An Intervention to Reduce Second Hand Smoke Exposure Among Pediatric Emergency Patients
Phase: NA
Conditions: Smoking Cessation
Sponsor: Children's Hospital Medical Center, Cincinnati

 
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Title of Study: An Intervention to Reduce Second Hand Smoke Exposure among Pediatric Emergency 
Patients  
 
Principal Investigators 
Melinda Mahabee-Gittens, MD, MS 
Professor of Pediatrics 
Division of Emergency Medicine  
Cincinnati Children’s Hospital Medical Center 
Office: (513) 636-4986 
melinda.mahabee-gittens@cchmc.org 
 
 
Co-Investigators 
 
Robert Ammerman, PhD 
Professor of Pediatrics 
Division of Behavioral Medicine and Psychology 
Cincinnati Children’s Hospital Medical Center 
 
 
Jane Khoury, PhD 
Associate Professor of Pediatrics 
Division of Biostatistics and Epidemiology 
Cincinnati Children’s Hospital Medical Center 
 
 
Judith Gordon, PhD 
Associate Professor and Associate Head for Research 
Dept. of Family and Community Medicine 
University of Arizona 
1450 N. Cherry Avenue 
Tucson, AZ 85719 
520-626-6452 
 
Ashley Merianos, PhD 
Associate Professor 
University of Cincinnati 
PO Box 210068 
Cincinnati, OH 45221-0068 
 
Roman Jandarov, PhD 
Assistant Professor 
University of Cincinnati 
Kettering Lab Building 
160 Panzeca Way 
Cincinnati, OH 45267-0056 
 
 
 
 
 
 

 
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ABSTRACT 
Caregiver smoking is an important cause of morbidity and mortality in both adult smokers and their 
children who are involuntarily exposed to secondhand smoke (SHSe). Our research has found that 
caregivers who visit the Pediatric Emergency Department (PED) with their children have a high 
prevalence of smoking (up to 48%), their children have high levels of SHSe equivalent to that of active 
smokers, and they regularly use the PED for nonurgent, SHSe-related complaints. These smokers are 
motivated to quit and eager to receive cessation counseling in this setting. Annually, more than 3 million 
PED visits involve treatment of children with SHSe-related illnesses. These visits provide a unique 
“teachable moment” to motivate caregiver quitting, given the relationship between quitting and 
improvements in their child’s health. Because of the long, unavoidable wait times and the frequent use 
of the PED for non-urgent care, this is an ideal venue for intervening with this population. Moreover, we 
and others have demonstrated the feasibility of conducting complex randomized trials in PEDs without 
disrupting clinical flow. Building on our prior research, we propose to conduct the first randomized trial 
to test whether a cessation intervention in the PED setting can reduce caregiver smoking and decrease 
children’s SHSe. This study will test the efficacy of a cessation intervention for caregivers in a large, 
inner-city PED that is a major nodal site for the federally funded Pediatric Emergency Care Applied 
Research Network (PECARN). The proposed Screening, Brief Intervention, and Assisted Referral to 
Treatment (SBIRT) will highlight the effects of SHSe on their child’s health. We will randomize 750 
caregivers who smoke who present to our PED with their child who has a SHSe-related illness to either 
one of two conditions: 1) SBIRT; or 2) Healthy Habits Control (HHC). The SBIRT condition will use 
components shown to be effective in the out-patient setting but not yet tested in the PED setting. It will 
include a brief form of the Clinical Practice Guideline: Treating Tobacco Use and Dependence, 
motivational interviewing, engaging and personalized materials on the effects of smoking and SHSe, 
immediate access to caregivers’ choice of cessation resources (e.g., Quitline, smokefree.gov, or 
smokefreeTXT), a 12-week supply of nicotine replacement therapy and booster materials for 12 weeks. 
The HHC program has been previously developed and used in the out-patient setting, and will be used 
as an attention control in which caregivers will receive instruction on healthy lifestyle choices to improve 
their child’s health. Cessation assistance will be offered at the study’s conclusion. If effective, the 
SBIRT model could be routinely used in the PED setting, which could reach at least one million 
smokers a year, and could result in significant reductions in caregivers’ tobacco use, SHSe-related 
pediatric illness, and costs in this population. In addition, our results will inform the conduct of public 
health research efforts aimed at adults via the PED. If successful, we will create a comprehensive 
package of materials for disseminating the implementation of the intervention throughout PECARN and 
non-PECARN PEDs, and EDs nationwide.  This study will also assess the prevalence and correlates of 
cannabis smoke exposure (CSE) among PED patients who are in the SHS-exposed group. 
 
 
PURPOSE 
We propose to conduct the first randomized controlled trial to test whether a cessation intervention in the PED 
setting can reduce caregiver smoking and decrease children’s SHSe. 
 
Primary Aim 1: To evaluate the efficacy of the SBIRT compared to Healthy Habits Control (HHC) condition. 
Primary outcomes are self-reported prolonged abstinence and point prevalence at 6-weeks and 6-months post-
enrollment, validated in all participants via expired carbon monoxide and salivary cotinine.  Secondary outcomes 
include number of cigarettes smoked, quit attempts, readiness to quit, and use of cessation resources.  

 
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Hypothesis 1: Caregivers who receive the SBIRT will have higher prolonged abstinence and point prevalence 
cessation rates compared to caregivers in the HHC condition. 
Primary Aim 2: To evaluate the efficacy of the SBIRT on reducing children’s SHSe. Outcomes are caregiver 
reports of total home/car smoking bans and reductions in SHSe (validated using salivary cotinine in children).  
Hypothesis 2: Children of SBIRT caregivers will have higher total home/car smoking bans and lower home/car 
smoking exposure compared to children of HHC caregivers.  
Primary Aim 3: To explore mediators and moderators of the SBIRT outcomes.  
Hypothesis 3: The SBIRT intervention effect on prolonged abstinence and point prevalence cessation rates will 
be mediated by the caregiver’s perception of the risk of smoking on their child’s health and the caregiver’s 
motivation to quit over time. The intervention effect will be moderated and attenuated by factors such as 
household smokers, financial strain, and low social support to quit.   
Secondary Aim 1: To conduct a cost analysis to determine the numbers of SHSe-related PED visits and 
hospitalizations in children of caregivers in the SBIRT condition compared to children of caregivers in the HHC 
condition. This will provide a basis for a future, full-scale cost-benefit analysis.    
Secondary Aim 2: Using the findings from this project and our prior research, we will develop a manual of 
operations and a comprehensive package of provider and patient materials that will be disseminated for use in 
other PEDs and EDs nationwide.   
Secondary Aim 3:  To quantify the prevalence and identify correlates of Cannabis Smoke Exposure and SHSe 
among SHS-exposed PED patients. 
Exploratory Aim:  To examine the DNA methylation (DNAm) patterns and associated clinical patterns in 
female children of smokers and their mothers compared to a control group of female children of nonsmokers. 
We will use cheek (buccal) swabs that have been collected from participants in this Aim. We will measure 
genome-wide gene expression and DNAm patterns to identify and compare differentially methylated cytosine-
[phosphate]-guanine (CpG) loci in children of smokers and their mothers, and children of nonsmokers, focusing 
on loci implicated by previous studies. We will also examine the association between DNAm levels compared 
to cotinine levels and maternal-reported TSE patterns in children, maternal-reported tobacco use patterns, and 
child illness types. 
 
 
BACKGROUND 
Involuntary exposure to secondhand smoke (SHSe) from caregivers who smoke is an important cause of 
morbidity and mortality in children. Annual healthcare costs associated with SHSe and adult smoking are over 
$100 billion and increasing.1 Our research has found that among children who visit the Pediatric Emergency 
Department (PED), there is high prevalence of caregivers who smoke (up to 48%) and children of these 
caregivers have high levels of SHSe equivalent to that of active smokers. These smokers have incomes at or 
below the poverty level (over 50%), have limited access to cessation resources, and frequently use the PED as 
a “safety net” for non-urgent, SHSe-related complaints such as colds and ear infections.2-6 In 2010, 56% of the 
29.8 million emergency department visits for children were triaged in the non- or semi-urgent category and these 
rates were highest in those who were uninsured or Medicaid recipients.7,8 These families are at increased risk 
for a variety of tobacco-related disparities including differences in: tobacco use, cessation rates, access to 
cessation resources, and adult and pediatric tobacco/SHSe-related morbidity.9-13 Encouragingly, these 
caregivers are motivated to quit and eager to receive cessation interventions in this setting.4,14-16                   
Annually, more than 3 million PED visits involve treatment of children with SHSe-related illnesses.8 These 
visits provide a unique “teachable moment” in which providers can leverage the caregiver’s desire to quit and 
the child’s current SHSe-related health condition.17-19 Moreover, the PED is an ideal venue for intervention as 
the environment already entails long natural wait times for non-urgent care, during which we and others have 
shown that even complex randomized trials can be achieved without disrupting clinical flow.20-22 The proposed 
study will be conducted in a PED that is one of the 7 main nodes in the federally funded Pediatric Emergency 
Care Applied Research Network (PECARN) which consists of 18 PEDs that conduct active clinical research with 
over 1 million children.20-25_ENREF_16 Although cessation research has been conducted in the adult ED,25-27 large 
controlled trials of interventions for adult caregivers in the PED have not been conducted. We propose a study 
that will represent an evolution in the use of the PED to improve the health of both caregivers and their children. 
The results of this trial would move the field forward, as the provision of cessation interventions for the caregiver, 
who is not the patient, is quite different than for an adult patient. Furthermore, the need for such interventions in 

 
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the PED setting is especially timely given the federal mandate for healthcare organizations to better manage 
population health in ways that will enlist providers to deliver more comprehensive and efficient care28-30 The 
proposed project is responsive to the mandate to help the “population to feel empowered to manage its health” 
thus “reducing the supply (and the demand) of unnecessary care”.29   
Low-cost interventions that will reduce tobacco-related consequences in caregivers, especially in low income 
caregivers with young, racial/ethnically diverse children, are urgently needed in the PED setting.26,31-33 The 
potential impact of such interventions, defined as reach (the number of people who would use the intervention) 
multiplied by efficacy (percentage of people who use the intervention), could have a substantial public health 
impact.34 For example, of the 3 million PED visits for SHSe-related illnesses, we can conservatively estimate 
that 35% are by caregivers who smoke and their children. Of these 1.1 million visits, if 20% of these caregivers 
quit, this equals over 200,000 new ex-smokers as a results of PED cessation interventions, annually.26,35 This 
will translate into many more children who will no longer be exposed to SHS in their homes, which will result in 
lasting pediatric health benefits and decreased child healthcare costs.  
Furthermore, the proposed project also represents an evolution in the use of the PED visit to conduct 
theoretically grounded research in this unique setting that can be used to target and improve the health of both 
adult smokers and children. The results will improve our understanding of how to conduct and interpret the results 
of health behavior research in this setting. The knowledge gained will have applications in other adult evidence-
based public health behavioral interventions in this setting. The results may be translated into other interventions 
in which screening and counseling is given to adults who bring their children to the PED such as interventions 
related to alcohol and drug use, domestic violence, and HIV testing and treatment.36,37   
Another aim of the project is to explore prevalence and correlates of cannabis smoke exposure (CSE) among 
PED patients who are in the SHS-exposed group. Trends reveal cannabis smoking is almost four times more 
common among cigarette smokers who live with children than among nonsmokers.38 Thus, cannabis smoke can 
also be involuntarily inhaled by children, and may be harmful to their health.39 Other smoke exposure-related 
chemicals (e.g., volatile organic compounds40) are also harmful to child health. 
 The prevalence, risk factors, and clinical effects of child cannabis smoke exposure (CSE) compared to 
SHSe is also important to understand.  However, little is also known on the prevalence of CSE and SHSe 
among PED patients and related risk factors, health effects, and healthcare utilization.  There is currently no 
precise estimate of CSE among SHS-exposed children.  Therefore, this study will also quantify the prevalence 
and identify correlates of CSE and SHSe among SHS-exposed PED patients.  
 
 
 
METHODS 
Study Design Overview  
Design. We will use a randomized, two-group design for the proposed study. We will recruit 750 caregivers who 
smoke and present to the PED with their child for a SHSe-related chief complaint. Participants will be randomly 
assigned to one of two study conditions: (1) Screening, Brief Intervention, and Assisted Referral to Treatment 
(SBIRT) Condition or (2) Healthy Habits Control (HHC) Condition.  
Pool of Potential Participants: Approximately 6,000 pediatric patients with a SHSe related illness will present to 
the PED with their caregiver in a 30 month period. Based on our research, we know that approximately 85% of 
caregivers (N=5,100) will be able to be screened by a Clinical Research Coordinator (CRC); at least 35% will be 
smokers (N=1,785); and at least 80% of these caregivers will consent (N=1,428).  
Assessments. Caregivers will complete an informed consent.  They will also complete the baseline electronic 
assessment on a study tablet. Caregivers will be assessed with questionnaires at baseline, approximately 6-
weeks, and approximately 6-months post-enrollment.  We will also contact participants via text messaging, email, 
phone, or social media to remind them of study participation.  Should we discover any missing data, we may call 
participants or conduct home visits at any time point during the study.  Before conducting these additional home 
visits, we would contact the participant first to obtain permission to conduct the home visit.  We will assess all 
children at baseline and at approximately 6-weeks post-enrollment.  At 6-weeks we will contact participants via 
phone calls, emails, social media, text messaging,,and home visits to children and caregivers in the SBIRT and 
HHC condition to: 1) verify abstinence on 100% of caregivers who report that they have not smoked in the past 

 
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7 days via expired carbon monoxide testing and/or salivary cotinine, 2) obtain a follow-up salivary cotinine level 
on 100% of children to validate total smoking bans, and 3) complete assessment of outcomes. At 6 months, we 
will assess all caregivers via phone or email.  We may contact them via social media or text messaging as well.  
Participant’s privacy will be maintained when contacting them through social media by sending messages that 
only the participant can see via social media.  PHI will not be used on these messages. Should the caregiver 
report abstinence and smoking bans, a home visit will be conducted to validate self-reported abstinence and 
total home smoking bans via salivary cotinine on the child and via expired carbon monoxide testing and/or 
salivary cotinine on the caregivers during home visits.  Follow-ups may be conducted at CCHMC hospital if the 
participant already has a scheduled appointment at the hospital.  If study staff is unable to make contact with the 
family during the course of the study to schedule the follow-ups an unannounced home visit may be conducted 
in order to complete study procedures.   
  
Randomization. We will stratify by gender of the primary caregiver and stage of readiness to quit smoking where 
participants will be in stages 1: pre-contemplation, 2: contemplation 1 or 2, or 3: preparation;41,42  thus there will 
be 8 strata for randomization. A random block randomization scheme will be compiled by the study biostatistician 
prior to the start of the study, and used by the CRC to allocate participants to each condition. The biostatistician 
has a SAS® program for creating the randomization scheme that has been tested and used for other studies. 
As it is anticipated that there will be fewer male caregivers, the random blocks used will be smaller than for the 
females. The randomization scheme will be accessed by the CRC by logging into a dedicated website and 
entering the gender and readiness to quit stage, the study group assignment and a study identification number 
will be returned. Backup will be opaque envelopes, kept within the PED with stratification and study identification 
number marked on the outside. 
Delivery of the SBIRT and HHC. Six or more clinical counselors/intake coordinators/research coordinators will 
be available in the PED to deliver the SBIRT  and HHC43_ENREF_65 interventions. The use of clinical 
counselors/intake coordinators/research coordinators will increase the generalizability of the intervention, as 
most U.S. emergency departments have clinical counselors/intake coordinators/research coordinators available.  
Resources for quitting marijuana use:  Should participants report that they are current marijuana users, they will 
be offered information  to help them quit marijuana use.   
Setting. This study will occur in the main PED or in the Urgent Care of CCHMC.  
Clinical Counselor/Intake Coordinator/Research Coordinator Activities, Training, and Monitoring   
     Three or more clinical counselors/intake coordinators/research coordinators will deliver the SBIRT 
intervention and three or more clinical counselors/intake coordinators/research coordinators will deliver the HHC 
intervention to caregivers while their child is waiting to be seen in the PED. All clinical counselors/intake 
coordinators/research coordinators will receive formal motivational interviewing (MI) training from an MI expert. 
This training, followed by booster session(s) after approximately 6 months or more, will teach them how MI can 
be used as a collaborative, person-centered form of guiding to elicit and strengthen motivation for change and 
will help them use specific skills related to MI. Clinical counselors/intake coordinators/research coordinators will 
be trained in MI strategies and techniques.  The MI trainer will review a selection of audio recordings of each 
clinical counselor/intake coordinator/research coordinator chosen randomly throughout the study period and they 
will receive individualized feedback on these sessions from the MI trainer. The reviews will be spread out over 
the course of recruitment period. The clinical counselors/intake coordinators/research coordinators’ audio-
recorded sessions will be independently rated for adherence using the Motivational Interviewing Treatment 
Integrity (MITI) system by our MI expert, who will provide individualized written and verbal feedback to each 
clinical counselor/intake coordinator/research coordinator.44These audio-recorded sessions will be collected in 
an ongoing basis to facilitate fidelity to MI. MI approaches have been successfully applied in the ED setting for 
a variety of issues, including alcohol and smoking.45  
     The clinical counselor/intake coordinator/research coordinator who delivers the SBIRT will be trained as 
a Tobacco Treatment Specialist at a TTS training center.  This training will teach the clinical counselors/intake 
coordinators/research coordinators how to deliver an evidence-based, cognitive behavioral treatment for nicotine 
dependence. Presentations and hands-on exercises will emphasize the understanding the addictive nature of 
tobacco use, its impact on health, and key clinical activities for assessing and treating the nicotine dependent 
individual. The PI will then provide this clinical counselor/intake coordinator/research coordinator with an 
“Assisted Referral” training session focused on study logistics, the delivery of brief cessation and SHSe reduction 

 
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counseling, and direct connection to the QL, or smokefreeTXT, or smokefree.gov during the PED visit. The 
clinical counselors/intake coordinators/research coordinators will be taught to frame the messages to increase 
caregiver’s risk perception of smoking to their child and themselves, and they will be trained to tailor the 
messages to motivation to quit and level of tobacco dependence. 46,47 The clinical counselors/intake 
coordinators/research coordinators who deliver the HHC intervention will receive training from the PI or study 
staff on the purpose and importance of talking to caregivers about healthy habits to improve their child’s health43 
_ENREF_65 and will be given guidance on engaging and delivering the intervention to caregivers during the PED 
visit; barrier identification and reduction techniques will be taught.  
     In order to promote fidelity and uniform implementation of the SBIRT and HHC interventions, the clinical 
counselors/intake coordinators/research coordinators will complete a fidelity checklist after each session. 
Separate checklists for each condition will include key prescriptive and proscriptive elements for each 
condition. Sample prescriptive elements for the SBIRT include recommending total home/car bans, asking 
visitors to smoke outside, using NRT and other cessation resources to quit; sample proscriptive elements are 
the presentation of the effects of SHSe on children, brief statistics on SHSe and child health outcomes, and 
benefits of quitting on children. Sample prescriptive elements for the HHS include recommending 5 fruits and 
vegetables each day, gradually decreasing screen time, and getting kids active with fun options; sample 
proscriptive elements are the presentation of the health effects of poor diet and inactivity. Although completing 
these checklists does not ensure ideal implementation, they provide reminders to the clinical counselors/intake 
coordinators/research coordinators to be aware of essential features that must be included in each session. In 
addition, every SBIRT and HHS intervention will be audio-recorded, except in cases where the caregiver 
declines to be audio recorded Approximately 10% of the audio recordings will be randomly selected and 
independently rated by blinded reviewers for adherence to the checklists and consistent implementation of the 
two conditions.   
  Booster training sessions and problem solving sessions will occur by the PI or study staff, if needed, every 
several months to problem solve issues that have come up and to provide refreshers and reminders about the 
key elements of the intervention to prevent drift and maximize consistency. 
 
SBIRT Condition 
SBIRT Protocol. After potential participants have been identified, CRCs will obtain informed consent and enroll 
eligible caregivers, and collect baseline data. The clinical counselors/intake coordinators/research coordinators 
will then provide caregivers with the brief  “Advise, Assess, Assist” intervention based on the Clinical Practice 
Guidelines, and tailored on levels of motivation to quit and tobacco dependence.32_ENREF_21 If both caregivers 
are present, eligible, and wish to receive the intervention, then the clinical counselors/intake 
coordinators/research coordinators will provide each caregiver with the “advise” portion of the intervention. 
However, only the primary caregiver (designated by the couple) will be enrolled in the study and assessed for 
data collection. The intervention components that will be provided are as follows:  
1. Advise. Discuss the effects of SHSe on their child’s health and the benefits of quitting, and how quitting could 
improve their child’s medical symptoms and decrease future PED visits. Motivational interviewing (MI) 
techniques will be used to increase caregiver’s risk perceptions of their child’s vulnerability to SHSe and the 
health risks associated with smoking to the smoker and child. 46,49,50 The clinical counselors/intake 
coordinators/research coordinators will elicit the caregiver’s beliefs about their tobacco use, the importance they 
place on quitting, and the confidence they have to quit. The clinical counselors/intake coordinators/research 
coordinators will ask about specific barriers or facilitators to quitting (e.g., financial stress, other household 
smokers, social support, home environment, prior quit attempts, and rewards associated with quitting). They will 
collaborate to increase confidence in quitting, problem-solve how to bypass barriers, and create action steps to 
quit. All caregivers will be encouraged to implement total smoking bans as a way to decrease SHSe. 51,52 For 
those not wanting to quit, options will be discussed, and goals set for reducing SHSe (e.g., gradually increasing 
the proportion of cigarettes smoked outdoors until eliminating indoor/car smoking completely).   
2. Assess. The clinical counselors/intake coordinators/research coordinators will assess caregivers’ readiness 
to quit by asking if they want to quit in the next 30 days.  MI techniques will be used to increase readiness to quit 
for caregivers who do not express an immediate interest in quitting, as well as to solidify and maintain 

 
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commitment in those ready to proceed.  
3.   Assist. This step will consist of 3 components:  
1) NRT: All caregivers who do not have any contraindications to NRT will be offered a free, 6 week supply of 
their choice of NRT patches or lozenges. . NRT will be stored in a locked cabinet in the CRC office in the PED. 
The clinical counselors/intake coordinators/research coordinator will screen all participants for eligibility and for 
any contraindications to NRT using a screening checklist (See Appendix F). If there are any questions about 
eligibility for NRT, the clinical counselors/intake coordinators/research coordinators will contact the PI or other 
study MD,. The PI or other study MD will be available in-person or by phone to address any questions. This 
arrangement has worked well for our most recent cessation trial (5K22CA163747). The screening checklist will 
be sent electronically to the PI or other study MD if there are any contraindications to NRT, who will 
approve/disapprove the distribution of NRT to the caregiver. If there are no contraindications to NRT on the 
checklist, the form will not be sent to the PI or other study MD, and the research coordinator may dispense NRT 
to the caregiver.  Study staff will instruct the caregiver on NRT use and they may use expired NRT to demonstrate 
to caregivers how to place the patch on and to show them what the lozenge looks like.  In addition, all caregivers 
will be provided a home visit for follow-up at 6-weeks during which they will be asked if they were given NRT at 
baseline, and if so, if they used the NRT. If they used approximately 80% of the NRT and wish to receive more 
NRT, they will be screened for eligibility and for any contraindications to NRT using the screening checklist in 
the same manner listed above as at baseline (See Appendix I). If eligible, they will receive 6 weeks of NRT.  If a 
home visit is not possible, the survey will be completed via phone or email and the sample may be obtained from 
the family via mail.  An approximately four week window for follow-up will be used.  The follow-up may also be 
completed at CCHMC or another mutually agreed upon location, if the participant has an already scheduled 
appointment.   
2) Immediate connection to cessation resources: All caregivers will be provided an “Assisted Referral” based on 
preference. These options will include: a) Quit Line: The clinical counselors/intake coordinators/research 
coordinators will dial a direct number to the Ohio QL. A QL counselor will initiate brief counseling which may 
include  counseling calls and free NRT53  If the caregiver prefers, a fax referral may be completed and faxed to 
the QL. 
b) Web-based: the clinical counselors/intake coordinators/research coordinators will help the caregiver log onto 
smokefree.gov using the computer that is in every patient’s PED room. This site has a variety of interactive tools 
including a LiveHelp online “chat” service, SHSe and cessation quizzes, a cessation mobile app, and other 
helpful resources; c) Text Messaging: the clinical counselors/intake coordinators/research coordinators will help 
the caregiver sign up with smokefreeTXT. These free mobile services provide encouragement, advice, and tips 
to help smokers quit.  
3) Intervention Materials: To supplement the baseline intervention, we will provide free caregiver materials shown 
to be effective in previous studies54,55  (See appendix B).  All or some of the materials listed in Appendix B will 
be provided to the caregiver, as applicable. Booster messages with reminders of the benefits of quitting will be 
sent by email, mail, or text message for 12 weeks.  
Feasibility and Generalizability: The SBIRT is feasible for deployment in PEDs and general EDs that serve both 
children and adults. The vast majority of these settings have clinical counselors/intake coordinators/research 
coordinators or equivalent professionals who could be trained to deliver the intervention. SBIRT is streamlined 
and efficient and can be integrated into acute care. Even in the most time-efficient ED settings, waiting times are 
inevitable. These provide opportunities for delivery of the SBIRT. The format of the intervention mirrors other 
successful prevention approaches in the ED setting. Our association with PECARN provides an infrastructure 
for rapid deployment of the intervention dissemination materials leading to widespread adoption. 
 
The Healthy Habits Control Condition 
Rationale for the use of an attention control condition. We will use an attention control condition in order to 
determine the efficacy of the SBIRT condition. In a RCT examining the effects of a behavioral intervention, the 
use of an attention control condition helps to reduce differential attention and expectancies of treatment in the 
intervention, and will decrease threats to internal validity.56-57  Controlling for attention will entail exposing control 
group participants to a meaningful clinical experience that takes as much time and provides as much contact 
with the CRC as the SBIRT. The use of this attention control condition is highly consistent with good clinical care, 
unrelated to the focus of the active intervention (i.e., smoking cessation), and likely to be perceived by families 
as both credible and useful. We will use a childhood obesity prevention program entitled “Let’s Go! 5-2-1-0” 

 
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which is a program which has been developed and used in the outpatient clinic and school setting. This program 
is designed to help children and families eat healthy and be active, by recommending the following daily 
behaviors: 5 fruits/vegetables, no more than 2 hours of TV/computers, 1 hour of physical activity, and 0 sugary 
drinks.43,58-60  The delivery of the HHC will mirror that of the SBIRT.   
 
HHC Protocol. After potential participants have been identified, CRCs will obtain informed consent, enroll eligible 
caregivers, and collect baseline data. The clinical counselors/intake coordinators/research coordinators will 
provide caregivers with the brief HHC intervention based on the “Let’s Go! 5-2-1-0” program43,58-60  and tailored 
on current diet and activity levels. If both caregivers are present, eligible, and wish to receive the intervention, 
then the clinical counselors/intake coordinators/research coordinators will provide each caregiver with the 
recommendations. However, only the primary caregiver (designated by the couple) will be enrolled in the study 
and assessed for data collection. The intervention components that will be provided are: 
1. Advise.  Caregivers will be advised by the clinical counselors/intake coordinators/research coordinators about 
helping their kids and families to eat healthy and be active.  He/she will give them recommendations on daily 
nutritional and healthy lifestyle guidelines with the 5-2-1-0 behaviors.  MI techniques will be used to increase 
caregiver’s risk perceptions of the benefits of healthy choices and the clinical counselors/intake 
coordinators/research coordinators will ask about specific barriers or facilitators to making and adhering to these 
choices.     
2. Assess. The clinical counselors/intake coordinators/research coordinators will assess caregivers’ readiness 
to make good lifestyle choices by asking which area of the 5-2-1-0 recommendations they want to improve in 
the next 30 days.  MI techniques will be used to increase readiness to change habits for caregivers who do not 
express an immediate interest, as well as to solidify and maintain commitment in those ready to proceed.  
3.   Assist. This step will consist of the following components:  
1) Water bottle : All caregivers will be offered a free colorful  water bottle to encourage children to drink more 
water. 
2) Immediate connection to 5-2-1-0 resources: All caregivers will be provided with the option to view a 5-2-1-0 
blog that has ideas on how to stay healthy such as ways that families have celebrated holidays without extra 
sugar and fats; ideas for non-TV or video game related activities; and information on how to read food labels.   
3) Intervention Materials: To supplement the baseline intervention, we will provide free caregiver materials used 
in other healthcare setting (see appendix C).  All or some of the materials listed in Appendix C will be provided 
to the caregiver, as applicable.  These materials are downloadable from www.letsgo.org.68,91-93  The caregivers 
will receive email/mail/text messages (caregiver’s preference), for 12 weeks, reminding them of healthy lifestyle 
behaviors. At 6-weeks we will contact participants via phone calls, emails, text messaging, social media, and 
home visits to children and caregivers in the SBIRT and HHC condition to: 1) verify abstinence on 100% of 
caregivers who report that they have not smoked in the past 7 days via expired carbon monoxide testing and 
salivary cotinine, 2) obtain a follow-up salivary cotinine level on 100% of children to validate total smoking bans, 
and 3) complete assessment of outcomes. At 6 months, we will contact all caregivers via phone, text messaging, 
social media or email.  Should the caregiver report abstinence and smoking bans, a home visit will be conducted 
to validate self-reported abstinence and total home smoking bans via salivary cotinine on the child and via 
expired carbon monoxide testing and/or salivary cotinine on the caregivers during home visits.  Follow-ups may 
be conducted at CCHMC hospital if the participant already has a scheduled appointment at the hospital.   If a 
home visit is not possible, the assessments will be conducted over the phone or via email.  An approximately 
four week window for the follow-up assessments will be used.  
At the study’s conclusion, the HHC group will be given brief information regarding resources for quitting smoking 
over the telephone.  A script will be used by the research coordinator to provide this information.   
Screening for missed eligible patients 
We will assess for missed eligible patients by screening for, but not limited to, second hand smoke exposure 
complaints in children 0-18 years old through our EMR periodically, and a chart review will be completed for 
those not enrolled in the study to gather data about missed eligible patients.  We are requesting a waiver of 
consent to review these patients’ charts.   Data about missed patients may be used to assess screening hours 
as well assess for training needs when missed eligible patients are identified during screening time.  Missed 
eligible data will include the patients’ encounter ID and medical record number, arrival date and time, age, who 
escorted the patient to the ED, triage code, spoken language, chief complaint and arrival complaint, triage start 

 
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time, departure time, disposition, city, state, and zip code, and if they were screened for another study.  We will 
also examine the charts of all children screened during the study period to determine the sociodemographics, 
geographic variability, and clinical characteristics of the entire screened population. We will conduct a chart 
review to extract data on their demographics, zip codes, address, clinical findings, medical test results, 
treatment, disposition, and healthcare visit patterns. Again, we are requesting a waiver of consent to review 
these patient’s charts.  These patients cannot be consented prior to participation.  However, their rights and 
welfare will not be affected by the data collection.  The patients’ data will be the same as those consented into 
the study and they will still receive the same care regardless of study participation. 
Participant Screening, Enrollment, and Exclusion 
     During the approximately 48-month or longer study enrollment period, CRCs and approximately 1-2 pairs of 
clinical counselors/intake coordinators/research coordinators (i.e., one from each condition) will provide study 
coverage every weekday. This increases the opportunities for recruitment and delivery of the interventions. Our 
prior research demonstrates that approximately 3 CRCs will be more than adequate to recruit 750 caregivers. 
Enrollment times will represent peak PED volumes. CRCs will screen consecutive caregivers of patients 
presenting to the PED using CCHMC’s EMR system, Epic. CRCs will identify caregivers by reviewing Epic 
records of registered patients.  A secure database will be used which will include all patients, their age, gender, 
race, chief complaint, enrollment status, and reasons for non-enrollment.   
     Eligible caregiver adult participants must: 1) be > or equal to age 18; 2) be accompanying a child 0-17 years 
of age 2) be a daily smoker; 3) speak and read English (if shown to be efficacious, we will translate the 
intervention materials and test it with multi-lingual CRCs and clinical counselors/intake coordinators/research 
coordinators in a future trial),  4) have a permanent address and a working cell or landline number, 5) live within 
an approximately 50 mile radius of CCHMC (since we will conduct home visits.)  
Eligible child participants must:  1) Not be a current smoker of tobacco or marijuana; 2) present to the 
PED with : (a) a stable condition, that is, patients who are not critically ill and do not require immediate treatment 
and intervention by the PED practitioner (triage levels 2-5) and (b) a potentially SHSe-related complaint (which 
will include complaints such as wheezing, difficulty breathing, cough, ear infection, cold, ear pain, runny nose, 
congestion, flu, asthma, shortness of breath) as outlined by the U.S. Surgeon General;48  or SHSe-related 
discharge diagnosis. 
 If both caregivers are present and eligible, they will be asked to identify the primary caregiver and if one 
or both want to receive the intervention. Although both caregivers may receive the intervention, only the primary 
caregiver will be enrolled and assessed for data collection. Based on our previous studies, we know that both 
caregivers are present in the PED and eligible for the study less than 5% of the time. Child participants will be 
excluded if they have a tracheostomy.  Adult caregivers will be excluded if they are tobacco chewers only, using 
pharmacologic cessation treatment,  plan to move within the study period (if they do not know their new address), 
or do not have a working phone number or permanent address The CRC will obtain informed consent. 
For the CSE study aim, caregiver survey data on cannabis use and child CSE and stored child urine 
samples will be assessed from the child-parent participants in the SHS-exposed group who consented to 
providing this additional data and child urine samples.   Eligibility criteria for the CSE study aim of this project 
are the same as the SHS-exposed group, and with the additional eligibility criteria that they will have: caregiver 
survey data on cannabis use and child CSE; a sub-sample of children have stored urine samples available for 
lab analysis of biomarkers of exposure; and provided informed consent to analyze the associated data and 
child urine samples.  
 
 
 
POTENTIAL BENEFITS 
There may be no direct benefit to adult participants other than the counseling and NRT that they will receive 
from the study in the intervention condition. The intervention may help them decrease their smoking. Cessation 
would reduce their risk of contracting lung and/or oral cancer, chronic obstructive pulmonary disease, coronary 
heart disease, or periodontal disease. Intervention participants will become more aware of the health risks 

 
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associated with smoking cigarettes than they may have had prior to their participation in this study. Even if they 
do not make a quit attempt, they will have been given information on how to go about quitting that could be 
useful to them in the future.  
There is no direct benefit to the children of participants. However, there is a potential indirect benefit to the 
children of the caregivers in the intervention condition: if their caregivers quit or decrease their smoking habits, 
then their children will be exposed to lower levels of SHS. In addition, the benefit to society and research on 
PED-based cessation is potentially great. Since patients who are economically disadvantaged or of minority 
status use PEDs disproportionately, the results of this study may especially help determine the effectiveness of 
cessation interventions in this setting which could benefit society and the scientific community. The intervention 
may be disseminated to other PEDs if found to be effective. The risks this research may have for participation 
are very small but the potential benefit far outweighs the risk of slight embarrassment, increased time in the PED, 
potential loss of confidentiality, and risks of NRT.  
 
POSSIBLE RISKS, DISCOMFORTS, OR INCONVENIENCES 
 
There are 4 possible risks with respect to study participation:   
(1) The potential to interfere with medical care that is ongoing: The study will specifically exclude caregivers 
of patients who are not medically stable during the ED visit. Only caregivers of patients who are stable, that is, 
who are not critically ill and do not require immediate treatment and intervention by the PED practitioner, will be 
eligible for enrollment in this proposed study. These patients are, by our triage criteria, clinically stable, not ill 
appearing, and not felt to be at high risk of deterioration or morbidity. All enrolled patients will be assessed, 
examined, and reassured by a triage nurse prior to enrollment.  We will stress in the consent that participation 
in the study will be entirely voluntary and will not affect the care in the emergency department. Caregivers who 
participate may have an additional 30-40 minute longer ED visit time; however, the interviews and surveys will 
not be done while medical care is being delivered;  
(2) Emotional discomfort when answering the issues raised by the interview: Some of our participants may 
feel uncomfortable answering some of the questions about their smoking habits, particularly in an ED setting 
where such questions are not anticipated.  The consent form will clearly state that caregivers will be asked 
questions such as “Do you smoke?” and “How many cigarettes do you smoke a day?”  
(3) Loss of confidentiality: Confidentiality issues dominate concerns for the successful completion of this 
study. Subjects are asked to provide the participants/family members/neighbor’s address, phone numbers: 
home number, work number, cell phone number; and email address. Participants may also be concerned 
about providing information on their demographics and smoking habits and the related lack of privacy. Special 
procedures will be put in place to assure that the data from the electronic questionnaires and follow-up 
questionnaires are kept secure and confidential.  In addition, there is the potential for breach of confidentiality 
from the audio recorded sessions.  In order to prevent this, no identifying information will be used in the audio 
recordings and the audio recordings will be destroyed at the end of the study.  
(4) Nicotine withdrawal and NRT effects: If the participant quits using tobacco, he or she could experience 
withdrawal symptoms from nicotine cravings such as hunger, anxiety, restlessness, or sleep disturbance. 
Individuals who quit their addiction to tobacco products commonly experience these symptoms. If the subject 
uses NRT, they might experience a negative reaction. We will include a statement on the informed consent 
form warning of the possible side effects of NRT use, and the contraindications for use of NRT. NRT will never 
be dispensed without review of the caregiver’s history by the PI and CRC. In addition, detailed information on 
the use of Nicotine Replacement Therapy (including contraindications for use) will be given to participants. 
Participants will be screened by the PI (a physician) or a trained CRC supervised by the PI for eligibility for 
NRT use. Participants receiving NRT will be instructed to call the PI if they encounter any questions, concerns 
or problems related to the NRT. The PI will be available via phone or in person to provide immediate, 
appropriate medical advice. If any adverse reactions or complications occur as a result of this study, we will 
contact the Institutional Review Board (IRB) Chairperson within five working days. 
 
Pregnancy: Pregnant smokers, nursing mothers, or women attempting to become pregnant during the course 
of this study will be allowed to participate in the study, but will not receive nicotine patches or lozenges.  
 

 
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RISK-BENEFIT ASSESSMENT 
Risk-Benefit Analysis:  We believe the benefits of this study outweigh the potential risks of participation.  It is 
recommended that this proposal be classified as minimal risk with potential direct benefit to the participants. 
 
DURATION 
   This project will take 7 years. In Year 1 (YI), we will: obtain IRB approval; finalize the SBIRT and HHC protocol, 
materials, and procedures; train CRC and clinical counselors/intake coordinators/research coordinators; provide 
practitioner in-services. Recruitment, follow-up assessments, and chart review to evaluate SHSe-related PED 
visits/hospitalizations will be complete by approximately month 54. The remainder of Y5 will be devoted to data 
and cost analyses; delivery of the cessation information to HHC caregivers; and if the intervention is found to be 
effective, the PI and Co-I (Dr. Gordon) will develop a comprehensive guide for implementation at other PEDs. In 
addition, we will develop dissemination and cost benefit analysis plans for CCHMC and other PEDs.   
For the CSE study aim, this study has caregiver survey assessment data available from caregivers who 
responded to the cannabis use and child CSE questions.  Stored urine samples from children in the SHSe 
group will be sent by CCHMC to the Centers for Disease Control and Prevention (CDC) Laboratory where they 
will conduct biochemical validation of smoke exposure. In Years 4-5, we will use the additional caregiver 
survey data on cannabis use and child CSE, electronic health record (EHR) data from CCHMC Epic, and 
stored child urine samples from CCHMC.  In Years 5-7, we will conduct statistical analyses and disseminate 
the additional CSE and SHSe results via publications and presentations.  It will take about 6-8 months to 
receive the urine sample analysis results.  
 
DATA ANALYSIS METHODS 
Data Collection, Retention Strategies, and Measures    
Data Collection and Participant Retention. All baseline assessments will be electronically sent to a central, 
secure, HIPAA-compliant firewalled CCHMC database.  We will use multiple strategies to retain the sample by 
relying on approaches successfully used by our PI and Co-Is in studies of high-risk, low income populations.61-
65  These strategies include: 1) Generous incentives:15_ENREF_92 Participants will be paid with increasing 
compensation of $30 at baseline, $50 at 6-weeks ($20 for phone assessment and $30 for home visit), and $65 
at 6-months ($30 for phone assessment and $35 for home visit); 2) Conducting home visits on all caregivers 
and children at the 6-week follow-up to assess outcomes and giving caregivers in the SBIRT group an 
additional 6 week supply of NRT if they have used approximately 80% of the NRT provided at baseline; 3) 
Hiring and training CRCs to carefully track participants, make home visits, and obtain follow-up data by making 
as many follow-up attempts as is necessary to locate participants; 4) Sending caregivers: weekly 
email/mail/text messages with cessation or healthy habits tips for 12 weeks, reminders of upcoming 
assessments. We will ask order of preference of type of reminders and follow-up; however if one technique is 
unsuccessful, the second and finally third choice will be used; 5) Branding study contact information in 
reminder postcards; 6) Collecting contact information of friends and family members completed at baseline that 
will contain contact information for the participant and their contacts. Cell phone numbers, e-mail addresses, 
and preferred times of contact will be obtained; 7)  Asking our on-site Co-I (Ammerman) to provide strategies 
to maximize retention through thorough tracking and monitoring of study participants.8) Study staff will attempt 
to contact participants via phone, text, email or traditional mail in order to complete the follow-ups.  In the event 
that a research participant becomes lost to follow-up and traditional re-contact methods (i.e. telephone, text, 
email, traditional mail, etc.) are unsuccessful, the use of a nationwide electronic search strategy will be 
employed,  This will include general use of public web-based search functionality, and as a last resort, the use 
of a 3rd party service (Accurint).  Accurint  will be administered through a centralized standard process 
managed by the CCHMC Center for Clinical and Translational Science and Training (CCTST).  Only 
demographic information will be utilized for the purpose of facilitating the Accurint search function.  Specific 
individual requests will be submitted to a designated member of the CCTST staff that will perform the search 
using the Accurint functionality.  CCTST staff will provide a report back to the research team that includes the 
most current available contact information for the requested research participant(s).  Records of each search 
will be maintained and available for IRB review if needed. 

 
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 Given our prior experience54  and proposed techniques, we conservatively project an 80% retention rate at 6 
months.  
Outcome Measures. Primary outcomes will be caregiver prolonged abstinence and 7-day point prevalence of 
tobacco use at 6-weeks and 6-months. Secondary caregiver outcomes will include cigarettes smoked, quit 
attempts, readiness to quit, and use of NRT and cessation resources (QL, smokefreeTXT, smokefree.gov). Child 
outcomes will be presence or absence of total home/car smoking bans, reported SHSe, and number of SHSe-
related PED visits and hospitalizations at CCHMC. 
Baseline Assessment. (Table 1) The brief baseline assessment (T0) will be conducted using a self-
administered electronic survey to be completed on a tablet computer. The assessment items chosen are 
empirically validated measures from studies conducted with low-income disadvantaged study populations.42,66-
71 39,63-68 The items are brief, easily comprehensible, and take into account low literacy levels. They are as 
follows:  
Table 1: Measures for Baseline and Follow-up Assessments by Assessment Point 
T0 T1 T2 
Demographics;  Financial Strain, , Household Smokers,  
✓  
 
Tobacco Use History, Nicotine dependence, , , Motivation to Quit 
✓ ✓ ✓ 
Risk Perceptions: Child; Benefits of Quitting: Child  
✓ ✓ ✓ 
Child’s SHSe, , Child SHSe - related PED visits or Hospitalizations   
✓ ✓ ✓ 
Healthy Habits Lifestyle- daily: fruits/vegetables, screen time, exercise, sugary drinks  
✓ ✓ ✓ 
SBIRT and HHC Satisfaction,  
✓  
 
Prolonged abstinence, point prevalence, nicotine dependence, readiness to change, quit attempts 
 ✓ ✓ 
Cessation Resource utilization: NRT, QL, SmokefreeTXTt, Smokefree.gov, or other resources 
 ✓ ✓ 
1. Demographics and tobacco use. We will collect gender, age, race/ethnicity, level of education, employment 
status, , number of cigarettes smoked daily, time to the first cigarette of the day, nicotine dependence, number 
of attempts to quit >24 hours, use of pharmacological and/or behavioral treatments for quitting, motivation to quit 
using the Contemplation Ladder, and stage of change in readiness to quit. 41,72 Questions will also be asked 
about marijuana use by the participant and household members; participants will not be required to answer these 
questions. Participants who consented prior to Version 11 of the protocol may be re-consented at follow-up such 
that we may obtain information about marijuana use.  
2. Financial Strain. Three items will be used to measure financial strain.74 The questions are: “How difficult is 
it for you to live on your total household income right now?”, “In the next three months, how often do you think 
that you or your family will experience a bad time such as poor housing or not having enough food?”, and “In 
the next three months, how often do you expect that you will have to do without the basic things that your 
family needs?” The three items will be measured on five-point scales and averaged to create a financial strain 
score (α = .802). Higher scores will reflect more financial strain. 
3. Risk perception to child. Perceived vulnerability regarding the effects of his/her smoking on their child will be 
assessed using adapted measures by Borelli et al. Perceived Vulnerability-Child will be measured with  items 
including: “How concerned are you that smoking will make your child’s illness worse?”. Higher scores indicate 
higher perceived vulnerability.77-79   
6. Benefits of quitting. We will assess whether the caregiver perceives that quitting smoking would have a 
beneficial effect on their child using the adapted precaution-effectiveness measures by Borelli, et. al. Precaution 
Effectiveness-Child (PE-C) will be measured by items including: “If you stop smoking, how much would that 
decrease your child’s symptoms?”. Higher scores indicate higher perceived vulnerability.77-79  
7. Child’s SHSe. Child’s SHSe will be assessed by asking about family and other individuals with whom the child 
came in contact during the past week who smoke, locations of smoking, and number of cigarettes smoked. We 
will use questions adapted from previous studies.52,80-83  Caregivers who report no smoking indoors, outdoors, 
or in a car will be considered to have a complete smoking ban. Epic chart review will be conducted to assess 
SHSe-related PED visits and hospitalizations to CCHMC for 6-months prior to baseline.  
8. Healthy Lifestyle Habits. We will assess healthy lifestyle practices (daily fruit/vegetable/sugary drink 
consumption, daily exercise and screen time) of all children.  
9. Consumer satisfaction measure. SBIRT and HHC caregivers will complete a satisfaction survey measuring 
intervention satisfaction and perceived usefulness.84   
10. Secondhand and Thirdhand tobacco smoke from tobacco and marijuana exposure. There is evidence that 
homes of smokers of tobacco and marijuana become reservoirs of persistent toxic tobacco smoke pollutants 
(including nicotine, polycyclic aromatic hydrocarbons (PAH),  tobacco-specific nitrosamine (TSNA), and other 
pollutants), to which nonsmokers may be exposed even after smoking cessation through inhalation, ingestion, 

 
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and dermal transfer. These thirdhand tobacco smoke exposure, thirdhand marijuana smoke exposure and 
pollution levels can be assessed by analyzing urine, and hand wipes of children and by analyzing dust and 
surface wipe samples from the home. Sometimes these samples can also be used to analyze secondhand 
smoke exposure levels as well. Thus, we may collect: 1) saliva samples from all children  and hand wipe 
samples of all children during the baseline visit, 2) urine samples from all children who can easily urinate into a 
cup or bag or who urinate in a diaper if there is time during the baseline visit, 3) hand wipe samples of all 
children during the 6-week home/other location visit, 4) urine samples from all children who can easily urinate 
into a cup or bag or who urinate in a diaper if there is time during the 6-week visit, 5) home dust samples and 
surface wipe samples and air samples from all home visits at 6-weeks if the CRC goes to the home, 6) hand 
wipe samples of children that have home/other location visits at 6 months, 7) home dust samples and surface 
wipe samples and air samples from any home visits at 6-months if the CRC goes to the home, 8) urine 
samples from all children who can easily urinate into a cup or bag or who urinate in a diaper if there is time 
during any 6-month visits; 9) cheek swabs from the caregiver and the child at six weeks and at six months, 10) 
home surface area measurements. Urine collection kits may be given to participants at any of the study time 
points and may be mailed to, given to, or collected from participants before or after follow-up visits. Urine that 
is collected by participants may be either refrigerated or frozen by the participants prior to collection by study 
staff and delivery to the CTRC. These biological and environmental samples will be stored in the CTRC and 
may be analyzed for thirdhand tobacco smoke, secondhand and thirdhand marijuana smoke exposure. Once 
sample analyses are completed, we may examine how SHS and THS tobacco and/or marijuana levels are 
associated with data that may include child demographics, caregiver tobacco and/or marijuana use, home 
characteristics, child clinical findings, disposition, and child healthcare visits once funds become available.  
Participants may opt out of having their samples analyzed for marijuana smoke exposure.  Participants who 
were consented prior to version 11 of the protocol may be re-consented at follow-up in order to use these 
samples for marijuana smoke exposure analyses.   If the follow-up visits do not occur in the participant’s home, 
then dust samples will not be obtained; although participants who do not have a home visit will be asked to 
bring a vacuum bag, if available.  When funds become available, biological and environmental samples from 
participants and their homes will be sent to the Measurement & Evaluation Research Group (MERG) at San 
Diego State University Research Foundation for analysis.  The San Diego State University site will be given 
information that may include data such as: type of specimen, study ID number, portions of baseline and follow-
up assessments (including sociodemographics), and measurements and description of the area of the home 
sampled.  Leftover samples will be returned to CCHMC.  A Materials Transfer Agreement is in place which 
details these procedures.  
For the CSE study aim, this study has caregiver survey assessment data available from caregivers who 
responded to the cannabis use and child CSE questions.  Stored urine samples from children in the SHS-
exposed group will be sent by CCHMC to the Centers for Disease Control and Prevention (CDC) Laboratory 
where they will conduct biochemical validation of smoke exposure. It will take about 6-8 months to receive the 
urine sample analysis results. Only secondary analysis of data will continue to occur at UC.  A Materials 
Transfer Agreement will take place, which will detail the procedures for sample transfer between CCHMC and 
the CDC.  A Data Transfer Agreement is currently in place between UC and CCHMC and details the 
procedures for data transfer.   
 
We have submitted an application to The Children’s Health Exposure Analysis Resource (CHEAR). As stated 
on the CHEAR Data Repository Data Submission Agreement: “CHEAR  was established by the National 
Institute of Environmental Health Sciences (NIEHS) to provide analytical and laboratory services to support 
researchers who want to include environmental exposure assessment in their studies. If our application is 

 
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accepted, The Center for Data Science (“Data Center”) at the Icahn School of Medicine at Mount Sinai will 
provide a data repository for storing epidemiologic and biomarker data that was previously collected in an 
approved CHEAR research study and for all new biomarker data generated by the CHEAR National Exposure 
Assessment Laboratory Network (“Lab Hubs”).” 
Should our application get accepted, the terms of the “CHEAR Data Repository Data Submission Agreement” 
and the “Data Sharing Plan for the CHEAR Data Repository” must be agreed upon and signed by the PI (Dr. 
Mahabee-Gittens) and an “IRB Attestation Letter for CHEAR Data Submission” from the CCHMC IRB must be 
signed and submitted to CHEAR.  
 
Should our application get accepted, we will share human data and samples on those participants who 
consented to future research, with the CHEAR Data Repository. As per the Data Sharing Plan and the CHEAR 
Data Repository Data Submission Agreement, this data will include individual-level data such as 
“…epidemiological data, information which has been collected and recorded from study participants. These 
data include, but are not limited to, research and clinical assessments and information obtained via interviews, 
direct observations, biomarker data, records reviews, genomic data (e.g., sequence, transcriptomic, 
epigenomic, and/or gene expression data), psychophysiological assessments, data from physical 
examinations, etc. Additionally, information necessary to interpret the data (e.g., study protocols, data 
collection instruments, survey tools) will be shared (Please see Data Sharing Plan).  The data will be submitted 
to the CHEAR Data Repository at the CHEAR Center for Data Science at Mount Sinai (CHEAR Data Center).   
    Within the embargo period, the data will be available only to the CHEAR Data Center and the Study PI 
through controlled-access.  After the embargo period, data stripped of personal identifiers will be available 
through unrestricted access. All submitted data will be made available for public use access, after an embargo 
period, as publically accessibledatasets that have been stripped of personal identifiers.  If appropriate, it is 
expected that the Study PI will have registered all studies in the database of Genotypes and Phenotypes 
(dbGaP) in addition to submitting the data to the relevant NIH-designated data repository (e.g., dbGaP, Gene 
Expression Omnibus (GEO), Sequence Read Archive (SRA), the Cancer Genomics Hub) after registration.  
     Data Submission and Release Timeline:  Data that has been stripped of personal identifiers will be shared 
no later than the acceptance for first publication of the findings from the data set (embargo period).”     
      
11. Clinical and cost data. We will be evaluating the clinical characteristics and associated costs/charges of the 
baseline visit and hospitalization (if the child is hospitalized) and any SHSe-related or other visits or 
hospitalizations for the period up to 12 months prior and/or 12 months after the baseline visit. We will extract 
clinical data and costs from the charts that may include data on the presenting illness and illness severity (e.g., 
heart rate, respiratory rate, oxygen saturation, physical exam findings, triage level, chief complaint, discharge 
diagnosis, disposition), lab tests, procedures, interventions, and test results (if any), during these visits and/or 
hospitalizations.  
12.   
Follow-up Assessments (Table 1). All participants will be assessed at 6-weeks (T1) during home visits and at 6-
months (T2) via phone or email; home visits will be made to conduct biochemical validation of caregivers and 
children when caregivers report that they have quit at T2. We will use self-report measures of prolonged 
abstinence and biochemically validated point prevalence at T1 and T2 to assess cessation.85-87  Point prevalence 
of tobacco use will be measured by the question: ‘‘Have you smoked, even a puff, in the last 7 days?’’ Caregivers 
will be considered abstainers if they report no tobacco use in the past 7 days. Prolonged abstinence will be 
measured by the question: ‘‘When did you last smoke a cigarette?’’ Response categories will range from ‘‘less 
than 1 month ago’’ to ‘‘more than 6 months ago.’’ Secondary outcomes will be assessed, including nicotine 
dependence, readiness to change, a quit attempt of > 24 hours, patterns of smoking, number of cigarettes 
smoked/day, treatment initiation, NRT or other pharmacotherapies used, QL, text, or web follow-up. As described 
above, we will use measures of child SHSe to assess children’s exposure and if home/car smoking bans are 
present. Secondary outcomes pertaining to the child’s SHSe, total home/car smoking bans, and SHSe-related 
healthcare utilization (PED visits or hospitalizations at CCHMC) will be assessed.  
Biochemical Validation. At 6-weeks, we will conduct home visits to: (1) verify abstinence on caregivers who report 
that they have not smoked in the past 7 days via expired carbon monoxide testing and salivary cotinine (2) obtain 

 
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a follow-up salivary cotinine level on children to validate total home smoking bans, and (3) complete assessment 
of outcomes. Cotinine is generally accepted to be the best of the available biomarkers, with over 95% specificity 
and sensitivity, it is noninvasive, and easily obtained in young children .85,86_ENREF_114 A standard protocol will 
be used to collect saliva samples from each child at baseline,  6-weeks, and possibly 6 months. Cotinine analyses 
will be performed with Enzyme Immunoassay techniques by Salimetrics LLC, Sate College, PA.   In the child 
samples, the lower limit of cotinine sensitivity is 0.05 ng/ml (range of sensitivity: 0.06-200 ng/ml); undetectable 
cotinine values will be recorded as 0 ng/ml.87,88 Alternatively, if additional funds are available, cotinine analyses 
may be assessed with liquid chromatography mass spectrometry (LCMS).  Caregiver abstinence will be 
established if the caregiver’s expired carbon monoxide level is at or below 6 ppm; salivary cotinine may be 
assessed to confirm abstinence in caregivers who report they have quit if their exhaled carbon monoxide does 
not provide verification.  At 6 months, we will assess all caregivers via phone or email, and validate self-reported 
abstinence and total home smoking bans via expired carbon monoxide testing and/or salivary cotinine.  
    
Data Management  
Data management will occur at CCHMC. Participants will complete the baseline assessment on a web-
enabled tablet research computer. Data will be collected and managed using REDCap (Research Electronic 
Data Capture).92_ENREF_116 The Redcap Mobile App may also be used in order to scan barcodes on samples.   
 
DATA ANALYSIS 
Sample Size and Power Estimates 
Sample Size. Our estimate of the number of caregivers that we plan to enroll is based on the average number 
of unique patients and the smoking prevalence of caregivers seen in a 12-month period in the PED at CCHMC.  
Based on enrollment in previous studies (which had average annual enrollment of 300-350 caregivers), and a 
30 month chart review on the number of annual visits for patients with SHS-related complaints (at least 6,000), 
we are conservatively expecting to enroll 300 caregivers who smoke over 12 months, for a total of 750 caregivers 
in 30 months. To obtain the effective sample size for power analyses of outcomes, the sample size must be 
adjusted for potential attrition of approximately 20% at 6 months, although all efforts will be used to decrease 
this attrition rate, leaving a total of 600; 300 per group.  
 
Estimate of effect sizes: Evaluation of outcomes. Based on the recommendations of Hughes et al.,85,86 we will 
use 2 criteria for abstinence: 6-month point prevalence and prolonged abstinence at 6-months. Based on a 
similar prior study, we expect that 6-month point prevalence in the HHC condition will be 6.3%.54 For prolonged 
abstinence, we are basing our estimation on the 2.1% rate for the HHC and 7% rate for SBIRT. We are 
conservatively estimating a point prevalence cessation rate of 6.3% and prolonged abstinence rate of 2.1% in 
the HHC group.54 We are basing our estimate of 6-month point prevalence of the SBIRT group on the odds ratio 
derived from meta-analyses assessing the effectiveness of NRT vs. a control, ranging from 1.4-4.6,54 to give a 
cessation rate of 10-12% in the SBIRT group. However, since a clinical counselor/intake coordinator/research 
coordinator will be conducting the intervention, we expect high compliance in implementation. Thus, we are 
estimating a cessation rate of 12% in the SBIRT group. Similarly, for prolonged abstinence, we are assuming a 
rate of 7% in the SBIRT group.  
 
 
Power (Table 2). Power analyses are based on estimates of differences in both 6-month point prevalence and 
6-month prolonged abstinence between groups.  With 300 subjects in each group, we would have 80% power 
to detect an increase of 6.4% in cessation rate. However, assuming a multiple imputation approach, we would 
be able to detect a 5.5% increase in cessation rate. 
For 6-month abstinence, we can detect an increase 
of 4.5% with 300 subjects per group and 4.2% with 
the 
multiple 
imputation 
assumption. 
These 
estimates are consistent with the predicted 
cessation rates shown above and published 
rates.54,93  For analyses based on regression 
techniques, using hierarchical linear modeling, 
sample sizes will be more than sufficient. The effect sizes of interest for these analyses are the correlation 
Table 2: Estimated Power for varying sample size 
N / group 
Odds ratio 
80% power- 
prevalence 
Odds ratio 
80% power- 
abstinence 
Assumption 
300 
2.16 
3.29 
20% loss 
375 
2.00 
3.05 
Multiple 
Imputation 

 
Version:  10Dec2021 
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coefficients and squared, semi-partial correlations (squared=incremental R2). To predict caregiver level variables 
(Primary Aim 1), with a sample size of 750 and 20% lost to follow-up, we will have >80% power to detect a 
correlation of 0.11 (r2=0.013). For examination of smoking bans (Primary Aim 2), these samples sizes would 
allow us to detect a difference of 12% with 80% power with 300 per group assuming a rate of between 50% and 
65% in the HHC group. Using multiple imputation and 375 per group, we could detect a difference of 11% with 
80% power.  
 
Analytic Plan 
Data analyses will be conducted at CCHMC and at the University of Cincinnati. A DTA will be established with 
study investigators at the University of Cincinnati.  Data will include demographics, smoking behavior, data from 
the parent assessments, clinical data, and EMR data.  The data will be a limited data set stripped of identifiers.  
It will be shared on an encrypted file.   
 
Preliminary Analyses. Univariate and bivariate examination of variables will be done first. Distributional properties 
of the continuous outcome variables will be examined. To control for non-normal distributions and heterogeneous 
error variances, we will use logarithmic transformation and report geometric means and associated 95% 
confidence intervals; this is particularly relevant for cotinine. We will conduct several preliminary analyses prior 
to addressing the Study Aims: (1) Examination for out of range values; (2) Comparison of baseline characteristics 
of caregivers and children across groups. If baseline differences are found, further analyses will include these 
variables as covariates in assessing caregiver and child outcomes as appropriate; and (3) Attrition analyses to 
assess if: Participants who were lost to follow-up are different from those retained. Although we do not expect 
differential attrition by group, it will be evaluated and if it occurs, we will weight the follow-up data to reflect the 
proportion assigned to each group. If key variables significantly predict attrition, we will examine the analysis 
with and without the drop-outs. Thus, we will compare our primary outcomes using a multiple imputation 
approach for missing data to allow maximum utilization of our data. When including those that were lost to follow-
up, the outcome data may be weighted using a response propensity analysis94,95  which uses the baseline 
distributions on these variables so that follow-up data has the same distributions on these variables as the 
baseline data. For all analyses we shall include in the model an indicator variable to account for which clinical 
counselor/intake coordinator/research coordinator was involved in the delivery of the SBIRT or HHC.  
General approach for addressing study aims. This is a two-group RCT, wherein caregivers are randomly 
assigned to the SBIRT Group vs. HHC group. The appropriate statistical models for analyses of data for inclusion 
of time dependent outcomes are General Linear Mixed Models (GLMM) for data either with a Gaussian/normal 
distribution or with a binomial or Poisson distribution, using the appropriate link function, invoking Generalized 
Estimating Equations (GEE) to account for the longitudinal aspect of the data.96  
   We will use GLMM to evaluate the relative effectiveness of the SBIRT versus HHC group on our primary 
outcomes: point prevalence and prolonged abstinence at 6-months. The analysis will be repeated with caregiver 
level differences between groups included as covariates. We will use mixed model analysis of covariance, with 
repeated measures to assess change (controlling for baseline differences between groups) to assess the effect 
of the SBIRT on secondary outcomes including reduction in use, number of quit attempts, and changes in 
readiness to quit.  Kappa statistic will be used to assess agreement between the caregiver’s self-report and the 
assessment of tobacco use based on expired carbon monoxide levels and/or salivary cotinine at 6 months. It is 
possible that use of and adherence to the NRT will influence outcomes in the intervention group. In addition, 
some of the participants in the control condition may obtain NRT during the study interval. We will examine NRT 
use or dose, defined as self-reported adherence, as a covariate in order to control for this possible relationship.  
Analyses for Primary Aims 1-3. 
  Primary Aim 1, Hypothesis 1: We hypothesize that SBIRT participants will have higher prolonged abstinence 
and point prevalence cessation rates compared to those in the HHC group. As stated above, our primary 
approach to the analysis is using multiple imputation, with  clinical counselors/intake coordinators/research 
coordinators included in the model. We shall then use analysis of covariance, to control for any baseline 
differences of caregivers between conditions. In addition we will also control for motivation to quit, considered a 
priori as a potential covariate, using the score on the contemplation ladder. As we are stratifying on motivation 
to quit and caregiver gender, we will initially enter this into the model as an interaction. To address child cotinine 
as the 6-month outcome, we will use a t-test and then an analysis of covariance to incorporate the variables 
different at baseline. Incorporating the 6-week outcome values, we will use GLMM invoking GEE for the repeated 

 
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measures and also a model including covariates. This approach will be used to assess the intervention’s effect 
on abstinence and point prevalence and child cotinine.  
   Primary Aim 2, Hypothesis 2: We will evaluate the effectiveness of the SBIRT on total home/car smoking bans 
and on child SHSe which will be measured by both caregiver report and child salivary cotinine, as recommended 
by Halterman et al.87 The reliability of caregiver’s reports will be examined by comparing amount of smoking and 
SHSe levels reported at 6-months using Pearson’s correlations. For validation, we will compare the child’s 
salivary cotinine concentrations for those reporting total home/car smoking bans and those not, we shall also 
examine the change in cotinine levels from baseline for those initiating bans versus not. The computational 
procedure will use data from the 2 measurement points, controlling for the within-subject correlation of measures 
repeated over time.97,98  The main analysis will use GLMM, first to assess the intervention effect alone and then 
including covariates. First, we will investigate immediate intervention effects based on change from baseline to 
6-weeks post-intervention. Next, we will investigate change from 6-weeks to 6-months to examine maintenance 
effects. To examine overall change, we will use GEE, examining linear and quadratic terms for time, group, and 
group × time interactions as explanatory variables.52 Use of NRT, described above, may be of particular interest 
as a covariate for this analysis. 
  Primary Aim 3, Hypothesis 3: We hypothesize that the SBIRT intervention effect on prolonged abstinence and 
point prevalence cessation rates will be mediated by the caregiver’s perception of the risk of smoking on their 
child’s health, or on their readiness to quit over time.42,66,67,69,70,99 Bivariate analyses will be used to initially 
examine if the variables measuring this phenomena, susceptibility, severity and benefits of quitting are 
associated with cessation at each time point and if there are any changes in perceived health risk from baseline 
to 6-months in the SBIRT versus HHC groups. We will build on the models from our primary aim to determine 
the association of these potential mediators.  Analysis assessing these effects will be conducted using 
abstinence at each follow-up point as the dependent variable and testing for interactions between treatment (i.e., 
intervention) and the potential mediator. Additionally, we will examine the main effects of the intervention within 
each level of the mediator to establish whether the intervention is effective in each subgroup, acknowledging 
that we may be underpowered for some subgroups.  
Mediation analysis:  To assess whether our intervention improved cessation outcomes via the proposed 
mediators, we will perform mediation analyses using both the criteria of Baron & Kenny100  and Holmbeck.101  
As our outcome variables are dichotomous, we will apply the method of Huang et al.,102 which involves a system 
of logistic regression models and the Monte Carlo method to assess posterior distributions of the direct, indirect, 
and relative indirect effects. Three sets of logistic regression analyses will be performed, as the variables of 
interest; outcome, intervention and mediator are mainly categorical. The first 2 steps are to assess the 
intervention effects on the outcome and the mediator. In the third step, we will assess the relationship between 
each of the proposed mediators and the study outcome at each follow-up. The same 3 steps will be repeated 
with adjustment for potential confounders and/or moderators as determined from analysis for Hypothesis 3. The 
mediating variables that will be considered are: perception of child’s risk from SHSe and the benefits to the child 
of quitting, also motivation to quit, self-efficacy.  Moderating variables are household smokers, financial strain, , 
nicotine dependence, and prior quit attempts. 
In the final analysis, the entire theoretical model to predict outcome will be examined using structural equation 
modeling (SEM). The strength of SEM in examining the entire model is that this method allows for the analysis 
of a hypothesized pattern of directional and non-directional linear relationships among a set of latent variables 
(e.g., caregiver beliefs about their child’s SHSe risk) and measured variables (e.g., point prevalence).103 This 
approach will allow us to examine the effect of perceived risk of SHSe and perceived child benefits of quitting; 
we will incorporate the former as latent variables over the study period. We will also be able to examine the 
relative relationship of caregiver’s beliefs and readiness to quit with the outcome of cessation. 
Analyses for Secondary Aim 1. Working closely with Dr. Laura Akers (health services and economic consultant), 
we will collect the cost data needed to conduct a cost analysis of the SBIRT intervention. The cost inventory may 
include costs and charges from the baseline PED visit and hospitalization (if the child is hospitalized) and from 
SHSe-related PED visits or hospitalizations for the period 6 months before and 6 months after the baseline visit. 
The cost inventory will also include data collected from CRCs and clinical counselors/intake 
coordinators/research coordinators in both conditions about cessation-related activities and expenses, self-
reported abstinence, and use of all tobacco products at each follow-up. Cost inputs will include staff time for 
tobacco screening, chart flagging, cessation counseling, giving informational materials and NRT, and referral to 
the QL, smokefreeTXT, or smokefree.gov.  To determine costs of SHSe-related PED visits and hospitalizations 

 
Version:  10Dec2021 
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at CCHMC, clinical and cost/charges data will be collected from hospital records for the 6 month period before 
and after baseline for SHSe-related illness PED visits and hospitalizations such as asthma, and compiling the 
associated costs    We anticipate that the main cost component for intervention delivery will be the minutes the 
clinical counselors/intake coordinators/research coordinators spends in counseling. Although the intervention 
will occur during the time the patient is waiting for care, the time the clinical counselor/intake coordinator/research 
coordinator spends represents an opportunity cost of other alternative ways of spending this time with caregivers 
and should be tracked for inclusion in the cost-effectiveness analysis. Because the intervention will be delivered 
during visits of normal length, we do not anticipate that PEDs will incur any other overhead costs (e.g., facilities) 
due to adoption of the intervention. It is possible that a final version of the SBIRT will require changes in CMS 
billing codes to accommodate payment for the service. It is premature to determine this now, and establishment 
of the evidence-base of the intervention is required to provide a justification for a full review of coding options. 
As we conduct the cost analysis, we will conduct a preliminary review of coding options in anticipation of 
continued empirical work with the SBIRT to optimize its adoptability in PED settings.  
Procedures for Secondary Aim 2.  If successful, using the findings from this project and our prior research, we 
will develop a manual of operations that will enable other PEDs and EDs to adapt and implement the intervention 
in their setting. Using the CEASE program as a model,55 this manual of operations will include step-by-step 
guides with tips and techniques for successful implementation of the intervention. This information will include 
how to obtain buy-in of policy/decision makers, clinicians, and ancillary staff members, and how to gather 
information from clinicians and staff on adapting the intervention for use in their site (e.g., taking into account 
differences in PED patient flow, patient acuity, PED operations, and PED staffing). The manual of operations will 
also include all provider training materials and intervention guides (e.g., screening for tobacco use, brief intake 
assessments, instructions on how to give the 3As, motivational interviewing tips, referral resources, and 
cessation medication prescribing). In addition, we will provide a comprehensive package of patient materials 
refined during the trial, such as fact sheets (e.g., health effects of SHSe, how to implement a home smoking ban) 
and cessation referral resources. Finally, we will include all assessments to allow local evaluation of program 
results.   
Analysis for Secondary Aim 3.  For the analysis of the CSE study aim, we will calculate descriptive statistics 
including means, confidence intervals, medians, and interquartile ranges of reported and biochemically 
measured CSE and SHSe.  Logarithmical transformation of the biomarkers may be performed to control for 
nonnormality and unequal variances.  We plan to perform a series of logistic or linear regression models (as 
appropriate) to assess the associations between reported and biochemically measured CSE and SHSe and 
child sociodemographics and other characteristics, and household smoking behavior.  We will fit linear and 
logistic regression models (as appropriate) to examine the effect reported and biochemically measured CSE 
and SHSe has on health effects and healthcare utilization.  We will also assess correlations of child SHSe and 
CSE.  We will consider using other appropriate models based on the nature of the data (e.g., fixed effects 
models, Poisson regression). 
Analysis for Exploratory Aim. For our primary goals, we will detect genomic features that distinguish TSE by 
a 2-fold change with P value < 0.05. For a clinical biomarker, it will be important that there is a large enough 
effect size to be useful in a clinical setting; thus, our pilot study is powered to give us the data we need to see if 
any robust effects warrant further study and replication. In addition to our genome-wide analysis, we will 
especially focus on those loci with significance in previous studies of TSE. Principal component analysis and 
unsupervised hierarchical clustering will be used to statistically distinguish patients and controls as assessed 
by a subsequent ROC analysis. Pathway analysis will be performed to identify groups of genes with similar 
functions or that act in the same biological pathway. We will also specifically evaluate changes in genes found 
to be altered in previous studies.  
 
 
CONFIDENTIALITY/SECURITY 
     All measures will be taken to ensure patient confidentiality. All information will be used for scientific 
purposes only. Only the primary investigator, co-investigators, and trained study staff will have direct access to 

 
Version:  10Dec2021 
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data collected. 
All study participants will complete the baseline questionnaire on a web-enabled tablet computer provided by 
the study. All study data will be collected and managed using REDCap. The CRC will collect the electronic 
participant surveys and she/he will store them in a secure data center located at CCHMC. Access to the 
firewalled data by the CCHMC research team is possible only through user specific usernames and 
passwords. Follow-up surveys will be completed in-person for all caregivers or prompted by a phone call or by 
an email that will contain a participant specific, REDCap survey link. No identifying information will be 
contained on the follow-up surveys; surveys will be identified only by an ID number. Timing of caregiver follow-
up assessments will be linked to the date of enrollment.  
 
Data safety and monitoring will be managed by the study staff, in accordance with the CCHMC Research 
Policy for reporting unanticipated events (CCHMC R-18).   
 
The participants will be informed in the consent form regarding limits of confidentiality.  Because of the 
potential legal implications of marijuana use, a Certificate of Confidentiality will be obtained from the U.S. 
Department of Health and Human Services for this study. Participant confidentiality will be breeched only to 
protect the safety and welfare of research participants and only in accordance with state and federal law.  
Participants will be made aware of this policy at the commencement of their involvement in the study. 
 
 
LOCAL FACILITIES/PERFORMANCE SITES  
This research will take place at CCHMC. Participants will be recruited and enrolled in the Emergency 
Department and/or Urgent Care.  The data will be stored and analyzed at CCHMC. 
 
 
FUNDING PLAN 
A grant from the National Institutes of Health/National Cancer Institute (1R01HD083354) was funded with a 
start date of August 1, 2015.   
COMPENSATION 
 _ENREF_92Payment for follow-up will be as follows:  
$20 for completing initial baseline assessment; $10 additional, if a urine sample is obtained. 
$20 for completing the 6-week follow-up questionnaire  
$30 for completing the 6-week follow-up home/other location visit; $10 additional if a urine 
sample is obtained; 
$30 for completing the 6-month follow-up questionnaire and $35 for completing the 6-month follow-up  
home/other location visit, if applicable.  An additional $10 will be given to participants who provide urine 
at this visit.   
$10 bonus for completing both follow-ups.  Completion bonus will be given if participants complete both the six 
week questionnaire and home visit as well as the 6 month questionnaire and home visit (if applicable). 
Additional payments for urine samples will be provided based on the schedule above.  This additional incentive 
is being added to encourage participants to provide urine samples because the rate of collection of urine 
samples for this study is low. The need to include this additional incentive was not anticipated prior to this point 
in the study.    
METHOD TO BE USED IN PROCURING CONSENT OF SUBJECTS 
Caregivers who meet inclusion criteria will be approached by the CRC or investigator. Written informed 
consent will be obtained from the parent/legal guardian.  Parents will be asked if they agree to have any of 
their child’s leftover saliva stored indefinitely for future research. Parents will be asked to initial their consent for 
this part of the study in the consent form.  Assent will be obtained from all children over age 10. 

 
Version:  10Dec2021 
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When child participants turn 18 years of age during the course of the study we will attempt to re-consent them 
until the participant has exceeded the window for the last data collection timepoint.  When child participants 
turn 18 years of age after the study has been completed, we will send them a letter describing the study 
procedures and give them the option to have their samples that have been stripped of personal identifiers 
destroyed rather than saved for future research.   
 
DATA SAFETY AND MONITORING PLAN 
The DSM Board will consist of individuals with expertise in behavioral research and human subject protection.   
The first meeting of the DSM Board for this project would occur shortly after recruitment begins. The first 
meeting would be devoted to reviewing study protocols, including plans for human subjects, and determining the 
frequency and content of interim data analyses (if warranted). Subsequent meetings would occur as determined 
by the DSMB at their first meeting, but will occur at least annually. During these subsequent meetings, the DSMB 
will evaluate various aspects of the trial, including progress, data quality, recruitment, etc. The DSMB, together 
with the IRB, will review the rates of adverse events and serious adverse events and provide recommendations 
to the PI for protocol revision or trial stopping. The PI will inform NIH of any significant action taken as a result of 
the DSMB finding. 
Frequency of DSM Reviews   
The Principal Investigator will monitor the data safety and efficacy of this trial on an on-going basis, 
implementing the Data and Safety Monitoring Plan (DSMP), and complying with the reporting requirements. The 
IRB or DSM Board may request more frequent reviews (based on reported Adverse Events or Serious Adverse 
Events or for other reasons), with which Dr. Mahabee-Gittens will comply. 
Collection and Reporting of AEs and SAEs 
For purposes of monitoring and reporting adverse events, the following NIH definitions will be used: “Adverse            
event (AE): Any untoward medical occurrence that may present itself during treatment or administration of an 
intervention, and which may or may not have a causal relationship with the treatment.” “Serious adverse event 
(SAE): Any medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or 
prolongation of existing hospitalization; creates persistent or significant disability/incapacity, or a congenital 
anomaly/birth defects.” 
We do NOT anticipate any SAEs to be reported as a result of participation in this study. If a subject experiences 
any AEs/SAEs as a result of this study, all study staff will be trained by the PI to report these events to their CRC 
or use the toll-free phone number to contact the PI or the IRB at CCHMC directly within 24 hours of report of the 
event. If an AE or SAE is reported to the CRC, the CRC must report the event to the PI within 24 hours of 
notification. Patients may report AEs or SAEs directly to CCHMC via a local phone number available in their 
copy of the consent form.  
The PI will report any AEs/SAEs to the CCHMC IRB within 24 hours of receipt of report from any source.  AEs 
and SAEs will be reviewed by the IRB and/or the DSMB in a timely manner (depending on the severity of the 
event). All AEs and SAEs will be reported to NIH at a minimum in the annual progress report, or within 24 
hours depending on the severity of the event. 
Reporting Mechanisms of AEs/SAEs to the IRB, FDA, and NIH 
All study CRCs will be trained to report any adverse event regarding patients enrolled in the study. These 
events would include severe withdrawal symptoms, reaction to use of nicotine replacement products, severe 
illnesses or death (from any cause).  
Study staff may contact the PI in person, or the IRB at CCHMC directly within 24 hours of report of the event. 
If an AE or SAE is reported to the CRC, the CRC must report the event to the PI within 24 hours of notification. 
Caregivers may report AEs or SAEs to the PI either in person or using the local study number to contact the 
PI or IRB at CCHMC directly. The Principal Investigator will report any AEs/SAEs to the CCHMC IRB within 24 
hours of receipt of report from the subject. AEs and SAEs will be reviewed by the IRB and/or the DSMB in a 

 
Version:  10Dec2021 
Page 21 of 25 
timely manner (depending on the severity of the event). All AEs and SAEs will be reported to NIH at a minimum 
in the annual progress report, or within 24 hours depending on the severity of the event. 
Reporting Mechanisms of IRB Actions to NIH 
Any IRB action that results in stopping or significantly altering the trial will immediately be reported (within 24 
hours of notification) to NIH by the CCHMC IRB Administrator. 
Report of Changes or Amendments to the Protocol 
The Principal Investigator will report and seek approval of the CCHMC IRB for any changes to the study 
protocol. A significant alteration of the study protocol will be reported to NIH by the IRB Administrator 
immediately. 
FDA Regulated Research 
Nicotine, an FDA-approved drug, does not require an Investigation New Drug (IND) application with the FDA, 
as the use in the current research is consistent with currently approved indications by the FDA. 
 
APPENDICES 
 
 
Appendix A:  (Baseline Assessment):  Intervention to Reduce SHSe 
 
Appendix B:  SBIRT Materials 
 
Appendix C:  HHC Materials 
  
Appendix D:  Caregiver Locator and Demographic Screener 
 
Appendix E:  Eligibility Screener 
 
Appendix F:  NRT Checklist and Receipt Documentation 
 
Appendix G:  Six Week Assessment 
 
Appendix H:  Six Month Assessment 
 
Appendix I:  NRT Checklist and Receipt Documentation- 6 Weeks 
 
 
 
 
 
 
 
 
 
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