Developing and Testing Waterpipe-specific Health Warning Labels Targeting Young People in Florida
Phase: NA
Conditions: Waterpipe Smoking, Health Warning Label, Harm Perception, Puffing Behaviour, Quitting Smoking, Health Risk Behaviors
Sponsor: Florida International University

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Study protocol with statistical analysis plan 
Official Title of the study: Understanding health warning effects on waterpipe (hookah) smokers’ 
experiences and exposures   
NCT number: Not applicable   
Date of the document: November 13, 2020

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Title: Developing and testing waterpipe-specific health warning labels targeting young 
people in Florida. 
 
 

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General Audience Abstract: (3,492/3,500 characters)  
Waterpipe (WP) smoking (a.k.a. hookah) has become one of the leading tobacco use methods 
among youth in Florida. The impact of this dramatic rise is likely amplified by the mounting 
evidence of WP addictive and harmful nature, as well as the lag of policy response to it. 
Evidence suggests WP use leads to nicotine addiction, and increases the risk of lung cancer, 
heart and respiratory disease and exposure to secondhand smoke. The spread of WP use 
among youth has been fueled by a misperception of reduced-harm compared to cigarettes. 
Health Warning Labels (HWLs) represent one of the most successful tobacco control strategies 
to communicate smoking-related risks, and studies have consistently shown that HWLs are 
associated with a decrease in smoking rates and smoking-related morbidity and mortality. 
Therefore, communicating WP risks to young people through HWLs has been identified as a 
priority by major health bodies in the US including the FDA.   
Currently, the FDA requires that WP tobacco packages have a textual HWL: “WARNING: This 
product contains nicotine. Nicotine is an addictive chemical.” While this represents a good step, 
it is inadequate given the; 1- limited contact WP smokers have with tobacco packaging, 2- the 
established harm of WP smoking beyond tobacco (e.g., charcoal), and 3- the superior 
performance of pictorial HWLs over text-only ones. Therefore, pictorial WP-specific HWLs 
involving other WP components (e.g. device) are expected to be more effective in 
communicating risks to WP smokers. Using the Delphi method among tobacco control experts, 
our team has developed a set of 12 WP HWLs corresponding to 4 health themes (health risks 
and addiction, harm to others, WP-specific harm, WP harm compared to cigarettes).  
 
Building on this work, and using a mixed-method approach incorporating qualitative and 
quantitative research, we propose to adapt the developed HWLs to young WP smokers in 
Florida and test them to answer an important policy question: Are pictorial HWLs on the WP 
device more effective than no-HWL (control) in increasing harm perception and intention to quit, 
and reducing smoking satisfaction, intensity, and exposure to toxicants? Accordingly, we will 
recruit young (18-29 yrs) WP users to:  
1. Conduct 6-8 mixed-gender focus groups (n ≈ 65) to adapt the 12 HWLs to our local 
population of young adults on risk communication, explore optimal HWLs placement and 
size, and select the top 4 HWLs for testing in Aim 2.  
2. Conduct a clinical lab experiment among 248 WP smokers categorized according their use 
frequency (beginner vs. established smokers) to test the performance of the top 4 HWLs on 
the WP device compared to no-HWL (control) on harm perception, intention to quit, puffing 
behavior, dependence (e.g. satisfaction, withdrawal), and toxicant exposure (CO, nicotine, 
oxidative stress). Three months later, participants will receive a phone call to assess longer-
term adaptations as a result of exposure to HWLs (e.g. quit intention, quitting). 
3. Partner with Golin, Tobacco-Free Workgroup, and Truth Initiative to advocate for the 
adoption of HWLs policies and disseminate knowledge about WP harmful effects to young 
people in Florida and nationally. 
Communicating WP risks through HWLs promises to reduce WP use and WP-related morbidly 
and mortality among young adults in Florida. This pioneering work will provide the first 
evidence-based WP HWLs to advance WP control in Florida, and a model for other states to 
respond to the WP epidemic.  
 
 

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Scientific Abstract: (2,083/2,100 characters) 
Waterpipe (WP) smoking has become one of the leading tobacco use methods among youth in 
Florida. The impact of this dramatic rise is amplified by the mounting evidence of WP addictive 
and harmful nature, as well as the lag of policy response to it. Evidence suggests WP use leads 
to nicotine addiction, and increases the risk of lung cancer, heart and respiratory disease and 
exposure to secondhand smoke. The spread of WP use among youth has been fueled by a 
misperception of reduced-harm compared to cigarettes. Health Warning Labels (HWLs) 
represent one of the most successful tobacco control strategies to communicate smoking-
related risks, and studies have consistently shown that HWLs are associated with a decrease in 
smoking rates and smoking-related morbidity and mortality. Therefore, communicating WP risks 
to young people through HWLs has been identified as a priority by major health bodies in the 
US including the FDA.   
Using the Delphi method among international tobacco control experts, our team has developed 
a set of 12 WP HWLs corresponding to 4 health themes; health risks/addiction, harm to others, 
WP-specific harm, WP harm compared to cigarettes. Building on this work, and using a mixed-
method approach incorporating qualitative and quantitative research, we propose to: 
Aim 1: Adapt the 12 HWLs to young WP smokers in Florida using exploratory focus groups.  
Aim 2: Test in a clinical lab experiment the performance of the top 4 HWLs on the WP device 
compared to no-HWL/control on harm perception, intention to quit, and toxicant exposure (CO, 
nicotine, oxidative stress).  
Aim 3: Use the knowledge obtained to advocate for the adoption of WP-HWLs policies and 
disseminate information about WP harmful effects to young people in Florida and nationally.  
Communicating WP risks through HWLs promises to reduce WP use and WP-related morbidly 
and mortality among young adults in Florida. This pioneering work will inform the FDA and 
public health advocates on the potential of WP-HWLs policies and provide a model for other 
states to respond to the WP epidemic.  
  
 
 
 

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Health Impact: (3,464/3,500) characters  
The rise of waterpipe smoking among young people in the US has been fueled by a widespread 
misperception of “reduced-harm” compared to cigarettes (Bhatnagar 2019). Evidence suggests 
WP smoking carries similar health risks as cigarettes. Moreover, unique risks of WP can stem 
from the contribution of charcoal (e.g. carcinogens), device and accessories (e.g. infectious 
disease) (CDC 2018). Compared to one cigarette, a single WP session involves exposure to 
150-180 times the amount of smoke (≈90,000 ml of smoke for WP vs. 500-600 ml for 
cigarettes), 1.7 times the nicotine, 8.4 times the CO, and 36 times the tar (Cobb 2010). 
Evidence from systematic reviews shows that WP smoking is associated with increased risk of 
lung cancer, and major cardio-pulmonary diseases (Jawad 2013, El-Zaatari 2015, Waziry 2016).  
Given that health warning labels (HWLs) represent a cornerstone strategy to communicate 
smoking-related risks and reduce cigarette-related morbidity and mortality (Noar 2016, a), 
leading public health and tobacco control bodies in the US consistently advocated for WP-
specific HWLs as a priority to reduce WP smoking and related health risks (CTP-FDA 2012, 
WHO 2015, FDA 2017). However, there have been no systematic efforts to develop WP-specific 
HWLs. Our team has started to address this gap, and this project builds on that work to develop 
pictorial WP-HWLs with the involvement of young WP smokers in Florida. We will then test 
these HWLs on important policy/regulatory outcomes (e.g., harm perception, intention to quit, 
exposure to toxicants).  
Communicating WP associated risks through HWLs promises to reduce WP smoking and WP-
related morbidly and mortality in Florida and nationally. Experience with using HWLs for 
cigarettes in Canada for example has resulted in 12-20% reduction in smoking prevalence and 
nearly 5,000 fewer smoking-attributable deaths annually (Azagba 2012, Huang 2014). Similarly, 
implementing HWLs policy in Ireland and the Netherlands in 2008 resulted in 464,493 fewer 
smoking-attributable deaths by 2010 (Nagelhout 2012, Currie 2013).  
HWLs can be expected to reduce tobacco-related health disparity as well, since their effect on 
reducing smoking-associated deaths was stronger among lower socio-economic groups in 
several countries, including the US (Van Minh , Mead 2015). Moreover, concerns about the 
“wear out” of HWLs effect is not substantiated by evidence, which shows that such effect is 
sustained years after the policy implementation (Huang 2014, Van Minh 2016). Even among 
those who tried to avoid noticing the HWLs, smoking prevalence was reduced by 12% and 
intention to quit increased 1.5 times two years after the HWLs implementation (Van Minh). 
This project will provide WP HWLs adapted for young WP smokers in Florida to advance WP-
HWLs policies and disseminate knowledge about WP harmful effects to young people in Florida 
and nationally. We expect our work to inform the FDA, policymakers and public health 
advocates on the potential of WP HWLs to curtail WP smoking and protect young people from 
this emerging public health problem. We also expect this work to become the foundation for 
further research in this field to evaluate other domains related to WP-HWLs, such as WP 
venues-based warnings (e.g. on the menu), and web-based warnings for WP café’s websites 
and WP internet retailers. 
 
 

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Tobacco Relatedness: (1971/2,100 characters) 
Compared to nonsmokers, WP smokers have a 2-3 times increase in respiratory disease (e.g., 
COPD), 4 times increase in oral cancer risk, 2 times increase in lung cancer, and 3 times 
increase in cardiovascular disease (Jawad 2013, El-Zaatari 2015, Waziry 2016). Furthermore, 
the use of charcoal to heat the tobacco in the WP results in additional exposures to high levels 
of carbon monoxide, metals, and cancer-causing chemicals (Monzer 2008, Nguyen 2013, CDC 
2018). Smoking in a group setting and sharing the same WP can furthermore, expose users to 
communicable diseases risks (e.g., tuberculosis, herpes) (Martin 2009, CDC 2018). WP 
smoking also releases secondhand smoke, which can be a health risk particularly to children 
living in WP smoking homes (Fromme 2009). Therefore,  this project is highly responsive to 
tobacco-related cancer, cardiovascular and pulmonary disease.  
WP-related health-damaging profile is consistent with the health effects of cigarette smoking, 
indicating that WP smoking is an important tobacco-related public health problem. By 
communicating these risks and providing evidence of effective ways to reduce WP smoking, WP 
smokers, public health advocates, and policymakers can start responding to the WP epidemic 
among young people in Florida and the US. Applying HWLs on cigarette packages was effective 
in reducing cigarettes smoking and its related health risk (Noar 2016, a). Similarly, adopting 
HWLs for the WP promises to impact smokers, and reduce WP smoking-related morbidity and 
mortality. This pioneering project will generate pictorial HWLs for the WP developed with the 
involvement of the target population, and tested on a variety of important policy/regulatory 
outcomes (e.g., harm perception, intention to quit, exposure to toxicants). Findings from this 
project will help advocate for the adoption of WP-specific HWLs and disseminate knowledge 
about WP harmful effects to young people in Florida and nationally.  
 
 
 

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Specific Aims: 2,081/2,100 characters 
Our Team developed 12 pictorial Health Warning Labels (HWLs) for the waterpipe (WP) 
corresponding to 4 themes; health risks/addiction, harm to others, specific harm, and harm 
compared to cigarettes. We will build on this work to advance HWLs policies and disseminate 
knowledge about WP harmful effects to young people in Florida and nationally through the 
following specific aims: 
1. Adapt the HWLs to young adults in Florida using focus groups. We will conduct mixed-
gender focus groups combined with brief survey with regular WP smokers (6-8 groups; n ≈ 
65; age 18-29 yrs) to 1- adapt the 12 HWLs to our target population, 2- explore their optimal 
placement and size, and 3- select the top 4 HWLs for testing (Aim 2). 
2. Test the top 4 HWLs in a clinical lab experiment. Using the top 4 HWLs on the device, we 
will recruit 2 groups of WP smokers (n= 248; age 18-29 yrs) based on their use frequency 
(beginners, established) for a within- (HWL vs no-HWL; pre- vs post- smoking) and 
between-subject (beginner vs. established; 4 HWLs) experiment. Participants will be 
randomly assigned to one of the 4 HWLs conditions and undergo 2 smoking sessions that 
differ by HWL (HWL vs. no-HWL), with pre-post smoking assessment of harm perception, 
intention to quit, and toxicant exposure. Participants will receive a follow-up phone call 3-
month after exposure to assess longer-term changes in quit attitude and behavior. We 
hypothesize that applying pictorial HWLs to the WP device will; 1- significantly increase 
harm perception and intention to quit, and reduce puffing behavior, satisfaction, and 
exposure to toxicants compared to no-HWL; 2- this effect will be more pronounced in 
beginner than established smokers.   
3. Disseminate knowledge. We will partner with Golin, Tobacco-Free Workgroup, and Truth 
Initiative to advocate for the adoption of HWLs policies and disseminate knowledge about 
WP harmful effects to young people in Florida and nationally. 
Impact: Communicating WP risks through HWLs promises to reduce WP use and WP-related 
morbidly and mortality among young adults in the US.  
 
 

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Research Strategy (68,000 characters) 69,450 
A. SIGNIFICANCE  
This application is a resubmission. We thank the reviewers for their constructive comments and 
positive evaluation of our application. It was encouraging that the reviewers identified several 
strengths and the overall value of our proposal and gave it an “Outstanding” total impact score 
of “2”. We equally recognize our application shortcomings identified by the reviewers and tried 
our best to respond to them thoroughly in this resubmission. Our response letter provides a 
summary of changes made (pls. see response letter), while the revisions introduced in the 
proposal are marked by italics. 
In the WP commonly used today, charcoal-heated air passes through the tobacco mixture to 
generate smoke that passes through water on its way to the smoker (Figure 1). Multiple 
surveillance data from Florida, show that WP smoking has become one of the leading tobacco 
use methods among youth. This dramatic rise of WP is amplified by the mounting evidence of 
its addictive and harmful nature, as well as the lag of policy response to it (Gathuru 2015, Sutfin 
2017). Evidence suggests that WP smoking is associated with increased risk of lung cancer, 
and major cardio-pulmonary diseases (Jawad 2013, El-Zaatari 2015, Waziry 2016). 
Recognizing the threat of WP to people’s health in the US, the FDA has recently extended its 
regulatory authority under the Tobacco Control Act (TCA) to cover WP products including WP 
tobacco, device and accessories (FDA 2017). This important development created the need for 
evidence to guide the implementation of effective policies to reduce WP use in the US.  
WP smoking rise among young people in Florida and nationally has been fueled by a 
widespread misperception of “reduced-harm” compared to cigarettes (Haddad 2015, Maziak 
2015, a, Bhatnagar 2019). Given that health warning labels (HWLs) represent a cornerstone 
strategy to communicate smoking-related risks and reduce tobacco use globally, leading public 
health authorities consistently recognize the importance WP-specific HWLs as a priority for 
reducing WP use (FDA 2017). In fact, the first measure adopted by the FDA to control WP 
smoking was requiring a text HWL on WP tobacco; “WARNING: This product contains nicotine. 
Nicotine is an addictive chemical” (FDA 2017). While a good first step, it is inadequate given: 1- 
the superior performance of pictorial HWLs over text, 2- the limited contact of WP users with the 
tobacco package in the popular WP/hookah café, and 3- the established toxic exposures and 
health effects of WP smoking beyond nicotine (e.g. from charcoal) (Salloum 2016, Sutfin 2017). 
The long contact with the device itself during a 1-hour average smoking cession moreover, 
provides a unique opportunity to engage WP smokers with health messages. Therefore, 
applying pictorial HWLs on the WP device is a promising tool to communicate the risks of WP 
smoking.  
Our project promises to stimulate the implementation of WP-HWLs control in Florida and 
nationally and provides a model for other states and jurisdictions to consider such interventions 
to protect their youth. This is consistent with the FDA mandate to establish HWLs on other 
tobacco products (e.g., WP), which also allows state and local authorities to impose warning 
requirements other than those on the tobacco product itself (e.g. HWLs on the WP device can 
be locally legislated) (FDA 2009). Thus, the scientific premise of our proposal are: 
1. WP smoking is an important public health problem in Florida. 
2. HWLs represent a priority strategy to curb WP smoking.  
3. HWLs are effective in reducing smoking rates and its related morbidity and mortality.  
4. The importance of the device as an optimal placement for WP HWLs.  
5. The importance of evidence dissemination to advance WP control in Florida and nationally. 
These areas are discussed briefly below. 

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A.1. WP smoking is an important public health problem in Florida. WP smoking in Florida 
is increasing dramatically, particularly in youth and young people. Data from the Florida Youth 
Tobacco Survey show that WP smoking in 2017 has exceeded cigarette smoking and become 
the No. 2 tobacco use among high school students (only behind e-cigarettes) for ever use 
(32.1% e-cigarette, 20.4% WP, and 18.6% cigarette) and past-month use (15.7% e-cigarette, 
6.2% WP, 4.2% cigarettes) (Florida Department of Health 2018) (Figure 2). Evidence from 
college students in Florida shows similar trends, where among 1,203 students at the University 
of Florida, WP smoking exceeded cigarette smoking for ever (46.4% vs. 42.1%) and past-year 
use (28.4% vs. 19.6%) (Barnett 2013). Evidence from 1,539 students (18-23 yrs.) at the 
University of Tampa shows that ever WP use reached 64%, a third of whom (34%) were current 
WP smokers (Martinasek 2016). WP smoking carries similar, or potentially more health risks 
than cigarettes, due to the added contribution of charcoal (e.g. carcinogens), device and 
accessories (e.g. infectious disease) (CDC 2018). WP use leads to nicotine addiction, and 
increases the risk of cancer, chronic diseases, and exposure to secondhand smoke (American 
Lung Association 2007, Waziry 2016, Awan 2017). More worrisome is the evidence that WP 
smoking can roll back successes achieved in tobacco control by providing a gateway to 
cigarettes smoking among youth (Soneji 2015). Thus, WP smoking has rapidly become a public 
health problem among young people in Florida and requires urgent evidence-based solutions.  
A.2. HWLs represent a priority strategy to curb WP smoking. Partially attributed to the 
“filtering” effect of passing smoke through water, many consider WP smoking to be a safer 
alternative to cigarettes (Haddad 2015). Studies among college students in Florida show that 
compared to cigarettes, WP smokers have positive perceptions about it, and that these 
favorable perceptions were predicting future WP use in longitudinal studies (Sidani 2013, 
Castañeda 2016, Barnett 2017). Therefore, communicating the health risks of WP smoking to 
young people represents an important avenue for WP control (Cornacchione 2016, Lopez 
2017). Applying HWLs on cigarettes packages was effective in raising awareness about 
smoking harms, preventing initiation and encouraging smoking cessation (Brewer 2016, Noar 
2016, b). However, similar evidence regarding the effect of HWLs on WP smoking is still 
lacking. Given that HWLs represent a cornerstone strategy to communicate smoking-related 
risks and reduce tobacco use globally, leading public health authorities and scientists 
consistently recognized HWLs as a priority strategy to reduce WP smoking (Salloum 2016, FDA 
2017).  
A.3. HWLs are effective in reducing smoking rates and smoking-related morbidity and 
mortality. Studies have shown consistently that HWLs are associated with a decrease in 
smoking rates and smoking-related morbidity and mortality. For example, adopting HWLs policy 
on cigarette packages in Canada resulted in 12-20% reduction in smoking prevalence and 
nearly 5,000 fewer smoking-related deaths annually (Azagba 2012, Huang 2014). Similarly, 
implementing HWLs policy in 1998 in Ireland and Netherlands resulted in almost 464,493 fewer 
smoking-related deaths by 2010 (Nagelhout 2012, Currie 2013). In addition, 25% to 60% of 
youth in Canada, the United Kingdom, and Australia reported that HWLs helped prevent them 
from initiating smoking (Green 2014). Moreover, HWLs policies are expected to reduce tobacco-
related health disparity, as their effect on reducing smoking-related deaths was stronger among 
lower socio-economic groups in several countries, including the US (Mead 2015, Van Minh 
2016). Concerns about the “wear out” of HWLs effect are not substantiated by evidence, which 
shows that such effect is sustained years after the policy implementation (Van Minh et al., 
Huang et al. 2014). Even among those who tried to avoid noticing the HWLs, smoking 
prevalence was reduced by 12% and intention to quit increased 1.5 times 2 years after the 
policy implementation (Van Minh 2016).  

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A.4. The importance of the device as an optimal placement for WP HWLs. WP’s multiple-
components, limited portability, and intermittent, yet long use sessions (≈1 hour) create a unique 
product configuration and use-setting that is very different from cigarettes (Salloum 2016, Lopez 
2017). A recent review of the challenges facing WP regulation in the US suggests that the 
current FDA text warning about nicotine on WP tobacco is inadequate given the: 1- limited 
contact with tobacco packaging in the common WP café setting; 2- established toxic exposures 
and health effects of WP smoking beyond nicotine (e.g., WP charcoal is a major source of 
carcinogens); 3- substantial body of evidence showing the superior performance of pictorial 
HWLs over text ones (Gathuru 2015, Sutfin 2017). Thus, the prolonged contact of consumers 
with the WP device during an average 1-hour smoking session provides a unique opportunity for 
extended engagement of consumers with HWLs (Maziak 2019, b). WP café setting represents a 
unique vector for the WP epidemic among youth (Bahelah 2018, Asfar 2019). For example, WP 
bars and cafés were reported as a usual place to smoke among 59.1% of men and 72.6% of 
women (18-24 years) in the US (Salloum 2017). Consumers in the WP café setting are usually 
not in contact with the tobacco packaging, where HWLs are usually positioned (Salloum 2017). 
A recent qualitative study in Egypt suggests that placing HWLs on the WP devices might 
increase salience, prevent initiation or trigger quit attempts (Mostafa 2018). 
A.5. The importance of evidence dissemination to advance WP control in Florida and 
nationally. There has been much debate recently about the “translation gap” between research 
evidence and their application (Brownson 2018). This is mainly due to researchers focusing on 
only peer-reviewed publications and scientific conferences to disseminate their research 
findings. While scientific publications are important, policy/regulatory relevant research needs to 
go beyond these channels to try to induce real change and help translate research evidence 
into strategies to improve people’s health (Bero 1998, Brownson 2017, Brownson 2018). In this 
project, we have partnered with health communication specialists and media developers with 
years of tobacco control experience in Florida (Goline) and nationally (Truth Initiatives) to 
communicate our research findings to two main end-users; 1- legislators and policymakers, and 
2- young people in Florida and nationally. We have also partnered with a broad scope of public 
health organizations in Florida to help disseminate our findings and advocate for the 
implementation of HWLs to curb WP smoking.  
Summary: This application is responsive to the dramatic popularity of WP smoking among 
young people in Florida and the urgent need for evidence-based solutions to help the state 
respond. Given the widespread misperception of reduced-harm among WP smokers, the 
prolonged contact of smokers with the WP device, and the established effect of HWLs on 
reducing tobacco use and its related morbidity and mortality, communicating WP risks through 
HWLs on the device represents a promising strategy for WP control. This project will provide 
tested WP HWLs to advocate for the adoption of WP-specific HWLs policies and disseminate 
knowledge about WP harmful effects to young people in Florida and nationally. This pioneering 
work will likely provide a model for other states to respond to the spread of WP smoking among 
their youth.  
B. INNOVATION 
There are two innovative aspects:  
B.1. Focusing on the application of HWLs on the device. HWLs are usually placed on the 
tobacco package (e.g. cigarette pack) (Hammond 2009, a), which is the placement for the 
current FDA WP text warning. However, given the multi-component nature of WP, and the 
importance of these components for smokers’ experience and exposures (Shihadeh 2005b, 
Asfar 2019), considering other WP components for the application of HWLs for the WP is 
needed (Salloum 2016, Salloum 2017). Recently, our team developed a WP-sensitive 

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framework to guide research into WP policies, emphasizing the importance of other WP 
components (e.g. device) for the placement of HWLs (Figure 3) (Salloum 2016). While testing 
all potential placements of HWLs is beyond this study, our decision to test the application of 
HWLs on the device is innovative and responsive to the unique configuration and use-setting of 
the WP.  
B.2. Using clinical lab methods to test the effect of HWLs on WP smokers, including 
Exhaled Breath Condensate (EBC) markers of oxidative stress. Clinical lab methods’ 
strength lies in their ability to provide quick and sensitive regulatory-relevant evidence, as the 
first testing of product modifications before real-life implementation (Breland 2006). However, 
such methods have not been applied to test the potential of HWLs for WP smokers. In 2016, 
Maziak received an R01 from FDA/NIDA (R01DA042477) to establish a clinical lab at Florida 
International University (FIU) and provide the FDA with evidence about the potential of flavor 
regulation for WP control (Ben Taleb 2018, Ben Taleb 2019, Maziak 2019, a). We will build on 
this investment to further advance important policy and regulatory avenues for the WP in 
Florida. Smoking a WP device fitted with HWLs will allow us to assess the effect of HWL on 
several important outcomes for WP control such as harm perception, intention to quit, puffing 
behavior, dependence measures (satisfaction, urge to smoke, withdrawal), and toxicant 
exposure (CO, nicotine, oxidative stress). Moreover, the use of novel and noninvasive EBC 
technology to look for markers of oxidative stress can provide valuable information about airway 
insult associated with WP smoking, and whether exposure to HWLs can ameliorate it (Figure 4). 
We will collect EBC and test it for 6 biomarkers (8-oxodGuo, 8-oxoGuo, 8-isoprostane, 
formaldehyde, acetaldehyde, and malondialdehyde) that are important for WP smoking (Hunt 
2002), and are predictive of long-term respiratory disease (Montuschi 2002).  
Summary: The originality of this project stems from its application of novel, WP-sensitive 
approach to provide pioneer evidence to guide the application of HWLs for WP products in 
Florida.  
C. APPROACH 
 
Despite the need to communicate WP risks to smokers, and the well-established effectiveness 
of HWLs in tobacco control, there have been no systematic efforts to develop HWLs for the WP 
(Islam 2016, Salloum 2016). In this proposal, we will apply a theory-guided, mixed-method 
approach to adapt and test HWLs for the WP. Current recommendations for designing and 
evaluating HWLs indicate the need to; 1- consider the target population’s perception of 
messages (Hammond 2009, b) in developing the HWL, and 2- to evaluat HWLs using a 
combination of qualitative evaluation, conducted while the HWLs are being developed, and 
quantitative evaluation and testing on the target population (Hammond 2008). In this project, we 
will follow these recommendations to adapt WP-HWLs to our target population of young adults 
in Florida and test them on policy-important and theory-driven outcomes in a clinical lab 
experiment. Our approach provides an optimal balance between qualitative assessments (focus 
groups) needed to get at our target population’s (young people in Florida) feedback about the 
HWLs, to quantitative assessment using experimental lab methods that allow for comprehensive 
and standardized testing of the developed HWLs. Such theory-driven, experimentally robust 
approach promises to provide the level of rigorous evidence needed to advance HWLs policy 
and regulation in Florida, and beyond.   
C.1. Preliminary Studies and Investigators.  
This project is a collaborative effort between investigators at the University of Miami (UM, 
Asfar), Florida International University (FIU, Maziak and Bursac), Florida Tobacco-Free 
Workgroup (Thurer), tobacco control media and advocacy specialist (Abrams; Golin), youth-
oriented anti-tobacco campaigns expert (Vallone; Truth Initiative), health communication 

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specialist from the University of Memphis (Schmidt), and FDA legal advisor (Lindblom). For the 
past decade, our team has been on the forefront of working together to provide evidence about 
WP harmful and addictive potential, and to elucidate its complex nature for regulatory/policy 
purposes. Since the main work of this application involves: 1) using qualitative research 
methods to develop the HWLs; 2) using clinical lab methods to test these HWLs; and 3) using 
communication approaches to disseminate research findings and advocate for policy change, 
below we summarize our experience in these 3 areas.  
C.1.1. Experience in applying qualitative methods to develop WP-related interventions. 
Asfar, Maziak, and Schmidt are long-time collaborators on NIH funded research and capacity-
building efforts to reduce WP smoking internationally. This team applied mixed qualitative and 
quantitative methods to understand WP smoking patterns and develop WP interventions 
(Maziak 2009, Asfar 2014, Asfar 2016). Asfar also led a thematic analysis of customers’ reviews 
of WP cafés in the US to identify factors contributing to their popularity. She showed that 
features related to WP’s 3 components; tobacco, device, and charcoal are important for 
consumers’ choice of WP cafés (Asfar 2019). Recently, our team was funded by NIH 
(R01TW010654) to develop WP-specific HWLs internationally. In this project, Asfar has led the 
first stage of developing 12 WP-HWLs using a Delphi study approach (Asfar 2019). First, we 
have developed 28 HWLs corresponding to 4 themes; health risks/addiction, harm to others, 
WP-specific harm, and WP harm compared to cigarettes. The top-ranked HWLs by an 
international expert panel in each theme were then selected for the final list of 12 HWLs (Figure 
5). These HWLs were then discussed in focus groups in 2 countries (Lebanon, Tunisia) for 
further adaptation to the target population (Ben Mansour 2019, Nakkash 2019). In this project, 
we build on this experience to systematically adapt and test these HWLs for young WP smokers 
in Florida. Schmidt, our public health graphic designer, has led over 60 health communication 
projects in various media platforms (graphic design, video, photography, animation) (Schmidt 
2008, Ullmann 2018). Thus, our team’s experience in WP science and in applying qualitative 
studies to adapt and further develop WP-specific HWLs demonstrate our ability to conduct the 
proposed Aim1. 
C.1.2. Experience in using clinical lab methods to provide evidence for WP regulation. 
Our team has pioneered the use of clinical lab methods to the study of WP, and has applied 
them recently to the study the potential of tobacco flavor regulation for the WP (Maziak 2009, 
Maziak 2019, a). In preparation for this application, Maziak and Asfar conducted a proof-of-
concept pilot study to test the potential effect of HWLs on the device on WP smokers’ 
satisfaction, and exposure to toxins (Maziak 2019, b). We recruited 30 WP smokers, who 
completed two, 45-minute ad libitum smoking sessions that differed by HWL undivided condition 
(with vs. without) in a crossover design study. Exhaled carbon monoxide (eCO) was measured 
before and after each smoking session, and participants completed questionnaires assessing 
their smoking experiences and perceptions. This pilot study showed that placing HWL on the 
WP device has the potential to reduce WP smoker’s positive experiences, and exposures (e.g. 
eCO). For example, we found lower levels of eCO following smoking the WP fitted with HWL 
(17.8 ppm) compared with smoking WP without HWL (24.5 ppm; P<0.05) (Figure 6). We will 
build on this experience by conducting a larger, well-powered, theory-driven study with a 
comprehensive assessment of change in harm perception and intention to quit, dependence, 
oxidative stress in EBC, and puffing behavior among young WP smokers in Florida.  
C.1.3. Experience in using communication approaches to disseminate research results 
and advocate for policy change. In the past 2 years, Maziak, Abrams, and Thurer have been 
collaborating to produce several educational videos about the harmful and addictive profile of 
WP smoking targeting different audiences (TV Channel 6). These videos have been used by 
Tobacco Free Florida to increase WP smokers and nonsmokers’ awareness about WP health 

13 
 
risk. In this application, we will build on this successful collaboration applying a more structured 
approach to disseminate our project results to wider audiences of policymakers, tobacco control 
advocates, public health organizations, and young adults. Vallone, our new collaborator from 
the Truth Initiative, is currently leading the evaluation of Truth®, one of the largest and most 
successful youth tobacco prevention campaigns (pls. see letter from Vallone). Vallone will use 
the messages and images we developed for the HWLs in their counter-tobacco campaigns, and 
evaluate them for harm perception and quit attitude as part of their standard evaluation (Vallone 
2017, a, Vallone 2017, b). Our team also includes Lindblom who served as Director of Office of 
Policy at FDA-CTP before joining Georgetown as Director of Tobacco Control and Food & Drug 
Law. Lindblom will guide our team on the legal aspects of applying HWLs to the WP consistent 
with FDA’s deeming rule, its statutory authorities, and state and local governments’ constraints 
(pls. see letter from Lindblom).  
Summary: Our team’s work on the WP spans more than a decade of research and theoretical 
developments using qualitative, quantitative, and clinical lab studies to inform the public and 
policymakers about WP smoking risks and effective interventions to reduce them. This 
experience and our leadership in the field of WP science will allow us to conduct the planned 
studies successfully.  
C.2. Conceptual model: For the evaluation of HWLs, we adopted the message impact 
framework that is based on communication (McGuire 1981, Petty 2018) and health behavior 
theories (Fishbein 1975), and has been used applied successfully in cigarette HWL research 
(Noar 2016, a). This model assumes that features of the HWLs will influence behavior through a 
chain of psychological events including how HWLs will: 1- attract smokers, 2- influence emotion 
(e.g. attention, fear), 3- affects cognitive reaction such as thinking about the risk (harm 
perception), then 4- intention to change the behavior (intention to quit), and ultimately 5- change 
behavior (e.g., reduce or quit smoking) (Figure 7). Our mixed-method approach will allow us to 
measure these outcomes throughout our proposed research. For example, Aim 1 will allow us to 
assess communication outcomes mainly (e.g. attention, reaction), while Aim 2 will allow us to 
measure additionally subjective and objective outcomes such as perceived harm, intention to 
quit, smoking behavior, and exposures. Applying a robust theoretical model, will allow us to 
study the effects of HWLs on important policy and regulatory outcomes, and suggest plausible 
mechanisms of HWLs action to advance HWL research. 
C.3. Considerations informing our approach:  
C.3.1. Participants. We are targeting young people aged 18-29 yrs, since this age group is 
particularly vulnerable to WP uptake and progression (Barnett 2017, Kasza 2017, Florida 
Department of Health 2018). As some of our outcomes in the lab study are related to nicotine 
dependence, we will target 2 groups of WP smokers based on their use frequency; beginner, 
and established smokers. This adds to the complexity of studies, but considering common WP 
use patterns among our target population and the reviewers’ comments, it seemed imperative to 
assess our outcomes in WP smokers at different stages of their smoking trajectory (Maziak 
2019, a). In addition, participants who participated in our previous research (e.g., pilot study) 
and those who will be recruited in the focus groups study will be excluded from the lab study to 
avoid contamination.   
C.3.2. HWLs development. Given the ample evidence about the advantage of pictorial (text + 
image) over text-only HWLs (Hammond 2011, Noar 2016, b), we focused here on developing 
and testing the potentially most effective pictorial HWLs tailored to young WP users in Florida. 
Moreover, in the lab study, we are comparing HWLs on the device with no-HWL (control) to 
compare the suggested intervention with the status quo (no-HWL on the device). For HWLs 
placement on the device in Aim 2, we will follow FDA’s and international recommendations 

14 
 
about HWL size (50% of principal display areas) (USDHHS. 2011, WHO FCTC 2011). Finally, in 
Aim 2 we are testing multiple (4) HWLs across different health themes to provide several 
options for HWLs application and rotation (Hammond 2009, a). 
C.4. Aim 1: Adapt the 12 HWLs to young WP smokers in Florida using exploratory focus 
groups (Month 6 Year 1 - Month 6 Year 2). In this aim we will adapt the 12 HWLs that we 
developed in the Delphi study (Asfar 2019) to our local population of young people in Florida 
through a 2-phase process; 1) conduct focus groups combined with a brief survey with member 
from the target population to obtain their feedback about the developed HWLs and how to 
enhance their design/effects and select the top-rated 4 HWLs from each theme, and 2) adapt 
and produce the 12 HWLs based on focus groups results to be used for dissemination (Aim 3), 
while the top-rated 4 HWLs will be tested in Aim 2 (Figure 8). 
C.4.1. Phase 1: Conduct focus groups with young WP smokers in Florida. Available 
evidence emphasizes the importance of considering the target population’s perception of HWLs 
messages (Hammond 2009, b). Therefore, using focus groups combined with a brief survey, 
this phase will allow us to adapt the 12 HWLs considering factors internal to our target 
population and WP smoking (e.g., beliefs, harm perception).  
Objectives. This study aims to: 1) adapt and enhance the design/effects of the developed 12 
HWLs based on the target population’s feedback on the HWLs in term of attention (notice, 
engagement, general design), reaction (fear, believability, avoidance), effect (e.g. harm 
perception, intention to quit), and improvement (e.g. relatedness to participants, message clarity 
and synergy with pictorials); 2) explore optimal placement and size of HWLs on each 
component (tobacco, device, charcoal), and 3) select the top 4 HWLs (one from each theme) 
based on participants’ rating (Hammond 2011, WHO FCTC 2011).  
Participants and recruitment. We will target young adults (age 18-29 years) in Florida who are 
regular WP smokers defined as smoking WP at least once a week in the past 6 months (Maziak 
2016); and are willing to provide informed consent and attend the focus group session as 
required. Individuals who report smoking cigarettes or other tobacco/nicotine products (e.g., e-
cigarettes, pipes, cigars) will be included to increase the generalizability of results given that 
concurrent tobacco use is common among young WP smokers in the US (Primack 2013, Kasza 
2017). We will recruit participants using a combination of online, offline and in-person 
recruitment methods to ensure successful recruitment (Buller et al., 2012). Offline items such as 
posters, flyers and study inserts will be posted and distributed on University of Miami and FIU 
campuses, nearby off-campus locations, and around WP cafés/bars in Miami. Online 
recruitment will include student listservs, Facebook, and other social media. In-person 
recruitment will involve handing out flyers and word-of-mouth targeting WP venues in Miami. 
Recruitment materials will be IRB approved and will have contact information (phone, e-mail) for 
initial eligibility screening. Interested callers will be screened by phone, and if eligible will be 
scheduled for a focus group session. Each participant will be compensated $36 at the end of the 
focus group session. 
Procedures. We will conduct 6-8 mixed-gender focus groups with regular WP smokers (n ≈ 65; 
age 18-29 years). We plan to recruit equal numbers of women and men. Using a grounded 
theory approach aimed at generating, confirming and modifying theory (Strauss 1990), data will 
be examined iteratively and data collection will continue until saturation is reached, indicating 
that no new themes are emerging; i.e. the planned groups’ number (6) is tentative. After the 
focus group discussion, participants will independently complete a brief survey to rate each 
HWL in term of self-perceived effectiveness. Dr. Asfar, a specialist in qualitative research will 
moderate the focus group and train a Research Assistant (RA) to help in conducting the focus 
groups. Open-ended questions and probes will be developed to guide the discussions and 

15 
 
ensure consistency across groups. The moderator guide and the brief survey will be developed 
by Asfar, Maziak and Schmidt our public health designer. 
Interested WP smokers who call the phone number included in the study ad will be screened for 
eligibility, asked for contact information to confirm their participation and be given directions 
about the time/place of their focus group. Each session will start with a general discussion on 
the nature, confidentiality and general interaction mode for the group discussion. After 
explaining the study and obtaining written informed consent, participants will be provided with a 
set of forms, including a Baseline Assessment Questionnaire (demographic characteristics, WP 
smoking history, use of other tobacco products) and a stapled set of Individual Rating Sheets, 
one for each of the 12 HWLs (3 HWLs in each of the 4 themes) (Survey Instrument Section 1; 
Focus Groups Tool A, B, C & D). The focus groups discussion will then entail 4 segments of 15-
20 min each (1 for each theme). Each segment will start with a PowerPoint presentation of 
theme-specific HWLs. Then, after viewing each theme’s HWLs, a discussion will ensue about 
participants’ reactions to the segment’s HWLs in terms of 1- attention (notice, engagement, 
general design); 2- reaction (fear, believability, avoidance); 3- effect (harm perception, intention 
to quit); 4- improvement (relatedness to participants, message clarity, language level and 
synergy with pictorials); and 5- optimal placement (size and durability of HWLs for each 
component - tobacco, device, charcoal). After the discussion, participants will independently 
complete a rating question for each label by responding to the question “How effective is this 
HWL overall?” on a 10-point Likert scale (Thrasher 2012).  
Analysis. Focus groups sessions will be audio-taped and transcribed verbatim to assist in the 
coding of themes related to the discussion. Data will be analyzed using Dedoose Software 
version 5.0.11 (SocioCultural Research Consultants, 2016), which allows hierarchical linkage of 
codes for clear visualization of data structure. Two team members (Asfar, RA) will 
independently review transcripts and develop a consensus plan to identify recurring themes and 
variants. Coding, data reduction, display, and interpretation will be conducted using Creswell’s 
7-step analysis framework (Creswell 2009). Overlapping themes will be given greater emphasis. 
All initial codes and categories both within and across groups will be sorted and compared until 
core categories of recurrent themes emerge as a basis for Grounded Theory (Corbin 2014). In 
addition to comparing responses within and between groups, we also will evaluate differences in 
themes according to important participant characteristics, such as gender. To select the top 
HWL in each theme, we will calculate the sum of the text and picture rating score in terms of 
overall perceived effectiveness of each of the 3 HWL/theme and select the top-rated one (with 
the highest score). Thus, while the information from the discussions will give more detailed 
feedback about important communication domains and suggests further adaptation and 
improvements, analysis of the rating forms will provide a snapshot of how the HWLs are 
perceived in term of overall effectiveness and will help to select the top HWL in each theme to 
be tested in Aim 2. 
C.4.2. Phase 2: Optimize and produce the 12 HWL. Guided by focus group results, we will 
work with our public health designer (Schmidt) to fine-tune the 12 HWLs. The top 4 HWLs that 
were selected from each themes will then be produced in high quality for testing on the device in 
Aim 2, while the developed 12 HWLs will be used for dissemination in Aim 3. To determine the 
optimal layout (size, placement) of the HWLs on the device, we will follow general guidelines 
(e.g., HWLs should cover 50% of the principal display areas) and use photos of a sample of the 
developed labels prepared in different sizes and shapes to see how it will fit the WP device 
(Hammond 2009, b). For example, given the device’s cylindrical shape, a round design, or 
multiple HWLs may be needed to be seen from all sides. A high-resolution photo of each of the 
top-rated 4 HWLs with the selected size and shape will be printed out as a sticker to be placed 
on the device for testing in Aim 2.  

16 
 
Impact. This study will generate 12 WP-specific HWLs adapted for young WP smokers in 
Florida to be used for knowledge dissemination about WP harmful effects (Aim 3), further 
development and adaptation by other researchers, and testing of the top 4 in Aim 2.  
C.5. Aim 2. Test the top 4 HWLs in a clinical lab experiment (Month 6 Year 2 – Month 6 
Year 5). Clinical lab methods have long been used to study emerging tobacco products for 
policy purposes (Breland 2006, Vansickel 2010). Their advantage over other methods lies in 
providing clear, quick and less biased estimates of the effect of manipulating parameters that 
are potentially important policy targets (e.g. nicotine, flavor) on smokers’ behavior and 
exposures (Ben Taleb 2018). Recognizing the limitation of lab studies vs. real-world WP use, 
such studies have been a mainstay to test the potential of regulatory-relevant product changes 
(e.g. flavor) (Ben Taleb 2018, Maziak 2019, a). Lab data from WP users moreover, are closely 
related to real-world use, as shown by a recent systematic review that concluded: “Health 
warnings based on early controlled laboratory studies were well-founded; if anything the findings 
suggest a greater exposure risk” (Jawad 2019).  
Maziak has recently received an R01 from NIDA/FDA (R01DA042477) to establish a clinical lab 
at FIU to study the effect of tobacco flavor manipulation on WP smokers’ experiences and 
behavior, as to guide the FDA of the expected effects of flavor regulation (pls. see FIU 
Resources) (Maziak 2019, a). In this proposal, we will utilize this lab model to study the effect of 
HWL manipulation on a myriad of WP smokers’ subjective (e.g. dependence, harm perception, 
intention to quit) and objective outcomes (e.g. puffing behavior, exposure to toxicants). The 
study will compare the main outcomes described below pre- vs post- WP smoking under HWL 
vs. no HWL conditions. We will use the 4 HWLs that performed best from each theme in Aim 1 
to assess the study’s outcomes as discussed below. 
Design and Setting. Utilizing clinical lab methods, this aim provides broad testing of the top 4 
HWLs on a myriad of WP smokers’ subjective and objective outcomes. We will recruit 2 groups 
of WP smokers (124 each, total 248; age 18-29 yrs) based on their use frequency (beginners: 
started WP smoking in the past 6 months, but smoke WP less than weekly; established: 
smoked at least once a week in the past 6 months) for a 2x2x2x4 within-subject (2: HWL vs no-
HWL x 2: pre- vs post- smoking) and between-subject (2: beginner vs established smokers x 4: 
HWLs) experimental study. Participant in each group (beginner, established smoker) will be 
randomly assigned to one of the 4 HWLs conditions, and undergo 2 WP smoking sessions that 
differ by HWL on the WP device (HWL vs. no-HWL), with pre-/post-smoking assessment of 
harm perception, intention to quit, puffing behavior, satisfaction, urge to smoke, and toxicant 
exposure (CO, nicotine, oxidative stress) (Figure 9). We will use Latin Square crossover design 
balanced for carry-over effect (random order of 4 HWL condition), and to ensure equal 
distribution of study participants across gender. Accordingly, every subject will undergo 2 WP 
smoking sessions in the clinical lab setting differing by label (HWL vs. no-HWL) in a balanced 
random sequence; the same number of subjects gets each label and its order (1st or 2nd 
session) the same number of times, and for each gender. As in (Evans 2015, Brewer 2016, 
Brewer 2019), all participants will receive a follow-up phone call assessment after 3 months of 
the last session to evaluate the longer-term effect of exposure to the HWLs in real-world setting 
including HWLs recall, social interactions about WP harms (talk about HWLs with 
family/friends), and behavioral adaptations in response to exposure to HWLs (e.g., harm 
perception, quit intention, quitting).  
Such an approach allows:  
1- Thorough comparisons without the need for large samples using powerful within-between 
subjects design. 
2- Comparative testing for HWLs with current practice (no label control). 
3- Comparative assessment of the 4 HWLs, and the themes they represent, on important 

17 
 
outcomes through between-subjects pre-post analysis. 
4- Assessment of the expected effect of HWLs on WP smokers at different stages of their 
smoking trajectory. 
Objectives and Hypotheses. To assess WP smokers’ responses to the developed pictorial 
HWLs and inform the state of Florida about HWLs potential to curb WP use among youth in 
Florida. The study will examine smokers’ harm perception, intention to quit, puff topography, 
satisfaction, dependence, and toxicants exposure (CO, nicotine, EBC oxidative stress) pre-post 
smoking under 2 conditions (HWL vs. no-HWL). We hypothesize that 1) HWLs on the device will 
reduce smoking (puffing) intensity, satisfaction, exposure to toxicants, dependence parameters 
and increase harm perception and intention to quit compared to no-HWL control; and 2) this 
effect will be more pronounced in beginning vs. established WP smokers.   
Participants, Recruitment, and Procedures. As in Aim 1, in this study we will recruit WP 
smokers through the same online, offline and in-person recruitment methods described in 
section (C.2.2. Recruitment, Aim 1). Individuals who report smoking cigarettes or other 
tobacco/nicotine products (e.g., e-cigarettes, pipes, cigars) will be included to increase the 
generalizability of results, as long as they identify themselves as primarily WP tobacco smokers 
(do not report using cigarettes/e-cigarettes/other tobacco products regularly > 4 times/month). 
Concurrent regular use of other tobacco/nicotine products would bias the measurement of WP 
associated outcomes (e.g. dependence measures) (Ben Taleb 2018).  Participants completing 
the 2 lab sessions and 3-month follow-up will be compensated $36 for each visit. Based on 
previous experience (Maziak 2019, a), we expect to study 8-10 subjects/month. We will 
continue recruitment until we reach the target sample (248 with complete sessions). While 
recruitment is always a challenge, our lab, led by Co-PI Maziak has easily recruited >150 WP 
users for two-session study (similar design) in the past 2 years with negligible drop out using 
comparable incentives (Maziak 2019, a). This is due to the widespread of WP smoking among 
college students in Florida (up to 34%) (Martinasek 2016), especially in a large university with 
about 57,00 students such as FIU, where our lab is located.  
Inclusion Criteria. Participants need to be generally healthy (at a screening physical 
examination), between the ages of 21-35 years, willing to provide written informed consent, 
attend the lab as required, abstain from WP or any tobacco/nicotine for ≥ 12 h prior to study 
verified by expired air carbon monoxide eCO<5 ppm (Ben Taleb 2018), and use a WP to smoke 
tobacco in the lab according to study protocol. The 12 hour abstinence period is needed to clear 
plasma nicotine from prior-to-study smoking (6–8 h after cessation is needed to clear plasma 
nicotine) (Benowitz 2009) and ensure that all study measures are influenced mainly by study 
conditions. Self-reported WP use will be used to define 2 groups of WP smokers (beginners, 
established), which mostly reflects smokers at different stages of their WP use trajectory 
(Maziak 2016). These are consistent with common WP use patterns among young people in the 
US, and our previous lab studies with WP smokers, which will enhance recruitment and 
generalizability of our results (Primack 2013, Haider 2015). 
Exclusion Criteria. As is standard for clinical lab studies involving smoking, safety concerns 
require that individuals with self-reported history of chronic disease, psychiatric conditions, 
history of cardiovascular disease, low or high blood pressure (BP) (systolic BP>150 mm Hg, or 
diastolic BP>100 mm Hg), seizures, or regular use of prescription medications (other than 
vitamins or birth control) be excluded (Ben Taleb 2018). Women will be excluded if they are 
breast-feeding or test positive for pregnancy (by urinalysis) at screening. Individuals who fail the 
eCO test may be rescheduled at another date. 
Sample Size. We built our calculation of the sample size for this study on eCO differences in 
our HWL pilot study (pls. see preliminary studies C.1.2. and Figure 6), which reported a small-

18 
 
to-medium effect size (Cohen’s f=0.19) depending on HWL condition (Maziak 2019, b). This 
study will include 248 WP smokers (124 beginners; 124 established) randomized to 4 groups 
(62 each) along the 4 tested HWLs. Using repeated measures ANOVA F test with 2 within and 2 
between factors, a total sample size of 240 participants will have at least 80% power to detect 
small-to-medium size effect (Cohen’s f=0.2) or larger for 2x224 within-subject (HWL condition 
and time) and between-subject (smoking frequency and 4 different HWLs) effects, as well as 
their interactions at 0.05 level of significance, assuming sphericity and a moderate correlation 
(0.5) among repeated measures (Cohen 1988). The proposed sample size will provide sufficient 
power to detect small to medium effects expected based on our pilot data (Maziak 2019, b). It is 
also feasible as we have not encountered any difficulty in recruiting a large number of WP 
smokers in our lab studies (Maziak 2019, a). 
Screening, Informed Consent. Individuals who are identified as potentially eligible based on 
the phone screening will be asked to attend an onsite-screening, which will involve assessment 
of inclusion/exclusion criteria, physical examination, and urine pregnancy testing for women. 
Prior to screening, potential participants will undergo a review of the study and consent 
procedures to ensure that they understand the study, its risks/benefits, and their rights as 
research participants. Consented (written) individuals will then undergo a physical examination 
conducted by the research nurse, who will have access to an on-call Medical Monitor 
(physician) in case of concern or for consultation at any point of the study as it is the standard 
practice in our lab (Maziak 2019, a, Maziak 2019, b). The physical examination will include 
measuring BP, heart rate, temperature, pulse oximetry, and weight/height. Successfully 
consented/screened participants will be scheduled for their 1st session and asked to abstain 
from all tobacco use 12 hours prior to it.   
Experimental Methods. Participants will be randomly assigned to one of the 4 HWLs 
conditions and attend the lab for two, ~2-h sessions, separated by a 48-h washout period, and 
differ by HWL on the device (HWL vs. no-HWL control). Session order will be randomly 
counterbalanced to avoid order effects; counterbalancing also will allow us to study the effect of 
HWL on smoking behavior prospectively (i.e. between sessions difference is expected to be 
less when the HWL condition is tested first). They will also be balanced across the 4 HWLs (62 
sessions for each HWL) to allow for equal numbers and robust comparisons of the 4 HWLs and 
their representative themes.  
At the beginning of the 1st session, participants will provide demographic and personal 
information including age, socioeconomic status, race/ethnicity, and detailed tobacco use 
history, especially WP use. Then abstinence will be verified by eCO<5 ppm. Those who have 
eCO>5 ppm will be rescheduled. Those who are abstinent will get familiarized with the study 
procedures, measures, and they will be given time to adapt to the lab.  
After adaptation, continuous measurement of physiological responses begins, and 10 ml of 
venous blood is sampled, and participants are asked to respond to subjective measures (pls. 
see below Outcome Measures). They will then begin a maximum 45 min WP smoking session 
(time recorded) using a device fitted with the pre-selected HWL or no-HWL according to 
condition. The HWL will be placed in a constant location/size on the device, which will be placed 
in front of participant seat (at vision level). For each participant, preferred brand/flavor of WP 
tobacco (verified at screening) will be used to neutralize the effect of nicotine/flavor on study 
outcomes. We will follow our tested lab protocol developed to study the WP (Ben Taleb 2018), 
where prior to each session, the lab staff will pack the WP head with 15 g of the participant’s 
favorite tobacco preparation and cover it with perforated foil. Tobacco will be heated with quick-
light charcoal disks (33 mm diameter; 6.2 g; Three Kings, Holland, or similar brand). Initially, a 
single charcoal disk will be used, and several (pre-weighed) ½ charcoal disks will be made 
available to the participants so they can add ad libitum (Cobb 2012). The timing of each 

19 
 
charcoal application will be noted as in (Shihadeh 2005a). Also for standardization, only one 
type of WP device will be used. Participants will inhale ad libitum and at the end of the smoking 
period 10 ml of blood will be sampled again, eCO will be measured, and subjective dependence 
measures (WP satisfaction, urge to smoke, withdrawal) will be assessed as in (Ben Taleb 
2018). The session will terminate 30 minutes after the last puff, and the 2nd session will be 
scheduled. Although it is difficult for a clinical lab environment to perfectly imitate the typical WP 
social setting (e.g. WP café), we will try our best to make the session area relaxing and 
entertaining to facilitate natural smoking behavior (e.g., access to fresh magazines, and 
background music). The same procedure will be conducted in the 2nd session. 
Outcome Measures. Outcome measures for this study and the timing of their 
measurement have been adopted based on our conceptual framework (Noar 2016, a) (Figure 
7); their suitability for our study’s objectives (Hanson 2009); being validated in studies of health 
communication and HWLs (Noar 2016, a); and their validated use in clinical lab studies of WP 
smokers (Ben Taleb 2019, Maziak 2019, a, Maziak 2019, b). These measures are described 
below (Table 1 & Survey Instrument, Section 2, Lab Study). 
1. Harm perception will be asked pre-/post-smoking and at 3-month assessment using 1 item 
“To what extent are you thinking about the serious health effects of WP smoking?” (Thrasher 
2012).  
2. Intention and motivation to quit will be asked pre-/post-smoking and at 3-month assessment 
using 3 items; “Do you intend to reduce WP smoking?”; “Do you intend to quit WP smoking?”,  
and “How motivated are you to quit WP smoking in the next month?” (Carpenter 2004). 
3. Recall will will be asked at 3-month assessment using 1 item “Try to recall what the HWLs 
warning information were stated and type it in the box below”(Kees 2010). 
4. Social interaction will be asked at 3-month assessment using 1 item “Since you started the 
study, how many times did you have a conversations with your family/friends about the 
HWLs?” (Brewer 2016). 
5. Change in WP smoking will be asked at 3-month assessment using 3 items; “Since you 
started the study, 1- did you stop smoking for 1 day or longer because you were trying to quit 
WP smoking?, 2- did you avoid smoking WP because you were thinking about the HWLs?, 
and 3- did you stop WP smoking completely because of the HWLs?” (Brewer 2016). 
6. Toxicant exposure includes eCO, plasma nicotine, and EBC oxidative stress.  
• eCo will be measured initially at the beginning of the smoking session (abstinence 
verification), and within 10 min after the WP smoking session via e-CO monitor 
(Vitalagraph, Lenexa, KS).  
• Plasma nicotine will be assessed pre-/post-smoking. The research nurse will draw Blood 
samples (~ 10 ml) via a butterfly needle from a forearm vein before smoking session onset 
and within 10 minutes of its end. Research staff will centrifuge blood samples and freeze 
plasma immediately, to be analyzed later by Forensic Chemistry Lab at FIU using Liquid 
Chromatography Mass Spectrometry. 
• Exhaled Breath Condensate (EBC) will be collected pre-post smoking session to test for 
markers of oxidative stress and DNA damage. We will test for 6 biomarkers (8-oxodGuo, 
8-oxoGuo, 8-isoprostane, formaldehyde, acetaldehyd and malondialdehyde) (Gong 2013, 
Hu 2015). Samples will be collected during 15 min of tidal breathing through a single-use 
disposable RTube TM collector (Respiratory Research, Inc., Charlottesville, Va., USA). 
After sample collection, a plunger will be used to pool the condensed material within the 
tube into a single sample (about 1.0-2 ml). EBC samples will be divided in aliquots and 
stored at -80°C. EBC samples will be analyzed by our Forensic Chemistry Lab at FIU 
using Online Solid-Phase Extraction and Liquid Chromatography Triple Quadrupole Mass 
Spectrometry (LC-QqQ-MS) and Gas Chromatography Mass Spectrometry (GC-MS) (Hu 
et al., 2015; Gong et al., 2013). malondialdehyde) (Gong 2013, Hu 2015). 

20 
 
7. Puff topography will be assessed continuously during smoking. It will be measured with a 
device that was developed by Shihadeh (Shihadeh 2005b), and validated in several WP 
studies (Maziak 2009, Cobb 2015). Briefly, a pressure transducer is integrated into the WP 
hose, and inhalation-induced pressure changes are amplified, digitized, and sampled at a 
rate of 1000 Hz. The software converts signals to airflow (ml/sec) and integrates the flow 
data, producing measures of puff volume, duration, number, and interpuff interval (IPI).  
8. Cardiovascular measures will be assessed continuously during smoking. Two physiological 
measures will be monitored during each session; heart rate and BP (systolic, diastolic, and 
mean arterial) using Noninvasive Patient Monitor 507E, Criticare Systems, Waukesha, WI. 
Physiological data transfer directly to a computer. Heart rate will be recorded every 20 
seconds and blood pressure will be measured every 5 minutes before and during WP use. 
9. Subjective dependence and satisfaction measures assess smoker’s satisfaction with 
smoking, and the direct effects of tobacco/nicotine consumption on dependence measures 
(e.g. withdrawal and craving). We will use 4 subjective measures: The Duke Sensory 
Questionnaire (DSQ) (Malson 2002, Pickworth 2002); The Cigarette/WP Evaluation Scale 
(WES) (Rose 2000, Malson 2002); The brief version of Questionnaire of Smoking Urges-brief 
(QSU) (Cox 2001); and Minnesota Nicotine Withdrawal Scale (MNWS) (Hughes 1986). 
Participants will use a computer keyboard and mouse to respond to these measures 
periodically in each label condition using Survey Monkey software. The first 2 measures 
(DSQ, WES) will be used only after smoking, while dependence (QSU, MNWS) measures 
will be assessed pre-post WP smoking (Ben Taleb 2018, Maziak 2019, b). Subjective 
measures’ assessment will take place within 20 minutes before and after WP smoking. 
Statistical Analysis. Prior to analysis, physiological data will be averaged to produce a single 
baseline value for each measure (10 minutes prior to WP use) and for each 10- minute that a 
participant was actually using the WP. Topography data will be processed automatically by the 
topography instrument software to eliminate closely spaced puffs (i.e., IPIs < 300 msec). Such 
puffs are assumed to be part of the previous puff and the recorded volume and duration values 
will be added to that preceding puff (Maziak 2009). After this procedure, any puffs less than 5 ml 
will be considered an artifact and automatically discarded. Remaining data will be averaged for 
each participant in each condition using all remaining values for puff volume, duration, number, 
and IPI (Shihadeh 2004). We will address the issue of stability of WP puff topography by 
correlating topography values across sessions (Shihadeh 2005a). For plasma nicotine, values 
below the limit of quantitation (LOQ) will be replaced with the value of the LOQ (Maziak 2011). 
Demographical data will be examined to determine if there are significant between-group 
differences on measures that may be related to study outcome (some differences are expected 
due to design such as past 30-day WP use) though these are expected to be minimized as a 
virtue of randomization. Unexpected between-group differences will be considered as potential 
adjustment covariates in the primary analysis (Evans 2006). The primary analysis of each 
outcome will involve a 4-factor analysis of variance (or covariance) with two within-subject 
factors; HWL (HWL vs. no-HWL/control) and time (pre-post smoking), and two between-subject 
factors; smoking frequency (beginner vs. established WP smokers) and HWL (4 group 
assignment). This approach will be extended into mixed-effects linear regression model in order 
to adjust for potential confounders such as gender, education, race, SES, and self-efficacy. To 
assess if gender has any effect on the results, it will be considered as a covariate and we will 
test the pre-planned interaction with it to determine heterogeneity of HWL by gender as well as 
potential differential effects. We will test for carry over effect statistically and will control for it 
when testing for the primary factors (Senn 2002). Significance levels will be adjusted for 
violations of the sphericity assumption using Huynh-Feldt corrections (Keppel 1991). The mean 
square error terms for the overall interaction will be used to conduct Tukey's honestly significant 
difference test (Keppel 1991), with comparisons at P < 0.05 considered significant.  

21 
 
Impact. This study will provide robust testing of the HWLs, and their themes, on a variety of 
outcomes that are important to assess the potential of HWLs on WP use and popularity among 
young people in Florida. It will also provide tested HWLs for further dissemination and 
implementation within the state and nationally.  
C.6. Aim 3: Communicate the knowledge obtained to advance WP control in Florida and 
nationally (Year 1 - 5). Concerns about our dissemination strategy and its target audience and 
outcomes necessitate clarifying that the main audiences for our proposed work are 
policymakers, regulators, and policy advocates, while young WP users are the ultimate target 
population when the HWLs are implemented. For this purpose, our partnership with Golin is 
optimal as they have extensive experience in advocacy for public health policy through their 
work with the Florida Dep. Health, CDC, and others. Still, in response to the review, we now 
expanded our dissemination to include young adults in collaboration with Truth Initiative, which 
has extensive experience in tobacco control advocacy focusing on youth. Truth Initiative will use 
the messages and images we developed in their counter-tobacco campaigns, and evaluate 
them for further message development and fine-tuning (e.g. Vallone et al., 2017; Hair et al., 
2017). We are also involving FDA staff, such as past policy director at the FDA Center for 
Tobacco Products to guide our team on the legal aspects of applying HWLs to the WP. 
We will apply the Dissemination Planning Tool Steps (Figure 10) to disseminate information 
about WP detrimental effects and advocate for policy solutions such as HWLs (Carpenter 2005). 
This Tool was built upon the concept that the process of implementing any research outcome 
begins with awareness when potential users learn about the products, or findings, and gain 
some understanding about how they work. The planning tool helps increase this awareness in a 
systematic way by combining the constructs of diffusion and dissemination (Carpenter 2005). 
Diffusion is defined as a passive process by which an innovation is communicated through 
channels over time in a social system (Rogers 2010). Dissemination involves a more active, 
tailored process of communication, with a goal of persuading users to adopt the innovation 
(Lomas 1993). Alone, neither construct offers sufficient guidance for successful dissemination of 
research results; together, the ideas complement and support each other. Both constructs are 
embodied in the development of this planning tool to guide the dissemination of research 
results. The Model has 6 elements: 1- research findings, 2- end users, 3- dissemination 
partners, 4- communication channels, 5- evaluation, and 6- work plan. Our team of 
communication scientists and professionals with years of experience in tobacco control will 
apply this framework to disseminate our findings and promote policy solutions for the WP 
epidemic as follows. 
1. Research Findings (What is going to be disseminated?): The research findings are the 
highlight of our overall effort, but we will also seek to generate newsworthy episodes across the 
five-year project. Specifically, we will seek to disseminate information regarding the grant and its 
scope, the final warning labels to be tested, a preview of overall findings, and lastly the formal, 
official findings of the study.  
2. End Users (Who will apply it in practice?): We identified two primary audiences for the 
information generated by our project: 
• Policymakers: Include those who will be considering the social impacts of the research 
findings, shaping public opinion, and determining policy interventions. These include state 
and local legislators, tobacco control and public health leaders, FDA staff, community 
leaders, and institutional leaders (e.g., superintendents, local health departments, public 
health administrators where WP venues proliferate). 
• Young adults and the public: Within this audience, groups that have a high level of interest 
in this topic can include, collage and high school students and faculty, parents and 

22 
 
parental groups (e.g., Parent Teacher Association), and medical professionals (e.g., 
nurses, pediatricians). 
3. Dissemination Partners (individuals, organizations or networks through whom we can reach 
end-users): Our primary dissemination partners will be stakeholders in the tobacco control and 
prevention community, the larger public health industry, and tobacco control advocacy groups in 
the state of Florida, including the county-level Tobacco-Free Workgroup and SWAT (pls. see 
letter from Dr. Thurer, Tobacco-Free Workgroup; Ms. Soto, Consortium For A Healthier Miami-
Dade; and Dr. Kobetz, Community Outreach Core at Sylvester Comprehensive Cancer Center; 
Ms. Rodas, Campaign for Tobacco-free Kids), Tobacco Free Florida grantees, through which 
public-facing awareness efforts (publicity and communications) will be launched and where 
implications for local policy change can be considered. The secondary dissemination partners 
are influential community leaders in Florida, particularly individuals and groups with an interest 
in public health and tobacco control issues related to youth and young adults, who can shape 
public opinion and support policy interventions. These would include tobacco control advocates, 
university and secondary school faculty, health foundation leaders, news editorial figures, 
among others.  
4. Communication Channels (How to convey the research outcomes?). We will use 3 specific 
channels for promoting the research findings and increase awareness about harms associated 
with WP smoking: a) the news media; b) partner outreach and mobilization; and c) social and 
digital media. 
• The news media: The news media effort will start with a media announcement, likely in 
Tallahassee, as the state capital boasts a large Capital Press Corps that influences media 
coverage statewide. The announcement would be broadcast live via digital and social 
media to local news and stakeholders in key markets throughout the state (e.g. Miami/Ft. 
Lauderdale, Orlando, Tampa, Jacksonville, Palm Beach, Naples/Ft. Myers, Gainesville, 
Tallahassee, Daytona, Panama City and Mobile, AL). We will recommend a “panel-style” 
format with representatives from three organizations signifying the various aspects of the 
research and advocacy including SCIENCE (UM, FIU); SOCIAL IMPACTS (our 
dissemination partners), and POLICY (e.g., Tobacco-free Kids). This group would be 
complemented with representatives of the “affected class” of the research, like a student 
from SWAT, a parent, or a former “hookah lounge” employee. All attendees will be 
prepared in advance with media training, a mock run-through, key messages, and proof 
points. The event will be coordinated by our agency partner, Golin, who handles such 
events for the Florida Department of Health, The U.S. CDC, and the U.S. Office of the 
Surgeon General, among others.   
• Partners’ outreach and mobilization: A toolkit will be created by the research teams and 
their organizations along with partners so that they may best leverage the findings to 
advance the cause of WP control at all levels. We will work also with partners and 
advocates to write "opposite the editorial page" (Op-Eds) and Letters to the Editor to frame 
the discussion among policymakers and influential stakeholders (e.g. The Miami Herald, 
The Tallahassee Democrat, etc.). Promotional assets in print, digital, video, static, 
infographic and partner materials will be produced in advance and made available. We will 
work closely with Tobacco Free Florida to further disseminate this information to 
stakeholders and partners in the tobacco control movement and plan a preview meeting a 
week in advance of the announcement to engage and motivate stakeholders.  
• Social and digital media: Following the announcement, a digital engagement effort will 
begin that features key findings of the research and a call-to-action (CTA). The CTA will 
direct the public to a micro-website that will contain further information and refer to 

23 
 
additional resources. This will also allow us to track and continue to engage our target 
audiences.   
5. Evaluation (How to determine what worked?). As part of our evaluation of our dissemination 
efforts, Golin will provide annual recap reports, ad hoc reports for media announcements, as 
well as a major ad-hoc launch report 30 days after the announcement of the major findings 
(e.g., Tallahassee event). The reports will capture:  
• News, digital and social media coverage analysis including impressions, reach, and 
message pull through. Golin will collect news coverage data and provide details about 
impressions and reach. Our team will then review each story and count the number of 
campaign messages that appear in the stories and where it appears to adopt messages 
with high reach and coverage.  
• Partner mobilization analysis including engagement and action by partners. Using 
appropriate tools (e.g. Facebook, Twitter ads, YouTube), Golin will identify posts by 
partners and report back those that have used campaign assets for more targeted 
messaging and partner mobilization.  
Golin will also provide key performance indicators (KPIs) to the investigators for evaluation.  
These KPIs include impressions and reach of materials, engagement with social media content, 
number of people who have shared content online, social conversations, the number of times 
video/images have been viewed, and the number of times people have visited a campaign 
website after seeing/receiving campaign materials. To provide a benchmark for comparison, we 
will use KPIs from two recent campaigns conducted by Golin (e.g. Tobacco Free Florida Week 
eEpidemic and/or the Florida Clean Indoor Air Act vaping ban) (Tobacco Free Florida 2015).  
In addition, Truth Initiative will use the messages and images we developed in their counter-
tobacco campaigns, and evaluate them for further message development and fine-tuning. Truth 
Initiative has standard and extensive evaluation process for their campaigns (e.g. Vallone et al., 
2017; Hair et al., 2017). This process briefly involves three types of studies: Formative, 
Implementation and Outcome.  Findings are continuously used to inform the process so that 
changes can be made in real-time help ensure campaign success (e.g. Hair et al., 2018).  
6. Work plan. Timing of various publications will dictate the release tactics, but generally, 
important announcements will be supported with a rigorous public relations launch and an 
engagement strategy that activates partners. When releasing scientific data, it is important to 
include timeliness of the news (through a media event), and a hook to current events. This 
process will be timed and repeated ahead of major policy pushes at all stages of the proposed 
project and will be supplemented with various related activities.  
Impact. As we have adopted a complementary approach for the development and testing of 
HWLs, each Aim feeds into the other, while also serving as a standalone study that will facilitate 
timely communication of our research findings to a variety of researchers, stakeholders, and 
policymakers involved in tobacco control in Florida. For example, the HWLs arising from our 
focus groups study (Aim 1) can be used by other researchers for further development and 
testing, while their messages and pictorials can be used within campaigns to increase young 
people in Florida awareness about the harms of WP smoking. Thus throughout the project we 
will produce and distribute toolkits, messaging, template social media assets, newsletters, and 
more (Table 2).  
C.7. Potential challenges and their solutions 
Long term effects of HWLs on smoking behavior is an important parameter that is rarely 
addressed in the HWLs literature (Noar 2016, a). However, given the complexity and limited 
portability of WP compared to cigarette pack, which complicates the assessment of HWLs on 

24 
 
smokers’ behavior prospectively, we opted to study the effect of HWLs on smokers’ behavior in 
a lab model (Aim 2). Thus, our proposed lab study provides a reliable method of gauging HWLs’ 
short-term potential on WP smokers in the form they will be delivered in the real world. 
Importantly, our planned short-term outcomes (e.g. reaction, harm perception, quit intention) 
have been shown to be strongly correlated with long terms outcomes of cessation (Borland 
2009, Fathelrahman 2009, Li 2012). Still, to gauge the potential of HWLs, we have now added a 
3-month follow-up assessment to evaluate longer-term recall, social interactions, and behavioral 
adaptations as a result of exposure to the HWLs (e.g., quitting and quit intention)(Brewer 2016).  
D. STUDY TIMELINE 
The total duration of this project is 5 years. During the first 6 months (Mon), we will hire and train 
study personnel, prepare study protocols and instruments, and obtain IRB approvals. Aim 1, will 
take place over the following 12 Mon (6 Mon for conducting focus groups, 3 Mon for focus 
groups analysis, and 3 Mon for optimizing and producing the new HWLs). Aim 2 (the lab study) 
starts in Year 2, Mon 6 and will continue over the following 36 months until the middle of Year 5. 
Aim 3 (dissemination) will start in Year 1, and continue throughout the grant’s 5 years. The final 
6 Mon of the grant will be devoted to data analysis and reporting, although we will expect 
continuous analysis and reporting of data throughout the grant’s 5 years (Table 3). 
 
 

25 
 
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