Randomized Trial of An Innovative Smartphone Intervention for Smoking Cessation
Phase: NA
Conditions: Smoking
Sponsor: Fred Hutchinson Cancer Center

iCanQuit Protocol 
 
 
1 
 
Study Protocol 
 
Title: Randomized Trial of an Innovative Smartphone Intervention for Smoking 
Cessation 
Protocol Date: 10/5/2018 
 
INVESTIGATORS & KEY STAFF 
 
Jonathan B. Bricker, Ph.D. (PI, Fred Hutch) 
Jaimee L. Heffner, Ph.D. (Co-I, Fred Hutch) 
Brie Sullivan (Project Manager, Fred Hutch) 
Kristin Mull (Statistical Research Associate, Fred Hutch) 
Noreen Watson (NIDA Post-Doctoral Fellow, Fred Hutch) 
Kim Le (User Experience Researcher, Fred Hutch) 
  
 
FUNDING 
National Cancer Institute 
 
 
PROJECT SUMMARY/ABSTRACT (DESCRIPTION) 
2 
SIGNIFICANCE & SPECIFIC AIMS 
 
3 
RESEARCH STRATEGY 
4 
Significance and Innovation 
4 
Approach 
10 
Research Plan and Methods  
13 
PROTECTION OF HUMAN SUBJECTS 
21 
  Potential Risks 
22 
  Inclusion of Women and Minorities 
24 
  Inclusion of Children 
25 
  Data and Safety Monitoring Plan 
25 
REFERENCES 
28 
 

iCanQuit Protocol 
 
 
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PROJECT SUMMARY/ABSTRACT (DESCRIPTION) 
 
There is tremendous need for smoking cessation intervention technologies with 
strong potential population-level impact at the lowest possible cost. That potential can 
be found in the newest technological innovation in quit smoking interventions: 
smartphone-based smoking cessation software applications (“apps”). There are over 
400 smoking cessation apps, which were downloaded in the United States 3.2 million 
times during the two-year period 2012 to 2013. No trials of any app’s effectiveness for 
general adult cessation have been published and no NIH-funded cessation intervention 
trials are in progress—despite the fact this is a high priority NIH funding topic. The 
enormous usage of smoking cessation apps contrasted with their unknown 
effectiveness creates a serious scientific gap that could stifle their population-level 
impact.  
Research on US Clinical Practice Guidelines (USCPG) apps begins to address 
that research gap. But only following the USCPG has had limitations in other modalities 
of delivery. An approach, called Acceptance & Commitment Therapy (ACT), addresses 
these limitations with both innovative intervention content and highly promising results 
from six published trials. ACT’s innovation is its dual focus on increasing willingness to 
experience physical cravings, emotions, and thoughts that cue smoking while making 
values-guided committed behavior changes. We recently developed the first ACT app 
for smoking cessation, called “SmartQuit,” and tested it in a pilot randomized controlled 
trial (N = 196), comparing it with an app that follows USCPG (National Cancer Institute’s 
“QuitGuide”). Results showed that SmartQuit had: (1) higher participant engagement 
and satisfaction than QuitGuide, (3) higher levels of acceptance of cravings than 
QuitGuide, and (3) descriptively higher quit rates (albeit non-significant) than QuitGuide 
at the two-month follow-up.  
Building on these promising results, we propose a fully-powered, randomized 
controlled trial (n = 1250 per arm) that compares a refined version of SmartQuit, called 
iCanQuit to QuitGuide, which follows the USCPG, to definitively determine whether an 
ACT app is more efficacious than a USCPG app.  
As millions of people are choosing smartphone apps to help them quit smoking, 
this innovative study shows exciting promise for improving the success rates of quit 
smoking apps and thereby lowering healthcare costs and reducing premature tobacco-
related deaths.  

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SIGNIFICANCE & SPECIFIC AIMS 
 
States’ funding for population-level smoking cessation programs remains far 
below their CDC-recommended levels. Consequently, there is tremendous need for 
intervention technologies with strong potential population-level impact at the lowest 
possible cost [1].  That potential can be found in the newest technological innovation in 
quit smoking interventions: smartphone-based smoking cessation software applications 
(aka, “apps”) [2-4]. There are over 400 smoking cessation apps [2] which were 
downloaded in the United States 3.2 million times during 2012 to 2013 [5]. No trials of 
any app’s efficacy for general adult cessation have been published and no NIH-funded 
randomized trials on apps for cessation are in progress —despite the fact this is a high 
priority NIH funding topic [7, 8]. The enormous usage of smoking cessation apps 
contrasted with their unknown efficacy creates a serious scientific gap that could stifle 
their population-level impact.  
Randomized trials on apps that follow the US Clinical Practice Guidelines 
(USCPG) begin to address that research gap. But only following the USCPG has had 
limitations in other modalities of delivery [9-15]. An approach, called Acceptance & 
Commitment Therapy (ACT), addresses these limitations with both innovative 
intervention content and highly promising results from six published trials [16-21]. ACT’s 
innovation is its dual focus on increasing willingness to experience physical cravings, 
emotions, and thoughts that cue smoking while making values-guided committed 
behavior changes [22]. We recently developed the first ACT app for smoking cessation, 
called “SmartQuit,” and tested it in a pilot randomized controlled trial (N = 196), 
comparing it with an app that follows USCPG (National Cancer Institute’s “QuitGuide”). 
The trial design was proven feasible, with successful national recruitment (N = 196 
recruited in 10 weeks) and strong outcome survey completion rate (84%). Results 
showed that SmartQuit had: (1) higher participant engagement and satisfaction than 
QuitGuide, (2) higher levels of acceptance of cravings than QuitGuide, and (3) 
descriptively higher quit rates (albeit non-significant) than QuitGuide at the two-month 
follow-up [21]. Building on these promising results, we propose a fully-powered, 
randomized controlled trial that compares a refined version of SmartQuit, called 
iCanQuit to QuitGuide, which follows the USCPG, to definitively determine whether an 
ACT app is more efficacious than a USCPG app. Thus we propose the following 
Specific Aims: 
 
Aim 1. Determine whether iCanQuit produces significantly higher abstinence 
than QuitGuide.  Primary endpoint: 30-day point prevalence abstinence at 12 months 
post-randomization. Importance of this aim: will determine the quit rates with precision 
and whether iCanQuit provides more robust quit rates than QuitGuide.   
 
Aim 2. Determine whether the iCanQuit (but not the QuitGuide) smoking 
cessation outcomes are mediated by these psychological processes central to the 
theoretical model underlying ACT: commitment to quitting and acceptance of internal (a) 
sensations, (b) emotions, and (c) thoughts that cue smoking. Importance of this aim: will 
identify ACT processes needing further targeting, and determine whether iCanQuit, but 
not QuitGuide, operates through ACT-specific theoretical processes. 
            Aim 3.  Determine whether iCanQuit is significantly more cost-effective than 
QuitGuide, as measured by cost per additional quitter, incremental cost-effectiveness 
ratio (ICER), and incremental cost per quality-adjusted life year (QALY).  Importance of 

iCanQuit Protocol 
 
 
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this aim: will provide payers (e.g., insurance companies) and policymakers results 
needed to decide whether to adopt iCanQuit.  
 
Exploratory Aim: Explore whether iCanQuit, as compared to QuitGuide, has 
higher quit rates for those with these baseline factors: (a) low acceptance of sensations, 
emotions, and thoughts that cue smoking, (b) heavy smoking (≥ 20 cigarettes/day), (c) 
current mental health symptoms, and (d) being racial/ethnic minority. Importance of this 
aim: will potentially identify key subgroups that benefit most from iCanQuit, and thereby 
aid in reducing tobacco-related health disparities.   
Innovations. (1) ACT’s innovative features augment the US Clinical Practice 
Guidelines; (2) ACT follows an innovative theory: Relational Frame Theory; (3) ACT on 
the smartphone is novel; (4) First randomized trial of a smartphone app for adult 
smoking cessation; (5) The first time that the following have been tested for any 
behavior outcome: (a) ACT delivered via smartphone, (b) mediation of the effects of a 
smartphone app, (c) cost-effectiveness of a smartphone app, and (d) exploration of 
subgroups who benefit most from a smartphone app. While there are thousands of apps 
and hundreds for smoking [2], testing an app’s efficacy is scientifically innovative. That’s 
a critical gap this application fills. 
 
 
 
Approach 
 
Randomized trial experimental design. We will conduct a fully-powered two-arm 
randomized controlled trial that compares iCanQuit to QuitGuide, which follows the 
USCPG. To balance baseline variables between the two conditions, we will stratify 
randomization by daily smoking frequency (≤20 vs. ≥ 21), education (≤ high school vs. ≥ 
some college), race/ethnicity (minority race/ethnicity vs. non-Hispanic White) and 
depression screen (CES-D score ≤ 15 vs. ≥ 16). Moderators will be measured at 
baseline. Mediators will be measured at baseline and three months post randomization. 
Consistent with cessation trial designs [60], cessation and cost-effectiveness outcomes 
will be measured at 3, 6, and 12 months post randomization.   
 
 
Figure 1. Experimental Design 
 
 
                                                  Screen, Consent & Baseline Survey 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomized (n=2500) 
SmartQuit (n=1250) 
Quit Guide (n=1250) 
3 Month Survey 
6 Month Survey 
12 Month Survey 
6 Month Survey 
12 Month Survey 
3 Month Survey 

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Eligibility: age ≥18 years; smoked ≥ 5 cigarettes a day for the past year; want to 
quit smoking within the next 30 days; if concurrently using any other tobacco products 
(e.g., e-cigarettes), wants to quit using them within the next 30 days; interested in 
learning skills to quit smoking; willing to be randomly assigned to either condition; 
resides in the United States; has daily access to their own iPhone or Android 
smartphone; knows how to download smartphone applications; willing and able to read 
in English; never used QuitGuide and not currently using other cessation treatment; 
never participated in our prior studies; no household members already enrolled; willing 
to complete outcome surveys, and provided contact information for themselves and two 
relatives. Participants not eligible for or interested in enrolling will be given the 
smokefree.gov website and the 800-QUIT-NOW phone number to reach their state’s 
quitline.  
 
Recruitment. We will use a recruitment process modeled after our the 
smartphone-delivered ACT pilot [21] as well as our web-delivered ACT pilot trial [20]). 
The study team will design our participant recruitment website which will provide basic 
information about the study, a FAQ, a brief video describing the study, information about 
the study team and Fred Hutch, and a portal to the informed consent form, screening, 
and baseline surveys. The team will also work with the Fred Hutch communications 
department to design of a series of press releases and Facebook advertisements to be 
distributed over the course of the recruitment period.  
We have extensive experience in designing recruitment materials for increasing 
racial/ethnic minority enrollment. Specifically, we will further adapt our approach to 
recruit at least 30% minority and 30% men: (1) the study team will design and distribute 
several culturally-relevant press releases; (2) develop effective strategies for using the 
media and the Internet to target minority smokers, including reaching out to minority-
specific media newswire services and including on our ads and enrollment website 
photos from target minority groups; (3), Partner with Fred Hutch’s Diversity Council staff 
design and disseminate minority-specific recruitment materials that will be disseminated 
to minority media (e.g., PR Newswire Multicultural Markets Newsline); (4) enrollment will 
be limited to no more than 70% White participants and no more than 70% women, to 
ensure racial/ethnic minority and male representation. 
Based on our ACT smartphone pilot RCT experience of 78 randomized per 
month, we estimate recruitment will take 17 months.  
 
Enrollment. We will use the identical enrollment method proven successful in our 
ACT smartphone pilot RCT. Specifically, for participants who screen eligible on the 
recruitment website and provide their email address, we will instantly send them an 
email (and two reminders over a 14-day period) inviting them to complete a secured 
online survey to provide informed consent and complete the baseline assessment. 
Those not consenting and completing the online enrollment process within 14 days will 
be sent an email notifying them that they were not enrolled and provide both the 
smokefree.gov website and the 800-QUIT-NOW phone number to reach their state’s 
quitline. Those randomized will be emailed a secured link to download their app (either 
iCanQuit or QuitGuide). All participants will be emailed identical once weekly reminders 
to use their assigned intervention.  
 
Research Plan and Methods  
 
ACT Intervention. We will use the iCanQuit intervention, which is based on ACT. 

iCanQuit Protocol 
 
 
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Table 3 contrasts ACT intervention strategies with the USCPG intervention strategies—
which are based on traditional cognitive behavioral therapy [62]. 
 
 
Table 3. Differences between ACT and US Clinical Practice Guidelines. 
Conceptual Level 
ACT 
US Clinical Practice Guidelines 
Philosophical Basis 
Functional Contextualism: One’s 
current and historical context influence 
all of the one’s external (e.g., walking) 
and internal (e.g., urges, thinking) 
behavior. The standard for determining 
whether a behavior needs to be 
changed is whether it is functional: 
pragmatic, useful, or helps one obtain a 
goal [70]. 
Critical Rationalism:  Knowledge has 
an objective truth. Knowledge can only 
be gained by attempting to validate 
beliefs that are derived from theories. 
(While not based on a specific 
philosophy, Critical Rationalism is 
arguably consistent with USCPG skills 
training) [71]. 
Theoretical Basis 
Relational Frame Theory: Overt 
environmental , cognitive, physiological, 
& emotional stimuli can be related to 
one another—and thereby take on each 
other’s qualities & functions—in every 
imaginable way: (Example:  seeing an 
actual cigarette→ thought “urge” → 
physical urge→ smoking a cigarette). 
Trying to control these processes just 
adds new relations and interferes with 
behavior change (Example: distraction 
from an urge → more urges).  In 
contrast, increasing willingness to 
experience (and not change) these 
processes increases value-guided 
behavior change [63]. 
Information Processing Theories: 
The mind processes information 
through the application of mental 
rules/strategies that guide behavior. 
Applying Illogical rules/strategies leads 
to dysfunctional behavior. (Example: 
Applying the illogical belief that 
“smoking controls stress” will lead one 
to smoke.)  In contrast, applying logical 
rules/strategies leads to more effective 
information processing and functional 
behavior [72]. 
 
Clinical Level 
ACT 
US Clinical Practice Guidelines 
General approach to 
intervening on urges, 
emotions, and 
thoughts that cue 
smoking 
Acceptance: Openness to experience 
urges, emotions, and thoughts as they 
are and without any intent that they 
change (e.g., no desire that urge 
reduces). Example: Asking:  “How 
willing are you to have, and not try to 
change, your urges to smoke?” [16, 73] 
Avoidance: Actively trying not to 
experience urges, emotions, & thoughts 
with the intent that that they change 
(e.g., desire for urge to reduce). 
Example: Asking:  “How can you avoid 
or control your urges to smoke?” ([62] 
pg. 74) 
Specific approach to 
intervening on urges 
and emotions that 
cue smoking 
Being Present: Being fully aware of the 
present moment with openness, 
interest, and receptiveness. 
Observation and non-judgmental 
description of experiences in the 
present moment. Example: while 
holding an unlit cigarette, take one 
minute to describe out loud its color, 
length, texture, smell. Next, describe in 
the present tense what urges and 
emotions come up [16, 73]. 
Urge/Emotion Coping Skills: A broad 
set of strategies designed to manage or 
control urges and emotions that cue 
smoking. Examples: avoiding places 
where you often smoke; engaging in a 
distracting activity (e.g., crossword 
puzzle); keeping hands active (e.g., 
gripping a stress ball); sucking on a 
hard candy  ([62] pg. 81).  
Specific approach to 
intervening on 
Cognitive Defusion: Stepping back 
from the process of thinking. 
Cognitive Restructuring: A method of 
changing the content of one’s 

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thoughts that cue 
smoking 
Recognizing thoughts, self-judgments, 
and memories as just words and 
pictures. Allowing them to come and go 
without trying to control or avoid them.  
Example: For a thought that often cues 
smoking (e.g., “I want to smoke.”), 
reduce it to one key word (e.g. "smoke") 
and then say the word out loud 
repeatedly for 30 seconds [16, 73]. 
unrealistic/irrational beliefs and/or 
replacing them with realistic/rational 
beliefs. Example: Change the thought 
“Smoking is how I cope with things” with 
this response: “Smoking does nothing 
to help a smoker cope, other than 
relieving withdrawal” ([62] pg. 41). 
Specific approach to 
increase motivation 
to quit smoking 
Values: Chosen life directions that 
guide actions. Values require no 
reasoning. Valuing is a process, not a 
life goal achieved or an outcome. 
Examples: “What really really matters to 
you?; How could quitting smoking be 
driven by  the things that matter to you?” 
[16, 73]. 
Reasons to Change: The specific 
expectations one would have for when a 
behavior has changed. Examining the 
advantages and disadvantages of a 
behavior change. Examples:  Listing 
expected benefits of quitting smoking; 
Listing all of the reasons for quitting and 
for not quitting smoking  ([62] pg. 49-58). 
 
 
Comparison app.  To address the question of whether iCanQuit is more 
efficacious than an app following USCPG, we chose QuitGuide as the ideal comparison 
intervention for four key reasons. First, it is one of the few apps (of the 400 available) 
that follow the USCPG [2].  Second, its content and structure are directly based on 
Smokefree.gov, the most accessed cessation website in the world. Third, QuitGuide’s 
content is non-proprietary and free to the public, thereby providing maximal 
transparency, accessibility, and replicability. Finally, because of our pilot RCT, 
QuitGuide is now the only app following USCPG with adult quit rate estimates that are 
based on a clinical trial [21].   
We also considered pharmacotherapy comparisons. But many participants would 
be ineligible for use (e.g., medical condition) and, if disseminated, many people would 
face access barriers (e.g., medication affordability). Some medications (e.g., 
varenicline) require a physician visit and prescription. For Nicotine Replacement 
Therapy (NRT), adequately addressing side effects for a nationally-recruited sample 
who will have had no prior personal contact with the study would be problematic [74, 
75]. 
Table 4. Participant surveys and time points when they will be administered.  
(All participants) 
 
Measure 
Screening Baseline 
3-
month 
6-
month 
12-
month 
Purpose 
Eligibility & Enrollment 
(24 items) 
x 
  
  
  
  
Eligibility, Enrollment, & 
Stratification 
Demographics               
(19 items) 
  
x 
  
  
  
Stratification & 
Exploratory 
Nicotine Dependence 
(6 items) 
  
x 
x 
x 
x 
Stratification & Aim 1 
Smoking/Tobacco 
History (4 items) 
  
x 
  
  
  
Exploratory Aim 
Tobacco Use                   
(6 items) 
  
x 
x 
x 
x 
Aim 1 

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Acceptance of cues (27 
items) 
  
x 
x 
  
  
Aim 2 & Exploratory 
Quality of Life                
(8 items) 
  
x 
x 
  
  
Exploratory Aim 
Quality of Life                
(6 items) 
  
  
  
x 
x 
Exploratory Aim 
Panic Symptoms           
(5 items) 
  
x 
x 
x 
x 
Exploratory Aim 
PTSD Symptoms           
(6 items) 
  
x 
x 
x 
x 
Exploratory Aim 
Generalized Anxiety 
Symptoms (7 items) 
  
x 
x 
x 
x 
Exploratory Aim 
Social Anxiety 
Symptoms (17 items) 
  
x 
x 
x 
x 
Exploratory Aim 
Depression Symptoms 
(20 items) 
  
x 
x 
x 
x 
Exploratory Aim 
Distress Tolerance       
(6 items) 
  
x 
x 
  
  
Exploratory Aim 
Values                              
(10 items) 
  
x 
x 
  
  
Aim 2   
Growth Mindset               
(6 items) 
  
x 
x 
  
  
Exploratory Aim 
Quitting Self-Efficacy   
(1 item) 
  
x 
  
  
  
Stratification 
Alcohol Use                       
(4 items) 
  
x 
x 
x 
x 
Exploratory Aim 
Mobile Device Use (8 
items) 
  
X 
  
  
  
Exploratory Aim 
Receptivity/utilization 
(14 items) 
  
  
x 
  
  
Acceptance/Adherence 
Receptivity/utilization 
(2 items) 
  
  
  
x 
x 
Acceptance/Adherence 
Cessation & Extra Aids 
(5 items) 
  
  
x 
x 
x 
Aim 1 and Exploratory 
Willingness to discuss 
(1 item) 
  
  
  
  
x 
Follow-up 
 
 
Primary assessments. Aim 1: Tobacco outcomes. Primary endpoint: 30-day 
point prevalence abstinence at 12-months post randomization, as readily comparable to 
other smoking cessation trials [60] and our ongoing web-based ACT intervention trial 
(R01CA166646). A 12-month main endpoint accounts for the relapse rates observed 
between 2 and 12 month follow-up [60, 76, 77]. Moreover, a 12-month endpoint directly 
addresses the overall need for technology-delivered cessation trials to show longer term 
benefit (e.g., 12 months) [9-15]. Secondary endpoints: prolonged abstinence (i.e., no 
smoking since three months after randomization, as consistent with ACT’s approach of 
allowing participants a grace period of several lapses as opportunities to practice ACT 
skills) and 7-day point prevalence [78]. All endpoints will also be examined at 3 and 6 
months post randomization. The secondary definition of cessation will include 
abstinence from cigarettes and these non-cigarette nicotine/tobacco products: e-
cigarettes, snus, chewing and smokeless tobacco, hookahs, cigars, cigarillos, tobacco 

iCanQuit Protocol 
 
 
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pipes, and kreteks (clove/tobacco cigarettes). Use of nicotine and tobacco products will 
be measured at baseline and all follow-up endpoints. We considered continuous 
monitoring of tobacco but elected not to because (1) it lowers response rates—a 
confound [30], and (2) effect sizes are similar to point prevalence [31]. 
We also considered biochemical validation but self-reported smoking is a 
standard method for assessing technology-based interventions. Evidence suggests 
false reporting is minimal for low-intensity interventions with no face-to-face contact [79, 
80]. Due to cost and low demand characteristics for false reporting, the SRNT 
Subcommittee on Biochemical Verification recommends biochemical confirmation has 
low response rates [69] and is unnecessary in population-based studies with limited 
face-to-face contact and studies where the optimal data collection methods are through 
the mail or telephone [81]. 
Aim 2: ACT Mediators. Acceptance of internal cues to smoke: Measured using 
the Avoidance and Inflexibility Scale (AIS;  = .93; [16, 20], which assesses one’s 
willingness to experience sensations (9 items), emotions (9 items), and thoughts (9 
items) that cue smoking. A sample item for the sensations scale is: “To what degree did 
you allow yourself to have urges to smoke?” Commitment to quitting. Commitment to 
quitting despite internal (e.g., cravings, anxiety) and external (e.g., smoking in the social 
environment) cues to smoke will be measured using the Commitment to Quitting Scale 
(CQS;  = .93; [59]). Sample item: “No matter how many people around me smoke, I 
won't let myself smoke once I quit.” Regarding assessment timing, three months post 
randomization is when we expect acceptance and commitment to increase the most, as 
consistent with past ACT smoking cessation studies [16, 17, 20, 82], and would allow 
testing of our hypothesized model of increases in acceptance and commitment at three 
months mediating the impact of the intervention on smoking cessation by twelve 
months.   
Aim 3: Costs of delivery, for cost-effectiveness analyses.  Costs associated 
with each app’s delivery include the cost to: (1) host the servers and databases, (2) 
conduct software updates to accommodate ongoing changes in operating systems, (3) 
have programming staff to answer technical questions, and (4) cost of facilities and 
equipment needed to maintain each (e.g., office space for personnel, computers). NCI, 
the host of QuitGuide, has agreed to provide these costs for QuitGuide [32]. Research-
related costs will not be included.  
Exploratory aim: Moderators of treatment outcome.  Hypothesized moderators 
of treatment effectiveness will be heaviness of smoking (smoking at least 20 cigarettes 
per day vs. less than 20 at baseline), acceptance of cravings to smoke (AIS scores 
below vs. above the median), mental health symptoms (positive vs. negative screen for 
depression, anxiety, or heavy alcohol use), and racial/ethnic minority status (Caucasian 
vs. minority).  Mental health symptoms will be assessed as follows: (1) depression 
screening via the 10-item Center for Epidemiologic Studies Depression Scale (CES-D; 
cutoff  ≥ 10) [83, 84]; (2) anxiety screening via the Generalized Anxiety Disorder Scale; 
(GAD-7; cutoff  ≥ 10, [85]); (3) alcohol screening via the Alcohol Use Disorders 
Identification Test—Consumption items (AUDIT-C; cutoffs ≥4 drinks/day for women, ≥5 
drinks/day for men or 7 drinks/week for women, 14 drinks/week for men [86, 87]).  
Treatment acceptability/adherence: Treatment satisfaction and utilization. 
Measured with the 8-item Treatment Satisfaction/Utilization Scale used in our pilot. 
Sample satisfaction item: “Overall, how satisfied are you with your assigned app?” 
Sample utilization items: “Overall, about how many times per week did you use the 
strategies taught in your assigned app?” and “How useful was your assigned app’s quit 
plan?”  
Cessation pharmacotherapy usage: Measures number of days per week, 
number of total weeks, and start/end dates, that participants on their own elected to use 
(1) nicotine replacement therapy (i.e., patch, gum, lozenge, inhaler, nasal spray), (2) 

iCanQuit Protocol 
 
 
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varenicline, (3) bupropion, and (4) other (fill in).  
Follow-up survey methods. For trial integrity, the follow-up data will be collected 
by our survey research unit that will be (1) blind to random assignment and (2) 
collecting cessation outcome data outside of the intervention apps. At each follow-up, 
we will send reminder letters. Each follow-up survey and Internet tracking will collect 
address information. The online-telephone-mailed sequence data collection protocol 
is as follows: 1) Three email attempts to complete the online version of the survey; 2) 
Eight attempts to complete a telephone version of survey (one call per day from a 
trained surveyor); 3) Send a paper version of the survey via US mail. Based on our 
ACT smartphone pilot RCT experience, we conservatively estimate this protocol will 
yield 84% retention. And to further boost retention, we will make the following protocol 
enhancements at all follow-up points: (1) mail a $2 pre-incentive letter (noncontingent 
incentives increase retention [88]) 2 weeks before the first online survey invitation (i.e., 
Day -14); (2) provide a $10 incentive for completing the online survey within 24 hours 
[89]; and (3) send a postcard with two questions about smoking status.  
 
Table 5. Schedule of key activities. 
 
 
 
a Set up study procedures, survey instruments, recruitment materials and advertising; IRB application.b3,6,&12 month 
outcome survey administration protocol (29 days long) timed to participant randomization date.cTelephone & mailed 
versions of each survey are data entered by a trained surveyor. A 20% random sample of entries are checked 
against audio-recorded telephone surveys and mailed hard copies. Errors over 1% trigger 100% batch re-entry and 
surveyor performance remediation.       
 
Analyses. Aim 1. Our primary outcome hypothesis is that iCanQuit will have 
significantly higher 30-day point prevalence abstinence at 12 months post-
randomization than QuitGuide. Analyses: For each comparison of the arms on the 
primary and all secondary endpoints, we will use a logistic regression model with 
complete case smoking cessation outcome [9-14]. The model will adjust for all 
stratification factors as well as baseline factors that might be imbalanced after 
randomization. In addition, we will conduct these analyses: (1) multiple imputation of 
missing outcomes [90-92], (2) missing equals smoking outcomes [9-14], (3) using a 
secondary cessation outcome of no use of cigarettes and other nicotine or tobacco 
products except FDA-approved nicotine replacement therapies. Finally, we will compare 
the two arms on utilization of their assigned app.  
Aim 2. We hypothesize that the iCanQuit arm’s (but not the QuitGuide arm’s) 
smoking cessation outcomes will be strongly mediated by these psychological 
measures that are central to the theoretical model underlying ACT: commitment to 
quitting and acceptance of internal (a) sensations, (b) emotions, and (c) thoughts that 
cue smoking. This hypothesis is consistent the ACT model and prior ACT for smoking 
cessation intervention studies [16, 17, 20, 82]. Analyses: For each mediator, the model 
is expressed as three regression equations that relate the main independent variable X 
Year of study
Quarter
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
1.  Refinement & Usability
XXX
XXX XXX
XXX
XXX
XXX
2. Set up a
XXX
XXX
XXX
XXX
XXX
3. Recruitment 
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XX
4. Interventions 
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
5. Outcome Surveys b 
XX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
6. Data Entry & QC c
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XX
7. Analyses
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
XXX
8. Dissemination
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iCanQuit Protocol 
 
 
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(ACT intervention), the mediator M (change from baseline to 3-months post 
randomization in the acceptance variable, and/or commitment to quitting smoking 
despite internal cues), and the binary endpoint Y at 12-months post-randomization (e.g., 
30-day abstinence). The first regression describes the total intervention effect (X) on the 
outcome (Y): logit (Y) = 1 + X, where the parameter  measures the total intervention 
effect. The second regression describes the impact of the intervention (X) on the 
mediator (M):  M = 2 + X. The third regression describes the simultaneous impacts of 
the intervention (X) and mediator (M) on the outcome (Y):  logit (Y) = 3 + X + M. 
Since the endpoint is binary, the mediation effect is the product term , whose 
empirical distribution will be estimated via 5000 bootstrapped samples. Bootstrapping is 
a resampling method which provides a powerful test of mediation that does not rely on 
normality assumptions [93-95]. Randomization should remove potential confounding 
effects [92, 93], and if needed, we will adjust each model by covariates that differ at 
baseline or predict outcome. Following VanderWeele and Preacher methods [94, 95], 
we will also explore any interactions between mediators and treatment arm. And we will 
explore whether utilization of assigned app and usage of cessation pharmacotherapy 
mediates cessation outcomes. 
Aim 3. We hypothesize that iCanQuit will be more cost-effective than QuitGuide, 
as measured by cost per quitter, incremental cost-effectiveness ratio (ICER), and 
incremental cost per quality-adjusted life year (QALY).  We will use current good 
practices of estimating cost-effectiveness, which were articulated by [96], as applied to 
smoking cessation interventions [77, 97]. First, to examine whether iCanQuit costs less 
than QuitGuide to help a person quit, we will estimate the incremental cost-per-quitter: 
difference in total cost of delivering the two interventions [98] divided by the difference in 
the number of 30-day abstinent participants at 12-months (Total CostiCanQuit – Total 
CostQuitGuide/# AbstinentiCanQuit – # AbstinentQuitGuide). Total delivery cost assessments are 
described in Section 3.3.11. Second, to estimate whether iCanQuit costs less than 
QuitGuide per life year added [77], we will calculate standard Incremental Cost-
Effectiveness Ratios (ICER): Total CostiCanQuit – Total CostQuitGuide/# Life Years 
AddediCanQuit – # Life Years AddedQuitGuide). Life years added attributable to each 
intervention’s 12-month primary endpoint effect size will be derived from the life years 
estimates, reported in Stapleton & West [77], that conservatively account for gender, 
age, discounting, relapse, and unaided cessation. Third, to examine whether iCanQuit 
costs less than QuitGuide to add greater quality to each life year added  [93], a separate 
ICER quality of life analysis called incremental cost-per-QALY will be conducted (Total 
CostiCanQuit – Total CostQuitGuide)/(QALYiCanQuit – QALYQuitGuide). This analysis will be 
calculated by adding a Generalized Linear Model-based weighted quality of life 
parameter derived from the standard EQ-5D quality of life measure [99] taken at the 12-
month endpoint. Finally, we will conduct multi-way sensitivity analyses of these results 
using 1000 Markov Chain Monte Carlo simulations that will derive a cost-effectiveness 
plane (and 95% CI ellipse) across a range of total costs and effect sizes.  In all 
estimates, we will adjust future costs to a standard reference year and discount future 
costs and benefits incurred after one year at 3% per annum as is recommended by the 
USPSTF on cost-effectiveness in health and medicine [100]. 
Exploratory Aim.  This aim will explore whether iCanQuit, as compared to 
QuitGuide, has higher quit rates for those with these baseline factors: (a) those scoring 
low on acceptance of sensations, emotions, and thoughts that cue smoking, (b) heavy 
smokers (≥ 20 cigarettes/day), (c) smokers screening positive for mental health 
symptoms, and (d) being a racial/ethnic minority. Analyses: This aim will explore key 
moderators of ACT treatment outcomes and aid in the critical effort to improve quit rates 
for these high-risk groups [101-105]. The ACT model suggests that, in addition to being 
a key mechanism (i.e., mediator) of treatment, baseline acceptance is a moderator of 
treatment outcome [22]. Specifically, we hypothesize that people who avoid their 

iCanQuit Protocol 
 
 
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triggers to smoke (i.e., low acceptance) will benefit most from ACT because ACT 
teaches skills to overcome avoidance. We also hypothesize that this focus on 
acceptance may be especially helpful for heavy smokers and those with mental health 
symptoms because physical, emotional, and cognitive cues to smoke are stronger for 
these individuals [106-109]. Finally, testing moderation by race/ethnicity will allow us to 
generate hypotheses about whether minorities overall respond differently to ACT than 
non-Hispanic Caucasians. We will explore moderation with separate logistic regression 
models for each moderator variable, where 30-day abstinence at 12-months post 
randomization is the outcome (Y). The model will include the moderator (Z), group 
assignment (X), and an interaction between moderator and group assignment (X*Z). 
Statistically significant interactions will be assessed with plots showing how the slope of 
Y on X is dependent on the value of Z. The slopes will be derived from logistic 
regressions that correspond to the prediction of Y from X at a single value of moderator 
Z. 
Power. We determined sample size with 5,000 iterative simulations aimed at 80% 
power for Primary Aim 1. We used the following parameters: (1) participants 
randomized to one of the two arms; (2) two-sided test with  = .05; (3) intent-to-treat 
analysis where, as standard in smoking cessation trials, all those with missing data are 
coded as smokers [11, 60]. The calculations do not account for potentially higher effect 
sizes from the adjustment of stratification factors. 
 
For Primary Aim 1, projected quit rates at 12 month follow-up were 
conservatively calculated using (1) quit rates at two-month follow-up in our pilot RCT 
(which used methods similar to this proposed R01) and (2) well-established relapse 
curves, which provide a data-derived estimate of the rate of decay of 2-month 
intervention effects by 12 month follow-up [60, 76, 77]. Specifically, the estimates 
account for a quit rate reduction from the observed two-month 13% quit rate in the pilot 
to an estimated 11% 12-month quit rate for ACT and from the observed two-month 8% 
quit rate in the pilot to an estimated 7% 12-month quit rate for QuitGuide. These 
reduction estimates are consistent with the relapse rates observed by 12 month follow-
up [60, 76, 77]. Having 80% two-tailed power to significantly detect a quit rate as low as 
11% for iCanQuit (vs. 7% for QuitGuide) required a sample size of 1622. However, we 
set the target recruitment to 2500 participants for the Exploratory Aim analyses. 
 
For Primary Aim 2, regarding the acceptance mediators, we estimated that they 
would explain at least 60% of ACT’s effect on quitting smoking, as based on prior trials 
[16, 17, 20, 82]. For the commitment to quitting mediator, we estimated that it would 
explain at least 25% of ACT’s effect on quitting smoking, as based on prior trials [16, 17, 
20, 82]. The 5000 iterative simulations showed that a sample size of 811 per arm would 
provide high power (>99%) to detect the estimated mediation effects for acceptance and 
commitment. 
 
  
 
 

iCanQuit Protocol 
 
 
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PROTECTION OF HUMAN SUBJECTS 
 
All procedures for this study will be reviewed by Fred Hutch’s IRB prior to human 
subjects’ participation. Based on our prior history with the pilot randomized trial which 
motivated this proposed trial, we expect no problems obtaining IRB approval. 
 
Experimental design 
We will conduct a fully-powered two-arm randomized controlled trial that 
compares iCanQuit to QuitGuide, which follows the USCPG [67]. To balance baseline 
variables between the two conditions, we will stratify randomization by daily smoking 
frequency (≤20 vs. ≥ 21), education (≤ high school vs. ≥ some college), race/ethnicity 
(minority race/ethnicity vs. non-Hispanic White) and depression screen (CES-D score ≤ 
15 vs. ≥ 16). Moderators will be measured at baseline. Mediators will be measured at 
baseline and three months post randomization. Cessation and cost-effectiveness 
outcomes will be measured at 3, 6, and 12 months post randomization. Enrollment and 
baseline data collection will occur via a SSL secured website hosted by Fred Hutch. The 
ACT intervention will occur on an app platform which will send, via 256-bit SSL 
encryption, study-ID coded usage data from smartphones to secured Fred Hutch 
servers. Outcome surveys occur via an online-telephone-mailed sequence conducted 
by Fred Hutch.  
 
Sources of material 
As shown in Table 3 of the Research Plan, these are sources of survey data for 
the study: (1) screening survey, (2) baseline survey, (3) 3-month follow-up survey, (4) 6-
month follow-up survey, and (5) 12-month follow-up survey. We will also collect 
automated utilization data from both apps. A description of these sources of data 
follows. 
 
Survey Data 
As further outlined in Table 4 and Research Plan, the Baseline Survey, hosted on 
our secured recruitment website, will collect data on (1) demographics, (2) current 
smoking status and smoking history, (3) readiness to quit, (4) nicotine dependence, (5) 
acceptance of internal cues to smoke, (6) commitment to quitting, (7) quality of life, (8) 
mental health, and (9) contact information needed for the study’s follow-up data 
collection activities – as well as information about whether or not it is acceptable to 
receive email or voice messages and mail from the study. The Three-Month survey will 
primarily collect data on cessation processes (e.g., acceptance of cues to smoke), 
progress (e.g., quit attempts) and outcomes (e.g., 30-day abstinence), and the 
participant’s experiences with their assigned smoking cessation intervention.  The Six 
and Twelve Month surveys will primarily collect data on cessation progress and 
outcomes. 
 
App utilization data and security 
Activation of the assigned app on the participant’s smartphone will be conducted 
by entering the login code sent to them in their trial enrollment email. Personal 
information collected from the apps is limited to a first name and optional email in the 
ACT version of the app. The apps send, via 256-bit SSL encryption, participant-specific 
utilization data from smartphones to secured Fred Hutch servers: (1) # of times app was 

iCanQuit Protocol 
 
 
14 
 
opened, (2) specific features used, and (3) tracking of smoking and exercise practice 
(iCanQuit only). These data are identified by alphanumeric IDs only. Fred Hutch Shared 
Resource programmers will be the only persons with the ability to re‐identify study 
participants based on the alphanumeric IDs. There will be secured backup and half-
yearly risk assessment and mitigation.  
. 
Follow-up surveys data collection procedures. 
For trial integrity, the follow-up data will be collected by our survey research unit 
that will be (1) blind to random assignment and (2) collecting cessation outcome data 
outside of the intervention apps. At each follow-up, we will send reminder letters using 
an “Address Service Requested” envelope, for automatic forwarding to new mailing 
addresses. Each follow-up survey and Internet tracking will collect address information. 
The online-telephone-mailed sequence data collection protocol is as follows: 1) Three 
email attempts to complete the online version of the survey; 2) Eight attempts to 
complete a telephone version of survey (one call per day from a trained surveyor); 3) 
Send a paper version of the survey via US mail.  
Based on our ACT smartphone pilot RCT experience, we conservatively estimate 
this protocol will yield 84% retention. And to further boost retention, we will make the 
following protocol enhancements at all follow-up points: (1) mail a $2 pre-incentive letter 
(noncontingent incentives increase retention [88]) 2 weeks before the first online survey 
invitation (i.e., Day -14); (2) provide a $10 incentive for completing the online survey 
within 24 hours [89]; and (3) send a second copy of the mailed survey 2 weeks after the 
first mailing.  
Telephone administration of the surveys will be conducted by trained staff. If the 
staff member gets voicemail, a short and simple message will be given letting the 
participant know the purpose of the call and encouraging him/her to call the study’s toll-
free number. Mailed surveys will include a letter inviting participants to complete the 
survey, a printed survey form, a self-addressed-stamped-return-envelope for the 
completed survey. 
 
Potential risks to participants 
The main risk to participation in this study is a small risk of breach of 
confidentiality. A breach could possibly occur if, for example, an unauthorized person 
accesses the study’s database records and/or hard copy records, telephone survey 
conversations are accidentally overheard by someone who does not know the 
participant smokes or is taking part in a smoking cessation study. Also, some 
participants might feel emotional upset during their assigned intervention or 
embarrassment when talking about their smoking during the telephone surveys. Finally, 
some smokers making quit attempts may experience some short-term discomfort 
associated with nicotine withdrawal. Participants will be fully apprised of all anticipated 
risks in the informed consent and other intervention materials. 
 
Protection against risk 
All research activities will be reviewed and approved by the IRB at Fred Hutch to 
ensure that participants are adequately protected against risk. The research aims and 
activities, as well as risks and benefits, will be explained in detail to all potential 
participants prior to obtaining informed consent. Steps to protect against risk are 
described below: 
 

iCanQuit Protocol 
 
 
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Protection against breach of confidentiality: How survey data are processed and stored 
in HIPAA compliant server 
All survey data records are stored in secured HIPAA compliant servers or in 
locked file cabinets inside locked (limited access) rooms in our secured building. 
Completed paper surveys have no identifying information other than the participant’s 
unique Study ID number. Access to paper and electronic study data and records, and to 
the link between participant names and Study ID numbers, is restricted to a limited 
number of need-to-know study personnel, and data may not be taken off the premises 
for any purpose. Users have no access to project computers unless they have a domain 
(network) account. All users must change passwords every 120 days. The electronic 
database resides on a server that is in a locked cabinet in a locked server room, with 
strictly limited, key-card access. The server also lies behind Fred Hutch’s firewall, which 
permits no access to the server at all from outside Fred Hutch, except through the 
database server port using a secure, encrypted channel.  The research group places 
additional restrictions, through DBMS software, on which data items users may view 
and the kinds of activities they are permitted. These permissions are based strictly on 
each staff member’s need to see and use the data. No staff member will be able to 
access the data by default. The Project web server also resides in the same secure 
room as the database server, and is similarly protected by firewalls, with no user access 
except through the web server software. The database administrators maintain a 
rigorous system of daily full tape backups of the database and web servers. The 
backups include sets of tapes stored at a secure distant site.  
Study participants will be recruited using a publicly accessible web site running 
on the Apache web server on a Linux operating system. The public web server is 
segregated from the rest of the Fred Hutch network within a DMZ (demilitarized zone). 
After indicating interest in the study, participants will complete online surveys via the 
256-bit secure sockets layer protocol (SSL). Employment of the SSL protocol will 
prevent anyone from intercepting data passed between the end user’s web browser and 
the web server. Once randomized, each treatment group will have access to their 
assigned smartphone application protected upon successful download.  
Surveys are implemented using a secure, metadata-driven system designed and 
tested by our software development team, which has been in use for the past five years 
for other research studies in which participants enter information about themselves.  
Surveys are hosted on a Web site running on the Apache web server on a Linux 
operating system. The public web server is segregated from the rest of the Fred Hutch 
network within a DMZ (demilitarized zone). Study participants who complete these 
online surveys will only have access to data that they have entered on in-process 
surveys.  Participants may access partially completed surveys via a participant-specific 
link provided by email and entry of the participant’s birthdate.  Once surveys are 
complete, the data are inaccessible from the data collection web site.  Participants and 
others will be prevented from accessing any other data on the Web server by a number 
of operating system, web server, and application controls. Users will connect to the web 
site to complete the surveys using the secure sockets layer protocol (SSL). Employment 
of the SSL protocol will prevent anyone from intercepting data passed between the end 
user’s web browser and the web server. 
 

iCanQuit Protocol 
 
 
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Protection against emotional upset or embarrassment. 
If participants feel uncomfortable answering research questions or participating in 
their assigned intervention they will be able to skip any assessment items that they are 
not comfortable answering. Participation during the intervention will also be voluntary. 
Participants may choose not to participate in any components of their assigned 
intervention which make them feel uncomfortable. All participants will have the option of 
contacting via email the PI, Dr. Bricker, a Licensed Clinical Psychologist with the 
experience and expertise to responding effectively to potential adverse emotional 
reactions. He will plan to respond within 24 hours. If a referral to treatment is needed, 
he is acquainted with appropriate referral facilities and processes of identifying 
treatment available throughout the United States.  
 
Protection against discomfort of nicotine withdrawal. 
Participants who quit smoking may experience some discomfort associated 
nicotine withdrawal. Participants will also be fully informed of the symptoms of nicotine 
withdrawal during the informed consent process. Interventions in all treatment arms 
provide strategies designed to cope more effectively with symptoms of nicotine 
withdrawal. Finally, participants in both treatment groups will be given information on 
pharmacotherapy for smoking cessation (e.g., nicotine patch) and how to obtain these 
medications.  
Reporting breaches and complaints 
Taken together, these measures will minimize risks to study participants. 
However, should a breach/complaint occur, or if a participant is not pleased with any of 
the surveys, or with the study’s procedures, the study’s scientific staff will attempt to 
address the concerns; if unsuccessful, the breach/complaint will be reported to the IRB 
office, and the participant will be referred to the Fred Hutch IRO Director.  
 
Potential benefits of the proposed research to the subjects and others  
Successfully assisting people who smoke to quit would have significant positive 
benefits to their health. Overall, participants assigned to any of the three interventions 
have the potential to benefit by quitting smoking and the potential short and long term 
health benefits of quitting.  
 
Importance of knowledge to be gained  
As millions of people are choosing smartphone apps to help them quit smoking, 
this innovative study shows exciting promise for improving the success rates of quit 
smoking apps and thereby lowering healthcare costs and reducing premature tobacco-
related deaths.  
 
Inclusion of women and minorities 
The population for this study will be 2500 adult male and female daily smokers who 
want to quit smoking. Recruitment and eligibility screening methods are designed to 
achieve a broad representation of adult smokers, including 70% female and 30% 
racial/ethnic minority. 
 
Inclusion of children 

iCanQuit Protocol 
 
 
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This is a study of adult smoking cessation; participants will be aged 18 or older. The 
NIH definition of children includes young adults up to age 21. By the NIH definition, the 
only “child” participants in this study will be those aged 18-21, over the age of majority 
and fully capable of participating in informed consent. Therefore, no special protections 
are required for their inclusion in this research.  
 
Children under the age of 18 will be excluded on the basis of the following: (1) 
Both interventions used in this trial have not been designed for or tested with adolescent 
smokers; (2) Youth may respond differently to intervention than do adults.  As such, 
data collected from these individuals may not generalize to the larger adult population; 
and, (3) Our standardized assessment measures were validated in adult samples and 
are not applicable to children.   
 
 
Data safety and monitoring plan 
Upon funding, the DSMP will be submitted for review by the Fred Hutch 
Institutional Review Board. The DSMP includes plans for the following required 
elements: (1) monitoring the progress of trials and safety of participants, (2) assuring 
compliance with requirements regarding the reporting of adverse events, (3) assuring 
that any action resulting in temporary or permanent suspension of the trial is reported to 
the sponsor, and (4) ensuring data accuracy and protocol compliance. The trial’s DSMP 
will be carried out by the scientific/management team, including the Principal 
Investigator, at weekly meetings. 
 
Data Management 
In addition to and in combination with meeting HIPAA regulations, data collected 
and managed will be securely handled to prevent unauthorized access or modification. 
All those in the study staff who have access to data on those screened and/or 
participating in the study will follow these procedures when handling the data: (1) 
education about the need for security and confidentiality, (2) signing a confidentiality 
agreement, (3) using passwords to control access to the electronic databases and 
regular changing of passwords, (4) keeping paper versions of surveys and any other 
paper versions of screened/participating individuals’ data in a locked room, & (5) 
servers will be protected by firewalls, McAfee Virus Scan Enterprise anti-virus software, 
daily full tape backups stored in a locked room, and encryption via the https protocol. 
 
Data Accuracy 
Data accuracy has two aspects in this trial: (1) accuracy of self-reported data by 
trial participants, and (2) accuracy of data management. The trial has procedures for 
both, which will be reviewed annually by the Project Manager and approved by the 
Principal Investigator.  
 
Monitoring Data Quality and Integrity 
Several procedures will be used to maintain data integrity. All databases will be 
stored in a centralized location at Fred Hutch on a secure server. Data will be backed 
up daily and access will be password protected and limited to persons working on the 

iCanQuit Protocol 
 
 
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project. Persons will only have access to specific data required for their project tasks. 
Identifying information will be stored separately from the assessment data. Data will be 
audited on an ongoing basis to ensure confidentiality safeguards are being maintained 
and data integrity is being maintained. Data entry systems will be set-up to allow field 
checks, range checks for continuous variables, valid value checks for categorical 
variables, and checks for logical consistency of responses. Queries and data reports will 
be generated on a routine basis to monitor data quality. 
 
Guidelines for Monitoring and Reporting Unexpected and Adverse Events  
 
Monitoring 
Throughout the study, the Principal Investigator, Co-Investigator, and Project 
Manager will monitor participants for adverse events and protocol compliance. The 
project manager will complete monthly reports on participant progress and status, any 
adverse events, and any protocol deviations. Protocol adherence will be monitored by 
the Principal Investigator.  
 
Reporting 
Study staff will be trained, and required, to report all unexpected and adverse 
events to the Principal Investigator. Adverse events beyond what would be expected in 
the course of smoking cessation will be reported to the Fred Hutch’s IRB in accordance 
with Fred Hutch policy.  
 
Definitions  
In general, unexpected events (UEs) include any event, adverse or otherwise, 
that was not described as part of the study risks. For this trial, an example of an 
unexpected event that is not adverse is a participant who has become very unhappy 
with trial procedures. Adverse events (AEs) are any untoward occurrence with a trial 
participant whether or not it can be considered to be related to their smoking cessation. 
An example of an adverse event in this trial could include an increase in depressive 
symptoms. Serious adverse events (SAEs) include any AE that results in death, a real 
risk of dying, inpatient hospitalization, persistent or significant disability/incapacity, or 
AEs that require intervention to prevent permanent impairment or damage. In this trial, 
an example of a serious adverse event would be a suicide attempt.  
UEs, AEs, and SAEs will be reported to the Principal Investigator as soon as staff 
members are aware of them. If there is any doubt as to whether an event qualifies as a 
UE, AE, or SAE, staff members will be trained and encouraged to err on the side of 
caution – and to bring the event to the Principal Investigator’s attention for review.  
 
 
 
Attribution 
The Principal Investigator, in consultation with the Co-Investigators, will decide if a 
UE should be classified as an AE. If an event is classified as an AE, further attribution 
will be determined, as follows: 

iCanQuit Protocol 
 
 
19 
 
• Related – AEs that are definitely, probably, or possibly related to the smoking 
cessation intervention. 
• Not Related – AEs that are doubtfully related or clearly not related to the smoking 
cessation intervention. 
 
Reporting 
1. SAE’s: For AE’s meeting the criteria for an SAE, regardless of its attribution, a Fred 
Hutch SAE Report form will be completed. The SAE Report form will be faxed by the 
Principal Investigator to the IRO office at 206-667-6831 within 24 hours of the internal 
report. All available information will be submitted. Should additional information 
become available after the initial report, a revised report will be submitted within 15 
days.  
2. AE’s that do not meet the criteria for SAE: For these events, the Principal 
Investigator or the Study Coordinator will complete and submit a Fred Hutch 
Adverse Event Reporting form within ten (10) calendar days of learning of the 
events. 
3. UE’s that do not meet the criteria for AE’s: For these events, the Study 
Coordinator will complete and submit a Fred Hutch UE Reporting Form within ten 
(10) calendar days of learning of the events. 
 
Complying with Trial Suspension Reporting Requirements 
Were the Fred Hutch’s IRB or Clinical Trial’s Office to issue a temporary or 
permanent suspension of the trial, the trial’s Principal Investigator will immediately 
contact the trial’s project officer. A Data Safety Monitoring Board will not be required 
since this is a minimal risk behavioral intervention.  
 
 

iCanQuit Protocol 
 
 
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