Clinical trial NCT03603496
Conditions: Smoking Cessation
Keywords: Tobacco Cessation Hospitalization eReferral Interactive Voice Response Tobacco Quitline
Sponsor: Massachusetts General Hospital
Start date: 2018-09-01; Completion date: 2020-11-17
Enrollment: 1416 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized controlled trial will compare the effectiveness of two models of post-discharge tobacco cessation treatment for adult smokers admitted to 3 U.S. hospitals.

Detailed description:
This multi-site randomized controlled trial (RCT) will compare the effectiveness of two models of post-discharge tobacco cessation treatment for adult smokers who are admitted to 3 large hospital systems in 3 U.S. regions (MA, PA, TN). All patients will receive guideline-based tobacco cessation treatment delivered in hospital by each site's existing Tobacco Treatment Service that is directed by a study investigator. Patients who plan to quit smoking after hospital discharge will be randomly assigned to 1 of 2 post-discharge tobacco treatment interventions and followed at 1, 3, and 6 months. One arm uses bidirectional electronic referral (eReferral) to the state tobacco quitline. The other arm, Personalized Tobacco Care Management (PTCM), combines proactive messages delivered by automated interactive voice response (IVR) phone calls, text messaging, and/or email with health coaching provided by a hospital-based tobacco counselor. Both groups will receive at least 1 month of nicotine replacement therapy.

Arms: arm 1: TTCM will provide 8 weeks of nicotine replacement therapy at hospital discharge and proactive contacts over 3 months delivered by automated IVR call. At each contact the patient is offered a return call from the hospital-based tobacco coach for counseling, medication advice, and coordination of care with the patient's outpatient health care team. arm 2: Referral from hospital to the state Quitline will be made by the research team on behalf of each enrolled patient. Quitline staff will contact patient to offer up to 5 proactive telephone calls from a tobacco coach. Patient may also be eligible for NRT sample. Feedback from the quitline will be sent back to the patient's medical chart.
Interventions: intervention 1: Transitional Tobacco Care Management (TTCM) intervention 2: eReferral to State Tobacco Quitline (QL) intervention 3: Nicotine replacement therapy
Intervention descriptions: intervention 1: PTCM will provide sustained care after discharge by offering (1) 8 weeks of nicotine replacement therapy at no cost provided at hospital discharge and (2) up to 7 proactive contacts over 3 months delivered by automated IVR call, supplemented by text messaging and email (patient choice). At each contact the patient is offered a return call from the hospital-based tobacco coach who offer counseling, medication advice, and coordination of care with the patient's outpatient health care team. intervention 2: Referral from hospital to the state Quitline will be made by the research team on behalf of each enrolled patient. Feedback from the Quitline will be included in the patient's medical chart. intervention 3: Up to 8 weeks of nicotine replacement therapy provided at no cost to the patient.

Protocol documents:
Prot_SAP_002.pdf: 
1 
 
 
 
DETAILED PROTOCOL 
 
 
TITLE: Comparative Effectiveness of Post-Discharge Strategies for Hospitalized Smokers 
 
mPIs: Nancy Rigotti, MD, Hilary Tindle, MD, MPH 
 
REGISTRATION:  Clinicaltrials.gov #NCT03603496 
GRANT: NIH-NHLBI #2R01-HL111821 
 
VERSION DATE: July 30, 2020 
 
 
 


2 
 
 
I. 
BACKGROUND AND SIGNIFICANCE 
  
Cigarette smoking is the United States’ leading cause of preventable death.1 Despite Healthy People 
2020’s objective to reduce adult smoking prevalence to less than 12%, 15% of U.S. adults smoked in 2014.24,25 
Smoking cessation has health benefits for all smokers, even those with smoking-related diseases.5-7 
 
Effective smoking cessation treatment exists but is underused. According to clinical practice guidelines 
from the U.S. Public Health Service (2008) and U.S. Preventive Services Task Force (2015), effective tobacco 
treatment consists of counseling (in-person or by phone) and pharmacotherapy with nicotine replacement 
(NRT), bupropion, or varenicline.9,26 Combining counseling and medication is more effective than either alone. 
However, few smokers trying to quit use behavioral methods (9%) or medication (32%).13,27  Increasing the 
proportion of smokers who use proven treatment when quitting would boost population quit rates. 
 
There is a compelling rationale to intervene with hospitalized smokers. Each year, nearly 4 million 
smokers (8.7% of all smokers) are hospitalized. This “teachable moment” provides an opportunity for a smoker 
to stop tobacco use because: (1) U.S. hospitals are smoke-free, requiring smokers to temporarily abstain from 
tobacco; (2) Illness, especially when tobacco-related, boosts motivation to quit14; (3) Smokers are accessible 
for intervention in the hospital.   
 
Smoking intervention started in the hospital improves tobacco abstinence, but only if contact 
continues after discharge. The 2012 Cochrane systematic review of 50 RCTs led by Dr. Rigotti confirmed the 
efficacy of hospital-initiated smoking intervention. Intervention begun in hospital increased tobacco abstinence 
at 6-12 month follow-up by 37% (RR 1.37, 95%CI 1.27-1.48) but only if intervention was sustained for >1 
month after discharge.2 Intervention was effective for smokers regardless of diagnosis. Adding NRT increased 
cessation rates over counseling alone (RR 1.54, 95%CI 1.34-1.79).  
 
There is a pressing need to translate interventions proven in efficacy studies into routine hospital 
practice.2,3 The main challenge is how to continue tobacco treatment after hospital discharge. Tobacco 
use is a chronic disease whose successful treatment requires sustained care.15,28 Coordinating care during the 
transition from inpatient to outpatient care is a key component of all chronic disease management programs.29 
It is especially critical for tobacco interventions because over half of smokers resume smoking within 3 days of 
hospital discharge,19,30 long before outpatient follow-up visits occur. In addition, cost and convenience are 
barriers to using NRT after discharge if health insurance does not cover it.31 Our previous research identified 
effective strategies (rapid outreach, provision of NRT) to overcome such barriers. The proposed study refines 
these strategies into a more comprehensive intervention to better promote abstinence after discharge. 
 
U.S. hospitals’ interest in adopting tobacco interventions is heightened by new financial incentives for 
adoption. The Joint Commission, which accredits hospitals, added new tobacco measures to the National 
Hospital Quality Measures (NHQM) in 2012. In 2014 they were endorsed by the National Quality Forum and 
adopted by Medicare.8 In 2016 Massachusetts Medicaid adopted them as required pay-for-performance 
measures and in 2018, psychiatric hospitals will face financial penalties for failure to implement them.32 NHQM 
require hospitals to (1) document smoking status of all admitted patients, (2) offer all smokers cessation 
counselling and medication in the hospital, and (3) actively connect smokers to tobacco treatment (both 
counselling and medication) after hospital discharge.33 Hospitals not meeting NHQM targets face financial risk 
(lower Medicaid/Medicare reimbursement), leading hospitals to seek efficient and effective ways to meet them. 
The proposed project will address hospitals’ need to meet this challenge. Hospitals have additional financial 
incentives to offer tobacco treatment as a way to reduce patients’ future health care utilization and cost if they 
participate in shared savings programs through accountable care organizations.34 
 
An intervention’s cost-effectiveness and impact on hospital readmissions are key issues for hospitals 
and payers. Smoking cessation is cost-saving in the long run,35-37 but its short-term effects on health care 
utilization and clinical outcomes after a hospital stay are not well studied. A pre-post study in 14 Canadian 
hospitals found a smoking intervention to be associated with fewer readmissions by 30 days and lower 


3 
 
mortality by 1 year but it did not assess program costs or cost-effectiveness.38 The proposed study will gather 
readmission and cost-effectiveness data to guide U.S. hospitals, health care systems, and payers.38 
 
The proposed project will compare the effectiveness and cost-effectiveness of two potentially scalable, 
disseminable, and sustainable interventions to provide tobacco cessation treatment after hospital 
discharge. Each meets NHQM standards but they differ in intensity and resources required. The models are:  
 
 
Personalized Tobacco Care Management (PTCM). Our prior work produced an effective and cost-
effective theory-based model (Sustained Care) that met the new NHQMs.39 It leveraged a novel health 
communication tool, computerized phone calls using interactive voice response (IVR), to reach out to smokers 
after discharge and link them to evidence-based treatment resources. We propose to improve the Sustained 
Care model’s effectiveness by incorporating advances in health communication and health information 
technology and by addressing the need for health care systems to coordinate the care of chronic diseases like 
tobacco dependence.27 This new model, Personalized Tobacco Care Management (PTCM), adds a tobacco 
coach to coordinate tobacco treatment, a key component of the Chronic Care Model for managing chronic 
diseases.29 The coach will have access to a health communication platform that expands and builds on what 
we have already found effective. The new model adds text messaging capabilities to IVR and live phone calls, 
allowing post-discharge contacts to be tailored to smoker preferences. Additionally, being based in the health 
care system, the coach can leverage the electronic health record (EHR) to integrate efforts with a smoker’s 
ongoing outpatient primary care provider (PCP) team.  
 
 
Electronic referral to a quitline (eReferral) is a less intensive alternative model built for easy 
dissemination. It uses the EHR to link hospitalized smokers to the national network of state-based quitlines for 
the provision of post-discharge cessation services. Quitlines deliver smoking cessation counseling and often a 
sample of NRT by phone at no cost to callers.13,14 The national network of quitlines has the potential to serve 
the nearly 4 million smokers hospitalized annually. Currently, to meet NHQMs, some hospitals refer smokers to 
a quitline via a fax referral or other method not integrated into the EHR. Recent studies found that referring 
hospitalized smokers to a quitline in this way did not improve quit rates over usual care, perhaps because the 
referral process was unreliable.40,41  eReferral is a new technologically-advanced strategy that links hospital 
EHRs to quitlines in a secure, bi-directional fashion. It automates the way that hospitals refer to and get 
feedback from a quitline, which may improve treatment uptake by patients after discharge. Due to its low cost, 
eReferral is likely to be attractive to hospitals and become the future standard of care for meeting NHQMs. 
However, how eReferral compares to PTCM for sustaining tobacco abstinence post-discharge is unknown. 
 
Both interventions harness technology to streamline the delivery of tobacco cessation treatment by 
automating intervention components and by integrating with new health information technology (i.e., certified 
EHRs). Yet the comparative effectiveness of eReferral and PTCM to maximize benefit for hospitalized smokers 
is unknown.  We hypothesize that PTCM will be more effective than eReferral at (1) reaching smokers to offer 
post-discharge treatment, (2) engaging smokers in using post-discharge tobacco cessation treatment, and 
ultimately (3) producing higher rates of tobacco abstinence after hospital discharge. 
      
Potential Impact: Strong evidence supports the efficacy of initiating tobacco cessation interventions in 
hospitals, but to have public health impact, this key research finding needs to be translated into routine clinical 
practice. The main challenge is sustaining tobacco treatment practically and economically after hospital 
discharge. This project compares the effectiveness and cost-effectiveness of PTCM and eReferral, two broadly 
disseminable models that address this challenge, satisfy NHQM standards, and thereby help translate 
research findings into clinical practice. A cost-effective model for hospitalized smokers could, if widely adopted, 
reduce population smoking rates, tobacco-related mortality and morbidity and health care costs.   
 
PRELIMINARY WORK 
Progress Report for #R01-HL11821 (Project Period 3/7/2012-6/30/2016)  
 
Helping HAND 1 (HH1) RCT: An earlier grant (#RC-1HL099668, PI: Rigotti) supported the Helping 
HAND 1 (Hospital-initiated Assistance for Nicotine Dependence) RCT done at MGH (2010-2012).70 It tested 
the effectiveness of the Sustained Care intervention for facilitating the delivery of post-discharge tobacco 
cessation treatment in 397 hospitalized smokers motivated to quit. Using IVR technology, it made 5 proactive 


4 
 
automated phone calls to smokers over 3 months, starting 3 days post-discharge. Smokers also received a 
free 30-day supply of their choice of FDA-approved cessation medication in hand at discharge (refillable twice). 
Each IVR call reminded smokers to stay quit and offered a call back from a hospital-based tobacco coach who 
provided brief counseling and medication refills. Acceptance of the IVR calls was high; a median of 4 of 5 calls 
was completed. Validated tobacco abstinence rates were 71% higher in the intervention group at 6 months 
compared to advice to use cessation medication and call a quitline (26% vs.15%, p<.01).9 The incremental 
cost-per-quit was $3217.39 This single-site study demonstrated the effectiveness of the Sustained Care 
intervention compared to standard care in a large hospital (Mass General Hospital, MGH). 
 
Helping HAND 2 (HH2) RCT: The current grant (#R01-HL11821,PI: Rigotti, site PI: Tindle).  
Aim 1: To test the effect of a Sustained Care intervention offered to hospitalized smokers on the use of 
tobacco treatment and on biochemically-validated tobacco abstinence [primary outcome measure] after 
hospital discharge. HH2 aimed to enhance the scalability of the HH1 intervention by incorporating referral to a 
telephone quitline, an evidence-based, nationally-accessible resource offering free cessation support by 
telephone to U.S. smokers.13,14 The new Sustained Care model aimed to link smokers seamlessly in one call 
from the IVR service to a quitline. Smokers had access to counseling and medication refills provided by a 
tobacco coach based at a quitline rather than at the hospital (as done in HH1). The multi-site HH2 RCT 
compared the new model to standard care among 1357 adult daily smokers admitted to 3 hospitals in 2 states 
(MGH and North Shore Medical Center in MA; University of Pittsburgh Medical Center in PA). All subjects 
received the same in-hospital smoking intervention. At discharge, subjects were randomized to the new 
Sustained Care model) or to Standard Care (passive referral to the state quitline for 3 months of counseling). 
Outcomes were assessed 1, 3, and 6 months post-discharge. Administrative data to assess readmission and 
mortality rates were collected for 12 months post-discharge. Progress Report: Recruitment was completed 
ahead of schedule. Outcomes were assessed in 81% (1 mo), 77% (3 mo), and 75% (6 mo) of enrollees. 
Sustained Care improved use of cessation treatment at 1, 3, and 6 months (p<.001). It increased self-reported 
quit rates at 1 month (43% vs. 32%, p<.001) and 3 months (37% vs. 30%, p=.008), but the effect waned by 6 
months (31% vs. 27%, p=.09). Validated 6 month abstinence (1o outcome) did not differ by group (17% vs. 
16%). In a post-hoc analysis, fewer smokers used counseling post-discharge in HH2 than in HH1. These 
results suggest, and participant reports corroborate, that real-time linkage from IVR calls to the quitline was 
cumbersome in practice.56 These shortcomings of Sustained Care likely led to lower patient engagement in 
behavioral counseling in HH2 compared to HH1. The outcomes paper, in the Appendix, is in press (Am J Prev 
Med, Oct 2016). Additional manuscripts are in preparation.  
 Aim 2: To assess incremental cost-effectiveness of Sustained Care vs. Standard Care. Progress Report: 
Because study arms did not differ in effectiveness, cost-effectiveness analysis could not be done. 
Exploratory aim: To examine the interventions’ effect on health and health care utilization (mortality, 
hospital readmissions) for 1 year after discharge. Progress Report: We are in the process of analyzing 
administrative data to accomplish this aim. We will compare readmissions and mortality by study arm and by 
post-discharge smoking status. We will also examine the impact of cessation on quality of life measures. 
 
Lessons learned from prior work. The Sustained Care Model has been tested in 2 RCTs that together 
enrolled over 1700 smokers.39,56,70,71 Reflecting on its successes and shortcomings, we conclude that the key 
components of a practical, effective intervention are (1) providing a sample of cessation medication in hand at 
discharge to ensure immediate use, (2) repeated proactive outreach starting right after discharge and 
continuing for several months, and (3) easy access to a coach to provide cognitive-behavioral and motivational 
support and promote adherence to cessation medication. The HH2 trial suggests that achieving high rates of 
patient engagement in treatment during outpatient care is a key challenge, especially when accessing 
treatment resources such as a quitline that are outside the health care system.56 We propose two strategies to 
promote engagement: (1) tailoring the frequency and format of outreach contacts to meet patients’ preferences 
for mode of contact (phone or text), and (2) enhanced care coordination with a health system-based tobacco 
coach. The latter strategy expands on the role of the counselor in the HH1 trial, who engaged smokers more 
effectively than in the HH2 trial. Unlike the quitline-based HH2 counselor, who was clearly outside the health 
care system, participants viewed the HH1 counselor as a familiar contact linked to their health care and saw 
this as a positive attribute. Taken together, these RCTs guided the design of PTCM, an improved, innovative, 
and highly disseminable intervention which incorporates successful aspects of past work. 
 


5 
 
Other pilot work conducted by the research team. 
Coordination of care by a tobacco coach increases use of proven quit aids. In a two-arm RCT of a 
proactive longitudinal care intervention for smoking among 633 low income veterans (Connect to Quit (CTQ), 
R01-CA141596, PI: Tindle, co-I: Rigotti), we demonstrated that a Chronic Care Model-based coordinated care 
intervention featuring a dedicated tobacco coordinator substantially increased the use of smoking cessation 
medication vs. a robust usual care condition without a dedicated coordinator (AOR 3.42, 95% CI (2.42-4.81).72 
The CTQ coordinator was based in the clinical setting, facilitated medication prescriptions via interactions with 
the PCP and primary care team, and documented care with notes in the EHR. This role resembles that 
planned for the tobacco coach in the PTCM model.   
 
Quitline eReferral. Working with the North American Quitline Consortium (NAQC), Dr. Tindle has 
pioneered the development of the eReferral model12 and demonstrated its feasibility to engage a clinical 
population of hospitalized smokers at all levels of readiness to quit smoking in one hospital (Am J Prev Med in 
press, see References).11 With the standardized Health Level 7, version 3 templates73, eReferral can be used 
by any EHR that is compliant with Meaningful Use Stage 2. For its interoperability and efficiency, this model 
has been endorsed by NAQC12 as a potential national standard of care (see letter of support, Bailey). Direct 
methods of quitline referral such as eReferral, in which quitline staff proactively reach out to smokers, result in 
higher initial connection rates than less active methods.74-79 Team members from the University of Pittsburgh 
and Vanderbilt University are participating in the Joint Commission Tobacco Electronic Clinical Quality 
Measure Task Force (Tob eCQM) to finalize and beta test strategies, including eReferral, to meet the NHQM.     
 
II. 
SPECIFIC AIMS  
Specific Aim: To conduct a randomized controlled comparative effectiveness trial of two strategies to promote 
smoking cessation in hospitalized patients: (1) Personalized Tobacco Care Management (PTCM) offering 
smokers 8 weeks of free nicotine replacement therapy (NRT) in hand at discharge and 7 proactive automated 
contacts over 3 months via interactive voice response (IVR) phone calls followed by email and/or text message 
and (2) eReferral, a one-time automated referral from the EHR to the state quitline at discharge.  The proposed 
randomized controlled trial will enroll 1350 adult smokers admitted to 3 large hospital systems in 3 U.S. regions 
(MA, PA, TN) selected to vary in size, type, and region in order to demonstrate the intervention model’s 
potential for dissemination. All patients will receive guideline-based tobacco cessation treatment delivered in-
hospital by each site’s existing Tobacco Treatment Service23 directed by a team member (Drs. Rigotti, Tindle, 
Davis). At discharge, subjects will be randomly assigned to PTCM vs. eReferral and followed at 1, 3, and 6 
months.  
 
Aim 1: To increase tobacco abstinence among hospitalized smokers after hospital discharge.  
Hypothesis 1: PTCM, vs. eReferral, will increase the proportion of smokers with biochemically-validated 7-
day point prevalence tobacco abstinence at 6 months after hospital discharge (1o outcome measure).  
 
Aim 2: To increase hospitalized smokers’ engagement in tobacco cessation treatment after discharge. 
Hypothesis 2: PTCM, vs. eReferral, will increase the proportion of smokers who are using smoking 
cessation treatment (counseling and/or medication) at 1 month and 3 months after hospital discharge. 
  
Aim 3:  To assess the incremental cost-per-quit, comparing PTCM and eReferral.  
Hypothesis 3: PTCM will cost more and be more effective than eReferral, but the incremental cost per quit 
will compare favorably to other tobacco cessation interventions (<$5000/quit). 
 
Exploratory Aims: Additionally, we will explore the interventions’ effect on health and health care utilization 
(mortality and hospital readmissions, respectively) 5-years post-discharge, and assess implementation fidelity 
of both arms.  
 
COVID-19 Quitline Data Specific Aims:   
Aim 1: To assess the effect of the COVID-19 pandemic on current cigarette smokers’ health perceptions, 
smoking behavior, efforts to quit smoking, and engagement in treatment resources. 
 
Aim 2: To explore the effect of the COVID-19 pandemic on the success of cigarette smokers’ attempts to quit. 


6 
 
 
Study Design: The proposed study is a 2-arm randomized controlled comparative effectiveness trial testing 
Personalized Tobacco Care Management (PTCM) vs. eReferral (Figure 2). 1350 smokers admitted to 3 
hospitals will be randomly assigned to study arm at discharge and followed at 1, 3, and 6 months. The 1o study 
outcome is cotinine-validated 7-day point prevalence tobacco abstinence at 6-months (Aim 1). Analyses will 
also test the effect of the interventions on use of treatment (Aim 2), hospital re-admissions, and assess their 
cost-effectiveness (Aim 3).   
 
Figure 2: Study Design 
 
 
Design Rationale: We omitted a “usual care” or “no treatment” arm because the NHQM standards are likely to 
make hospitals reluctant to withhold tobacco treatment, and the strength of the evidence makes it ethically 
inappropriate to do so. Further, the ubiquity of quitlines and spread of EHRs makes it very likely that the 
eReferral condition will become “standard care” going forward. We decided against comparing eReferral vs. 
eReferral + PTCM due to concern of confusing subjects with simultaneous post-discharge outreach calls from 
both IVR and quitline. 
 
Study Sites: Subjects will be recruited from 3 large private non-profit academic hospitals in 3 U.S. regions 
(Boston, MA, Pittsburgh, PA, Nashville, TN). Table 1 shows the hospital characteristics. All 3 hospitals already 
have in place established inpatient Tobacco Treatment Services (TTS) directed by members of the study team 
who are their hospitals’ “tobacco champions” and who have strong support from hospital leadership (see LOS 
from Drs. Slavin, Shapiro, and Mr. Edgeworth). The in-hospital TTS care and post-discharge quitline services 
are uniform across sites.  
 
Table 1: Characteristics of the 3 participating hospitals 


7 
 
Hospital 
Health Care System 
MGH 
Partners 
HealthCare 
Vanderbilt 
Vanderbilt 
University 
MUH / PUH 
Univ of Pittsburgh 
City/State 
Boston, MA 
Nashville, TN 
Pittsburgh, PA 
Site leader  
Nancy Rigotti, MD 
Hilary Tindle, MD 
Esa Davis, MD 
# Beds 
999 
1004 
799 
# Admissions (2015) 
50,679 
46,063 
39,275 
     % Male 
51 
46 
52 
     % White 
77 
71 
77 
Electronic health 
record 
Epic 
StarPanel* 
Cerner 
Quitline vendor for 
study 
Nat Jewish Health 
Nat Jewish Health 
Nat Jewish Health 
Smokers identified 
by 
EHR (RN admit 
note) 
EHR (RN admit 
note) 
EHR (RN admit 
note) 
Smokers identified 
(2015) 
7670 
6619 
9309 
Smokers seen 
(2015) 
4471 
** 
4523 
Smoking counselor 
types 
Nurse, RT, HlthEd 
NP, PA, RN 
MSW, HlthEd 
Smoking counselor 
FTEs 
3.5 
2.5 
3.0 
Median counseling 
time 
9 min 
** 
8 min 
NRT on Formulary:  
Patch, gum, 
lozenge 
Patch, gum, 
lozenge 
Patch, gum, 
lozenge 
Study recruitment 
goal 
n=550 
n=250 
n=550 
MGH=Massachusetts General Hospital; MUH=Montefiore University Hospital; 
PUH=Presbyterian University Hospital; EHR=electronic health record; 
RT=respiratory therapist; HlthEd=health educator; *Vanderbilt switches EHR to Epic 
in 2018. ** Vanderbilt TTS  launched in 2015. Annual # counseled and median 
counseling time are not known but expected to be comparable to MGH and UPMC. 
 
Innovation: The project’s novelty is the creative way in which proven tobacco dependence treatments are 
adapted to a specific clinical situation (hospitalization) and packaged into two practical models for delivery by 
and dissemination to hospitals and health care systems. Both interventions provide proactive outreach to 
sustain tobacco treatment during the transition from inpatient to outpatient care and both interventions meet 
quality improvement milestones (NHQMs). The interventions innovatively adapt proven treatments into 
systems that reach smokers during the critical post discharge transition. The project leverages modern 
communications technology to deliver post-discharge medication and counseling, link inpatient care to 
community and health care-based treatment, and tailor treatment to smokers’ preferences. The interventions 
align with the evolution of health care delivery by leveraging the EHR’s capacity to deliver and track smoking 
cessation treatment.43   
 
III. 
SUBJECT SELECTION 
Subjects 
Inclusion criteria: Adult current smokers who are admitted to a study hospital, are seen by a hospital 
smoking counselor, and plan to try to quit smoking after discharge. Because smokers may reduce tobacco 
use when ill, current smoking is defined as smoking >1 cigarette in the week before admission and >1 
cigarette/day when smoking at baseline rate in the month before admission.  
 


8 
 
Exclusion criteria: Inability to give informed consent or participate in counseling due to serious cognitive or 
psychiatric disorder (e.g., dementia, psychosis); life expectancy <6 months; females who are pregnant or 
breastfeeding, medical instability precluding study participation; no reliable telephone access or inability to 
use telephone; non-English speaking; living in a state not covered by National Jewish Health (vendor for 
state quitline): Arkansas, Colorado, Idaho, Iowa, Kentucky, Massachusetts, Michigan, Nevada, New 
Hampshire, North Dakota, Ohio, Pennsylvania, Rhode Island, Vermont, and Wyoming (NOTES: 1) 
Permanent residence gleaned from site EHR; 2) Tennessee residents are included only at VUMC site. 
 
IV. SUBJECT ENROLLMENT 
Recruitment and Enrollment: Subjects will be recruited as part of MGH’s, VUMC’s, and MUH/PUH’s 
standard treatment protocol for inpatients who smoke. All study sites have inpatient TTS programs that 
purposely resemble the evidence-based 3-step MGH program based on the successful Ottawa Model:85 (1) 
Routine smoking status documentation in the EHR at admission by a nurse produces a daily list of smokers 
sent to the TTS. (2) A trained tobacco counselor visits these smokers to offer brief bedside counseling and 
medication support. (3) The counselor links the smoker to post-discharge resources by referral to the free state 
tobacco quitline (using older methods not integrated into the EHR, e.g., fax referral).  
 
At the end of the hospital visit, TTS counselors will screen each smoker for study eligibility, alert eligible 
patients to the availability of a study offering post-discharge smoking cessation assistance, and ask about 
interest. The research assistant (RA) will visit a patient at the bedside to verify eligibility, explain the study in 
detail using a written handout that is given to the patient, and obtain verbal informed consent.  Screening for 
eligibility will include reviewing the TTS counselor’s progress note, the admission note, and contacting the 
patient’s nurse and case manager to determine exclusion criteria.   If the patient wishes to have more time to 
consider study participation, he or she will be given the name of the RA and study phone number.  Because 
lengths of stay are short, it is possible that the patient will be discharged before being able to enroll in the 
study.  
 
Baseline data collection will include demographic factors, admitting diagnosis, admitting service, smoking and 
quitting history, measures of nicotine dependence (cigarettes smoked/day in month before admission and time 
to first morning cigarette), intention to remain abstinent from tobacco after hospital discharge, and detailed 
contact information for the patient and up to 3 close contacts. Some of the data is routinely collected by the 
TTS counselor and entered into the TTS electronic database. It will be supplemented by additional data 
collected by the study research assistant at the bedside.  The research assistant will use a password protected 
iPad, connected to the hospital’s secure wireless connection, to enter baseline data directly into a RedCap 
project.  
 
Assignment to Study Arm: Randomization will be stratified by (1) study site, (2) primary admitting diagnosis 
(cardiac vs. other), and (3) cigarettes/day (>10, <10) to ensure that the treatment groups are balanced on 
these potential confounders. Prior work identified these significant independent predictors of post-discharge 
abstinence. After the patient enrolls, the RA will randomly assign the subject to 1 of 2 treatment conditions 
using the computer-generated randomization scheme created by the study statistician for the corresponding 
stratum. Subjects will receive a handout describing their assigned treatment condition. Intervention subjects 
will also receive instruction sheets on how to take nicotine patch, gum, and/or lozenge provided through the 
study at discharge.  The PTCM and eReferral interventions begin at hospital discharge and will continue for 3 
months.  
 
Subject Payment:  Subject payments are being managed by UPMC’s internal/standard study subject payment 
system – Vincent.  Vincent is the next generation of software first created in 2007 as a solution for the payment 
of compensation to medical study participants. Its unique features and functionality allow for the issuance of 
anonymous, reloadable, MasterCard-branded, instant-issue, stored value cards with multiple redemption 
options. Vincent allows for payments to be made in a controlled, auditable, decentralized environment with 
complete, centralized control and accounting to General Ledger with minimal risk and exposure to staff or 
clients.  
 


9 
 
At the time of enrollment, the RA will enter study subjects directly into Vincent’s payment system via 
password protected web interface.  The RA will enter the subject’s name, address, and SSN (with 
permission).  If the subject does not provide their SSN, they can still receive payment, however, their 
payment will be reduced by 24% for tax purposes. If the subject’s card is lost or stolen a new card will be 
sent via USPS. The subject will be charged for the cost of the additional card by subtracting the amount 
($1.25 from their payment or balance). The balance will be transferred to the new card. Subjects will be 
informed of these exceptions during the consent process.  Once the subject is entered into Vincent 
payment system, they will receive a Vincent payment card, which will be loaded with payments throughout 
the study.   All participants will receive $20 for each of the 3 follow-up telephone calls (1, 3, 6 months) that 
they complete, for a total compensation of $60, in addition to $20 for each of the optional qualitative phone 
surveys at 3- and 6-months.  Participants in the PTCM condition will also receive up to 8 weeks of FDA-
approved smoking cessation medication and up to 7 free smoking cessation counseling sessions at no 
cost.  At 6 months, all participants who report that they are not smoking will be asked to provide a saliva 
sample as biochemical confirmation of abstinence or come in to conduct an expired CO reading (if on 
NRT).  If the participant is unable to come in to conduct a CO, then a personal CO device (CoVita iCO 
Smokerlyzer) will be mailed to the participant to complete the CO reading remotely.  Participants will be 
paid $150 when we receive the saliva sample or the expired CO reading, regardless of whether it confirms 
nonsmoking.  
 
V. 
STUDY PROCEDURES 
Prior to study enrollment, all subjects will receive standardized in-hospital smoking intervention provided at 
clinical services at each study site. This infrastructure ensures consistent implementation of the in-hospital 
treatment and provides ready access to eligible participants at all 3 sites. The PTCM and eReferral 
interventions begin at hospital discharge and continue for 3 months. Table 2 summarizes how each treatment 
component is operationalized in each intervention. 
 
Table 2.  Operationalization of Treatment Components in the 
Interventions 
Treatment 
Component 
eReferral Model 
PTCM Model 
Post-discharge 
outreach 
    Modality 
    Frequency 
 
Phone call 
1 time  
 
Automated contacts within 3 
months after discharge 
(welcome at discharge, 3d, 
2, 4, 6, 8, 10, 12wks). 
Contact modalities: 
automated IVR call, 
followed by automated 
email/text message.   
Free Counseling 
    Services offered 
    When offered 
    Provider, 
location 
 
5-call QL protocol (3 
mo)  
At initial quitline call 
Tobacco coach (based 
at NJH) 
 
Tobacco coach (based at 
hospital) offered at 7 
automated contacts through 
IVR call//email/  
Free Medication 
    Type 
    When provided 
 
NRT x 4 wks 
Mailed by QL after 
discharge  
 
NRT x 8 wks 
Given at discharge 
Care 
coordination 
Feedback reports sent 
QL→EHR (no dedicated 
coordinator) 
Tobacco coach interfaces 
with PCP team via EHR 
messages; if EHR not 
available (outside hospital 


10 
 
system), then communicate 
via faxed notes 
EHR integration 
Yes  (link to QL) 
Yes (via Coach)  
Patient choice 
n/a 
IVR call followed by 
email/text message 
(patient’s choice) 
QL=quitline, NJH=National Jewish Health quitline, EHR = electronic health 
record, IVR = interactive voice response, PCP = primary care provider, 
SmokefreeTXT = free NCI text messaging program 
 
Interventions  
1. Personalized Tobacco Care Management (PTCM).  Adding to the components of the Sustained Care 
Model, PTCM will incorporate a tobacco coach based at each hospital to coordinate care with the patient and 
gradually transition care to the patient’s outpatient primary health care team. There are three main components 
to the intervention: 
• Proactive Automated Contacts (IVR Phone, Email and/or Text Message): PTCM aims to enhance 
patient engagement by adding the option of email and text messaging to the outreach done by IVR calls in 
HH1 and HH2 trials.  An automated communication platform will generate 7 personalized, automated 
outbound contacts to smokers by IVR followed by their choice of email and/or text message for 3 months 
post-discharge (at 3 days and 2, 4, 6, 8, 10, and 12 weeks). TelASK Technologies (Ottawa, Canada), our 
technical partner, developed and implemented the IVR platform successfully in the HH1 and HH2 trials. 
Each IVR call/email/text will assess: (1) current smoking status and intention to quit, (2) current smoking 
cessation medication use, and (3) medication side effects. At each contact patients will have the option to 
request additional support from the tobacco coach; separately, some responses will trigger a call back 
from the coach.  Criteria to trigger a live counseling call will be: (1) patient’s request; (2) patients who 
resumed smoking after discharge but still want to quit; (3) patients who stopped using pharmacotherapy 
before the end of an 8-week course; (4) patients reporting medication side effects.  
 
• Tobacco Coach: The tobacco coach is the “human face” of the intervention to the patient and performs a 
dual role as coordinator and counselor. In the coordinator role, the coach will interact with the automated 
technology platform that makes outbound contacts by IVR, email and/or text message, respond to 
patients’ requests for return calls, and coordinate tobacco treatment with the patients’ outpatient primary 
care team, using the EHR. In the counselor role, the coach will provide brief (10-15 min) supervised 
protocol-driven behavioral counseling and medication management support upon patient request. In 
addition, the coach will document in the EHR at study entry and intervention completion (3-months) to the 
patients’ primary care team indicating the patient’s study enrollment, interest in quitting, medication 
dispensed at discharge, and tailored suggestions for addressing smoking. This process ensures that every 
patient receives cessation support regardless of their response to IVR/email/text outreach.  At any 
outreach contact, patients can request a call back, which will be made within 48 hours. At that call, the 
coach will (1) offer 10-15 minutes of protocol-driven counseling and medication support, (2) refer the 
patient to additional free counseling support as needed provided by local resources, phone (state quitline) 
or text message (enrolling the patient in the National Cancer Institute’s free SmokefreeTXT program), (3) 
facilitate additional medication requests by documenting in the patient’s encounter in the EHR and 
requesting additional smoking cessation medications.   The tobacco coach will follow a detailed protocol to 
provide motivational, cognitive-behavioral smoking cessation and relapse prevention tools, tailored to the 
smoker’s characteristics and provide medication management and adherence support, with the goal of 
completing a full course of cessation medication.70 Each site’s PI (a physician) or delegate will provide 
clinical supervision for the coach.  Each coach will complete the University of MA online basic tobacco 
cessation training course and in-person 4-day Core Training course (or equivalent),86 and 6 hours of 
observing the site’s senior CTTS counseling inpatient smokers. Sites will have monthly (or as needed) 
case reviews to provide a forum for working through challenging clinical scenarios.  Post-discharge 
counseling will be evaluated by the site’s PI or delegate to ensure that counselors are completing relevant 
counseling modules, necessary database documentation, and adhering to principles of Motivational 
Interviewing (MI).  Completion of HH4 counseling modules and HH4 database documentation will be used 


11 
 
to measure “what” is discussed during a counseling session.  Monitoring and coding HH4 post-discharge 
counseling calls, using the Brief Intervention (BI) Checklist and The Motivational Interviewing Treatment 
Integrity (MITI) Coding Manual 4.2.1 (Moyers, et al., 2014), will be used to measure “how” post-discharge 
counseling is being delivered.  The site’s investigator or delegate will randomly select days for monitoring 
counseling calls, totaling 5% of their cases, and code each counseling session using the BI checklist and 
MITI 4.  The site’s investigator or delegate will also review documentation in database (DB) to ensure that 
the counseling module selected in the DB is consistent with the counseling content discussed during the 
call and that necessary database documentation is completed.  Permission to audio record or listen to 
counseling calls will be obtained when the coach initiates the counseling call with the patient (refer to HH4 
Audio Recording-Monitoring Verbal Consent).  For audio recording, a small tape recorder on 
speakerphone or other technology, if available, will be used to tape counseling calls.  No identifiers will be 
used, digital files will be transcribed, and tapes (or digital files) will be destroyed after the study.  For real-
time monitoring, the site’s investigator or delegate will listen to the counseling call when it is taking place.  
 
• Smoking Cessation Medication: At hospital discharge, smokers receive a free standard 8-week course 
of treatment of their choice of nonprescription NRT (patch, gum, lozenge or a combination of patch + gum 
or lozenge). The drug regimen can be a continuation of NRT started in the hospital or be new at 
discharge. Patients in the HH1 and HH2 trials had a choice of any FDA-approved cessation medication 
and 95% used NRT. Only NRT is used in this trial for simplicity. We include combination NRT because 
some but not all studies have found it to outperform single NRT. 2,87 Following a protocol and with patient 
input, the inpatient TTS counselor selects NRT product and dosage, which the hospital physician must 
approve and prescribe. NRT is delivered to the patient before discharge with written information on use 
and side effects. This workflow was successful in HH2. It resembles 
new “Meds to Beds”88-90 programs being implemented in the study 
hospitals, providing an avenue for future sustainability.  
 
2.  eReferral, the second intervention, is a new technologically-
advanced, automated strategy that links hospital EHRs to a quitline via a 
bi-directional connection11 using Direct, a national encryption standard for 
securely exchanging clinical healthcare data (Figure 3). Quitlines offer free 
cessation support (counseling and often an NRT sample) to U.S. smokers 
who call a toll-free number.13,14 Proactive telephone counseling is an 
efficacious smoking cessation treatment method that incorporates 
motivational interviewing, cognitive-behavioral counseling, and relapse 
prevention strategies, usually in a multi-session call format.9,91,92 For the 
study, the RA enrolling the patient will make the eReferral from the EHR at 
discharge. Quitline staff will then attempt to contact the smoker by phone 
within 72 hours to offer the standard services offered by the state quitline 
(multiple-call counseling protocol and 4 weeks NRT).12,73 Up to 3 contact 
attempts are made but in practice successful connection may take several 
weeks. A report of the quitline referral is sent securely to the EHR where the patients’ primary health care team 
can access it and act upon it as needed. In accordance with best practices for Federal Health IT as determined 
by the Office of the National Coordinator for Health Information Technology, eReferral employs standardized 
recommendations for message structure, content, transport, and delivery to maximize interoperability. The 
standardized data elements facilitate quality improvement and reporting metrics for NHQM. The quitline 
provider for this study, National Jewish Health (NJH), currently serves all MA and PA patients under state 
contract93 and will also serve Vanderbilt study participants to ensure uniformity of eReferral across sites.  
 
VI. BIOSTATISTICAL ANALYSIS 
Data Collection 
 
Baseline data:  Each site’s RA will do a baseline survey after enrollment and collect contact 
information for the patient and up to 3 close contacts in order to minimize loss to follow-up. To minimize burden 
on hospitalized subjects, some data will be obtained from hospital records and the standardized data collection 


12 
 
form used by smoking counselors who provide inpatient counseling at each site.  Smoking counselors and RAs 
will be trained to ensure that they complete data forms consistently across all sites. 
Blood collection for future potential genetic analyses (Vanderbilt site only): The NIH’s precision medicine 
initiative, All of Us, aims to understand how genetics, in conjunction with a person’s environment and lifestyle, 
can optimize prevention and treatment of illness. The GSCAN results recently published in Nature Genetics115 
identified hundreds of new genetic variants related to smoking initiation, rate, maintenance, and cessation. 
New information continues to become available regarding the role of genetic variation in smoking cessation 
and response to pharmacotherapy.  The Vanderbilt University Medical Center (VUMC) site study staff will 
initiate a protocol to collect a blood sample on newly-enrolled and consented participants for genotyping 
(GWAS). The updated informed consent document thoroughly incorporates language recommended by NIH 
guidelines for genetic studies https://osp.od.nih.gov/wp-content/uploads/NIH_GDS_Policy.pdf.  For 
participants who consent to provide a genetic sample, a single blood sample of approximately 15 ml (3 
teaspoons) will be collected at the bedside by clinical phlebotomy/study staff.  
 
 
 
Outcome assessment: Outcome assessments for all sites will be conducted at 1, 3, and 6 months 
after hospital discharge by RedCap-initiated surveys, MGH-based study staff, and mailed survey (6-month).  In 
response to the coronavirus, a separate RedCap survey will be administered to all patients enrolled in the 
study who have not withdrawn or died to explore the impact of coronavirus on tobacco use behaviors and 
related constructs. Study participants will receive $20 uploaded to their payment card for completing this 
optional coronavirus survey. Study participants will select preferred method/s of contact (Participant Contact 
Sheet).  RedCap follow-up surveys will be accessible through a password protected link sent to subjects by 
email and/or text message. Subjects can click on the link via computer or mobile device. Participants who do 
not complete the assessment by email or text, will be contacted by MGH study staff and mailed survey (6-
month survey only).  If participants cannot be reached, study staff will reach out to subjects’ alternate contacts 
to find newer contact information. Subjects will receive $20 uploaded to their payment card (provided at 
enrollment) for each follow-up assessment completed.  An additional audio-recorded qualitative survey will be 
offered to participants at 3- and 6-months to solicit feedback about participants’ experience in participating in 
the study. 
In addition to the HH4 Quantitative COVID Survey and HH4 Qualitative Interview (AMEs 36-38), study 
investigators will leverage the parent study’s existing partnership with the large US state quitline operator, 
National Jewish Health (NJH) to address much larger population-based statewide samples. Approximately 
16,000 individuals, during a one-year period, who smoke and/or vape and who are calling their state quitline in 
Massachusetts (MA), Pennsylvania (PA), Kentucky (KY), and Minnesota (MN) for help during the pandemic will 
be asked 3 questions to assess COVID-19 pandemic-related effects on their risk perceptions, motivation, and 
smoking and/or vaping behavior. These questions harmonize with the existing HH4 Quantitative COVID 
Survey. Survey questions will be administered by trained quitline staff as part of the standard intake process 
(web or phone).  
Data will be maintained by NJH with permission of the Departments of Health in each state, who 
consider the COVID-19 related survey questions to be part of quitline care (i.e., not requiring informed 
consent). The HH4 team will analyze de-identified aggregated state quitline data provided by NJH. With 
quitline data, investigators will explore the impact of coronavirus on individuals’ risk perception, change in 
motivation to quit, change in tobacco use, and engagement in treatment resources, as well as explore 6-month 
quit rates during the pandemic as compared to 1 year earlier, adjusting for any imbalance in caller 
characteristics. 
 
Measures  
Intervention Effectiveness: Smoking Cessation  
1o Outcome measure: Verified 7-day point prevalence tobacco abstinence at 6-month follow-up 
The proposed measure is self-reported abstinence from all tobacco products (including electronic cigarettes) 
for the past 7 days, confirmed by a saliva cotinine of <10 ng/ml or CO<9 ppm, which are consensus values.96,97 
We will obtain saliva samples by mail, an accepted method.98 Our definition of tobacco abstinence does not 
allow for e-cigarette use because the FDA has deemed e-cigarettes to be tobacco products99, but it allows for 
NRT use, as recommended.96 Because of uncertainty about the risk/benefit of e-cigarettes for cessation, we 
will calculate a secondary tobacco abstinence measure that allows for use of e-cigarettes but no other tobacco 
products. (In the HH2 trial, the alternative calculation produced very small differences in abstinence rates that 


13 
 
did not change study results.) Because NRT use produces a false positive cotinine, the biochemical validation 
criterion for a patient reporting NRT use at 6 months will be an expired-air carbon monoxide measurement of 
<9 ppm, obtained at an in-person visit.100  Subjects who self-report smoking, do not provide a saliva sample or 
CO measurement, whose cotinine or CO measures exceed the cut-offs, or who are lost to follow-up at 6 
months will be counted as smokers.96,97,100 Obtaining saliva samples in low-contact intervention trials, including 
recent studies in hospitalized smokers, is challenging.55,101 We will offer a $150 incentive uploaded to their 
payment card for return of a sample, which produced a 69% return rate in HH2 (with no difference by study 
arm).   
 
2o Outcome measures of tobacco use: to be calculated using standard definitions.96  
• 
Self-reported 7-day and 30-day point prevalence tobacco abstinence at 1 month, 3 months, 6 months 
• 
Sustained [repeated point prevalence] tobacco abstinence (= self-reported abstinence at 1, 3, and 6 
months) 
• 
Duration of continuous tobacco abstinence after hospital discharge (self-report) 
 
Engagement in Tobacco Cessation Treatment  
• 
Proportion of participants who use smoking cessation counseling or pharmacotherapy after discharge  
• 
Duration (days) of medication use, number of counseling contacts after discharge 
Definitions: Counseling can be from any evidence-based source, including clinicians, and occur in person, 
by phone or text message. Neither quitline registration calls nor IVR calls will be counted as counseling, but 
speaking to a tobacco coach at either the quitline or hospital will count. Medication includes all FDA-approved 
smoking cessation medications. 
 
To succeed in promoting tobacco abstinence, post-discharge interventions must engage patients in 
tobacco treatment. To do so, they must reach patients after discharge, and patients must agree to use 
evidence-based pharmacotherapy and/or counseling. Table 3 shows how we will measure these concepts, 
using a combination of patient self-reports at each assessment and records of treatment offer or delivery 
obtained from TelASK (IVR vendor), NJH (quitline), and SmokefreeTXT internal monitoring systems as well as 
from the EHR. EHR data will include (1) quitline feedback reports; (2) tobacco coach records of patient contact 
and coordination of care activities; (3) pharmacy records of NRT prescriptions provided by the study; (4) use of 
SmokefreeTXT. (Usage data from SmokefreeTXT will be visible to the tobacco coach in the EHR through the 
Epic-Smokefree.gov interface that is currently being programmed and will be publically available by 2017 
(personal communication with Dr. Erik Augustson, Smokefree.gov Director). This approach utilizes the capacity 
of EHRs to capture data on tobacco treatment use for assessing the outcomes of interventions and illustrates 
how tobacco treatment interventions can be integrated into EHRs.  
 
Table 3: Treatment engagement / use measures  
Post-
discharge 
Interventions 
Personalized Tobacco Care Management 
(PTCM) 
eReferral to Quitline (eReferral) 
 
Measure 
Data sources 
Measure 
Data sources 
Surve
ys 
Other 
source 
Surve
ys 
Other 
source 
Outreach 
contact  
% complete any 
IVR/Email/TXT contact  
# of IVR/ Email/TXT 
contacts completed  
x 
n/a 
Vendor 
records 
% reached by 
QL 
x 
QL report 
(EHR) 
Treatment 
Use   
    -  
Medication  
 
% given NRT at d/c 
Duration of NRT use, other 
med use 
x 
x 
EHR 
records 
 
%  given NRT at 
d/c 
% sent NRT 
sample 
%  receive NRT 
 
 
x 
EHR 
records 
QL report 
(EHR) 
    -  
Counseling 
% talk to coach, # of calls 
completed 
x 
n/a 
EHR 
records 
% enroll in 
counseling 
x 
n/a 
QL report 
(EHR) 


14 
 
% referred to QL or 
SmokefreeTXT 
Usage details of QL, 
SmokefreeTXT 
x 
EHR 
records 
QL/TXT 
records 
# of calls 
completed 
 
 
Health and health care utilization outcomes 
All-cause hospitalizations, cardiac and respiratory hospitalizations, all-cause deaths over 1 year.  We will 
compare rates of hospitalizations and mortality in the two study arms. These will be secondary, exploratory 
analyses. There is some evidence that hospital-initiated tobacco treatment programs can reduce readmissions 
by 30 days and mortality by 1 year follow-up.38 At all follow-up surveys, we will ask subjects about subsequent 
hospital admissions, using standard items from the National Health Interview Survey. To corroborate patient 
reports, we will review administrative data from our hospitals and ask permission to review the discharge 
summaries from any admission to an outside hospital. Among subjects lost to follow-up, mortality will be 
detected via proxy contacts, by reviewing hospital records, and, if necessary, the National Death Index.  
 
Covariates (moderators) - All done at baseline. [ * = also repeated at follow-ups.] 
• 
Sociodemographic: age, sex, education, race, ethnicity, marital status, employment, health insurance 
type. 
• 
Smoking history and behavior: cigarettes/day (month before admission), intention to remain abstinent 
after discharge (5-point Likert scale), years smoked, past >24 hour quit attempt (ever, in past year), 
past use of treatment (FDA-approved meds, counseling by phone, text message, website, physician).  
• 
Nicotine dependence: Fagerström Test for Nicotine Dependence (6-items).102  
• 
Self efficacy to quit: importance, confidence in ability to quit (1 item each, 5-point Likert scale).80,103 
• 
Medical history (from hospital record): tobacco-related diagnoses CHD, COPD, stroke, cancer; CVD 
risk factors (hypertension, diabetes, hyperlipidemia). 
• 
Hospital course (from hospital record): primary and secondary discharge diagnoses, length of stay. 
• 
*Depressive symptoms: 8-item Center for Epidemiologic Studies Depression Scale104 at baseline and 
follow-up. Rationale: depression is common in smokers,105  depressive symptoms predict post-
discharge relapse.106   
• 
*Alcohol use:  AUDIT-C,107 a 3-item survey assessing frequency, quantity, and binge drinking. 
Rationale: heavy alcohol use is associated with difficulty quitting. 
• 
*Other substance use: Any past month use.  Rationale: other substance use is common in smokers and 
may be associated with lower quit rates after treatment.   
 
 
Implementation and Process Measures.  Data at each site will be collected to monitor rates of study 
eligibility, refusal, intervention delivery, and follow-up completion, using the following RE-AIM model 
constructs.108  Reach: % of identified smokers admitted during the study who are seen by a TTS counselor, are 
eligible for the study, and enroll. Effectiveness: the 1o trial outcome. Implementation: % of subjects assigned to 
each study arm who receive relevant components (See Table 3). These data will be obtained from TelASK, 
NJH, and SmokefreeTXT internal monitoring systems as well as from the EHR.   
 
Statistical methods  
Sample Size  
A total sample of 1350 (675/group) will have 84% power to detect a 6.5% absolute difference in primary 
outcome, verified 7-day point-prevalence abstinence at 6 months, assuming rates of 16.5% (eReferral group) 
and 23% (PTCM group), and a 2-tailed type I error rate of .05. The rate ratio (1.39 =.23/.165) is clinically 
meaningful and resembles the ratio found in the Cochrane meta-analysis of smoking cessation interventions 
for hospitalized patients.2  Rationale: eReferral: We conservatively estimate the abstinence rate from the HH2 
trial (17% and 16%)56; patients in both conditions were referred to a quitline. PTCM: Intervention resembles 
that of HH1 (25% abstinence rate);39 we conservatively estimate 23%.  
 
VII. RISKS AND DISCOMFORTS  
The potential risks to subjects include potential psychological distress from speaking with a counselor or 
answering questions about their smoking, and a loss of confidentiality of their healthcare data.  In addition, 


15 
 
those patients who are randomly assigned to receive a free supply of FDA-approved smoking cessation 
medication may be subject to the potential side effects of using nicotine replacement therapy (NRT). 
 
• 
Nicotine patch: The most common side effect is irritated skin where the patch is applied, which is 
commonly managed by rotating patch sites and/or applying an OTC corticosteroid cream (such as 1% 
hydrocortisone).  In rare cases nausea, dizziness, tachycardia can occur.  Nicotine patches are sold 
without prescription in the U.S., which is an indication of the FDA’s view of their relative safety. 
• 
Nicotine gum or lozenge: The most common side effects are sore jaw, sores in the mouth, hiccups, 
dyspepsia, and nausea.  In rare cases nausea, dizziness, or tachycardia can occur. Many of the side 
effects of the gum are the result of chewing the gum improperly and can be avoided by proper 
technique of the gum.  Nicotine gum and lozenges are sold without prescription in the U.S., which is 
an indication of the FDA’s view of their relative safety. 
Other risks: 
Participants are at some risk for loss of privacy/confidentiality.  If patients opt to receive phone calls on a 
shared phone, a family member may inquire about the nature of the phone calls.  Study staff will not disclose 
information about participants’ participation in the study to others who share a phone line with participants. 
They will leave the minimum amount of information necessary on participant answering machines. 
 
There is a risk of counseling bringing up issues that are upsetting to participants.  Counselors will do their best 
to be supportive to patients.  In addition, participants will be told that they can refuse to answer any questions 
or terminate contact with counselors at any time. 
 
VIII. POTENTIAL BENEFITS 
Participants in this study may benefit by being connected better to effective tobacco treatment resources after 
hospital discharge.  They will receive up to 8 weeks of FDA-approved smoking cessation medication at no 
cost. As a result, they may be helped to quit smoking.  Generally, there is nothing better for smokers’ health 
than stopping smoking. 
 
IX. MONITORING AND QUALITY ASSURANCE 
 
Data Monitoring Plan: Study staff will provide TelASK Technologies, Inc., the vendor who will conduct 
outreach attempts via IVR call/email/text message with patient names and relevant contact information.  This 
information will be transferred bi-directionally through a secure FTP.  During the study, TelASK will establish a 
secure website interface to the data management system in which study staff can view outreach and outcome 
results in real time.    
 
Data quality (including visits completed during intervention window, missing data, and recruitment rates) will be 
monitored monthly by the database manager, Dr. Susan Regan, and systemic data problems will be reported 
to the PI.  IVR calls, emails, and text messages provided by TelASK, Inc. will be monitored for quality 
assurance.  In addition, the Project Manger will review 10% of the counseling progress notes for adherence to 
the protocol.  Outcomes data will be analyzed by Dr. Yuchiao Chang, a biostatistician, using logistic regression 
and survival analysis.  The alpha level will be set at 5%.  Interim data analysis will be conducted halfway 
through the trial and results will be reported in the annual NIH progress report. 
 
The principal investigator, Dr. Rigotti, and the Project manager will be responsible for monitoring the safety and 
effectiveness of this trial, executing the data safety and monitoring (DSM) plan, and complying with reporting 
requirements.  Dr. Rigotti will supply a summary of the DSM report to the NIH on an annual basis as part of the 
progress report.   
 
Safety Monitoring Plan: The main risks to participation in the study include the potential for psychological 
discomfort during counseling sessions and side effects to the FDA-approved medications.   We will protect 
against risks of psychological discomfort by using language that is meant to offer assistance and promote 
health, rather than demonstrate blame or guilt.  In order to protect against risk from pharmacotherapy usage, 
these steps will be taken:   


16 
 
 
(1) Medication is being provided only to patients in the PTCM intervention arm. These participants also 
receive automated telephone calls by IVR 7 times in the 3 months after hospital discharge, especially soon 
after discharge (at 3 days and 2, 4, 6, 8, 10, and 12 weeks).  At each call, patients are specifically asked about 
any side effects or problems.  Those who report them are advised to speak to a live tobacco counselor.  
Patients who request a medication refill after the initial 30 day supply are required to speak to a live counselor, 
who asks about medical problems before authorizing a refill of medication.  Study staff will be required to report 
any unexpected or questionable reports of adverse effects to the study PI (Dr. Rigotti).  These will be reviewed 
at the weekly study staff meeting.  If more urgent, the PI will review immediately. 
 (2)  The study PI (Dr. Rigotti) will review provide back up to study staff for all medical questions that 
arise during participant enrollment or study progress.  
(3)  The study PI (Dr. Rigotti) will review any serious adverse events and report them appropriately to 
the IRB.  SAEs that represent hospital readmissions are anticipated to be frequent in this population of patients 
with medical illness.  Each will be reviewed by the study PI to ensure that the readmission is not related to 
study medication. 
 
Adverse Events Reporting: Participants who report any adverse events to the smoking counselor will be 
advised to discuss these side effects with their doctor.  The reports of the adverse events will be summarized 
and reviewed by the PI on a monthly basis and reported to the IRB upon renewal of approval and to the 
funding agency upon continuing review.  Serious adverse events will be reported immediately to the PI who will 
contact the participant, the participant’s physician and the IRB. 
 
X. 
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