Conditions: Tobacco Use Cessation
Keywords: tobacco treatment
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1000
Healthy volunteers: yes

Brief summary:
The purpose of this study is to determine the impact and efficacy of a new approach to smoking cessation treatment versus the traditional approach.

Detailed description:
In many health conditions, the default treatment approach is to first identify the health condition and then begin treatment. In this scenario, the physician discusses treatment options with the patient. The patient is free to decline treatment as they wish. If patients do nothing though, they will receive care.

For tobacco users, the default treatment is for them to "opt in" to receive smoking cessation assistance. The provider asks the smoker if they are ready to quit, and they offer medication and support only to those who respond back "yes". This limits the amount of smokers that receive treatment because only 1 in 3 smokers say they are ready to quit.

This study is looking at a novel approach to smoking cessation treatment. This study will compare the traditional, "standard of care" approach to opting in against a new approach where all smokers are provided with cessation medication and counseling unless they refuse it.

Arms:
arm 1: Participants in this arm will be first enrolled to receive cessation treatment and will only not receive it by "opting out". Participant will receive a Opt Out treatment program. Participants will receive counseling and nicotine replacement therapy. arm 2: Traditional approach to tobacco treatment program. Participants must first indicate they are ready to quit smoking by "opting in" to receive Opt In treatment program.

Interventions: intervention 1: Opt Out Treatment Program intervention 2: Nicotine Replacement Therapy intervention 3: Opt In Treatment Program intervention 4: Nicotine Replacement Therapy
Intervention descriptions: intervention 1: Tobacco Treatment (UKanQuit) staff will complete a treatment plan for all participants. intervention 2: Unless they Opt Out all participants will be provided with a 14 day supply of the nicotine patch and nicotine mini-lozenges or nicotine gum, depending on study related criteria. intervention 3: Tobacco Treatment (UKanQuit) staff will complete a treatment plan for participant's who are ready to quit smoking. For patient's not ready to quit, motivational counseling will be provided to participants based on principles of Motivational Interviewing. intervention 4: Participants ready to quit will be provided with a 14 day supply of the nicotine patch and nicotine mini-lozenges or nicotine gum, depending on study related criteria.

Protocol document:
Prot_000.pdf: 
 
 
1 
STUDY PROTOCOL  
CHANGING THE DEFAULT FOR TOBACCO TREATMENT 
ClinicalTrials.gov Identifier: NCT02721082 
Date: 10/01/2021 
 
 
 
HYPOTHESIS AND SPECIFIC AIMS 
Globally, one billion people will die from tobacco-related illnesses this century. Most health care providers, 
however, fail to initiate medication therapy or cessation support with their smokers, even where these resources 
are readily available. This may in part be due to the cessation treatment “default.” Current treatment guidelines 
recommend that providers a) ask patients if they are willing to quit and b) provide cessation-focused medications 
and counseling only to smokers who state they are willing to quit.  
For other health conditions—diabetes, hypertension, asthma, and even substance abuse—the treatment default 
is to a) identify the health condition and b) initiate evidence-based treatment. For example, when patients are 
newly diagnosed with diabetes, they aren’t asked if they are ‘willing’ to start treatment. The physician simply 
begins with a discussion of treatment options. As with any healthcare treatment option, patients are free to 
decline—they can “opt out” if they wish to refuse care. If patients do nothing, they will receive care. For tobacco 
users, however, the default is that they have to “opt in” to receive cessation assistance: providers ask smokers 
if they are willing to quit, and only offer medications and cessation support to those who say “yes”. This drastically 
limits the reach of cessation services because, at any given encounter, only 1 in 3 smokers say they are ready 
to quit. As a result, few receive medications or cessation counseling. Recent studies suggest that, when provided 
with cessation medications and counseling, “unmotivated” smokers are as likely to quit as “motivated” smokers. 
Hence, there is a critical need to examine the impact of changing the treatment default on utilization and quitting. 
Our long-term goal is to save lives through novel systems of evidence-based care delivery. The objective of this 
application is to determine the impact of providing all smokers with cessation pharmacotherapy and counseling 
unless they refuse it (OPT OUT) versus current practice—screening for readiness and only offering cessation 
assistance to smokers who say they are ready to quit (OPT IN).  
Our central hypothesis is that OPT OUT will result in significantly higher rates of medication use, receipt of 
cessation counseling, and cessation compared to OPT IN. Tobacco treatment is an excellent policy arena for 
testing the effects of changing the treatment default because most smokers report they would ultimately like to 
quit smoking. Paradigm-shifting research on organ donation, and numerous other studies, demonstrate that 
changing defaults dramatically changes decisions, behaviors, and outcomes. The default is created by the way 
choices are presented. Changing the way providers offer treatment could harness the ambivalence smokers feel 
about smoking and “nudge” them toward accepting treatment and quitting.  
We will conduct the trial in an academic hospital. The study is a posttest-only randomized clinical trial with 
delayed informed consent. For OPT IN, clinicians will, in accordance with current guidelines, ask smokers if they 
are ready to quit. With smokers who say “yes”, clinicians will ask if they would like cessation medication and/or 
referral to the state tobacco quitline. Smokers will receive each component of care to which they opt in. With 
smokers who say “no” clinicians will provide brief motivational counseling designed to increase readiness to quit. 
For OPT OUT, clinicians will explain that the hospital provides free tobacco treatment to all smokers, provide the 
smoker with cessation medications, and refer all smokers to the quitline. As with all medical care, smokers in 
OPT OUT will be free to decline any aspect of treatment.  
The trial employs a Bayesian adaptive design study—an efficient and ethical strategy for comparative 
effectiveness clinical trials design, because it allocates more patients to effective treatments. We project that 
1,000 patients, 500 in each arm, will be required to test differences at 1- and 6-months post randomization. The 
study has the following aims and hypotheses:  
First Aim: To determine the population impact of changing the default for tobacco cessation treatment.   


 
 
2 
Hypothesis 1: Significantly more patients in OPT OUT will participate in counseling, use cessation 
medications, and be abstinent from smoking at 1 month post-randomization compared to OPT IN. 
Second Aim: To identify long-term impact, mediators of effectiveness, and costs.  
Hypothesis 2: Significantly more smokers in OPT OUT will be abstinent from smoking, and mediation 
analyses will find that counseling participation, medication use, and default-theory based variables will partially 
or fully explain the effect of OPT OUT on cessation at 6 months post-randomization.  
Hypothesis 3: OPT OUT will be more costly—in terms of upfront costs—but will be more effective than OPT 
IN. As a result, OPT OUT will be more cost-effective from a provider perspective.  
This is a population-based study that targets an endpoint of vital interest; applies minimal eligibility criteria to 
broaden generalizability; and utilizes hospital staff for interventions to ensure long-term sustainability. The study 
employs a highly innovative design to evaluate a major shift in our approach to care. If effective, this change 
would expand the reach of tobacco treatment from 30% to 100% of smokers.   
 
SIGNIFICANCE 
Based on current rates of tobacco use uptake and cessation, twenty million Americans will die from tobacco 
related illnesses between 2000-2050.1 Due to the 20-40 year time lag between starting smoking and the onset 
of tobacco related illnesses2, helping smokers quit is the best way to immediately reduce illness and deaths.   
 
Guidelines-based tobacco treatment consists of two branches3: motivational counseling, based on principles of 
Motivational Interviewing4, for patients not willing to make a quit attempt; and cessation-oriented 
pharmacotherapy and counseling for smokers who are prepared to make a quit attempt. The goal of motivational 
treatment is focused on building smokers’ motivation to quit; findings on its effectiveness for smoking cessation 
are, at best, mixed.5  
Cessation-oriented pharmacotherapy and counseling doubles or even triples quit rates over no-treatment 
controls,6 but the ‘default option’ for smoking cessation is ‘no treatment’.  With each step of guidelines-based 
tobacco treatment, smokers must say ‘yes’ (they would like to quit, would like to use medications, would like 
counseling) in order to receive evidence based care—they must ‘opt in’.  This is in stark contrast to treatment of 
other common medical conditions, such as hypertension, where the default option is ‘treatment’: physicians 
identify and initiate treatment for high blood pressure7, and patients must ‘opt out’ if they don’t want care.  
Consequently, less than 1 in 5 smokers actually get assistance in quitting on any given outpatient encounter with 
their health care providers.8 In hospitals, an even smaller percentage of smokers receive assistance: a meta-
analysis found that only 14% of inpatient smokers were provided with a prescription for cessation medication 
and 12% received referrals for follow up.9 Moreover, because smokers must opt in for cessation counseling and 
medication separately, few receive both components of evidence-based care.10 Many would blame this treatment 
gap on smokers and their lack of motivation to quit smoking.  This application, and a peer-reviewed article 
prepared in tandem with this application11, proposes that smokers fail to receive effective cessation treatment 
due to how the U.S. structures the tobacco treatment default.  The application examines the effects of pro-
actively providing cessation-oriented treatment to all smokers.  
How Do Defaults Influence Health Choices?  
For any given choice, there is a default option—the option that will occur if the chooser does nothing.12 For most 
chronic health conditions—diabetes, hypertension, asthma, and even substance abuse—guidelines direct health 
care providers to identify the health condition and initiate treatment.13 As with any healthcare treatment option, 
patients are free to refuse.  
In this manner, healthcare providers act as “choice architects” by creating a context in which the patient is 
presented with, and makes, a decision.12 Defaults are unavoidable in any context because there must be a rule 
that determines what should occur at decision points should no action be taken—consider for example computer 
configuration defaults and defaults on annual health insurance options. In healthcare, most treatment guidelines 
direct clinicians to provide evidence-based treatment, which the patient will receive by default unless she or he 
refuses treatment. In fact, this choice architecture is arguably the most ethical. Where there is strong clinical 
evidence that support an appropriate therapy, that therapy should be presented as the default.14  Hence, the 
exceptional position that smokers should be asked if they are “ready” to quit creates a rate-limiting step in tobacco 
treatment that should be critically examined.   


 
 
3 
A wide range of studies demonstrate that defaults powerfully affect choices and behaviors. Changing default 
options changes consumers’ choices of health care plans15, information shared on the internet16, and organ 
donation17.  Opt out policies for students and parents greatly facilitate participation in health and educational 
interventions and research.18 Disney World changed its default sides for kids meals to include apples and milk 
rather than fries and soft drink; although pre-change data are not available, 65% of children now receive apples 
and 68% milk following the change.19  
Although choice research is a relatively new field, defaults are hypothesized to be highly influential because they 
capitalize on implied recommendations for courses of action and status quo biases.  For example, the way a 
healthcare provider presents a choice may “leak” information about the provider’s attitudes toward options as 
well as their implied recommendation for a course of action.20  Provider preferences could be leaked by tone of 
voice, phrasing of options, order of options, omission of options, or what option is presented as the default option. 
In addition, people making decisions consistently exhibit a status quo bias—when an opportunity exists to either 
do something or do nothing, people tend to do nothing.15 Taken together, information leakage by choice 
architects and status quo biases on the part of decision makers can tip the balance in favor of some choices, 
and against others. Regardless of how carefully or thoughtlessly options are presented, they can have a powerful 
impact on choices.12   
Decision theorists suggest that institutions should structure default choices to be the options that make the 
choosers better off, as judged by themselves.21 Tobacco treatment is an excellent candidate for a default that 
favors treatment because 70% of smokers state they ultimately want to quit smoking.10 Choosing to quit in the 
near future, however, is extremely difficult for smokers because they get the pleasures of smoking, and the pain 
of abstaining from smoking, in the present but suffer the terrible consequences of smoking in the future.12 This 
may be why fewer smokers state that they are ready to quit in the near future. They could use a “nudge” to 
accept treatment in order to reach their ultimate goal of quitting.   
Research Contribution 
The contribution of this trial will be to identify the impact of default tobacco treatment, for an entire population of 
smokers, on treatment uptake and cessation. It will identify the costs and cost-effectiveness of changing the 
default, and examine psychological mediators of change based on decision theory. This contribution is significant 
because it will definitively determine the impact of routinely assessing smokers’ readiness to quit in real world 
clinical practice. Assessing readiness is an integral step in the “5 As” of tobacco treatment (Ask, Advise, Assess 
[readiness to quit], Assist, Arrange).3 Currently, the Assess step is supported by “C” level evidence of 
effectiveness, as there are no trials that establish that it has a positive impact on cessation.3 Because most (70%) 
of the 46 million adult U.S. smokers will visit a health care provider in a given year,22 study findings will either 
support—or dramatically change—a clinical practice that affects treatment and outcomes for millions of patients 
per year.  
The benefits that flow from this contribution are significant. Regardless of outcome, the trial will provide a model 
of how to alter and evaluate the impact of health care defaults. If OPT OUT proves to be more effective, it will 
expand the population eligible for cessation treatment by over 300%--from 30% to 100% of smokers. It will also 
simplify the tobacco treatment algorithm, and relieve busy health care providers of the burden of evaluating 
patients’ readiness to quit.   
Evidence for Study Components, Theoretical Model, and Design Considerations 
This study tests the utility of assessing readiness for tobacco treatment. In conducting the trial we adhere to 
evidence-based recommendations for treating hospitalized smokers. We will provide post-discharge counseling. 
We will provide nicotine replacement for post-discharge medication. Our intervention will operationalize key 
features of treatment defaults. To assess mediating effects, we will measure patient perceptions of these 
features.  We review each of these areas below.  
Guidelines-based tobacco treatment. Clinical Practice Guidelines for Treating Tobacco Use and Dependence3 
recommend providers use the “5 As” to intervene systematically with patients: Ask the patient if she or he uses 
tobacco; Advise him or her to quit; Assess willingness to quit; Assist with quit attempt using patient-centered 
counseling and pharmacotherapy; and Arrange for follow-up to prevent/address relapse. Guidelines-based 
counseling strategies for smokers ready to quit include developing a quit plan, discussing and selecting 
medications, and providing practical counseling that includes problem solving and skills training; effective support 


 
 
4 
may be provided by providers or tobacco quitlines. The highest abstinence rates are achieved with a combination 
of counseling and pharmacotherapy.23  
Recommended counseling for smokers not ready to quit employs a Motivational Interviewing approach and 
covers the “5 Rs”: Relevance—address why quitting is personally relevant; Risks—explore the risks of continuing 
to smoke; Rewards—explore the potential rewards of quitting; Roadblocks—explore barriers to quitting; and 
Repetition—repeat motivation each time the patient visits the healthcare setting.  
The intervention includes one study arm (OPT IN) that follows all 5 As, and one study arm (OPT OUT) that omits 
the Assess step.  In the OPT IN arm, patients will be screened for readiness. Those who state they are ready to 
quit (i.e., who “opt in” to treatment) will be referred to outpatient counseling and sent home with a 14-day ‘starter 
pack’ of nicotine replacement (NRT) to bridge their transition to outpatient care. In OPT OUT, all patients will be 
referred to outpatient counseling and given an NRT starter pack (i.e., patients will have to “opt out” to not receive 
care). During times when face to face contact with hospitalized patients is not feasible, these starter packs will 
be mailed to patients’ homes following hospital discharge. 
Treatment for both study groups will be consistent with the 2012 Cochrane Review of Interventions for Smoking 
Cessation in Hospitalized Patients24 which found that, to be effective, behavioral interventions must start in the 
hospital and continue at least one month after discharge to be effective. The review also examined the impact 
of starting cessation medications in the hospital. Among all first line medications (varenicline, bupropion, and 
NRT), only NRT significantly increased quit rates over counseling alone, which guided our decision to provide 
NRT to patients in this trial.  
Proactive tobacco quitlines. Quitlines are effective and cost effective for smoking cessation.25 They are available, 
free, to most U.S. smokers26; services are delivered via telephone which minimizes many access barriers; 
hospitals do not incur costs for the services; and many quitlines are undersubscribed and eager to increase their 
reach.27 We will provides outpatient counseling services that mimic current quitline services. We will provide the 
outpatient telephone base counseling ourselves since the quitline’s current protocol involves only counseling 
smokers who state they are ready to quit smoking.   
Theoretical model. We hypothesize that smoker perceptions of what course of action their cessation counselor 
recommends, and what type of treatment is the status quo at the hospital, will affect their counseling participation, 
medication use, and quit rates (Figure 1). Mediation analyses are described under Data Analysis.  
Figure 1. Theoretical Model 
Design considerations: readiness to quit. 
One possible objection to the proposed 
study is the widely held belief that smokers 
must be motivated in order to quit. However, 
numerous clinical trials have found that 
smokers who report they are not ready to 
quit actually quit at the same rates as those 
who report they are ready to quit28, possibly because intentions to quit can change rapidly.29 In fact, a majority 
of smokers quit as a result of unplanned, spontaneous, quit attempts30—which suggests that motivation is highly 
variable and that other factors may help to trigger quit attempts. Moreover, smokers who are not planning to quit 
will accept treatment.  The population-based Inter99 intervention trial in Copenhagen offered all smokers 
attending a lifestyle modification consultation the opportunity of enrolling in smoking cessation groups. Even 
though only 11% had reported they were planning to quit in the next month, over 1 in 4 (27%) enrolled in 
cessation groups.31 Thirty-five percent of all participants were abstinent by the end of the groups. Among 
successful quitters, only 16% were those who had been planning to quit smoking at the beginning of the trial.32 
If Inter99 had followed guidelines endorsed by the Danish Medical Society, it would have restricted its offer of 
treatment to those few smokers who were planning to quit, and failed to help many achieve abstinence.  
A meta-analysis by Aveyard and colleagues suggests that physicians will more effectively treat tobacco 
dependence by providing opt-out care.33 Four studies identified in the meta-analysis offered nicotine replacement 
therapy (NRT) to all participants regardless of readiness to quit. Compared to brief advice alone, smokers who 
were also given NRT were 49% more likely to quit (RR 1.49, 95% CI: 1.17-1.89).  Another trial examined the 
Perceived 
Recommendation 
OPT OUT 
vs. 
 
OPT IN 
Perceived 
Status Quo 
Counseling 
Participation 
Medication 
Use 
 
Cessation 


 
 
5 
effects of opt-out behavioral support for cessation, compared to brief advice to quit.34  Although opt-out care did 
not conclusively outperform advice to quit in promoting abstinence (RR 3.10, 95% CI: 0.38-25.51), it did prompt 
more quit attempts (1.69, 95% CI: 1.24-2.31).  Importantly, patients found the provision of behavioral support 
more helpful than simply being advised to quit.      
Design considerations: motivating smokers. Another concern is that many believe that, for unmotivated smokers, 
tobacco cessation intervention should focus on increasing readiness to quit.  However, it is important to first test 
the assumption that smokers must state they are ready to quit in order to be able to quit. Several non-randomized 
trials, in secondary analyses, have found that non-motivated participants quit at the same rates as motivated 
participants.35 If the present study hypothesis proves correct, simply providing treatment to all smokers will result 
in higher quit rates. If so, screening for readiness should not be universally performed, as screening for readiness 
would simply reduce the number of patients receiving treatment. If, however, our hypothesis proves wrong and 
screening for readiness results in similar or better quit rates, then the next logical and crucial research step 
indeed will be to develop effective methods for motivating smokers to quit.  Either way, the present study 
addresses the gap in knowledge that must be filled before advancing other strategies to expand the reach of 
cessation treatment. 
Design considerations: providing tobacco treatment, without first asking if the smoker is ready to quit, might be 
paternalistic or coercive. We believe this is an open question in light of the findings from Slama and colleagues’ 
opt-out treatment for behavioral counseling34—that patients found the offer of behavioral support more helpful 
than simply being advised to quit.  Viewed from another perspective, asking patients if they are ready to quit, 
and only offering medications or cessation-oriented counseling to those who say “yes”, could also be 
considered paternalistic. In order to collect data to address this issue, we will, at 6-month follow-up, ask 
participants to rate how paternalistic they perceived their hospital tobacco treatment providers to be and will 
include this in mediation analyses to understand any differences in perceived paternalism between groups and 
the impact of these perceptions on quit behaviors.  


 
 
6 
 
INNOVATION 
It is not possible to randomly assign participants to be 
“ready” or not.  Perhaps because motivation is often viewed 
as an innate characteristic of an individual36, no 
experimental 
studies 
have 
examined 
whether 
the 
requirement that smokers be “ready to quit” is a useful step 
in tobacco treatment.  However, recent research on 
motivation and decision theory suggest that environmental 
influences such as treatment defaults, the context in which 
a decision is made, and treatment provider counseling style, 
have a great deal of influence on individual choices and 
outcomes.37  
As described under Significance, providers miss many 
opportunities for treating tobacco dependence, which has 
created a large treatment gap. This study innovatively 
reframes this gap as a direct result of our treatment default.  
Current guidelines recommend providers screen for 
readiness, which in turn requires smokers to ‘opt in’ for 
treatment.  Viewed from this perspective, the effects of 
screening for readiness on tobacco treatment can be tested 
by changing the way treatment is offered to smokers.  The 
study is also innovative because it identifies a major rate-
limiting step in access to tobacco treatment.  Regardless of 
what population, setting, or approach is used to disseminate 
tobacco treatment, as long as providers screen for 
readiness, the majority of smokers will report they are not 
ready to quit—and they will not receive care.   
Other unique features of the trial include the posttest only 
delayed-consent randomized control group design38, and 
Bayesian adaptive trial design.39 The posttest-only design 
controls for all of the threats to internal validity that a pretest-
posttest design controls for. In addition, it avoids testing effects by minimizing repeated measurement—
especially prior to the intervention. This will enable us to see the true effects of changing the default on initial 
treatment choices. The Bayesian adaptive design study determines our sample size and how patients are 
allocated to groups.39 Bayesian designs are becoming widely used in PCORI pragmatic clinical trials, because 
they are efficient and ethical—they can get answers to research questions early, and they allocate more patients 
to the better-performing treatment arm (described in detail under Approach).40 The study will also evaluate the 
impact of psychological mediators on treatment participation and smoking cessation, in order to gain insight into 
why and how changing the default did—or did not—work.  
Features of this application will benefit research far beyond the field of tobacco control. It will provide a model 
for how to experimentally test the effects of health care defaults.  The post-test only design is also extremely 
useful in examining brief interventions, such as vaccination policies, HIV testing, and procedures that might be 
included on hospital order sets.41 Last but not least, patients will benefit by receiving care in institutions that 
critically examine how they present choices to patients, and ensure those “choice architectures” are designed to 
help patients reach their long-term and short-term health goals. 
RESEARCH STRATEGY  
Overview 
In the 6-month planning phase, we will finalize all protocols, data collection forms, and ethics approvals.  We 
also will train participating hospital staff. The trial employs a 2-arm design with individual randomization to groups 
(Figure 2). After patients are admitted to the hospital, research staff will identify every smoker via the electronic 
health record (EHR), randomly select the daily quota of study participants, and provide the quota to UKanQuit 
Figure 2. Study flow diagram 
-------------------------------------In Hospital--------------------------
 
Admission—ID Smoking Status 
 
 
 
 
 
 
Random Selection into Trial 
 
 
 
 
 
Brief Advice to Quit + Pamphlet 
 
 
 
 
 
UKanQuit Bedside 
Eligibility/Intake Assessment 
 
 
 
 
 
 
Random Allocation into Groups 
 
 
 
 
 
 
 
OPT OUT 
 
OPT IN 
 
 
 
 
 
Provide 
-Treatment Plan 
-Counseling 
-Medication 
 
 
Screen for readiness 
 
 
 
 
 
Ready 
Not Ready 
 
 
 
 
 
 
 
 
 
Offer 
-Treatment Plan 
-Counseling 
-Medication 
 
Provide 
Motivational 
Intervention 
 
 
 
 
 
------Post-Discharge-----
 
 
 
 
Quitline sessions 1~3 
 
 
 
 
 
 
1. UKanQuit 1-Month Assessment  Aim 1 
2. Informed Consent 
3. Extended 1-Month Survey for Consenters Aim 2 
 
 
 
 
Quitline sessions 4~5 
 
 
 
 
 
 
6-month Follow Up for Consenters Aim 3 


 
 
7 
hospital staff.  At the bedside, or over the telephone during the COVID-19 pandemic when staff are unable to 
meet at the bedside, UKanQuit staff will briefly advise all smokers to quit, provide an 8-page pamphlet on 
cessation resources, and use a tablet computer to randomly assign patients to one of 2 study arms: OPT OUT 
or OPT IN. UKanQuit staff will administer the appropriate intervention. UKanQuit staff will collect contact 
information for their 1-month post treatment phone assessment, which is standard practice for the service and 
accords with Joint Commission follow-up recommendations.  
 
After discharge, UKanQuit staff will contact all smokers seen. They will collect month 1 service data, describe 
the research study, collect verbal consent and transfer patients to research staff extended month 1 data 
collection. Research staff will conduct a similar assessment at month 6 among consenting patients. Outcomes 
include biochemically-verified 7-day point prevalence abstinence at 1 and 6 months, post-discharge counseling 
utilization, and medication utilization. We will also assess psychological mediators and cost-effectiveness. We 
estimate 1,000 participants, 500 in each arm, will be required to detect the expected treatment effect on 
abstinence.  
Preliminary Studies  
The study is highly feasible due to the unique relationship the research team has with the University of Kansas 
Hospital and the expertise our team has in conducting hospital-based research.  
UKanQuit clinical service. The University of Kansas Hospital founded UKanQuit in 2006, and operates it via a 
contract with the Department of Preventive Medicine and Public Health (Service Directors Richter and Ellerbeck). 
UKanQuit is fully integrated into hospital protocols and electronic systems. In its first 6 years of operation it 
treated 7,700 smokers. UKanQuit has been the subject of two quality improvement studies42 and has served as 
the platform for two clinical trials (EQUIP and a PCORI trial, P.I. Ellerbeck). UKanQuit demonstrates our ability 
to work in hospitals and collect data from clinical services.  
Enhancing Quitline Use among Inpatients (EQUIP). (U01 HL105232, Richter, P.I.). EQUIP built on the UKanQuit 
clinical service to test two novel ways of linking smokers with post-discharge care: 1) fax-referring smokers post-
discharge to the state quitline versus 2) providing an inpatient “warm handoff”—linking smokers to the quitline 
while they are still in the hospital by calling the quitline at the patients’ bedside and having the patient enroll and 
complete their first counseling session during their hospital stay43. We hypothesize the warm handoff will enroll 
twice as many smokers in quitline services and result in much higher quit rates than fax referral.  EQUIP employs 
many of the procedures that we will use for the present study, including utilization of UKanQuit staff for identifying 
and intervening with smokers, bedside randomization via computer tablet, referral to quitline, collaboration with 
quitline vendors and the state purchasers of quitline services, phone-based research follow up at 1 and 6 months, 
verification of cessation via mailed salivary cotinine and/or proxy, and assessment of costs for cost-effectiveness 
analyses. EQUIP recruited 1,054 Kansas smokers; month 1 follow up rates were 89%; month 6, 85%. EQUIP 
demonstrated the team has the expertise and tools to successfully conduct the present project.  
Proactive versus Reactive Referral to Quitline.44 This pilot project tested the effects of OPT IN (reactive) versus 
OPT OUT (proactive) for referral to counseling via the state tobacco quitline. We employed a pre-test, post-test 
comparison group design in which a script-based OPT IN approach was employed over a two-week period and 
a script-based OPT OUT approach was employed in the following two-week period. Scripts were inserted into 
the counseling protocols of the UKanQuit inpatient treatment program. The OPT IN group had an overall quitline 
enrollment rate of 36% (9/25). The OPT OUT group achieved an overall enrollment rate of 55% (11/20). This 
pilot study suggests that smokers at all levels of readiness are willing to enroll in treatment, and that providing 
OPT OUT quitline referral expands the reach of quitline counseling.  
Motivational Interviewing and Smoking Cessation.45 Team investigators Richter, Catley, and Ellerbeck conducted 
a clinical trial that compared motivational interviewing (MI) to brief advice (BA) and health education (HE) for 
motivating quit attempts among smokers who were not ready to quit (R01 CA133068; P.I. Catley). Participants 
had very low (1.9 on a 0-10 scale) level of readiness and motivation to quit. Participants in BA received one brief 
in-person session while those in MI and HE received 4 individual time-matched counseling sessions over 18 
weeks. Surprisingly, even in this low-motivated sample, the proportion of quit attempts at 24 weeks post 
randomization ranged from 45% (BA) to 61% (HE) and did not differ significantly across the three study groups. 
Rates of cessation were also equivalent across groups. This study suggests that even brief advice is powerful 
enough to prompt high rates of quit attempts among unmotivated smokers, which supports the hypothesis that 


 
 
8 
an opt-out treatment default will lead to high rates of treatment uptake and cessation.  
Other collaborations. Ellerbeck (P.I.) and Richter (Co-I) are collaborating on two NIH-funded studies 
(R01CA101963, Ellerbeck P.I.; R01-HL08764301; Richter, P.I.) that are set respectively in Kansas hospitals and 
Kansas primary care clinics. Dr. Shireman is co-investigator on both of our hospital-based studies, managing 
their respective cost-effectiveness analyses. This demonstrates our strong collaborative history and ability to 
conduct research with quitline services in a broad range of clinical care settings.   
Study  Planning 
Current practice, UKanQuit hospital tobacco treatment service. UKanQuit hospital staff currently treat all 
hospitalized smokers that request treatment, or whose physicians have ordered treatment, via the EHR. 
UKanQuit policy is to first address smokers’ comfort before raising the subject of quitting. At the hospital bedside, 
or during the COVID-19 pandemic when staff were unable to meet at the bedside then over the telephone, 
UKanQuit staff greet patients, confirm they are smokers, and assess/address current level of craving and 
withdrawal. Staff immediately work with patients’ nurses and physicians to order/increase nicotine replacement 
or other medications to reduce abstinence-induced discomfort. UKanQuit has found this disarms any potential 
resistance from patients and leads to very low refusal rates. For example, in the most recent quarter of 
operations, staff approached 349 patients but only 5 (1%) refused care (internal data). UKanQuit staff then 
collects service intake data, provides brief, personalized advice to quit as recommended by current treatment 
guidelines3, and provides the UKanQuit service pamphlet that describes the risks of smoking, the benefits of 
quitting, the effectiveness of counseling and medications, and resources for quitting (Appendix 1).  
 
Current UKanQuit tobacco treatment adheres to current guidelines and corresponds to the OPT IN (control) 
condition of this trial. Staff screens for readiness to quit, provides motivational counseling to smokers who are 
not ready to quit, and provides assistance in quitting to smokers that are ready to quit. Motivational intervention 
involves engaging patients in a discussion of the guidelines-recommended “5 Rs” (Relevance, Risks, Rewards, 
Roadblocks, Repetition) (see Motivational Counseling Checklist, Appendix 2).3 For patients ready to quit, 
treatment consists of brief practical counseling3, including problem solving barriers to quitting, identifying sources 
of support and discussing how quitline counseling works, and discussing and selecting medications. Staff 
complete a treatment plan with patients (Appendix 3) that documents reasons for quitting, the patients choice of 
post-discharge medication, and sources of support, including referral to the state tobacco quitline. All treatment 
is recorded in the hospital EHR using “smart notes”—drop-down menus using controlled vocabulary to ensure 
consistent documentation. Recommendations for discharge medications are provided to the patient care team, 
and UKanQuit staff fax-refer to the quitline all patients who accept quitline services. At one month post-discharge, 
in accordance with Joint Commission guidelines, UKanQuit staff call all smokers to assess tobacco use status, 
quit attempts, and treatment adherence. Under Clinical Trial Phase (below), we describe how we will augment 
UKanQuit protocols to test the OPT OUT approach.  
UKanQuit staff training. UKanQuit staff have masters’ degrees in healthcare or addictions case management 
and counseling.  All have completed intensive tobacco treatment training and one counselor is fluent in Spanish. 
UKanQuit staff are familiar with quitline fax-referral procedures as this is one of the study arms in EQUIP. Training 
will include lecture, demonstration, and practice between staff, mock patients, and actual hospital patients. Dr. 
Cately from Children’s Mercy Hospitals and Clinics has a PhD in Counseling Psychology and will lead the 
development of the final treatment protocols and will assist in the development of tools to assess counselors’ 
fidelity in delivering the OPT IN or OPT OUT treatment protocols.  Staff will provide input into the final treatment 
protocols, which will be codified into checklists that will be included in treatment packets and used for fidelity 
monitoring. The training will be incorporated into UKanQuit staff weekly team meetings, will span 4-6 weeks of 
30-minute sessions per week, and will include homework on practicing verbal consent, OPT OUT, and OPT IN 
procedures. Staff will be considered trained to criteria when they are able to correctly perform all components of 
both conditions with three exemplar patients. Fidelity monitoring will be used to provide ongoing feedback and a 
summative assessment at the end of the trial.    
Study Design Considerations 
Overall study design and setting. We considered conducting a pre-test, post-test control group design. This 
common design collects data from participants at the outset of the trial and would require patients to consent to 
study procedures before enrolling in the trial. This would, however, require patients to “opt in” to treatment 


 
 
9 
intervention. Pre-trial assessment and consent might discourage some smokers from participating. We rejected 
this design, as it is the very experimental condition we seek to test. Our IRB and the hospital are supportive of 
this approach as it is will not adversely impact participants and is consistent with current UKanQuit practice and 
U.S. treatment guidelines (see Human Subjects and Letters of Support).  
Measuring main outcome at 1 month post-intervention. Baker and colleagues46 suggested a framework for 
developing and testing tobacco cessation interventions that divides the process of quitting into 4 phases: 
motivation, pre-cessation, cessation, and maintenance. The present study is focused on how best to get smokers 
into treatment and initiate cessation. Assessing outcomes at 1 month will best capture the immediate impact of 
OPT IN vs. OPT OUT on treatment utilization, quit attempts, and short term abstinence.47 Moreover, assessing 
outcomes at 1 month accords with Joint Commission guidelines and UKanQuit follow-up practice for post-
discharge follow-up of hospitalized smokers.48 Perhaps most importantly, one month represents an important 
timeframe for hospitals, as hospitals with excessive 1-month readmission rates for selected diagnoses will 
receive decreased Medicare reimbursements.49 Should our intervention prove effective, it could pave the way 
for future studies on the impact of smoking cessation on reduced 30-day readmission rates for specific 
diagnoses. Moreover, although we have powered the study to detect 1-month outcomes, our power will remain 
acceptable to detect differences and mediators of effects at month 6. 
Clinical Trial Timeline and Procedures   
The trial employs a post-test-only randomized study design among 1,000 inpatients with consent for extended 
data collection at month 1 and follow-up at month 6.  It will be implemented in 4 stages over 4 ½ years (Table 
1). Throughout the Research Plan, we address potential problems and alternative strategies after sections that 
pose potential risks in implementation.  Below, we describe how we will alter the UKanQuit service’s current 
practice to create the OPT OUT study arm and conduct the trial.  
Random selection for the trial. 
UKanQuit also has access via the 
EHR 
to 
a 
real-time, 
comprehensive list of all smokers 
in the hospital—the tobacco use 
list. For the purposes of the study, 
research 
staff 
will 
randomly 
select patients from the tobacco 
use list for the trial, and provide 
selected 
patients’ 
names 
to 
UKanQuit 
staff 
for 
baseline 
assessment, randomization, and 
intervention. Random selection of 
participants serves 2 purposes. 
First, it ensures that we will test the change of default among a sample representative of all hospitalized smokers, 
which will enhance generalizability of the findings.  Second, it ensures that smokers not seeking tobacco 
treatment will be included in the trial, which will enhance our ability to detect the effect of changing the default 
among smokers who have not requested, and who are not “ready”, for treatment.  Patients who requested or 
who have orders for tobacco treatment will be treated as usual by UKanQuit, and will only be included in the trial 
if they are randomly selected.  
Eligibility and intake assessment. UKanQuit hospital staff will visit all randomly selected smokers. For all study 
patients, staff will assess and address patient comfort, provide brief advice to quit, and provide the 8-page 
pamphlet to all OPT OUT patients and to OPT IN patients who state their willingness to quit smoking.  A 2-page 
brochure will be provided to all OPT IN patients who state they are not willing to quit smoking when they leave 
the hospital.  UKanQuit staff will then assess eligibility and collect intake data. Study eligibility criteria are minimal: 
1) be age 18 or over, 2) speak English or Spanish, 3) have access to a telephone or mobile phone, 4) not be 
currently pregnant or breast feeding, 5) have no significant co-morbidity that precludes participation (i.e. acute, 
life-threatening illness, communication barriers such as a tracheal tube placement, or altered mental status such 
as dementia, or discharged to hospice or palliative care), 6) be a permanent resident of the state of Kansas or 
Missouri, 7) not currently prescribed or taking nicotine replacement therapy or varenicline during this 
Table 1.  Clinical Trial Timeline 
Mo 
Stage 
Milestones (by end of year, unless otherwise stated) 
6-23 
1: Early 
Implementation 
400 participants randomized 
6-month outcome data collected on 200 participants 
Manuscript on study design under review  
24-39 2: Implementation 
Baseline data collected on 800 participants 
6-month data collected on 600 of participants 
Data cleaned and prepared for analysis, ½ of participants 
40-51 3: Early Analyses 
Complete recruitment of final 200 participants by midyear 
6-month data collection completed on all participants 
Mscpt on baseline characteristics of participants published 
52-60 4: Analysis/ 
Dissemination 
All data cleaned and prepared for analysis   
Conduct all outcome, mediator/moderator analyses 
Manuscripts on study outcomes under review 


 
 
10 
hospitalization, 8) medically eligible to use nicotine replacement therapy (patient currently hospitalized with 
burns, acute myocardial infarction/STEMI, cardiac arrest, unstable angina, uncontrolled arrhythmia, stroke, 
peripheral arterial disease vascular surgery will not be eligible for inclusion), 9) patient not already seen by 
UKanQuit staff as part of the hospital based clinical service, 10) provided a secondary phone to ensure one 
month follow-up survey completion, 11) smoke one or more cigarettes on 25 out of the past 30 days 12) not 
taking medication to help in quitting smoking prior to admission, 13) not currently participating in a quit smoking 
program, 14) has been admitted to the hospital greater than three days 15) completed all eligibility questions 16) 
not in the process of being discharged and 17) already screened for eligibility greater than two times. Based on 
EQUIP data, we estimate that 8% of potential participants will be excluded due to age, language, or comorbidity. 
UKanQuit staff will record eligibility for the study on their clinic service tablet computer, along with standard 
service administrative data, which includes demographics, smoking characteristics including readiness to quit, 
and contact information for 1-month follow up.  These administrative data will constitute baseline data for the 
clinical trial. The few patients who are not eligible will be provided UKanQuit services (as outlined in OPT IN 
procedures, below) but will not be enrolled into the trial.  
Random allocation to study groups.  A function will be programmed into the tablet intake form so that UKanQuit 
staff will select a key to randomize eligible smokers to either OPT OUT or OPT IN. UKanQuit staff will assist 
smokers to quit in accordance with the treatment to which patients are randomized. 
OPT IN and OPT OUT intervention procedures—framing the default treatment. We have created draft language 
that constitutes the “choice architecture” for each study condition (Table 2).  We have crafted these phrases to 
be short and simple, to enable UKanQuit staff to reliably use them. Based on the patients’ group assignment, 
staff will frame the default and provide the appropriate intervention. OPT IN is the current protocol, using the 
same language, as UKanQuit staff use in their current procedures.  
For OPT OUT language, we operationalize constructs thought to underpin the power of the default.20 These 
terms: 1) signal the provider’s positive attitude towards treatment, and 2) state that the hospital’s status quo is 
to provide tobacco treatment. Using this OPT OUT language, UKanQuit staff will make it clear that they feel the 
patient should accept treatment, and that the hospital routinely treats all smokers.  
Table 2. Choice Architecture, By Study Arm 
Components 
Default: OPT OUT 
Default: OPT IN 
FRAME TREATMENT: 
“Because quitting is the best thing 
you can do for your health, KUMed 
provides free tobacco treatment for 
everyone who smokes.”  
“Quitting is the best thing you can do for your health. Are you ready 
to quit smoking in the next 30 days?” 
             
yes 
 
                no  
 
 
 
 
FRAME INPATIENT 
COUNSELING:  
“Let’s create a brief treatment plan 
that outlines your thoughts, feelings, 
and plans to treat your tobacco use” 
“If you’d like, we can create a 
brief treatment plan that outlines 
your thoughts, feelings, and 
future plans about your tobacco 
use.” 
Brief motivation: ‘If it’s ok with 
you, I’d like to talk with you about 
the risks of continuing to smoke 
and the roadblocks you’re facing 
in trying to quit.” 
FRAME REFERRAL  
TO OUTPATIENT 
COUNSELING: 
“We refer everyone to Kansas’ free 
Tobacco Quitline—KanQuit.” 
“Would you like to participate in 
the free Kansas Tobacco 
Quitline?” 
 
 
FRAME TAKE-HOME 
NICOTINE REPLACEMENT:  
“We send everyone who is medically 
eligible home with 2 weeks of free 
nicotine replacement.” 
“If you are medically eligible, 
would you like 2 weeks of free 
nicotine replacement?”  
 
 
Inpatient counseling. For all patients in OPT OUT, staff will provide brief practical counseling and complete a 
treatment plan as outlined under UKanQuit current practice (Appendix 3). Staff provide a paper copy of the plan 
to the patient. For patients contacted over the telephone due to the COVID-19 pandemic, a copy of this plan will 
be mailed to the patient’s home following discharge. For patients in OPT IN, staff will screen for readiness to 
quit. Patients who are ready to quit will be offered the same counseling and treatment planning as patients in 
OPT OUT. Patients who are not ready will receive brief motivational intervention using the “5 Rs.”  
Post-discharge counseling. UKanQuit staff will enroll all OPT OUT patients into counseling for tobacco treatment 
after discharge. To OPT IN patients who are ready to quit, UKanQuit staff will offer counseling postdischarge.  If 
the patient accepts, the enrollment will be made the same way as OPT OUT. Postdischarge telephone-based 
counseling will be provided by UKanQuit hospital staff. Patients who initially engage in counseling but at some 


 
 
11 
point decide they no longer want any more post discharge counseling calls will be mailed a letter reminding them 
that they may contact us at any time if they decide they would like to reengage in counseling for their tobacco 
use.  We will also remind the patient that we will be calling them one month post discharge to assess their 
experience with our program and their current tobacco use. 
Post-discharge nicotine replacement therapy (NRT) “starter pack” and medication planning. All patients in OPT 
OUT will be provided with 14 days of either a) nicotine patches, b) nicotine mini-lozenges and/or c) nicotine gum, 
depending on contraindications, past history of success/failure, and personal preferences.3 We opted to provide 
NRT because, in the most recent Cochrane meta-analysis of hospital interventions for smoking cessation, the 
addition of NRT significantly increased cessation rates over counseling alone, but addition of bupropion or 
varenicline did not improve post-discharge quit rates.24  At the close of the session, UKanQuit staff will deliver 
the medication starter pack, with instructions for use, to the patients’ bedside. During the COVID-19 pandemic 
when staff are unable to deliver medication to the patient’s bedside, this medication will be mailed to the patient’s 
home following discharge. If for any reason the resident, attending physicians, or the patient’s floor pharmacist 
might have concerns regarding the patient using over the counter nicotine replacement medication upon 
discharge the medical team may contact the UKanQuit medical director, and present study co-investigator, Dr. 
Edward Ellerbeck, to discuss concerns.  If it is determined the patient is not medically eligible for nicotine 
replacement medication the patient will be dis-enrolled in the clinical trial and treated as an UKanQuit patient.  
To OPT IN patients who are ready to quit, UKanQuit staff will offer nicotine replacement.  If the patient accepts, 
the medications will be provided in the same way as OPT OUT.  All patients provided with starter packs will also 
complete a pharmacotherapy guidance form with patients to select a long-term cessation medication and plan 
how they will obtain and fill prescriptions (if necessary) post-discharge.  UKanQuit staff will then approach the 
patient’s floor pharmacist to recommend a discharge prescription be ordered for the patient if medically 
acceptable to the patient’s physician and medical team. 
Design considerations: medications. We decided to provide starter packs and medication planning in order to 
help patients bridge the gap between hospital discharge and outpatient care. With the implementation of the 
Affordable Care Act, tobacco treatment is an Essential Health Benefit.50 In addition, Kansas Medicaid covers all 
forms of first-line medication, and the national Pfizer Pharmacy Assistance Program provides varenicline and 
the nicotine inhaler free of charge. Last, nicotine replacement therapies are available over the counter at low 
cost. Consequently, some type of tobacco treatment medication should be covered for virtually all patients. The 
actual nature of these benefits, however, varies substantially across health plans, is constantly evolving, and 
requires some time for patients and providers to sort out.  In order to reduce the impact of variable medication 
access on study outcomes, we elected to ‘standardize’ medication access by providing starter packs of NRT in 
both treatment arms, and helping patient plan for how they will obtain medications post-discharge. The 
medication planning procedures used here will be very similar to the pharmacotherapy guidance provided by Dr. 
Richter’s staff as part of a study examining the impact of telemedicine-delivered smoking cessation counseling 
(R01-HL08764301).51 
Quitline services. All patients in OPT OUT and patients ready to quit in OPT IN will be enrolled in post-discharge 
counseling. Participants who accept enrollment into counseling services will receive up to 4 proactive counseling 
calls . Each call is designed to provide practical counseling to help participants develop problem-solving and 
coping skills, secure social support, and design a plan for successful cessation and long-term abstinence. Initial 
calls last approximately 30 minutes and follow-up calls last on average 15 minutes. Once participants quit, 
UKanQuit counselors review high-risk situations, coping skills, and stress management to prevent relapse. When 
participants slip, counselors troubleshoot relapse situations and encourage smokers to quit again. We will create 
custom computer systems to store data for all callers, including number of attempts to reach the smoker, number 
of calls completed, and duration of calls.  All counseling calls will be recorded for quality control as per the 
UKanQuit treatment service protocol. Patients will be informed at the beginning of the call that the session will 
be recorded. Patients will have the option to opt out of having the session recorded. A random selection of 
sessions will be reviewed for quality. Peer group supervision and one on one supervision will be conducted by 
listening to a 1-2 recordings each week to improve the overall counseling.  Recordings will be stored in a secure, 
access limited location on the Share drive.  Recordings will be deleted on an ongoing monthly basis. 
Month 1 UKanQuit call for service data collection, informed consent, and reimbursement. In accordance with 
current service protocol, UKanQuit staff will call all study participants at 1 month-post randomization to assess 


 
 
12 
UKanQuit service outcomes including smoking status, quit attempts, counseling utilization, medication use, and 
other factors related to quitting (see Table 3, Core Study Measures). At the close of the call, UKanQuit staff will 
verbally debrief patients on the clinical trial, invite patients to consent to the first in-hospital phase of the trial 
(Phase 1) and invite patients to participate in extended follow up surveys (Phase 2). UKanQuit staff will transfer 
consenting patients to research staff for data collection. Trained research assistants blinded to treatment 
allocation will conduct extended assessments at one month and 6 months following randomization. Additional 
details on consent and reimbursement are provided under Protection of Human Subjects, below.   
Patients will be reimbursed $10 at baseline for time the intake assessment requires of patients. Patients who 
participate and complete Phase 1 will be reimbursed an additional $25 at month one for activities completed 
regardless if they consent to Phase 1 allowing us to utilize the data collected as a part of our clinical trial.  
Study staff will reimburse patients who consent to participating in Phase 2 with an additional $25.  All 
reimbursements will be via reloadable debit cards. The debit cards utilize the MasterCard payment system and 
are accepted at virtually every institution that accepts a credit card. Issuing debit cards and providing a minimal 
payment of $10 to patients at baseline will enhance patient’s willingness to provide their social security number 
(in person) versus providing it one-month post discharge over the telephone. Credibility will also be enhanced 
when UKanQuit staff call to complete a survey one-month post discharge, since this will allow the staff to refer 
to the debit card number provided in the hospital. Providing the debit card at baseline will also build patient 
confidence that UKanQuit are affiliated with KUMC and aren’t trying to gain access to their social security 
number illegally. Participants will be reimbursed $25 for each survey completed.  Participants who indicate they 
have quit smoking participating in Phase 1 or Phase 2 of the clinical trial will be asked to provide either a 
salivary sample for cotinine testing or a carbon monoxide breath test to verify their quit status. During the 
COVID-19 pandemic carbon monoxide testing in-person was discontinued. Participants who provide 
verification will be reimbursed $150. 
Potential Problems & Alternative Strategies  
Hard to reach patients and patients who choose to opt out. As with standard inpatient counseling, staff may 
initially find patients occupied with hospital procedures, but will return when patients are free to participate in 
counseling.  Similarly, at times counseling sessions are interrupted, if the hospital procedure is brief the 
counselors will wait and resume the session afterwards. If it is lengthy the counselor will contact the patient at a 
later time. For patients in the OPT OUT arm who choose to opt out from any component of care (such as post 
discharge counseling, or medications), UKanQuit staff will encourage participants to use the contact information 
in the UKanQuit treatment pamphlet to obtain counseling and/or medications as soon as possible. 
Patients who visit the hospital frequently. Data from EQUIP suggests 20% of smokers will be re-admitted within 
6 months of discharge.  To adhere to current treatment guidelines48, all patients readmitted within 6 months will 
receive another bedside or telephone consult from UKanQuit. Patients will remain within the groups to which 
they were initially assigned, and they will receive the treatment to which they were originally assigned. 
Consequently, some patients in each study arm will receive multiple interventions. This should occur in real-
world practice. Sensitivity analyses will be conducted to assess the impact of multiple hospitalizations on 
outcome. 
Subject follow-up. Our ability to contact and recruit a high percentage (80% or more) of patients seen at baseline 
is essential to the success of this study. EQUIP has been able to retain 89% of study participants at one month, 
and 85% of participants at 6 months, following randomization. We are confident we will be able to recruit 80% of 
eligible inpatients into our trial for the following reasons: 1) we will collect multiple methods for contacting patients 
after discharge, including phone numbers, emails, and social network contacts (Facebook pages); 2) we will 
offer $10 at baseline and a $25 gift card for each assessment point, 3) patients will be consenting to very minimal 
research participation, consisting of survey items and a mailed salivary cotinine or anabasine sample or a carbon 
monoxide sample among those who report quitting (during the COVID-19 pandemic carbon monoxide testing 
was discontinued); 3) patients will be asked for verbal consent, to reduce attrition from mailed consent 
procedures; 4) we will inform patients after the counseling session (in the hospital or over the telephone) that we 
will be calling them at one month post discharge to evaluate our services and for completing this call we will 
reimburse them $25; 5) we will reimburse smokers who complete Phase 1 regardless if they consent to 
participate in Phase 1 or 2 of the clinical trial; 6) we will mail participants reminder letters and postcards about 
the upcoming one month survey; 7) we will obtain written permission from patients to send text messages 


 
 
13 
reminding them we will be calling them in 1-2 days at one month post discharge to evaluate our services. Text 
messages will be sent to patient’s cell phones who gave permission. Text messages will be sent via the UKanQuit 
service cell phone which is password protected and is used by treatment service team only. Finally, 8) we will 
provide home visits for participants who need them, except during the COVID-19 pandemic. 
 
Attrition due to failure to provide consent. We expect to see minimal and equivalent attrition in both study arms.  
Due to the large sample size and random allocation, there should be equal proportions of patients who are 
motivated to quit in each study arm.  If, therefore, patients who are less motivated to quit decline participation at 
month 1, they should withdraw in equal proportions across groups. Hence, any bias that will be introduced by 
attrition at month 1 should affect the overall study findings, not differences between the groups. We will minimize 
attrition by offering participants to consent to Phase 1 of the study only if they are not willing to consent to Phase 
2, keeping Phase 2 activities to a minimum, and reimbursing participants for their participation in Phase 2. As 
described under Preliminary Studies, we typically have very low subject attrition (11% at 1-month) in our 
hospital studies. In order to examine whether there is any differential attrition between groups, we will compare 
the composition of each study group before and after the 1-month follow up.  Should we find significant 
differences between the pre- and post-follow up groups, we will conduct post-hoc sensitivity analyses to assess 
the impact of attrition on findings.   
Project Measures (Table 3) 
Data reside in the UKanQuit service database, which our database manager, Niaman Nazir, manages. Among 
participants who provide consent, we will conduct additional surveys at months 1 and 6 and collect data on 
counseling participation.  
Tobacco abstinence. Outcome measures are adapted from the Society for Research on Nicotine and Tobacco’s 
Workgroup on Abstinence Measures and Workgroup on Biochemical Verification.52 Our primary endpoint is 7-
day, self-reported and verified cigarette abstinence at 1 month after randomization. In accordance with common 
analytic procedures for tobacco treatment trials, patients who do not consent to follow up, and those not reached 
or not verified, will be counted as smokers. 
Verification of abstinence. We will use either mailed salivary cotinine or anabasine or in-person carbon 
monoxide (CO) testing to confirm smoking status. During the COVID-19 pandemic carbon monoxide testing 
was discontinued. Using this combination, we have verified the proportions of participants who self-reported 
abstinence and verified by cotinine and CO were 94% and 3.0% respectively. Participants who report 7-day 
point prevalence abstinence, and who are not taking nicotine replacement, will be asked to provide a salivary 
cotinine sample. Cotinine is the measure of choice because of its sensitivity and specificity.53 We will use a cut-
point of <10 ng/ml to differentiate smokers 
from nonsmokers.54 During the COVID-19 
pandemic when carbon monoxide testing is 
discontinued, we will use mailed salivary 
anabasine testing for participants who report 
not having smoked in the past 7 days, but 
who report use of nicotine replacement, 
electronic cigarettes or other tobacco 
products. The cut-point for anabasine will be 
<1 ng/ml to differentiate smokers from 
nonsmokers. Samples will be stored in a -20o 
freezer until laboratory analysis. Participants 
who are still using nicotine replacement, or 
who refuse salivary cotinine, will be verified 
via CO, except as described above. Those 
with <10 ppm will be considered abstinent. 
 
Secondary outcomes, mediators, and 
moderators. Counseling data will be collected 
throughout the trial, which will be summarized as ‘total counseling time’ for analyses. We will assess the type, 
the dose, and the number of days medication was used via the method of Williams et al.55 This will be 
Table 3. Core Study Measures  
Baseline 
Mo. 1/6 
UKanQuit Service Measures (all participants) 
 
 
Demographics: age, gender, race 
ü 
 
Readiness to quit, craving/withdrawal 
ü 
ü 
# Cigarettes per day (cpd); time to first cigarette 
ü 
ü 
Motivation/confidence quit/stay quit 
ü 
ü 
7-day point-prevalence abstinence 
 
ü 
# of quit attempts since enrollment 
 
ü 
Medication use/adherence 
 
ü 
Research Assistant collected measures (consenting participants) 
Biochemical quit verification 
 
ü 
Default constructs (perceived status quo, implied 
recommendation, perceived paternalism) 
 
ü 
Length of hospital stay (for index visit) 
ü 
 
Reason for hospitalization (index visit) 
ü 
 
Re-hospitalization w/in 30 days of discharge 
 
ü 
Outpatient counseling use/adherence 
 
ü 
5-Trial Adjusting Delay Discounting Task 
 
ü 
Cost measures (consenting participants) 
Counseling (calculated from UKQ/Alere data)  
 
ü 
NRT (calculated from patient self-reported use) 
 
ü 


 
 
14 
summarized as “number of days of medication use” for analyses. Default-related variables are derived from the 
literature on choice theory and include smokers’ perceptions of provider attitudes toward tobacco treatment 
(implied recommendation), smokers perceptions of the degree to which their provider recommends tobacco 
treatment (implied recommendation), perceptions of the “status quo” for hospital tobacco treatment (status quo 
bias), and perceptions of paternalistic treatment by UKanQuit staff.56 We will develop several new survey 
questions to measure aspects of changing the default. In order to do so, we will adapt 2 validated surveys—the 
Working Alliance Inventory (WAI), and the MacArthur Admission Experience Survey.  We will slightly change 
the language in each, and reduce the number of items in the WAI.   In order to test the “usability” of these 
adapted surveys, we will administer these to an anonymous sample.  Amazon M*Turk is a crowdsourcing 
software designed by Amazon and is regarded as a valid method for research in social and behavioral 
sciences (e.g. Mason & Suri, 2012; Buhrmester, Kwang, & Gosling, 2011).  In order to test the readability and 
psychometrics of our modified survey items, we will post a request for completion of a questionnaire on 
M*Turk. Written informed consent will not be collected, as the surveys are about very low-risk information and 
we will not collect any respondent identifiers.  
 
We will request that MTurk collect responses from 100 individuals, for a 5-minute survey, for $1.00 per 
respondent.  Eligibility criteria include Turkers who are 18 years or older, have smoked on a daily basis within 
the past 6 months, and had a health care provider advise them to quit in the past 6 months.  Once this order is 
completed, MTurk will make available a spreadsheet for download.  We will download the data and factor 
analyze data to see if we will be able to eliminate extraneous items from our proposed scales.  The final 
questions will be utilized for the clinical trial and will be included as part of the one month survey.   
 
We will use MTurk to also validate a new measure, Tobacco Working Alliance Inventory (TWAI), against the 
established published measure the Working Alliance Inventory (WAI). This will establish the credibility of the 
TWAI as a shorter measure of the “gold standard” WAI.  We will request that MTurk collect responses from 100 
individuals, for a 5-minute survey, for $1.00 per respondent.  Eligibility criteria include Turkers who are 18 
years or older, have smoked on a daily basis within the past 6 months, and had a health care provider advise 
them to quit in the past 6 months.  Once this order is completed, MTurk will make available a spreadsheet for 
download.  We will download the data and factor analyze it to further assess the validity of our adapted 
instrument, the TWAI.  
 
Additionally participants will perform a one minute 5-Trial Adjusting Delay Discounting Task during the baseline, 
month 1 and 6 surveys (Koffarnus and Bickel, 2014). Participants will be read in person (baseline) or over the 
telephone (follow-up) a series of discounting tasks.  Responses on these tasks will be recorded. Individuals who 
discount delayed rewards at a high rate may be more likely to engage in treatment. 
Intervention costs. We will prospectively track variable intervention costs.  Costs will include inpatient counselor 
services, postdischarge counselor time, and initial pharmacotherapy dispensed at baseline. During the 6-month 
follow-up call, we will ask participants to recall their use of pharmacotherapy after the initial supply.  Personnel 
time will be valued at Bureau of Labor Statistics (www.bls.gov) wages plus benefits for an appropriately trained 
health promotion professional.  Pharmacotherapy costs will be based upon retail prices estimated from on-line 
pharmacy websites, e.g., www.drugstore.com during the study. Intervention costs will be tracked as they are 
incurred. We will exclude research costs.  Given that all costs are short-term (<6 months), we will not discount 
either costs or benefits.   
Fidelity monitoring. Fidelity to components will be assessed by in-person fidelity assessment checks during 
hospital consults and by digitally recording inpatient counseling sessions. To assess the quality of the 
intervention and control conditions, we will assess the degree to which UKanQuit staff accurately: 1) identify 
eligible/ineligible participants; 2) provide brief advice and the study pamphlet; 4) randomize patients and perform 
the appropriate intervention for OPT OUT and OPT IN; 5) address post-discharge medications; and 6) provide 
information regarding the post discharge counseling to the appropriate patients. Digitally recording will only be 
conducted on patients who provide written consent for the audio recording of the counseling session.  Recording 
will allow for increased fidelity monitoring of patient counseling sessions.  Recordings will be stored in a secure, 
limited access location on the share drive.  The sessions will be coded and entered into the fidelity database.  
Recordings will also be used during group and one on one supervision sessions to improve the overall quality of 


 
 
15 
the counseling sessions.  Recordings will be permanently deleted at the conclusion of the clinical trial.  Data on 
fidelity will be entered into a database and reported back to hospital staff on a monthly basis to encourage 
adherence to protocols. 
 
 
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Fiore MC, Jaen CR, Baker TB, et.al. Treating Tobacco Use and Dependence: 2008 Update. Clinical 
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Miller WR, Rollnick S. Motivational Interviewing: Preparing people for change. 2nd ed. ed. New York: 
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SAP_001.pdf: 
 
1 
 
 
STATISTICAL ANALYSIS PLAN 
CHANGING THE DEFAULT FOR TOBACCO TREATMENT 
ClinicalTrials.gov Identifier: NCT02721082 
Date: 10/01/2021 
 
Data Management 
Data management will follow procedures developed for EQUIP. UKanQuit service data, and survey data 
collected by research assistants, will be directly entered via tablet into REDCap. Project Director Mussulman will 
coordinate data retrieval from the EHR. Data manager Mr. Nazir will conduct initial data cleaning, identifying and 
tagging any crossovers, conversion into proper format for data analysis, and recoding using standard operating 
procedures. All data will be imported into SAS for study analyses. Cleaning and management routines (e.g. 
conversion of birth dates to ages, logical checks for continuous variables, compliance with skip patterns, missing 
data codes) will be conducted using SAS.  
Data Analysis: Overview of Hypotheses and Analyses  
The overall study design is a posttest only design with random assignment to groups. We will conduct process, 
outcome, mediation, and cost analyses. Prior to initiating outcome analyses of quantitative data, we will compare 
baseline data across groups to evaluate whether random allocation achieved equivalent groups. Bayesian 
analysis (see Statistical Model, below) will answer our main outcome. After verifying adequate SEM fit to the 
data, i.e., that CFI >.9 and RMSEA < .8, we will use SEM to perform classic mediation analysis using the strategy 
outlined by Baron & Kenney1. When conducting the final analysis we will exclude the following: participants who 
refused consent, patients who died or are incarcerated. We will test whether there are any systematic differences 
between the enrolled and non-enrolled population by comparing the demographic and tobacco use patterns of 
all non-enrolled participants (unable to reach, deceased, incarcerated, refused consent) to those who enrolled 
(consented) at baseline. This comparison will strengthen considerably the scientific merit of the study by enabling 
reviewers and readers to judge how representative our study population was to all hospitalized smokers treated.   
Study hypotheses, measures, and analytic strategy  
Purpose 
Variables 
Analytic Strategy 
Hypothesis 1:  Compared to OPT IN, significantly more in OPT 
OUT will participate in counseling, use cessation medications, 
and be abstinent from smoking 
Abstinence: Treatment condition and 1-month 
7-day point prev. abstinence 
Bayesian analysis 
Counseling: Treatment condition and total 
counseling time by 1 month 
T-test  
Medication: Treatment condition and number 
of days of medication use 
T-test 
Hypothesis 2:  Significantly more smokers in OPT OUT will be 
abstinent from smoking, and mediation analyses will partially or 
fully explain the effects. 
Treatment condition and 6-month and 
-7-day point prev. abstinence 
-Default variables 
-Counseling/medication use 
Structural equation 
modeling with a logistic 
outcome 
Hypothesis 3: OPT OUT will be more costly but also more 
effective than OPT IN 
Treatment condition and 1-month 
-7-day point prev. abstinence 
-Variable costs 
Incremental cost/quit 
  
Data Analysis: Bayesian Study Design, Outcome Analyses, and Cost Effectiveness 
We will perform a prospective randomized comparative effectiveness Bayesian adaptive design study.2 This 
approach is a highly efficient and ethical strategy for comparative effectiveness clinical trials design, because it 
allocates more patients to effective treatments and can answer the research question earlier than conventional 
designs.3 In Bayesian adaptive designs, one primary endpoint is used to drive the adaptive randomization. This 
endpoint is compared across study groups periodically, and more patients are randomized to the stronger arm, 
until a predetermined probability that one arm has “maximum utility” is reached, which signals the end of the 
comparative trial. Our endpoint is the percentage of patients who quit smoking at 1-month (4 weeks) post-study 
randomization. We will perform our first planned interim analyses when we have randomized 400 patients. Based 
on the 400 randomized patients, the first interim analysis final set will be sub-selected via patients consenting to 


 
2 
be enrolled or patient unable to reach for the 1-month survey, and patients with 1-month survey window closed. 
The arm that appears to be performing the best will get more participants allocated to it in the subsequent 
randomization period. A new adaptive randomization structure will be updated every 13 weeks, using up-to-date 
outcome data, until a) trial meets early success or b) randomize all 1,000 participants. All outcome analyses will 
use an intent-to-treat approach, in which all participants will be included in the group to which they were originally 
assigned.    
Virtual participant response. In accordance with guidelines for adaptive design power analyses2, we assumed 
several virtual (or “pretend”) responses to determine the power, sample size and time (duration) needed for our 
study.  We created several scenarios for quit rates using three assumptions. One virtual response is the 
‘expected’ quit rates, another is ‘small but unlikely’ quit rates, and the third is ‘no differences’ in quit rates. 
Accrual (enrollment) patterns. Accrual patterns refer to how rapidly we enroll patients in the trial. These are 
important to Bayesian adaptive designs for determining the length of the trial. Based on accrual patterns for 
EQUIP and other hospital 
studies conducted by Drs. 
Richter and Ellerbeck, we 
assume 
that 
the 
accrual 
patterns will follow a Poisson 
distribution with an average of 
6.7 patients per week.   
Statistical model. For this study the primary endpoint is modeled SQj|nj~Bino(nj ,θQj) quitting. In addition, we 
provide “weakly informative” priors, logit(θQj)~N(0,1002).  Using the endpoint data and the prior probabilities, we 
then use Markov Chain Monte Carlo computations to obtain the Bayesian posterior distributions for the endpoint 
(i.e., quitting.)  We will stop the randomizing into the comparative trial if the probability of a study arm having best 
utility is greater than 0.9925 at both 1-month AND 6-months. The arm (or drug) having the maximum quit rate is 
MT=max(θQ1, θQ2).  The stopping rule is mathematically P(θQ1 > θQ2) >.9925 or P(θQ1 < θQ2) >.9925), this would 
take place both at 1-month AND 6-month endpoints. If a best arm is not identified after 500 patients randomized, 
this procedure and accrual will continue until a best arm is identified or we randomize all 1000 patients.  Should 
we reach our stopping rule before 1,000 patients randomized, we will continue to recruit patients, but we will stop 
randomization and recruit the remaining patients into the more effective study arm. We will do so because this 
is the first trial to experimentally test the impact of changing a treatment default. We believe it is important to 
maximize our cases to enable us to conduct mediation analyses that will determine the mechanisms that underlie 
the impact of treatment defaults.  
Adaptive Randomization: allocation. After the best utility probability is evaluated the next round of patients are 
randomized using a formula, which is V*j=sqrt(P(θQj > θQj’)Var(θQj)/(nj+1)) and θQj and θQj’ are the utility parameter 
(i.e. smoking quitting rate parameter) of the two arms at 1-month only, that takes advantage of the information 
gained from our analyses up to that point. The newly enrolled patient allocated to the jth arm is proportional to 
V*j=sqrt(P(θQj > θQj’)Var(θQi)/(njT+1)). This type of allocation tends to have more desirable properties then simply 
using Pr(MjT= θQ1).  In other words, using this approach will allow us to assign more patients to the most promising 
arm, and fewer patients to the least.  Regardless of when the probability cutpoint is reached, we will confirm this 
finding with a subsequent analysis and evaluation (>.99), which can be at 1-month OR 6-month endpoints, after 
all data from patients are obtained, as some will still be actively in the study when the early success criterion is 
identified.   
Power, sample size, and trial duration. We performed three sets of trial simulations based on the various 
combinations of quit rates endpoints for both 1-month and 6-months. Each set involved many trial simulations 
that identified power (the probability of success) in two scenarios—one for early success (i.e., being able to stop 
randomization early) and one for late success (i.e., upon randomizing all 1000 patients). While two of these 
combinations are very unlikely to occur, we included all scenarios.  First, under the ’expected’ quit rates at 1-
month and ‘expected’ at 6-months, we estimated (identified) that 75% of the simulated trials had early success, 
24% late success, and only 1% had incomplete results. Thus this scenario had 99% power.  The average sample 
size of this trial scenario was 789 patients with more than half (546) in the better OPT-OUT arm. The average 
length of these simulated trials was 145 weeks. Second, if there is ‘expected’ quit rates at 1-month and  ‘small 
but unlikely’ quit rates at 6-months, we estimated (identified) that 23% of the simulated trials had early success, 
68% had late success, and 9% had incomplete results. This trial scenario had 91% power and the sample size 
Virtual response patterns for quit rate endpoint 
 
OPT IN 
OPT OUT 
 
 
Efficacy 
 
No differences 
15.7% 
15.7% 
Both have equal quit rates 
Small but unlikely 
15.7% 
20.0% 
Opt-Out is moderately better 
Expected 
15.7% 
25.2% 
Opt-Out is better at expected differences 


 
3 
of this trial scenario was on average 947 with more than half (696) in the better OPT-OUT arm. The average 
length of this trial scenario was 167 weeks. Third, we examined the scenario that serves as our null hypothesis 
(no differences) at both 1-month and 6-months. In this scenario there are no differences in quit rates among the 
arms.  The extent to which this scenario is “successful” actually reflects our Type I error rate. For this scenario, 
we estimated (identified) that 0% of the simulated trials had early success, 5% late success. Thus this trial 
scenario produced an appropriate expected Type I error (α=.05,). The sample size of this scenario on average 
was 1000 patients, with half (500) in the OPT OUT arm. The average length of the trials under this scenario was 
175 weeks— approximately 3 years of recruitment. Hence, our sample size of 1,000, in 3 years of recruitment, 
provides ample time and participants to identify project outcomes under all 3 scenarios.   
Cost analyses for Hypothesis 3. We will conduct a cost-effectiveness analysis to explicitly document the relative 
costs and benefits of OPT OUT versus OPT IN. This analysis will be conducted in collaboration with Dr. Theresa 
Shireman at Brown University.  Dr. Nazir and Dr. Shireman will manage the cost effectiveness analysis.  Dr. 
Nazir will send Dr. Shireman de-identified data sets through secure electronic channels to ensure the protection 
of the confidentiality of participants.  Our cost analytic framework generally follows the guidelines adopted by the 
Centers for Disease Control (CDC) in accordance with the consensus Panel on Cost-Effectiveness in Health and 
Medicine.4-6 We will divide the analysis into two components: first, intervention only costs, and second, 
intervention plus short-term (<=6 months) costs post-discharge. The primary cost-effectiveness analysis will be 
set up as an incremental cost-effectiveness ratio (ICER).  We anticipate that OPT OUT will be more costly and 
more effective than OPT IN.  Incremental cost-effectiveness analysis identifies the marginal benefit of switching 
from one intervention to the other and is the ratio of the difference in costs divided by the difference in 
effectiveness between the two treatment options. The outcome assessed will be biochemically verified 7-day 
point prevalence abstinence. The ICER will indicate the added cost per additional quitter OPT OUT versus OPT 
IN, a metric that will allow comparisons to other smoking cessation economic studies. In designing these 
analyses, we considered using a societal perspective, as recommended by current national guidelines. The 
societal perspective, however, requires quality-adjusted life years (QALYs) as the denominator. Since this is a 
short-term study, we decided against attempting to estimate changes in QALYs, and focus instead on cost per 
quit.   
The data derived for this cost analysis come from several clinical trials based in Kansas. In sensitivity analyses, 
we will adjust wages rates upwards to the national average. In order be able to generalize our findings from this 
one clinical trial to other populations, we will explore how the variation in counseling time and effectiveness 
influence the relative cost-effectiveness of the treatment strategies. Our analyses will vary time and effectiveness 
until breakeven points are achieved between the treatment options. 
 
 
 
 
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