psychiatric provider. For those who do not opt 
out and for those who had a provider referral, an HCMC 
employee will reach out to patients over the phone to discuss 
the study and complete an eligibility screening. (SMI Smokers 
Screening Form V1.1) If a patient is eligible to proceed and 
interested in participating, the HCMC screener will forward the 
patient’s contact information on to UMN study staff who will 
reach out to schedule the in person baseline visit.  
University of Minnesota Clinics Recruitment:  
The outpatient Psychiatry Clinic in the Department of Psychiatry at the 
University of Minnesota provides new patients the opportunity to indicate 
whether they are interested in being contacted to hear about research 
studies or whether they prefer to not be contacted. Access to this contact 
information is managed by the Department of Psychiatry Clinical Research 
Advocate (CRA). The CRA will provide us with a list of patients who are 
interested in being contacted for research studies and who meet our study’s 
minimum requirements to be screened. The CRA will also hang posters and 
hand out study cards containing contact information to patients in the 

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Department of Psychiatry. If study staff are contacted directly by a patient in 
response to a poster, we will have a two-step process for verifying their 
mental health diagnosis. Step one will be to look for their name on the list 
received from the CRA. If they are not on the list, Dr. Linda Skalski, an 
Assistant Professor and licensed clinical psychologist within the Department 
of Psychiatry who is Co-I on this study and has legitimate access to 
patients’ medical records, will verify diagnosis.  
 
After the screening process is complete: 
Those who are interested and who meet initial eligibility criteria will be 
invited to the ECRC study site for further assessment and enrollment in 
the study. We plan to recruit a minimum of 60 participants with close to 
equal distribution from HCMC and UMN clinics. During the first in person 
visit, participants will be randomly allocated to the intervention or control 
group with approximately 30 in each.  
 
11.2 Identification of Potential Participants:  
We may be hanging flyers in the HCMC and UMN psychiatric clinics which 
contain study information. Patients who are interested in the study will then 
be able to reach out to study staff to get more information. 
At HCMC, a chart review of patients attending smoking cessation or 
psychiatric clinics will be used to identify potential participants. Letters that 
include a brief description of the study, information about opting out of 
the recruitment phone call, and an HCMC study phone number will be 
sent to patients. HCMC medical and psychiatric providers may also refer 
their patients to the study.  
UMN Department of Psychiatry maintains a database of patients who have 
agreed to be contacted about research studies. The Clinical Research 
Advocate will be using this database to find patients interested in being 
participants and will then run a query of the database to find patients who 
meet our minimum requirements to be screened.    
11.3 Recruitment Materials:  
In addition to the proactive methods described above, we may also place 
flyers describing the study and containing study contact information within 
the clinics so that patients may self-identify for the study. Study recruitment 
flyers are attached in the ETHOS recruitment section.  
11.4 Payment:  
Patients will receive a $30 incentive for completing the baseline survey, a 
$50 incentive for completing the 8-week survey, and a $50 incentive for 
completing the final survey at six months post baseline assessment. All 
counseling sessions and related materials, including NRT, will be given to 
the patients free of charge. Participants will also be given $30 to help cover 
the cost of transportation to the in-person sessions. If a candidate comes in 

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for the baseline visit and is deemed unable to give informed consent based 
on the results of the UCSD Brief Assessment of Capacity to Consent for 
Minimal Risk research, they will be given $10 to help with travel expenses 
for the appointment.  
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances:  
Because we are using an intention-to-treat paradigm, subjects will be 
encouraged to continue their participation even if they are unsuccessful 
in quitting or making significant reductions in smoking. Participants may 
choose to withdraw from the study at any time without penalty. The PI and 
Co-PI may withdraw a patient from the study without their consent if that 
patient has an active psychotic episode or is hospitalized due to suicidal 
ideation or suicidal behavior. If this happens, trained study staff will have a 
conversation with the participant explaining the reasons for their withdrawal 
from the study.  
12.2 Withdrawal Procedures:  
If a participant withdraws from the study, no new data will be collected on 
that participant.  
12.3 
Termination Procedures:  
If a participant in terminated from the study, no new data will be collected on 
that participant.  
  
13.0 Risks to Participants 
13.1 Foreseeable Risks:  
Our study procedures involve minimal risk. Patients may experience 
discomfort from quitting or attempting to quit smoking. Use of NRT has 
led to skin irritation in the case of the patch and occasionally to nausea 
in the case of the lozenge or patch. We will provide instructions in 
correct use of NRT and will advise patients to discontinue use in the 
event of significant nausea or discomfort.  
Patients will need to make in-person visits as well as be available for 
phone counseling sessions. Both of these could pose an inconvenience 
and we will do our best to accommodate patients’ schedules and needs. 
In addition to the above mentioned minimal risks, we will also store all 
study related data in secured locations separately from personal 
identifiers to ensure information remains strictly confidential.  
14.0 Potential Benefits to Participants 
14.1 Potential Benefits:  

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The potential benefits to participation in our study include all of the benefits 
related to a reduction in smoking or quitting smoking, including improving 
cardiovascular health.  
15.0 Statistical Considerations 
15.1 Data Analysis Plan:  
Feasibility analyses (e.g. recruitment rate, retention rate) and acceptability 
analyses (e.g., satisfaction scores, sessions attended, uptake of NRT) will 
be primarily descriptive. Given the limited number of participants, primary 
and secondary outcome analyses will be exploratory and will be used for 
effect size estimates for a potential larger future trial. 
15.2 Power Analysis:  
Although we are not powered to detect differences in abstinence, the 
current study will provide a necessary demonstration of the feasibility of 
our approach. 
15.3 Statistical Analysis:  
All analyses will be conducted on the intent to treat sample, with all 
randomized participants included in the analysis. We will estimate the effect 
of the intervention on smoking cessation (biochemically verified 7-day point 
prevalence abstinence) over 6 months using a single repeated measures 
regression model implemented with generalized estimating equations (GEE) 
and robust standard errors. Specifically, we will regress smoking status on 
intervention group and potential covariates using binomial errors, a logit link 
function, and a working unstructured correlation to accommodate within-
subject correlation. For continuous secondary outcomes we will use linear 
regression models. 
15.4 Data Integrity:  
All study staffed will be trained on how to collect and store data. Data quality 
will be evaluated by study staff through review and assessment of gathered 
data to ensure completeness. Data will be kept in locked files or on a secure 
server, to both of which only authorized study personnel will have access. 
All identifying data will be stored separately. 
16.0 Confidentiality 
16.1 Data Security: 
All study personnel will be trained on and follow standard operating 
procedures for interacting with participants and managing data to ensure 
proper handling and security of data. All data will remain strictly 
confidential and will be stored in secured locations separately from 
personal identifiers. Only approved study personnel will have access to 
collected data. All paper documents will be stored in a locked file 
cabinet. We will be using either RedCap or Box (or both) to digitize and 

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share data. As described on the UMN RedCap website, Redcap uses a 
MySQL database via a secure web interface with data checks used 
during data entry to ensure data quality. REDCap includes a complete 
suite of features to support HIPAA compliance, including a full audit trail, 
user-based privileges, and integration with the institutional LDAP server. 
The MySQL database and the web server will both be housed on secure 
servers operated by the University of Minnesota Academic Health 
Center’s Information Systems group (AHC-IS).   
The phone counseling sessions will be audio-recorded. The audio recording 
devices will be stored in a locked file cabinet that only study staff have 
access to. The recordings will be uploaded and stored in Box where only 
study personnel will have access to them. As described on the UMN Box 
Secure Storage website, Box is a secure environment delivered by the 
Center of Excellence for HIPAA Data intended for storing, sharing and 
accessing sensitive and private-highly restricted files. The security of Box 
includes encryption, activity logging, Duo Two-Factor Authentication, and 
access controls such as view-only access. After uploading the sessions, 
they will be deleted from the audio recording device.  
17.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
17.1 Data Integrity Monitoring.  
This study involves no more than minimal risk. The study team, including 
the PI, Co-PI, and study coordinator will all be involved in monitoring the 
data to ensure the safety of the participants. We will ensure participants are 
fully aware of the expectations of participating in the study during the 
enrollment and consent process. The minimal risks associated with the 
study will be clearly outlined. Data will be reviewed for completeness, 
counseling sessions will be reviewed for accuracy and competence. Any 
adverse reactions to the NRT or the counseling sessions will be monitored 
and recorded and adjustments made for individual participants when 
necessary. 
17.2 
Data Safety Monitoring.  This purpose of this study is not to diagnose or 
evaluate psychiatric symptoms or behaviors. That being said, if study staff 
observe a participant acting in a way that causes concern for either the physical 
or mental health of the participant or others, the staff will report this to Dr. 
Skalski, whom we have added to the study team with the specific responsibility of 
monitoring for worsening symptoms. If warranted, Dr. Skalsi will contact the 
participant to determine if they should be referred for help. If there is an 
immediate medical emergency, study staff will call 911. All paper data will be 
stored in locked file cabinets and all digital data will be stored in UMN Secured 
BOX or REDCap to which only study team members who need to use the data 
will have access. 
18.0 Provisions to Protect the Privacy Interests of Participants 

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18.1 Protecting Privacy:  
Study personnel will meet with participants in the ECRC building in private 
rooms designated specifically to the study. Participants will be encouraged 
to schedule their counseling phone calls at times that allow them to have 
privacy.   
18.2 Access to Participants: 
The UMN Department of Psychiatry Clinical Research Advocate has a pre-
determined list of patients who have given written consent to be contacted 
about studies for which they are potentially eligible to participate. This list 
will be shared with the study team through Secure Box for recruitment and 
screening purposes. If medical records need to be reviewed as part of the 
recruitment process, Dr. Skalski is able to do that.  
19.0 Compensation for Research-Related Injury 
19.1 Compensation for Research-Related Injury: N/A 
19.2 Contract Language: N/A 
20.0 Consent Process 
20.1 Consent Process (when consent will be obtained): 
All potential participants will give their written consent to participate in the 
study in a private study room in the ECRC building with a study staff 
member who has been trained on the enrollment and consenting SOP. 
There will be time between the initial contact with a potential participant and 
the consenting/enrollment/baseline session. All participants will have the 
opportunity to read the consent form and to ask any questions they may 
have. The study staff member will also review the form with all potential 
participants asking open-ended questions about the study to ensure 
understanding. As mentioned previously, we will also administer a brief quiz 
to potential participants during the consenting process to ensure they are 
able to give informed consent.   
20.2 Waiver or Alteration of Consent Process (when consent will not be 
obtained): N/A. 
20.3 Non-English Speaking Participants: N/A 
20.4 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 
years of age): N/A 
20.5 Cognitively Impaired Adults, or adults with fluctuating or diminished capacity 
to consent: 
The target population for this study is adults who have a diagnosis of a 
severe mental illness (and who smoke). We will take all precautions 
necessary to ensure participants fully understand the purpose of the study, 
the requirements of participation, and the demands that participation may 

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place on them. We will mitigate any confusion about the study through a 
clear informed consent process that will include using the UCSD Brief 
Assessment of Capacity to Consent for Minimal Risk research. If a potential 
participant is deemed unable to provide informed consent, they will not be 
enrolled in the study.  
20.6 Adults Unable to Consent: N/A 
21.0 Setting 
21.1 Research Sites: 
Recruitment of potential participants will take place in HCMC and UMN 
clinics. Research procedures, including all in-person visits, will take place in 
the ECRC building.  
 
21.2 International Research: N/A 
22.0 Multi-Site Research: N/A 
 
23.0 Resources Available 
23.1 Resources Available:  
Dr. Busch has experience in recruiting participants from the HCMC clinics 
and we have the support of the Clinical Research Advocate at the UMN 
clinics to assist in recruitment of patients. We have access to the patients 
attending UMN and HCMC smoking cessation and psychiatric clinics as our 
base for recruiting potential participants. We plan to recruit 60 into the 
study.  
Study staff with be housed in the Division of Epidemiology and Community 
Health and ECRC. Within the Division, we have access to all needed office 
supplies, printers, and technical assistance. The division also offers 
administrative support for research projects. The study coordinator will also 
have space designated to the study at the ECRC building. This is where the 
all in-person visits will take place. The ECRC also has basic office support 
and resources available for study use. In addition, ECRC has an Emergency 
Response Team (ALERT) that responds to any emergency that may occur 
within the clinic. All study staff members have experience in conducting 
human subjects research and will be trained by the PI and/or the study 
coordinator on standard operating procedures that need be followed for 
every aspect of the study.   
We will be following the UMN Psychiatry Department’s “Unanticipated 
Problem/Crisis Communication Plan for Research Activity” flowchart for any 
psychiatric issues that arise while we are meeting or speaking with our 
study participants. We will also be employing a clinically licensed UMN 
employee (TBD) who will provide psychiatric safety information and 
guidance to study staff.  

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24.0 References 
Cook BL, Wayne GF, Kafali N, et al. Trends in smoking among adults with mental 
illness and association between mental health treatment and smoking cessation. JAMA. 
2014;311(2),:172-182. 
 
Fiore MC, Jaen CR, Baker TB, et al. Treating Tobacco Use and Dependence: 2008 
Update. Clinical Practice Guideline. Rockville, MD: U.S. Department of Health and 
Human Services. Public Health Service. May 2008. 
 
Gfroerer J, Dube SR, King BA, et al. Current cigarette smoking among adults aged 
greater than or equal to 18 years with mental illness- United States, 2009-2011. 
MMWR. 
2013;62:81-87. 
 
Kelly DL, McMahon RP, Wehring HJ, et al. Cigarette smoking and mortality risk in 
people with schizophrenia. Schizophrenia Bulletin. 2011;37(4):832-838. 
 
Lawn S, Lucas T. Addressing smoking in supported residential facilities for people with 
severe mental illness: has any progress been achieved? Int J Environ Res Public 
Health. 2016;13(10):e996 
 
McGinty EE, Zhang Y, Guallar E., et al. Cancer incidence in a sample of Maryland 
residents with serious mental illness. Psychiatr Serv. 2012;63(7):714-717. 
 
Prochaska JJ. Smoking and mental illness: Breaking the link New Eng Med. 
2011;365(3):196-198. 
 
Prochaska JJ, Gill P, Hall SM. Treatment of tobacco use in an inpatient psychiatric 
setting. Psychiatr Serv. 2004;55( 11):1 265-1 270. 
 
Serious mental illness (SMI) among U.S. adults. Retrieved January 4, 2018, from 
htt p:/ /www .nimh.nih .gov/ health /statistics/preyalence/serious-mental -illness-sm i- a 
mong-us-ad ults.shtml 
 
Steinberg ML, Williams JM, Li Y. Poor mental health and reduced decline in smoking 
prevalence. Am] Prev Med. 2015;49(3):362-369. 
 
Treating Tobacco Use and Dependence: 2008 Update. Content last reviewed January 
2018. Agency for Healthcare Research and Quality, Rockville, MD. 
http:/ /ww w.ahrq.g:oy/ pro fessiona ls / clinicians -providers / guide li nes- 
recommendations /tobacco/index.html 
 
 
 

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